bromochloroacetic-acid and Skin-Neoplasms
bromochloroacetic-acid has been researched along with Skin-Neoplasms* in 913 studies
Reviews
74 review(s) available for bromochloroacetic-acid and Skin-Neoplasms
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Primary Epithelioid Sarcoma of the Conchal Bowl in a 64-Year-Old Male: A Case Report and Review of the Literature.
Epithelioid sarcoma (ES) is a distinctive malignant mesenchymal neoplasm with atypical epithelioid cells palisading around a central zone of necrosis. ES is a rare entity even in soft tissue pathology. Immunohistochemically, tumors usually show diffuse epithelial membrane antigen and cytokeratin expression and loss of nuclear INI1 (SMARCB1) expression. Here, we report a case of a 64-year-old man with ES arising in the left conchal bowl. Given the clinical presentation including patient's age, sun-exposed area of skin, and slow-growing, asymptomatic, small pink pearly papule, this patient was initially misdiagnosed with basal cell carcinoma clinically and treated with topical imiquimod at an outside facility. The lesion continued to grow and eventually became symptomatic despite the treatment after which biopsy was obtained. Despite the unusual anatomic site and the patient's age, the microscopic and immunohistochemical findings were characteristic of conventional-type ES. Our case shows that ES can arise in rare locations and in older adults where it may be more easily misdiagnosed clinically and pathologically as a nonmelanoma skin cancer. Topics: Aged; Biomarkers, Tumor; Biopsy; Humans; Keratins; Male; Middle Aged; Sarcoma; Skin Neoplasms; SMARCB1 Protein | 2023 |
Basal cell carcinoma (BCC) is a very common tumor, of which the diagnosis is generally easy. Clinical prediction of histopathological subtype however is however often difficult, i.e. the majority of sclerosing BCCs believed to be morpheaform are in fact trabecular or nodular. There is a subgroup of aggressive BCCs, including trabecular (the most common), morpheaform (rare) and micronodular (very rare) subtypes. Differentiating trichoblastoma from BCC is not always easy, but there are distinctive histopathologic criteria and preferential expression of Berp4 in BCC and PHLDA1 in trichoblastoma that may be of help. The group of trichoblastic tumors comprises giant but benign trichoblastomas and trichoblastic carcinomas at the end of the spectrum (of low or high grade). In case of metastatic BCC, one must rule out trichoblastic carcinoma. Morphologic variants of BCC such as pigmented, clear cell, granular cell BCC or BCC with areas of keratinisation are not of poorer prognosis than the classic types. On the opposite, BCC with sebaceous differentiation (in fact sebaceomas) belong to the spectrum of tumors found in Muir-Torre and must be identified. Basosquamous BCCs should be treated like squamous cell carcinomas as they are more aggressive than the nodular subtype. Cet article fait partie du numéro supplément Prise en charge des carcinomes basocellulaires difficiles à traiter réalisé avec le soutien institutionnel de Sun Pharma. Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Differentiation; Diagnosis, Differential; Humans; Keratins; Neoplasm Proteins; Neoplasms, Basal Cell; Neoplasms, Fibroepithelial; Receptors, Androgen; Skin Neoplasms; Transcription Factors | 2018 |
Spindle cell squamous cell carcinoma arising in Bowen's disease: Case report and review of the published work.
A 79-year-old Japanese woman presented with an ulcerated, brown-red nodule in the center of a sharply demarcated, tan-brown plaque situated on the left side of her right breast. Histologically, the plaque demonstrated an acanthosis with an intraepidermal epithelioma of Borst-Jadassohn. Small oval nests of bland-appearing basophilic cells in the periphery gradually enlarged into nests of various sizes and irregular shapes, composed of densely cohesive, atypical basophilic cells above the central nodule. The atypical keratinocytes shifted to atypical spindle cells beneath the acanthotic epidermis, penetrating deep into the subcutaneous tissue. In addition to vimentin and p63, the spindle cells were positive for several cytokeratin (CK) markers, including AE1/AE3, 34βE12 and CK5/6, which showed more intense signals closer to the epidermis. Basophilic cells in the clonal nests were positive for p63, AE1/AE3, 34βE12 and CK5/6. The MIB-1 index was estimated at approximately 40-50% in both the bland-appearing and the atypical basophilic cells. We describe the first case of spindle cell squamous cell carcinoma arising in an intraepidermal epithelioma expressed by clonal Bowen's disease, which was difficult to differentiate from clonal seborrheic keratosis. Topics: Aged; Biomarkers, Tumor; Bowen's Disease; Breast; Carcinoma, Squamous Cell; Dermoscopy; Diagnosis, Differential; Epidermal Cells; Epidermis; Female; Humans; Immunohistochemistry; Keratinocytes; Keratins; Keratosis, Seborrheic; Skin Neoplasms | 2017 |
Cornoid lamellation revisited: apropos of porokeratosis with emphasis on unusual clinicopathological variants.
Porokeratosis is a family of several disorders characterized histologically by the presence of cornoid lamellae. The presence of cornoid lamellae represents an abnormal form of keratinization, which unifies all types of porokeratosis. A significant variation in lesional morphology can result from peculiarities involving the cornoid lamellae and changes related to epidermal hyperplasia and dermal inflammation. This diversity has led to the recognition of several unusual clinicopathological variants of porokeratosis in recent years. Cornoid lamellation, however, is not pathognomonic of porokeratosis and can be seen in some inflammatory and inherited cutaneous disorders and also as an incidental finding. Some of these conditions can be confused with an atypical presentation of porokeratosis and vice versa. An awareness of the broad morphological spectrum of porokeratosis is crucial to avoid missing the diagnosis when appearances are far from typical. This issue is critical in patient management given the potential premalignant nature of porokeratosis. Topics: Biomarkers; Diagnosis, Differential; Humans; Keratinocytes; Keratins; Porokeratosis; Precancerous Conditions; Predictive Value of Tests; Prognosis; Skin; Skin Neoplasms | 2015 |
Atypical Fibroxanthoma: A case series and review of literature.
Atypical Fibroxanthoma (AFX) is a rare cutaneous neoplasm arising from myofibroblast or fibroblast-like cells that predominantly affects the head and neck region. It commonly mimics more invasive neoplasms and is a diagnostic challenge to clinicians. The aim of this study was to develop a better understanding of AFX, focusing on recent developments in diagnosis and management.. A retrospective case series and review of recent literature were carried out.. Over a 17-year period, seven cases were identified (six male, mean age at presentation was 75.9 years). Two patients underwent complete excision and five patients had curettage and cauterisation. Two patients developed local recurrence but none demonstrated signs suggestive of metastatic spread. Histologically all seven lesions displayed a spindle cell pattern. Where performed, immunohistochemical staining was positive for Vimentin, CD10, CD68 and actin, and negative for CAM 5.2, CD34, Melan-A, S100 protein, HMB45, Cytokeratin A1/A3.. Our patient demographics, histopathology and immunohistochemistry are comparable to previous studies. Although advances have been made in immunohistochemical analysis, we are yet to discover a specific diagnostic immunostain for AFX. Clinical findings should therefore be correlated with histology and a panel of immunohistochemical stains should be used. Given the potential for recurrence or metastases, Moh's Micrographic Surgery with regular follow-up may be the preferred management. Topics: Actins; Aged; Aged, 80 and over; Antigens, CD; Antigens, CD34; Antigens, Differentiation, Myelomonocytic; Biomarkers; Cautery; Cohort Studies; Curettage; Female; Head and Neck Neoplasms; Humans; Keratins; Male; MART-1 Antigen; Middle Aged; Mohs Surgery; Neoplasm Recurrence, Local; Neoplasms, Connective Tissue; Neprilysin; Retrospective Studies; S100 Proteins; Scalp; Skin Neoplasms; Vimentin | 2015 |
[Pathologic diagnosis of malignant rhabdoid tumor of skin].
Topics: Chromosomal Proteins, Non-Histone; Diagnosis, Differential; DNA-Binding Proteins; Follow-Up Studies; Humans; Infant; Infant, Newborn; Keratins; Male; Mucin-1; Phosphopyruvate Hydratase; Rhabdoid Tumor; Rhabdomyosarcoma; S100 Proteins; Sarcoma; Sarcoma, Clear Cell; Skin Neoplasms; SMARCB1 Protein; Transcription Factors; Vimentin | 2014 |
Merkel cell carcinoma: is this a true carcinoma?
Recent years have brought an enhanced understanding of Merkel cell carcinoma (MCC) biology, especially with regard to the Merkel cell polyoma virus as a causative agent. Differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative MCC in morphology; gene expression, miRNA profiles and prognosis have been reported. Origin of MCC is controversial. Presence of neurosecretory granules has suggested that these carcinomas originate from one of the neurocrest derivatives, most probably Merkel cells; the name Merkel cell carcinoma is now widely accepted. Expression of PGP 9.5, chromogranin A and several neuropeptides, initially regarded as specific markers for neural and neuroendocrine cells, has recently been shown in a subset of lymphomas. MCC commonly expresses terminal deoxynucleotidyl transferase and PAX5. Their co-expression under physiologic circumstances is restricted to pro/pre-B cells and pre-B cells. These findings lead to the hypothesis by zur Hausen et al. that MCC originates from early B cells. This review was intended to critically appraise zur Hausen's hypothesis and discuss the possibility that MCC is a heterogenous entity with distinct subtypes. Topics: B-Lymphocytes; Carcinoma, Merkel Cell; Chromogranin A; Gene Expression Regulation, Neoplastic; Genetic Markers; Humans; Keratins; Merkel cell polyomavirus; Neuroendocrine Cells; Neuropeptides; PAX5 Transcription Factor; Phenotype; Polyomavirus Infections; Skin Neoplasms | 2014 |
Mycosis fungoides in plaque stage with pronounced eosinophilic infiltration, folliculotropism, and concomitant invasive squamous cell carcinoma.
Mycosis fungoides (MF) is a relatively rare cutaneous T-cell malignancy. Only two cases of MF with marked eosinophilia have been reported. In addition, MF with concomitant squamous cell carcinoma (SCC) occurring in the site of MF has not been reported. The author reports herein a very rare case of MF in the plaque stage showing pronounced eosinophilic infiltration, folliculotropic pattern, and in situ development of poorly differentiated squamous cell carcinoma (SCC). A 75-year-old man was found to show high prostate specific antigen (PSA, 13 hg/ml) and prostatic biopsy showed well differentiated prostatic adenocarcinoma of Gleason score 6. Imaging techniques showed no metastatic lesions. He was treated by estrogen therapy. At 80 years, he consulted our hospital because of erythematous patch in the trunk. Biopsy showed mild infiltrations of lymphocyte and eosinophils. The lesion disappeared spontaneously. At 82 years, he consulted our hospital of because of erythematous patch at the back, and biopsy showed mildly atypical lymphocytes positive for CD20 and CD45, but negative for CD30, CD45RO, S100 protein, and cytokeratin (CK). Lymphoma was suspected but not definite. The lesions spontaneously disappeared. At 86 ages, he also consulted our hospital because of plaques in the face. Biopsy showed proliferation of atypical lymphocytes, marked infiltration of mature eosinophils, marked infiltration of these cells in the fair follicles (folliculotropism), and poorly differentiated invasive SCC arising from follicular cells. An immunohistochemical analysis showed that the atypical lymphocytes are T-lymphoma cells with T-cell markers, cyclinD1, p53, and high Ki67 labeling (50%) but without B-cell markers, NK-cell markers and plasma cell markers. The eosinophils were mature, and lacked p53 and showed low Ki67 labeling (4%). The carcinoma was positive for CK, p53, cyclinD1, and high Ki67 labeling (35%). A diagnosis of MF in the plaque stage with marked non-neoplastic eosinophilic infiltration, marked folliculotropism, and coexistent poorly differentiated invasive SCC was made by the author. Post-biopsy imaging techniques showed no metastasis or lymphadenopathy in the body. The patient was now treated by chemotherapy. Topics: Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; Cell Movement; Comorbidity; Cyclin D1; Drug Therapy; Eosinophils; Hair Follicle; Humans; Keratins; Male; Mycosis Fungoides; Neoplasms, Multiple Primary; Skin Neoplasms; Tumor Suppressor Protein p53 | 2013 |
Clear-cell variant of calcifying epithelial odontogenic tumor (Pindborg tumor) in the mandible.
We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed. Topics: Biopsy; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratins; Mandibular Neoplasms; Middle Aged; Odontogenic Tumors; Radiography, Panoramic; Skin Neoplasms | 2013 |
Trichogerminoma, a rare cutaneous follicular neoplasm with indolent clinical course: report of two cases and review of literature.
Trichogerminoma is a rare cutaneous adnexal neoplasm of the hair germ cell and usually associated with benign clinical course and favorable outcome. Since its first description by Sau et al. in 1992, only a few cases have been reported up to date. Herein, we report two additional cases occurring in the hip and right thigh, respectively. Both patients are male, one is 78 years old, the other is 29 years old. Histological examination reveals well-circumscribed dermal nodule composed of lobules of basaloid cells with surrounding pseudocapsule. The distinct characteristic of the tumor is that most of the lobules display a special pattern of round nests or cell balls arranged in the central part with the peripheral palisading. Immunostaining showed ring-like fashion of CK5/6, P63 and Bcl-2 with negative or weak staining in the "cell balls". There was no recurrence after complete excision during the period of follow-up. To the best of our knowledge, this is the first report of trichogerminoma in Chinese population. In contrast to the previously reported cases, ours present the similar morphological features with distinct immunohistochemical characteristics. We consider the concept of trichogerminoma exists with no doubt by its identifiable morphological features, and it should be classified as a variant of trichoblastoma. Because of its malignant potential, complete excision is a prior choice of treatment for this rare but distinctive tumor.. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1558612241110439. Topics: Adult; Aged; China; Dermatologic Surgical Procedures; Germinoma; Humans; Keratins; Male; Membrane Proteins; Proto-Oncogene Proteins c-bcl-2; Skin; Skin Neoplasms; Treatment Outcome | 2013 |
Calcifying epithelial odontogenic tumor: case report with immunohistochemical and ultrastructural study and review of the literature.
Topics: Amyloid; Cell Nucleus; Collagen; Cytoplasm; Diagnosis, Differential; ErbB Receptors; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mandibular Neoplasms; Membrane Proteins; Microscopy, Electron, Transmission; Middle Aged; Odontogenic Tumors; Proto-Oncogene Proteins c-bcl-2; Radiography, Panoramic; Skin Neoplasms; Tomography, X-Ray Computed; Tumor Suppressor Protein p53; Vimentin | 2013 |
Expression of keratins in cutaneous epithelial tumors and related disorders--distribution and clinical significance.
Keratins are a highly diverse family of cytoskeletal proteins and important markers of epithelial cell differentiation. In this review, applying the new keratin nomenclature recently introduced, we summarize and discuss the distribution and significance of keratin patterns in cutaneous epithelial tumors in relation to the epithelial structures of normal human skin. The available literature data show that the analysis of keratin profiles broadens our understanding of the differentiation, nature and histogenetic origin of the various, highly singular epithelial tumors arising in the skin. Moreover, keratins may aid in histological diagnosis and, in certain instances, may be helpful for the recognition of tumor malignancy and aggressiveness. Furthermore, we briefly address the topic of keratin-related skin disorders. Topics: Animals; Humans; Keratins; Neoplasms, Glandular and Epithelial; Skin; Skin Neoplasms | 2011 |
Cutaneous collision cancers: a report of two squamomelanocytic malignancies and review of the literature.
Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Proliferation; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Nose Neoplasms; S100 Proteins; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck | 2011 |
Genetically engineered mouse models for skin research: taking the next step.
Genetically engineered mouse models are invaluable to investigators in nearly all areas of biomedical research. The use of genetically engineered mice has allowed researchers to explore fundamental functions of genes in a mammal that shares substantial similarities with human physiology and pathology. Genetically engineered mice are often used as animal models of human diseases that are vital tools in investigating disease development and in developing and testing novel therapies. Gene targeting in embryonic stem cells allows endogenous genes to be specifically altered. As knowledge regarding precise genetic abnormalities underlying a variety of dermatological conditions continues to emerge, the ability to introduce corresponding alterations in endogenous gene loci in mice, often at a single base pair level, has become essential for detailed studies of these genetic diseases. In this review, we provide examples of mouse models harboring modified endogenous gene(s), generated using the technique commonly referred to as the "knock-in" approach, to exemplify the important and sometimes superior role of this methodology in dermatological research. Topics: Animals; Disease Models, Animal; Gene Targeting; Genes; Hyperkeratosis, Epidermolytic; Keratins; Mice; Mice, Knockout; Mice, Transgenic; Recombination, Genetic; Skin Neoplasms; Skin Physiological Phenomena | 2008 |
Primary cutaneous carcinosarcoma: case report with expanded immunohistochemical analysis.
Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Basal Cell; Carcinosarcoma; Female; Histone Deacetylases; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms; Telomerase; Vimentin | 2008 |
Unusual occurrence of a melanoma with intermixed epithelial component: a true melanocarcinoma?: case report and review of epithelial differentiation in melanoma by light microscopy and immunohistochemistry.
We report a case of a 27-year-old woman with a nonpigmented lesion on the right scalp. Histological examination showed a malignant nodular neoplasm with 2 distinct but intimately admixed components: a malignant melanoma with a spindle component and an unusual glandular component. Immunohistochemical studies demonstrated epithelial differentiation on the basis of cytokeratin (CAM5.2 and AE1/AE3) expression in the glandular component and melanocytic differentiation (HMB-45, PNL2, MITF, and S-100) of the spindle cell component. A single melanocytic marker (MITF) was expressed in both components, raising the possibility of dual differentiation in a single tumor, rather than the alternative considerations of a collision tumor or a reactive pseudoepitheliomatous hyperplasia with eccrine duct lumen formation within a melanoma. This unusual tumor with both melanocytic and epithelial components may represent a true melanocarcinoma, which becomes a plausible consideration, in view of melanoma plasticity and recent experimental evidence and speculation about the role of stem cells in melanoma. Topics: Adenocarcinoma; Adult; Cell Differentiation; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Melanocytes; Melanoma, Amelanotic; Microphthalmia-Associated Transcription Factor; Neoplasms, Glandular and Epithelial; Neoplasms, Multiple Primary; Scalp; Skin Neoplasms | 2007 |
Disorders of keratinisation.
Topics: Carcinoma, Squamous Cell; Humans; Keratins; Keratoacanthoma; Keratosis; Photography; Skin Neoplasms; Warts | 2007 |
Rippled-pattern sebaceoma: a report of a lesion on the back with a review of the literature.
A 68-year-old Japanese man presented with a nodule that had been present for 5 to 6 years on the right side of the back. Physical examination revealed a dome-shaped, 12 x 13-mm, dark red nodule. It was excised with a 2 to 3-mm margin. The patient remained free of disease during 77 months of follow-up. Microscopic examination revealed a bulb-like tumor in the dermis, contiguous with the overlying epidermis. It was composed of small, monomorphous, cigar-shaped basaloid cells in linear, parallel rows, resembling the palisading of nuclei of Verocay bodies, and presenting a rippled-pattern. There were scattered cells showing sebaceous differentiation with vacuolated cytoplasm and scalloped nuclei. There were tiny, duct-like spaces. The tumor revealed characteristics of rippled-pattern sebaceoma. The present case is the first reported rippled-pattern sebaceous neoplasm on the back. Many spindle cell tumors, such as basal cell carcinoma, pleomorphic adenoma, dermatofibrosarcoma protuberans, myofibroblastoma, and leiomyoblastoma, in addition to trichoblastoma and sebaceoma, can have a rippled-pattern. Topics: Aged; Back; Biomarkers, Tumor; Follow-Up Studies; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Neoplasm Proteins; Neoplasms, Basal Cell; Sebaceous Gland Neoplasms; Skin Neoplasms; Time Factors; Treatment Outcome | 2006 |
Basal cell nevus syndrome. Presentation of six cases and literature review.
Basal cell nevus syndrome, also known as Gorlin-Goltz syndrome, is an autosomal dominant inherited disorder which is characterised by the presence of multiple maxillary keratocysts and facial basal cell carcinomas, along with other less frequent clinical characteristics such us musculo-skeletal disturbances (costal and vertebrae malformations), characteristic facies, neurological (calcification of the cerebral falx, schizophrenia, learning difficulties), skin (cysts, lipomas, fibromas), sight, hormonal, etc. On occasions it can be associated with aggressive basal cell carcinomas and malignant neoplasias, for which early diagnosis and treatment is essential, as well as family detection and genetic counselling. Currently there are new lines of investigation based on biomolecular studies, which aim at identifying the molecules responsible for these cysts and thus allowing an early diagnosis of these patients. In its clinical management and follow up, the odonto-stomatologist, the maxillofacial surgeon and several other medical specialists are involved. In this paper a review of the literature, and six cases of patients affected by multi-systemic and varied clinical expression of basal cell nevus syndrome, are presented. Topics: Adolescent; Adult; Basal Cell Nevus Syndrome; Facial Neoplasms; Female; Humans; Jaw Cysts; Keratins; Male; Skin Neoplasms | 2005 |
Inherited disorders of the skin in human and mouse: from development to differentiation.
The last ten years has revealed some of the key players in the development and differentiation of the hair follicle and the epidermis in general. In this review, we discuss how our current understanding of these processes has been made possible by the elucidation of the molecular basis of human inherited diseases and mouse mutants which display defects in the hair and epidermis. For examples, the study of ectodermal dysplasias and the basal cell carcinoma predisposition disease Gorlin syndrome have allowed the determination of signalling hierarchies critical in the formation of the hair follicle. Epidermolytic diseases and hyperkeratoses have focussed attention on the importance of the programs of keratin expression, while ichthyoses provide insight in the final stage of epidermal development, cornification. Finally, the increasing range of diseases and mouse models exhibiting alopecias are revealing the critical pathways in control of the hair follicle cycle. Topics: Alopecia; Animals; Basal Cell Nevus Syndrome; Cell Differentiation; Epidermis; Forecasting; Genetic Predisposition to Disease; Humans; Keratins; Keratosis; Mice; Mice, Transgenic; Models, Biological; Mutation; Skin; Skin Diseases; Skin Neoplasms | 2004 |
DNA microarray technology and its applications in dermatology.
The use of DNA microarray technology in biomedical research has dramatically increased during the past years. In the present report, we provide an overview on the basic DNA microarray technology and biostatistical methods for gene expression analysis. A focus is then put on its applications in dermatological research. In recent years, a series of gene expression studies have been performed for various dermatological diseases, such as malignant melanoma, psoriasis and lupus erythematosus. These analyses have identified interesting target genes as well as putative disease susceptibility loci. However, further functional studies will be needed for a more complete understanding of the pathogenesis of these diseases. This may be performed by means of the recently developed RNA interference technology. Besides its role in large-scale gene expression studies, DNA microarray technology has proved to be a valuable tool for genomic screens of genetic alterations, e.g. single nucleotide polymorphisms. These play a role in tumour development and progression, and also function as genetic markers for disease susceptibility. Taken together, DNA microarray technology opens enormous perspectives for dermatologists. It may help us understand the complex pathogenesis of a wide variety of dermatologic diseases and identify their genetic background. Topics: Cell Differentiation; Gene Expression Profiling; Humans; Hybridization, Genetic; Keratinocytes; Keratins; Melanoma; Oligonucleotide Array Sequence Analysis; Psoriasis; RNA, Messenger; Skin Neoplasms; Ultraviolet Rays | 2004 |
[Carcinoma developing in extragonadal endometriosis--analysis of two cases].
Two cases of invasive carcinoma developing in extragonadal endometriosis are presented. Each case had a different clinical course. In addition to routine histopathologic studies immunohistochemical studies to assess the expression of cytoceratin and glycoprotein CD-44 were performed. In both cases CK-7 expression was higher in malignancy then in the endometrioid tissue. Very high expression of CD-44 protein (marker of metastatic potential) was found in patients with poor progress of the disease. Topics: Abdomen; Adult; Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Endometriosis; Female; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors; Keratin-7; Keratins; Perineum; Skin Neoplasms; Up-Regulation | 2002 |
Pilomatrix carcinoma: case report and review of literature.
We report the case of a 57-year-old immunocompromised man with a pilomatrix carcinoma in his left forearm. Pilomatrix carcinoma is the rare malignant counterpart of pilomatrixoma. It has a potential for local recurrence and can metastasise to distant sites. We discuss the differential diagnosis of this rare tumour, and the difficulty in distinguishing this lesion from an atypical proliferating pilomatrixoma. Ultrastructural features of pilomatrix carcinoma are also discussed. Topics: Carcinoma; Desmosomes; Diagnosis, Differential; Hair Diseases; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Male; Middle Aged; Mucin-1; Pilomatrixoma; Skin Neoplasms | 2001 |
Merkel cell carcinoma.
Merkel cell carcinoma is an unusual cutaneous malignancy with a propensity for spreading to regional lymph nodes, either at presentation or as a first site of relapse. Complete surgical resection is the mainstay of treatment of the primary tumor. Because the nodotrophic behavior of the tumor is recognized, lymphatic mapping with sentinel lymph node biopsy is becoming increasingly popular in the initial surgical staging of these patients. The role of elective lymphadenectomy in patients with clinically negative regional nodal basins is unknown. The role of adjuvant radiotherapy, either to the primary site or regional nodal basin, remains undefined. The role of adjuvant chemotherapy in diminishing the risk of subsequent systemic recurrence in patients with positive nodes remains undefined. Overall response rates to combination chemotherapy for surgically unresectable distant metastatic disease are generally high, although responses are transient. Topics: Carcinoma, Merkel Cell; Chromogranins; Female; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Sentinel Lymph Node Biopsy; Skin Neoplasms | 2001 |
Primary cutaneous adenosquamous carcinoma: a case report and review of the literature.
Adenosquamous carcinoma (ASC) of skin is a rare but distinctive neoplasm that usually exhibits an aggressive course. To date, 13 well-documented and undisputed cases of primary cutaneous ASC have been reported. This term has been used for tumors with better prognosis, such as mucoepidermoid carcinomas and acantolytic squamous cell carcinomas, originating confusion. We report a primary cutaneous ASC and review the literature.. In this report a woman with primary ASC of the skin was studied. Histopathological examination and immunohistochemical stains were performed.. The tumor had two components: conventional squamous cell carcinoma merging with adenocarcinoma. After a local recurrence and lymph node metastases, the patient has no evidence of disease 8 months later.. Pathologists should reserve the term ASC for tumors exhibiting the above mentioned appearance. In such circumstances, a metastatic origin must always be excluded. Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Adenosquamous; Diagnosis, Differential; Female; Humans; Keratin-5; Keratins; Scalp; Skin Neoplasms | 2001 |
Highly aggressive extraocular sebaceous carcinoma.
Extraocular sebaceous carcinoma is an uncommon neoplasm usually localized on the head and neck. We report a case of sebaceous carcinoma of the axillary skin with a highly aggressive behavior. The patient was a 43-year-old black man who developed multiple cutaneous and lymph node metastases shortly after the excision of primary sebaceous carcinoma of the axillary skin. Many neoplastic aggregations were identified within the lumina of the dermal lymphatic vessels in the excised specimen of the primary neoplasm. Although extraocular sebaceous carcinoma has been traditionally considered a less aggressive neoplasm than its ocular counterpart, a review of the literature and this case demonstrate that extraocular sebaceous carcinoma may also lead to disseminated metastatic disease. Topics: Axilla; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Lymphatic Metastasis; Male; Middle Aged; Mucin-1; Sebaceous Gland Neoplasms; Skin Neoplasms | 2001 |
Small cell neuroendocrine carcinoma with skeletal muscle differentiation: report of three cases.
Three cases of neuroendocrine carcinoma showing skeletal muscle differentiation are presented. The tumors were located in the skin and subcutaneous tissue, the urinary bladder, and the nasal cavity respectively, and were composed by two cell types admixed intimately with each other. One cell type had features identical to those seen in conventional small cell neuroendocrine carcinoma, including scanty cytoplasm, round nuclei with fine granular chromatin, immunohistochemical reactivity for neuron-specific enolase, chromogranin and cytokeratins, and electron-dense granules on ultrastructural examination. The second cell type was either plasmacytoid or elongated and straplike, with abundant eosinophilic cytoplasm and irregular nuclei with prominent nucleoli. These cells showed immunohistochemical positivity for desmin, sarcomeric actin, myoglobin, and myogenin. They also exhibited ultrastructural evidence of rhabdomyoblastic differentiation in the form of contractile filaments with abortive Z-band formation. An origin from a cell capable of dual differentiation toward neuroendocrine and rhabdomyoblastic elements is postulated for these tumors. Topics: Aged; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Chromogranins; Cytoplasmic Granules; Fatal Outcome; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Muscle, Skeletal; Nose Neoplasms; Phosphopyruvate Hydratase; Rhabdomyosarcoma; Skin Neoplasms; Urinary Bladder Neoplasms | 2000 |
Epithelioid sarcoma arising on the nose of a child: a case report and review of the literature.
A 4-year-old boy presented with a 6-month history of a red papule on the nasal septum. Physical examination was otherwise unremarkable. A biopsy specimen showed an epithelioid sarcoma characterized by nodular collections of epithelioid tumor cells with central, tumor cell necrosis. By immunohistochemistry the tumor cells were positive for cytokeratin, epithelial membrane antigen, vimentin, and CD34, but negative for S-100, CD31, factor VIII-related antigen, CD68, actin, desmin and myoglobin. Epithelioid sarcoma is an uncommon tumor of uncertain histogenesis that typically arises in the extremities of young adults. Both the age of our patient and the location of his tumor are unusual, emphasizing the spectrum of presentations that may occur with epithelioid sarcoma. Epithelioid sarcoma should be considered in the differential diagnosis of granulomatous diseases and epithelioid tumors of children, even in unusual locations. Topics: Antigens, CD34; Biomarkers, Tumor; Child, Preschool; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Neoplasm Proteins; Nose; Sarcoma; Skin Neoplasms; Vimentin | 2000 |
Glandular malignant peripheral nerve sheath tumor: an unusual case showing histologically malignant glands.
In this report, we describe a highly unusual case of glandular malignant peripheral nerve sheath tumor presenting as a neck mass in a previously healthy 29-year-old man. Grossly, the tumor was found to arise from a swollen peripheral nerve trunk. The tumor was largely composed of spindle cells that demonstrated marked nuclear pleomorphism and numerous abnormal mitotic figures. In addition, histologically malignant glandular structures lined by simple nonciliated columnar cells with goblet cells were found clustered in the center of the tumor. Examination of the swollen peripheral nerve trunk revealed the presence of a plexiform neurofibroma. The spindle cells were positive for S100. The glands were negative for S100 but positive for keratin, epithelial membrane antigen, and neuroendocrine markers (somatostatin, chromogranin, Leu-7, and calcitonin). This patient was subsequently diagnosed as having von Recklinghausen disease and died of tumor metastasis to the lungs 34 months after the presentation. To our knowledge, only 3 similar cases have been previously described in the literature. Topics: Adult; Biomarkers; Carcinoembryonic Antigen; Cell Nucleus; Epithelial Cells; Fatal Outcome; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mitosis; Mucin-1; Nerve Sheath Neoplasms; Neurofibromatosis 1; S100 Proteins; Skin Neoplasms | 2000 |
Basal cell carcinoma with tumor epithelial and stromal giant cells: a variant of pleomorphic basal cell carcinoma.
A case of basal cell carcinoma with giant cells of the central epithelial and surrounding stromal components is presented. The lesion was an 8-mm dome-shaped papule on the ear of a 66-year-old man. The giant cells of the epithelial component shared the immunophenotype of the more typical cells of the basal cell carcinoma (keratin, smooth muscle actin, and bcl-2 positive), whereas the stromal giant cells were positive only for bcl-2. This case represents a peculiar variant of pleomorphic basal cell carcinoma, the significance of which is unknown. Topics: Actins; Aged; Carcinoma, Basal Cell; Epithelial Cells; Female; Giant Cells; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Muscle, Smooth; Proto-Oncogene Proteins c-bcl-2; Skin Neoplasms; Stromal Cells | 1999 |
Association of primary intracranial meningioma and cutaneous meningioma of external auditory canal: a case report and review of the literature.
A cutaneous meningioma of the external auditory canal occurred in a 48-year-old Filipino woman who had undergone subtotal resection of a dural-based intracranial meningioma at the ipsilateral cerebellopontine angle 36 months previously. Radiologic findings demonstrated a recurrence of intracranial meningioma with surface erosion and heterogeneous densities of the mastoid bone, without extension to the area of the external auditory canal. Meningioma in the external ear canal is extremely rare. To our knowledge, there have been only two previously reported cases, both without intracranial lesion. In this case, the auditory canal lesion may represent either an ectopic meningioma arising from an arachnoid cell rest or an occult direct extension from intracranial menigioma. Topics: Actins; Brain Neoplasms; Chromogranins; Ear Canal; Female; Humans; Immunohistochemistry; Keratins; Meningioma; Middle Aged; Mucin-1; Neoplasms, Unknown Primary; Skin Neoplasms; Synaptophysin; Tomography, X-Ray Computed | 1998 |
Atypical mixed tumor of the skin: histologic, immunohistochemical, and ultrastructural features in three cases and a review of the criteria for malignancy.
Three cases of cutaneous mixed tumor with atypical features are described. These biphasic tumors comprise cords and nests of often plasmacytoid cells with areas of tubule formation, set in a chondroid stroma. The tumor cells show immunohistochemical positivity for both CAM 5.2 and S-100 and ultrastructural features of myoepithelium. The atypical histological features of an infiltrative margin, satellite tumor nodules, and tumor necrosis, which were present in these cases, have been described in malignant chondroid syringoma; however, a review of the small number of previous case reports demonstrates that histological appearances did not always correspond with apparent malignant potential in this tumor. The term atypical mixed tumor is recommended for tumors in which there are histological features of malignancy, especially local invasion, without proven metastases. Complete excision of the tumor and careful follow-up are advised, as at present the malignant potential of these tumors cannot be reliably predicted from their histological appearance. Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Keratins; Male; Microscopy, Electron; Radiography; S100 Proteins; Skin Neoplasms; Sweat Gland Neoplasms | 1998 |
Cutaneous parachordoma. A light microscopic and immunohistochemical report of two cases and review of the literature.
Parachordomas are rare cutaneous tumors that show virtually identical histologic findings to chordomas. Therefore, the major differential diagnosis in a case of parchordoma is metastatic chordoma. Parachordomas are benign neoplasms and most often develop on the extremities adjacent to tendons, synovium or osseous structures, as opposed to chordomas, which are malignant tumors located along the craniospinal axis. While recurrences may occur in cases of parachordoma, metastases have not been reported. In this report, two cases of parachordomas are reported and the literature reviewed. By light microscopy, parachordomas show eosinophilic bands of fibrous tissue separating lobules of cells with variably vacuolated cytoplasm (physaliphorous cells) admixed with more epithelioid cells in a myxoid stroma. Parachordomas and chordomas share immunohistochemical and ultrastructural features. Both stain with S-100 protein and vimentin, and ultrastructurally both demonstrate cytoplasmic vacuoles, intermediate filaments, pinocytotic vesicles, celljunctions, and cytoplasmic membranes with microvillous processes. Chordomas more frequently express cytokeratin (98% vs. 66% in parachordomas) and epithelial membrane antigen (90% vs. 20% in parachordomas) and chordomas have a larger number of rough endoplasmic reticulum-mitochondrial complexes. Thus, positive staining with epithelial membrane antigen and the identification of a large number of rough endoplasmic reticulum-mitochondrial complexes are suggestive of metastatic chordoma. However, the definitive distinction remains a clinical one after appropriate radiologic studies of the skull and spinal chord. Topics: Adolescent; Adult; Chordoma; Extremities; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Skin Neoplasms; Vimentin | 1998 |
Malicious masquerade: myxoid melanoma.
The morphological spectrum of malignant melanoma is broad. Unusual stromal changes can distract pathologists from the correct diagnosis. Fibroblastic, chondroid, osteoid, and myxoid stroma have been documented in melanomas. Myxoid melanoma is problematic--introducing carcinomas and soft tissue sarcomas into the differential diagnosis. This review examines the clinicopathologic aspects of myxoid malignant melanoma, with emphasis on its differential diagnosis. Topics: Adult; Aged; Diagnosis, Differential; Female; Humans; Keratins; Male; Melanins; Melanoma; Middle Aged; Mucins; S100 Proteins; Skin; Skin Neoplasms; Stromal Cells | 1998 |
The genetics of human skin diseases.
Molecular genetic analyses during the past half-decade have brought unexpected insights into the molecular defects underlying a wide variety of abnormal skin phenotypes. Highlights of the efforts in the past year include the identification of mutations in an epidermal transglutaminase gene in lamellar ichthyosis as well as mutations in an additional five keratin genes causing four different abnormal phenotypes, and mutations in beta 4 integrin and bullous pemphigoid antigen 2 genes in junctional epidermolysis bullosa and in the p16NK-4a gene in 50% of kindreds with familial melanoma. Topics: Epidermolysis Bullosa, Junctional; Humans; Ichthyosis, Lamellar; Keratins; Melanoma; Skin Diseases; Skin Neoplasms | 1996 |
[Merkel cell tumor of the hand in a 104-year-old patient. Case report with review of the literature].
Merkel cell tumors represent a rare subepidermal tumor of the skin. Despite the high tumor-mitosis-rate, the survival rate is rather high. This characterizes the biologic behavior of these tumors. We report on a 104-year-old female patient who presented with a histologically proven Merkel cell tumor of the finger existing over a period of more than 15 years. Based on our case report, the specific behavior of these tumors is documented. The pertinent literature is discussed. Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Merkel Cell; Chromogranins; Female; Fingers; Humans; Keratins; Phosphopyruvate Hydratase; Skin; Skin Neoplasms | 1996 |
Carcinosarcoma of the skin. Case report and literature review.
A case of carcinosarcoma arising in the skin of the left arm of a 69-year-old woman is reported with a review of the literature. The tumor was composed of low-differentiated squamous cell carcinoma, which was intermingled with a pleomorphic sarcoma. The carcinomatous component had keratin and lacked vimentin, whereas the phenotype of the sarcomatous portion was the reverse. The former presented additionally focal expression of S-100 protein, which was lacking in other portions of the carcinoma. The phenotypic data, supplemented by p53 immunostaining, which was present in both components, suggest their common origin in this tumor. Topics: Aged; Arm; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Nucleus; Chromatin; Coloring Agents; Epithelium; Female; Humans; Keratins; Mitosis; Organelles; Phenotype; S100 Proteins; Sarcoma; Skin Neoplasms; Tumor Suppressor Protein p53; Vimentin | 1996 |
Differentiation and tumor progression.
Clinical and experimental experience indicate that differentiation and malignancy are inversely correlated. However, more recent experimental studies using mouse and human keratinocyte systems have demonstrated that complete or even substantial loss in overall epithelial differentiation is not a prerequisite for malignant growth of cancer cells. Major defects in differentiation are also not a prerequisite for premalignant stages, in particular for cell immortalization, which is considered an early and essential step in the transformation process. Moreover, progressive dedifferentiation, often associated with advanced tumor stages, is also found in immortalized cell lines which are, however, nontumorigenic. On the other hand, malignant cell lines may have maintained a high degree of their normal differentiation program and sensitivity to differentiation modulators. However, to date no transformed keratinocyte cell lines with completely normal differentiation have been observed. Since epidermal keratinization is a very complex process involving many different parameters and is fully expressed only under in vivo conditions, an exact and quantitative comparison of such ill-defined phenomena (differentiation and malignancy) is still problematic. Obviously, both phenomena are under separate control and not causally linked. Nevertheless, a better understanding of factors and mechanisms regulating differentiation and of their disturbance in carcinogenesis would offer new possibilities to design novel tumor therapeutic strategies in the field of differentiation therapy. Topics: Biomarkers; Carcinoma, Squamous Cell; Cell Differentiation; Cell Survival; Cell Transformation, Neoplastic; Disease Progression; Epidermal Cells; Epithelial Cells; Humans; Keratins; Neoplasm Proteins; Neoplasms; Protein Precursors; Skin Neoplasms; Tumor Cells, Cultured | 1995 |
Carcinosarcoma of skin.
Topics: Aged; Aged, 80 and over; Biopsy; Carcinosarcoma; Ear, External; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Skin Neoplasms; Vimentin | 1995 |
Keratins and the skin.
Keratins are the major structural proteins of the vertebrate epidermis and its appendages, constituting up to 85% of a fully differentiated keratinocyte. Together with actin microfilaments and microtubules, keratin filaments make up the cytoskeletons of vertebrate epithelial cells. Traced as far back in the evolutionary kingdom as mollusks, keratins belong to the superfamily of intermediate filament (IF) proteins that form alpha-helical coiled-coil dimers which associate laterally and end-to-end to form 10-nm diameter filaments. The evolutionary transition between organisms bearing an exoskeleton and those with an endoskeleton seemed to cause considerable change in keratin. Keratins expanded from a single gene to a multigene family. Of the approximately 60 IF genes in the human genome, half encode keratins, and at least 18 of these are expressed in skin. Vertebrate keratins are subdivided into two sequence types (I and II) that are typically coexpressed as specific pairs with complex expression patterns. The filament-forming capacity of a pair is dependent upon its intrinsic ability to self-assemble into coiled-coil heterodimers, a feature not required of the invertebrate keratins (Weber et al 1988). Approximately 20,000 heterodimers of type I and type II keratins assemble into an IF. Mutations that perturb keratin filament assembly in vitro can cause blistering human skin disorders in vivo. From studies of these diseases, an important function of keratins has been unraveled. These filaments impart mechanical strength to a keratinocyte, without which the cell becomes fragile and prone to rupturing upon physical stress. In this review, studies on the pattern of expression, structure, and function of skin keratins are summarized, and new insights into the functions of these proteins and their involvement in human disease are postulated. Topics: Amino Acid Sequence; Animals; Base Sequence; Embryo, Mammalian; Embryo, Nonmammalian; Epidermolysis Bullosa Simplex; Gene Expression Regulation; Hair; Humans; Hyperkeratosis, Epidermolytic; Keratins; Mammals; Molecular Sequence Data; Multigene Family; Nevus; Oligodeoxyribonucleotides; Point Mutation; Protein Structure, Secondary; Skin; Skin Diseases; Skin Neoplasms; Skin Physiological Phenomena; Vertebrates | 1995 |
Epithelioid hemangioendothelioma with multiple site involvement. Literature review and observations.
This report is a case of epithelioid hemangioendothelioma presenting as multiple lytic lesions of the ilium with radiographic findings of diffuse, bilateral lung involvement and biopsy-proven scalp involvement. Histologically, the tumor within bone and skin exhibited cords and nests of plump, epithelioid-appearing cells exhibiting rudimentary vascular differentiation within a myxohyaline stroma. Aggressive histologic features were not present. Immunohistochemical reactivity for Factor VIII-related antigen, Q-bend 10 (CD34), and cytokeratin were demonstrated. Ultrastructural studies revealed abundant intermediate cytoplasmic filaments, pinocytotic vacuoles, and Weibel-Palade bodies. The concurrent bone, skin, and lung involvement, low-grade histologic type, and female sex of the patient aroused speculation about the role of hormones in the development and possible treatment of the tumor, but estrogen and progesterone receptors were not detected. Despite intense combination chemotherapy, the patient died of widely metastatic disease. This report demonstrates the aggressive potential of histologically low-grade epithelioid hemangioendothelioma and the need for a thorough evaluation for metastases. Topics: Adult; Antigens, CD; Antigens, CD34; Female; Hemangioendothelioma, Epithelioid; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Neoplasms, Second Primary; Receptors, Estrogen; Receptors, Progesterone; Skin Neoplasms; Tomography, X-Ray Computed; von Willebrand Factor | 1994 |
Cytokeratin subtyping in normal and neoplastic epithelium: basic principles and diagnostic applications.
Topics: Adult; Digestive System Neoplasms; Endocrine Gland Neoplasms; Epithelium; Female; Humans; Keratins; Lung Neoplasms; Male; Neoplasms; Precancerous Conditions; Skin Neoplasms; Urogenital Neoplasms | 1994 |
[Positive cytokeratin results in malignant melanoma. Pitfall in differential immunohistologic diagnosis of occult neoplasms].
Immunohistology was performed on 84 paraffin-embedded surgical specimens of malignant melanomas (MM) from a total of 74 patients. The series consisted of 62 cutaneous primary tumors and 22 (partly selected) secondary manifestations (9 cutaneous recurrences and 13 metastases). In 4 patients with lymph node MM infiltrates, clinical investigations failed to identify a cutaneous primary tumor. In the primary and secondary manifestations respectively, the following proportions of immunohistologically positive cases were recorded: vimentin 100% each, S100-protein 95% each, NSE 87%/77%, HMB45 97%/64%, NKI/C3 97%/95%, cytokeratins (CK) (antibodies KL1, CAM5.2 and 35 beta H11) 0%/23%. Four of the 5 CK-positive lesions belonged to 3 patients in whom MM had occurred at first or exclusively as a lymph node infiltration. These findings confirm the results of other authors who report that positive staining results for CK can be expected in paraffin sections of secondary manifestations of MM in up to 10% of cases in large, nonselected series. This phenomenon appears, however, to be rare in primary cutaneous MM. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Unknown Primary; Skin; Skin Neoplasms | 1994 |
Gastric carcinoma metastatic to the site of a congenital melanocytic nevus.
Cutaneous metastasis from gastric carcinoma is uncommon. We describe a patient with a metastasis from gastric carcinoma to a congenital melanocytic nevus. The diagnosis was confirmed by positive immunohistochemical staining for cytokeratin 20 and lack of cytokeratin 7. Topics: Carcinoma; Collagen; Cytoplasm; Female; Hair; Humans; Keratins; Melanocytes; Middle Aged; Neoplasms, Multiple Primary; Nevus, Pigmented; S100 Proteins; Skin Neoplasms; Stomach Neoplasms; Sweat Glands; Vimentin | 1993 |
Cutaneous cylindroma with malignant transformation.
Malignant cutaneous cylindroma is a rare tumor. It has been described in 26 cases, both in the solitary form and in the autosomal dominant inherited multiple tumor form. The authors present two new cases that occurred in one family with a history of multiple cylindromas.. Clinical and histopathologic data of both tumors were compared with those of 26 other cases in the literature. Immunohistochemical examinations were performed.. The malignant tumors were distinguished from the benign lesions by rapid growth, long-standing ulceration, or bleeding. Histopathologic examination showed a well-differentiated carcinoma in one patient and a poorly differentiated tumor in the other. In the latter, lymph node metastasis developed, and the patient died 2.5 years later. Histopathologic criteria of malignancy included cell pleomorphism, frequent mitoses and loss of jigsaw pattern, peripheral palisading, hyaline sheaths, and dual cell population.. These observations are in accord with those in the literature. Malignant cutaneous cylindroma developed more often in the multiple tumor form than in the single tumor form. Malignant cylindroma is an aggressive carcinoma with a tendency to local destructive growth and metastases. Topics: Aged; Antigens, Neoplasm; Carcinoma; Carcinoma, Adenoid Cystic; Cell Transformation, Neoplastic; Cytoplasm; Female; Humans; Hyalin; Keratins; Lymphatic Metastasis; Male; Membrane Glycoproteins; Mucin-1; S100 Proteins; Skin Neoplasms | 1993 |
Keratinocyte alterations in skin tumour development.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Keratinocytes; Keratins; Reference Values; Skin Neoplasms | 1993 |
[Cytokeratins. Markers of epithelial differentiation].
Topics: Biomarkers, Tumor; Cell Differentiation; Humans; Keratins; Microscopy, Electron; Skin; Skin Neoplasms | 1993 |
Transgenic models of skin diseases.
Transgenic animals have greatly enhanced our understanding of the contribution of various structural and regulatory components to epidermal biology. The expression of mutant versions of these components in the epidermis of transgenic mice has generated animal models of specific human skin diseases.. The expression of mutant keratin genes has produced animal models of epidermolysis bullosa simplex and epidermolytic hyperkeratosis and, in doing so, has focused attention on the genetics of keratins in these and other skin disorders. Similarly, the generation of mice overexpressing growth factors and/or oncogenes, exclusively in the epidermis, has identified the role of these factors in normal skin and produced models of disease states where the regulation of these factors is perturbed.. These models of keratin disorders and other diseases not only enable the determination of the cause of these disorders, but also allow evaluation of novel therapeutic techniques for the amelioration of these skin diseases. Topics: Animals; Animals, Newborn; Epidermal Growth Factor; Gene Expression; Genes, Dominant; Genes, fos; Genes, ras; Humans; Keratins; Mice; Mice, Transgenic; Models, Biological; Mutation; Phenotype; Skin; Skin Diseases; Skin Neoplasms; Transforming Growth Factor alpha; Transforming Growth Factor beta | 1993 |
[Expression of cytokeratins during embryogenesis and in pathologic epithelia].
Epithelial cell intermediate filaments, or cytokeratins, are excellent markers for cell differentiation. During embryogenesis, cytokeratins specific of a stage of differentiation step always become detectable before corresponding morphologic changes: for instance, cytokeratins 5 and 14 are found around the eight week, shortly before stratification of the epithelium occurs, and cytokeratins 1 and 10 are produced before morphologic evidence of keratinization becomes detectable. Among potential diagnostic applications, analysis of cytokeratin patterns of epidermal cells desquamated in the amniotic fluid may provide earlier and less invasive diagnosis than fetoscopic biopsies. Similarly, a review of cytokeratins expressed in a variety of epithelial diseases (involving the epidermis, digestive tract, respiratory tract, urogenital tract, or breast) demonstrated persistence of the original tissue pattern in some instances (this was the case for the majority of simple epithelia) but not in others (complex epithelia). This suggests that cytokeratins may prove valuable as markers for specific tumor stages or types and may provide earlier information than morphologic studies. Topics: Breast Neoplasms; Digestive System Neoplasms; Epidermis; Female; Genital Neoplasms, Female; Genital Neoplasms, Male; Humans; Keratins; Male; Psoriasis; Skin Neoplasms | 1992 |
[Cytokeratins--survey of incidence in normal and diseased skin. II. Cytokeratin expression in diseased skin].
The distribution patterns of cytokeratins demonstrated by different authors in benign and malignant tumours of the skin are presented and the resulting possibilities for histological differentiation are discussed. The monoclonal antibody A53-B/A2 made in GDR may be useful in the diagnosis of Merkel cell tumours or of the extramammary Morbus Paget. -For different dermatoses, especially some disease with abnormal types of keratinization, the expressed polypeptides are described. Topics: Biomarkers, Tumor; Diagnosis, Differential; Humans; Keratins; Peptides; Skin; Skin Diseases; Skin Neoplasms | 1990 |
Vulvar epithelioid sarcoma metastatic to the scalp. A case report and review of the literature.
We report a case of vulvar epithelioid sarcoma with metastases to the scalp, an inguinal lymph node, lungs, liver, and kidneys. Epithelioid sarcoma typically involves the extremities of young men and may be confused histologically with various benign and malignant processes. Only five cases of primary vulvar epithelioid sarcoma have been previously reported. The present case represents the first report of cutaneous metastases from this primary site. We also review the literature pertaining to the clinical, pathologic, and immunohistochemical features of this rare tumor. Topics: Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Sarcoma; Scalp; Skin Neoplasms; Vulvar Neoplasms | 1990 |
The premalignant nature of mouse skin papillomas: histopathologic, cytogenetic, and biochemical evidence.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Chromosome Aberrations; Chromosome Disorders; Karyotyping; Keratins; Mice; Papilloma; Precancerous Conditions; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors | 1989 |
Keratin expression in mouse epidermal tumors.
Topics: Animals; Carcinoma; Cell Differentiation; DNA Probes; Keratins; Mice; Papilloma; Precancerous Conditions; Skin Neoplasms | 1989 |
Malignant dermal cylindromas. Do they exist? A morphological and immunohistochemical study and review of the literature.
Malignant dermal cylindromas are very rare. We present a case of multiple cylindromas of the scalp with metastasis to a cervical lymph node. The morphology of the tumour was unusual in that it contained eccrine spiradenoma-like areas and foci of squamous differentiation with keratin formation. The immunohistochemical phenotype of the eccrine spiradenoma-like areas and the metastatic tumour was similar, but different from the areas of typical cylindroma. Although alleged "malignant" cylindromas have been reported, none have been described to have metastasized, whereas metastatic eccrine spiradenoma is well-documented. We reiterate that overlaps between dermal cylindroma and eccrine spiradenoma are more common than has been documented. In the rare event of metastases, it is the eccrine spiradenomatous component that is metastatic. We contend that there is no evidence that pure dermal cylindromas have metastasized. Topics: Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Scalp Dermatoses; Skin Neoplasms; Staining and Labeling | 1989 |
Retinoids and the epidermis.
Topics: Animals; Epidermis; Humans; Keratins; Psoriasis; Reference Values; Retinoids; Skin Neoplasms | 1988 |
Aberrant differentiation in mouse skin carcinogenesis.
Topics: Animals; Calcium; Cell Differentiation; Cell Transformation, Neoplastic; Keratins; Mice; Neoplastic Stem Cells; Skin Neoplasms | 1988 |
Desmosomal proteins: new markers for identification and classification of tumors.
Topics: Adenocarcinoma; Adenoma, Islet Cell; Animals; Antibodies, Monoclonal; Breast Neoplasms; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cytoskeletal Proteins; Desmoplakins; Desmosomes; Electrophoresis, Polyacrylamide Gel; Granulosa Cell Tumor; Humans; Immunosorbent Techniques; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Kidney Neoplasms; Lung Neoplasms; Melanoma; Membrane Proteins; Meningioma; Mesothelioma; Microscopy, Electron; Microscopy, Fluorescence; Neoplasms; Neurosecretory Systems; Skin Neoplasms | 1986 |
Immunoperoxidase techniques. II. Application to cutaneous neoplasms.
Topics: Adenocarcinoma; Carcinoma; Diagnosis, Differential; Endocrine System Diseases; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Melanoma; Neoplasm Invasiveness; Neoplasms, Germ Cell and Embryonal; Skin Neoplasms; Sweat Gland Neoplasms | 1986 |
Defective responses of transformed keratinocytes to terminal differentiation stimuli. Their role in epidermal tumour promotion by phorbol esters and by deep skin wounding.
Epidermal tumourigenesis can be achieved in rodents by the application of a single subthreshold dose of a carcinogen (initiation) followed by repeated applications of a tumour promoter such as 12-0-tetradecanoyl phorbol, 13-acetate (TPA). TPA induces terminal differentiation in the majority of epidermal keratinocytes in vitro. However, transformed keratinocytes respond weakly to this terminal differentiation signal, and it is suggested that this property allows initiated cells and their progeny to obtain a selective advantage over their normal counterparts during promotion of papilloma formation by TPA. New data are reviewed which suggest that a putative wound hormone TGF-beta has similar differential effects on normal and transformed epithelial cells to those of TPA. It is proposed that the release of TGF-beta from platelets following deep skin wounding may be an explanation as to why wounding is a promoting stimulus but milder forms of epidermal injury are not. Weakly promoting hyperplasiogenic agents are also discussed within the context of a selection theory of tumour promotion. Topics: Animals; Carcinogens; Cell Differentiation; Cell Transformation, Neoplastic; Epidermis; In Vitro Techniques; Keratins; Mice; Mitosis; Oncogenes; Papilloma; Peptides; Phenotype; Phorbols; Protein Kinase C; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transforming Growth Factors | 1985 |
The nature and significance of differential keratin gene expression.
Topics: Amino Acid Sequence; Epidermis; Gene Expression Regulation; Humans; Intermediate Filament Proteins; Keratins; Skin Neoplasms | 1985 |
Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms.
Topics: Animals; Carcinoma; Cytoplasm; Digestive System; Embryonic and Fetal Development; Epidermal Cells; Female; Humans; Hyperplasia; Keratins; Male; Melanocytes; Neuroblastoma; Neurosecretory Systems; Rats; Skin; Skin Neoplasms | 1985 |
Retinoids: a review.
The retinoids are synthetic derivatives of vitamin A. Isotretinoin (13-cis-retinoic acid) is now being widely used in the United States for severe acne and etretinate is available in Europe and other countries for psoriasis. These drugs are also effective for a number of other skin diseases. This is an attempt to review basic knowledge of retinoids with which the practicing dermatologist should be familiar, to review the current status of studies, and to speculate on the present and future roles of these drugs in dermatology. Topics: Acne Vulgaris; Etretinate; Humans; Inflammation; Isotretinoin; Keratins; Psoriasis; Retinoids; Sebum; Skin Diseases; Skin Neoplasms; Sweat Gland Diseases; Tretinoin; Vitamin A | 1984 |
Dermatologic birth defects and congenital skin disease.
Topics: Alopecia Areata; Child; Collagen Diseases; DNA; Genetic Counseling; Humans; Keratins; Male; Nevus; Pharmaceutical Preparations; Pharmacogenetics; Research; Skin Abnormalities; Skin Diseases; Skin Diseases, Vesiculobullous; Skin Neoplasms; Syndrome | 1984 |
Immunohistochemistry of adnexal neoplasms.
Topics: Animals; Antibodies, Monoclonal; Carcinoembryonic Antigen; Female; Goats; Humans; Immunoenzyme Techniques; Keratins; Mice; Pregnancy; Protein Precursors; Rabbits; S100 Proteins; Skin Diseases; Skin Neoplasms | 1984 |
Flow cytometry of keratinocytes.
A prerequisite for using flow cytometry (FCM) is the availability of isolated single cells. Procedures for separation and isolation of keratinocytes from animals and man are available, and the resulting single cell suspensions have been subjected to FCM measurements. The major advantage of the method is the accuracy and speed with which a variety of cellular constituents can be quantified. FCM of keratinocytes has, hitherto, been mainly confined to measurements of nuclear DNA for estimation of cell-cycle distributions and for ploidy studies. In mouse epidermis, cell-cycle distributions were estimated from sequentially obtained DNA histograms and evaluated with other cell kinetic measurements, resulting in new information about epidermal cell-cycle progression, not achievable by any of the methods alone. The best way, therefore, to increase our knowledge of keratinocyte proliferation, is the combined use of DNA FCM and other cell kinetic methods. DNA FCM has also been applied to healthy and diseased human epidermis, and may add valuable information to the classification of skin disease in selected cases. It is believed that further progress in the characterization of keratinocyte growth and development will depend on parameters other than DNA alone. Topics: Animals; Cell Cycle; Cell Separation; Circadian Rhythm; Cricetinae; DNA; Epidermal Cells; Epidermis; Epithelium; Flow Cytometry; Humans; In Vitro Techniques; Keratins; Mice; Mice, Hairless; RNA; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1983 |
Interaction of T cells with the epidermis.
Topics: Animals; Cell Differentiation; DNA Nucleotidylexotransferase; Guinea Pigs; Humans; Keratins; Lymphoma; Mice; Mice, Inbred C3H; Mice, Nude; Skin; Skin Neoplasms; T-Lymphocytes | 1982 |
Advances in genetics in dermatology.
Topics: Acrodermatitis; Amino Acid Metabolism, Inborn Errors; Basal Cell Nevus Syndrome; Epidermolysis Bullosa; Hair Diseases; Humans; Ichthyosis; Keratins; Keratosis; Neurofibromatosis 1; Psoriasis; Refsum Disease; Skin; Skin Diseases; Skin Neoplasms; Tuberous Sclerosis; Tyrosine; Warts; Xeroderma Pigmentosum | 1982 |
Enzyme of keratinization.
Topics: Animals; Carboxy-Lyases; Deoxyribonucleases; Estriol; Fetus; gamma-Glutamyltransferase; Hair; Humans; Ichthyosis; Keratins; Male; Ornithine Decarboxylase; Rats; Skin; Skin Neoplasms; Sulfatases | 1981 |
Carcinoma (epithelioma) cuniculatum: a clinico-pathological study of nineteen cases and review of the literature.
Nineteen patients with carcinoma cuniculatum are presented. Of these, 17 were male and two were female. The age range was from 26 to 73 years with a mean of approximately 54 years. Sixteen tumours were located on the foot, the other three were situated on the knee, wrist and finger respectively. The pathological features of carcinoma cuniculatum are described and the aetiology of the tumour is discussed. Topics: Adult; Aged; Carcinoma, Squamous Cell; Cytoplasmic Granules; Female; Foot Diseases; Humans; Inflammation; Keratins; Male; Middle Aged; Mitosis; Neoplasm Invasiveness; Skin Neoplasms | 1981 |
[Cutaneous cysts and cystic skin tumors].
The nomenclature and pathogenesis of cutaneous cysts is discussed along the lines of their pathological properties. On the basis of histological and experimental evidence it is concluded that most cysts represent benign neoplasms derived from pluripotential cells. Topics: Adenoma, Sweat Gland; Cysts; Dermoid Cyst; Epidermal Cyst; Hamartoma; Humans; Keratins; Pilonidal Sinus; Skin Diseases; Skin Neoplasms; Sweat Gland Diseases | 1979 |
Homeostatic regulation of epidermal cell proliferation.
Topics: Animals; Carcinogens; Cell Differentiation; Cell Division; Cell Survival; Cell Transformation, Neoplastic; Epidermal Cells; Epidermis; Growth Inhibitors; Hematopoietic Stem Cells; Homeostasis; Hyperplasia; Keratins; Metaplasia; Mice; Mitogens; Models, Biological; Phorbol Esters; Skin Neoplasms; Wound Healing | 1978 |
Epidermolytic hyperkeratosis and focal acantholytic dyskeratosis: a unified concept.
Topics: Cell Membrane; Cytoplasmic Granules; Humans; Ichthyosis; Keratins; Nevus; Organoids; Skin Diseases, Vesiculobullous; Skin Neoplasms; Vacuoles | 1978 |
Lysosomes and the skin.
Topics: Acid Phosphatase; Animals; Cathepsins; Chediak-Higashi Syndrome; Fabry Disease; Inflammation; Keratins; Langerhans Cells; Light; Lysosomes; Melanophores; Microscopy, Electron; Peptide Hydrolases; Phagocytosis; Pigmentation; Protease Inhibitors; Sebaceous Glands; Skin; Skin Diseases; Skin Neoplasms; Vitamin A | 1975 |
The artificial induction of coat colour--a final report and a review.
Topics: Animals; Flavins; Hair; Humans; Keratins; Mutation; Neoplasms, Experimental; Pigmentation; Pigments, Biological; Rats; Skin Neoplasms | 1973 |
Trials
3 trial(s) available for bromochloroacetic-acid and Skin-Neoplasms
Article | Year |
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Expression of CK7, Cam 5.2 and Ber-Ep4 in cutaneous squamous cell carcinoma.
Cytokeratin 7 (CK7) and Cam 5.2 are often used to differentiate extramammary Paget's disease (EPD) from squamous cell carcinoma (SCC) in situ because they are generally considered to be expressed in the former but not in the latter. However, we have encountered CK7+ and Cam 5.2+ SCCs.. We evaluated CK7, Cam 5.2 and Ber-Ep4 expression in SCC and EPD.. We found significant CK7 and Cam 5.2 positivity in SCCs, particularly in those with a pagetoid pattern. Only one case expressed Ber-Ep4.. We conclude that CK7 and Cam 5.2 expression may occur in SCC. A panel including Ber-Ep4 is advisable for immunohistochemical differentiation of EPD from SCC. Topics: Biomarkers; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Gene Expression Regulation; Humans; Keratin-7; Keratins; Male; Neoplasm Proteins; Skin Neoplasms | 2013 |
Selective transitional zone sampling approach versus random biopsy in cases with malignant liver masses: is there any superiority?
Currently, the diagnostic sensitivity of malignant liver mass biopsies is an important problem in the definitive diagnosis. In this study, we aimed to investigate the role of selective peripheral approach to lesion biopsies for diagnostic sensitivity of liver masses.. Between June 2007 and March 2011, totally 88 patients (50 male, 38 female), referred to our Interventional Radiology Department for sonographically guided Tru-cut biopsies for liver lesions, were examined.All biopsies were performed by an experienced radiologist with an 18-gauge Tru-cut biopsy needle with a spring-loaded biopsy gun under sonographic guidance. We describe two locations (peripheral and central) for liver lesions, with the inner 2/3 part of the mass as central and the outer 1/3 part as peripheral. We obtained biopsy from both of these locations, and samples were transferred to the Pathology Department separately.. According to pathological and immunohistochemistry studies, there were 42 hepatocellular carcinomas and 46 metastases. All of the metastatic tumors were stained by cytokeratin (10 lung adenocarcinoma, 15 breast adenocarcinoma, 16 gastrointestinal tract, 4 prostate, and 1 malignant melanoma of these 46 metastases were reported as primary). According to histopathological results, diagnostic sensitivity was 97.7% in peripherally located biopsies and 86.3% in biopsies taken from the center of the masses (p=0.0063).. Selective peripheral biopsy approach in Tru-cut biopsies of liver lesions has better sensitivity rates for histopathologic diagnosis compared to the centrally located and random biopsies. Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Biopsy, Needle; Breast Neoplasms; Carcinoma, Hepatocellular; Creatine Kinase; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Humans; Keratins; Liver Cirrhosis; Liver Neoplasms; Lung Neoplasms; Male; Melanoma; Middle Aged; Prostatic Neoplasms; Sensitivity and Specificity; Skin Neoplasms | 2012 |
Clinical application of multiphoton tomography in combination with high-frequency ultrasound for evaluation of skin diseases.
The first-ever application of high-frequency ultrasound combined with multiphoton tomography (MPT) and dermoscopy in a clinical trial is reported. 47 patients with different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases, and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond laser multiphoton tomograph and (iii) dermoscopes. Dermoscopy provides two-dimensional color images of the skin surface with a magnification up to 70 x. Depending on the ultrasonic frequencies from 7.5 MHz to 100 MHz, the signal depth varies from about 1 mm to 80 mm. Vertical ultrasound wide-field images provide fast information on depth and volume of the lesion. The 100 MHz ultrasound allows imaging with resolutions down to 16 μm (axial) and 32 μm (lateral). Multiphoton tomography provides 0.36 x 0.36 x 0.001 mm³ horizontal optical sections of a particular region of interest with submicron resolution down to 200 μm tissue depth. The autofluorescence of mitochondrial coenzymes, keratin, melanin, and elastin as well as the network of collagen structures can be imaged. The combination of ultrasound and MPT opens novel synergistic possibilities in diagnostics of skin diseases with a special focus on the early detection of skin cancer as well as the evaluation of treatments. Topics: Adult; Aged; Aged, 80 and over; Coenzymes; Collagen; Elastin; Female; Fluorescence; Humans; Keratins; Lasers; Male; Melanins; Microscopy, Fluorescence, Multiphoton; Middle Aged; Skin; Skin Diseases; Skin Neoplasms; Tomography, Optical; Ultrasonics | 2010 |
Other Studies
836 other study(ies) available for bromochloroacetic-acid and Skin-Neoplasms
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Keratinic amyloid deposition in canine hair follicle tumors.
Keratinic primary localized cutaneous amyloidosis is a disease in humans; however, no similar condition has been reported in animals. This study aimed to investigate cutaneous keratinic amyloid deposition in dogs and elucidate its etiology. Canine hair follicle tumor tissues were histopathologically analyzed. Immunohistochemistry and mass spectrometry-based proteomic analyses were performed to identify precursor protein candidates. Structural prediction and in vitro fibrillization analyses were conducted to determine the amyloidogenic region and gene sequencing analysis was performed to assess mutations. Of the 266 samples, 16 had amyloid deposition. Amyloid deposits were found in the stroma of tumors and in the margins of keratin debris and around normal hair follicles. Cytokeratin 5 (CK5) was identified as a precursor protein candidate. C-terminal truncation of CK5 was observed in amyloid deposits, and the truncation sites varied depending on the deposition pattern. There was a significantly higher incidence of amyloid deposition in Shiba dogs, and CK5 amino acid polymorphisms were identified in these dogs. A part of the C-terminal region of both canine and human CK5 exhibited highly amyloidogenic properties in vitro. This study revealed the existence of cutaneous keratinic amyloid deposition in animals and identified CK5 as an amyloid precursor protein, providing novel insights into understanding the etiology of cutaneous amyloidosis. Topics: Amyloid; Amyloidosis; Animals; Dog Diseases; Dogs; Hair Follicle; Keratins; Plaque, Amyloid; Proteomics; Skin Neoplasms | 2023 |
Usefulness of SynCAM3 and cyclin D1 immunohistochemistry in distinguishing superficial CD34-positive fibroblastic tumor from its histological mimics.
Superficial CD34-positive fibroblastic tumor (SCPFT) is a fibroblastic/myofibroblastic soft tissue tumor of rarely metastasizing intermediate malignancy. Some recent studies have described a relationship between SCPFT and PRDM10-rearranged soft tissue tumor (PRT) based on SynCAM3 and PRDM10 expression on immunohistochemistry. We performed CD34, cytokeratin AE1/AE3, SynCAM3, and PRDM10 immunohistochemistry in SCPFT and its histological mimics, including myxoinflammatory fibroblastic sarcoma (MIFS), superficially localized myxofibrosarcoma (MFS), and undifferentiated pleomorphic sarcoma. We also examined cyclin D1 expression because it is expressed in MIFS and MFS. We conducted fluorescence in situ hybridization (FISH) of PRDM10 rearrangement in SCPFT cases. On immunohistochemistry, only SCPFT showed strong and diffuse SynCAM3 expression. SCPFT also exhibited strong nuclear and weak cytoplasmic cyclin D1 expression, which was similar to that observed in MIFS. Two of five SCPFT cases exhibited nuclear PRDM10 expression. FISH revealed PRDM10 split signals in 44% and 24% of tumor cells in two SCPFT cases showing nuclear PRDM10 expression on immunohistochemistry, respectively. A minority of non-SCPFT cases showed focal SynCAM3 expression, but a combination of SynCAM3 and cyclin D1 in addition to CD34 and cytokeratin AE1/AE3 may be useful for the differential diagnosis of SCPFT and its histological mimics. Topics: Biomarkers, Tumor; Cyclin D1; Fibrosarcoma; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Skin Neoplasms; Soft Tissue Neoplasms | 2023 |
Does the understanding of signalling pathways pave the way to therapies for keratinization disorders?
Topics: Humans; Ichthyosis; Keratins; Signal Transduction; Skin Neoplasms; Toll-Like Receptor 2 | 2023 |
Non-cutaneous syncytial myoepitheliomas are identical to cutaneous counterparts: a clinicopathologic study of 24 tumors occurring at diverse locations.
Cutaneous syncytial myoepithelioma (CSM) is a rare myoepithelioma variant of skin, characterized by intradermal syncytial growth of spindle cells with a distinct immunophenotype of EMA and S100 positivity and infrequent keratin expression. While CSM was first described as a cutaneous tumor, singular non-cutaneous cases have since been reported in bone. We aimed to investigate the clinicopathological features of this variant across all anatomic sites through a large multi-institutional study.. We complied a total of 24 myoepitheliomas with syncytial growth from our files. The tumors occurred in 12 male and 12 female patients (M:F = 1:1), with a median age of 31 years (range, 9-69 years). While the majority of tumors (75%, n = 18) occurred in skin, a significant subset (25%, n = 6) arose in non-cutaneous sites, including bone (n = 3), bronchus/trachea (n = 2), and interosseous membrane of tibia/fibula (n = 1). Tumor size ranged from 0.4 to 5.9 cm. Clinical follow-up (7 patients; range 14-202 months; median 56.5 months) showed a single local recurrence 8 years after incomplete skin excision but no metastases; all patients were alive at the time of last follow-up without evidence of disease. Histologically, all tumors were pink at low-power and characterized by a syncytial growth of bland ovoid, spindled, or histiocytoid cells with eosinophilic cytoplasm and prominent perivascular lymphoplasmacytic inflammation. One-third displayed adipocytic metaplasia (8/24). Rare cytologic atypia was seen but was not associated with increased mitotic activity. All tumors expressed S100, SMA, and/or EMA. Keratin expression was absent in most cases. Molecular analysis was performed in 16 cases, all showing EWSR1-rearrangments. In total, 15/15 (100%) harbored an EWSR1::PBX3 fusion, whereas 1 case EWSR1 FISH was the only molecular study performed.. Syncytial myoepithelioma is a rare but recognizable morphologic variant of myoepithelioma which may have a predilection for skin but also occurs in diverse non-cutaneous sites. Our series provides evidence supporting a reappraisal of the term "cutaneous syncytial myoepithelioma," as 25% of patients in our series presented with non-cutaneous tumors; thus, we propose the term "syncytial myoepithelioma" to aid pathologist recognition and avoidance of potentially confusing terminology when referring to non-cutaneous examples. The behavior of syncytial myoepithelioma, whether it arises in cutaneous or non-cutaneous sites, is indolent and perhaps benign with a small capacity for local recurrence. Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Child; Female; Humans; Keratins; Male; Middle Aged; Myoepithelioma; Neoplasms, Glandular and Epithelial; Skin Neoplasms; Young Adult | 2023 |
Dermoscopy of atypical pigmented lesions of the face: Variation according to facial areas.
Atypical pigmented facial lesions (aPFLs)-including lentigo maligna (LM) and lentigo maligna melanoma (LMM), solar lentigo (SL), pigmented actinic keratosis (PAK), atypical nevi (AN), seborrheic keratosis (SK) and lichen planus-like keratosis (LPLK)-can exhibit clinical and dermoscopic overlapping features. We aimed to investigate if and how 14 dermoscopic features suggestive for the aforementioned aPFLs vary according to six facial sites among 1197 aPFLs cases (excised to rule out malignancy) along with lesion and patients' metadata. According to distribution and association analysis, aPFLs on the forehead of a male patient aged > 69 years displaying the obliterated follicular openings pattern, appear to be more at risk of malignancy. Of converse, aPFLs of the orbital/cheek/nose area with evident and regular follicular openings with diameter < 10 mm in a female aged below 68 are probably benign. The obliterated follicular openings, keratin plugs, evident and regular follicular openings and target-like pattern features differed significantly among six facial areas in all aPFLs cases. Lesion of the nose may show both features suggestive of malignancy and benignity (e.g. many SL and PAK may display target-like pattern and some LM/LMM cases display keratin plugs and evident and follicular openings), making these features less specific. Topics: Dermoscopy; Diagnosis, Differential; Female; Humans; Hutchinson's Melanotic Freckle; Keratins; Keratosis, Actinic; Lentigo; Male; Pigmentation Disorders; Skin Neoplasms | 2023 |
Primary cutaneous anaplastic large-cell lymphoma with aberrant cytokeratin expression: An unusual mimicker of poorly differentiated carcinomas.
An 81-year-old male presented with a rapidly growing cheek nodule. Biopsy revealed a dermal infiltrate of large atypical cells, some exhibiting a horseshoe-shaped nucleus. Immunohistochemistry revealed positivity for CD4, CD3, CD45, and CD30 (>95%). Melanocytic markers, cytotoxic markers, CD20, CD56, ALK1, synaptophysin, CD1a, and ETS-related gene (ERG) were negative. Notably, there was weak but diffuse expression of pan-cytokeratin (AE1/AE3) and Oscar keratin. There was also a weak expression of epithelial membrane antigen (EMA). CAM 5.2, p40, and IRF4/DUSP22 rearrangement were negative. Further staging revealed skin-limited disease. A diagnosis of primary cutaneous anaplastic large-cell lymphoma (PC-ALCL) was rendered. We present a rare case of cytokeratin positive PC-ALCL, a finding never reported in the literature. Both PC-ALCL and systemic ALCL (S-ALCL) evoke a broad differential. CD45, EMA, and cytokeratin stains help differentiate from metastatic carcinomas. There have been rare prior reports of cytokeratin expression in S-ALCL, which tend to stain with an unusual cytoplasmic and membranous pattern like our case, have variable co-expression of EMA, and null T-cell phenotypes. These show the significant diagnostic challenges that can arise in differentiating ALCL from metastatic or primary skin carcinomas. Awareness, careful attention to morphology (e.g., hallmark cells), and considering routine CD30 can help lead the pathologist to the correct diagnosis. Topics: Aged, 80 and over; Humans; Keratins; Lymphoma, Large-Cell, Anaplastic; Male; Mucin-1; Skin Neoplasms | 2022 |
Cutaneous Myoepithelial Neoplasms on Acral Sites Show Distinctive and Reproducible Histopathologic and Immunohistochemical Features.
Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the extremities. Their malignant counterparts, myoepithelial carcinoma, and malignant mixed tumor are exceptionally rare in the skin, and the morphologic criteria for malignancy are only poorly defined. The aim of the present study was to characterize the clinicopathologic features of myoepithelial neoplasms presenting on acral skin. The clinical and histopathologic features of 11 tumors were recorded, and follow-up was obtained. Immunohistochemistry was performed for S100, SOX10, glial fibrillary acidic protein, keratins, epithelial membrane antigen, p63, p40, smooth muscle actin, desmin, and PLAG1. The tumors mainly affected the feet of adults (range: 26 to 78 y; median: 47 y) with a predilection for the great toe and a male predominance of 1.8:1. Most tumors (91%) displayed a lobular architecture composed of solid and nested growth of epithelioid cells with plasmacytoid features in a myxoid or angiomatous stroma. Scattered cytologic atypia and rare duct differentiation were frequently noted. Three tumors with confluent cytologic atypia, infiltrative growth, and lymphovascular invasion were classified as malignant. By immunohistochemistry, the tumors were positive for S100, SOX10, keratins AE1/AE3, CK5/6 and CK7, and PLAG1. Local recurrence and bilateral pulmonary metastasis were observed in a patient presenting with a histopathologically benign-appearing tumor. Two patients with malignant tumors experienced local recurrences, and 1 developed metastasis to soft tissue, lung, and mediastinal lymph nodes. All patients are currently alive, all but 1 with no evidence of disease after a median follow-up interval of 96 months (range: 2 to 360 mo). In conclusion, acral myoepithelial neoplasms show distinctive and reproducible histopathologic and immunohistochemical features. They are best regarded as a distinctive subset of mixed tumors with features reminiscent of their salivary gland counterparts. While most tumors pursue a benign disease course, histopathologic features appear to be a poor indicator of prognosis. Topics: Adenoma, Pleomorphic; Adult; Aged; Biomarkers, Tumor; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myoepithelioma; Skin Neoplasms | 2022 |
Recurrent YAP1::MAML2 fusions in "nodular necrotizing" variants of myxoinflammatory fibroblastic sarcoma: a comprehensive study of 7 cases.
Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue tumor with a predilection for the distal extremities and a tendency for local recurrence. Morphologically, MIFS consists of spindle and bizarre epithelioid cells resembling virocytes embedded in a fibrous to myxoid stroma with an abundant inflammatory infiltrate. Importantly, the molecular landscape of MIFS is wide and includes: VGLL3 amplification, BRAF fusion/amplification and OGA/TGFBR3 rearrangements. In this study, we describe a variant of MIFS showing a frequent nodular configuration associated with necrosis and recurrent YAP1::MAML2 fusions. The cohort consisted of 7 patients (4 females and 3 males) ranging in age from 21 to 71 years (median: 47 years). Two tumors (28%) occurred in acral locations while the remaining cases were more widely distributed (thigh, n = 2; arm, n = 1; neck; n = 1; chest-wall, n = 1). Tumor size ranged from 10 to 38 mm (median: 20 mm). Histologically, lesions frequently presented as nodules with central areas of necrosis, and were predominantly composed of sheets of epithelioid cells with large vesicular nuclei and prominent nucleoli (Reed-Sternberg-like cells or virocytes). The stroma was mostly fibrous and showed a polymorphous inflammatory infiltrate. Myxoid stromal changes were focally seen in one case, and pseudolipoblasts were absent. The immunophenotype was nonspecific, with only pan-keratin (AE1-AE3) and cyclin D1 expression in a subset of cases. RNA-Sequencing detected YAP1::MAML2 fusions in 3/7 cases; aCGH showed no significant gene copy number variations in 4 tested cases, and FISH analysis showed no VGLL3 amplification in 1 tested case. Follow-up was available for 6 cases, ranging from 7 to 63 months (median: 42 months). Local recurrence and metastasis were not seen and one tumor showed spontaneous regression following initial biopsy. In conclusion, we describe a novel variant of MIFS with distinctive clinicopathological and molecular features for which we propose the term "nodular necrotizing" MIFS. Topics: Cyclin D1; DNA Copy Number Variations; Female; Fibrosarcoma; Humans; Keratins; Male; Necrosis; Proto-Oncogene Proteins B-raf; RNA; Skin Neoplasms; Soft Tissue Neoplasms; Trans-Activators; Transcription Factors; YAP-Signaling Proteins | 2022 |
Subungual Pigmented Squamous Cell Carcinoma in a Dog.
An 11-year-old spayed female Miniature Schnauzer dog was presented with loss of a claw caused by a nail bed mass. Histopathological evaluation revealed that the mass comprised neoplastic squamous cells with abundant cytoplasmic melanin pigment. Immunohistochemically, the neoplastic cells were positive for cytokeratin and negative for vimentin and ionized calcium-binding adaptor molecule 1, supporting a diagnosis of pigmented squamous cell carcinoma. To our knowledge, this is the first report of subungual pigmented squamous cell carcinoma in animals. Topics: Animals; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Female; Keratins; Nail Diseases; Skin Diseases; Skin Neoplasms | 2022 |
Cytokeratin-Derived Amyloid Mimicking Invasive Squamous Cell Carcinoma: Overcoming a Potential Pitfall of Pan-Cytokeratin Immunohistochemistry-Assisted Mohs Micrographic Surgery.
Topics: Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Mohs Surgery; Skin Neoplasms | 2022 |
A Hybrid Epithelial to Mesenchymal Transition in Ex Vivo Cutaneous Squamous Cell Carcinoma Tissues.
While most cases of cutaneous squamous cell carcinoma (cSCC) are benign, invasive cSCC is associated with higher mortality and is often more difficult to treat. As such, understanding the factors that influence the progression of cSCC are important. Aggressive cancers metastasize through a series of evolutionary changes, collectively called the epithelial-to-mesenchymal transition (EMT). During EMT, epithelial cells transition to a highly mobile mesenchymal cell type with metastatic capacities. While changes in expression of TGF-β, ZEB1, SNAI1, MMPs, vimentin, and E-cadherin are hallmarks of an EMT process occurring within cancer cells, including cSCC cells, EMT within tissues is not an "all or none" process. Using patient-derived cSCC and adjacent normal tissues, we show that cells within individual cSCC tumors are undergoing a hybrid EMT process, where there is variation in expression of EMT markers by cells within a tumor mass that may be facilitating invasion. Interestingly, cells along the outer edges of a tumor mass exhibit a more mesenchymal phenotype, with reduced E-cadherin, β-catenin, and cytokeratin expression and increased vimentin expression. Conversely, cells in the center of a tumor mass retain a higher expression of the epithelial markers E-cadherin and cytokeratin and little to no expression of vimentin, a mesenchymal marker. We also detected inverse expression changes in the miR-200 family and the EMT-associated transcription factors ZEB1 and SNAI1, suggesting that cSCC EMT dynamics are regulated in a miRNA-dependent manner. These novel findings in cSCC tumors provide evidence of phenotypic plasticity of the EMT process occurring within patient tissues, and extend the characterization of a hybrid EMT program occurring within a tumor mass. This hybrid EMT program may be promoting both survival and invasiveness of the tumors. A better understanding of this hybrid EMT process may influence therapeutic strategies in more invasive disease. Topics: Biomarkers, Tumor; Cadherins; Carcinoma, Squamous Cell; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Humans; Keratins; Skin Neoplasms; Vimentin | 2022 |
Cutaneous Malignant Squamomelanocytic Tumor: A Case Report of a Rare Neoplasm.
Cutaneous squamomelanocytic tumor (SMT) is an exceedingly rare cutaneous malignancy characterized by the presence of both squamous cell carcinoma and malignant melanoma within a single tumor. SMT typically presents clinically as keratotic skin papulonodules, most commonly occurring on the face, scalp, or other sun-exposed areas of middle-aged to elderly White male patients. Owing to the rare nature of this tumor, the histogenesis and prognosis remain relatively unclear. Histopathological examination of the tangential biopsy revealed an invasive cutaneous malignancy consisting of 2 distinct yet closely associated atypical cell populations: (1) a population of atypical squamoid epithelial cells arranged in cords and keratin pearls and (2) a population consisting of atypical, spindled cells with fine melanin pigment arranged in confluent sheets. Both populations of atypical cells emanated in an invasive pattern from the underside of the overlying epidermis into the deep dermis. Squamomelanocytic tumors are among the rarer types of collision tumors between 2 malignant lesions as most are basomelanocytic. For most reported SMTs, the melanoma population comprises epithelioid cell morphology, whereas our tumor is composed of spindled cell morphology. In this article, we exemplify a unique case of SMT in an 87-year-old male patient. Topics: Aged; Aged, 80 and over; Humans; Immunohistochemistry; Keratins; Male; Melanins; Melanoma; Middle Aged; Skin Neoplasms | 2022 |
Malignant Trichoblastoma with Sarcomatous Stroma in a Rabbit.
A 10-year-old female rabbit developed an unencapsulated and asymmetrical superficial dermal mass on the neck. The tumour was invasive with central ulceration and contained three different histological components, namely trichoblastomatous, basal cell carcinoma (BCC)-like and undifferentiated carcinomatous. In the trichoblastomatous component, which occupied most of the tumour, epithelial neoplastic cells formed ribbon-like cellular trabeculae with a palisaded appearance and stromal giant cells. The BCC-like component was a unique lesion composed of epithelial foci and sarcomatous stroma. The sarcomatous stroma consisted of pleomorphic mesenchymal cells with collagen fibres and frequent giant cells with one or more bizarre nuclei. In the undifferentiated carcinomatous component, neoplastic cells had a sheet-like growth pattern without trichoblastic or squamous differentiation. Immunohistochemically, neoplastic epithelial cells were positive for p63 and cytokeratin (CK) while the stromal and giant cells were immunopositive for vimentin but negative for CK and p63. This is the first report of a malignant trichoblastoma with a sarcomatous stroma in animals. Topics: Animals; Carcinoma, Basal Cell; Epithelial Cells; Female; Keratins; Rabbits; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms | 2022 |
Loss of FAM83H promotes cell migration and invasion in cutaneous squamous cell carcinoma via impaired keratin distribution.
FAM83H is essential for amelogenesis, but recent reports implicate that FAM83H is involved in the tumorigenesis. We previously clarified that TRIM29 binds to FAM83H to regulate keratin distribution and squamous cell migration. However, little is known about FAM83H in normal/malignant skin keratinocytes.. To investigate the expression of FAM83H in cutaneous squamous cell carcinoma (SCC) and its physiological function.. Immunohistochemical analysis and RT-PCR of human SCC tissues were performed. Next, we examined the effect of FAM83H knockdown/overexpression in SCC cell lines using cell proliferation, migration, and invasion assay. To investigate the molecular mechanism, immunoprecipitation of FAM83H was examined. Further, Immunofluorescence staining was performed. Finally, we examined the correlation between the expressions of FAM83H and the keratin distribution.. FAM83H expression was lower in SCC lesions than in normal epidermis and correlated with differentiation grade. The mRNA expression levels of FAM83H in SCC tumors were also lower than in normal epidermis. The knockdown of FAM83H enhanced SCC cell migration and invasion, whereas the overexpression of FAM83H led to decreases in both. Furthermore, the knockdown of FAM83H enhanced the cancer cell metastasis in vivo. FAM83H formed a complex with TRIM29 and keratins. The knockdown of FAM83H altered keratin distribution and solubility. Clinically, the loss of FAM83H correlates with an altered keratin distribution.. Our findings reveal a critical function for FAM83H in regulating keratin distribution, as well as in the migration/invasion of cutaneous SCC, suggesting that FAM83H could be a crucial molecule in the tumorigenesis of cutaneous SCC. Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; DNA-Binding Proteins; Epidermis; Female; Gene Expression; Gene Knockdown Techniques; Humans; Keratinocytes; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Proteins; RNA, Messenger; Skin Neoplasms; Transcription Factors | 2021 |
Dermal and Intraepidermal Merkel Cell Carcinoma With Squamous Cell Carcinoma: A Report of a Rare Case With Special Reference to the Touch Dome.
In skin containing hair follicles, specialized epithelial structures known as "touch domes (TDs)" are located where the Merkel cells are clustered. We explored the histogenetic relationship between intraepidermal and dermal Merkel cell carcinomas (MCCs) and investigated which transformed progenitor cells can develop into intraepidermal MCC. We encountered an association between an extremely rare case of dermal and intraepidermal MCC with squamous cell carcinoma, which was examined using standard immunohistochemical methods with various epithelial, neuroendocrine, and TD markers including several immunohistochemical markers. Differential expression levels of CK20 and CD56 were found between intraepidermal and dermal MCCs, indicating molecularly distinct MCC populations. CK15 and CK17, expressed in TDs, were partially expressed in the intraepidermal neuroendocrine component at the tumor periphery in intraepidermal MCC with squamous cell carcinoma. These differences may suggest that the origin of dermal and intraepidermal MCCs is different under pathological conditions. We hypothesize that intraepidermal MCC is derived from tissue-specific stem cells localized within TDs. Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Cell Lineage; Female; Humans; Immunohistochemistry; Keratins; Merkel Cells; Neoplasms, Complex and Mixed; Neoplastic Stem Cells; Skin Neoplasms | 2021 |
Low recurrence rates for challenging squamous cell carcinomas using Mohs micrographic surgery with AE1/AE3 cytokeratin immunostaining.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Margins of Excision; Middle Aged; Mohs Surgery; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Retrospective Studies; Skin; Skin Neoplasms | 2021 |
Histomorphological and immunophenotypical spectrum of cutaneous myoepitheliomas: A series of 35 cases.
Myoepithelial tumors comprise a group of mesenchymal lesions that show heterogeneous histomorphological features, including dual epithelial, neural, and myoid differentiation. Cutaneous myoepithelioma is a rare neoplasm that is composed primarily of myoepithelial cells and represents one end of a histopathological spectrum of cutaneous myoepithelial neoplasms including chondroid syringoma and myoepithelial carcinoma. These tumors display a wide histopathological spectrum and immunophenotypical profile often showing epithelial and myoepithelial differentiation. In this series, we studied 35 cases of cutaneous myoepitheliomas. Our cases highlighted the broad histopathological range where most cases showed a non-infiltrative and non-encapsulated tumor exclusively located in the dermis and with no subcutaneous involvement. The majority of our cases had a solid growth pattern (syncytial pattern) and the remainder of cases had a multinodular growth pattern. The tumor cells were epithelioid in 23 cases, spindled in eight cases and there was a mixture of epithelioid and spindled cells in four cases. Mitotic figures ranged from 0 to 5 per 10 HPF. By immunohistochemistry epithelial membrane antigen (EMA) was expressed in 59% of cases S100 was positive in 88% of cases, CAM 5.2 was positive in 16% of cases, AE1/AE3 was positive in 44% of cases, p63 was positive in 17% of cases, smooth muscle actin was positive in 38% of cases, desmin was positive in 6% of cases, calponin was positive in 22% of cases, and glial fibrillary acidic protein was positive in 36% of cases. In addition, there were five cases without EMA, keratin, or p63 expression that only showed S100 expression. We describe a large series of cutaneous myoepitheliomas delineating their histomorphological spectrum and immunophenotypical profile. Awareness of some of the unusual histopathological features and the heterogeneous immunohistochemical may pose difficulties for the diagnosis. Topics: Actins; Adenoma, Pleomorphic; Adult; Anion Exchange Protein 1, Erythrocyte; Awareness; Biomarkers; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Carcinoma; Chloride-Bicarbonate Antiporters; Desmin; Diagnosis, Differential; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Male; Membrane Proteins; Microfilament Proteins; Mucin-1; Myoepithelioma; S100 Proteins; Skin Neoplasms | 2021 |
Transcript levels of keratin 1/5/6/14/15/16/17 as potential prognostic indicators in melanoma patients.
Keratins (KRTs), the intermediate filament-forming proteins of epithelial cells, are extensively used as diagnostic biomarkers in cancers and associated with tumorigenesis and metastasis in multiple cancers. However, the diverse expression patterns and prognostic values of KRTs in melanoma have yet to be elucidated. In the current study, we examined the transcriptional and clinical data of KRTs in patients with melanoma from GEO, TCGA, ONCOMINE, GEPIA, cBioPortal, TIMER and TISIDB databases. We found that the mRNA levels of KRT1/2/5/6/8/10/14/15/16/17 were significantly differential expressed between primary melanoma and metastatic melanoma. The expression levels of KRT1/2/5/6/10/14/15/16/17 were correlated with advanced tumor stage. Survival analysis revealed that the high transcription levels of KRT1/5/6/14/15/16/17 were associated with low overall survival in melanoma patients. GSEA analysis indicated that the most involved hallmarks pathways were P53 pathway, KRAS signaling, estrogen response early and estrogen response late. Furthermore, we found some correlations among the expression of KRTs and the infiltration of immune cells. Our study may provide novel insights for the selection of prognostic biomarkers for melanoma. Topics: Biomarkers, Tumor; Databases, Nucleic Acid; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Kaplan-Meier Estimate; Keratins; Melanoma; Mutation; Prognosis; Protein Interaction Maps; RNA, Messenger; Signal Transduction; Skin Neoplasms | 2021 |
Immunohistochemical expression of PAX8, PAX2, and cytokeratin in melanomas.
Deviations from the classic melanocytic immunophenotype in melanoma can present a diagnostic challenge. PAX8 and PAX2 are common markers for renal or Müllerian differentiation. While most PAX8+ or PAX2+ carcinomas are seldom confused with melanoma, some cases may show a more ambiguous immunophenotype, especially when MiTF family altered renal cell carcinoma (MiTF-RCC) is in the differential diagnosis. Neither PAX8 nor PAX2 expression has been reported in melanoma to date. We aimed to better characterize PAX8, PAX2, and cytokeratin immunoreactivity in a large series of melanomas.. Tissue microarrays consisting of 263 melanomas were immunostained for PAX8, PAX2, and cytokeratin and graded by an h-score.. PAX8 expression was seen in 7.9% of melanomas and was significantly associated with spindle cytomorphology. PAX2 was positive in one (0.4%) melanoma. Cytokeratin positivity was seen in three (1.2%) cases and was associated with metastases.. PAX8 is expressed in a subset of melanomas and may be strong/extensive. As PAX8 positivity does not exclude a diagnosis of melanoma, it should be used in conjunction with other immunohistochemical markers, such as cytokeratin and PAX2, when melanoma, MiTF-RCC, and other PAX8+ tumors are in the differential diagnosis. Topics: Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Melanoma; Melanoma, Cutaneous Malignant; PAX2 Transcription Factor; PAX8 Transcription Factor; Skin Neoplasms | 2021 |
In vivo two-photon-excited cellular fluorescence of melanin, NAD(P)H, and keratin enables an accurate differential diagnosis of seborrheic keratosis and pigmented cutaneous melanoma.
Seborrheic keratoses (SKs) are harmless pigmented skin lesions (PSLs) that may be confused clinically not only with other benign conditions but also with cutaneous melanoma (CM). As SKs are one of the most common neoplasms in adults, the importance of their correct diagnosis is high. Misclassifying SK as malignant is not rare and leads to a high number of unnecessary biopsies. On the other hand, misdiagnosing CM as SK may have a large impact on prognosis or therapy.. In the non-invasive technique of dermatofluoroscopy, the fluorophores in melanocytes and keratinocytes are excited in vivo with nanosecond laser pulses and the resulting spectrally resolved, melanin-dominated fluorescence signals are used to differentiate between pigmented benign lesions and CM.. In this single-center, non-interventional study, 33 PSLs of 20 patients were scanned with dermatofluoroscopy in vivo. For all included cases, dermatofluoroscopic signals were compared to pathology classification.. The characteristic spectral features of SK were identified, where the signals are dominated by keratin, NAD(P)H, and melanin. The fluorescence spectra of SKs differed substantially from those of CM: a characteristic spectrum of SK has been identified in 27 of 28 SKs.. The high-accuracy differential diagnosis between CM and SK is possible with dermatofluoroscopy. Topics: Adult; Diagnosis, Differential; Humans; Keratins; Keratosis, Seborrheic; Melanins; Melanoma; NAD; Skin Neoplasms | 2021 |
Epidermolytic Hyperkeratosis.
Topics: Humans; Hyperkeratosis, Epidermolytic; Keratins; Skin; Skin Neoplasms | 2021 |
Human basal cell carcinoma: the induction of anagen hair follicle differentiation.
Consistent with cancer stem cell driven pattern of growth, human basal cell carcinomas (BCCs) demonstrate differentiation along hair follicle (HF) lineages.. To define the pattern of differentiation and therapeutic targets that promote BCC differentiation and therefore BCC cancer stem cell exhaustion.. An alkaline phosphatase substrate kit was used to determine dermal papilla cells within the BCC stroma. Autonomous HF cycle-dependent gene expression was identified by analysis of the human homologues of a murine gene set (total 2289 genes) that is differentially expressed in hair cycle phases. The findings were validated by quantitative real-time PCR and immunofluorescence, as well as in vitro transforming growth factor (TGF)-β2 stimulation of BCC cancer stem cell colonies.. As in the HF, keratin expression in the inner root sheath and matrix in BCC correlated with proliferative index and was tightly regulated, despite the absence of dermal papilla cells. Cross-species microarray analysis comparing human BCC and murine synchronous HF growth cycle datasets revealed 74% concordance with telogen differentiation compared with anagen (23%, P < 0.01) and catagen (49%; P < 0.01). Incomplete anagen differentiation within BCC was characterized by reduced expression of the anagen master regulator DLX3 (-5.5-fold), and increased expression of telogen-associated genes: AEBP1 (2.2-fold), DEFB8 (35.3-fold), MMP3 (106.0-fold) and MMP12 (12.9-fold). Restoration of dermal papilla signals by in vitro addition of TGF-β2 enhanced anagen differentiation.. Our findings show that BCC cells differentiate along HF lineages and may be susceptible to exogenous HF cycle modulators. Topics: Animals; Carcinoma, Basal Cell; Cell Differentiation; Cell Transformation, Neoplastic; Fluorescent Antibody Technique; Gene Expression; Hair Follicle; Humans; Keratins; Mice; Oligonucleotide Array Sequence Analysis; Real-Time Polymerase Chain Reaction; Skin Neoplasms | 2020 |
Trichoblastic infundibular cyst should be renamed infundibular cyst with unique papillary projections.
Trichoblastic infundibular cyst (TBIC) was previously reported as a unique keratinous cystic lesion, which was characterized by the papillary projections of follicular germinative-like cells emanating from the cyst wall. Here, we report three additional cases of this cyst and discuss the pathogenesis of this unique entity. In all cases, a unilocular cyst contained keratin, and the cyst wall was composed of squamous epithelium. A number of cords and papillary projections emanated from the basal layer of the cyst wall. They were composed of cells with large nuclei and scant cytoplasm arranged in a peripheral palisade. Immunohistochemically, anti-cytokeratin 15, anti-cytokeratin 20, and anti-epithelial cell adhesion molecule antibodies were negative. Thus, these cells resembled follicular germinative cells or sebaceous mantle morphologically, but we failed to prove the differentiation immunohistochemically. The cyst was surrounded by fibrotic stroma and inflammatory cells, suggesting previous rupture of the cyst. We speculate that the cells of the projections possibly differentiate into the mantle rather than follicular germinative cells, even though we could not provide sufficient immunohistochemical evidence. We also suggest that they may be induced by special reaction to fibrohistiocytic stroma surrounding the infundibular cyst. Therefore, TBIC should be renamed infundibular cyst with unique papillary projections. Topics: Adult; Aged; Asian People; Diagnosis, Differential; Epidermal Cyst; Follicular Cyst; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Margins of Excision; Middle Aged; Skin Neoplasms | 2020 |
Mutations in KRT10 in epidermolytic acanthoma.
Epidermolytic acanthoma (EA) is a rare acquired lesion demonstrating a characteristic histopathological pattern of epidermal degeneration referred to as epidermolytic hyperkeratosis (EHK). On histopathological analysis, EA appears nearly identical to inherited EHK-associated dermatoses such as epidermolytic ichthyosis and ichthyosis bullosa of Siemens. While it has been speculated that EA is caused by mutations in KRT10, KRT1, or KRT2 found in these inherited dermatoses, none have yet been identified. Herein, we aim to identify the contributions of keratin mutations to EA.. Using genomic DNA extracted from paraffin-embedded samples from departmental archives, we evaluated a discovery cohort using whole-exome sequencing (WES) and assessed remaining samples using Sanger sequencing screening and restriction fragment length polymorphism (RFLP) analysis.. DNA from 16/20 cases in our sample was of sufficient quality for polymerase chain reaction amplification. WES of genomic DNA from lesional tissue revealed KRT10 c.466C > T, p.Arg156Cys mutations in 2/3 samples submitted for examination. RFLP analysis of these samples as well as eight additional samples confirmed the mutations identified via WES and identified four additional cases with Arg156 mutations. In sum, 6/11 screened cases showed hotspot mutation in KRT10.. Hotspot mutations in the Arg156 position of KRT10, known to cause epidermolytic ichthyosis, also underlie EA. Topics: Acanthoma; Adult; Aged; Aged, 80 and over; Exome Sequencing; Female; Genomics; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis Bullosa of Siemens; Keratin-10; Keratins; Male; Middle Aged; Mutation; Skin Neoplasms | 2020 |
A rare case of invasive melanoma likely arising from passenger melanocytes of a basal cell carcinoma.
Neoplasms consisting of different cell lineages within a single skin specimen are rare, yet well documented in the literature. However, to date, there appears to be no report of invasive melanoma arising directly from the passenger melanocytes of a basal cell carcinoma (BCC). We present a case of a 91-year-old male with a suspicious lesion on the ear. Histopathology and immunohistochemical staining revealed BCC closely intertwined with invasive melanoma that exhibited foci of chondroid differentiation. The melanoma appeared to arise from the benign-appearing passenger melanocytes of the BCC and lacked connection to the overlying epidermis or an in situ component. Multiple dermatopathologists reviewed the case and agreed that the most likely explanation for the histopathologic findings was that the invasive melanoma arose from the passenger melanocytes within the BCC. Topics: Aged, 80 and over; Carcinoma, Basal Cell; Ear Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Melanocytes; Melanoma; Melanoma, Cutaneous Malignant; Neoplasm Invasiveness; Neoplasms, Multiple Primary; S100 Proteins; Skin Neoplasms; SOXE Transcription Factors; Treatment Refusal | 2020 |
Primary intrafascial desmoplastic melanoma with pseudoglandular differentiation and aberrant cytokeratins expression: An exceptional presentation.
Desmoplastic melanoma (DM) is an uncommon variant of malignant melanoma (MM), histologically characterized by a mainly dermal proliferation of spindled cells within a desmoplastic stroma. Normally, involvement of deeper tissues by DM is the result of direct extension down from the overlying dermis. MM is widely known to harbor a striking potential for morphological and phenotypic variability; among MM morphological variants, pseudoglandular MM is characterized by extensive discohesion within cords and nests of malignant cells and ensuing formation of so-called pseudolumina, thus mimicking adenocarcinoma. We present an exceptional case of DM characterized by intrafascial origin, partly pseudoglandular differentiation, and aberrant experession of cytokeratins in the pseudoglandular component; genetic data from next-generation sequencing supported the final diagnosis of DM, as well as the ontogenetic identity of the pseudoglandular component. Prior to this report, pseudoglandular features had never been described in DM. Additionally, our case is unusual because of the deep origin of the tumor, arising below the subcutaneous fat of the scalp, as well as the aberrant experession of cytokeratins in the pseudoglandular component, thus posing a challenging differential diagnosis with several soft tissue tumors. Topics: Aged; Biomarkers, Tumor; Cell Differentiation; Diagnosis, Differential; Head and Neck Neoplasms; Humans; Keratins; Male; Melanoma; Predictive Value of Tests; Scalp; Skin Neoplasms | 2019 |
Frozen-Section Tissue Processing in Mohs Surgery.
Mohs micrographic surgery (MMS) is the most reliable tissue-sparing technique in the management of cutaneous malignancies. Although the concept is simple, there is considerable variability in the mapping and processing techniques used by Mohs surgeons and histotechnicians.. This review article aims to examine the frozen-section tissue processing techniques. Existing variations will be discussed and pearls offered to optimize the frozen processing technique.. A PubMed search was performed for publications on methods of tissue processing in MMS.. Our review highlights variations in debulking, embedding, processing adipose tissue, cartilage, and wedge resections. We offer pearls on how to avoid false-positive and false-negative margins and discuss advances in immunohistochemistry.. Our article provides a how-to format on the different stages of tissue processing with pearls and techniques to optimize practice and improve accuracy. Topics: Antibodies; Coloring Agents; Cytoreduction Surgical Procedures; Frozen Sections; Humans; Immunohistochemistry; Keratins; Margins of Excision; Mohs Surgery; Quality Control; Skin Neoplasms; Tolonium Chloride | 2019 |
Dedifferentiated Melanoma With Expression of Cytokeratin and GATA3 in a Patient With History of Breast Carcinoma.
Melanoma is one of the great mimickers in pathology because it has diverse morphologies and can be mistaken for carcinoma or sarcoma. In most cases, immunochemistry is helpful in supporting the diagnosis and excluding other differentials. However, metastatic melanoma may lose immunohistochemical melanocytic markers and express nonmelanocytic lineage markers, which often poses a diagnostic dilemma and may be misdiagnosed as a poorly differentiated carcinoma or sarcoma. We report the case of a 52-year-old woman who had a history of recurrent melanoma on her right shoulder with axillary lymph node metastasis (BRAF V600K-mutated melanoma) and right-side breast-invasive ductal carcinoma (stage pT1b N0sn). One year later, she presented with a left-sided chest wall mass and enlarging left axillary lymph nodes. Needle core biopsies were obtained from both lesions, and histologic examination showed a poorly differentiated tumor with pleomorphic/anaplastic morphology and necrosis. The tumor cells were strongly immunoreactive for GATA-3 without expression of melanocytic markers (S100, Melan A, HMB45, SOX10, MITF, and tyrosinase). The history of melanoma prompted molecular analysis, and the lesion was found to harbor the BRAF V600K mutation, consistent with metastatic dedifferentiated melanoma. Recognition of metastatic dedifferentiated melanoma is important to avoid misdiagnosis of carcinoma, especially in patients with a previous history of carcinoma. Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Cell Dedifferentiation; Female; GATA3 Transcription Factor; Humans; Keratins; Lymphatic Metastasis; Melanoma; Middle Aged; Neoplasms, Second Primary; Skin Neoplasms | 2019 |
Sarcomatoid Carcinoma With Quasi-Complete Loss of Cytokeratin Expression or Keratin-Positive Atypical Fibroxanthoma.
We report the case of a 94-year-old man with a rapidly growing nodule on the preauricular area, which on histology showed a poorly differentiated spindle cell tumor with negative p63 and p40 antibody immunostains, negative high- and low-molecular-weight cytokeratins albeit for a focal expression of cytokeratin AE1/AE3. Spindle cell melanoma, angiosarcoma, and leiomyosarcoma were excluded. We explore the diagnostic approach to this challenging conundrum. Certain authors have suggested that sarcomatoid carcinoma and atypical fibroxanthoma (AFX) may lie within a spectrum of "sarcoma-like tumors of the head and neck" and that they may all run a similarly indolent clinical course. However, AFX appears to remain a diagnosis of exclusion, and expert consensus is that by definition AFX cannot express any cytokeratin antigens. Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Face; Hemangiosarcoma; Humans; Keratins; Leiomyosarcoma; Male; Melanoma; Mohs Surgery; Skin; Skin Neoplasms | 2019 |
EWSR1-PBX3 gene fusion in cutaneous syncytial myoepithelioma.
Cutaneous syncytial myoepithelioma (CSM) is a recently recognized, histopathological variant of myoepithelial (ME) tumors of the skin. It is characterized by a syncytial arrangement of spindled, ovoid, and/or epithelioid cells forming a well-circumscribed, unencapsulated dermal nodule. There is a paucity of intervening stroma, and absent duct or gland formation. Strong immunohistochemical staining for S100 and epithelial membrane antigen (EMA) has been described, while cytokeratin expression has been uncommon. The majority of CSMs harbor a rearrangement involving the EWSR1 gene. Although various fusion partner genes have been discovered in ME tumors at other anatomic sites, none has yet been described in CSM. We present a case of CSM represented clinically by a papule on the mid-upper back of a healthy 44-year-old female. It exhibited morphological and immunohistochemical features of a CSM with strong, diffuse S100 and alpha-actin expression, and focal positivity for EMA and cytokeratin AE1/AE3. Fluorescence in-situ hybridization showed an EWSR1 gene rearrangement. Massively parallel next-generation RNA sequencing revealed PBX3 as the fusion partner. The EWSR1-PBX3 gene fusion has been previously identified in three cases of ME tumors of bone and soft tissue, and in a case of retroperitoneal leiomyoma. This is the first report of an EWSR1-PBX3 fusion in CSM. Topics: Adult; Biomarkers, Tumor; Female; Homeodomain Proteins; Humans; Keratins; Myoepithelioma; Oncogene Fusion; Oncogene Proteins, Fusion; Proto-Oncogene Proteins; RNA-Binding Protein EWS; Skin Neoplasms | 2019 |
Dual Immunostaining With SOX10 and AE1/AE3 to Confirm Perineural Invasion on Mohs Sections
Perineural invasion (PNI) is associated with high risk keratinocyte carcinomas. Identification of PNI during Mohs surgery is important for staging and post-adjuvant treatment decisions but can be challenging. To confirm or exclude PNI suspected on hematoxylin and eosin sections, we performed immunohistochemical double staining on Mohs frozen sections. Neural marker SOX10 and pan-cytokeratin marker AE1/AE3 were combined in a simultaneous assay using species-specific (mouse and rabbit) antibodies and horseradish peroxidase and alkaline phosphatase detection systems. Of 23 Mohs cases with suspected PNI, 18 were confirmed to have definitive nerve involvement by tumor using double staining. Double staining frozen tissue is feasible and can be beneficial for real time confirmation of PNI during Mohs.\ \ J Drugs Dermatol. 2019;18(3):262-264. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Frozen Sections; Humans; Immunohistochemistry; Keratins; Mohs Surgery; Neoplasm Invasiveness; Peripheral Nerves; Skin; Skin Neoplasms; SOXE Transcription Factors | 2019 |
Cytokeratin Profile of Basal Cell Carcinomas According to the Degree of Sun Exposure and to the Anatomical Localization.
Basal cell carcinoma (BCC) seems to originate from ultraviolet light-induced mutations involving the bulge or the outer sheath of the hair follicle cells. However, the etiopathogenic mechanisms involved in the development of these tumors in nonphotoexposed and in hairless areas remain unclear. The cytokeratin (CK) profile (including CK5/6, CK7, CK14, CK15, CK17, and CK19) from a series of different BCC subtypes developing in sun-exposed and non-sun-exposed areas, including hairless regions, was evaluated. The authors have observed that CK7 expression in BCC is associated with the anatomical localization of the tumor and its sun-exposition, but not with other factors such as histological subtype. The expression of this CK is higher in BCCs located in non-sun-exposed and nonhairy areas, such as the vulvar semimucosa and the nipple. Because CK7 is a marker of simple glandular epithelia, the authors suggest a glandular origin for BCCs located in hairless and nonphotoexposed areas. Topics: Adult; Carcinoma, Basal Cell; Female; Hair Follicle; Humans; Keratins; Male; Neoplasms, Adnexal and Skin Appendage; Skin Neoplasms; Sunlight | 2018 |
Intense Pulsed Light: Friend or Foe? Molecular Evidence to Clarify Doubts.
Intense pulsed light (IPL) has been extensively applied in the field of dermatology and aesthetics; however, the long-term consequences of its use are poorly unknown, and to the best of our knowledge there is no study on the effect of IPL in neoplastic lesions. In order to better understand the molecular mechanisms underlying IPL application in the skin, we used an animal model of carcinogenesis obtained by chemical induction with 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA).. Institute of Cancer Research (ICR) mice were administered DMBA and/or TPA and treated with IPL. Skin was evaluated by histopathology and 2DE-blot-MS/MS analysis.. Our data evidenced an inflammatory response and a metabolic remodeling of skin towards a glycolytic phenotype after chronic exposure to IPL, which was accomplished by increased oxidative stress and susceptibility to apoptosis. These alterations induced by IPL were more notorious in the DMBA sensitized skin. Keratins and metabolic proteins seem to be the more susceptible to oxidative modifications that might result in loss of function, contributing for the histological changes observed in treated skin.. Data highlight the deleterious impact of IPL on skin phenotype, which justifies the need for more experimental studies in order to increase our understanding of the IPL long-term safety. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Carcinogens; Disease Models, Animal; Female; Glycolysis; Intense Pulsed Light Therapy; Keratins; Mice; Mice, Inbred ICR; Oxidative Stress; Random Allocation; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate | 2018 |
SOX10/keratin dual-color immunohistochemistry: An effective first-line test for the workup of epithelioid malignant neoplasms in FNA and small biopsy specimens.
The characterization of poorly differentiated neoplasms in fine-needle aspiration (FNA) and small biopsy specimens usually requires immunohistochemistry (IHC) with a panel of markers. Because of an increasing need to preserve limited diagnostic material for tumor genotyping and a mounting demand for cost containment, the authors investigated the usefulness of dual-color IHC with antibodies directed against broad-spectrum keratins and SOX10, a neuroectodermal transcription factor consistently expressed in melanoma, in the workup of epithelioid malignant neoplasms.. A total of 107 cases of FNA cell blocks (49 cases) and small biopsies (58 cases) were selected, including 34 melanomas, 31 epithelioid/pleomorphic sarcomas, and 42 carcinomas. IHC was performed on all specimens using a peroxidase-based brown chromogen for SOX10 and an alkaline phosphatase-based red chromogen for keratins AE1/AE3. The presence or absence of staining in lesional cells was scored.. The majority of tumors demonstrated 1 of 3 distinct patterns: 1) malignant melanomas with nuclear SOX10 (sensitivity of 94% and specificity of 95%); 2) epithelioid/pleomorphic sarcomas negative for both SOX10 and AE1/AE3 (sensitivity of 84% and specificity of 88%); and 3) carcinomas with cytoplasmic AE1/AE3 (sensitivity of 76% and specificity of 98%). In addition, a fourth pattern with cytoplasmic AE1/AE3 and nuclear SOX10 was observed in a subset of carcinomas, most notably triple-negative breast cancers.. SOX10/keratin dual-color IHC appears to be an effective, sensitive, and specific test to distinguish between melanoma, sarcoma, and carcinoma. This approach can identify melanoma, prioritize additional studies, and limit the number of markers needed to workup an epithelioid malignant neoplasm, thereby potentially reducing costs and preserving valuable tissue for ancillary studies with which to guide therapy. Cancer Cytopathol 2018;126:179-89. © 2018 American Cancer Society. Topics: Biopsy, Fine-Needle; Cell Differentiation; Color; Humans; Immunohistochemistry; Keratins; Limit of Detection; Melanoma; Skin Neoplasms; SOXE Transcription Factors | 2018 |
Use of a novel 1-hour protocol for rapid frozen section immunocytochemistry, in a case of squamous cell carcinoma treated with Mohs micrographic surgery.
For squamous cell carcinoma (SCC) treated using Mohs micrographic surgery (MMS), interpretation of haematoxylin and eosin-stained frozen sections can be challenging. In these situations, ancillary use of immunostaining is a useful tool for the Mohs surgeon. However, use of immunostaining in MMS laboratories is limited, mainly because current manual immunostaining platforms are subject to operator error, and automated immunostaining, albeit accurate, is too slow for inclusion in MMS. In this report, we describe a novel 1-hour protocol for rapid frozen section immunocytochemistry, using the pancytokeratin markers AE1/AE3. This protocol has been specifically designed to integrate the speed of manual techniques and the accuracy of automated platforms, making it a valuable addition to the MMS laboratory. We propose that in selected or histologically challenging cases, there is a role for the use of this novel protocol, allowing the Mohs surgeon to more confidently declare tumour clearance, thus preventing further unnecessary surgery and preserving healthy tissue. Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Frozen Sections; Humans; Immunohistochemistry; Keratins; Male; Mohs Surgery; Skin Neoplasms | 2018 |
Immunohistochemical investigation of predictors of response or aggressiveness of bowen disease after photodynamic therapy.
Photodynamic therapy (PDT) is a good option for the treatment of Bowen's disease (BD). However, BD occasionally can progress into a squamous cell carcinoma (SCC) after PDT.. Find predictors of aggressiveness of BD after PDT METHODS: Two biopsies of patients with BD treated with PDT with progression to SCC within three months were selected for immunohistochemical (IHC) studies. Conventional PDT was applied. IHC analysis was performed together with hematoxylin-eosin in the biopsies prior to and after treatment with PDT.. Among the IHC markers studied, none showed different expressions between pre-treatment and post-treatment biopsies except for HSP70 CONCLUSIONS: The expression of Hsp70 in BD may predict future aggressive behaviour in BD when treated with PDT. Nevertheless, due to the small number of biopsies studied, further investigations are required to draw conclusions. Topics: Aged; Aminolevulinic Acid; beta Catenin; Bowen's Disease; Cell Cycle; Humans; Immunohistochemistry; Keratins; Male; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms | 2018 |
Immunohistochemical staining patterns of alpha-keratins in normal tissues from two reptile species: implications for characterization of squamous cell carcinomas.
Cytokeratins with epitopes in common with those of alpha (acidic and basic) mammalian keratins have been immunohistochemically demonstrated in the epidermis of reptiles. However, there are no reports of immunohistochemical staining patterns of alpha-keratins in other tissues from reptiles. Because the epithelial tumours usually retain the keratin patterns of their normal epithelial origin, it is necessary to know in advance these patterns in the major normal epithelia and organs. We used anti-alpha human keratin AE1 and AE3 monoclonal antibodies to study the staining patterns of alpha-keratins in the major normal epithelia and organs from two reptile species [the bearded dragon (Pogona vitticeps) and the loggerhead sea turtle (Caretta caretta)]. We also studied the immunolocalization of alpha-keratins in squamous cell carcinomas (SCCs) in a bearded dragon and two loggerhead turtles.. Acidic alpha-keratin (AE1 positive) was detected in many of the epithelial tissues of the bearded dragons; however, the detection of basic alpha-keratin (AE3 positive) was much more limited. Alpha-keratins were detected in a greater number of tissues of loggerhead turtles compared with those observed in bearded dragons. In the bearded dragon SCC, all layers of the nests of neoplastic cells, including the cornified layer of the keratin pearls, were strongly reactive with the AE1 antibody. However, a weak reactivity using the AE3 antibody was detected in the basal and intermediate layers of these nests. In the cutaneous SCCs of both sea turtles, acidic alpha-keratin was detected in the basal and suprabasal layers, and in all of the invasive neoplastic cords, while basic alpha-keratin was mainly detected in the invasive neoplastic cords. The pattern observed in the metastases in both turtles consisted of immunohistological detection of acidic alpha-keratin in all metastatic foci, and limited or lack of detection of basic alpha-keratin.. This study provides, for the first time, information about the immunohistochemical staining patterns of alpha-keratins in normal tissues from bearded dragons and loggerhead sea turtles, and confirms the usefulness of AE1 and AE3 monoclonal antibodies in these reptile species. The use of these antibodies also contributed to a better characterization of SCCs in these species. Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Epidermis; Intestinal Mucosa; Keratins; Lizards; Male; Skin Neoplasms; Turtles | 2018 |
[Chronic papulosquamous lesion: papilloma should be suspected].
Papilloma is a benign tumor of the malpighian layer, usualy affecting the skin. Thickened epithelium doesn't show cytological or architectural abnormalities; the epithelial proliferation is still clearly separated from the dermis by the basal membrane, that is to say absence of tumor infiltration. We here report the case of a 15-year-old boy presenting with oozing plague in his left elbow that had evolved over the previous two months. The patient had no particular previous history. Physical examination showed good general condition and a papular, squamous, itchy, oozing lesion measuring 4 cm along its longer axis. The remainder of the physical examination was normal. He was treated with topical emollient, antimycotics and quinolone antibiotics. Drying of the purulent oozing was observed, but no improvement in the general appearance of the lesion. Laboratory tests, including glucose tolerance test, were normal. A biopsy of the lesion was performed. Anatomo-pathological examination of skin biopsy specimen showed no abnormal cells, rather an elongation of the epidermal ridges as well as of the connective papillae, extensive keratinization of the surface and thickening of the malpighian layer. The diagnosis of papilloma was retained. Surgical excision of the tumor resulted in complete healing. Topics: Adolescent; Biopsy; Humans; Keratins; Male; Papilloma; Skin Neoplasms | 2018 |
Hierarchical Cluster Analysis of Cytokeratins and Stem Cell Expression Profiles of Canine Cutaneous Epithelial Tumors.
The diagnosis of cutaneous epithelial tumors (CETs) in dogs is based on predominant histological differentiation patterns. However, the expression of a broad panel of antigens has not been comprehensively examined with immunohistochemistry. The present study aims to establish a comprehensive expression profile and identify useful diagnostic markers for each CET type. Cytokeratin (CK), stem cell, and other associated markers were immunohistochemically examined in 110 canine CETs. Among these, CK16 was useful for differentiating between basal and squamous cell carcinomas. Acantholytic squamous cell carcinomas were positive for CK8, CK18, and CK19, suggesting their close association with the apocrine duct. Unlike their benign counterparts, sebaceous carcinomas coexpressed CK5/6 and adipophilin. Smooth muscle actin (SMA) and p63 immunostaining were useful for accurately distinguishing between glandular and ductal differentiation in apocrine tumors. A case of apocrine carcinoma and malignant myoepithelioma was identified using anti-SMA antibodies. Stem cell expression profiles (CK8, CK15, CK19, and CD34) of hair follicle tumors were discrete and indicative of their anatomic origins. The effectiveness of immunohistochemistry for tumor diagnosis was further confirmed by hierarchical cluster analysis, through which selected markers were able to sort CETs into specific groups: CK5/6, CK8, CK14, CK16, CK18, CK19, p63, adipophilin, and SMA sorted tumors of epidermal, apocrine, or sebaceous origin; while CK8, CK14, CK15, CK16, CK19, CD34, and p63 sorted hair follicle tumors in agreement with their histological differentiation. In conclusion, the present study provides comprehensive immunohistochemical information, which could complement histomorphological features for the future classification of canine CETs. Topics: Animals; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cluster Analysis; Dog Diseases; Dogs; Epithelial Cells; Keratin-18; Keratin-19; Keratin-8; Keratins; Skin; Skin Neoplasms; Stem Cells | 2018 |
[Keratoacanthoma of the left forearm].
We here report the case of a 54-year old woman presenting with a swelling in the left forearm occurred eight weeks before and rapidly increasing in volume. Clinical examination showed ulcero-budding painless purplish skin lesion measuring 2 cm along its longer axis (A). The patient underwent simple biopsy. Histological examination showed dyskeratosic, disorganized, hyperplastic epithelium with cytonuclear abnormalities, suggesting malignant transformation. Given the absence of infiltration in the chorion and the presence of hyperkeratosis, the diagnosis of keratoacanthoma was made. Resection of the tumor was indicated to confirm or deny this diagnosis. Histological examination revealed a protruding epithelial tumor-like lesion circumscribed by two species of lateral "bird beaks" delineating a crater filled with many layers of keratin. The crater was bordered by hyperplastic epithelium. The crater base was characterized by irregular papillomatous projections as well as by few cellular strands which seemed to shred in the underlying dermis. These were basophilic made up of cells displaying a certain degree of cytonuclear abnormalites arranged in one or two peripheral areas and, in their center, some eosinophilic, keratin, homogeneous cells, few mitoses as well as many horny globes, most often completely keratinized (B). The diagnosis of keratoacanthoma was retained. Keratoacanthoma is a well defined anatomo-clinical entity which can be very difficult to distinguish from squamous cell carcinoma, whose incidence is three times higher. A distinction between these two lesions is necessary due to their different management. Topics: Biopsy; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Forearm; Humans; Keratins; Keratoacanthoma; Middle Aged; Skin Neoplasms | 2018 |
Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms.
We used allogeneic bone marrow transplantation (BMT) and a mouse multistage cutaneous carcinogenesis model to probe recruitment of bone marrow-derived epithelial cells (BMDECs) in skin tumors initiated with the carcinogen, dimethylbenz[a]anthracene (DMBA), and promoted with 12-O-tetradecanolyphorbol-13-acetate (TPA). BMDECs clustered in the lesional epithelium, expressed cytokeratins, proliferated, and stratified. We detected cytokeratin induction in plastic-adherent bone marrow cells (BMCs) cultured in the presence of filter-separated keratinocytes (KCs) and bone morphogenetic protein 5 (BMP5). Lineage-depleted BMCs migrated towards High Mobility Group Box 1 (HMGB1) protein and epidermal KCs in ex vivo invasion assays. Naive female mice receiving BMTs from DMBA-treated donors developed benign and malignant lesions after TPA promotion alone. We conclude that BMDECs contribute to the development of papillomas and dysplasia, demonstrating a systemic contribution to these lesions. Furthermore, carcinogen-exposed BMCs can initiate benign and malignant lesions upon tumor promotion. Ultimately, these findings may suggest targets for treatment of non-melanoma skin cancers. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Bone Marrow Cells; Bone Marrow Transplantation; Bone Morphogenetic Protein 5; Cell Movement; Cell Plasticity; Cell Transformation, Neoplastic; Coculture Techniques; Epithelial Cells; Female; Hair Follicle; HMGB1 Protein; Keratinocytes; Keratins; Male; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness; Papilloma; Skin Neoplasms; Stem Cells; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured | 2018 |
Desmoplastic tricholemmoma in a dog.
A 10-year-old mixed breed dog was presented with a 0.8 cm diameter mass below the left eye region. The mass was surgically removed and processed for histopathological examination. Microscopically, tumor cells proliferated in small lobules, nests and cords, and the tumor parenchyma was separated by desmoplastic stroma. Majority of the tumor cells were periodic acid-Schiff (PAS)-positive, and the desmoplastic stroma was densely collagenous and mucinous. Immunohistochemical results showed that the tumor cells were diffusely positive for cytokeratin 15, cytokeratin 19 and CD 34, while cytokeratin 8 reactivity was limited to the tumor cells proliferating in cords. Few tumor cells were positive for nestin. Based on the histopathological findings, the tumor was diagnosed as desmoplastic tricholemmoma. Topics: Animals; Dermis; Diagnosis, Differential; Dog Diseases; Dogs; Female; Hair Diseases; Hair Follicle; Immunohistochemistry; Keratins; Skin Neoplasms | 2017 |
Might tumor secreted cathepsin proteases leave specific molecular signals in skin, hair and nails years before a cancer becomes clinically apparent?
X-ray fiber diffraction analysis (FDA) of the fibrous macromolecules in hair, nails and skin has been shown to non-invasively diagnose various cancers, at sites remote from the cancer, years before the cancer becomes clinically apparent. The technology is not widely accepted because of reproducibility issues (that can be easily resolved) and lack of an explanation as to how a clinically unapparent tumor can leave molecular "signatures" at remote sites. However, there is evidence that tumor-specific cathepsins (lysosomal proteases) circulate systemically long before a cancer is clinically apparent. As such, we hypothesize that cathepsins, by virtue of their proteolytic activity, impart molecular changes in tissues remote from the primary tumor. These subtle molecular changes, which are specific for various tumors, can be readily detected by FDA of hair, nails and skin. We call for more research in the utility of FDA and tumor specific cathepsins for the early and non-invasive diagnosis of various malignancies. Topics: Aged; Cathepsin B; Cathepsins; Cell Proliferation; Collagen; Extracellular Matrix; Follow-Up Studies; Hair; Humans; Keratins; Lysosomes; Nails; Peptide Hydrolases; Precancerous Conditions; Reproducibility of Results; Skin; Skin Neoplasms; United States; United States Food and Drug Administration; X-Ray Diffraction | 2017 |
Immunohistochemical dissection of cystic panfolliculoma focusing on the expression of multiple hair follicle lineage markers with an insight into the pathogenesis.
Panfolliculoma (PF) is a rare benign tumor with signs of differentiation toward all components of the hair follicle (HF). Cystic panfolliculoma (CPF) is a subset of PF with histological similarity to trichofolliculoma making the differential diagnosis difficult in some cases. Immunohistopathological investigations of PF have been reported; however, previous studies focused mostly on the expression profile of the outer root sheath markers. Herein, we report a case of CPF. A panel of antibodies was developed and used for the detection of the expression of cytokeratin (CK) 10, CK13, CK14, CK15, hair-hard keratin (AE13) and EpCAM within the lesion, supporting the differentiation of all epithelial lineages of the HF and the diagnosis of CPF. Immunohistopathological examinations clearly showed the spatial distribution pattern of each subset of tumor cells with distinct HF differentiation marker expression. Intriguingly, fibroblastic dermal cells were distributed preferentially near CK15-negative epithelium or CK13-positive HF-like structures, suggesting a role for epithelial-mesenchymal interactions (EMIs) in CPF pathogenesis. Further characterization of EMIs between the tumor and surrounding mesenchymal cells in CPF may provide an explanation for immature HF differentiation. These findings suggest that the more intense and coordinated EMI in the analogous tumorigenesis gives rise to mature HF structures, resulting in trichofolliculoma, which may explain their histological resemblance. Topics: Aged; Gene Expression Regulation, Neoplastic; Hair Follicle; Humans; Keratins; Male; Neoplasm Proteins; Skin Neoplasms | 2017 |
CD117 expression in adenosquamous carcinoma.
Topics: Apocrine Glands; Biomarkers, Tumor; Carcinoma, Adenosquamous; Eccrine Glands; Humans; Keratins; Membrane Proteins; Proto-Oncogene Proteins c-kit; Skin Neoplasms | 2017 |
Reexcision Perineural Invasion and Epithelial Sheath Neuroma Possibly on a Spectrum of Postinjury Reactive Hyperplasia Mediated by IL-6.
Epithelial sheath neuroma is a rarely recognized but established entity in the medical literature. First described in 2000 by Requena et al, there have only been 7 published cases to date, mostly in female patients and presenting as symptomatic solitary lesions on the back without a known history of trauma. In 2006, Beer et al described and reviewed a dozen cases in which epithelial sheath neuroma-like features were seen in the advent of a surgical procedure, which was termed "re-excision perineural invasion" and attributed to possible eccrine duct implantation during surgery. Our case is a 66-year-old male patient who underwent an excision of a melanocytic neoplasm in which a reactive epithelial sheath neuroma was incidentally discovered in the excision specimen, adjacent to the biopsy site cicatrix. Histologically, there was benign cutaneous nerve hyperplasia with a proliferation of squamous epithelium in intimate apposition to the nerve bundles in the superficial dermis. We postulate that the process active in the formation of re-excision perineural invasion is the same as in epithelial sheath neuroma and that minor trauma not appreciable on histologic examination is responsible in the latter entity. We performed IL-6 staining and documented that IL-6 was upregulated at the interface of the nerve and reactive epithelium, but was absent in nerves distant from the site of surgery, suggesting that IL-6 may be essential to the lesion's development. The recognition of reactive epithelial sheath neuroma including the subcategory of re-excision perineural invasion is crucial for the dermatopathologist to prevent mislabeling this reactive entity as a perineural squamous cell carcinoma, which has clinical consequences for the patient such as wider re-excision and radiation treatment. Additionally, we have identified a potential pathophysiologic basis for this lesion. Topics: Adult; Aged; Aged, 80 and over; Back; Biomarkers, Tumor; Biopsy; Cicatrix; Dysplastic Nevus Syndrome; Epithelial Cells; Female; Fluorescent Antibody Technique; Humans; Hyperplasia; Interleukin-6; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neuroma; Peripheral Nerves; Skin Neoplasms; Up-Regulation | 2017 |
Cytokeratin AE1/AE3 immunostaining and 3D-histology: improvement of diagnosis in desmoplastic squamous cell carcinoma of the skin.
Desmoplastic squamous cell carcinoma (DSCC) as a rare subtype of cutaneous SCC has specific histological features, characterized by columns, bands, and strands of squamoid cells infiltrating a dense collagenous stroma. To decrease the high rates of local recurrence in DSSC, improvement of diagnostic methods is highly demanded. Objective was to evaluate whether immunohistochemistry (IHC) is suited to increase diagnostic accuracy. A total number of 18 patients were included in this study. After recutting of the original paraffin blocks, parallel staining of serial sections with conventionally H&E and cytokeratin AE1/AE3-immunohistochemical staining was performed. Results were evaluated by an experienced dermatohistopathologist. In 55.6% (n = 10), the margins of 3D-histology still showed no evidence of neoplastic lesions in both stainings. In contrast, we found neoplastic lesions in 5 of 18 cases (27.8%) with cytokeratin AE1/AE3 staining, while H&E-staining remained negative. In addition, neoplastic lesions were found in both, H&E as well as cytokeratin AE1/AE3 staining in three cases (16.7%). The data presented show improvement of diagnosis in 27.8% of cases using IHC and 3D-histology. This method is suitable to improve the diagnosis of DSCC. Topics: Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; Female; Humans; Imaging, Three-Dimensional; Immunohistochemistry; Keratins; Male; Margins of Excision; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Skin Neoplasms | 2017 |
Vitis vinifera peel and seed gold nanoparticles exhibit chemopreventive potential, antioxidant activity and induce apoptosis through mutant p53, Bcl-2 and pan cytokeratin down-regulation in experimental animals.
Several studies suggest surface modifications of gold nanoparticles (AuNPs) by capping agents or surface coatings could play an important role in biological systems, and site directed delivery. The present study was carried out to assess the antioxidant and apoptotic activities of the Vitis vinifera peel and seed gold nanoparticles in experimentally induced cancer in Swiss albino mice. 12-dimethylbenz [a] anthracene (DMBA) (single application) and 12-O-tetradecanoylphorbol 13-acetate (TPA) (thrice a week) were applied on the dorsal area of the skin to induce skin papillomagenesis in Swiss albino mice for 16 weeks. Gold nanoparticles were synthesized using Vitis vinifera peel and seed aqueous extracts and characterized by Transmission electron microscopic (TEM) analyses. On topical application, peel and seed gold nanoparticles demonstrated chemopreventive potential by significantly (p<0.05) reducing the cumulative number of tumors while increasing the antioxidant enzyme activities in the gold nanoparticles treated mice. The down-regulated expression of mutant p53, Bcl-2 and the levels of pan-cytokeratins might have facilitated the process of apoptosis in the chemical carcinogenesis process. The results were supported by the histopathological evaluation which exhibited mild dysplasia and acanthosis in the skin tissues of Vitis vinifera peel and seed AuNPs treated mice. Based on the present study, the chemopreventive action of Vitis vinifera peel and seed AuNPs is probably due to its ability to stimulate the antioxidant enzymes within the cells and suppressed abnormal skin cell proliferation that occurred during DMBA-induced skin papillomagenesis. Topics: Animals; Anticarcinogenic Agents; Antioxidants; Apoptosis; Chemoprevention; Down-Regulation; Gene Expression Regulation; Gold; Keratins; Male; Metal Nanoparticles; Mice; Neoplasms, Experimental; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Seeds; Skin Neoplasms; Tumor Suppressor Protein p53; Vitis | 2017 |
Case of isolated epidermolytic acanthoma: Genetic and immunohistochemical analysis.
Topics: Acanthoma; Aged; Diagnosis, Differential; Humans; Hyperkeratosis, Epidermolytic; Immunohistochemistry; Keratins; Male; Skin Neoplasms | 2016 |
Morpheaform Basal Cell Carcinomas With Areas of Predominantly Single-Cell Pattern of Infiltration: Diagnostic Utility of p63 and Cytokeratin.
Morpheaform basal cell carcinoma (BCC) is a variant of BCC characterized by narrow strands and nests of basaloid cells with dense sclerotic stroma. The histologic extent often exceeds the clinical impression, leading to high recurrence rates after standard excision. The authors encountered a case with single-cell invasion distant from the main tumor. To date a systematic review of single-cell infiltration in morpheaform BCC has yet to be performed.. Ten morpheaform BCCs, 10 nonmorpheaform aggressive BCCs, 5 desmoplastic trichoepitheliomas, and 2 microcystic adnexal carcinomas were identified by database search and confirmed on hematoxylin and eosin. Cases were evaluated by hematoxylin and eosin, immunohistochemical staining for p63, and (in a subset) broad-spectrum cytokeratin. Single-cell pattern was defined as individual cells, 2-cell clusters, or single-file invasion.. Three types of single-cell pattern were identified: intratumoral (single cells within the main tumor mass), peripheral, and distant. Single cells were typically a minor component relative to larger tumor nodules and strands. Eight of the 10 cases of morpheaform BCC demonstrated areas of single-cell pattern: 3 intratumoral, 3 peripheral, and 2 with distant spread (0.75 and 1.0 mm from the main tumor). Eight of the 10 aggressive BCC demonstrated a peripheral single-cell pattern. Rare intratumoral single cells were identified in 3/5 desmoplastic trichoepitheliomas and 1/2 microcystic adnexal carcinomas.. Single-cell pattern is frequently a component of morpheaform BCC. Tumor cells at a significant distance from the main component were unique to morpheaform BCC. Thus, when evaluating margins for morpheaform BCC, increased caution is recommended, and immunohistochemical stains for p63 or cytokeratins may be helpful. Topics: Biomarkers, Tumor; Biopsy; Carcinoma, Basal Cell; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Predictive Value of Tests; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins | 2016 |
Trichogerminoma: A Neoplasm With Follicular Differentiation and a Characteristic Morphology.
Topics: Aged; Biomarkers, Tumor; Biopsy; Cell Differentiation; Diagnosis, Differential; Epidermal Cyst; Humans; Keratins; Male; Neoplasms, Basal Cell; Skin Neoplasms | 2016 |
Consensus of Melanoma Gene Expression Subtypes Converges on Biological Entities.
Topics: Adult; Aged; Aged, 80 and over; Cell Proliferation; Cells, Cultured; Consensus; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Keratins; Male; Melanocytes; Melanoma; Microphthalmia-Associated Transcription Factor; Microphthalmos; Middle Aged; Neurogenesis; Pigmentation; Skin Neoplasms; Young Adult | 2016 |
Cytokeratin-positive fibroblastic reticular cell: a pitfall for dermatopathologists assessing lymph nodes for Merkel cell carcinoma.
Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Merkel Cell; Fibroblasts; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Skin Neoplasms | 2016 |
Ultrastructural Examination of a Case of Pagetoid Bowen Disease Exhibiting Immunohistochemical Features in Common With Extramammary Paget Disease.
A panel of immunohistochemical markers may be used to differentiate between pagetoid Bowen disease (PBD) and primary extramammary Paget disease (EMPD) in selected cases. Although diffuse staining with cytokeratin 7 (CK7), CAM5.2, carcinoembryonic antigen, epithelial membrane antigen (EMA), and gross cystic disease fluid protein 15 generally supports diagnosis of EMPD, cases have been reported where PBD also expressed CK7, EMA, and CAM5.2. Based on these findings, some authors suggested that the 2 entities may arise from the same multipotent stem cell, capable of further differentiation toward squamous and secretory lines. To the best of our knowledge, this issue has never been investigated by comparing PBD and EMPD at the ultrastructural level. We performed the first ultrastructural study of a case of PBD exhibiting common immunohistochemical features with EMPD. The lesion displayed some ultrastructural features often observed in Bowen disease and some that are typically found in EMPD. These findings indicate the presence of a bidirectional differentiation--secretory and squamous--within the same lesion, thus supporting the hypothesis that PBD and primary EMPD may arise from a common progenitor cell. Topics: Aged; Bowen's Disease; Carcinoembryonic Antigen; Carrier Proteins; Glycoproteins; gp100 Melanoma Antigen; Humans; Keratins; Male; Melanoma-Specific Antigens; Membrane Transport Proteins; Mucin-1; Paget Disease, Extramammary; Receptor, ErbB-2; S100 Proteins; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins; Ultrasonography | 2015 |
Ghost cells in pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic tumor: histological, immunohistochemical, and ultrastructural study.
Pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic tumor are the main entities presenting ghost cells as an important histological feature, in spite their quite different clinical presentation; it seems that they share a common pathway in the formation of these cells. The aim of this study is to examine and compare the characteristics of ghost and other cells that form these lesions.. Forty-three cases including 21 pilomatrixomas, 14 craniopharyngiomas, and eight calcifying cystic odontogenic tumors were evaluated by immunohistochemistry for cytokeratins, CD138, β-catenin, D2-40, Glut-1, FAS, CD10 and also by scanning electron microscopy.. The CKs, CD138, β-catenin, Glut-1, FAS, and CD10 were more often expressed by transitional cells of craniopharyngioma and calcifying cystic odontogenic tumor, compared with pilomatrixoma. Basaloid cells of pilomatrixoma showed strong positivity for CD138 and CD10. Differences on expression pattern were identified in transitional and basal cells, as ghost cells were negative for most antibodies used, except by low expression for cytokeratins. By scanning electron microscopy, the morphology of ghost cells were similar in their fibrillar cytoplasm, but their pattern varied from sheets in pilomatrixoma to small clusters in craniopharyngioma and calcifying cystic odontogenic tumor.. Mechanisms involved in formation of ghost cells are unknown, but probably they follow different pathways as protein expression in the basal/transitional cells was not uniform in the three tumors studied. Topics: beta Catenin; Craniopharyngioma; Epithelial Cells; fas Receptor; Glucose Transporter Type 1; Hair Diseases; Humans; Immunohistochemistry; Jaw Neoplasms; Keratins; Microscopy, Electron, Scanning; Neprilysin; Odontogenic Cyst, Calcifying; Odontogenic Tumors; Pilomatrixoma; Pituitary Neoplasms; Skin Neoplasms; Syndecan-1 | 2015 |
TGF-β1-dependent induction and nuclear translocation of FHL2 promotes keratin expression in pilomatricoma.
Pilomatricoma is a tumour derived from hair matrix cells, which shows progressive keratin expression. Tumorigenesis is frequently associated with activating mutations in β-catenin gene inducing nuclear expression of β-catenin protein. The present study analysed the role of transforming growth factor-β1 (TGF-β1) and four-and-a-half LIM domain protein 2 (FHL2) in pilomatricoma in synopsis with their expression patterns in human anagen hair. Human anagen hair showed TGF-β1 and nuclear FHL2 expression in the outer root sheath layer separated from nuclear β-catenin staining, which was observed in cells of matrix and inner root sheath layers. Correspondingly, 41 out of 50 pilomatricomas showed co-labelling of TGF-β1 and nuclear FHL2 in tumour cells, which mostly lacked nuclear β-catenin expression. Tumoural proliferation (ki67) was associated with nuclear β-catenin staining but not with expression of nuclear FHL2. In early pilomatricomas, TGF-β1 expression was observed in few peripheral tumour cells showing absent or faint nuclear FHL2 co-staining. TGF-β1 expression extended in growing tumours going along with strong nuclear FHL2 co-labelling as well as progressive keratin 14 and keratin 1 expression. In vitro, cultured human keratinocytes showed weak to marked autocrine TGF-β1 expression; in case of enhanced TGF-β1 expression associated with keratin 10 staining. TGF-β1-treatment of cultured human keratinocytes induced nuclear and cytoplasmatic FHL2 staining as well as keratin 14 staining. Accordingly, siRNA-mediated FHL2 knockdown of TGF-β1-stimulated keratinocytes reduced keratin 14 staining. In conclusion, tumoural TGF-β1 secretion seems to induce nuclear translocation of co-factor FHL2 mediating progressive keratin expression in pilomatricoma. Topics: Active Transport, Cell Nucleus; Adolescent; Adult; Aged; Child; Child, Preschool; Female; Hair Diseases; Humans; Immunohistochemistry; Infant; Infant, Newborn; Keratins; LIM-Homeodomain Proteins; Male; Middle Aged; Muscle Proteins; Pilomatrixoma; Skin Neoplasms; Transcription Factors; Transforming Growth Factor beta1; Young Adult | 2015 |
Cystic trichoblastoma: a report of two cases with an immunohistochemical study.
We herein report two cases of cystic trichoblastoma with an immunohistochemical study. The histopathological findings in these cases included new information, namely, their being composed of two and three cysts, the cystic components had features of a steatocystoma and a hybrid cyst in one case, and there were projections of an aggregation of trichoblastoma, as well as papillary projections of follicular germinative cells, from the cyst walls. The follicular germinative cells observed in the papillary projections and in the aggregations of trichoblastoma expressed cytokeratin-15 (clone C8/144B) and PHLDA1, markers of follicular stem cells. Cystic trichoblastoma is a unique type of trichoblastoma, which originates from the cyst walls of an infundibular cyst (usually) or steatocystoma/hybrid cyst (rarely). In some cases, a trichoblastic infundibular cyst is considered to be a minor form (or possibly a primitive stage) of cystic trichoblastoma. Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Follicular Cyst; Hair Diseases; Humans; Immunohistochemistry; Keratins; Male; Skin Neoplasms; Transcription Factors | 2015 |
Clinical and Pathologic Study of Feline Merkel Cell Carcinoma With Immunohistochemical Characterization of Normal and Neoplastic Merkel Cells.
The authors herein describe the morphologic and immunohistochemical features of normal Merkel cells as well as the clinicopathologic findings of Merkel cell carcinoma in cats. Merkel cells were characterized as vacuolated clear cells and were individually located in the epidermal basal layer of all regions examined. Clusters of Merkel cells were often observed adjacent to the sinus hair of the face and carpus. Immunohistochemically, Merkel cells were positive for cytokeratin (CK) 20, CK18, p63, neuron-specific enolase, synaptophysin, and protein gene product 9.5. Merkel cell carcinoma was detected as a solitary cutaneous mass in 3 aged cats (13 to 16 years old). On cytology, large lymphocyte-like cells were observed in all cases. Histologic examinations of surgically resected tumors revealed nests of round cells separated by various amounts of a fibrous stroma. Tumor cells were commonly immunopositive for CK20, CK18, p63, neuron-specific enolase, and synaptophysin, representing the characteristics of normal Merkel cells. Topics: Animals; Biomarkers, Tumor; Carcinoma, Merkel Cell; Cat Diseases; Cats; Female; Keratins; Male; Merkel Cells; Neurons; Phosphopyruvate Hydratase; Skin Neoplasms; Synaptophysin | 2015 |
Regulation of C-X-C chemokine gene expression by keratin 17 and hnRNP K in skin tumor keratinocytes.
High levels of the intermediate filament keratin 17 (K17) correlate with a poor prognosis for several types of epithelial tumors. However, the causal relationship and underlying mechanisms remain undefined. A recent study suggested that K17 promotes skin tumorigenesis by fostering a specific type of inflammation. We report here that K17 interacts with the RNA-binding protein hnRNP K, which has also been implicated in cancer. K17 is required for the cytoplasmic localization of hnRNP K and for its role in regulating the expression of multiple pro-inflammatory mRNAs. Among these are the CXCR3 ligands CXCL9, CXCL10, and CXCL11, which together form a signaling axis with an established role in tumorigenesis. The K17-hnRNP K partnership is regulated by the ser/thr kinase RSK and required for CXCR3-dependent tumor cell growth and invasion. These findings functionally integrate K17, hnRNP K, and gene expression along with RSK and CXCR3 signaling in a keratinocyte-autonomous axis and provide a potential basis for their implication in tumorigenesis. Topics: Animals; Chemokines, CXC; Gene Expression Regulation, Neoplastic; HeLa Cells; Heterogeneous-Nuclear Ribonucleoprotein K; Humans; Keratinocytes; Keratins; Mice, Knockout; Neoplasm Proteins; Receptors, CXCR3; Signal Transduction; Skin Neoplasms | 2015 |
Squamous cell carcinoma developed on chronic venous leg ulcer.
Chronic venous leg ulcers (VLU), especially long-lasting non-healing ulcers, are among the risk factors for squamous cell carcinoma (SCC). Malignant transformation of a VLU is a rare finding and the relative risk of carcinomatous transformation is quite low (about 5.8). SCC arising in the context of a VLU has a particularly aggressive behavior. A 76-year-old male patient with no relevant medical familial history, with chronic venous insufficiency CEAP C6 for 10 years [recurrent leg ulcers with favorable outcome (healing) after specific local and systemic treatment], showing for about three years one ulcerated lesion located on the anterior upper third of the right calf non-responsive to specific treatment, which subsequently increased their size and merged. Biopsy sample was taken. Histopathology showed epidermal acanthosis, papillomatosis, intense parakeratosis, pseudoepitheliomatous hyperplasia, dysplasia and moderately differentiated squamous cell carcinoma with areas of acantholysis. Immunohistochemistry (Ki67, EMA, cytokeratin 34βE12 and p63) was performed and all types of immunostaining were moderately to intense positive. Above-knee leg amputation and specific oncologic treatment were proposed as possible curative solutions but the patient refused. Ten months after diagnosis and discharge form the Department of Dermatology, the patient died. Patients with chronic venous leg ulcers and clinically suspicious lesions should be evaluated for malignant transformation of the venous lesion. When diagnosed, malignancy complicating a chronic venous leg ulcer requires a resolute treatment as it may be fatal. Topics: Aged; Amputation, Surgical; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Leg; Leg Ulcer; Male; Mucin-1; Risk Factors; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins; Varicose Ulcer | 2015 |
Pleomorphic spindle cell dermal neoplasm with dot-like keratin reactivity: keratin-positive AFX or carcinoma?
Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm of pleomorphic myofibroblast-like cells. Diagnosis requires exclusion of other undifferentiated spindle and pleomorphic cell neoplasms by immunohistochemistry. We report two patients with p63-non-reactive spindle cell neoplasms which resembled AFX but demonstrated anomalous dot-like immunolabeling with antibodies to high molecular weight keratin and keratin 5. One case recurred locally, suggesting such lesions may behave aggressively. Whether these lesions represent keratin-positive dermal sarcomas or poorly differentiated carcinomas is debatable. Regardless of exact classification, our experience suggests such cases should be managed as high-risk non-melanoma skin cancers. Topics: Aged; Carcinoma, Squamous Cell; Diagnosis, Differential; Histiocytoma, Malignant Fibrous; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Mohs Surgery; Neoplasm Recurrence, Local; Nevus, Spindle Cell; Skin Neoplasms; Xanthomatosis | 2015 |
Pan-cytokeratin markers for rapid frozen section immunocytochemistry from head and facial Mohs cases of basal cell carcinoma: a comparison and evaluation to determine the marker of choice.
The application of immunocytochemistry in the field of Mohs micrographic surgery (MMS) is well established. This study evaluates the use of pan-cytokeratins (AE1/AE3, MNF116 and AE1/AE3+PCK26) in the assessment of basal cell carcinoma (BCC) on frozen tissue debulk specimens. Fifty-five cases of BCC, all from head and facial sites, were assessed in the study. In addition to staining all cases for the three cytokeratin antibodies under investigation, sections were also stained with haematoxylin and eosin (H&E) to demonstrate tumour architecture and morphology. All sections for immunocytochemistry were stained on a Roche Ventana BenchMark Ultra automated platform employing a rapid frozen section protocol. Results were assessed based on the intensity of staining of keratinocytes (scale: 0-100%), as well as sensitivity of staining determined by the total percentage of keratinocytes stained within the tissue section. AE1/AE3 demonstrated the most consistent staining both in terms of intensity of staining and sensitivity, with a mean of 99.1% and 99.9%, respectively. AE1/AE3+PCK26 average results indicated scores of 70.6% for intensity and 87.2% for sensitivity, with MNF116 scoring 92.9% for intensity but only 57.3% for sensitivity. The data indicate that AE1/AE3 is the best pan-cytokeratin antibody to use in the assessment of BCC in MMS. The use of cytokeratin immunocytochemistry is justified in morphologically complex cases of BCC, or in cases where dense inflammatory infiltrate surrounding any suspicious cells make identification of small numbers of tumour cells difficult to determine with just an H&E stain. The significant rationale is that cytokeratin staining is a valuable adjunct in the study of tumour cell assessment in cases of MMS for BCC. In addition, the use of anti-AE1/AE3 cytokeratin antibodies provides the most consistent staining results for such cases. Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Facial Neoplasms; Frozen Sections; Humans; Immunohistochemistry; Keratins; Mohs Surgery; Sensitivity and Specificity; Skin Neoplasms | 2015 |
Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis: the involvement of keratin-17.
Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17. Topics: Animals; Carcinoma, Squamous Cell; Caspase 7; Cells, Cultured; Epidermis; Female; Gene Knockout Techniques; Keratinocytes; Keratins; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Proteolysis; Radiation Injuries, Experimental; Skin Neoplasms; Sunlight; Tumor Burden | 2015 |
Four cases of cell cannibalism in highly malignant feline and canine tumors.
Four cases of tumors in which cell internalization was frequently visualized are reported: one feline mammary carcinoma, one feline cutaneous squamous cell carcinoma, one canine pulmonary squamous cell carcinoma and one canine pleural mesothelioma. Cell internalization was observed by cytology in two of these cases (the feline mammary tumour and the pleural effusion in the canine mesothelioma) and by histopathology in all but the canine mesothelioma. Immunohistochemical staining for pancytokeratin was positive for both internalized and host cells, while E-cadherin expression was frequently absent, although internalized cells occasionally stained positive. This cell-to-cell interaction seems to be associated with tumors displaying a strong epithelial-mesenchymal transitional phenotype, in which cancer cells become engulfed by other cancer cells. Such event could be regarded as an important hallmark of very high malignancy. Topics: Animals; Biomarkers, Tumor; Biopsy; Cadherins; Carcinoma, Squamous Cell; Cat Diseases; Cats; Cytophagocytosis; Dog Diseases; Dogs; Female; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mammary Neoplasms, Animal; Mesothelioma; Pleural Neoplasms; Skin Neoplasms | 2015 |
Unexpected maspin immunoreactivity in Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous neuroendocrine tumor, which multifactorial etiopathogenesis seems to be related to ultraviolet radiation, Merkel cell polyomavirus (MCV), and immunosuppression. In this paper, we present three cases of diagnosed MCC in apparently healthy Caucasians, two of them located in a sun-exposed area. They represented 0.25 % of all cutaneous malignant tumors diagnosed in our department. In the first case, MCC was diagnosed in the frontal region of a 67-year-old male, the second case was located in the right thigh of a 55-year-old female, whereas the third case involved the upper trunk of a 62-year-old female. All of these cases were diagnosed in the pT1 stage, having a diameter smaller than 2 cm, but the invasion depth involved the hypodermis. Microscopically, they consisted of small cells with round-oval nuclei having finely dispersed chromatin and well-defined nucleoli. Immunohistochemically, the tumor cells displayed positivity for keratin 20 and neuroendocrine markers, being negative for keratin 7 and S100 protein. Maspin immunoreactivity was seen in cases 1 and 3. Not one of the cases expressed DOG-1 or even TTF-1. Furthermore, this is the first report in literature about maspin positivity in MCC that might be related to sun exposure. Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Merkel Cell; Female; Humans; Keratins; Male; Merkel cell polyomavirus; Neoplasm Invasiveness; Skin Neoplasms; Ultraviolet Rays | 2015 |
Primary cutaneous carcinosarcomas: a morphological histogenetic concept revisited.
To present and define diagnostic criteria for primary cutaneous carcinosarcomas (CSs). Neoplasms of 6 patients with primary cutaneous CSs were retrospectively analyzed. A panel of histopathologic parameters and immunophenotypic expression of distinct markers of differentiation were investigated. All cases had medium-to-poorly differentiated squamous cell carcinoma representing the epithelial component intermingled with a variable amount of malignant sarcomatous tissue proliferation. The authors identified 3 distinct morphological criteria for the diagnosis of primary cutaneous CSs with features of (1) a clearly defined dual neoplasm with explicit morphological characterization using histology and immunohistochemistry with distinct marker panels while, (2) metastases from distant sites and true collision neoplasms must be excluded, and (3) recognition of the neoplasm as a solid coherent proliferation with careful exclusion of sarcomatous stromal changes in the surrounding neoplasm stroma has to be assured. The low incidence of this entity and a plethora of different synonymous terms in the dermatopathologic literature often cause diagnostic problems and hamper the accurate comparative analysis of cases published previously. Herein, the authors propose defining criteria and a clearly defined morphological approach to contribute to more accurate dermatopathologic diagnoses and provide an unprecedented summary on this neoplastic entity. Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinosarcoma; Desmin; Female; gp100 Melanoma Antigen; Humans; Keratins; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Retrospective Studies; S100 Proteins; Skin Neoplasms | 2014 |
Clinical utility of a circulating tumor cell assay in Merkel cell carcinoma.
Quantitation of circulating tumor cells (CTCs) has utility in managing breast, colon, and prostate carcinomas.. We sought to determine whether a commercially available CTC assay provides prognostic information in Merkel cell carcinoma (MCC), insight into treatment responses, or both.. We analyzed CTCs in 52 specimens from 34 patients with MCC.. The presence of CTCs correlated with extent of disease at blood draw (P = .004). Among 15 patients with regional nodal disease, CTC-negative patients had 80% disease-specific survival at 2 years after the test, versus 29% for CTC-positive patients (P = .015). Among the entire cohort, those without CTCs had 72% MCC-specific survival whereas CTC-positive patients had 25% survival (n = 34, median follow-up 19 months, P = .0003). Fifty seven percent of patients with MCC had a cytokeratin "dot" visible in 20% or more of CTCs, a feature that was absent among CTCs from other carcinomas (0 of 13 cases).. CTC assay was performed at variable times after diagnosis and heterogeneity in extent of disease affects interpretability of the data.. CTC detection in MCC is feasible and appears to add prognostic information, particularly in patients with regional nodal disease. It may also assist clinical management in certain situations, including differentiating metastatic MCC cells from those of other carcinomas. Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; Carcinoma, Merkel Cell; Disease-Free Survival; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Longitudinal Studies; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Cells, Circulating; Prognosis; Risk Assessment; Skin Neoplasms; Statistics, Nonparametric; Survival Analysis | 2014 |
What is your diagnosis? Dermal mass in a dog.
Topics: Animals; Biopsy, Fine-Needle; Carcinoma, Basal Cell; Diagnosis, Differential; Dog Diseases; Dogs; Female; Immunohistochemistry; Keratinocytes; Keratins; Skin Neoplasms | 2014 |
Lymphoepithelioma-like carcinoma vs inflamed squamous cell carcinoma of the skin.
Topics: Aged; Carcinoma, Squamous Cell; Humans; Keratins; Male; Middle Aged; Mucin-1; Neoplasms, Multiple Primary; Parotid Neoplasms; Skin Neoplasms | 2014 |
A rare case of multiple clear cell acanthoma with a relatively rapid development of the lower legs.
Clear cell acanthoma, firstly described by Degos as "an epidermal tumor with a particular aspect", although quite a rare lesion, raised an important interest because it may be easily confused with other dermatologic lesions, in the absence of a histopathological examination. Its clinical aspect is of a solitary nodule, with a red-brown varying color, with a size of 3 mm to 2 mm, sometimes covered with a thin scall. We present a case of a multiple rare cell acanthoma (seven nodular formations), having a rapid development (about two months) diagnosed in a 71-year-old patient within the lower 1/3 of the right shin. Topics: Acanthoma; Aged; B-Lymphocytes; Dermis; Female; Glycogen; Humans; Immunohistochemistry; Inflammation; Keratinocytes; Keratins; Leg; Lymphocyte Count; Skin Neoplasms; T-Lymphocytes | 2014 |
Cutaneous epithelioid sarcomalike (pseudomyogenic) hemangioendothelioma: a little-known low-grade cutaneous vascular neoplasm.
Epithelioid sarcomalike (pseudomyogenic) hemangioendothelioma (ES-H) is a recently described and little-known vascular neoplasm that frequently presents with dermatologic lesions. Histopathologic characterization includes sheets or fascicles of plump, spindled and epithelioid, rhabdomyoblastlike neoplastic cells involving the dermis and often extending to subcutaneous tissue. Immunohistochemical analysis reveals neoplastic cells that show a constant immunophenotype characterized by immunoreactivity for cytokeratins and endothelial markers.. We described the clinical, histopathologic, and immunohistochemical features of 2 cases of cutaneous ES-H. Clinical examination revealed multifocal lesions that consisted of erythematous nodules on the leg and foot in case 1 and small perioral papules in case 2. Neoplastic cells had a rhabdomyoblastic appearance, with large nuclei and ample eosinophilic cytoplasm. Immunohistochemical analysis revealed expression of cytokeratin AE1/AE3, CD31, ERG, and FLI-1, with focal and weak positivity for CAM 5.2 and smooth muscle actin. The nuclei of neoplastic cells showed intact expression of INI-1. This immunoprofile, especially the ERG positivity, demonstrated the endothelial nature of proliferating cells.. We recommend adding the low-grade neoplasm ES-H to the large list of cutaneous vascular proliferations. Dermatologists should be aware of this low-grade cutaneous vascular tumor. Topics: Adult; Biomarkers, Tumor; Female; Hemangioendothelioma, Epithelioid; Humans; Immunohistochemistry; Keratins; Male; Skin; Skin Neoplasms; Young Adult | 2013 |
Malignant combined squamomelanocytic tumor: a clinical case.
A combined squamomelanocytic tumor is an exceedingly rare occurrence; little is known about its pathogenesis. A definitive diagnosis can only be made via histological examination. We describe herein an 83 year-old man who was discovered to have this combined tumor and recommend the appropriate management for such a lesion. Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Facial Neoplasms; gp100 Melanoma Antigen; Humans; Keratins; Male; MART-1 Antigen; Melanins; Melanoma; Melanoma-Specific Antigens; Neoplasms, Multiple Primary; S100 Proteins; Skin Neoplasms | 2013 |
Paranuclear dot-like cytokeratin MNF116 positivity in cutaneous myoepithelioma.
Topics: Adult; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Myoepithelioma; Skin Neoplasms | 2013 |
A case of small-cell prostate cancer with a metastasis to the scalp.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy; Bone Neoplasms; Carcinoma, Small Cell; Chromogranin A; Fatal Outcome; Head and Neck Neoplasms; Humans; Keratins; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Scalp; Skin Neoplasms; Tomography, X-Ray Computed | 2013 |
A cutaneous horn--benign or malignant?
This is a case report of a cutaneous horn, which was difficult to diagnose as benign or malignant. It demonstrates how these lesions can be approached in terms of diagnosis and management. Topics: Carcinoma, Squamous Cell; Cheek; Diagnosis, Differential; Facial Neoplasms; Humans; Keratins; Keratoacanthoma; Male; Middle Aged; Radiotherapy, Adjuvant; Skin Neoplasms | 2013 |
Diffuse CK7, CAM5.2 and BerEP4 positivity in pagetoid squamous cell carcinoma in situ (pagetoid Bowen's disease) of the perianal region: a mimic of extramammary Paget's disease.
Topics: Aged; Biomarkers; Biomarkers, Tumor; Bowen's Disease; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasms, Second Primary; Paget Disease, Extramammary; Skin Neoplasms; Vulvar Neoplasms | 2013 |
Cutaneous basal cell carcinoma with dual differentiation into squamous cell carcinoma and spindle cell squamous cell carcinoma: a case report with immunohistochemical studies.
Topics: Aged, 80 and over; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Skin Neoplasms; Tumor Suppressor Protein p53 | 2013 |
CD200-expressing human basal cell carcinoma cells initiate tumor growth.
Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC. Topics: Animals; Antigens, CD; Carcinoma, Basal Cell; Cell Differentiation; Cell Proliferation; Humans; Keratins; Kruppel-Like Factor 4; Mice; Mice, Inbred NOD; Mice, Nude; Mice, SCID; Receptors, G-Protein-Coupled; Skin Neoplasms; Smoothened Receptor; Transplantation, Heterologous; Tumor Stem Cell Assay | 2013 |
Pseudoangiosarcomatous squamous cell carcinoma in an old surgical scar of an African woman.
Squamous cell carcinoma, a malignant proliferation of keratinocytes, can be found in many regions of the body covered by stratified squamous epithelium and in areas covered by other epithelia but which had undergone squamous metaplasia. Squamous cell carcinoma has many variants.. We, retrospectively, reviewed the case file and histological features of a 75 year old trader with a rare variant of squamous cell carcinoma arising from an old surgical scar.. The 75-year-old African female trader presented to the hospital with three and a-half month history of a swelling in the anterior aspect of the left leg arising from an old surgical scar. Clinical examination showed an irregularly shaped ulcer measuring 14 x 16 cm with an everted edge and a hyperpigmented floor. Histologic sections of the specimen showed the infiltration of the papillary and reticular dermis of the skin by sheets of atypical spindle cells with areas of squamous differentiation. There was a contiguous area of capillary-like structures constituting about 30% of the sections examined. The neoplastic cells were positive for vimentin and cytokeratin but were negative for CD34. The diagnosis was pseudoangiosarcomatous squamous cell carcinoma.. This tumour can be found in Africans and in an old surgical scar. It can coexist with other variants of squamous cell carcinoma. There may be need in the future to add a new mixed variant to the current classification scheme. Topics: Aged; Carcinoma, Squamous Cell; Cicatrix; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Retrospective Studies; Skin Neoplasms; Vimentin | 2012 |
Spindle cell squamous cell carcinoma not expressing stratified but simple epithelial cytokeratin: efficacy of simple epithelial cytokeratin immunoreactivity.
We present two cases of spindle cell squamous cell carcinoma, which were derived from solar keratosis and burn scar in two elderly Japanese patients, respectively. The tumors involved the whole dermis and subcutis in connection with the overlying epidermis. They were composed mainly of anaplastic spindle cells partially forming storiform patterns. The tumor cells were diffusely positive for vimentin and cytokeratin 8/18 (clone CAM5.2, simple epithelial cytokeratin), but negative for cytokeratin 1/5/10/14 (clone 34βE12, stratified epithelial cytokeratin). Ultrastructural analysis of a patient demonstrated desmosomes and tonofilaments in the tumor cells. Although spindle cell squamous cell carcinoma is usually positive for vimentin, detailed cytokeratin profile is controversial. The present cases revealed immunohistochemistry not expressing stratified but simple epithelial cytokeratin and vimentin. We should be reminded of the efficacy of simple epithelial cytokeratin immunoreactivity in spindle cell squamous cell carcinoma. Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Skin Neoplasms; Vimentin | 2012 |
Cytokeratin 10-negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease.
The histopathologic pattern of clonal seborrheic keratosis (SK) is quite similar to the nested pattern of pagetoid Bowen's disease [squamous cell carcinoma in situ (SCCIS)], and differentiation between the two can be challenging, especially when only small pieces are available for interpretation.. Eleven examples of clonal SK and 13 examples of pagetoid SCCIS were examined histopathologically (tabulating necrotic keratinocytes, suprabasal mitoses, infiltrate, parakeratosis housing plump nuclei, crowding of nuclei) and immunohistochemically (using Ki-67, bcl-2, cytokeratin 7 and cytokeratin 10). Sensitivity, specificity, p-values (Fisher's exact test, two-tailed) and positive/negative likelihood ratios (+LR/-LR) were calculated.. Significant differences were seen with regard to crowding (p = 0.0009) and mitoses (p = 0.0006); however, only complete absence of necrotic keratinocytes or of crowding appeared to be diagnostically convincing for a diagnosis of clonal SK (-LR < 0.01). Significant differences were also seen with bcl-2 (p = 0.0005) and cytokeratin 10 antibodies (p < 0.00001). Both markers displayed a typical nested pattern in clonal SK, nests being bcl-2-positive and cytokeratin 10-negative. Cytokeratin 10-negative nests were the most convincing criterion for differentiation between clonal SK and pagetoid SCCIS (+LR > 10, -LR < 0.01).. The most reliable marker to distinguish clonal SK from pagetoid SCCIS is cytokeratin 10 when it spares nests. Other criteria that assist in the differential diagnosis are bcl-2 expression, absence of crowding and of mitoses. Topics: Biomarkers, Tumor; Bowen's Disease; Female; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Keratins; Keratosis, Seborrheic; Male; Mitosis; Neoplasm Proteins; Skin Neoplasms | 2012 |
Role of CD10, wide-spectrum keratin, p63, and podoplanin in the distinction of epithelioid and spindle cell tumors of the skin: an immunohistochemical study of 81 cases.
Cutaneous epithelioid and spindle cell neoplasms occasionally pose a significant diagnostic challenge on purely histologic grounds. Given the substantial clinicopathologic overlap between these lesions, especially in small biopsies, the use of immunohistochemical studies are essential. We evaluated the utility of a battery of immunohistochemical markers, including podoplanin (D2-40), CD10, p63, and wide-spectrum cytokeratin, for distinguishing cutaneous epithelioid and spindle cell tumors. A total of 81 cases, including 42 atypical fibroxanthoma (AFX), 13 spindle cell melanoma, 10 sarcomatoid carcinoma, 9 leiomyosarcoma (LMS), and 7 leiomyoma, formed the basis of our study. Immunohistochemical results were as follows-AFX: CD10 (35 of 42), p63 (1 of 42), CK (1 of 42), and podoplanin (19 of 42); spindle cell melanoma: CD10 (7 of 13), p63 (0 of 13), CK (0 of 13), and podoplanin (2 of 13); sarcomatoid carcinoma: CD10 (5 of 10), p63 (7 of 10), CK (4 of 10), and podoplanin (7 of 10); LMS: CD10 (4 of 9), p63 (0 of 9), CK (2 of 9), and podoplanin (1 of 9); and leiomyoma: CD10 (0 of 7), p63 (0 of 7), CK (0 of 7), and podoplanin (1 of 7). Our findings showed that the combination of certain immunohistochemical markers may be a useful adjunct in the evaluation of epithelioid and spindle cell tumors of the skin. In this study, we found that a combination of wide-spectrum cytokeratin and p63 are most helpful in the distinction of sarcomatoid carcinomas from other tumors; however, there remains a substantial minority of cases of sarcomatoid carcinoma that will consistently demonstrate negative staining for these markers. We also found that CD10 and podoplanin (D2-40) have limited diagnostic utility in epithelioid and spindle cell tumors of the skin; however, a strong and diffuse pattern of staining will favor the diagnosis of AFX. Caution should also be observed in the diagnosis of spindle cell malignant melanoma because some cases may express CD10, p63, and podoplanin while being nonreactive to S100 protein. Awareness of the limitations of the use of these stains and familiarity with their staining patterns in spindle and epithelioid cell tumors of the skin are extremely important because the prognostic and therapeutic implications for such neoplasms may be quite different. Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Epithelioid Cells; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Neprilysin; Predictive Value of Tests; Sarcoma; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins; Wisconsin; Young Adult | 2012 |
An immunohistochemical comparison of cytokeratin 7, cytokeratin 15, cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in differentiating porocarcinoma from squamous cell carcinoma.
The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of cytokeratin 7, cytokeratin 15, cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, cytokeratin 19, cytokeratin 7, CAM 5.2, cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By χ(2) test, statistically significant P values (<.05) were observed for cytokeratin 7, cytokeratin 19, and nestin in the distinction of porocarcinoma from squamous cell carcinoma. However, in a logistic regression and stepwise selection for predicting a porocarcinoma, statistical significance was observed only for cytokeratin 19 (P = .0003). In conclusion, we found cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include cytokeratin 7, cytokeratin 19, and nestin. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Diagnosis, Differential; Eccrine Porocarcinoma; Female; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Nerve Tissue Proteins; Nestin; Sensitivity and Specificity; Skin Neoplasms; Sweat Gland Neoplasms | 2012 |
Anetodermic pilomatricoma: molecular characteristics and trauma in the development of its bullous appearance.
Pilomatricoma is a common benign neoplasm of the skin characterized by a solid cutaneous nodule of hair matrix origin. The anetodermal or lymphangiectatic variant of pilomatricoma is rare, and its bullous appearance is often associated with attenuated collagen and elastic fibrils and dilated lymphatic vessels in the overlying dermis. However, the tumors of anetodermic pilomatricoma have never been characterized at the molecular level, and the exact mechanism for their development is unknown. In this study, we evaluated histological and molecular features of a bullous pilomatricoma along with 5 control tumors and determined that tumors of both anetodermic and control pilomatricoma comprise similar molecular features, such as nuclear lymphoid enhancer binding factor 1 (LEF1) localization and the expression of keratins. In addition, we associated the development of the anetodermic pilomatricoma with mechanical trauma, scar tissue formation, and increased numbers of blood and lymphatic vessels. This study suggests that the development of the anetodermic form of pilomatricoma is unlikely to be associated with the intrinsic properties of the tumor but with the mechanical trauma that disrupts the dermal integrity and vascular microenvironment. Topics: Adolescent; Adult; Biomarkers, Tumor; Blister; Blood Vessels; Female; Fluorescent Antibody Technique; Hair Diseases; Humans; Immunohistochemistry; Keratins; Lymphatic Vessels; Lymphoid Enhancer-Binding Factor 1; Male; Middle Aged; Pilomatrixoma; Skin Neoplasms; Stress, Mechanical; Young Adult | 2012 |
Atypical fibroxanthoma--a retrospective immunohistochemical study of 42 cases.
Atypical fibroxanthoma is a cutaneous dermal malignancy that presents on the sun-damaged skin of elderly people. It requires a definitive diagnosis, from a high-grade sarcoma to a nonmesenchymal neoplasm. The recommended treatment protocol differs from similar histologically related tumors; thus, a diagnosis of atypical fibroxanthoma should fulfill strict histologic and immunohistochemical stain criteria. The use of these standards will exclude other skin malignancies, including malignant fibrous histiocytoma, angiosarcoma, malignant melanoma, and squamous cell carcinoma. This study was performed with the aim of identifying key immunostains to develop diagnostic criteria.. Forty-two cases were studied retrospectively over a 10-year period using a panel of immunostains.. The average age at presentation was 78 years, with a male predominance. The scalp was found to be the most common site of occurrence, although other investigators have found the forehead, cheeks, nose, and ears as the prevailing sites of presentation.. An extensive panel of immunohistochemical stains can be used to prove a diagnosis of atypical fibroxanthoma. Topics: Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Diagnosis, Differential; Female; Head and Neck Neoplasms; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Proteins; Retrospective Studies; Skin Neoplasms; Vimentin | 2012 |
Montagna Symposium 2011: 60th Anniversary--Advances in Science and Medicine Catalyzed by Pioneering Skin Research.
Topics: DNA Damage; DNA Repair; Genes, p53; Genes, ras; Hedgehog Proteins; Humans; Interleukin-1alpha; Keratins; Signal Transduction; Skin Neoplasms | 2012 |
Pleomorphic dermal sarcoma: adverse histologic features predict aggressive behavior and allow distinction from atypical fibroxanthoma.
The behavior of atypical fibroxanthoma is benign, if strict diagnostic criteria are applied. Tumors with similar pathologic features but deep subcutaneous invasion, necrosis, and/or lymphovascular or perineural invasion are thought to be associated with adverse outcome and are better regarded as pleomorphic dermal sarcoma or undifferentiated pleomorphic sarcoma of skin. This tumor group is not well documented in the literature, and its characteristics are only poorly defined. To study the clinical and pathologic spectrum more comprehensively, we retrieved 32 pleomorphic dermal sarcomas from our departmental files. The tumors were large (median: 25 mm) and exclusively presented on sun-damaged skin with a strong predilection for the head. Typically, elderly men were affected (median age: 81 y). Histologically, these often ulcerated tumors were poorly marginated, asymmetrical, and deeply invasive into deep subcutaneous, muscular, and/or fascial tissues. The tumors were cellular and composed of pleomorphic epithelioid cells, atypical spindle cells, and multinucleated tumor giant cells in varying proportions. Mitotic count was brisk and often atypical. Tumor necrosis was observed in 53%, lymphovascular invasion in 26%, and perineural infiltration in 29%. The majority of tumors showed a predominance of atypical spindle cells in a fascicular arrangement. A sheet-like growth of pleomorphic epithelioid cells or mixed spindle and epithelioid cell features were less frequently observed. Myxoid and keloidal change, a desmoplastic stromal response, pseudoangiomatous and storiform growth patterns, and admixed osteoclast-like giant cells were additional morphologic features in some cases. No immunoreactivity was noted for multiple cytokeratins, S100, HMB-45, desmin, and CD34. Smooth muscle actin was expressed in 70%, CD31 in 48%, epithelial membrane antigen in 16%, Melan A in 6%, and p63 in 1 case. CD10 was expressed in all cases stained. Follow-up (available for 29 patients; median: 24 mo) showed local recurrence in 28% and a metastatic rate of 10%, mainly in the skin. Progressive metastatic disease was observed in 2 patients. Remission was achieved in 1 patient using systemic chemotherapy. The second patient died in the setting of advanced-stage non-Hodgkin lymphoma. No disease-related mortality was noted. Our data underscore the importance of recognizing adverse histologic features in tumors otherwise resembling atypical fibroxanthoma. Deep subcutaneous invasion, tum Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Comorbidity; Diagnosis, Differential; Female; Humans; Keratins; Male; Middle Aged; Sarcoma; Scotland; Skin Neoplasms; Xanthomatosis | 2012 |
Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene.
Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and KRT14 genes. Squamous cell carcinoma (SCC) represents the second most frequent skin neoplasia with complex aetiology. The molecular events disrupting the orchestrated interplay between the cytoskeleton, cell adhesion molecules and signalling proteins are ill understood in SCC. We describe the molecular background and the unusual course of the disease in a patient with EBS Dowling-Meara, severe keratoderma and a massive verrucous carcinoma. Skin and tumour samples from the patient were analysed using light microscopy, immunohistochemistry and immunofluorescence mapping. Mutation analysis of the KRT5 and KRT14 genes identified the novel KRT5 mutation p.E477D. Invasive tumour areas were characterized by downregulation of keratins 5 and 14, reduced and irregular desmocollin-2 expression and increased expression of keratins 6, 16 and 17. Levels of Ki-67 were increased and levels of E-cadherin strongly reduced in the tumour tissue. In this case a novel KRT5 mutation led to increased fragility of keratinocytes. Desmosome and adherens junctions were destabilized, which may trigger keratinocyte-mediated inflammation, possibly via p120-catenin-dependent signalling, suggesting a link between a keratin mutation and SCC, which adds weight to the hypothesis that disturbance of the cytoskeleton represents a major cause in the appearance of the malignant phenotype. Some individuals with EBS may be at risk of developing secondary SCC. Topics: Adult; Cadherins; Carcinoma, Verrucous; DNA Mutational Analysis; Down-Regulation; Epidermolysis Bullosa Simplex; Fluorescent Antibody Technique, Indirect; Humans; Immunohistochemistry; Keratin-14; Keratin-5; Keratinocytes; Keratins; Ki-67 Antigen; Mutation; Skin Neoplasms; Tomography, X-Ray Computed | 2012 |
Folliculocentric squamous cell carcinoma with tricholemmal differentiation: a reappraisal of tricholemmal carcinoma.
The diagnostic criteria for tricholemmal carcinoma remain controversial, and even the existence of tricholemmal carcinoma has been the subject of debate. Follicular (infundibular) squamous cell carcinoma (SCC) is a distinctive subset of SCC, which develops solely with folliculocentricity, and displays the features of conventional SCC without tricholemmal differentiation.. To examine the existence of pure folliculocentric SCCs showing tricholemmal differentiation, that is, tricholemmal carcinoma.. In total, 812 SCCs were examined, and those meeting the following diagnostic criteria were selected: (i) pure folliculocentricity without any associated Bowen's disease or actinic keratosis; (ii) composition primarily of lightly eosinophilic cells or clear cells containing glycogen; (iii) columnar lightly eosinophilic or clear cells aligned in a palisade along a discernible basement membrane; (iv) tricholemmal keratinization; (v) glycogen contained within the pale/clear cells; and (vi) cytological atypia and or infiltrative growth. We also evaluated whether the immunohistochemical profile [cytokeratin (CK)1, CK10, CK17, CD34 and D2-40] seen in normal hair follicles was retained in the selected lesions.. Only two lesions met the criteria. The immunohistochemical profile of the normal outer root sheath cells was generally retained in these lesions, except for CD34.. Tricholemmal carcinoma is a rare occurrence, but it does exist, and at least one type of tricholemmal carcinoma is considered to be related to follicular (infundibular) SCC. Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms | 2012 |
Tri-modal confocal mosaics detect residual invasive squamous cell carcinoma in Mohs surgical excisions.
For rapid, intra-operative pathological margin assessment to guide staged cancer excisions, multimodal confocal mosaic scan image wide surgical margins (approximately 1 cm) with sub-cellular resolution and mimic the appearance of conventional hematoxylin and eosin histopathology (H&E). The goal of this work is to combine three confocal imaging modes: acridine orange fluorescence (AO) for labeling nuclei, eosin fluorescence (Eo) for labeling cytoplasm, and endogenous reflectance (R) for marking collagen and keratin. Absorption contrast is achieved by alternating the excitation wavelength: 488 nm (AO fluorescence) and 532 nm (Eo fluorescence). Superposition and false-coloring of these modes mimics H&E, enabling detection of cutaneous squamous cell carcinomas (SCC). The sum of mosaic Eo+R is false-colored pink to mimic the appearance of eosin, while the AO mosaic is false-colored purple to mimic the appearance of hematoxylin in H&E. In this study, mosaics of 10 Mohs surgical excisions containing invasive SCC, and five containing only normal tissue were subdivided for digital presentation equivalent to 4 × histology. Of the total 50 SCC and 25 normal sub-mosaics presented, two reviewers made two and three type-2 errors (false positives), respectively. Limitations to precisely mimic H&E included occasional elastin staining by AO. These results suggest that confocal mosaics may effectively guide staged SCC excisions in skin and other tissues. Topics: Absorption; Acridine Orange; Artifacts; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Collagen; Cytoplasm; Eosine Yellowish-(YS); False Positive Reactions; Humans; Keratins; Microscopy, Confocal; Mohs Surgery; Neoplasm Invasiveness; Reproducibility of Results; Skin; Skin Neoplasms | 2012 |
Dermokine-β impairs ERK signaling through direct binding to GRP78.
Dermokine-β is abundant in stratified epithelia and in differentiating cultured keratinocytes. In this study, we investigated the role of dermokine-β in differentiation of keratinocytes. Treatment of keratinocytes or skin tumor cells with dermokine-β attenuated phosphorylation of extracellular-signal-regulated kinase (ERK). Exposure of cells to dermokine-β, as well as its carboxyl-terminus domain peptide, interrupted phosphorylation of ERK and stimulated dermokine gene expression. Inhibition of ERK signaling by its specific inhibitor also increased dermokine expression level. A combination of chemical cross-linking and immunoprecipitation, followed by proteomics analyses, identified glucose-regulated protein 78 (GRP78) as a dermokine-β-associated protein. Blockage of GRP78 expression by a specific siRNA abrogated actions of dermokine-β. These findings provide novel insights into the physiological significance of dermokine-β in the epidermis. Topics: Dose-Response Relationship, Drug; Endoplasmic Reticulum Chaperone BiP; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Heat-Shock Proteins; Humans; Intercellular Signaling Peptides and Proteins; Keratinocytes; Keratins; Models, Biological; Phosphorylation; Protein Isoforms; Protein Structure, Tertiary; Proteins; Signal Transduction; Skin Neoplasms | 2012 |
Sinonasal non-keratinizing squamous cell carcinoma with nasal skin extension as the initial presentation.
Sinonasal non-keratinizing squamous cell carcinoma (SCC), previously designated as transitional cell carcinoma or cylindrical cell carcinoma, is an uncommon malignant neoplasm with distinct histopathological features, considered to be a low-grade malignancy that usually occurs in elderly patients. Extensive local invasion is uncommon. Here we report a case of 90-year-old woman whose original presentation was as erythematous nasal skin nodules, biopsy of which showed a dermal tumor with features of sinonasal non-keratinizing SCC. No epidermal dysplasia was present. A subsequent computed tomography scan confirmed the presence of an endophytic tumor on the nasal sidewall. The initial presentation of sinonasal non-keratinizing SCC as a skin lesion is previously unreported to our knowledge. Diagnosis in this context requires accurate evaluation of the histopathology as well as a comprehensive knowledge of pathology specific to this anatomic location. Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Keratins; Neoplasm Invasiveness; Paranasal Sinus Neoplasms; Skin; Skin Neoplasms | 2012 |
Immunohistochemical expression of podoplanin in so-called hard α-keratin-expressing tumors, including calcifying cystic odontogenic tumor, craniopharyngioma, and pilomatrixoma.
Podoplanin, a transmembrane sialomucin-like glycoprotein, is a specific marker of lymphatic vessels, and its expression is also considered to be associated with tumor invasion and tooth development. In this study, we examined the expression of podoplanin in calcifying cystic odontogenic tumor (CCOT) in comparison with that in other so-called hard α-keratin-expressing tumors such as craniopharyngioma (CP) and pilomatrixoma (PM). Immunohistochemical staining for podoplanin was carried out using surgical specimens of 15 CCOTs of the jaw, 19 CPs of the pituitary gland, and 15 PMs of the skin. Positivity for hard α-keratin was evident in ghost, shadow and transitional cells in all of these tumors (100%). The podoplanin expression in CCOTs was evident in the periphery of ameloblastoma-like epithelium (86.6%) and the epithelial cells adjacent to ghost cells (60%). On the other hand, in adamantinomatous-type CPs, podoplanin expression was observed in epithelial components corresponding to the stratum intermedium (100%), but not in the periphery of ameloblastoma-like epithelium (0%). In squamous-type CPs podoplanin was expressed in basal cells (100%), but all of the PMs were podoplanin-negative (0%). In the periphery of the ameloblastoma-like epithelium or basophilic cell layer, podoplanin was expressed more strongly in CCOTs than in CPs or PMs. These findings suggest that the expression of podoplanin in CCOTs may reflect rapid turnover of cytoskeletal filaments and local invasiveness. Topics: Basophils; Biomarkers, Tumor; Craniopharyngioma; Cytoskeleton; Epithelial Cells; Humans; Immunohistochemistry; Jaw Neoplasms; Keratins; Membrane Glycoproteins; Neoplasm Invasiveness; Odontogenic Tumors; Odontoma; Pilomatrixoma; Pituitary Neoplasms; Skin Neoplasms | 2012 |
Anti-cytokeratin CAM5.2 should not be mistaken for cytokeratin 8/18 monoclonal antibody: comment on "spindle cell squamous cell carcinoma not expressing stratified but simple epithelial cytokeratin: Efficacy of simple epithelial cytokeratin immunoreactivi
Topics: Carcinoma, Squamous Cell; Female; Humans; Keratins; Male; Skin Neoplasms; Vimentin | 2012 |
Primary cutaneous rhabdomyosarcoma: a clinicopathologic review of 11 cases.
Rhabdomyosarcoma is a malignant mesenchymal tumor with skeletal muscle differentiation. Primary cutaneous rhabdomyosarcoma is rare. We report a series of 11 cases of primary cutaneous rhabdomyosarcoma.. Cases diagnosed as rhabdomyosarcoma arising in the dermis/subcutis with no identified primary tumor elsewhere were retrospectively reviewed. Follow-up was obtained.. The tumors occurred in five children and six adults. The adult subset consisted of pleomorphic, epithelioid and not otherwise specified (NOS) subtypes while the pediatric subset showed alveolar and embryonal subtypes. All cases showed immunohistochemical staining consistent with the diagnosis of rhabdomyosarcoma. Three adult cases showed immunoreactivity for cytokeratins (one pleomorphic, one epithelioid and one NOS.. Primary cutaneous rhabdomyosarcoma shows a bimodal age distribution and male predominance, correlating with rhabdomyosarcoma in deep soft tissue. Follow-up, available on all patients, showed aggressive behavior in both children and adults. Primary cutaneous rhabdomyosarcoma should be considered in the differential diagnosis of tumors with abundant eosinophilic cytoplasm and those with "small round blue cell" morphology. Desmin, myogenin and MYOD1 are a trio of markers with high sensitivity and specificity for primary cutaneous rhabdomyosarcoma. Cytokeratin immunoreactivity in primary cutaneous rhabdomyosarcoma represents a potential diagnostic pitfall in the differential diagnosis with sarcomatoid carcinoma. Topics: Adolescent; Age Factors; Aged; Aged, 80 and over; Biomarkers, Tumor; Child, Preschool; Cytoplasm; Dermis; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Infant; Keratins; Male; Middle Aged; MyoD Protein; Neoplasm Proteins; Retrospective Studies; Rhabdomyosarcoma; Sex Factors; Skin Neoplasms | 2012 |
Discrimination of squamous cell carcinoma in situ from seborrheic keratosis by color analysis techniques requires information from scale, scale-crust and surrounding areas in dermoscopy images.
Scale-crust, also termed "keratin crust", appears as yellowish-to-tan scale on the skin's surface. It is caused by hyperkeratosis and parakeratosis in inflamed areas of squamous cell carcinoma in situ (SCCIS, Bowen's disease) and is a critical dermoscopy feature for detecting this skin cancer. In contrast, scale appears as a white-to-ivory detaching layer of the skin, without crust, and is most commonly seen in benign lesions such as seborrheic keratoses (SK). Distinguishing scale-crust from ordinary scale in digital dermoscopy images holds promise for early SCCIS detection and differentiation from SK. Reported here are image analysis techniques that best characterize scale-crust in SCCIS and scale in SK, thereby allowing accurate separation of these two dermoscopic features. Classification using a logistic regression operating on color features extracted from these digital dermoscopy structures can reliably separate SCCIS from SK. Topics: Area Under Curve; Carcinoma, Squamous Cell; Databases, Factual; Dermoscopy; Diagnosis, Differential; Humans; Image Processing, Computer-Assisted; Keratins; Keratosis, Seborrheic; Logistic Models; ROC Curve; Skin Neoplasms | 2012 |
Cytokeratin expression patterns in multiple infundibulocystic basal cell carcinoma.
Infundibulocystic basal cell carcinoma (IBCC) is a variant of basal cell carcinoma. Sporadic cases usually represent a solitary tumor and multiple IBCC is rare. There have been no reports in which the tumor differentiation is characterized immunohistochemically. We report a case of multiple IBCC which developed on a patient's scalp by performing histopathological and immunohistochemical examinations, using monoclonal antibodies against cytokeratins (CKs). A 76-year-old female had noticed multiple small papules on her scalp. She noticed that the tumors were growing when she underwent systemic chemotherapy for metastatic lung cancer. Routine histopathological specimens from skin biopsies revealed findings typical of IBCC. The tumor cells expressed CK14 and CK17. However, CK1 and CK10 were expressed only in a few cells in the inner area of the tumors. The present case is unique in two points. First, multiple tumors developed on the patient's scalp during the systemic chemotherapy for the lung cancer. Second, the tumor showed CK expression patterns characteristic to infundibular and trichilemmal epithelia. Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carboplatin; Carcinoma, Basal Cell; Docetaxel; Female; Humans; Immunohistochemistry; Irinotecan; Keratins; Lung Neoplasms; Neoplasms, Second Primary; Skin Neoplasms; Taxoids | 2011 |
Tropism of herpes simplex virus type 1 to nonmelanoma skin cancers.
Current treatments for nonmelanoma skin cancer include surgery, Mohs micrographic surgery, radiation, cryosurgery, photodynamic therapy, local chemotherapy and application of immunomodulators such as imiquimod. However, all have a 5-year recurrence rate of 1-40%. Gene therapy for the treatment of skin cancers is a promising new approach, as delivery of the vectors to the skin is simple and safety issues can be properly addressed.. To develop an ex-vivo organ culture system for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) tumours, and to test the feasibility of applying oncolytic viruses to these tumours.. We first optimized conditions for the maintenance of BCC and SCC tissues in organ culture, and demonstrated viability of the tissues ex vivo for 3-7 days. The tropism of two potential oncolytic viral vectors, herpes simplex virus type 1 (HSV-1) and adenovirus (AD), was next evaluated.. Immunohistological analysis revealed that HSV-1 targeted tumour cells that expressed p63 and did not express keratin 15 or keratin 14 markers of keratinocytes. Further examination indicated that uninfected BCC and SCC tissues express two isoforms of p63 mRNA, and HSV-1 infection specifically enhanced expression of the TAp63 isoform. Furthermore, following infection, both HSV-1 and AD induced apoptosis in the BCC and SCC cells as indicated by the induction of activated caspase-3.. The results indicated a specific pattern of viral tropism to skin cancer cells that are critical for maintenance of the tumour. This new experimental system should aid in the analysis of new therapeutic modalities, such as oncolytic viruses, for future treatment of these skin tumours. Topics: Adenoviridae; Apoptosis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Caspase 3; Herpesvirus 1, Human; Humans; Immunohistochemistry; Keratinocytes; Keratins; Organ Culture Techniques; Skin Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Viral Tropism | 2011 |
Comparative immunohistochemical analyses on the modes of cell death/keratinization in epidermal cyst, trichilemmal cyst, and pilomatricoma.
Keratinization is a kind of cell death called terminal differentiation and includes various patterns such as epidermal keratinization (EK), trichilemmal keratinization (TK), and shadow cell differentiation (SCD), whereas these have not been comparatively investigated from a standpoint of cell death. In the present study, surgically extirpated specimens of epidermal cyst, trichilemmal cyst, and pilomatricoma (10 cases in each) were subjected to immunohistochemistry for single-strand DNA (ssDNA), gamma-H2AX, cleaved caspase-3, cleaved lamin A, caspase-14, and CD138 to compare the modes of cell death and keratinization pattern. Transitional cells in pilomatricoma were immunoreactive, although not in whole part, for ssDNA and gamma-H2AX, and negative for cleaved caspase-3 and cleaved lamin A. Epidermal and trichilemmal cyst were negative for these 4 markers, except for ssDNA or cleaved lamin A in a small number of parakeratotic cells in a few cases. The keratinizing component showed caspase-14(+)/CD138(-) in epidermal cyst, caspase-14(-)/CD138(+) in trichilemmal cyst, and caspase-14(-)/CD138(-) in pilomatricoma. These results indicate that EK, TK, and SCD have a common property of apoptosis-like programmed cell death without caspase-3 activation or nuclear fragmentation. Meanwhile, they show different characteristics one another as follows: (A), DNA double-strand breaks occur in the transitional cells of SCD but not in EK/TK; and (B), EK, TK, and SCD can be distinguished by expression pattern of caspase-14 and CD138 in the keratinizing component. Topics: Biomarkers, Tumor; Caspase 14; Cell Death; Cell Differentiation; DNA Breaks, Double-Stranded; Epidermal Cyst; Hair Diseases; Humans; Immunohistochemistry; Keratins; Pilomatrixoma; Skin Diseases; Skin Neoplasms; Syndecan-1 | 2011 |
Primary cutaneous epithelioid angiosarcoma: a clinicopathologic study of 13 cases of a rare neoplasm occurring outside the setting of conventional angiosarcomas and with predilection for the limbs.
Epithelioid angiosarcomas are rare aggressive neoplasms that occur most frequently in deep soft tissues. Primary cutaneous lesions are rare, and there are discrepant findings in the literature regarding their behavior. In this study, we report a series of 13 cases of primary cutaneous epithelioid angiosarcoma and analyze their clinicopathologic features. The tumors arising in the conventional settings for cutaneous angiosarcoma (ie, in the head and neck region of elderly patients, and those occurring postradiation or associated with lymphedema) were excluded. Primary cutaneous epithelioid angiosarcoma occurred in adults (mean age, 66 y) with an equal sex distribution, and presented as solitary (n=10) or multiple (n=3) nodules ranging in size from 8 to 80 mm, with a predilection for the limbs (n=10). Histopathologically, the tumors comprised infiltrative sheets of atypical epithelioid cells within the dermis with or without the involvement of the subcutis. Vascular channel formation and intracytoplasmic lumina were seen, at least focally, in most cases. Mitoses were readily identified and necrosis was seen in 40% of the cases. The tumors were immunoreactive for vascular markers, with CD31 and FLI-1 offering the highest sensitivity. Pancytokeratin was positive in two thirds of the cases, and epithelial membrane antigen was positive in one-quarter of the cases. There was rare focal expression of Melan-A (n=2) and smooth muscle actin (n=3). Follow-up information was available for 11 patients. Six patients died of metastatic disease after a median follow-up of 12 months (range, 3 to 36 mo), and 1 patient died of unrelated causes. These findings suggest that primary cutaneous epithelioid angiosarcoma occurring outside the conventional settings of angiosarcoma is a highly aggressive malignant tumor with mortality rates in excess of 55% after 3 years. Topics: Actins; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Epithelioid Cells; Extremities; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; MART-1 Antigen; Microfilament Proteins; Middle Aged; Mitosis; Mucin-1; Neoplasm Invasiveness; Neoplasm Staging; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Cytoplasmic and Nuclear; Skin Neoplasms; Time Factors; Trans-Activators; Treatment Outcome | 2011 |
Basaloid squamous cell carcinoma of the skin.
Basaloid squamous cell carcinoma (BSCC), an aggressive tumor of the aerodigestive tract, was described over 20 years ago, and its defining histologic parameters remain largely unchanged. While rare reports have noted cutaneous metastatic deposition, primary tumors have not been previously described.. Although most cutaneous malignancies with basaloid features comprise variants of basal cell carcinomas, a subset exhibit histologic attributes suggestive of more aggressive tumors. We evaluated 3 such tumors submitted to our dermatopathology service over a 6-month period.. Immunohistochemical stains useful in differentiating the lineage of cutaneous malignancies with basaloid-appearing tumor cells were employed. Human papillomavirus (HPV) detection and typing were performed by using polymerase chain reaction and sequencing.. The tumor cells expressed high molecular weight cytokeratin (34βE12) and cytokeratin 5/6 but not Ber-EP4 or bcl-2. This pattern of immunohistochemical staining and the histologic attributes of the neoplasms are inconsistent with those expected in better defined cutaneous basaloid malignancies but are characteristic of BSCC. Two of the tumors arose in the inguinal crease of middle-aged men, and two patients were known to be immunosuppressed. HPV genotype 33 was detected in the tumor tissue from both inguinal lesions.. The number of cases available for evaluation is small and any prognostic implications therefore tenuous.. The differential diagnosis of cutaneous malignancies exhibiting basaloid cells should include BSCC, a tumor with an unusual pattern of immunohistochemical staining and a potentially poor prognosis. Topics: Aged; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Risk Assessment; Sampling Studies; Skin Neoplasms; Survival Rate; Treatment Outcome | 2011 |
Cutaneous metastasis in an old surgical scar revealing gastric linitis.
Topics: Biopsy; Carcinoma, Signet Ring Cell; Cicatrix; Fatal Outcome; Humans; Keratins; Linitis Plastica; Male; Middle Aged; Pulmonary Embolism; Skin Neoplasms; Stomach Neoplasms | 2011 |
Subungual trichoadenoma showing differentiation toward follicular infundibulum.
Topics: Adenoma; Humans; Keratins; Male; Middle Aged; Nails; Skin Neoplasms | 2011 |
EWSR1 gene rearrangement occurs in a subset of cutaneous myoepithelial tumors: a study of 18 cases.
Cutaneous myoepithelial tumors form a clinicopathological spectrum ranging from mixed tumor to myoepithelioma and myoepithelial carcinoma. Recently, EWSR1 rearrangement has been described in a subset of soft tissue myoepithelial tumors, whereas the cutaneous counterparts showed this aberration in a minority of cases. This raises the question whether cutaneous myoepithelial tumors have comparable genetic alterations. We examined 18 cases of cutaneous myoepithelial tumors arising in 7 female and 11 male patients (age range, 34-86 years; mean, 58 years). Eight mixed tumors occurred at the head, and one at the scrotum. Six myoepitheliomas arose at the extremities, and one case each at the back and head. One myoepithelial carcinoma occurred at the cheek. The tumor size ranged from 0.3 to 1.7 cm (mean, 1.0 cm). All mixed tumors and three myoepitheliomas were limited to the dermis. Four myoepitheliomas and the myoepithelial carcinoma involved the subcutis. Mixed tumors and myoepitheliomas were composed of myoepithelial cells with a variable cytomorphology, architecture and stromal background. Ductal structures were seen by definition in mixed tumors. The myoepithelial carcinoma represented an infiltrative dermal neoplasm consisting of atypical spindle cells. Immunohistochemically, all cases tested were positive for EMA and calponin, whereas S100, CK, ASMA and GFAP were expressed in 90%, 80%, 78% and 50% of the cases tested, respectively. By fluorescent in situ hybridization analysis, 7 out of 16 cases (44%) exhibited EWSR1 rearrangement. Four of them were mixed tumors, two were myoepitheliomas and one was a myoepithelial carcinoma, confirming that these lesions represent a spectrum of dermal myoepithelial tumors. Follow-up information, available for five patients (including the patient with a myoepithelial carcinoma), revealed no evidence of disease in all cases (range, 6-72 months). Our study provides a genetic relationship of myoepithelial tumors of the skin with their counterparts in soft tissue, bone and visceral localization by sharing EWSR1 rearrangement. Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Biomarkers, Tumor; Calcium-Binding Proteins; Calmodulin-Binding Proteins; Calponins; Carcinoma; Female; Gene Rearrangement; Germany; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Male; Microfilament Proteins; Middle Aged; Mucin-1; Myoepithelioma; Nerve Tissue Proteins; RNA-Binding Protein EWS; RNA-Binding Protein FUS; RNA-Binding Proteins; S100 Proteins; Skin Neoplasms; Tumor Burden | 2011 |
The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid (spindle cell) squamous cell carcinoma.
The role of CD10 needs clarification in a broader immunohistochemical battery for distinguishing atypical fibroxanthoma (AFX) from spindle cell squamous cell carcinoma (sSCC).. We retrospectively reviewed 23 cutaneous spindle cell tumors previously classified as AFX (n = 11) or as sSCC (n = 12). Each tumor was stained with CD10, S-100, p63 and two or more cytokeratin stains. Defining AFX as a diagnosis of exclusion based on multiple negative cytokeratin stains and negative p63 staining, we reclassified four squamous cell carcinomas (SCCs) as AFX. CD10 staining was reviewed and graded in all tumors.. Fifteen tumors were classified as AFX. Strongly positive CD10 staining was observed in all 15 AFXs, as well as four (50%) of the eight SCCs. Expression of p63 was seen in six sSCCs (75%).. CD10 is consistently expressed by AFX. However, CD10 is also often strongly expressed by sSCC. Positive staining with p63 favors a diagnosis of sSCC. An immunohistochemical battery useful for distinguishing AFX from sSCC may include CD10, p63 and two cytokeratin markers. However, CD10 alone should not be relied upon in the distinction of these entities. Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Membrane Proteins; Neprilysin; Retrospective Studies; Sarcoma; Skin Neoplasms; Xanthomatosis | 2011 |
Cutaneous squamous cell carcinoma associated with proliferation of osteoclast-like giant cells.
Proliferation of osteoclast-like giant cells in a cutaneous squamous cell carcinoma is a rare phenomenon and so far only four cases have been reported. In previous reports, osteoclast-like giant cells were admixed with sarcomatoid component of squamous cell carcinoma and it is therefore debatable if the osteoclast-like giant cells represent a reactive phenomenon or a part of the malignant tumour. A case of cutaneous squamous cell carcinoma associated with osteoclast-like giant cells is reported. However, sarcomatous component of squamous cell carcinoma was not identified in this case. Morphologically, the osteloclast-like giant cells appeared to be benign. The localization of the squamous cell carcinoma and the osteoclastic-like giant cells were separate from one another. Immunohistochemically, squamous cell carcinoma was positive for high molecular weight cytokeratin, cytokeratin-5 and p63, whereas the osteloclast-like giant cells were positive for histiocyte marker CD68 and vimentin and negative for epithelial markers supporting a reactive nature of osteoclast-like giant cells to the cutaneous malignancy. Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Proliferation; Giant Cells; Humans; Keratins; Male; Osteoclasts; Skin Neoplasms; Vimentin | 2011 |
Ligand activation of peroxisome proliferator-activated receptor-beta/delta and inhibition of cyclooxygenase-2 enhances inhibition of skin tumorigenesis.
Ligand activation of peroxisome proliferator-activated receptor (PPAR)-beta/delta and inhibition of cyclooxygenase-2 (COX-2) activity by nonsteroidal anti-inflammatory drugs can attenuate skin tumorigenesis. There is also evidence that attenuation of skin tumorigenesis by inhibition of COX-2 activity occurs through PPARbeta/delta-independent mechanisms. The present study examined the hypothesis that combining ligand activation of PPARbeta/delta with inhibition of COX-2 activity will cooperatively inhibit chemically induced skin tumor progression using both in vivo and ex vivo models. A two-stage chemical carcinogenesis bioassay was performed in wild-type and Pparbeta/delta-null mice. After 22 weeks, cohorts of both mouse lines were divided into four experimental groups: (1) control, (2) topical application of the PPARbeta/delta ligand GW0742, (3) dietary administration of the COX-2 inhibitor nimesulide, or (4) both GW0742 and nimesulide. Ligand activation of PPARbeta/delta did not influence skin tumor progression, while a modest decrease in skin tumor multiplicity was observed with dietary nimesulide. Interestingly, the combined treatment of GW0742 and nimesulide increased the efficacy of the decrease in papilloma multiplicity for 6 weeks in wild-type mice, but this effect was not found at later time points and was not found in similarly treated Pparbeta/delta-null mice. Neoplastic keratinocyte lines cultured with GW0742 and nimesulide also exhibited enhanced inhibition of cell proliferation coincident with increased expression of Keratin messenger RNAs. Results from these studies support the hypothesis that combining ligand activation of PPARbeta/delta with inhibition of COX-2 activity can inhibit chemically induced skin tumor progression by modulating differentiation. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2 Inhibitors; Dinoprostone; Disease Models, Animal; Female; Keratinocytes; Keratins; Keratoacanthoma; Ligands; Mice; Mice, Inbred C57BL; Mice, Knockout; Papilloma; PPAR delta; PPAR-beta; RNA, Messenger; Skin Neoplasms; Sulfonamides; Thiazoles; Time Factors | 2010 |
Immunohistochemical study as a tool in differential diagnosis of pediatric malignant rhabdoid tumor.
Malignant rhabdoid tumors (MRTs) are aggressive childhood neoplasms, occurring mainly in the kidney and brain. We describe 2 unusual cases of extrarenal and noncranial location (liver and soft tissue with dissemination) mimicking hepatoblastoma, neuroblastoma or Ewing sarcoma. Both cases revealed a polyphenotypic profile, combined with cytokeratin, vimentin, and CD99 expression. INI1/BAF-47 showed negative protein nuclear expression in both cases, suggesting a diagnosis of MRT. An extensive immunohistochemical panel was performed to exclude pediatric tumors reminiscent of MRT. The genetic studies failed to detected MYCN amplification, 11q23 deletion, and EWS break-apart positivity. No alterations of 22q integrity were demonstrated with the probes used for the study (N25 Di George/22q11.2, 22qter, and EWS/22q12). We discuss the differential diagnosis in pediatric polyphenotypic tumors (Wilms tumor, neuroblastoma, desmoplastic small round cell tumor, and Ewing sarcoma). Analysis of INI1/BAF-47 expression can offer important clues in the diagnosis of pediatric tumors with rhabdoid phenotype. The integration of clinical, morphologic, immunohistochemical, and genetic data is required to approach a correct diagnosis of pediatric tumor in unusual location with atypical or undifferentiated morphology. Topics: 12E7 Antigen; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Cell Adhesion Molecules; Chromosomal Proteins, Non-Histone; Chromosome Aberrations; Diagnosis, Differential; DNA-Binding Proteins; Drug Resistance, Neoplasm; Fatal Outcome; Female; Humans; Immunohistochemistry; Infant; Infant, Newborn; Keratins; Liver Neoplasms; N-Myc Proto-Oncogene Protein; Neoplasms, Multiple Primary; Nuclear Proteins; Oncogene Proteins; Rhabdoid Tumor; RNA-Binding Protein EWS; Skin Neoplasms; SMARCB1 Protein; Transcription Factors; Vimentin | 2010 |
Primary mucoepidermoid carcinoma of the skin expressing p63.
Primary mucoepidermoid carcinoma (MEC) of the skin is an unusual neoplasm with few cases reported in the English medical literature. It has to be differentiated from adenosquamous carcinoma, usually a high-grade neoplasm with poorer outcome, and metastasis from a primary MEC arising elsewhere in the body. We report a 78-year-old woman with an abdominal skin lesion of recent onset. Histopathological examination revealed a dermal located carcinoma with variable proportions of squamous differentiation and goblet cells. The patient died in a very short time for an unrelated disease. Immunohistochemical study showed staining for cytokeratins (AE1AE3, 7, and 34betaE12), epithelial membrane antigen (EMA), and p63, whereas cytokeratins 18 and 20 and gross cystic disease fluid protein (GCDFP15) were negative. We conclude that primary MEC of the skin is usually a slow-growing neoplasm that should be differentiated from adenosquamous carcinoma. The immunohistochemical staining for p63 is helpful to differentiate primary and metastatic MEC in the skin. Topics: Aged; Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Mucoepidermoid; Diagnosis, Differential; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Leiomyosarcoma; Liver Neoplasms; Neoplasms, Multiple Primary; Peritoneal Neoplasms; Skin Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins | 2010 |
Anti-cytokeratin CAM 5.2 does not act as a surrogate of the cytokeratin 8/18 monoclonal antibody. Comment on: "Utility of p63 in the differential diagnosis of atypical fibroxanthoma and spindle cell squamous cell carcinoma", in J Cutan Pathol 2009; 36: 54
Topics: Antibodies, Monoclonal; Biomarkers; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratin-18; Keratin-8; Keratins; Skin Neoplasms | 2010 |
Contralateral cranial polyneuropathy due to perineural invasion by a cutaneous squamous cell carcinoma.
Cutaneous malignancies may spread to underlying nerves, a process known as perineural invasion (PNI). We report a patient who was found to have PNI presenting as a cranial polyneuropathy on the contralateral side of the face many years after the resection of a squamous cell carcinoma. All diagnostic testing was unrevealing until nerve biopsy was performed. This emphasizes the long asymptomatic period between treatment of a cutaneous malignancy and detection of PNI, and the development of PNI at a site distant from the original malignancy. Biopsy of a clinically involved nerve may permit diagnosis of PNI when other studies are normal. Topics: Aged; Carcinoma, Squamous Cell; Cranial Nerve Neoplasms; Functional Laterality; Humans; Keratins; Male; Skin Neoplasms | 2010 |
Metastatic cutaneous carcinosarcoma to the tongue.
Carcinosarcoma is a rare malignant tumour composed of a mixture of carcinomatous and sarcomatous elements. Carcinosarcoma metastatic to the tongue is extremely rare. An 84-year-old woman presented with a rapidly growing mass on the tongue. She had a history of surgery for carcinosarcoma of the occipital skin 9 months before. An excisional biopsy of the tongue mass was performed, and the lesion was histopathologically diagnosed as carcinosarcoma. PET after diagnosis showed multiple hot uptakes in the whole body. The patient died of the disease 2 months after diagnosis. Therapies for patients with metastatic malignant tumours to the oral cavity are difficult, especially in aggressive case such as this. To the authors' knowledge, this is the first case of metastatic carcinosarcoma to the tongue. Topics: Actins; Aged; Biopsy; Carcinosarcoma; Fatal Outcome; Female; Humans; Keratin-20; Keratins; Phosphopyruvate Hydratase; Positron-Emission Tomography; Scalp; Skin Neoplasms; Tongue Neoplasms; Vimentin | 2010 |
Multicentric cutaneous neuroendocrine (Merkel cell) carcinoma in a dog.
Multicentric cutaneous neuroendocrine (Merkel cell) carcinoma was diagnosed in a 5-year-old castrated male Keeshond dog with multiple firm nodular cutaneous masses. The neoplastic tissue locally effaced the periadnexal and deep dermis and consisted of densely cellular confluent clusters of round to polygonal cells supported by a delicate fibrovascular stroma. The cells were moderately immunoreactive with chromogranin A, synaptophysin, and cytokeratin. Ultrastructurally, the cells had characteristic membrane-bound dense-core neuroendocrine granules approximately 120 nm in diameter and randomly dispersed throughout the cytoplasm. Effacement of dermal structures and multicentric distribution suggested low-grade malignant phenotype. These findings contrast with the typical benign behavior of canine cutaneous neuroendocrine tumors. Topics: Animals; Carcinoma, Merkel Cell; Chromogranin A; Dog Diseases; Dogs; Fatal Outcome; Keratins; Male; Skin; Skin Neoplasms; Synaptophysin | 2010 |
Nuclear and cytoplasmic expression of Met in oral squamous cell carcinoma and in an organotypic oral cancer model.
Met, the hepatocyte growth factor receptor, is important in transducing signals for tumour growth and metastasis. The aim of this study was to examine the pattern of Met expression and its value as a prognostic factor in oral squamous cell carcinomas (OSCCs). The material consisted of 53 OSCCs and five healthy controls from normal oral mucosa supplied with cell lines, 10 organotypic models supplied with oral cancer cells, and three organotypic models supplied with normal keratinocytes. Met protein expression was assessed by immunohistochemistry and western blotting. Met expression was scarce and limited to the basal layer in normal oral mucosa, but was more extensive in the tumours. Cytoplasmic expression of Met was found in the majority of the tumours, and nuclear expression was found in 72%, including a high fraction of the cells located at the invasive front. Organotypic models with normal or malignant oral cells yielded principally similar results as in the mucosa and the cancers, respectively. A smaller amount of Met immunoreactivity was detected, by western blotting, in the nuclear fraction of cultured oral cancer cells. In conclusion, Met was upregulated in OSCCs and was also found in the nucleus. However, Met was not a marker for prognosis in this study. Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Cell Culture Techniques; Cell Line; Cell Nucleus; Cells, Cultured; Coculture Techniques; Cytoplasm; Female; Fibroblasts; Gingiva; Humans; Keratinocytes; Keratins; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Prognosis; Proto-Oncogene Proteins c-met; Skin Neoplasms; Tissue Scaffolds; Tongue Neoplasms; Up-Regulation | 2010 |
Advances in immunostains used in Mohs surgery.
In recent years, Mohs micrographic surgery (MMS) has become a widely utilized method of removal for a variety of cutaneous neoplasms. Certain clinical scenarios, however, make it difficult to visualize residual tumor cells, potentially decreasing the efficacy of the Mohs procedure. Immunohistochemical (IHC) stains are now available and are being utilized to delineate cells of interest intraoperatively when routinely stained slides are equivocal. While useful, IHC stains have not gained wide acceptance as an adjunct to MMS, particularly due to increased processing time, cost and workload required. There have been multiple recent advances, however, in the utilization of IHC stains in MMS. In this article, the authors discuss recent advances in IHC stains used in MMS for the treatment of melanoma as well as nonmelanoma skin cancers, potentially making their routine use in select cases more feasible. Topics: Humans; Immunohistochemistry; Keratins; Melanoma; Mohs Surgery; Skin Neoplasms | 2010 |
Metastatic Merkel cell carcinoma with an unknown primary tumour presenting as lichenoid dermatitis.
Metastatic Merkel cell carcinoma uncommonly presents with an unidentified primary tumour. We report a patient who first presented with lichenoid dermatitis and was found to have Merkel cell carcinoma involving lymph nodes with an unknown primary site. With the rising incidence of Merkel cell carcinoma, it is important to recognize unusual manifestations of this disease as they may become more common in the future. Topics: Aged, 80 and over; Carcinoma, Merkel Cell; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; CD56 Antigen; Comorbidity; Dermatitis; Fatal Outcome; Humans; Keratins; Lichenoid Eruptions; Lymphatic Metastasis; Male; Neoplasms, Unknown Primary; Phosphopyruvate Hydratase; Skin Neoplasms; Synaptophysin | 2010 |
Epidermal cyst with pilomatricoma (follicular hybrid cyst): immunohistochemical study with epithelial keratins and filaggrin.
Topics: Epidermal Cyst; Filaggrin Proteins; Hair Diseases; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Pilomatrixoma; Skin Neoplasms; Young Adult | 2010 |
Keratin 17 promotes epithelial proliferation and tumor growth by polarizing the immune response in skin.
Basaloid skin tumors, including basal cell carcinoma (BCC) and basaloid follicular hamartoma, are associated with aberrant Hedgehog (Hh) signaling and, in the case of BCC, an expanding set of genetic variants including keratin 5 (encoded by KRT5), an intermediate filament-forming protein. We here show that genetic ablation of keratin 17 (Krt17) protein, which is induced in basaloid skin tumors and co-polymerizes with Krt5 in vivo, delays basaloid follicular hamartoma tumor initiation and growth in mice with constitutive Hh signaling in epidermis. This delay is preceded by a reduced inflammation and a polarization of inflammatory cytokines from a Th1- and Th17-dominated profile to a Th2-dominated profile. Absence of Krt17 also attenuates hyperplasia and inflammation in models of acute dermatitis. Re-expression of Krt17 in Gli2(tg); Krt17(-/-) keratinocytes induces select Th1 chemokines that have established roles in BCC. Our findings establish an immunomodulatory role for Krt17 in Hh driven basaloid skin tumors that could impact additional tumor settings, psoriasis and wound repair. Topics: Animals; Blotting, Western; Carcinoma, Basal Cell; Ear; Epithelial Cells; Female; Hamartoma; Hedgehog Proteins; Hyperplasia; Immunoprecipitation; Keratinocytes; Keratins; Kruppel-Like Transcription Factors; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Skin Neoplasms; Zinc Finger Protein Gli2 | 2010 |
Dermal melanocytoma-acanthoma in an adult mixed breed dog.
A cutaneous melanocytoma-acanthoma was diagnosed in a 7-year-old intact female mixed breed dog. Grossly, this tumor was a solitary and darkly pigmented nodule located in the face. Histologically, the lesions consisted of melanocytic and epithelial tumor cells. The melanocytic component consisted predominantly of large round-to-polygonal and heavily pigmented melanocytic cells arranged in nests and clusters. These melanocytes were positive for S-100 and vimentin. The epithelial component was composed of multiple small horn cysts with concentric keratin within the cyst lumina and was positive for cytokeratin. Atypism was not observed in both components. Since this tumor has previously been reported in only two dogs, this report adds to the data that will help determing predilections of age, breed, sex and site. Topics: Acanthoma; Animals; Cell Division; Diagnosis, Differential; Dog Diseases; Dogs; Female; Keratins; Melanocytes; Skin Neoplasms; Vimentin | 2010 |
[Lymphoepithelioma-like carcinoma of skin: report of a case].
Topics: Aged, 80 and over; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Diagnosis, Differential; Granuloma; Humans; Keratins; Male; Mucin-1; Skin Neoplasms | 2010 |
Metastatic hepatocellular carcinoma of skin diagnosed with hepatocyte paraffin 1 and a-fetoprotein immunostainings.
A rare case of skin metastasis of hepatocellular carcinoma diagnosed with an aid of immunohistochemical stainings of hepatocyte paraffin 1 and a-fetoprotein is reported in this study. An 86-year-old Japanese man was admitted to our hospital due to cutaneous mass in the right chest. An incisional biopsy was performed, which showed proliferation of malignant cells with eosinophilic or clear cytoplasm arranged in solid nests. No trabecular pattern was recognized. Sebaceous carcinoma, clear cell sarcoma, malignant granular cell tumor, metastatic renal cell carcinoma, and metastatic hepatocellular carcinoma were suspected on hematoxylin and eosin preparations. An immunohistochemical study showed that the tumor cells were positive for cytokeratins, hepatocyte paraffin 1, and a-fetoprotein but negative for vimentin, desmin, a-smooth muscle actin, S-100 protein, epithelial membrane antigen, carcinoembryonic antigen, chromogranin, neuron-specific enolase, CD10, CD30, CD34, CD45, CD68, and HMB45. Metastatic hepatocellular carcinoma of the skin was diagnosed pathologically. This case suggests that skin tumors with eosinophilic cytoplasm should be examined by hepatocyte paraffin 1 and a-fetoprotein. Topics: Aged, 80 and over; alpha-Fetoproteins; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Hepatocellular; Hepatocytes; Humans; Keratins; Liver Neoplasms; Male; Skin Neoplasms | 2010 |
Epidermotropic skin metastasis from gastric cancer: immunohistochemical analysis using cytokeratins.
Topics: Biomarkers, Tumor; Humans; Keratins; Male; Middle Aged; Neoplasm Proteins; Skin Neoplasms; Stomach Neoplasms | 2009 |
Cytokeratin expression in malignant melanoma: potential application of in-situ hybridization analysis of mRNA.
Occasional reports indicated cytokeratin (CK) protein expression (mainly by immunohistochemistry) in malignant melanoma (MM) and suggested an association with unfavorable clinical parameters. However, the mRNA expression of CK and its clinicopathologic significance in MM has not been specifically evaluated. We investigated the mRNA and protein expression of nine CKs in melanoma cell lines and tissues, in particular the prognostic significance of CK18 mRNA expression. Reverse transcription (RT)-PCR (CK6-10, 14 and 18-20), in-situ hybridization (ISH) (CK18), and western blotting (CK18 and pan-cytokeratin AE1/AE3) were performed on MM cell lines A375, A875, M14, and SK-MEL-1. Eighty MM tissue samples were analyzed by ISH and immunohistochemistry for CK18 expression. The mRNA of CK6-8, 10, 14, 18, and 19 (but not CK9 and 20) was detected in one to four of the melanoma cell lines by RT-PCR. CK18 was detected in all four cell lines by RT-PCR, ISH, and western blotting. CK18 mRNA ISH was positive in three of 30 (10.0%), 10 of 25 (40.0%), and 12 of 25 (48.0%) of primary cutaneous, primary mucosal, and metastatic melanomas, respectively (overall positivity: 25 of 80, 31.3%). CK18 immunostaining was only observed focally in eight of 80 (10.0%) of MM tissue samples, and AE1/AE3 immunostaining was altogether negative. Significantly, CK18 mRNA ISH positivity (but not protein immunohistochemistry) was associated with poorer prognosis by both univariate analysis (P<0.001) and multivariate analysis (relative risk=5.430, 95% confidence interval 2.246-13.128, P<0.001). CK18 mRNA could be identified in one-third of melanoma tissue samples and is an adverse prognostic factor. ISH is superior to immunohistochemistry for analyzing CK18 expression in MM. Topics: Blotting, Western; Bone Neoplasms; Brain Neoplasms; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; In Situ Hybridization; Kaplan-Meier Estimate; Keratin-18; Keratins; Lymphatic Metastasis; Melanoma; Neoplasm Proteins; Prognosis; Proportional Hazards Models; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Skin Neoplasms | 2009 |
Prevention of KLF4-mediated tumor initiation and malignant transformation by UAB30 rexinoid.
The transcription factor KLF4 acts in post-mitotic epithelial cells to promote differentiation and functions in a context-dependent fashion as an oncogene. In the skin KLF4 is co-expressed with the nuclear receptors RARgamma and RXRalpha, and formation of the skin permeability barrier is a shared function of these three proteins. We utilized a KLF4-transgenic mouse model of skin cancer in combination with cultured epithelial cells to examine functional interactions between KLF4 and retinoic acid receptors. In cultured cells, activation of a conditional, KLF4-estrogen receptor fusion protein by 4-hydroxytamoxifen resulted in rapid upregulation of transcripts for nuclear receptors including RARgamma and RXRalpha. We tested retinoids in epithelial cell transformation assays, including an RAR-selective agonist (all-trans RA), an RXR-selective agonist (9-cis UAB30, rexinoid), and a pan agonist (9-cis RA). Unlike for several other genes, transformation by KLF4 was inhibited by each retinoid, implicating distinct nuclear receptor heterodimers as modulators of KLF4 transforming activity. When RXRalpha expression was suppressed by RNAi in cultured cells, transformation was promoted and the inhibitory effect of 9-cis UAB30 was attenuated. Similarly as shown for other mouse models of skin cancer, rexinoid prevented skin tumor initiation resulting from induction of KLF4 in basal keratinocytes. Rexinoid permitted KLF4 expression and KLF4-induced cell cycling, but attenuated the KLF4-induced misexpression of cytokeratin 1 in basal cells. Neoplastic lesions including hyperplasia, dysplasia and squamous cell carcinoma-like lesions were prevented for up to 30 days. Taken together, the results identify retinoid receptors including RXRalpha as ligand-dependent inhibitors of KLF4-mediated transformation or tumorigenesis. Topics: Animals; Antineoplastic Agents; Cell Differentiation; Cell Line; Fatty Acids, Unsaturated; Gene Expression Regulation, Neoplastic; Humans; Keratins; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Mice; Naphthalenes; Neoplasms, Squamous Cell; Rats; Receptors, Retinoic Acid; Recombinant Fusion Proteins; Retinoic Acid Receptor gamma; Retinoid X Receptor alpha; Skin Neoplasms; Tretinoin | 2009 |
Fiber diffraction of skin and nails provides an accurate diagnosis of malignancies.
An early diagnosis of malignancies correlates directly with a better prognosis. Yet for many malignancies there are no readily available, noninvasive, cost-effective diagnostic tests with patients often presenting too late for effective treatment. This article describes for the first time the use of fiber diffraction patterns of skin or fingernails, using X-ray sources, as a biometric diagnostic method for detecting neoplastic disorders including but not limited to melanoma, breast, colon and prostate cancers. With suitable further development, an early low-cost, totally noninvasive yet reliable diagnostic test could be conducted on a regular basis in local radiology facilities, as a confirmatory test for other diagnostic procedures or as a mass screening test using suitable small angle X-ray beam-lines at synchrotrons. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Infant, Newborn; Keratins; Male; Middle Aged; Nail Diseases; Nails; Neoplasms; Sensitivity and Specificity; Skin; Skin Neoplasms; Synchrotrons; X-Ray Diffraction; Young Adult | 2009 |
[Merkel cell carcinoma--immunohistochemical study in a group of 11 patients].
The aim of our work was to confirm an immunohistochemical profile of routine markers of epithelial and neuroendocrine differentiation in eleven cases of Merkel cell carcinoma, as well as to study the expression of two markers of early phases of neuronal differentiation, namely reelin and class III beta-tubulin, markers which have not yet been studied in Merkel cell carcinomas. In all the investigated tumours the characteristic "dot-like" pattern of cytokeratin 20 immunoexpression, as well as negative immunostaining for cytokeratin 7 and thyroid transcription factor 1 (TTF-1) were disclosed; all the tumours showed neuroendocrine differentiation, expressing either neuron specific enolase (NSE) or chromogranin A(CgA), or both. An interesting finding was observed when the anti-cytokeratin monoclonal antibody MNF 116 was used. The characteristic "dot-like" pattern was detected in high proportion of tumours, including two samples of local recurrence of one of the carcinomas, where neoplastic cells have lost the expression of cytokeratin 20. The majority (91%) of Merkel cell carcinomas included in our group showed positive immunodetection of class III beta-tubulin when TU-20 antibody was used, while TuJ-1 immunostaining was surprisingly negative in all the investigated tumours. Detection of reelin was negative in almost all the studied Merkel cell carcinomas except for cases, where neoplastic cells revealed weak focal immunostaining in a minor portion of neoplastic cells. Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Merkel Cell; Cell Adhesion Molecules, Neuronal; Extracellular Matrix Proteins; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nerve Tissue Proteins; Reelin Protein; Serine Endopeptidases; Skin Neoplasms; Tubulin | 2009 |
Innovative 19-minute rapid cytokeratin immunostaining of nonmelanoma skin cancer in Mohs micrographic surgery.
Dense inflammation can obscure nonmelanoma skin cancer (NMSC) on frozen sections, prompting removal of additional layers to ensure negative margins. Cytokeratin (CK) immunostaining in Mohs micrographic surgery (MMS) has been examined and found to be useful but is limited by lengthy 1-hour processing.. Our objective was to develop an effective ultrarapid CK frozen section immunostain to be used during MMS in cases of NMSC with dense or perineural inflammation.. An ultrarapid immunostain with a mixture of AE1/AE3 monoclonal antibodies was performed in 21 MMS cases and compared with permanent sections prepared from the same material.. The ultrarapid CK protocol stained all of the cells in each of the 21 examples of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in frozen tissue in a way equivalent to immunostains being applied to permanent sections.. The 19-minute CK immunohistochemistry protocol in frozen tissue appears to be as effective at labeling tumor cells of SCC and BCC as methods requiring permanent sections. It is hopeful that this technique may prevent recurrences after MMS and limit the number of Mohs layers required to obtain free margins when inflammation is abundant. It also is effective in uncovering subtle perineural invasion. Topics: Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Frozen Sections; Humans; Immunohistochemistry; Keratins; Male; Mohs Surgery; Skin Neoplasms; Staining and Labeling; Time Factors | 2009 |
Pilomatricoma can differentiate not only towards hair matrix and hair cortex, but also follicular infundibulum, outer root sheath and hair bulge.
Pilomatricoma is believed to differentiate towards the hair matrix and hair cortex. To elucidate the origin of differentiation in pilomatricoma, we studied the expression of epithelial keratin (K) and filaggrin (filament aggregating protein) in pilomatricoma. An immunohistochemical study has been made of 53 cases of pilomatricoma using 10 monospecific anti-keratin antibodies and anti-filaggrin antibody. Basophilic cells, transitional cells and shadow cells did not react with epithelial keratins and filaggrin antibodies as well as hair matrix and hair cortex. Instead, infundibular-type epithelium was positive for K1, K10 and filaggrin. Epithelium showing trichilemmal keratinization was positive for K14 and K16. The hair bulge-like structure was positive for K19. The differentiation of pilomatricoma is diversified, and is heterogeneous in epithelial keratin and filaggrin expression. Our results for keratin and filaggrin expression suggested that pilomatricoma can differentiate not only towards hair matrix and hair cortex, but also follicular infundibulum, outer root sheath and hair bulge. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Female; Filaggrin Proteins; Hair; Hair Diseases; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pilomatrixoma; Skin; Skin Neoplasms | 2009 |
Utility of p63 in the differential diagnosis of atypical fibroxanthoma and spindle cell squamous cell carcinoma.
Atypical fibroxanthoma (AFX), spindle cell squamous cell carcinoma (SCSCC) and spindle cell melanoma are the primary entities in the differential diagnosis of a cytologically atypical spindle cell tumor arising on sun-damaged skin. AFX is generally regarded as a diagnosis of exclusion in this context: in the absence of S100 or keratin reactivity, a diagnosis of AFX is favored. However, keratin reactivity may be focal or even absent in SCSCC, and although numerous positive markers of AFX have been proposed, none has shown sufficient sensitivity and specificity for routine diagnostic use. We evaluated 20 AFX and 10 SCSCC with a panel of cytokeratins and p63 to assess the utility of the latter antibody in this differential diagnosis. All 10 SCSCC showed strong expression of p63, whereas all 20 AFX were p63 negative. Two additional cases (excluded from the study) were negative for keratins and S100 on initial shave biopsies, resulting in a favored diagnosis of AFX, but p63 stains performed retrospectively were positive. However, review of the excision specimens in both cases revealed deep subcutaneous extension, excluding AFX. p63 reactivity argues against the diagnosis of AFX and is therefore a useful addition to the standard immunohistochemical panel for cutaneous spindle cell neoplasms. Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; S100 Proteins; Skin Neoplasms | 2009 |
Aberrant cytokeratin expression during arsenic-induced acquired malignant phenotype in human HaCaT keratinocytes consistent with epidermal carcinogenesis.
Inorganic arsenic is a known human skin carcinogen. Chronic arsenic exposure results in various human skin lesions, including hyperkeratosis and squamous cell carcinoma (SCC), both characterized by distorted cytokeratin (CK) production. Prior work shows the human skin keratinocyte HaCaT cell line, when exposed chronically for >25 weeks to a low level of inorganic arsenite (100nM) results in cells able to produce aggressive SCC upon inoculation into nude mice. In the present study, CK expression analysis was performed in arsenic-exposed HaCaT cells during the progressive acquisition of this malignant phenotype (0-20 weeks) to further validate this model as relevant to epidermal carcinogenesis induced by arsenic in humans. Indeed, we observed clear evidence of acquired cancer phenotype by 20 weeks of arsenite exposure including the formation of giant cells, a >4-fold increase in colony formation in soft agar and a approximately 2.5-fold increase in matrix metalloproteinase-9 secretion, an enzyme often secreted by cancer cells to help invade through the local extra-cellular matrix. During this acquired malignant phenotype, various CK genes showed markedly altered expression at the transcript and protein levels in a time-dependent manner. For example, CK1, a marker of hyperkeratosis, increased up to 34-fold during arsenic-induced transformation, while CK13, a marker for dermal cancer progression, increased up to 45-fold. The stem cell marker, CK15, increased up to 7-fold, particularly during the later stages of arsenic exposure, indicating a potential emergence of cancer stem-like cells with arsenic-induced acquired malignant phenotype. The expression of involucrin and loricrin, markers for keratinocyte differentiation, increased up to 9-fold. Thus, during arsenic-induced acquired cancer phenotype in human keratinocytes, dramatic and dynamic alterations in CK expression occur which are consistent with the process of epidermal carcinogenesis helping validate this as an appropriate model for the study of arsenic-induced skin cancer. Topics: Arsenites; Biomarkers, Tumor; Carcinogens; Cell Line; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Keratins; Membrane Proteins; Phenotype; Skin Neoplasms; Tumor Stem Cell Assay | 2009 |
Trichogerminoma.
A case of distinctive benign follicular neoplasm previously reported under the designation of trichogerminoma is described. A 45-year-old man presented with an asymptomatic nodule on the scalp since 3 years. Histologically, the lesion corresponded to a well-organized, symmetrical dermal nodule made up of basophilic lobules included in a fibrocytic stroma. The lesion had the characteristics of hair germ tumors; however, most lobules depicted a distinctive pattern of rounded nests of concentrically arranged clear cells. Small follicle bulb-like basophilic structures, foci of sebaceous differentiation, and areas of infundibulocystic, isthmic, and outer sheath keratinization were also seen. This neoplasm and the other tumors with hair germ differentiation such as trichoblastoma and panfolliculoma seem to represent the same spectrum of hair follicle neoplasms only distinguishable by their degree of differentiation. Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Diagnosis, Differential; Hair Diseases; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasms, Adnexal and Skin Appendage; Scalp; Skin Neoplasms | 2009 |
Response to a novel multitargeted tyrosine kinase inhibitor pazopanib in metastatic Merkel cell carcinoma.
Topics: Aged; Base Sequence; Biomarkers; Carcinoma, Merkel Cell; DNA Mutational Analysis; Fatal Outcome; Female; Humans; Indazoles; Keratins; Mutation; Neoplasm Metastasis; Phosphopyruvate Hydratase; Protein Kinase Inhibitors; Pyrimidines; Receptor, Platelet-Derived Growth Factor alpha; Scalp; Skin Neoplasms; Sulfonamides | 2009 |
Cutaneous clear cell adnexal carcinoma in a dog: special reference to cytokeratin expression.
A 5-year-old, male Bichon-Frise dog presented with a cutaneous mass in the basal region of the auricle. Histologically, the cutaneous neoplasm was comprised of lobules with solid cellular proliferation separated by thin fibrous septa. Neoplastic cells varied in size, with moderate to abundant amounts of PAS-positive cytoplasm, large nuclei and prominent nucleoli. Immunohistochemical examinations showed that tumor cells were positive for pan-cytokeratin (CK) (AE1/AE3 and CAM5.2), CK8 and CK18, but negative for pan-CK (KL1), CK7, CK14, CK16 and CK20. Double-labeled immunofluorescence testing indicated that neoplastic cells frequently co-expressed CK and vimentin, suggesting divergent differentiation of tumor cells. Based on these findings, the tumor was diagnosed as canine clear cell adnexal carcinoma. Topics: Animals; Carcinoma; Dog Diseases; Dogs; Gene Expression Regulation, Neoplastic; Keratins; Male; Skin Neoplasms | 2009 |
Evaluation of CD10 and procollagen 1 expression in atypical fibroxanthoma and dermatofibroma.
Atypical fibroxanthoma (AFX) (dermal pleomorphic sarcoma) remains a somewhat controversial entity. Some authors have averred that AFX is a fiction, suggesting that such lesions merely represent misclassified examples of spindled squamous cell carcinoma. In addition, the immunoperoxidase confirmation of AFX has been less than straightforward and has historically been approached as a diagnosis of exclusion because of the lack of sensitivity and specificity of available "positive" reagents. Procollagen 1 (PC1) and CD10 represent recently developed immunoperoxidase reagents that have been forwarded as useful in this setting, and we sought to characterize our experience, both to confirm the utility of these antibodies and to compare them. Our investigation included 3 separate data sets. Group 1 consisted of a retrospective review of 98 consecutive cases in which PC1 was used in the evaluation of dermatopathology specimens in routine practice during a 13-month interval. Group 2 consisted of a direct comparison of 11 AFX, 11 dermatofibroma (DF), and 7 epithelioid dermatofibroma (EDF) using the CD10 reagent on cases identified by database search. Group 3 consisted of a retrospective review of 47 cases in which CD10 was used in routine practice during a 10-month interval. Group 1 included 47 AFX, 13 carcinomas, and 6 melanomas. PC1 expression was observed in 45 of 47 AFX (96%), with a strong reaction in 78% of cases. Among a comparison group of carcinomas, 13 of 13 displayed strong keratin immunopositivity and 11 of 13 (85%) lacked PC1 expression whereas 2 showed focal weak labeling. Six of six melanomas exhibited avid S100 expression and none labeled with PC1. In group 2, strong CD10 immunoreactivity was present in 11 of 11 AFX. Similarly, 11 of 11 DFs were also positive. In contrast, 6 of 7 cases of EDF lacked CD10 expression. Group 3 included 38 AFX and 9 miscellaneous spindle cell proliferations. Of the 38 AFX, 37 (97%) labeled with CD10 and in 34 (92%) the reaction was strong. PC1 immunostaining was also completed in 34 of 38 AFX from group 3 and 27 (79%) cases showed positive labeling. Our results confirm that both PC1 and CD10 can be used as positive markers of AFX. We believe that CD10 and PC1 immunostaining can be used as a useful adjunct to supplement the diagnosis of AFX, within the context of an immunoperoxidase panel. Not surprisingly, CD10 expression is also common in DF, a benign analog of AFX, with the exception of its epithelioid variant. In direc Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Collagen Type I; Diagnosis, Differential; Epithelioid Cells; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Middle Aged; Neprilysin; Predictive Value of Tests; Procollagen; Reproducibility of Results; Retrospective Studies; S100 Proteins; Sarcoma; Skin Neoplasms; Xanthomatosis | 2008 |
Transcriptional profiling identifies an interferon-associated host immune response in invasive squamous cell carcinoma of the skin.
Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the 2 most common types of nonmelanoma skin cancer. Both derive from keratinocytes but show a distinct biological behavior. Here we present transcriptional profiling data of a large cohort of tumor patients (SCC, n = 42; BCC, n = 114). Differentially expressed genes reflect known features of SCC and BCC including the typical cytokeratin pattern as well as upregulation of characteristic cell proliferation genes. Additionally, we found increased expression of interferon (IFN)-regulated genes (including IFI27, IFI30, Mx1, IRF1 and CXCL9) in SCC, and to a lower extent in BCC. The expression of IFN-regulated genes correlated with the extent of the lesional immune-cell infiltrate. Immunohistological examinations confirmed the expression of IFN-regulated genes in association with a CXCR3+ cytotoxic inflammatory infiltrate on the protein level. Of note, a small subset of SCC samples with low expression of IFN-regulated genes included most organ transplant recipients receiving immunosuppressive medication. Collectively, our findings support the concept that IFN-associated host responses play an important role in tumor immunosurveillance in the skin. Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Differentiation; Cell Proliferation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Interferons; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasms, Basal Cell; Skin Neoplasms; Transcription, Genetic | 2008 |
Immunohistochemical characterization of mammary squamous cell carcinoma of the dog.
Squamous cell carcinoma of the mammary gland is rare in both veterinary and human medicine. Whereas human metaplastic and squamous variants are known, the objectives of the current study were to ascertain the presence of such entities in canine mammary tumors and to distinguish them from other (epidermal, sweat gland) squamous tumors that may develop in the same area. A panel of antibodies (anti-cytokeratin [CK] 19, CK 14, CK 5/6, pancytokeratin, and vimentin) was used on 18 mammary gland malignancies with squamous features and 16 malignant skin tumors (11 squamous cell carcinomas of the skin and 5 sweat glands). Fifteen of the 18 mammary carcinomas were classified as metaplastic carcinomas, and the remaining 3 were classified as squamous cell carcinomas. The 2 most useful markers to establish the histogenesis of mammary tumors were pancytokeratin and CK 19. All other antibodies were equally expressed (CK 14 and 5/6) in all histotypes. The antibody panel discriminated primary epidermal squamous tumors (pancytokeratin positive and CK 19 negative) from gland-derived squamous neoplasms (pancytokeratin positive and CK 19 positive) but failed to distinguish primary mammary tumors from other squamous tumors of glandular origin. Topics: Animals; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Keratins; Mammary Glands, Animal; Neoplasm Proteins; Neoplasms; Skin Neoplasms; Vimentin | 2008 |
Keratoacanthoma occurring within the red dye of a tattoo.
Keratoacanthoma (KA) is a common keratinizing squamous cell neoplasm of unknown origin characterized by rapid growth and spontaneous involution. Trauma-induced forms have been observed with various types of skin injury. To our knowledge, reports of KA arising at tattoo sites are scarce in the literature. A 41-year-old woman with no medical history presented for a rapidly growing nodule confined to the red part of a tattoo located on the scapula. Histology showed a keratin-filled cuplike crater with an epithelial proliferation (hyperkeratosis, parakeratosis, no keratinocyte atypia). An inflammatory infiltrate in the dermis composed of lymphocytes and histiocytes intermixed with red ink-related exogenous pigments was noted. Lack of papillomatosis and viral inclusions ruled out the diagnosis of viral wart, absence of granulomatous reaction ruled out deep fungal or mycobacterial infection and lack of cytological atypia and frank architectural abnormalities did not favour a squamous cell carcinoma. KA should be included in the list of cutaneous complications related to tattooing. Diagnosis can be challenging as differential diagnoses include pseudoepitheliomatous hyperplasia and squamous cell carcinoma. Removal of the entire area, thorough histological examination and careful follow up are mandatory. Topics: Adult; Carcinoma, Squamous Cell; Coloring Agents; Diagnosis, Differential; Female; Histiocytes; Humans; Keratinocytes; Keratins; Keratoacanthoma; Lymphocytes; Skin Diseases; Skin Neoplasms; Tattooing | 2008 |
Lymphoepithelioma-like carcinoma arising in the scar from a previously excised basal cell carcinoma.
We report a case of a primary lymphoepithelioma-like carcinoma of the skin (LELCS) associated with scar from a previous excision of basal cell carcinoma. The patient was a 68-year-old female with a 3.0 mm skin-colored pearly papule on her forehead that developed over 2-3 months. The patient had a history of a basal cell carcinoma in the same location, which was completely excised 1 year earlier. A biopsy and subsequent excision of the tumor were performed. The tumor consisted of small islands of large pleomorphic mitotically active epithelioid cells surrounded by a very dense lymphoplasmacytic infiltrate. The tumor was associated with dermal scar. There was no connection of tumor with the unremarkable epidermis. Immunohistochemical examination showed that the epithelioid tumor cells were positive for pan-cytokeratin and epithelial membrane antigen, supporting the morphologic impression of LELCS. The lesion was negative for Epstein-Barr virus. Retrospective review of the original excision specimen confirmed the diagnosis of an ordinary basal cell carcinoma. Forty-five cases of LELCS have been reported to date. We report the first case of LELCS to arise in the scar from an excision of a cutaneous malignancy. Topics: Aged; Biomarkers, Tumor; Carcinoma; Carcinoma, Basal Cell; Cicatrix; Female; Humans; Keratins; Mohs Surgery; Mucin-1; Neoplasms, Second Primary; Skin Neoplasms | 2008 |
SAG/ROC2/RBX2 E3 ligase promotes UVB-induced skin hyperplasia, but not skin tumors, by simultaneously targeting c-Jun/AP-1 and p27.
Sensitive to apoptosis gene (SAG)/regulator of cullins-2/RING box protein 2 is a stress-responsive RING component of Skp-1/Cullins/F-box protein E3 ubiquitin ligase. When overexpressed, SAG inhibits apoptosis induced by reactive oxygen species or hypoxia. Here, we report that SAG overexpression inhibits ultraviolet (UV) B-induced apoptosis in mouse JB6 epidermal cells. Using a transgenic mouse model, in which SAG expression was targeted primarily to epidermis by a K14 promoter, we showed that, at the early stage of UVB skin carcinogenesis (10 weeks post-UVB exposure), c-Jun, p27, p53, c-Fos and cyclin D1 were strongly induced. While having no effect on UVB-induced p53, c-Fos and cyclin D1, SAG-transgenic expression reduced the levels of c-Jun and p27 and inhibited AP-1 activity. The net outcome of SAG-mediated inhibition of c-Jun/AP-1 (pro-tumor promotion) and of p27 (antiproliferation) increased skin hyperplasia, with no apparent effect on apoptosis, as evidenced by increased skin thickness, and increased rate of DNA synthesis, but hardly any apoptosis. Although skin hyperplasia was promoted, SAG-transgenic expression had no significant effect on tumor formation in the later stage of UVB carcinogenesis. Thus, by simultaneously targeting c-Jun and p27, SAG accelerates UVB-induced skin hyperplasia, but not carcinogenesis. Topics: Animals; Cell Line; Epidermis; Humans; Hyperplasia; In Situ Nick-End Labeling; Keratins; Lung; Mice; Mice, Transgenic; Proliferating Cell Nuclear Antigen; Promoter Regions, Genetic; Radionuclide Imaging; Skin; Skin Neoplasms; Transcription Factor AP-1; Ubiquitin-Protein Ligases; Ubiquitination; Ultraviolet Rays | 2008 |
Primary cutaneous PEComa: distinctive clear cell lesions of skin.
PEComas arising in somatic soft tissue or skin are rare. To further characterize the clinicopathologic spectrum, we herein report a series of 10 primary cutaneous PEComas. Eight patients were female and 2 patients were male. The age at presentation ranged from 15 to 81 years (median, 52y). None had tuberous sclerosis. Tumor size ranged from 0.7 to 2 cm (median size, 1.5 cm). Eight tumors were located on the limbs and 2 on the back. The tumors involved the dermis and commonly showed infiltration into the subcutaneous fat. Architecturally, a nested, focally trabecular growth pattern with prominent vasculature composed of delicate thin-walled capillaries was observed. Six tumors were composed of epithelioid cells and 4 showed mixed epithelioid and spindle cell morphology. Tumor cells had clear, palely eosinophilic or granular cytoplasm. Multinucleate tumor giant cells were observed in 3 cases. Mitotic activity ranged from 0 to 2 mitoses per 30 high power fields (mean < 1/10 HPF). Pleomorphism or necrosis was absent. All cases showed at least focal positivity for HMB-45. Melan A was positive in 5/7. In cases where HMB-45 was positive in fewer than 5% of tumor cells (5/10), microphthalmia transcription factor was positive in the majority of the tumor cell nuclei. Desmin positivity was observed in 5 and smooth muscle actin in 1 case, respectively. The other muscle markers (caldesmon, calponin) and also pan-keratin and epithelial membrane antigen were negative. Follow-up data were available in 6 cases and ranged between 3 and 108 months (median, 47 mo). None has recurred to date. Primary cutaneous PEComas are rare and thus far apparently benign cutaneous tumors. Accurate recognition of this entity is essential because of potential misdiagnosis as malignant tumors, especially malignant melanoma. Topics: Actins; Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Calcium-Binding Proteins; Calmodulin-Binding Proteins; Calponins; Dermis; Desmin; Diagnosis, Differential; Female; Giant Cells; Humans; Immunohistochemistry; Keratins; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Microfilament Proteins; Microphthalmia-Associated Transcription Factor; Middle Aged; Mitotic Index; Mucin-1; Neoplasm Invasiveness; Neoplasm Proteins; Skin Neoplasms; Subcutaneous Fat | 2008 |
Unexpected expression of Hsp47, a replacement of one amino acid (Val 7 Leu) in the amino terminal region, in cultured human tumorigenic cell lines.
In general, it has been stated that keratin (K) molecules are glycosylated. During biochemical studies of K subunits, we encountered a glycoprotein that does not judge K subunits.. This study was intended to elucidate how the above glycoprotein co-exists in the K fraction prepared from ISO-HAS (cultured angiosarcoma cell line).. We analyzed and sequenced a remarkable spot, which was shown as a glycoprotein by periodic acid Sciff's (PAS) staining, in the K fraction prepared from ISO-HAS.. The glycoprotein was identified as an N-terminal amino acid sequence covering 10 residues of the spot. A homology search showed that it was identical to that of Hsp47 (matured type), except for one amino acid (seventh amino acid: Val 7 Leu). Similar results were confirmed for four other tumorigenic cell line types. Subsequent PAS staining using the same samples after 2D-PAGE revealed no glycosylated Ks.. No glycosylated Ks were found by PAS staining in the K fraction prepared from four tumorigenic cell line types. During K preparation from cultured human tumor cell lines, Hsps might be associated with K expression in tumor cells. Topics: Amino Acid Sequence; Amino Acid Substitution; Carcinoma, Squamous Cell; Cell Line, Transformed; Fibrosarcoma; Gene Expression Regulation, Neoplastic; Glycosylation; HeLa Cells; Hemangiosarcoma; HSP47 Heat-Shock Proteins; Humans; Keratinocytes; Keratins; Melanoma; Molecular Sequence Data; Periodic Acid-Schiff Reaction; Skin Neoplasms | 2008 |
Squamous cell carcinomas with single cell infiltration: a potential diagnostic pitfall and the utility of MNF116 and p63.
Numerous variants of squamous cell carcinoma (SCC) have been described. We recently encountered four examples of SCC composed primarily of single, atypical cells that were cytokeratin (CK) MNF116-positive and p63-positive. One case was particularly difficult to diagnose as the single cells were obscured by a dense inflammatory infiltrate. We have also noted similar single cell infiltration toward the periphery of four additional cases of more typical SCC. These foci resemble the single tumor cells that may infiltrate at the borders of spindle cell and desmoplastic SCCs. CK MNF116 and p63 were useful in identifying each of these neoplasms. This single--cell pattern of SCC can easily be misdiagnosed, and CK MNF116 and/or p63 are diagnostically helpful in recognizing it. Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Mohs Surgery; Neoplasm Invasiveness; Skin Neoplasms | 2008 |
Immunohistochemical distinction of cutaneous spindle cell carcinoma.
Cutaneous spindle cell squamous carcinoma is an uncommon variant of squamous cell carcinoma in which keratinocytes infiltrate the dermis as single cells with elongated nuclei rather than as cohesive nests or islands, and signs of keratinization of conventional squamous cell carcinoma are insubstantial or nonexistent. Spindle cell carcinoma must be distinguished from spindle cell/desmoplastic melanoma, cutaneous leiomyosarcoma, atypical fibroxanthoma (AFX), and scar. In instances when there is no definitive evidence of squamous differentiation, immunohistochemical studies may confer diagnostic discrimination. Twenty-four cases consisting of 12 spindle cell squamous cell carcinomas, 3 AFXs, 3 leiomyosarcomas, 3 desmoplastic melanomas, and 3 scars were evaluated with a battery of immunohistochemical stains, with the specificity and sensitivity of each marker calculated. The immunohistochemical battery consisted of S-100, desmin, CD68, and smooth muscle actin and cytokeratins P KER (keratins predominantly of molecular weight 56 and 69 kd) and low-molecular weight keratin (CAM 5.2), AE1/AE3, p63, and 34 beta E12 (CK903). Spindle cell squamous carcinomas were negative for S-100, CD68, smooth muscle actin, and desmin with the exception of 2 cases with weak staining for smooth muscle actin. 34 beta E12 provided positive results for each spindle cell squamous carcinoma. The other cytokeratin stains were less sensitive for spindle cell squamous carcinoma than 34 beta E12. The final immunohistochemical results were as follows: 34 beta E12 (12/12, 100%), p63 (10/12, 80%), AE1/AE3 (8/12, 67%), low-molecular weight keratin (7/12, 58%), and P KER (4/12, 33%). The 3 AFXs were positive for CD68 and negative for all other stains, whereas the 3 leiomyosarcomas stained positively for desmin and smooth muscle actin and negatively for all other stains. The 3 melanomas stained positively for S-100 and negatively for all other immunohistochemistry. The scars were negative for all stains. In conclusion, our study of 34 beta E12 proved most promising in distinguishing spindle cell squamous carcinoma from the histologic mimickers, AFX, spindle cell melanoma, scar, and leiomyosarcoma. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Cicatrix; Diagnosis, Differential; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratinocytes; Keratins; Leiomyosarcoma; Male; Melanoma; Middle Aged; Predictive Value of Tests; Skin Neoplasms | 2008 |
Cytokeratin profile in basal cell carcinoma.
Origin of basal cell carcinoma (BCC) is still unclear. We studied the cytokeratin (CK) profile in BCC using monoclonal antibodies against 12 CKs to further investigate the suggested origin of the tumor from follicular matrix cells or from follicular outer root sheath cells and to determine if BCC subtypes can be identified on the basis of their CK profiles. Cases of pilomatricoma and samples of fetal skin served as controls to establish the CK profile in matrical cells and developing follicles during intrauterine life, that of the epidermis and cutaneous adnexa in adult life having been determined in a previous study. The most significant findings were as follows: (a) CK 5 and CK 17 positivity in all the BCCs studied; (b) CK 7, CK 8, CK 18, and CK 19 positivity in 30/52, 33/52, 42/52, and 14/52 BCCs, respectively; (c) CK 14 negativity in almost all the BCCs studied; and (d) lack of CK 1 expression only in 2/2 morpheiform BCCs and 4/10 nodular BCCs. The study suggests a tumorous differentiation toward follicular outer root sheath cells and, in most cases, also toward the glandular components of the pilosebaceous-apocrine unit. No significant difference in the CK profile among the BCC subtypes studied was found. Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Fetus; Gestational Age; Hair Diseases; Hair Follicle; Humans; Keratinocytes; Keratins; Pilomatrixoma; Skin; Skin Neoplasms | 2008 |
Lipomatous mixed tumor of the skin.
An unusual tumor of the neck in a 56-year-old female is reported. The tumor was composed of tubules and small cords of epithelial cells dispersed in the fibromyxoid and adipose stroma. At the periphery, the tumor was not encapsulated and its border was intermingled with the subcutaneous fat. Lack of decapitation secretion and the absence of long tubules suggested an eccrine origin; however, in some of the tumor areas, the cells showed brightly eosinophilic copious cytoplasm that may indicate an apocrine differentiation. As an area of chondroid metaplasia was identified, the diagnosis of a mixed tumor was rendered. This unusual type of skin adnexal neoplasm with unique relation of the epithelial component to the surrounding adipose tissue requires differentiation with the primary cutaneous and metastatic carcinomas. Topics: Adipocytes; Adipose Tissue; Biomarkers, Tumor; Diagnosis, Differential; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lipoma; Middle Aged; Neoplasm Metastasis; Neoplasms, Complex and Mixed; Skin Neoplasms | 2008 |
Dermal squamomelano-cytic tumor: neoplasm of uncertain biological potential.
We report a case of exceedingly rare cutaneous neoplasm with histological features of malignancy and uncertain biological potential. The nodular, darkly pigmented facial tumor with central exulceration, size 12 x 10 x 7 mm, of the skin 61-year-old man preauricular left was completely exised. Histologically tumor consists of atypical squamous cells, which express signs of moderate to significant pleomorphism, mitotically active, with foci forming of parakeratotic horn cysts ("pearls"). Characteristically tumor also consists of large number of atypical melanocytes with multifocal pattern, inserted between atypical squamous cells, and which contain large amount of dark brown pigment melanin. Immunohistochemically, squamous cells stain positively with keratin (CK116), melanocytes were stained with S -100 protein, HMB 45, and vimentin, but failed to stain with CK 116. To our knowledge this is the sixth reported case in world literature. The follow-up time of four years no evidence of recurrence or metastasis, similar all reported cases, but it is too short period in estimation to guarantee a benign course. However, it appears that this group of neoplasm may have different prognosis from pure squamous carcinoma or malignant melanoma. Topics: Carcinoma, Squamous Cell; Cell Differentiation; Facial Neoplasms; Humans; Keratins; Male; Medical Oncology; Melanocytes; Melanoma; Middle Aged; S100 Proteins; Skin Neoplasms; Vimentin | 2008 |
Merkel cell tumour of the external ear. Report of a case.
Merkel cells carcinoma (MCC) is an uncommon skin lesion, considered a malignancy of the neuroendocrine system, which is found mainly in elderly people. Its incidence is highly correlated with sun exposure or immunodeficiency syndromes. MCC is often an aggressive tumour with high tendency for local recurrence, lymph node involvement and distant metastasis. To our best knowledge 20 cases originated from the auricle have been described, 2 of them arising from external ear canal. The authors report a case of the ear canal characterized by two others synchronous tumours and the occurrence of a malignant high grade lymphoma, in which contribute of the pathologist was essential for a critical review. MCC diagnosis is not always easy for its pathological and clinical features and it should always be considered in presence of lymphoma. A multidisciplinary approach is basic. Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy, Fine-Needle; Carcinoma, Merkel Cell; Ear Neoplasms; Ear, External; Fatal Outcome; Head and Neck Neoplasms; Humans; Keratins; Lymphoma, Follicular; Magnetic Resonance Imaging; Male; Neoplasms, Second Primary; Parotid Gland; Skin Neoplasms | 2007 |
Cutaneous ciliated cyst in a 16-year-old girl.
A 16-year-old girl was seen for a painless subcutaneous mass of 1 year's duration. On excisional biopsy, a collapsed cystic structure lined by stratified, ciliated, columnar epithelium was noted; findings were consistent with cutaneous ciliated cyst. Immunohistochemical staining for progesterone receptor and epithelial membrane antigen were positive, whereas it was negative for carcinoembryonic antigen, which supports the theory of heteropia of the ciliated epithelium from the Müllerian epithelium in its histopathogenesis. Topics: Adolescent; Biomarkers, Tumor; Choristoma; Cysts; Diagnostic Errors; Epithelial Cells; Female; Humans; Keratins; Lipoma; Mucin-1; Mullerian Ducts; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Progesterone; Puberty; Receptors, Progesterone; Skin Neoplasms; Thigh | 2007 |
Pinkus tumor may originate from intraepidermal eccrine ducts and proliferate in the dermis.
To clarify the histopathogenesis of Pinkus tumor (fibroepithelial basal cell carcinoma, FEBCC), we have studied cytokeratin (CK) expression in FEBCC using ten different anti-keratin antibodies against CK 1, 7, 8, 10, 14, 15, 16, 17, 18 and 19. Tumor nests consisted of two epithelial components: duct-like structures and basaloid cells of anastomosing strands. In duct-like structure, CK 1, 10, 14, 16, 17 and 19 were detected. CK expression of duct-like structure showed the hyperproliferative state of eccrine intraepidermal ducts. In basaloid cells of anastomosing strands, CK 14 and 17 were detectable. These results suggested that duct-like structure originates from the intraepidermal duct and proliferates to spread in the dermis. Topics: Aged, 80 and over; Antibodies; Carcinoma, Basal Cell; Eccrine Glands; Eosine Yellowish-(YS); Epithelial Cells; Hematoxylin; Humans; Immunohistochemistry; Keratins; Male; Neoplasms, Fibroepithelial; Skin Neoplasms; Staining and Labeling | 2007 |
Trichoblastic sarcoma: a high-grade stromal tumor arising in trichoblastoma.
We report a case of primary sarcoma of the skin with a biphasic histological pattern, being composed of areas of mixed mesenchymal-epithelial cell proliferation and areas of purely sarcomatous growth. The tumor occurred in the posterior cervical region of a 93-year-old man, and its history was marked by sudden, rapid enlargement after many years of stable duration. The excised lesion was about 4 cm in diameter, had a firm consistency and was covered by intact skin. Histological examination showed a multifocal proliferation of follicular germinative cells arranged in corymbiform and petaloid shapes with an overall retiform growth pattern. Epithelial cords and strands were composed of cytologically uniform cells with bland nuclear features and were surrounded by a prominent, fibroblast-rich stroma reminiscent of a perifollicular sheath. In many areas of the tumor the stroma showed abrupt transition into a pleomorphic proliferation of large sarcomatous cells with frequent and often atypical mitoses. Multinucleated neoplastic cells infiltrated the epithelial structures to cause their partial or total obliteration in many fields of the lesion. Immunohistochemically, the epithelial cells displayed expression of various keratins, with a particularly intense staining for 34betaE12, and were partly positive for the CD10 antigen. A strong immunostaining for this antigen was also observed in malignant-appearing stromal areas, where no expression of cytokeratins was detected. Moreover, nuclear positivity for p53 protein was seen in sarcomatous cells, whereas it resulted in total lack of epithelial elements. Our case emphasizes that high-grade sarcoma may occur in the spectrum of trichoblastic tumors and that it may share some features of other noncutaneous biphasic neoplasms, such as mammary cystosarcoma phyllodes. Topics: Aged, 80 and over; Cell Proliferation; Cell Transformation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Keratins; Male; Neprilysin; Sarcoma; Skin Neoplasms; Stromal Cells; Tumor Suppressor Protein p53 | 2007 |
Nox1 induces differentiation resistance in immortalized human keratinocytes generating cells that express simple epithelial keratins.
We have shown that superoxide radical-generating NADPH oxidase 1 (Nox1) is increased in intermediate human transformed cells. It was unknown whether Nox1 overexpression could accelerate early transformation steps. We demonstrated that Nox1 rendered human immortalized (GM16) keratinocytes resistant against Ca(2+)/serum-induced differentiation. Nox1-transfected cells produced fast dividing resistant cells within 7-10 days after DMEM exposure. Progenitor lines (or Nox1 lines) were reproducibly generated from Nox1-transfected cells, while no lines were obtained from control transfections. From several attempts to generate control cells, one resistant population was obtained from untransfected GM16 cells after a 6-week DMEM exposure. Prolonged passaging of the control line could induce Nox1. Compared with the control line, Nox1 lines showed greater expression of Nox1, Rac1, p47phox, p67phox, NOXO1, and NOXA1 with concomitant increased superoxide generation. All five Nox1 lines contained varying amounts of E-cadherin, involucrin, vimentin, and K8/K18, while the control line did not. Since vimentin and K8/K18 are associated with malignant progression in different types of human epithelial tumors, our data demonstrate that Nox1 accelerated neoplastic-like progression by inducing generation of progenitor cells. Our data also emphasize the importance of Nox1 in inducing resistance against differentiation-induced cell death, suggesting a contribution of Nox1 and its oxidants during early stage of cell transformation. Topics: Calcium; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Disease Progression; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Keratins; Models, Biological; NADPH Oxidase 1; NADPH Oxidases; Reactive Oxygen Species; Skin Neoplasms; Transfection | 2007 |
Two cases of cytokeratin positivity in atypical fibroxanthoma.
Topics: Aged; Biomarkers, Tumor; Facial Neoplasms; False Positive Reactions; Head and Neck Neoplasms; Histiocytoma, Benign Fibrous; Humans; Keratins; Male; Neoplasm Proteins; Scalp; Skin Neoplasms | 2007 |
p63 in Primary Cutaneous Carcinosarcoma.
Primary cutaneous carcinosarcomas (PCCs) are rare malignant neoplasms that are characterized by biphasic epithelial and mesenchymal differentiation. When the biphasic nature is not evident, immunohistochemical studies may be important in the diagnosis of PCCs. Although AE1/AE3 is frequently used to demonstrate the epithelial component, it may not be strongly expressed in epithelial cells that are not well-differentiated. p63 is a protein homologue of p53 that is expressed in poorly differentiated epithelial cells. We report 3 cases of PCC. The clearly epithelial areas of each tumor were frequently positive for both markers, whereas the sarcomatous areas were negative for both markers. Epithelial cells that were poorly differentiated and not easily identifiable were positive for p63 but negative for AE1/AE3. Of interest, transitional areas showed positivity for p63 alone. These 3 cases suggest that the use of both p63 and routine cytokeratin markers such as AE1/AE3 can increase the sensitivity for distinguishing epithelial cells over a range of differentiation states, which we propose will aid in the diagnosis of PCCs. In addition, the staining pattern of AE1/AE3 and p63 in these cases further supports the conversion theory of PCC. Topics: Aged; Aged, 80 and over; Anion Exchange Protein 1, Erythrocyte; Antiporters; Biomarkers, Tumor; Carcinosarcoma; Cell Differentiation; DNA-Binding Proteins; Epithelial Cells; Humans; Keratins; Male; Middle Aged; Skin Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Vimentin | 2007 |
Clear-cell acanthoma versus acanthosis: a psoriasiform reaction pattern lacking tricholemmal differentiation.
Clear-cell acanthoma (CCA) has been reported to be a benign epidermal neoplasm; however, several authors have suggested alternative differentiation as well as other nosologic categories, including a reactive dermatosis. Fourteen CCAs, ten tricholemmomas, and seven cases of psoriasis were reviewed with conventional microscopy, periodic acid-Schiff stains, and immunohistochemical stains. Twelve of fourteen (86%) CCAs were associated with underlying or adjacent conditions. The CCAs stained immunohistochemically in a pattern similar to normal epidermis and psoriasis. Tricholemmomas stained in a distinctly different pattern with MNF116 and NGFR/p75. These cases demonstrate CCA in settings that reflect chronic inflammation, primarily scars and stasis dermatitis, and with an immunophenotype that parallels psoriasis. These findings support the contention that CCA does not show outer follicular sheath (tricholemmal) differentiation. Furthermore, these cases lend additional support to the contention that CCA represents a psoriasiform reaction pattern, which, in appropriately taken biopsies, usually has a demonstrable associated condition. Nonetheless, the precise nosology of this phenomenon has yet to be elucidated completely. Topics: Acanthoma; Adult; Aged; Aged, 80 and over; Cicatrix; Dermatitis; Epidermis; Female; Hair Follicle; Hidradenitis Suppurativa; Humans; Hyperplasia; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Molecular Weight; Neoplasms, Basal Cell; Nerve Tissue Proteins; Psoriasis; Receptors, Nerve Growth Factor; Skin; Skin Neoplasms | 2007 |
Cytokeratin expression in squamous cell carcinoma arising from hidradenitis suppurativa (acne inversa).
We have studied cytokeratin (CK) expression in two cases of well-differentiated and poorly differentiated squamous cell carcinoma (SCC) arising from hidradenitis suppurativa (HS) (acne inversa). In both cases, type A (infundibular-like keratinized) epithelia were observed. In type A epithelia, CK 1 and 10 expressions were decreased, and CK 14 and 17 were detectable in the whole layers. CK 7, 8, 15, 16 and 18 were not detected in type A epithelia. In tumor nests of well-differentiated SCC, CK 1 and 10 expressions were downregulated, and CK 14 expression was upregulated. In tumor nests of poorly differentiated SCC, CK 1 and 10 were not expressed, but simple epithelial keratins (CK 8, 18 and 19) were expressed. These changes of CK expression are related to malignant transformation from the sinus tract (type A epithelium) in HS to SCC. Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Fatal Outcome; Hidradenitis Suppurativa; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Skin Neoplasms | 2007 |
Combined Bowen disease and extramammary Paget disease.
The histological resemblance between extramammary Paget disease and Bowen disease has been described since Bowen's original article was published in 1912.. We herein describe a case of vulval primary extramammary Paget disease in a 61-year-old women with the histological features of Bowen disease.. Histological examination of a biopsy specimen showed acanthosis with full-thickness cellular atypia, focal hyperkeratosis and parakeratosis in the epidermis, and no characteristic Paget cells were observed. However, histological examination of an operative specimen revealed areas characteristic of Paget disease and Bowen disease. Overall, the areas characteristic of Bowen disease and Paget disease occupied 6% and 32% of the total operative specimen, respectively. The two areas were sharply separated. Immunohistochemical findings showed carcinoembryonic antigen to be expressed in areas containing Paget cells, but not in the areas characteristic of Bowen disease. Cytokeratin 7 (CK7) (OV-TL 12/30) and CK8 (35betaH11) were strongly expressed in both of these areas. The staining for high-molecular-weight cytokeratins was negative in both of these areas.. Our findings indicated that primary extramammary Paget disease and squamous cell carcinoma in situ arose multifocally from a common cell in the epidermis. Topics: Biomarkers, Tumor; Bowen's Disease; Carcinoembryonic Antigen; Carcinoma in Situ; Female; Humans; Keratins; Middle Aged; Neoplasms, Multiple Primary; Paget Disease, Extramammary; Skin Neoplasms; Treatment Outcome; Vulvar Neoplasms | 2007 |
Spindle cell neoplasm of skin: diagnostic dilemma.
Poorly differentiated, spindle cell malignancies, on sun damaged skin frequently pose a diagnostic challenge for pathologists. The vast majority of these neoplasms ultimately are diagnosed as either atypical fibroxanthoma (AFX), spindle cell melanoma (SCM), and very rarely as spindle cell squamous cell carcinoma (SCSCC), leiomyosarcoma or angiosarcoma. Light microscopic clues may suggest one of these neoplasms, but subtle and overlapping characteristics often render precise diagnosis impossible based on morphological features alone. Immunohistochemistry therefore is necessary to firmly and accurately diagnose the majority of spindle cell malignancies on sun damaged skin. Aim of this case report is to highlight the practical approach to such diagnostic dilemmas. Topics: Aged, 80 and over; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Melanoma; S100 Proteins; Sarcoma; Skin Neoplasms; Vimentin; Xanthomatosis | 2007 |
Differential induction of connexins 26 and 30 in skin tumors and their adjacent epidermis.
Gap junctions (GJs) have been shown to play a role in tumor progression including a variety of keratinocyte-derived and non-keratinocyte-derived skin tumors. Here we show that the synthesis of the GJ proteins connexin 26 and connexin 30 (Cx26 and Cx30) is induced in keratinocyte-derived epithelial skin tumors whereas there is either no change or a downregulation of Cx43. Cx26, Cx30, and Cx43 are absent in non-epithelial skin tumors. Further, Cx26 and Cx30 are induced in the epidermis adjacent to malignant melanoma but absent in the epidermis adjacent to benign non-epithelial skin lesions (melanocytic nevi and angioma). The keratinocyte-derived skin tumors are very heterogeneous regarding the Cx26/Cx30 pattern in the epidermis at the periphery of the tumors. We did not observe any difference in the localization of the very similar proteins Cx26 and Cx30 but a variation in intensity of immunoreactivity. As the staining patterns of Cx26 and Cx30 antibodies are not identical to those of CK6, a marker for hyperproliferation, and CK17, a marker for trauma, we discuss that the induction of these gap junctional proteins exceeds a reflection of reactive hyperproliferative or traumatized epidermis. We further discuss the putative roles of these gap junctional proteins in tumor progression. Topics: Animals; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Connexin 26; Connexin 30; Connexins; Epidermis; Hemangioma; Humans; Keratinocytes; Keratins; Keratosis; Liver; Melanoma; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Nevus, Pigmented; Skin Neoplasms; Warts | 2006 |
Loss of intercellular adhesion activates a transition from low- to high-grade human squamous cell carcinoma.
The relationship between loss of intercellular adhesion and the biologic properties of human squamous cell carcinoma is not well understood. We investigated how abrogation of E-cadherin-mediated adhesion influenced the behavior and phenotype of squamous cell carcinoma in 3D human tissues. Cell-cell adhesion was disrupted in early-stage epithelial tumor cells (HaCaT-II-4) through expression of a dominant-negative form of E-cadherin (H-2Kd-Ecad). Three-dimensional human tissue constructs harboring either H-2Kd-Ecad-expressing or control II-4 cells (pBabe, H-2Kd-EcadDeltaC25) were cultured at an air-liquid interface for 8 days and transplanted to nude mice; tumor phenotype was analyzed 2 days and 2 and 4 weeks later. H-2Kd-Ecad-expressing tumors demonstrated a switch to a high-grade aggressive tumor phenotype characterized by poorly differentiated tumor cells that infiltrated throughout the stroma. This high-grade carcinoma revealed elevated cell proliferation in a random pattern, loss of keratin 1 and diffuse deposition of laminin 5 gamma2 chain. When II-4 cell variants were seeded into type I collagen gels as an in vitro assay for cell migration, we found that only E-cadherin-deficient cells detached, migrated as single cells and expressed N-cadherin. Function-blocking studies demonstrated that this migration was matrix metalloproteinase-dependent, as GM-6001 and TIMP-2, but not TIMP-1, could block migration. Gene expression profiles revealed that E-cadherin-deficient II-4 cells demonstrated increased expression of proteases and cell-cell and cell-matrix proteins. These findings showed that loss of E-cadherin-mediated adhesion plays a causal role in the transition from low- to high-grade squamous cell carcinomas and that the absence of E-cadherin is an important prognostic marker in the progression of this disease. Topics: Animals; Cadherins; Carcinoma, Squamous Cell; Cell Adhesion; Cell Movement; Cell Proliferation; Disease Progression; Humans; Keratin-1; Keratins; Laminin; Male; Matrix Metalloproteinases; Mice; Mice, Nude; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; Phenotype; Prognosis; Skin Neoplasms; Tissue Culture Techniques | 2006 |
Conditional ablation of C/EBP beta demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis.
The CCAAT/enhancer binding protein beta (C/EBP beta) is implicated in the regulation of many different molecular and physiological processes. Mice with a germline deletion of C/EBP beta (C/EBP beta(-/-)) display phenotypes in a multitude of cell types and organ systems, including skin where C/EBP beta(-/-) mice exhibit increased apoptosis in epidermal keratinocytes in response to carcinogen treatment and are completely resistant to carcinogen-induced skin tumorigenesis. To determine the contribution of systemic versus cell autonomous functions of C/EBP beta to specific phenotypes, mice with a conditional 'floxed' C/EBP beta null allele were generated. Epidermal-specific deletion of C/EBP beta was achieved by Cre recombinase expression from a keratin 5 (K5) promoter. Similar to C/EBP beta(-/-) mice, K5-Cre;C/EBP beta(fl/fl) mice were completely refractory to 7,12 dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis and these mice displayed increased DMBA-induced apoptosis in epidermal keratinocytes compared to wild-type mice. In contrast, mice lacking the related gene, C/EBP delta, were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role of C/EBP beta in skin tumor development. Our findings demonstrate that C/EBP beta exerts an essential, keratinocyte-intrinsic role in cell survival in response to carcinogen treatment and the elimination of C/EBP beta in keratinocytes is sufficient to confer complete resistance of the skin to chemical carcinogenesis. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Carcinogens; CCAAT-Enhancer-Binding Protein-beta; Female; Integrases; Keratin-15; Keratin-5; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Mice, Knockout; Promoter Regions, Genetic; Skin Neoplasms; Tetradecanoylphorbol Acetate | 2006 |
Histopathological and immunohistochemical studies of poroid hidradenoma.
Poroid hidradenoma (PH), a less common subtype of poroid neoplasm (PN) than eccrine poroma (EP), has not been immunohistochemically studied before. Six cases of PH (four solitary PH and two PH coexisted with other types of PN) were included in the study. Fifteen cases of EP were also included for comparison. Hematoxylin and eosin, Masson-Zimmerman silver stain, and a variety of immunohistochemical stains were used. Microscopically, PH is not connected to the epidermis. All six PH contained small poroid cells and larger, paler cuticular cells. Some PH showed separate or clusters of sebocytes (2/6), horn cysts (1/6), juxtaposed lymphoid follicles in the stroma (1/6) and foci of keratohyaline granules (2/6), none of which was seen in the 15 EP. Immunohistochemically, the keratin distribution of PH was very similar to that of EP. PH has a very small number of Langerhans cells (significantly lower than the overlying epidermis, P=0.045), and a sparse deposition of melanin. We conclude that except the location, the histopathological and immunochemical differences between PH and EP were small. Sebaceous differentiation in two PH lesions suggested the possibility of an apocrine origin. The deeper parts of eccrine apparatus other than basaloid cells may have been more actively involved in the histogenesis of PH. Topics: Adenoma, Sweat Gland; Aged; Cell Transformation, Neoplastic; Eccrine Glands; Epidermis; Humans; Immunohistochemistry; Keratins; Male; Melanins; Middle Aged; Skin Neoplasms; Sweat Gland Neoplasms | 2006 |
Seborrheic keratosis with basal clear cells: a distinctive microscopic mimic of melanoma in situ.
We observed seborrheic keratoses with many basilar clear cells, creating a microscopic pattern that mimicked a seborrheic keratosis involved by melanoma in situ.. We sought to report a series of these seborrheic keratoses and the immunohistochemical stains used to reach a proper diagnosis.. We reviewed 9 cases of seborrheic keratosis that had a distinctive pattern of basal clear cells with ample cytoplasm. All cases were evaluated by conventional microscopy, and Melan-A, S-100, and high molecular weight keratin 903 immunostains.. The basal clear cells failed to react with Melan-A and S-100 protein antisera. In contrast, these cells labeled with an antikeratin antibody in all cases. In all, 7/9 (78%) showed immunopositivity only at the peripheries of cells, creating a pattern that could be mistaken for a negative stain if not examined at high magnification.. This is a retrospective review of cases limited to a large referral dermatopathology service.. We describe a previously uncharacterized pattern of seborrheic keratosis that can microscopically mimic melanoma in situ. Careful conventional microscopy coupled with a panel of immunostains can allow the proper diagnosis to be reached. Topics: Aged; Aged, 80 and over; Antibodies; Antigens, Neoplasm; Diagnosis, Differential; Female; Humans; Immune Sera; Immunoenzyme Techniques; Keratins; Keratosis, Seborrheic; Male; MART-1 Antigen; Melanoma; Middle Aged; Neoplasm Proteins; Retrospective Studies; S100 Proteins; Skin Neoplasms; Staining and Labeling | 2006 |
Expression patterns of hair and epithelial keratins and transcription factors HOXC13, LEF1, and beta-catenin in a malignant pilomatricoma: a histological and immunohistochemical study.
We have previously shown that benign pilomatricomas not only maintain the sequential expression of the hair matrix and precortex keratins hHa5 and hHa1 of normal hair follicles in their transitional cell compartment, but also preserve the association of hHa5 expression with that of its regulatory homeoprotein HOXC13 in the lower transitional cell compartment. In contrast, hHa1 expression in the upper transitional cell compartment is uncoupled from the nuclear co-expression of the LEF1/beta-catenin complex seen in normal hair follicles (Cribier et al., J Invest Dermatol 2004; 122: 1078).. Formalin-fixed paraffin sections of the tumor were examined using a panel of mono- and polyclonal hair and epithelial keratin antibodies as well as antibodies against HOXC13, LEF1, and beta-catenin.. Morphologically, the malignant pilomatricoma investigated here clearly deviated from the described major tumor type by a large number of differently sized parakeratotic squamoid whorls emerging within the mass of basaloid cells and surrounded by cells remembering transitional cells, but only rarely containing shadow cells and signs of calcification. We show that hHa5/HOXC13 co-expression was maintained in transitional cell areas, in which hHa1 expression was much stronger than in benign pilomatricomas, but again uncoupled from concomitant nuclear LEF1/beta-catenin expression. Surprisingly, however, and in clear contrast to benign pilomatricomas, these transitional cells co-expressed the epithelial keratins K5, K14, and K17, with the latter being as strongly expressed as hHa1, both also staining the entire inner mass of the parakeratotic whorls.. Although the malignant pilomatricoma investigated here was distinctive in that it contained a multitude of parakeratinizing whorls and no signs of calcification, it shared both hHa5/HOXC13 co-expression and disrupted hHa1/beta-catenin-LEF1 expression in its transitional cell compartment around the whorls with benign pilomatricomas. However, in clear contrast to the latter, transitional cells of the malignant tumor also strongly expressed the epithelial keratins K5, K14, and K17. We speculate that the observed dominance of the epithelial differentiation pathway over the competing conventional shadow cell differentiation pathway may prevent massive calcification of the tumor. Topics: Aged, 80 and over; beta Catenin; Biomarkers, Tumor; Epithelial Cells; Hair; Hair Diseases; Homeodomain Proteins; Humans; Immunohistochemistry; Keratins; Lymphoid Enhancer-Binding Factor 1; Male; Pilomatrixoma; Skin Neoplasms; Transcription Factors | 2006 |
PTEN loss promotes rasHa-mediated papillomatogenesis via dual up-regulation of AKT activity and cell cycle deregulation but malignant conversion proceeds via PTEN-associated pathways.
PTEN tumor suppressor gene failure in ras(Ha)-activated skin carcinogenesis was investigated by mating exon 5 floxed-PTEN (Delta5PTEN) mice to HK1.ras mice that expressed a RU486-inducible cre recombinase (K14.creP). PTEN inactivation in K14.cre/PTEN(flx/flx) keratinocytes resulted in epidermal hyperplasia/hyperkeratosis and novel 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas, whereas HK1.ras/K14.cre/PTEN(flx/flx) cohorts displayed a rapid onset of papillomatogenesis due to a synergism of increased AKT activity and extracellular signal-regulated kinase (ERK) elevation. High 5-bromo-4-deoxyuridine labeling in Delta5PTEN papillomas showed that a second promotion mechanism centered on failures in cell cycle control. Elevated cyclin D1 was associated with both HK1.ras/ERK- and Delta5PTEN-mediated AKT signaling, whereas cyclin E2 overexpression seemed dependent on PTEN loss. Spontaneous HK1.ras/Delta5PTEN malignant conversion was rare, whereas TPA promotion resulted in conversion with high frequency. On comparison with all previous HK1.ras carcinomas, such TPA-induced carcinomas expressed atypical retention of keratin K1 and lack of K13, a unique marker profile exhibited by TPA-induced K14.cre/PTEN(flx/flx) papillomas that also lacked endogenous c-ras(Ha) activation. Moreover, in all PTEN-null tumors, levels of ras(Ha)-associated total ERK protein became reduced, whereas phosphorylated ERK and cyclin D1 were lowered in late-stage papillomas returning to elevated levels, alongside increased cyclin E2 expression, in TPA-derived carcinomas. Thus, during early papillomatogenesis, PTEN loss promotes ras(Ha) initiation via elevation of AKT activity and synergistic failures in cyclin regulation. However, in progression, reduced ras(Ha)-associated ERK protein and activity, increased Delta5PTEN-associated cyclin E2 expression, and unique K1/K13 profiles following TPA treatment suggest that PTEN loss, rather than ras(Ha) activation, gives rise to a population of cells with greater malignant potential. Topics: Animals; Carcinogens; Cell Differentiation; Cell Transformation, Neoplastic; Keratin-13; Keratins; MAP Kinase Signaling System; Mice; Mice, Transgenic; Mifepristone; Oncogene Protein v-akt; Papilloma; PTEN Phosphohydrolase; ras Proteins; Skin Neoplasms; Tetradecanoylphorbol Acetate; Up-Regulation | 2006 |
Lymphoepithelioma-like carcinoma of the skin in a tunisian patient.
Lymphoepithelioma-like carcinoma of the skin (LELCs) is a rare cutaneous neoplasm with histologic features resembling lymphoepitheliomatous tumors of the nasopharynx. The association of lymphoepitheliomas with Epstein-Barr Virus (EBV) at some extracutaneous sites is well documented. In contrast, the presence of EBV in LELCs has never been shown in either Caucasians or Asian patients. We present the first case of LELCs in a Tunisian patient, a 78-year-old woman who presented with a nodule of the right cheek of 2 months' duration. The patient underwent surgical excision and there was no evidence of local recurrence 6 months later. Histologically, the entire dermis was occupied by lobules composed of atypical epithelial cells surrounded by a dense lymphoplasmacytic infiltrate. Immunohistochemical examination showed that the epithelial tumor cells were positive for cytokeratin and epithelial membrane antigen. In situ hybridization investigations for the presence of EBV-encoded RNA showed negative results. Our findings suggest that LELCs is not related to EBV among North African patients. Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Disease-Free Survival; Epstein-Barr Virus Infections; Female; Humans; Keratins; Mucin-1; Skin Neoplasms | 2006 |
Cylindroma as tumor of hair follicle origin.
Topics: Aged; Carcinoma, Adenoid Cystic; Cell Differentiation; Deubiquitinating Enzyme CYLD; Female; Hair Follicle; Humans; Keratins; Keratins, Hair-Specific; Keratins, Type II; Middle Aged; Skin Neoplasms; Tumor Suppressor Proteins | 2006 |
Primary cutaneous signet ring cell carcinoma expressing cytokeratin 20 immunoreactivity.
Primary cutaneous signet ring cell carcinoma (PCSRCC) is a very unusual but distinctive clinicopathologic entity that can simulate metastatic adenocarcinomas. It is defined as a diffuse malignant epithelial neoplasia localized in the dermis and subcutis without epidermal involvement, showing variable amounts of signet ring cells, without evidence of visceral adenocarcinoma. We present 2 cases of PCSRCC, which involved eyelids and axilla respectively. Despite thorough systemic workup, primary sources could not be demonstrated in either case. The tumor cells are positive for gross cystic disease fluid protein 15 in addition to a variety of glandular markers. Furthermore, both cases were immunostained with cytokeratin 20 (CK20). In conclusion, we report 2 cases of PCSRCC expressing CK20 immunoreactivity. CK20-positive primary cutaneous tumors should include PCSRCC in addition to Merkel cell carcinoma. Topics: Aged; Carcinoma, Signet Ring Cell; Humans; Keratin-20; Keratins; Male; Middle Aged; Skin Neoplasms | 2006 |
Tenascin-C expression in Merkel cell carcinoma lymph node metastasis.
Expression of tenascin-C (Tn-C) has been shown to correlate with invasion and metastasis in Merkel cell carcinoma (MCC). Cytokeratin-20 (CK-20) is used in differential diagnostics of the primary tumour. The aim of this study was to demonstrate the expression of Tn-C in MCC lymph node metastases. Immunohistochemical staining was performed for five metastatic lymph nodes using a monoclonal antibody against Tn-C and CK-20. All five metastatic lymph nodes expressed Tn-C. The expression concentrated around the vascular structures, invasion borders and fibrotic septae. One of the metastatic lymph nodes was strongly positive for CK-20 while the others showed a focal or negative pattern. The normal lymphoid tissue was negative for Tn-C. Tn-C detected metastatic MCC tissue within the lymph nodes undisputedly. There was a clear distinction between the metastatic and normal lymphatic tissue. Furthermore, invasion to the surrounding tissue was easily demonstrated. Contrary to previous studies, CK-20 expression seemed to fluctuate. Topics: Biomarkers, Tumor; Carcinoma, Merkel Cell; Humans; Immunohistochemistry; Keratin-20; Keratins; Lymph Nodes; Lymphatic Metastasis; Skin Neoplasms; Tenascin | 2006 |
Cystic panfolliculoma.
Panfolliculoma is a rare follicular neoplasm with differentiation toward both upper (infundibulum and isthmus) and lower (stem, hair matrix, and bulb) segments of a hair follicle. We present an unusual case of cystic panfolliculoma. A 33-year-old Hispanic woman presented with an 8-month history of a 3.0-cm cystic scalp mass. The lesion was excised, and the histologic sections showed a cystic follicular neoplasm that contained corneocytes in basket-woven and laminated array, trichohyalin granules of the inner root sheath, germinative cells, papillae, matrical cells, and "shadow" cells. Cytokeratin 903 and cytokeratin 5/6 immunostains uniformly highlight the tumor cells. Ber-EP4 strongly labels the germinative cells but not the follicular papillae. CD34 labels the surrounding fibrotic stroma and focally the epithelial component. Topics: Adult; Biomarkers, Tumor; Epidermal Cyst; Female; Follicular Cyst; Hair Follicle; Humans; Keratins; Neoplasms, Basal Cell; Skin; Skin Neoplasms | 2006 |
The lysyl oxidase LOX is absent in basal and squamous cell carcinomas and its knockdown induces an invading phenotype in a skin equivalent model.
Lysyl oxidase initiates the enzymatic stage of collagen and elastin cross-linking. Among five isoforms comprising the lysyl oxidase family, LOX is the better studied. LOX is associated to an antitumor activity in ras-transformed fibroblasts, and its expression is down-regulated in many carcinomas. The aim of this work was to shed light on LOX functions within the epidermis by studying its expression in human basal and squamous cell carcinomas and analyzing the effect of its enzymatic activity inhibition and protein absence on human keratinocytes behavior in a skin equivalent. In both carcinomas, LOX expression by epidermal tumor cells was lacking, while it was up-regulated around invading tumor cells in association with the stromal reaction. Lysyl oxidase activity inhibition using beta-aminoproprionitrile in a skin equivalent model prepared with both primary human keratinocytes and HaCaT cell line affected keratin 10 and filaggrin expression and disorganized the collagen network and the basement membrane. In spite of all these changes, no invasion phenotype was observed. Modelization of the invasive phenotype was only noticed in the skin equivalent developed with LOX antisense HaCaT cell line, where the protein LOX is specifically absent. Our results clearly indicate that lysyl oxidase enzymatic activity is essential not only for the integrity maintenance of the dermis but also for the homeostasis of the epidermis. Moreover, LOX protein plays a role in the skin carcinomas and invasion but not through its enzymatic activity. Topics: Aminopropionitrile; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cells, Cultured; Collagen; Dermis; Fibroblasts; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratin-10; Keratinocytes; Keratins; Models, Biological; Neoplasm Invasiveness; Phenotype; Protein-Lysine 6-Oxidase; Skin Neoplasms | 2006 |
Spontaneous cutaneous squamous cell carcinoma in a sooty mangabey (Cercocebus atys): a case report.
An adult sooty mangabey (Cercocebus atys) with a solid mass arising from the skin of the dorsolateral cervical area was presented to the veterinary clinical staff. Grossly, the mass was firm, elongated, ulcerated at the tip, and measured 2.7 x 2.0 x 2.3 cm. It was surgically excised and then submitted for histopathologic evaluation. On histopathology, this tumor was composed of irregular masses and cords of neoplastic squamous epithelial cells that invaded the dermis and subcutis, often undergoing keratinization and forming numerous keratin pearls. On the basis of these histologic findings, the mass was diagnosed as a squamous cell carcinoma. Additional tests, including hematologic evaluations and radiographic views of the abdominal, thoracic, and cervical areas, were normal. Sections of the tumor were analyzed by electron microscopy and showed no evidence of viral particles. To the authors' knowledge, this is the first reported case of a spontaneous cutaneous squamous cell carcinoma in a sooty mangabey. Topics: Animals; Animals, Laboratory; Carcinoma, Squamous Cell; Cercocebus atys; Histocytochemistry; Keratins; Male; Microscopy, Electron, Transmission; Monkey Diseases; Neck; Radiography; Skin Neoplasms | 2006 |
Overexpression of the prostaglandin E2 receptor EP2 results in enhanced skin tumor development.
We previously showed that the EP2 knockout mice were resistant to chemically induced skin carcinogenesis. The purpose of this study was to investigate the role of the overexpression of the EP2 receptor in mouse skin carcinogenesis. To determine the effect of overexpression of EP2, we used EP2 transgenic (TG) mice and wild-type (WT) mice in a DMBA (7,12-dimethylbenz[alpha]anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate) two-stage carcinogenesis protocol. EP2 TG mice developed significantly more tumors compared with WT mice. Overexpression of the EP2 receptor increased TPA-induced keratinocyte proliferation both in vivo and in vitro. In addition, the epidermis of EP2 TG mice 48 h after topical TPA treatment was significantly thicker compared to that of WT mice. EP2 TG mice showed significantly increased cyclic adenosine monophosphate levels in the epidermis after prostaglandin E2 (PGE2) treatment. The inflammatory response to TPA was increased in EP2 TG mice, as demonstrated by an increased number of macrophages in the dermis. Tumors and 7 x TPA-treated and DMBA-TPA-treated (6 weeks) skins from EP2 TG mice produced more blood vessels than those of WT mice as determined by CD-31 immunostaining. Vascular endothelial growth factor (VEGF) protein expression was significantly increased in squamous cell carcinoma (SCC) samples from EP2 TG mice compared that of WT mice. There was, however, no difference in the number of apoptotic cells in tumors from WT and EP2 TG mice. Together, our results suggest that the overexpression of the EP2 receptor plays a significant role in the protumorigenic action of PGE2 in mouse skin. Topics: Animals; Animals, Newborn; Bromodeoxyuridine; Carcinoma, Squamous Cell; Cattle; Cell Culture Techniques; Cell Proliferation; Female; Humans; Hyperplasia; Inflammation; Keratinocytes; Keratins; Mice; Mice, Transgenic; Neovascularization, Pathologic; Polymerase Chain Reaction; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP2 Subtype; Skin Neoplasms; Tetradecanoylphorbol Acetate; Up-Regulation | 2006 |
Immunohistochemical distinction between merkel cell carcinoma and small cell carcinoma of the lung.
We assessed the usefulness of several immunohistochemical stains in distinguishing these two neoplasms, including cytokeratin 7, cytokeratin 20 (CK20), neuron-specific enolase, chromogranin, synaptophysin, neurofilaments (NF), thyroid-transcription factor-1 (TTF-1), CD56 antigen, S-100 protein, vimentin, c-erbB-2 oncoprotein, and CD117 antigen. All 13 cases of Merkel cell carcinoma evaluated were positive for CK20, and negative for TTF-1. Twelve of 13 Merkel cell carcinoma cases were positive for NF. Eleven of 13 cases of small cell lung carcinoma were positive for TTF-1. All small cell lung carcinoma cases were negative for NF, and all but one were negative for CK20. In terms of the remaining antigens, there were no differences of significance between the two neoplasms. These findings suggest that a set of three immunohistochemical stains, including CK20, NF, and TTF-1, is useful in affording a distinction between Merkel cell carcinoma and small cell lung carcinoma. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Merkel Cell; Carcinoma, Small Cell; CD56 Antigen; Chromogranins; Female; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Neurofilament Proteins; Nuclear Proteins; Phosphopyruvate Hydratase; Proto-Oncogene Proteins c-kit; Receptor, ErbB-2; S100 Proteins; Skin Neoplasms; Synaptophysin; Thyroid Gland; Thyroid Nuclear Factor 1; Transcription Factors; Vimentin | 2006 |
Cutaneous dermoid cyst: cytokeratin and filaggrin expression suggesting differentiation towards follicular infundibulum and mature sebaceous gland.
We experienced two cases of cutaneous dermoid cysts (DC). To elucidate the histogenesis of DC, we have studied cytokeratin (CK) expression in DC using ten different anti-keratin antibodies against CK1, 7, 8, 10, 14, 15, 16, 17, 18 and 19, and anti-filaggrin (filament aggregating protein) antibody. In the cyst wall of DC, CK1 and 10 were expressed in suprabasal layer, and CK14 was limited to the basal layer. In sebaceous gland-like structures, CK14 was detected in sebaceous acinus, and CK17 was detected in sebaceous duct. The other CKs were not detected. Filaggrin was intensely detected in the granular layer in the cyst wall of DC. CK expression profile of DC was similar to follicular infundibulum and sebaceous gland. These results suggested that DC differentiates towards follicular infundibulum and mature sebaceous gland. Topics: Adult; Antibodies; Cell Differentiation; Dermoid Cyst; Female; Filaggrin Proteins; Head and Neck Neoplasms; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Sebaceous Glands; Skin Neoplasms | 2006 |
Long-term establishment, characterization and manipulation of cell lines from mouse basal cell carcinoma tumors.
There have been few reports of successful long-term culture of cells established from cutaneous basal cell carcinoma (BCC) tumors. Here, we describe techniques that have enabled us to establish three long-term cultures of BCC cells isolated from BCC tumors that arose in irradiated Patched 1 (Ptch1)(+/-) mice. All three cell lines showed cellular morphology similar to that of BCC tumors and could be propagated for at least 20 passages. In addition, similar to BCC tumors, all cell lines had lost the wildtype Ptch1 allele, expressed BCC molecular markers, and responded similarly to cyclopamine, a small molecule inhibitor of Hedgehog signaling. Finally, we describe an efficient electroporation technique for DNA transfection into the BCC cell lines and show that they have activated Hedgehog signaling activity, albeit at a level lower than that of murine BCCs in vivo. These data indicate that the cell lines are bona fide long-term cultures of BCC cells and that DNA plasmids can be introduced into the BCC cell lines with relatively high transfection efficiency using a modified electroporation technique. Topics: Animals; Carcinoma, Basal Cell; Cell Culture Techniques; Cell Line, Tumor; Electroporation; Keratins; Kruppel-Like Transcription Factors; Mice; Patched Receptors; Patched-1 Receptor; Receptors, Cell Surface; Skin Neoplasms; Transfection; Zinc Finger Protein GLI1 | 2006 |
Expression of cytokeratin subtypes in intraepidermal malignancies: a guide for differentiation.
Among intraepidermal malignancies of epithelial origin, Bowen's disease, bowenoid actinic keratosis (BAK), intraepidermal malignant eccrine poroma (MEP), and Paget's disease may pose diagnostic difficulties.. Histologic features and immunohistochemical profiles of 24 cases of Bowen's disease, 21 cases of BAK, 18 cases of intraepidermal MEP, and 11 cases of Paget's disease were analyzed.. Using multivariate logistic regression test, multinuclear giant cells and solar degeneration were found to be the only histologic parameters of diagnostic help. On the other hand, a widespread positive reaction for CK 5/8, CK 7, CK 19, and negative reaction for CK 10, was a helpful feature in the differentiation of Paget's disease from Bowen's disease and BAK. The widespread and strong expression of CK 10 was seen in almost all cases of Bowen's disease in contrast to BAK. The widespread expression of CK 5/8 and CK 7, and negative reaction for CK 10, was in favor of Paget's disease, compared to intraepidermal MEP. On the other hand, widespread expression of CK 19 was a common finding in intraepidermal MEP, in contrast to Bowen's disease.. An immunohistochemical panel may provide significant hints on the differentiation of common intraepidermal malignancies, especially in problematic cases. Topics: Bowen's Disease; Diagnosis, Differential; Humans; Keratins; Keratosis; Neoplasms, Glandular and Epithelial; Paget Disease, Extramammary; Paget's Disease, Mammary; Regression Analysis; Skin Neoplasms; Sweat Gland Neoplasms | 2006 |
Onycholemmal carcinoma.
A 70-year-old Japanese man presented with a 5-year history of refractory indolent onycholysis of the little finger of the right hand. Roentgenograms did not show involvement of the bone. Histological examination revealed an epithelial tumor consisting of lobular masses varying in size. The tumor was composed of keratinocytes varying in atypicality and showed infiltrative growth into the dermis but not into the phalangeal bone. The tumor had cystic structures composed of eosinophilic amorphous keratin and a surrounding thin layer of keratinocytes. Characteristically, the epithelium in the center of the tumor abruptly changed into amorphous keratin without the formation of intervening keratohyaline granules. From these findings, the mass was diagnosed as onycholemmal carcinoma. Immunohistochemically, the tumor showed a keratin profile comparable to that of the nail bed epithelium and a smaller number of Ki-67-positive proliferating tumor cells compared with those of a previous case of onycholemmal carcinoma. Topics: Aged; Biopsy; Carcinoma; Cell Proliferation; Humans; Keratins; Male; Nail Diseases; Skin Neoplasms | 2006 |
Fine needle aspiration diagnosis of metastatic Merkel cell carcinoma with multinucleated bizarre tumour cells in a post-renal transplant patient.
Topics: Biomarkers, Tumor; Biopsy, Fine-Needle; Carcinoma, Merkel Cell; Chromogranin A; Female; Giant Cells; Humans; Immunocompromised Host; Keratins; Kidney Transplantation; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Postoperative Complications; Skin Neoplasms | 2006 |
Immunophenotyping of amelanotic melanoma. A case report.
Amelanotic malignant melanoma (AMM) is a subtype of cutaneous melanoma with little or no pigment upon visual inspection. The lack of pigmentation is the reason for late diagnosis of lesions and a poor prognosis. We report a case of a 55-year-old female with an AMM diagnosed by immunophenotyping. Monoclonal antibodies S-100, HMB-45, and antibodies to cytokeratin were used. Our patient underwent a wide local excision (a 2 cm wide margin) 2 years ago. So far there are no signs of a recurrence. In doubtful cases, immunophenotyping with monoclonal antibodies HMB-45 and S-100 is important for confirming the correct diagnosis of AMM. Topics: Antibodies; Antibodies, Monoclonal; Combined Modality Therapy; Diagnosis, Differential; Female; Humans; Immunophenotyping; Keratins; Melanoma, Amelanotic; Middle Aged; S100 Proteins; Skin Neoplasms | 2006 |
Herpetiform cutaneous metastases from transitional cell carcinoma of the urinary bladder: immunohistochemical analysis.
The case of an 83-year-old woman with an uncommon presentation of cutaneous metastases from muscle-invasive transitional cell carcinoma of the urinary bladder is reported. The band-like eruption of the metastatic lesion can often be misdiagnosed and treated initially as herpes zoster. A detailed immunohistochemical analysis is also described to differentiate metastatic lesions from other sources. Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Transitional Cell; Diagnosis, Differential; Fatal Outcome; Female; Herpes Zoster; Humans; Keratins; Neoplasm Proteins; Skin Neoplasms; Urinary Bladder Neoplasms | 2006 |
Primary angiosarcoma of the non-irradiated parotid gland: a most uncommon, highly malignant tumor.
This case report discusses the clinical presentation, imaging, surgery and further treatment and course of a primary angiosarcoma of a non-irradiated parotid gland. Topics: Aged; Aged, 80 and over; Hemangiosarcoma; Humans; Keratins; Leukocyte Common Antigens; Magnetic Resonance Imaging; Male; Neoplasm Staging; Neoplasms, Second Primary; Parotid Neoplasms; Skin Neoplasms; Tomography, X-Ray Computed | 2005 |
Cutaneous spindle cell carcinoma following basal cell carcinoma.
A spindle cell carcinoma arose three years after the seeming excision of a so-called "infiltrative" basal cell carcinoma (IBCC) in the cheek of an 87-year-old Japanese woman. The patent had no history of irradiation. The tumor was composed of short fascicles and whorling arrangements of spindle to polygonal cells without residual IBCC. Immunohistochemically, the tumor was positive for vimentin, cytokeratin 8 & 18, epithelial membrane antigen, and alpha-smooth muscle actin. Ultrastructurally, the tumor cells had tonofilaments and desmosomes. The patient died after a local recurrence with metastatic lesions in the lung and the neck lymph nodes that were indicated by CT scanning and MRI at nine months after diagnosis. This case and others support the concept that spindle cell carcinoma can pursue an aggressive clinical course. Topics: Actins; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Carcinoma, Basal Cell; Fatal Outcome; Female; Humans; Keratins; Mucin-1; Neoplasms, Second Primary; Skin Neoplasms; Vimentin | 2005 |
Expression of hard alpha-keratins in pilomatrixoma, craniopharyngioma, and calcifying odontogenic cyst.
To examine the properties of shadow and ghost cells, 3 kinds of antibodies were raised against human hair proteins and their immunoreactivity was examined in tumors expressing those cells: pilomatrixoma, 14 cases; craniopharyngioma, 17 cases; and calcifying odontogenic cyst (COC), 14 cases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses demonstrated that 2 polyclonal antibodies, PA-HP1 and PA-HP 2, reacted strongly with type I acidic and type II neutral/basic hard alpha-keratins. The other monoclonal antibody, MA-HP1, reacted with type II neutral/basic hard alpha-keratins. Immunohistochemical examination revealed that all 3 antibodies reacted only with the hair shaft in sections of normal skin and dermoid cyst. In all pilomatrixoma cases, 3 antibodies reacted with the cytoplasm of transitional and shadow cells but not with that of basophilic cells. Positive reactions were found only in shadow cells of all 13 adamantinomatous craniopharyngiomas. In all COCs, the antibodies reacted only with ghost cells, not with other epithelial components. Immunoreactivity for phosphothreonine, detected in hard alpha-keratins, also was found in transitional, shadow, and ghost cells. The appearance of shadow or ghost cells might represent differentiation into hair in these 3 kinds of tumors. Topics: Animals; Biomarkers, Tumor; Blotting, Western; Cells, Cultured; Craniopharyngioma; Hair; Hair Diseases; Humans; Hybridomas; Immunoenzyme Techniques; Jaw Neoplasms; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Neoplasms; Odontogenic Cyst, Calcifying; Pilomatrixoma; Pituitary Neoplasms; Skin Neoplasms | 2005 |
Development of skin tumors in mice transgenic for early genes of human papillomavirus type 8.
The cutaneous human papillomavirus (HPV) 8 is clearly involved in skin cancer development in epidermodysplasia verruciformis patients and its early genes E2, E6, and E7 have been implicated in cell transformation in vitro. To examine the functions of these genes in vivo we integrated the complete early region of HPV8 into the genome of DBA/Bl6 mice. To target their expression to the basal layer of the squamous epithelia the transgenes were put under the control of the keratin-14 promoter. Transgenic mice were back-crossed for up to six generations into both FVB/N and Bl6 mouse strains. Whereas none of the HPV8 transgene-negative littermates developed lesions in the skin or any other organ, 91% of HPV8-transgenic mice developed single or multifocal benign tumors, characterized by papillomatosis, acanthosis, hyperkeratosis, and varying degrees of epidermal dysplasia. Squamous cell carcinomas developed in 6% of the transgenic FVB/N mice. Real-time reverse transcription-PCR showed highest expression levels for HPV8-E2, followed by E7 and E6. There was no consistent difference in relative viral RNA levels between healthy or dysplastic skin and malignant skin tumors. Whereas UV-induced mutations in the tumor suppressor gene p53 are frequently detected in human skin carcinomas, mutations in p53 were not observed either in the benign or malignant mouse tumors. Nonmelanoma skin cancer developed in HPV8-transgenic mice without any treatment with physical or chemical carcinogens. This is the first experimental proof of the carcinogenic potential of an epidermodysplasia verruciformis-associated HPV-type in vivo. Topics: Animals; Genes, p53; Genes, Viral; Keratin-14; Keratins; Mice; Mice, Inbred DBA; Mice, Transgenic; Mutation; Papillomaviridae; Promoter Regions, Genetic; Skin Neoplasms; Transcription, Genetic | 2005 |
Skin carcinoma arising from donor cells in a kidney transplant recipient.
The incidence of skin cancer is increased in transplant recipients. UV radiation, papillomaviruses, and immunosuppression participate in the pathogenesis of these tumors. In addition, donor cells may leave the grafted organ, reach peripheral tissues and either induce immune phenomena or possibly take part in tissue remodeling. Herein, we investigated the possible involvement of donor cells in the development of skin tumors in kidney allograft recipients. We analyzed a series of 48 malignant and benign cutaneous tumors developing in 14 females who had been grafted with a male kidney. The number of male cells was measured on microdissected material by quantitative PCR for Y chromosome. In the samples with high levels of male cells, fluorescent in situ hybridization (FISH) with X and Y probes and/or immuno-FISH with anticytokeratin antibodies were carried out. Male cells were detected in 5/15 squamous cell carcinomas and Bowen disease (range 4-180 copies), 3/5 basal cell carcinomas (91-645), 6/11 actinic keratosis (7-102), 2/4 keratoacanthoma (22-41), and 2/5 benign cutaneous lesions (14-55). In a basal cell carcinoma specimen with a high number of male cells, FISH showed that most cells within the tumoral buds were XY. In this lesion, immuno-FISH showed the presence of XY cytokeratin-positive cells indicating that the tumor nests contained male keratinocytes. In contrast, in other female transplants, male cells present in the tumors were not epithelial. In conclusion, stem cells originating from a grafted kidney may migrate to the skin, differentiate, or fuse as keratinocytes that could, rarely, undergo cancer transformation. Topics: Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Fusion; Chromosomes, Human, X; Chromosomes, Human, Y; Female; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Karyotyping; Keratinocytes; Keratins; Keratoacanthoma; Keratosis; Kidney Transplantation; Male; Reverse Transcriptase Polymerase Chain Reaction; Skin Diseases; Skin Neoplasms; Stem Cells; Tissue Donors; Transplantation, Homologous | 2005 |
Vulvar trichogenic tumors: a comparative study with vulvar basal cell carcinoma.
Trichogenic tumors are very rare in genital skin and often cause diagnostic problems because they are mitotically active and they share some histologic features with basal cell carcinomas (BCCs). We present the clinical and histologic features of 16 vulvar trichogenic tumors (6 plaque-like, 10 nodular; average age, 65 years) in comparison with 16 BCCs (11 plaque-like, 5 nodular; average age, 78 years). All trichogenic tumors, except 1 case with HSV infection, were nonulcerated tumors. Superficial plaque-like trichogenic tumors featured basal keratinocyte proliferations with peripheral nuclear palisading but no clefting at the epithelial-stromal interface. Nodular trichogenic tumors consisted of solid lobules of squamous cells and anastomosing cords and reticulations of follicular germinative cells with mitoses and apoptosis. Large pink cells with trichohyaline granules and melanocytes resembling the inner hair sheath, and clear cells resembling the outer root sheath were common. Most cysts were keratinized, but some fluid-filled cysts showed apocrine and sebaceous differentiation. The well-defined mesenchymal component of trichogenic tumors was pale and mucinous, and contained fibrocytes and fibrillary collagen bundles. All BCCs showed surface ulcerations and clefting at the stromal-epithelial interface. BCCs showed no trichogenic differentiation and lacked an organized mesenchymal tumor component. The tumor stroma of BCCs was paucicellular, mucinous, or granulation tissue-like with an inflammatory infiltrate. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasms, Adnexal and Skin Appendage; Skin Neoplasms; Vulvar Neoplasms | 2005 |
Production of the long and short forms of MFG-E8 by epidermal keratinocytes.
Mouse milk fat globule-EGF factor 8, MFG-E8, is the ortholog to the human mammary tumor marker, lactadherin, and comprises two spliced variants, the L and S forms. Recent studies have suggested that MFG-E8-L produced by macrophages and Langerhans cells in the skin serves as a linker between phagocytic cells and apoptotic cells, and that MFG-E8-S, also termed SED1, facilitates sperm-egg interaction for fertilization. However, Mfge8 gene expression occurs in various tissues apparently unrelated to these critical events. Our in situ hybridization study has revealed that Mfge8 is expressed in the periderm (the premature epidermis) on embryonic day-14, well before Langerhans cells begin to grow in the prenatal phase. Mfge8 transcript is detectable in the basal and spinous layers throughout skin development, whereas immunostaining has revealed MFG-E8 protein accumulation in the spinous layer. Cultured keratinocyte stem cells consistently express Mfge8-L and -S mRNAs and produce the L protein, which is primarily detectable in the culture supernatant, and the S protein, which is mostly associated with the cells. Upon Ca(2+)-stimulated differentiation, which is detected by a decrease in keratinocyte stem cell marker p63(p51) and the induction of keratin1, we have observed suppression of Mfge8, and the protein becomes localized to the cell-cell borders. Papillomas and carcinomas caused by chronic UV-B irradiation produce MFG-E8 as determined by immunostaining. Thus, undifferentiated and poorly differentiated keratinocytes produce the L and S forms of MFG-E8 during normal and pathological tissue development, probably to support an as yet unidentified membrane function. Topics: Animals; Animals, Newborn; Antigens, Surface; Calcium; Cell Differentiation; Cell Membrane; Cells, Cultured; Epidermis; Gene Expression Regulation, Developmental; Keratin-1; Keratinocytes; Keratins; Mice; Mice, Inbred ICR; Milk Proteins; Molecular Weight; Organ Specificity; Phosphoproteins; RNA, Messenger; Skin Neoplasms; Stem Cells; Trans-Activators | 2005 |
Microarray profiles of human basal cell carcinoma: insights into tumor growth and behavior.
Basal cell carcinoma (BCC) is the most common human neoplasm. Much interest lies in determining the genetic basis of BCC to explain the unique locally invasive phenotype and infrequent metastatic behavior of these skin tumors.. We sought to examine a gene expression profile for BCC to elucidate new molecules responsible for its unique growth characteristics.. We analyzed gene expression patterns of 50 BCC tumors using spotted cDNA microarrays of 1718 characterized human genes related to cancer and immunity. This is the largest and most comprehensive gene expression study ever performed for BCC. Nodular and sclerosing histological subtypes of BCC were examined and compared to normal control skin. After statistical filtering, 374 significantly dysregulated genes were sorted by hierarchical clustering to determine trends of gene expression and similarities between patient gene expression profiles.. A total of 165 upregulated genes and 115 downregulated genes were identified. These covered a range of categories, including extracellular matrix, cell junctions, motility, metastasis, oncogenes, tumor suppressors, DNA repair, cell cycle, immune regulation and angiogenesis. Clusters of genes were either commonly dysregulated across the 50 patient sample, or selectively affected in subsets of tumors. Histological subtypes were not distinguishable by hierarchical clustering. Many of the genes elucidated, including collagen type IV subunits and other novel candidates, possess functions related to extracellular matrix remodeling and metastasis.. These results suggest a gene profile which may explain the invasive growth yet rarely metastatic behavior of BCC. The genes identified may also be potential targets for therapeutics aimed at further controlling invasiveness and local destruction of BCC. Topics: Carcinoma, Basal Cell; Caveolin 1; Caveolins; Collagen; DNA-Binding Proteins; Gene Expression Profiling; Humans; Keratins; Kruppel-Like Transcription Factors; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Phosphoprotein Phosphatases; Skin Neoplasms; Zinc Finger Protein Gli2 | 2005 |
Aberrant expression of caspase-14 in epithelial tumors.
Cysteine-dependent aspartate-specific proteases (caspases) are the cellular executors of apoptosis. Caspase-14 is the most divergent member of the family of mammalian caspases and displays a variety of unique characteristics. It is expressed in a limited number of tissues and has the shortest amino acid sequence within the caspase protein family. During induction of apoptosis, it is not processed, whereas terminal differentiation in skin leads to cleavage of caspase-14. Here we show that 40% of lung squamous cell carcinomas, 22% of breast cancers, and about 80% of cervical carcinomas express caspase-14. Immunohistochemistry reveals that caspase-14 is localized in areas of ongoing differentiation close to necrotic sites but is not strictly associated with the differentiation markers keratin-1/-10. Caspase-14 is neither mutated nor alternatively spliced in the tumors analyzed. Furthermore, caspase-14 is not processed into a small and large subunit, a process critical for the proteolytic activation of known effector caspases. We conclude that conditions exist in tumors leading to re-expression of this normally silent gene. Topics: Alternative Splicing; Animals; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Caspase 14; Caspases; Cell Differentiation; Cell Line, Tumor; DNA Primers; DNA, Complementary; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Immunohistochemistry; Keratin-1; Keratin-10; Keratins; Microscopy, Fluorescence; Mutation; Necrosis; Neoplasms, Glandular and Epithelial; Polymerase Chain Reaction; Skin Neoplasms; Tissue Distribution | 2005 |
Cytokeratin contents of basal cell carcinoma, epidermis overlying tumour, and associated stromal amyloidosis: an immunohistochemical study.
Cytokeratins (CKs) are expressed specifically in the cytoplasm of epithelial cells. We investigated the expression of CKs immunohistochemically in basal cell carcinomas (BCCs), epidermis overlying tumour, and skin tumor-associated amyloidosis (STA). Twenty cases of BCC, 11 of which had STA were included to the study. The primary antibodies of CK1-8 (AE3), CK10 (DEK-10), CK14 (LL002), CK17 (E3), CK18 (DC10), CK19 (KS19.1), CK 5/6/18 (LP34), CK8/18 (5D3) were applied to the section immunohistochemically. In BCCs without STA, CK1-8, CK14 and CK17 antibodies were expressed by tumour tissue in all biopsy specimens. In the BCCs with STA, tumour tissue was immunoreactive always with CK1-8 and CK17 antibodies, and commonly immunoreactive with anti-CK 14 antibody. In the epidermis overlying tumour tissue, there was positive immunoreactivity with anti-CK 1-8, CK 5/6/18, CK 10 and CK 14 antibodies in all biopsy specimens. Anti-CK 17 antibody was also positive in 17 biopsy specimens. STA is immunoreactive with anti-CK1-8 in all specimens. There was mild staining with anti-CK5/6/18 and with anti-CK19 whereas no immunoreactivity with anti-CK10 and CK18 antibodies was found. In conclusion, we could not find a significant CK expression difference between BCCs with and without STA. Weak positivity and a few number of CKs were shown in STA when compared with those of BCC and epidermis overlying tumour tissue expressing the more variable CKs. Interestingly, although CKs coexpressed in pairs consisting of one basic and one acidic CK, we detected predominantly basic CKs in STA. Topics: Amyloidosis; Carcinoma, Basal Cell; Epidermis; Humans; Immunoenzyme Techniques; Keratins; Skin Neoplasms; Stromal Cells | 2005 |
Transient expression of keratin 19 is induced in originally negative interfollicular epidermal cells by adhesion of suspended cells.
Keratin 19 and nuclear reactivity to an endogenous lectin, galectin-1, represent a potential marker of epidermal stem cells. We detected expression of keratin 19 and nuclear binding sites for galectin-1 in adult cells migrating from the hair follicle, where cells expressing keratin 19 are located in the bulge region. The results were compared with the expression of both markers in cells adhering from suspension prepared from the interfollicular epidermis without keratin-19-positive cells and with nuclear binding sites for galectin-1. The results were compared with data from basal cell carcinomas. All cells were analyzed concerning size, as it is known that cell diameter influences the clonogenic potential of keratinocytes. The major result of this study is the observation of transient expression of keratin 19 and nuclear galectin-1 binding sites in originally negative interfollicular epidermal cells induced by adhesion. These cells were very small in size, similar to basal cells of the interfollicular epidermis or the bulge region of the hair follicle. The influence of the suspension regimen on beta1-integrin expression, cell diameter and growth was also monitored. A population of cells highly positive for beta1 integrin of the same diameter as keratin-19-positive cells insensitive to induction of terminal differentiation by lack of anchorage was characterized. Cells of the same size were also observed in the keratin-19-positive cells of basal cell carcinomas. In conclusion, the expression of poor levels of differentiation induced by cell adhesion is transient. Also, keratin 19 expression should not be exclusively regarded as a marker of stem cell activity. Topics: Carcinoma, Basal Cell; Cell Adhesion; Cell Culture Techniques; Cell Movement; Cells, Cultured; Epidermal Cells; Epidermis; Galectin 1; Galectin 3; Hair Follicle; Humans; Integrin beta1; Intermediate Filament Proteins; Keratin-10; Keratin-20; Keratinocytes; Keratins; Skin Neoplasms; Time Factors | 2005 |
Mechanisms of SEPA 0009-induced tumorigenesis in v-rasHa transgenic Tg.AC mice.
Genetically engineered mouse models with altered oncogene or tumor suppressor gene activity have been utilized recently for carcinogen identification. The v-rasHa transgenic Tg.AC mouse, with its enhanced susceptibility to skin tumorigenesis, is thought to be well suited for examining the carcinogenicity of topically applied agents. Tg.AC mice were used to examine the carcinogenicity of SEPA 0009, a rationally designed organic molecule designed to enhance drug penetration through the skin. Fifty mg SEPA 0009/kg body weight, 1500 mg SEPA 0009/kg body weight, or the vehicle alone was applied daily to the skin of Tg.AC mice. Nontransgenic FVB/N mice were also treated with the vehicle alone or 1500 mg SEPA 0009. Daily application of a high-dose of SEPA 0009 caused severe and chronic irritation by 1 week that was maintained throughout the experiment. The irritation was accompanied by increased proliferation, increased apoptosis, and expression of the wound-associated keratin 6. High-dose SEPA 0009 induced squamous papillomas in Tg.AC, but not in nontransgenic mice, by 6 weeks. In mice treated with the high dose SEPA 0009, transgene expression was detected in papillomas at week 9, well after the onset of skin irritation and hyperplasia. In contrast, low-dose SEPA 0009 was not irritating to the skin and did not induce papillomas. Thus, SEPA 0009-induced tumorigenesis was associated with chronic and severe irritation. We propose that SEPA 0009-induced tumorigenesis in Tg.AC mice proceeds through an indirect mechanism that is secondary to cutaneous irritation. Topics: Animals; Carcinogenicity Tests; Carcinogens; Cell Death; Cell Proliferation; Dermatitis, Irritant; Dioxolanes; Dose-Response Relationship, Drug; Epidermis; Female; Gene Expression; Genes, ras; Hyperplasia; Keratin-6; Keratinocytes; Keratins; Mice; Mice, Transgenic; Papilloma; Precancerous Conditions; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors | 2005 |
Trichoadenoma: cytokeratin expression suggesting differentiation towards the follicular infundibulum and follicular bulge regions.
Topics: Adenoma; Cell Differentiation; Female; Hair Diseases; Humans; Keratins; Middle Aged; Skin Neoplasms | 2005 |
Early epidermal destruction with subsequent epidermal hyperplasia is a unique feature of the papilloma-independent squamous cell carcinoma phenotype in PKCepsilon overexpressing transgenic mice.
Protein kinase C epsilon (PKCepsilon) overexpressing transgenic (PKCepsilon Tg) mice develop papilloma-independent squamous cell carcinomas (SCC) elicited by 7,12-dimethylbenz[a]anthracene (DMBA) tumor initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) tumor promotion. We examined whether epidermal cell turnover kinetics was altered during the development of SCC in PKCepsilon Tg mice. Dorsal skin samples were fixed for histological examination. A single application of TPA resulted in extensive infiltration of polymorphonuclear neutrophils (PMNs) into the epidermis at 24 h after TPA treatment in PKCepsilon Tg mice while wild-type (WT) mouse skin showed focal infiltration by PMNs. Complete epidermal necrosis was observed at 48 h in PKCepsilon Tg mice only; at 72 h, epidermal cell regeneration beginning from hair follicles was observed in PKCepsilon Tg mice. Since the first TPA treatment to DMBA-initiated PKCepsilon Tg mouse skin led to epidermal destruction analogous to skin abrasion, we propose the papilloma-independent phenotype may be explained by death of initiated interfollicular cells originally destined to become papillomas. Epidermal destruction did not occur after multiple doses of TPA, presumably reflecting adaptation of epidermis to chronic TPA treatment. Prolonged hyperplasia in the hair follicle may result in the early neoplastic lesions originally described by Jansen et al. (2001) by expanding initiated cells in the hair follicles resulting in the subsequent development of SCC. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma, Squamous Cell; Cell Death; Cell Differentiation; Cell Proliferation; Chemotaxis, Leukocyte; Cocarcinogenesis; Disease Models, Animal; Epidermis; Female; Hair Follicle; Hyperplasia; Keratin-10; Keratinocytes; Keratins; Mice; Mice, Transgenic; Neutrophils; Phenotype; Precancerous Conditions; Protein Kinase C-epsilon; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors | 2005 |
Bronchogenic adenocarcinoma in a cat: an unusual case of metastasis to the skin.
A 6-year-old, spayed, female, domestic shorthair cat was presented for decreased activity. A nodular lesion was found in the skin extending into the subcutaneous tissue of the right abdominal flank. On lateral and ventrodorsal radiographs of the thorax, an opacity involving the entire right caudal lung lobe and pleural effusion were noted. Cytologic evaluation of cells in the thoracic fluid and in the mass revealed a population of atypical epipthelial cells with marked anisocytosis and high N:C ratios, organized in acinar-like clusters. Multinucleated cells and several mitotic figures were found. The cytologic interpretation was carcinoma. Because of the progressive severity of clinical signs, the cat was euthanized. Histologic evaluation of tissues obtained at necropsy indicated a bronchogenic adenocarcinoma in the lung, with metastasis to the skin of the right flank, but no involvement of the digits. Based on immunohistochemical stains, the neoplastic cells strongly co-expressed cytokeratin and vimentin, and were negative for S-100 and actin-specific antigen. Bronchogenic adenocarcinoma is an uncommon neoplasm in cats, and the digits are the most common sites of metastasis. This case was unusual in that the skin of the abdominal wall was the primary site of metastasis, with no involvement of the digits. Topics: Adenocarcinoma; Animals; Carcinoma, Bronchogenic; Cat Diseases; Cats; Female; Immunohistochemistry; Keratins; Pleural Effusion, Malignant; Skin Neoplasms; Vimentin | 2005 |
Spindle cell squamous cell carcinoma showing continuous mesenchymal dedifferentiation in a single tumor.
We report the case of an 85-year-old man who presented with an enlarging tumor on the right temple. Histologically, spindle-shaped cells were proliferating continuously within well-differentiated squamous cell carcinoma that was immunohistochemically negative for vimentin and alpha-smooth muscle actin (ASMA) but positive for cytokeratin (AE1/3). These spindle-shaped cells expressed vimentin and ASMA but not cytokeratin (AE1/3). Intermediate cells with round nuclei and small amounts of cytoplasm displayed slight expression of vimentin, ASMA, and cytokeratin. This case illustrated spindle cell squamous cell carcinoma with mesenchymal metaplasia of malignant epithelial cells. Topics: Actins; Aged, 80 and over; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Mesoderm; Skin Neoplasms; Vimentin | 2005 |
[Expression and significance of cytokeratins in skin adenexal tumor].
Topics: Adenoma, Sweat Gland; Diagnosis, Differential; Humans; Keratin-14; Keratin-17; Keratin-18; Keratin-7; Keratins; Papilloma; Sebaceous Gland Neoplasms; Skin Neoplasms; Sweat Gland Neoplasms | 2005 |
Genetic deficiency or pharmacological inhibition of cyclooxygenase-1 or -2 induces mouse keratinocyte differentiation in vitro and in vivo.
Previously we demonstrated that genetic deficiency of the cyclooxygenases (COX-1 or COX-2) altered keratinocyte differentiation in mouse skin [Tiano et. al. (2002) Cancer Res. 62, 3395-3401]. In this study, we show that topical application of SC-560 (a COX-1 selective inhibitor) or celecoxib (COX-2 selective) to TPA-treated wild-type skin caused fivefold increases in the number of basal keratinocytes expressing the early differentiation marker keratin 1 (K1). In contrast to skin, COX-2 not COX-1 was the major isoform expressed in cultured primary keratinocytes. COX-1 was predominantly expressed in detached, differentiated cells, whereas COX-2 was found in the attached, proliferating cells. High Ca++ medium induced K1 and COX-1 in wild-type keratinocytes but did not change COX-2 expression. As observed in skin, COX-1-/- and COX-2-/- primary keratinocytes expressed fivefold more K1 than wild-type cells. K1 levels in cultured wild-type keratinocytes were also increased by treatment with celecoxib and indomethacin. However, unlike its in vivo effect, SC-560, possibly due to low COX-1 expression in cultured mouse keratinocytes, did not increase K1 levels. Furthermore, no increases in apoptotic cell numbers were observed in COX-deficient keratinocytes or COX-inhibitor treated wild-type cells. Thus, a major effect of COX inhibitors and COX-deficiency is the induction of keratinocyte differentiation. Topics: Animals; Antineoplastic Agents; Apoptosis; Celecoxib; Cell Differentiation; Cells, Cultured; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Epidermal Cells; Isoenzymes; Keratinocytes; Keratins; Membrane Proteins; Mice; Mice, Knockout; Prostaglandin-Endoperoxide Synthases; Protein Precursors; Pyrazoles; Skin Neoplasms; Sulfonamides | 2004 |
Follicular squamous cell carcinoma of the skin: a poorly recognized neoplasm arising from the wall of hair follicles.
In the last decades, a number of clinicopathologic subtypes of squamous cell carcinoma (SCC) of the skin, ranging from highly aggressive tumors with a tendency to recur and metastasize to neoplasms with a favorable prognosis, have been described. SCCs arising from the wall of hair follicles have been briefly mentioned by some authors but never reported in a series.. Cases of SCC arising from the wall of hair follicles were collected from the files of two large German Centers for Dermatopathology and analyzed clinicopathologically and immunohistochemically.. Sixteen cases of SCC developing in hair follicles were found among more than 7000 cases of cutaneous SCC reviewed. In most cases, tumors arose on sun-damaged skin of the face of elderly persons. There was a male predominance (11/5). The most common clinical diagnosis was basal cell carcinoma (BCC). Microscopically, tumors developed in the upper part of hair follicles without or with focal involvement of the overlying epidermis at the border with the involved follicle. Immunohistochemically, tumors were positive for cytokeratin and negative for a battery of immunomarkers, including antibodies against the most common carcinogenic human papillomaviruses (HPV) of the skin. Most tumors were excised by simple excision. In two cases, a recurrence was noted after incomplete excision. No further recurrences or metastasis have been noted after a follow-up period ranging from 11 months to 12 years.. SCC of the hair follicle represents a poorly recognized but distinctive subset of SCC of the skin that should be considered in the differential diagnosis of other cutaneous epithelial tumors. The term follicular SCC (FSCC) is proposed for this neoplasm. Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Hair Follicle; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms | 2004 |
Proximal-type epithelioid sarcoma: case report and result of comparative genomic hybridization.
Epithelioid sarcoma is a rare mesenchymal neoplasm. Recently, a more aggressive, so-called "proximal type" epithelioid sarcoma has been described.. A 40-year-old-woman presented with 5 x 4 cm, erythematous, indurated, non-movable, painful mass on the pubic area. Histopathology demonstrated diffuse tumor-cell infiltration into the subcutaneous and fascia, which was consisted of prominent epithelioid cells and scattered rhabdoid cells. A multinodular growth pattern or granulomatous appearance with central necrosis was not observed. The tumor cells showed positive reactions for vimentin, cytokeratin (AE1/AE3), and CD34. Despite the surgery, left inguinal mass with lymphadenopathy occurred one month later. We also carried out comparative genomic hybridization (CGH) with tumor cells. CGH revealed chromosomal gain of 5q32-qter, 12q24-qter, and 22q.. We report a case of proximal-type of epithelioid sarcoma, which showed the chromosomal gains of 5q32-qter, 12q24-qter, and 22q by CGH. Topics: Adult; Antigens, CD34; Biomarkers, Tumor; Chromosome Aberrations; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 5; DNA, Neoplasm; Female; Humans; Image Processing, Computer-Assisted; Keratins; Nucleic Acid Hybridization; Sarcoma; Skin Neoplasms; Spectral Karyotyping; Vimentin | 2004 |
The diagnostic utility of p63, CK5/6, CK 7, and CK 20 in distinguishing primary cutaneous adnexal neoplasms from metastatic carcinomas.
Distinguishing primary cutaneous adnexal neoplasms (PCANs) from metastatic carcinomas (MCs) can be difficult. We study the utility of p63, CK 5/6, CK 7, and 20 expression in PCAN vs. MC.. Twenty-one PCAN with sweat gland differentiation (six benign, 15 malignant), one sebaceous carcinoma, and 15 MC (14 adenocarcinomas, one urothelial carcinoma) to skin were retrieved from the pathology files. Immunostains for p63, CK 5/6, CK 7, and CK 20 were performed and graded as follows: 1, <10; 2, 11-50; and 3 >50% of tumor cells stained.. Twenty of 22 PCAN expressed p63 and CK 5/6. Four of 15 and two of 15 MC were positive for CK 5/6 and p63, respectively. Thirteen of 22 PCAN and 13 of 15 MC were positive for CK 7, respectively. All PCAN were negative for CK 20, two of 15 MC were positive. The sensitivity and specificity for the diagnosis of PCAN were 91 and 73% for CK 5/6, 91 and 100% for p63, and 60 and 13% for CK 7, respectively.. For distinguishing PCAN from MC: (1) positivity for p63 and CK 5/6 are relatively specific and sensitive for PCAN, (2) CK 7 and 20 are neither sensitive nor specific, and (3) CK 7 positivity in PCAN was focal with a specific pattern in contrast to the diffuse positivity for MC. Topics: Biomarkers, Tumor; Carcinoma; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Membrane Proteins; Neoplasms, Adnexal and Skin Appendage; Retrospective Studies; Skin Neoplasms | 2004 |
Epidermal and hair follicle progenitor cells express melanoma-associated chondroitin sulfate proteoglycan core protein.
Basal keratinocytes in the epidermis and hair follicle are biologically heterogeneous but must include a stable subpopulation of epidermal stem cells. In animal models these can be identified by their retention of radioactive label due to their slow cycle (label-retaining cells) but human studies largely depend on in vitro characterization of colony forming efficiency and clonogenicity. Differential integrin expression has been used to detect cells of increased proliferative potential but further stem cell markers are urgently required for in vivo and in vitro characterization. Using LHM2, a monoclonal antibody reacting with a high molecular weight melanoma-associated proteoglycan core protein, a subset of basal keratinocytes in both the interfollicular epidermis and the hair follicle has been identified. Coexpression of melanoma-associated chondroitin sulfate proteoglycan with keratins 15 and 19 as well as beta 1 and alpha 6 integrins has been examined in adult and fetal human skin from hair bearing, nonhair bearing, and palmoplantar regions. Although melanoma-associated chondroitin sulfate proteoglycan coexpression with a subset of beta 1 integrin bright basal keratinocytes within the epidermis suggests that melanoma-associated chondroitin sulfate proteoglycan colocalizes with epidermal stem cells, melanoma-associated chondroitin sulfate proteoglycan expression within the hair follicle was more complex and multiple subpopulations of basal outer root sheath keratinocytes are described. These data suggest that epithelial compartmentalization of the outer root sheath is more complex than interfollicular epidermis and further supports the hypothesis that more than one hair follicle stem cell compartment may exist. Topics: Animals; Cell Compartmentation; Chondroitin Sulfate Proteoglycans; Epidermal Cells; Epidermis; Gene Expression; Hair Follicle; Humans; Integrin alpha6; Integrin beta1; Keratin-15; Keratinocytes; Keratins; Melanoma; Membrane Proteins; Mice; Skin Neoplasms; Stem Cells | 2004 |
Breast metastases from colorectal carcinoma.
A case history is presented of a 53-year-old woman with an incidental finding of a breast lump, identified after having had chemotherapy for lung metastases from a rectal carcinoma. Clinical examination, ultrasound, mammography, fine needle aspiration and core biopsies could not prove definitively whether the breast lump represented a metastasis from colorectal carcinoma. Following local excision, the final diagnosis of metastatic colorectal carcinoma to the breast was based on the absence of any site of origin within the breast (i.e. no surrounding DCIS) and on the expression of cytokeratin CK7 and CK20 on immunohistochemistry. Postoperative chemotherapy was initiated. Four months later, although without local recurrence in the breast, the patient developed cutaneous metastatic deposits and active treatment was stopped. A review of other cases of breast metastases from extramammary sources is presented. Possible mechanisms for this rare and unusual phenomenon are discussed. Topics: Adenocarcinoma; Biomarkers; Breast Neoplasms; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Middle Aged; Skin Neoplasms | 2004 |
Expression of keratin and involucrin in keratoacanthoma: an immunohistochemical aid to diagnosis.
Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Protein Precursors; Skin Neoplasms | 2004 |
Pigmented mammary Paget's disease mimicking melanoma.
Our case of pigmented mammary Paget's disease simulated melanoma clinically and dermoscopically. Histologically, the lesion was characterized by microscopic features similar to those seen in malignant melanoma and, to a lesser extent, in Bowen's disease (intra-epidermal squamous cell carcinoma). Immunohistochemical studies demonstrated that the tumor cells were positive for keratins (Cam 5.2+MNF 116) and AE1-AE3 and negative for HMB-45 and S-100 proteins. In conclusion clinical and dermoscopic examination cannot reliably distinguish melanoma from epithelial pre-neoplastic or neoplastic disease, therefore the differentiation of pigmented Paget's disease from superficial spreading of melanoma and Bowen's disease is based on histopathologic integrated with immunohistochemical criteria. Topics: Adult; Breast Neoplasms; Diagnosis, Differential; Female; Humans; Keratins; Melanoma; Paget's Disease, Mammary; Skin Neoplasms | 2004 |
On the regulation of hair keratin expression: lessons from studies in pilomatricomas.
Human hair follicles exhibit a complex pattern of sequential hair keratin expression in the hair matrix, cuticle, and cortex. In pilomatricomas, that is, benign skin tumors thought to arise from germinative matrix cells of the hair follicle and retaining morphological signs of cortical differentiation, this differential hair keratin pattern has been shown to be faithfully preserved in the lower and upper transitional cell compartments of the tumors. Here we show that also the co-expression of hair keratin hHa5 with its regulatory nuclear homeoprotein HOXC13 in matrix cells of the hair follicle is maintained in lower transitional cells of pilomatricomas. In contrast, the nuclear co-expression of LEF1 and beta-catenin, which in the hair follicle has been postulated to initiate cortex cell differentiation through the induction of hair keratin hHa1 expression (Merill et al, Genes Dev 15:1688-1705, 2001), is not preserved in upper transitional cells of pilomatricomas. Although these cells correctly express hHa1, they are completely devoid of LEF1 and nuclear LEF1/beta-catenin co-expression is shifted to a subpopulation of hair keratin-free basaloid cells of the tumors. These data imply that unlike the normal hair follicle, cortical differentiation in pilomatricomas is not under the control of the canonical Wnt signaling pathway. Topics: beta Catenin; Cytoskeletal Proteins; DNA-Binding Proteins; Hair Diseases; Hair Follicle; Homeodomain Proteins; Humans; Immunohistochemistry; Keratin-5; Keratins; Lymphoid Enhancer-Binding Factor 1; Pilomatrixoma; Signal Transduction; Skin Neoplasms; Trans-Activators; Transcription Factors | 2004 |
Transcriptional profiling of dysplastic lesions in K14-HPV16 transgenic mice using laser microdissection.
In the K14-HPV16 transgenic mouse model of human papillomavirus (HPV)-associated squamous cell cancers, HPV16 E6 and E7 oncogenes and E1 and E2 regulatory genes are driven by the K14 keratinocyte-specific promoter. HPV transcription varies within the different layers of the epithelium. The correlation between HPV transcription patterns and disease pathogenesis is not well understood. Understanding these patterns is critical to designing and testing new HPV-specific therapeutic strategies. We examined HPV gene expression in homogenous populations of cells microdissected from the stratum basale, stratum spinosum, and stratum corneum of lesions from the transgenic mice using PALM microlaser technology. RNA extracted from each cell layer was subjected to two-step gene-specific RT-PCR and real-time quantitative nested PCR. To ensure specific amplification of spliced transcripts, the primers used for real-time nested PCR spanned the splice sites. High levels of E2 were detected in the basal and supra-basal layers of hyperplastic and dysplastic lesions. E7 and E6* levels increased significantly over time in stratum basale and stratum spinosum. E6** was expressed at much lower levels. We showed that the transgenic mice express correctly spliced E2 transcripts and are suitable as a preclinical model to test a therapeutic strategy using transcriptional regulation by the E2 protein. Topics: Animals; Carcinoma, Squamous Cell; Computer Systems; Disease Models, Animal; Dissection; DNA-Binding Proteins; Epidermis; Genes, Viral; Humans; Keratin-14; Keratins; Lasers; Mice; Mice, Transgenic; Micromanipulation; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; Papillomavirus Infections; Polymerase Chain Reaction; Promoter Regions, Genetic; Repressor Proteins; Skin Neoplasms; Transcription, Genetic; Transgenes | 2004 |
Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal.
Cutaneous tumor metastasis may be the first manifestation of cancer, but more often is a harbinger of advanced disease that portends an ominous prognosis. All skin accessions over the past 10 years from a large Veterans Administration (VA) hospital were reviewed.. Archived histories, glass slides, and the immunohistochemical battery (IHC), were assessed to determine diagnostic accuracy.. Of the 100,453 cases reviewed, there were a total of 77 cases (75 males and 2 females) of cutaneous metastasis from the lungs (28.6%), metastatic melanoma (18.2%), gastrointestinal tract (14.2%), genitourinary tract (10.4%), head and neck (9.1%), hematologic (5.2%), breast (5.2%), and miscellaneous (<2%). Metastasis represented the first indication of an internal malignancy in 7.8% of cases. The cutaneous sites of involvement included the head and neck (28%), the trunk (40%), the extremities (18%), and multiple sites (14%). The age range was 38-83 years, with a mean of 62 years. The average time interval between diagnosis of internal malignancy and cutaneous presentation was 33 months (range: <1 month-22 years), and the average survival following diagnosis was 7.5 months (range: <1 month-8 years). In a cohort of subjects, a truncated immunohistochemical battery consisting of CK-7, CK-20, and S-100 was consistent with the expected staining pattern of the primary source of cutaneous metastasis in 83.33% of the patients.. Excluding the potential for age and gender bias in this study conducted in a VA setting, cutaneous metastases represent an uncommon, deadly, and late-developing occurrence in many patients. Compared with previous studies, lung carcinoma remains the most common of the cutaneous metastases, with a relative rise in the incidence of metastatic melanoma. The immunohistochemical battery of CK-7, CK-20, and S-100 is a helpful adjunct in narrowing the differential diagnosis of the primary site of a large proportion of cutaneous metastases, particularly tumors with an epithelioid appearance such as carcinomas and melanomas. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Retrospective Studies; S100 Proteins; Skin Neoplasms | 2004 |
Fine needle aspiration cytology of lymph node with metastatic undifferentiated carcinoma and granulomatous (sarcoid-like) reaction.
Topics: Aged; Biopsy, Fine-Needle; Bronchiectasis; Carcinoma; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Giant Cells; Granuloma; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Nasopharyngeal Neoplasms; Neoplasms, Multiple Primary; Skin Neoplasms | 2004 |
Epithelial markers in primary sinonasal mucosal melanoma.
Topics: Antigens, Neoplasm; Biomarkers; Carcinoembryonic Antigen; Epithelium; Humans; Immunohistochemistry; Keratins; Melanoma; Melanoma-Specific Antigens; Nasal Mucosa; Neoplasm Proteins; Paranasal Sinus Neoplasms; S100 Proteins; Skin Neoplasms | 2004 |
Epidermal abnormalities and increased malignancy of skin tumors in human epidermal keratin 8-expressing transgenic mice.
Keratins K8 and K18 are the major components of the intermediate filament cytoskeleton of simple epithelia. Increased levels of these keratins have been associated with invasive growth and progression to malignancy in different types of human and murine epithelial tumors (including skin tumors), and even in tumors from nonepithelial origin. However, it has not yet clarified whether K8/K18 expression in tumors is cause or consequence of malignancy. Given the increasing incidence of epidermal cancer in humans (40% of all tumors diagnosed), we generated a mouse model to examine the role of simple epithelium keratins in the establishment and progression of human skin cancer. Transgenic mice expressing human K8 in the epidermis showed severe epidermal and hair follicle dysplasia with concomitant alteration in epidermal differentiation markers. The severity of the skin phenotype of these transgenic mice increases with age, leading to areas of preneoplastic transformation. Skin carcinogenesis assays showed a dramatic increase in the progression of papillomas toward malignancy in transgenic animals. These results support the idea that K8 alters the epidermal cell differentiation, favors the neoplastic transformation of cells, and is ultimately responsible of the invasive behavior of transformed epidermal cells leading of conversion of benign to malignant tumors. Topics: Aging; Animals; Animals, Newborn; Cell Differentiation; Cell Transformation, Neoplastic; Disease Progression; Epidermis; Hair Follicle; Humans; Keratins; Mice; Mice, Transgenic; Precancerous Conditions; Skin Abnormalities; Skin Neoplasms; Transgenes | 2004 |
Cloning and characterization of antikeratin human antibodies using a semisynthetic phage antibody library.
Antikeratin autoantibodies (AK auto Abs) are very important elements of the human immune system. To improve the outcome of studies on AK auto Abs, it is necessary to generate antikeratin human monoclonal antibodies. The purpose of present study was to isolate antikeratin human monoclonal antibodies by panning a phage antibody library. A semisynthetic phage antibody library with capacity of 4.0x10(8) members was previously constructed. Panning of the library was performed against human epidermal keratin extracted from psoriatic scales. At the last round of the panning, individual colonies were grown in culture for expression of phage antibodies. Their binding activities and specificities to keratin were determined by ELISA, and positive clones were analyzed by DNA fingerprinting. The selected clones were induced with IPTG to express soluble Fab fragments, which were further characterized by ELISA, immunohistochemistry and Western blotting. Finally, DNA sequencing of the variable regions was performed. A human antibody clone which was able to express soluble Fab fragments and recognize Mr 46,000 keratin (K17) was isolated. DNA sequencing demonstrated that the VH and VL of the antibody came from the human VH1 and Vkappa2 families, respectively. We conclude that phage antibody library technology is a powerful way to generate human monoclonal antibodies. The antikeratin antibody we isolated in the present study would be useful in the research on AK auto Abs. Topics: Amino Acid Sequence; Antibodies, Monoclonal; Bacteriophages; Base Sequence; Blotting, Western; Cloning, Molecular; Enzyme-Linked Immunosorbent Assay; Epidermis; Gene Expression; Gene Library; Humans; Immunoenzyme Techniques; Immunoglobulin Fab Fragments; Keratins; Molecular Sequence Data; Psoriasis; Skin Neoplasms; Staining and Labeling | 2004 |
Human keratin 14 driven HPV 16 E6/E7 transgenic mice exhibit hyperkeratinosis.
Human papillomavirus type 16 (HPV16) has been known as a major causative factor for the development of uterine cervical carcinomas. To investigate the in vivo activity of HPV16 expressed in squamous epithelia, transgenic mice harboring HPV16 E6/E7 with human keratin 14 (hK14) promoter were generated. Grossly, hK14 driven HPV16 E6/E7 transgenic mice exhibited multiple phenotypes, including wrinkled skin that was apparent prior to the appearance of hair in neonates, thickened ears, and loss of hair in adults. Transgenic mice with phenotype exhibiting severe wrinkled skin and a lack of hair growth died at the age of 3-4 weeks. Histological analysis revealed that in transgenic mice survived beyond the initial 3-4 weeks, HPV16 E6/E7 causes epidermal hyperplasia in multiple transgenic lineages with high incidence of transgene penetration. This epithelial hyperplasia was characterized by an expansion of the proliferating compartment and keratinocytes, and was associated with hyperkeratosis. Such activities were significantly higher in the skin of transgenic mice than that of the normal mice. Thus, these transgenic mice appeared to be useful for the expression of HPV16 E6/E7 gene and subsequent analysis on hyperkeratosis. Topics: Animals; Humans; Keratin-14; Keratins; Keratosis; Mice; Mice, Transgenic; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Promoter Regions, Genetic; Repressor Proteins; Skin Neoplasms | 2004 |
Loss of keratin 10 leads to mitogen-activated protein kinase (MAPK) activation, increased keratinocyte turnover, and decreased tumor formation in mice.
Keratin 10 (K10) is the major protein in the upper epidermis where it maintains keratinocyte integrity. Others have reported that K10 may act as a tumor suppressor upon ectopic expression in mice. Although K10(-/-) mice show significant epidermal hyperproliferation, accompanied by an activation of the mitogen-activated protein kinase (MAPK) pathway, they formed no spontaneous tumors. Here, we report that K10(-/-) mice treated with 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) developed far less papillomas than wild-type mice. BrdU(5-bromo-2'-deoxyuridine)-labeling revealed a strongly accelerated keratinocyte turnover in K10(-/-) epidermis suggesting an increased elimination of initiated keratinocytes at early stages of developing tumors. This is further supported by the absence of label-retaining cells 18 d after the pulse whereas in wild-type mice label-retaining cells were still present. The concomitant increase in K6, K16, and K17 in K10 null epidermis and the increased motility of keratinocytes is in agreement with the pliability versus resilience hypothesis, stating that K10 and K1 render cells more stable and static. The K10(-/-) knockout represent the first mouse model showing that loss of a keratin, a cytoskeletal protein, reduces tumor formation. This is probably caused by an accelerated turnover of keratinocytes, possibly mediated by activation of MAPK pathways. Topics: Animals; Cell Division; Epidermal Cells; Epidermis; Female; Integrin alpha6; Keratin-10; Keratinocytes; Keratins; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Mice, Knockout; Papilloma; Skin Neoplasms | 2004 |
Cornification (keratinization) in Basal cell carcinoma: a histopathological and immunohistochemical study of 16 cases.
The concept of keratotic BCC is obscure and not well-defined. To elucidate the histopathological and immunohistochemical properties of cornification in BCC and to clarify the concept of keratotic BCC, by careful examination of 600 BCC specimens, we selected 16 cases of BCC that showed cornification. We investigated the precise histopathological features of these 16 cases, and studied the immunohistochemical expression patterns of anticytokeratin (CK) antibodies (CKs 1, 10, 13, 14, 17) and other antibodies in these cornifying (keratotic) BCCs. We compared these data to those from normal adult hair follicles and three types of cornifying cysts (epidermal cyst, tricholemmal cyst and steatocystoma). Six types of cornification were observed in these BCCs; 1) infundibular type (4 cases) with thin laminated corneocytes expressing CKs 1 and 10, 2) tricholemmal (isthmus) type (9 cases) showing compact, homogenous cornified contents with CK 17 expression on the surrounding cells, 3) inner root sheath type (1 case) characterized by compact, blue-gray corneocytes lined by CK 13 positive-squamous cells with red trichohyalin granules, 4) sebaceous duct type (1 case) characterized by crenulated cornified cells expressing CK 17, 5) apocrine acrosyringium type (2 cases) characterized by small duct-like structures lined by eosinophilic cuticle expressing CEA, in association with keratohyaline granules, and 6) cornifying microcyst type (10 cases) characterized by micro and small cystic structures containing the debris of cornified cells, which was associated with the infundibular or tricholemmal type and could be classified as having the primitive features of the tricholemmal type of cornification. The tricholemmal type could be subdivided into two groups: one with keratohyaline granules and the other without keratohyaline granules, and the cornified contents in approximately 30% of the cornified areas in this type were positive for CK 17. The matrical type of cornification (seventh type) was not seen in our study. The examples described as "keratotic BCC" thus far were similar to BCCs with cornification of the tricholemmal (isthmus) or infundibular type. The cornification in BCCs could be classified into seven types. Excluding the cornifying microcyst type, the tricholemmal type is the most common type of cornification. This type will be abnormal and incomplete in attempts to cornify in the form of an isthmus, occasionally with concomitant exhibition of lower infundibular Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Case-Control Studies; Face; Female; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms | 2004 |
Impaired antigen presentation and effectiveness of combined active/passive immunotherapy for epithelial tumors.
Although immunization with tumor antigens can eliminate many transplantable tumors in animal models, immune effector mechanisms associated with successful immunotherapy of epithelial cancers remain undefined.. Skin from transgenic mice expressing the cervical cancer-associated tumor antigen human papillomavirus type 16 (HPV16) E6 or E7 proteins from a keratin 14 promoter was grafted onto syngeneic, non-transgenic mice. Skin graft rejection was measured after active immunization with HPV16 E7 and adoptive transfer of antigen-specific T cells. Cytokine secretion of lymphocytes from mice receiving skin grafts and immunotherapy was detected by enzyme-linked immunosorbent assay, and HPV16 E7-specific memory CD8+ T cells were detected by flow cytometry and ELISPOT.. Skin grafts containing HPV16 E6-or E7-expressing keratinocytes were not rejected spontaneously or following immunization with E7 protein and adjuvant. Adoptive transfer of E7-specific T-cell receptor transgenic CD8+ T cells combined with immunization resulted in induction of antigen-specific interferon gamma-secreting CD8+ T cells and rejection of HPV16 E7-expressing grafts. Specific memory CD8+ T cells were generated by immunotherapy. However, a further HPV16 E7 graft was rejected from animals with memory T cells only after a second E7 immunization.. Antigen-specific CD8+ T cells can destroy epithelium expressing HPV16 E7 tumor antigen, but presentation of E7 antigen from skin is insufficient to reactivate memory CD8+ T cells induced by immunotherapy. Thus, effective cancer immunotherapy in humans may need to invoke sufficient effector as well as memory T cells. Topics: Adjuvants, Immunologic; Adoptive Transfer; Animals; Antigen Presentation; Carcinoma; CD8-Positive T-Lymphocytes; Cytokines; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gene Expression Regulation, Neoplastic; Graft Rejection; Immunization, Passive; Immunotherapy, Active; Interferon-gamma; Keratin-14; Keratinocytes; Keratins; Mice; Mice, Transgenic; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Repressor Proteins; Skin Neoplasms; Skin Transplantation | 2004 |
Cutaneous mixed tumors: an immunohistochemical study using two antibodies, G-81 and C8/144B.
Topics: Antibodies, Monoclonal; Humans; Immunohistochemistry; Keratin-15; Keratins; Mixed Tumor, Malignant; Peptides; Skin Neoplasms | 2004 |
Cytokeratin 10 and Ki-67 nuclear marker expression in keratoacanthoma and squamous cell carcinoma.
The most frequent consideration in the clinical and histologic differential diagnosis of keratoacanthoma is squamous cell carcinoma. In the present study, cytokeratin 10 expression and proliferation rate as measured by Ki-67 expression were compared between 50 clinically and histologically diagnosed keratoacanthomas and 50 squamous cell carcinomas. Tissue sections from the skin were immunohistochemically stained with anti-cytokeratin 10 and anti-Ki-67 monoclonal antibodies. The distribution of cytokeratin 10 expression and proliferative cell count were analyzed. Study results showed higher cytokeratin 10 expression in keratoacanthomas than in squamous cell carcinomas and different distribution of staining in the two entities. The analysis of cytokeratin 10 expression showed a much wider range of values and statistically higher median (p<0.001) in keratoacanthomas than in squamous cell carcinomas. Additionally, the proliferation index of keratinocytes as measured by Ki-67 expression was significantly higher in squamous cell carcinomas than in keratoacanthomas (p<0.01). These results may prove helpful in histologic differentiation of these disorders. Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Keratoacanthoma; Ki-67 Antigen; Skin Neoplasms | 2004 |
Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression.
We have generated mice with a floxed fak allele under the control of keratin-14-driven Cre fused to a modified estrogen receptor (CreER(T2)). 4-Hydroxy-tamoxifen treatment induced fak deletion in the epidermis, and suppressed chemically induced skin tumor formation. Loss of fak induced once benign tumors had formed inhibited malignant progression. Although fak deletion was associated with reduced migration of keratinocytes in vitro, we found no effect on wound re-epithelialization in vivo. However, increased keratinocyte cell death was observed after fak deletion in vitro and in vivo. Our work provides the first experimental proof implicating FAK in tumorigenesis, and this is associated with enhanced apoptosis. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Blotting, Western; DNA Primers; Flow Cytometry; Fluorescent Antibody Technique; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Gene Deletion; Genotype; Hydroxytestosterones; Immunohistochemistry; Integrases; Keratin-14; Keratinocytes; Keratins; Mice; Mice, Transgenic; Neoplasm Metastasis; Protein-Tyrosine Kinases; Receptors, Estrogen; Skin Neoplasms; Tamoxifen | 2004 |
Cytokeratin 5/6 immunostaining in cutaneous adnexal neoplasms and metastatic adenocarcinoma.
The differentiation of primary cutaneous adnexal neoplasms (CANs) from dermal-based metastatic lesions can be difficult. Cytokeratin 5/6 (CK 5/6) has a relatively limited expression profile, being relatively specific for mesothelium and other "pavement" type epithelium such as squamous epithelium. To date, the degree and distribution of CK 5/6 expression in cutaneous neoplasms has not been extensively studied. We speculate that since most of CANs arise from similar epithelium, they should express CK 5/6 and, therefore, CK 5/6 could potentially be helpful in distinguishing these lesions from most of metastatic neoplasms, which usually do not express this marker. Formalin-fixed, paraffin-embedded tissue sections from 228 previously classified CANs and 27 metastatic adenocarcinomas (17 breast, 4 colon, 2 prostate, 2 ovary, 1 lung, and 1 esophagus) were immunostained with anti-CK 5/6. Anti-CK 5/6 labeled 2 of 2 proliferating trichilemmal tumors, 6 of 6 poromas, 4 of 5 hydrocystomas, 10 of 10 cylindromas, 10 of 10 eccrine acrospiromas, 8 of 10 pilomatricoma, 10 of 10 nevus sebaceus, 9 of 9 desmoplastic trichoepitheliomas, 7 of 7 nevus sebaceus with basal cell carcinomas, 10 of 10 pilar cysts, 14 of 14 trichilemmomas, 10 of 10 syringomas, 6 of 7 chondroid syringomas, 10 of 10 hidradenoma papilliferum, 9 of 9 sebaceus adenomas, 3 of 3 microcystic adnexal carcinomas, 10 of 10 eccrine spiradenomas, 4 of 4 syringocystadenoma papilliferum, 3 of 5 ocular sebaceous carcinomas, 28 of 28 basal cell carcinomas, 16 of 16 trichoepitheliomas, and 33 of 33 trichoepitheliomas with basal cell features. By contrast, 9 of 27 metastatic adenocarcinomas stained positively, although only two of these stained strongly. Cumulatively, CK 5/6 was expressed by most (97%) of CANs, while only 33% of metastatic adenocarcinomas showed positive expression. The sensitivity of this marker in the malignant lesions (other than basal cell carcinoma) is 78%, while the specificity is 67%. If all lesions are considered, the sensitivity increases to 97%. Therefore, CK 5/6 may prove to be a useful adjunct marker in distinguishing CANs from metastatic lesions. Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Neoplasms, Adnexal and Skin Appendage; Sensitivity and Specificity; Skin Neoplasms | 2004 |
A basaloid neoplasm with ductal differentiation.
Topics: Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Sebaceous Glands; Skin Neoplasms | 2003 |
Impaired NF-kappa B activation and increased production of tumor necrosis factor alpha in transgenic mice expressing keratin K10 in the basal layer of the epidermis.
Both the diversity and the precisely regulated tissue- and differentiation-specific expression patterns of keratins suggest that these proteins have specific functions in epithelia besides their well known maintenance of cell integrity. In the search for these specific functions, our previous results have demonstrated that the expression of K10, a keratin expressed in postmitotic suprabasal cells of the epidermis, prevents cell proliferation through the inhibition of Akt kinase activity. Given the roles of Akt in NF-kappa B signaling and the importance of these processes in the epidermis, a study was made into the possible alterations of the NF-kappa B pathway in transgenic mice expressing K10 in the proliferative basal layer. It was found that the inhibition of Akt, mediated by K10 expression, leads to impaired NF-kappa B activity. This appears to occur through the decreased expression of IKK beta and IKK gamma. Remarkably, increased production of tumor necrosis factor alpha and concomitant JNK activation was observed in the epidermis of these transgenic mice. These results confirm that keratin K10 functions in vivo include the control of many aspects of epithelial physiology, which affect the cells not only in a cell autonomous manner but also influence tissue homeostasis. Topics: Animals; Cells, Cultured; Epidermis; Genes, Reporter; Heterozygote; Homozygote; Humans; Keratin-10; Keratinocytes; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; NF-kappa B; Plasmids; Skin Neoplasms; Transfection; Tumor Necrosis Factor-alpha | 2003 |
Basal cell carcinoma with tricholemmal (at the lower portion) differentiation within seborrheic keratosis.
Recent genetic investigations support the idea that basal cell carcinoma (BCC) is trichoblastic carcinoma. However, it is generally thought that clear cell basal cell carcinoma is a result of degeneration rather than tricholemmal differentiation.. We report a case of BCC, with clear cell components, that developed within seborrheic keratosis, with histopathological and immunohistochemical findings.. The clear cell components in the present case showed the following four characteristics: (i) at the periphery of the aggregations, columnar clear cells were aligned in a palisade along a well-defined basement membrane; (ii) the nuclei of the columnar clear cells were at the pole opposite the basement membrane; (iii) the clear cells contained glycogen; (iv) in the aggregations with clear cell components, there was diffuse positive staining for cytokeratin 7 (CK7) (OV/TLR/30), but only the inner region stained positive for CK17. These four characteristics are comparable to those of the lower portion of normal outer root sheath. In addition, the BCC in the present case was partly composed of squamous cells that contained glycogen and were selectively positive for CK17 - features similar to those of squamous cells in normal outer root sheath.. Some clear cell BCCs are simply the result of degenerative change, but other clear cell BCCs may be the result of tricholemmal (at the lower portion) differentiation. Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Immunoenzyme Techniques; Keratin-7; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Skin Neoplasms | 2003 |
Epithelioid sarcoma: an immunohistochemical analysis evaluating the utility of cytokeratin 5/6 in distinguishing superficial epithelioid sarcoma from spindled squamous cell carcinoma.
Epithelioid sarcoma (ES) is a rare, aggressive soft tissue tumor characterized by nodular aggregates of epithelioid and/or spindled cells that are immunoreactive to cytokeratins (CKs) and epithelial membrane antigen. ES that arises in the dermis may cause epidermal ulceration and can resemble, clinically, morphologically and immunohistochemically, cutaneous squamous cell carcinoma. CK 5/6 has recently been found to be an excellent marker of squamous cell carcinoma, including spindled variants, but it is not known if this marker can be utilized to distinguish superficial ES from cutaneous spindled squamous cell carcinoma (SSCC).. Twenty-four cases of ES with typical histologic features and 10 cases of SSCC with ultrastructural evidence of epithelial differentiation were studied. Immunohistochemical analysis using an antibody to CK 5/6 was performed. The extent of immunoreactivity was evaluated in a semiquantitative manner using the following scale: 0, < 5% of cells staining; 1+, 6-25% of cells staining; 2+, 26-50% of cells staining; 3+, 51-75% of cells staining; 4+, > 75% of cells staining.. CK 5/6 was expressed in all 10 cases of SSCC, including one case with 3+ staining and six cases with 4+ staining. In contrast, CK 5/6 staining was found only in rare tumor cells (1+ staining) in one of 24 (4%) cases of ES.. CK 5/6 staining is useful in distinguishing superficial ES from cutaneous SSCC. Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-5; Keratins; Sarcoma; Skin Neoplasms | 2003 |
Adjuvant cytokeratin staining in Mohs micrographic surgery for basal cell carcinoma.
Mohs micrographic surgery (MMS) is a technique that offers excellent cure rates in the treatment of basal cell carcinoma (BCC). One of the reasons for its success is the 100% visualization of the resection margins. Still, recurrences do occur in 2% to 5% of the treated BCCs. It has been suggested that BCC cells in frozen sections stained with hematoxylin and eosin (H&E) may be missed.. To determine whether an additional immunohistochemical staining with a cytokeratin marker (MNF 116) indicates BCC cells in sections in which the H&E-stained frozen sections were negative.. The Mohs procedure was performed under standard conditions in which H&E-stained slides were judged by the Mohs surgeon and the pathologist. After the H&E slides where judged negative, an extra slide was stained using immunohistochemistry and a monoclonal antibody against cytokeratin (MNF 116).. A total of 143 complete slides were stained and judged by two Mohs surgeons and a pathologist. One of the 143 slides stained with MNF 116 showed positive staining where the H&E slides were negative, which is 0.7% of the slides. However, this single slide represents a failure of nearly 2% of the treated patients.. Frozen sections stained with H&E in MMS offer enough security in detecting BCC cells during surgery; however, adjuvant cytokeratin staining can be useful in very selected cases of aggressive growing BCC. Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma, Basal Cell; Coloring Agents; Eosine Yellowish-(YS); Frozen Sections; Hematoxylin; Humans; Immunohistochemistry; Keratins; Middle Aged; Mohs Surgery; Skin Neoplasms | 2003 |
Expression of enhancing factor/phospholipase A2 in skin results in abnormal epidermis and increased sensitivity to chemical carcinogenesis.
Enhancing factor (EF), a growth factor modulator, is the mouse homologue of human secretory group II phospholipase A(2). EF exhibits growth-promoting activity in vitro, in the presence of epidermal growth factor, and also brings about phenotypic transformation of normal cells. In order to ascertain the role of EF in vivo, a human keratin-14 promoter was used to drive the expression of EF ectopically to squamous epithelial cells. The founder mouse and its progeny showed abnormal whiskers and a scaly, beaded tail. In these mice, keratinization pattern of the epidermis was disturbed and parakeratosis and acanthosis were noted. The transgenic mice, TgK14-EF, expressed EF in the suprabasal layers of tail epidermis as well as in the epithelial cells of hair follicle and sebaceous glands of skin. Expression of EF along with hyperplasia was also observed in other squamous epithelia such as buccal mucosa, tongue and oesophagus. TgK14-EF mice homozygous for the transgene showed delayed and scanty hair growth although the mice were healthy and fertile. The hemizygous TgK14-EF mice were sensitive to a two-stage chemical carcinogenesis and developed a higher number of papillomas than their normal littermates over the course of the experiment. The conversion rate of papilloma to carcinoma was two fold higher in the transgenic mice. Topics: 9,10-Dimethyl-1,2-benzanthracene; Abnormalities, Multiple; Animals; Carcinogens; Carcinoma, Squamous Cell; Epidermis; Fibrosarcoma; Genetic Predisposition to Disease; Genotype; Group II Phospholipases A2; Humans; Keratins; Mice; Mice, Transgenic; Neoplasms, Basal Cell; Papilloma; Phenotype; Phospholipases A; Promoter Regions, Genetic; Recombinant Fusion Proteins; Skin; Skin Neoplasms; Tail; Tetradecanoylphorbol Acetate; Transgenes; Vibrissae | 2003 |
Clear cells of Toker in accessory nipples.
Clear cells of Toker are intraepithelial cells with clear to pale staining cytoplasm and bland cytologic features found in approximately 10% of normal nipples. Toker cells have been hypothesized as a precursor of extramammary Paget's disease (EMPD), although the distribution of Toker cells outside of the nipples has not been studied. Using immunohistochemistry, we studied 20 cases of accessory nipples for the presence of Toker cells.. A retrospective study of 20 cases of accessory nipples was performed using routine hemotoxylin and eosin staining, as well as immunohistochemical staining for CK7, CK20, EMA, and GCDFP-15.. Thirteen out of 20 accessory nipples (65%) demonstrated Toker cells with CK7 staining. Toker cells in six of the 13 cases were also positive for EMA. Only one case with Toker cells showed immunoreactivity for antibodies to GCDFP-15.. Toker cells occur outside the normal nipple epidermis in the epidermis of accessory nipples. The distribution of Toker cells along the milk line correlates with the distribution of most cases of EMPD along the milk line, especially in the groin and axillae. Further studies are necessary to define the relationship between Toker cells and EMPD. Topics: Apolipoproteins; Apolipoproteins D; Biomarkers; Carrier Proteins; Choristoma; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Male; Membrane Transport Proteins; Mucin-1; Nipples; Paget Disease, Extramammary; Retrospective Studies; Skin Neoplasms | 2003 |
Blue light inhibits the growth of skin tumors in the v-Ha-ras transgenic mouse.
12-O-Tetradecanoylphorbol-13-acetate (TPA) was applied to the back skin of v-Ha-ras (TG-AC) female transgenic mice at a dose of 2.5 microg/200 microl twice a week for 9 weeks. The back skin was then exposed to blue light (wavelength, 470 nm; irradiance, 5.7 mW/cm2) for 1 h daily for 9 weeks. The mice to which TPA was applied developed skin tumors at 6 weeks after the start of application. The tumor incidence rates at 6, 7, 8 and 9 weeks after the start of application were 70%, 80%, 100% and 100%, respectively, and the numbers of tumors 1 mm or more in diameter were 1, 5, 10 and 19, respectively. In the mice that were exposed to blue light after TPA application, the tumor incidence rates were 10%, 40%, 60% and 80%, respectively, and the numbers of tumors 1 mm or more in diameter were 0, 2, 5 and 9, respectively. Histopathological examination of the skin revealed that TPA application induced diffuse hyperplasia, exaggerated keratinization, and papillomas in all 10 mice. A localized form of epidermal hyperplasia was also observed in 4 mice. The incidence rate of papillomas in the mice that were exposed to blue light after TPA application was lower and the degree of exaggerated keratinization was greater. Exaggerated keratinization was considered to represent a regressive change following exposure. These findings suggest that exposure to blue light may be a promising new approach in the treatment of skin tumors. Topics: Animals; Epidermis; Female; Genes, ras; Hyperplasia; Keratins; Mice; Mice, Transgenic; Oncogene Protein p21(ras); Papilloma; Phototherapy; Precancerous Conditions; Recombinant Fusion Proteins; Skin Diseases; Skin Neoplasms; Tetradecanoylphorbol Acetate; Weight Gain | 2003 |
Acral lentiginous melanoma: an immunohistochemical study of 20 cases.
Though acral lentiginous melanoma (ALM) is a major type of malignant melanoma, no immunohistochemical study on this type of melanoma has been reported.. The purpose of this study is to analysis the immunohistochemical findings of ALM using routinely used immune markers.. An immunohistochemical study was performed on paraffin sections of 20 ALMs using S-100 protein, HMB-45, MART-1, vimentin, epithelial membrane antigen (EMA) and CAM 5.2.. S-100 protein (95%) was found to be a more sensitive marker than either HMB-45 (80%) or MART-1 (70%) for recognizing ALM. Melanin bleaching was useful for recognizing heavily pigmented ALM using both S-100 protein and HMB-45. The intensity of HMB-45 correlated well with the melanin content. However, there was no significant correlation between the intensity of S-100 protein and the melanin content. One and two out of 20 cases stained focally with EMA and CAM5.2, respectively, but these cases stained also with HMB-45 and/or S-100 protein.. S-100 protein and HMB-45 were relatively sensitive markers for recognizing ALM. Despite the occasional positivity for the epithelial markers in ALM, all epithelial marker-positive cases stained also with HMB-45 and/or S-100 protein. Therefore, we recommend that the panel of antibodies used for recognizing ALM should contain at least S-100 protein and HMB-45. Topics: Aged; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Mucin-1; Neoplasm Proteins; S100 Proteins; Skin Neoplasms | 2003 |
IL-1 alpha, innate immunity, and skin carcinogenesis: the effect of constitutive expression of IL-1 alpha in epidermis on chemical carcinogenesis.
Tumor promoters such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) are proinflammatory agents, and their mechanism of action in epithelial carcinogenesis has been linked to the release of IL-1 alpha and the induction of chronic inflammation in skin. To test the role of IL-1 alpha and inflammation in models of cutaneous carcinogenesis, we used our previously described FVB/N transgenic mice overexpressing 17-kDa IL-1 alpha in the epidermis under the keratin 14 (K14) promoter. Strikingly, the K14/IL-1 alpha mice were completely resistant to papilloma and carcinoma formation induced by a two-stage DMBA/TPA protocol, while littermate controls developed both tumor types. K14/IL-1 alpha mice crossed with the highly sensitive TG.AC mice, constitutively expressing mutant Ha-Ras, also failed to develop papillomas or carcinomas. When the K14/IL-1 alpha transgene was bred onto a recombinase-activating gene-2-deficient background, the resistance persisted, indicating that innate, but not acquired, mechanisms may be involved in the resistance to the initiation/promotion model. As an alternative approach, a complete carcinogenesis protocol using repetitive application of DMBA alone was applied. Surprisingly, although the IL-1 alpha mice still did not develop papillomas, they did develop carcinomas de novo at an accelerated rate compared with controls. We conclude that constitutive IL-1 alpha expression rendered FVB mice completely resistant to carcinomas that required evolution from prior papillomas, but facilitated carcinomas that did not evolve from papillomas, as in the complete carcinogenesis protocol. Thus, the role of IL-1 alpha and, by extension that of other proinflammatory factors, in epithelial carcinogenesis are more complex than previously appreciated. These mice may provide a mechanism to investigate the validity of these models of human skin tumorigenesis. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; DNA-Binding Proteins; Epidermis; Female; Humans; Immunity, Innate; Interleukin-1; Keratin-14; Keratins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Nuclear Proteins; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transgenes | 2003 |
Glucocorticoid receptor functions as a potent suppressor of mouse skin carcinogenesis.
Glucocorticoids are effective inhibitors of epidermal proliferation and skin tumorigenesis. Glucocorticoids affect cellular functions via glucocorticoid receptor (GR), a well-known transcription factor. Recently, we generated skin-targeted transgenic mice overexpressing GR under control of the keratin5 promoter (K5-GR mice). To test the hypothesis that GR plays a role as a tumor suppressor in skin, we bred K5-GR transgenic mice with Tg.AC transgenic mice, which express v-Ha-ras oncogene in the skin, and compared the susceptibility of F1 offspring to TPA-induced skin carcinogenesis. GR overexpression in the epidermis dramatically inhibited skin tumor development. In K5-GR/ras+ double transgenic mice papillomas developed later and the average number of tumors per animal was 15% (in males) and 40% (in females) of the number seen in wild type (w.t./ras+) littermates. In addition, the papillomas in w.t./ras+ animals were eight to nine times larger. GR overexpression resulted in a decrease in keratinocyte proliferation combined with a modest increase in apoptosis and differentiation of keratinocytes in K5-GR/ras+ papillomas. Our data clearly indicate that interference of GR transgenic protein with nuclear factor kappa B (NF-kappaB) transcription factor had resulted in NF-kappaB blockage in K5-GR/ras+ tumors. We discuss the role of NF-kappaB blockage in tumor-suppressor effect of GR. Topics: Animals; Apoptosis; Cell Differentiation; Cell Division; Epidermis; Female; Keratin-15; Keratin-5; Keratinocytes; Keratins; Mice; Mice, Transgenic; NF-kappa B; Oncogene Protein p21(ras); Papilloma; Receptors, Glucocorticoid; Skin Neoplasms; Tumor Suppressor Proteins | 2003 |
The PDZ ligand domain of the human papillomavirus type 16 E6 protein is required for E6's induction of epithelial hyperplasia in vivo.
Human papillomaviruses (HPVs) are the causative agent of warts. Infections with high-risk HPVs are associated with anogenital and head and neck cancers. One of the viral genes responsible for HPV's oncogenic activity is E6. Mice expressing the HPV-16 E6 protein in their epidermis (K14E6(WT)) develop epithelial hyperplasia and squamous carcinomas. Numerous cellular proteins interact with E6, some of which can be grouped based on common amino acid motifs in their E6-binding domains. One such group, the PDZ partners, including hDLG, hSCRIBBLE, MUPP1, and MAGI, bind to the carboxy-terminal four amino acids of E6 through their PDZ domains. E6's interaction with the PDZ partners leads to their degradation. Additionally, E6's binding to PDZ proteins has been correlated with its ability to transform baby rat kidney cells in tissue culture and to confer tumorigenicity onto cells in xenograft experiments. To address whether the ability of E6 to bind PDZ domain partners is necessary for E6 to confer epithelial hyperproliferation in vivo, we generated transgenic mice that express in stratified squamous epithelia a mutant of E6 lacking the last six amino acids at its carboxyl terminus, E6(Delta 146-151), from the human keratin 14 (K14) promoter. The K14E6(Delta 146-151) mice exhibit a radiation response similar to that of the K14E6(WT) mice, demonstrating that this protein, as predicted, retains an ability to inactivate p53. However, the K14E6(Delta 146-151) mice fail to display epithelial hyperplasia. These results indicate that an interaction of E6 with PDZ partners is necessary for its induction of epithelial hyperplasia. Topics: Adaptor Proteins, Signal Transducing; Animals; Carrier Proteins; Cell Transformation, Neoplastic; Discs Large Homolog 1 Protein; DNA Damage; Guanylate Kinases; Humans; Hyperplasia; Keratin-14; Keratins; Ligands; Membrane Proteins; Mice; Mice, Transgenic; Oncogene Proteins, Viral; Papillomaviridae; Proliferating Cell Nuclear Antigen; Proteins; Rats; Repressor Proteins; Skin Neoplasms | 2003 |
The magnitude of hedgehog signaling activity defines skin tumor phenotype.
Gain-of-function mutations in SMO have been implicated in constitutive activation of the hedgehog signaling pathway in human basal cell carcinomas (BCCs). We used a truncated keratin 5 (DeltaK5) promoter to assess the potential role of the human M2SMO mutant in BCC development in adult transgenic mice. DeltaK5-M2SMO mouse epidermis is hyperproliferative, ex presses BCC protein markers and gives rise to numerous epithelial downgrowths invading the underlying dermis. Lesions strikingly similar to human basaloid follicular hamartomas develop, but BCCs do not arise even in elderly mice. Hedgehog target gene transcripts were only modestly upregulated in mouse and human follicular hamartomas, in contrast to the high levels detected in BCCs. Cyclins D1 and D2 were selectively upregulated in mouse BCCs. Our data suggest that the levels of hedgehog pathway activation and G(1) cyclins are major determinants of tumor phenotype in skin, and strongly implicate deregulated hedgehog signaling in the genesis of human basaloid follicular hamartomas. Expression of an activated SMO mutant in keratinocytes appears to be insufficient for the development and/or maintenance of full-blown BCCs. Topics: Alopecia; Animals; Carcinoma, Basal Cell; Cell Differentiation; Hamartoma; Hedgehog Proteins; Humans; Hyperplasia; Keratin-15; Keratin-5; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Phenotype; Promoter Regions, Genetic; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Signal Transduction; Skin Neoplasms; Smoothened Receptor; Trans-Activators | 2003 |
A novel mutation in the keratin 4 gene causing white sponge naevus.
White sponge naevus (WSN) is a rare, autosomal dominant disorder that predominantly affects noncornified stratified squamous epithelia, most commonly the buccal mucosa. Clinically, WSN manifests as thickened spongy mucosa with a white opalescent tint in the mouth and may be confused with other disorders that cause white lesions on oral mucosa. Recent studies have identified pathogenic mutations in KRT4 and KRT13, the genes encoding mucosa-specific keratins, in WSN.. To search for possible mutations in KRT4 and KRT13.. We report a case of WSN in a young man who presented with diffuse irregular whitish plaques involving the buccal and gingival mucosae and the tongue. Results Pathologically, the affected mucosa showed epithelial thickening, parakeratosis and extensive vacuolization of the suprabasal keratinocytes. Mutation analysis revealed a heterozygous missense mutation 1345G-->A in KRT4, predicting an amino acid change, E449K, in the 2B domain of the K4 polypeptide.. We report the first mutation analysis of a Taiwanese patient with WSN. Potentially this novel mutation could disrupt the stability of keratin filaments and result in WSN. Topics: Adult; Amino Acid Sequence; Base Sequence; Humans; Keratins; Male; Molecular Sequence Data; Mouth Mucosa; Mouth Neoplasms; Mutation; Nevus; Pedigree; Polymerase Chain Reaction; Skin Neoplasms | 2003 |
Discriminating expression of differentiation markers evolves in transplants of benign and malignant human skin keratinocytes through stromal interactions.
Accumulating evidence indicates a decisive role for the adjacent stroma in tumour growth and dissemination. However, it is not clear how far altered differentiation such as expression of aberrant keratins and vimentin, common in invasive human carcinomas, may reflect intrinsic cell properties or a response to the tumour environment. We have addressed this by transplanting benign and malignant human HaCaT-ras keratinocytes, seeded on collagen matrix, onto nude mice. Initially, epithelia derived from benign and malignant cells, being separated from host stroma by collagen, were poorly organized and exhibited the same differentiation markers, as identified by immunofluorescence and in situ hybridization. Epidermal basal and suprabasal keratins were expressed persistently even upon contact with newly formed stroma and malignant cell invasion. In contrast, non-epidermal keratins (K4/K13, K8/18, K19), which were similarly synthesized by benign and malignant cells in culture and in early transplants, were differentially regulated with increasing stromal vicinity. While both proteins and mRNAs were downregulated in benign epithelia, the malignant, invasive tumour cells continuously expressed these non-epidermal keratins throughout (K19), suprabasally (K4/13) or at invasive sites (K8/18). Furthermore, the mesenchymal protein vimentin was expressed de novo in invasive areas confronting tumour stroma. Thus, atypical tissue markers, similarly synthesized in isolated cells in vitro, are downregulated in benign but maintained and upregulated in malignant epithelia. This is presumably caused by the neighbouring stroma being permanently activated by malignant epithelia. Topics: Animals; Antigens, Differentiation; Cell Transformation, Neoplastic; Down-Regulation; Epidermis; Fluorescent Antibody Technique; Humans; In Situ Hybridization; Keratinocytes; Keratins; Mice; Neoplasm Invasiveness; Neoplasm Proteins; RNA, Messenger; RNA, Neoplasm; Skin Neoplasms; Tumor Cells, Cultured; Vimentin | 2003 |
Multiply recurrent trichilemmal carcinoma with perineural invasion and cytokeratin 17 positivity.
Trichilemmal carcinoma is an uncommon cutaneous malignancy that is thought to be the malignant counterpart of the trichilemmoma. Despite histologic features such as pronounced cytologic atypia, trichilemmal carcinoma is often described as having a rather benign clinical course. Cases of tumor recurrence after therapy are uncommon, and tumor neurotropism has never been described.. A case of multiply recurrent trichilemmal carcinoma with perineural invasion is described. The outer root sheath differentiation of this neoplasm is confirmed with the use of novel antibodies directed toward cytokeratins that are expressed in this area of the hair follicle.. The trichilemmal carcinoma was excised using the Mohs surgical technique. Tissue obtained during the extirpation of the tumor was subjected to immunohistochemical staining for cytokeratin 15, cytokeratin 17, and c-erb-B2.. Tumor neurotropism was noted. The trichilemmal carcinoma demonstrated abundant cytoplasmic staining for cytokeratin 17 and c-erb-B2.. In distinction to previous reports, this case reveals that trichilemmal carcinoma can demonstrate significant biological aggression, as reflected by tumor neurotropism and by failure to respond to multiple surgical excisions. The purported outer root sheath differentiation of this neoplasm is confirmed with the use of novel immunohistochemical staining. This immunohistochemical staining may be useful in differentiating trichilemmal carcinoma from other clear cell neoplasms. Topics: Aged; Humans; Immunohistochemistry; Keratins; Male; Mohs Surgery; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Perineum; Skin Neoplasms | 2003 |
Keratin profile of intraepidermal cells in Paget's disease, extramammary Paget's disease, and pagetoid squamous cell carcinoma in situ.
Although the histopathologic differential diagnosis of pagetoid neoplasms is broad, unique histopathologic identifiers and clinical correlation can often identify the process. However, in the case of mammary Paget's disease (MPD) or extramammary Paget's disease (EPD) without an obvious underlying malignancy, distinction from pagetoid squamous cell carcinoma in situ (PSCCIS) can be challenging. Our goal was to better define the immunohistochemical staining patterns of these three entities in the hope of determining distinctive staining patterns.. We evaluated nine cases of PSCCIS, five cases of MPD, and 10 cases of EPD with the immunohistochemical antibodies CAM 5.2 and CK 5/6. In addition, only PSCCIS was stained with CK 7, as the staining patterns of CK 7 in MPD and EPD are well known from prior studies.. CAM 5.2 diffusely stained all cases of MPD and EPD and failed to stain any case of PSCCIS. Furthermore, CK 7 only focally stained two of the 10 cases of PSCCIS. CK 5/6 was difficult to interpret due to the high functional background staining of the normal keratinocytes in the epidermis.. Based on these results, our data supports the use of CAM 5.2 and CK 7 immunoperoxidase markers in differentiating between difficult cases of PSCCIS and MPD or EPD. An antibody panel consisting of S-100, CAM 5.2, and CK 7 will aid in the accurate diagnosis of almost all pagetoid neoplasms of the breast or genital skin. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Keratinocytes; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Skin Neoplasms | 2003 |
Trichilemmoma: an immunohistochemical study of cytokeratins.
The histogenesis of trichilemmoma remains unclear.. To clarify the histogenesis of trichilemmoma by evaluating its cytokeratin (CK) expression.. In three cases of trichilemmoma, CK expression was studied immunohistochemically using seven antikeratin antibodies against CK1, 10, 14-17 and 19, respectively.. CK1 and CK10 were present in keratinizing ductal epithelium. CK14 was present in the whole layer. CK15 was present in suprabasal layers in two cases. CK16 was present in the suprabasal layer, but was absent in keratinizing ductal epithelium. CK17 was present in suprabasal layers and the sebaceous duct-like structure. CK19 was totally absent.. These results showed that trichilemmoma may differentiate mainly towards two directions: infundibular keratinization and proliferation of the outer root sheath with undifferentiated and pluripotent characteristics. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Cell Differentiation; Female; Hair Diseases; Hair Follicle; Humans; Keratins; Middle Aged; Neoplasm Proteins; Skin Neoplasms | 2003 |
RasGRP1 represents a novel non-protein kinase C phorbol ester signaling pathway in mouse epidermal keratinocytes.
The mouse skin model of carcinogenesis has been instrumental in our appreciation of the multistage nature of carcinogenesis. In this system, tumor promotion is a critical step in the generation of tumors and is usually achieved by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Although it is generally assumed that protein kinase C (PKC) is the sole receptor for TPA in this system, we sought to evaluate whether non-PKC pathways could also contribute to the effects of phorbol esters in skin. We documented expression of the high affinity non-PKC phorbol ester receptor and Ras activator RasGRP1 in mouse primary keratinocytes. Overexpression of RasGRP1 in keratinocytes increased the level of active GTP-loaded Ras. TPA treatment further elevated this Ras activation in a PKC-independent manner and induced the translocation and down-regulation of RasGRP1. Overexpression of RasGRP1 in keratinocytes also caused apoptosis. Finally, induction of keratinocyte differentiation by elevation of extracellular calcium suppressed expression of endogenous RasGRP1, whereas overexpression of RasGRP1 inhibited expression of the differentiation markers keratins 1 and 10 induced by high calcium in the medium. Taken together, our results demonstrate that RasGRP1 is an additional diacylglycerol/phorbol ester receptor in epidermal keratinocytes and suggest that activation of this novel receptor may contribute to some of the phorbol ester- and Ras-mediated effects in mouse epidermis. Topics: Animals; Annexin A5; Apoptosis; Blotting, Western; Cell Differentiation; Cells, Cultured; DNA-Binding Proteins; Dose-Response Relationship, Drug; Down-Regulation; Epidermal Cells; Epidermis; Flow Cytometry; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate; Immunoblotting; Keratin-10; Keratinocytes; Keratins; Mice; Neoplasms, Experimental; Phorbol Esters; Precipitin Tests; Protein Kinase C; Protein Transport; Rats; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Skin Neoplasms; Tetradecanoylphorbol Acetate | 2003 |
Overexpression of Sonic Hedgehog suppresses embryonic hair follicle morphogenesis.
The Sonic Hedgehog (Shh) signalling pathway plays a central role in the development of the skin and hair follicle and is a major determinant of skin tumorigenesis, most notably of basal cell carcinoma (BCC). Various mouse models involving either ablation or overexpression of key members of the Shh signalling pathway display a range of skin tumours. To further examine the role of Shh in skin development, we have overexpressed Shh in a subset of interfollicular basal cells from 12.5 dpc under the control of the human keratin 1 (HK1) promoter. The HK1-Shh transgenic mice display a range of skin anomalies, including highly pigmented inguinal lesions and regions of alopecia. The most striking hair follicle phenotype is a suppression in embryonic follicle development between 14.0 and 19.0 dpc, resulting in a complete absence of guard, awl, and auchene hair fibres. These data indicate that alternative signals are responsible for the development of different hair follicles and point to a major role of Shh signalling in the morphogenesis of guard, awl, and auchene hair fibres. Through a comparison with other mouse models, the characteristics of the HK1-Shh transgenic mice suggest that the precise timing and site of Shh expression are key in dictating the resultant skin and tumour phenotype. Topics: Animals; beta Catenin; Carcinoma, Basal Cell; Cell Division; Cytoskeletal Proteins; Hair Follicle; Hedgehog Proteins; Homeostasis; Keratins; Mice; Mice, Transgenic; Morphogenesis; Skin Neoplasms; Trans-Activators | 2003 |
Detection of nonmelanoma skin cancer micrometastases in lymph nodes by using reverse transcriptase-polymerase chain reaction for keratin 19 mRNA.
A new sensitive method for the detection of skin cancer micrometastases in lymph nodes is based on amplification of keratin 19 (K19) mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).. To compare results of RT-PCR with those of histological examination in terms of the detection rate of skin cancer micrometastases.. Twenty-six lymph nodes obtained from 13 patients with squamous cell carcinoma (SCC), eccrine porocarcinoma and Paget's disease were investigated by histological examination (haematoxylin and eosin sections) and RT-PCR. RT-PCR was performed on extracted RNA by using K19 primer pairs. RT-PCR products were visualized by ethidium bromide staining and confirmed by non-radioactive hybridization with K19-specific probes.. All of 10 histologically positive lymph nodes yielded the expected 460-bp band. Of the 16 histologically negative lymph nodes, one (6%) was found by RT-PCR to express K19 mRNA, indicating the presence of micrometastases which could not be detected by histological examination. A serial dilution study using RNA extracted from SCC cells mixed with RNA extracted from normal lymph node cells showed a detection sensitivity of K19 RT-PCR of 10-5 micro g cancer cell RNA in 1 micro g lymph node RNA. Nested RT-PCR showed a detection sensitivity of one tumour cell in 106 lymphocytes.. These results demonstrate the usefulness of K19 RT-PCR for the detection of skin cancer micrometastases in lymph nodes. Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Keratins; Lymphatic Metastasis; Neoplasm Proteins; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Skin Neoplasms | 2003 |
Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge.
Putative epithelial stem cells in the hair follicle bulge are thought to play pivotal roles in the homeostasis, aging, and carcinogenesis of the cutaneous epithelium. Elucidating the role of bulge cells in these processes has been hampered by the lack of gene promoters that target this area with specificity. Here we describe the isolation of the mouse keratin 15 (K15) promoter and demonstrate its utility for preferentially targeting hair follicle bulge cells in adult K15/lacZ transgenic mice. We found that patterns of K15 expression and promoter activity changed with age and correlated with levels of differentiation within the cutaneous epithelium; less differentiated keratinocytes in the epidermis of the neonatal mouse and in the bulge area of the adult mouse preferentially expressed K15. These findings demonstrate the utility of the K15 promoter for targeting epithelial stem cells in the hair follicle bulge and set the stage for elucidating the role of bulge cells in skin biology. Topics: Animals; Cell Differentiation; Cell Division; Epithelial Cells; Hair Follicle; Humans; Keratin-15; Keratins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Promoter Regions, Genetic; Skin Neoplasms; Stem Cells; Wound Healing | 2003 |
[Keratoacanthoma: two cases with intravascular spread].
We report two patients with keratoacanthoma, simple in one and multiple in the other, displaying typical histological features except for intravascular spread. Although this spread points to malignancy, it did not allow to rule out the diagnosis of keratoacanthoma. These aggressive histological features, as well as perineural invasion, are not linked to malignant clinical course, according to the literature. Intravascular spread suggests that keratoancanthoma could be considered as a peculiar form of well differentiated squamous cell carcinoma. Comparison between clinical and pathological observations should lead to more specific diagnosis. Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Humans; Keratins; Keratoacanthoma; Male; Neoplasm Invasiveness; Skin Neoplasms; Treatment Outcome | 2003 |
Immunohistochemical characterization of tumor cells and inflammatory infiltrate associated with cutaneous melanocytic tumors of Duroc and Iberian swine.
The immunophenotype of tumor cells and inflammatory infiltrate associated with cutaneous melanocytic lesions (29 melanocytomas, two malignant melanomas, and 23 residual lesions) from 54 adult Iberian and Iberian x Duroc pigs were examined using a panel of nine antibodies. All neoplastic cells were vimentin+, cytokeratin-, and alpha-1-antitrypsin- and the majority were S100+, whereas all pigmented macrophages were vimentin+, cytokeratin-, and S100- and most expressed alpha-1-antitrypsin. Regressing tumors were characterized by zones with low density of neoplastic cells accompanied by heavy infiltration of CD3+ T lymphocytes, whereas zones with high density of neoplastic cells showed very low numbers of CD3+ T lymphocytes. The infiltrate of CD79a+ B cells and IgG, IgM, and IgA plasma cells was low. The majority of lymphocytes of the peri- and intratumoral infiltrate were major histocompatibility complex class II+, but neoplastic cells did not express class II antigen. The 17 residual lesions examined were composed of macrophages containing abundant melanin pigment and low to moderate numbers of CD3+ T lymphocytes. The results of the present study suggest that the local cellular immune response plays a crucial role in the host response that induces regression of cutaneous melanomas and melanocytomas of the Iberian and crossbred Iberian x Duroc pigs. Topics: alpha 1-Antitrypsin; Animals; Antigens, CD; B-Lymphocytes; CD3 Complex; CD79 Antigens; Histocompatibility Antigens Class II; Immunohistochemistry; Keratins; Melanocytes; Melanoma; Neoplasm Regression, Spontaneous; Plasma Cells; Receptors, Antigen, B-Cell; S100 Proteins; Skin Neoplasms; Swine; Swine Diseases; T-Lymphocytes; Vimentin | 2002 |
The onychomatricoma: additional histologic criteria and immunohistochemical study.
Onychomatricoma (OM) is a tumor of the nail matrix typified histologically by multiple distal fibroepithelial projections and a thick keratogenous zone forming multiple V-shaped invaginations at the level of epithelial ridges, with the formation of a thick nail plate. In its proximal portion, the thickness of the nail looks like a spur originating from the ventral part of the nail plate. In its distal part, beyond the lunula, the nail plate is globally thickened and filled with cavities containing serous fluid. Often, however, the pathologist is not provided with the nail plate. The diagnosis then rests on the presence of a fibroepithelial tumor. In this article the histologic criteria of OM without nail plate are refined and OM is characterized immunohistochemically using three tumors fixed in liquid nitrogen and examined separately from the nail plate. On longitudinal section OM without nail plate appears as a unique pedunculated fibroepithelial tumor i.e., the multiple distal epithelial digitations arranged along a transversal plane are not seen. The feature is reminiscent of fibrokeratoma. When OM is visualized in longitudinal section, 3 main criteria differentiate OM from fibrokeratoma: the presence of epithelial-lined invaginations around optical cavities, a stroma organized in 2 layers, and the absence of horny corn. Patterns of expression of cytokeratins and integrins in OM are identical to that observed in the normal nail matrix. Involucrin finds expression from the basal layer through to the top of the epithelium, where it is more marked and where transglutaminase 1 is restricted. Merkel cells detected by CK 20 are increased in number and sometimes disposed in clusters. The fibrous component of OM is composed of 2 layers: a superficial stroma made of numerous fines fibrils of collagen IV intermingled with collagen I, and deep stroma made principally of collagen I. Antibody AE13, specific to trichocytic keratins Ha 1-4, represent a good potential marker of OM. Its V-shaped expression in epithelium ridges offers early identification of the keratogenous zone of OM, on tumors separated from their nail plates and limited to their fibroepithelial components. Topics: Biomarkers, Tumor; Diagnosis, Differential; Fibroma; Fluorescent Antibody Technique, Indirect; Humans; Integrins; Keratins; Keratosis; Microscopy, Fluorescence; Nail Diseases; Skin Neoplasms | 2002 |
Carcinoma arising in a proliferating trichilemmal cyst expresses fetal and trichilemmal hair phenotype.
Carcinomas that arise in a proliferating trichilemmal cyst (PTC) have been described under a variety of names. Monoclonal antibodies (mAbs) indicating follicular differentiation have become available and were used here in two rare tumors with uncommon biologic behavior. To further elucidate the histogenesis of carcinomas arising in a PTC, mAbs to hair follicle stem cells and to hair follicle differentiation-specific cytokeratins (mAbs to cytokeratin [CK] 7, CK8, CK18, and CK19 as well as mAbs to CD8/CK15 and CD34) were studied on paraffin-embedded sections of two cases of carcinoma arising in a PTC, one anaplastic carcinoma, and one poorly differentiated squamous cell carcinoma (SCC). For comparison, concurrent PTCs and trichilemmal cysts as well as four SCCs from controls were studied. The anaplastic carcinoma showed expression of CK7, indicating a fetal hair root phenotype, and expression of CD34, indicating trichilemmal differentiation. In contrast, the poorly differentiated SCCs as well as the control SCCs stained negative for most of the mAbs applied. Expression of fetal and trichilemmal hair follicle phenotypes suggests differentiation from hair stem cells and might explain differences in biologic behavior. Topics: Aged; Biomarkers; Carcinoma, Squamous Cell; Cell Division; Epidermal Cyst; Female; Hair Diseases; Hair Follicle; Humans; Keratins; Phenotype; Scalp; Skin Neoplasms | 2002 |
Genetic analyses of mouse skin tumor progression susceptibility using SENCAR inbred derived strains.
Susceptibility to tumor development varies among individuals in the human population. This variability can also be found among different strains of mice, particularly in the mouse skin chemical carcinogenesis model. The genetic mechanisms underlying mouse skin tumor susceptibility are not fully understood. The SENCAR stock has been found to be the most sensitive mice for skin carcinogenesis studies; however, little is known about the genes underlying tumor susceptibility, particularly, those involved in tumor progression. Experiments with the SSIN/Sprd mice, an inbred strain derived from the outbred SENCAR stock, suggested that papilloma development, tumor promotion, and their conversion into squamous cell carcinomas (SCCs), progression, are regulated by different genes. In the highly sensitive SSIN/Sprd mice, papillomas rarely progress to SCC. Using crosses between the outbred SENCAR and the SSIN/Sprd mice, we previously determined that papilloma progression in the SENCAR stock could be controlled by at least one autosomal dominant gene. However, the outbred nature of the SENCAR stock precluded us from extending those findings. More recently, another inbred strain was developed from the outbred SENCAR stock, the SENCARB/Pt. These mice have similar tumor promotion sensitivity to the SSIN/Sprd but in contrast, have high papilloma progression susceptibility, similar to the outbred original stock. In the present study, we generated F(1), F(2), and backcross hybrids between the SSIN/Sprd and SENCARB/Pt mice to determine a possible model for tumor progression susceptibility and to map the putative tumor susceptibility genes. Our tumor data suggests that papilloma progression susceptibility in the SENCAR mouse skin model could be genetically determined by one susceptibility gene. Our preliminary linkage analysis failed to identify one strong susceptibility locus to confirm this but provided some evidence for at least one possible susceptibility locus in mouse chromosome 14. Topics: Animals; Carcinoma, Squamous Cell; Chimera; Chromosome Mapping; Chromosomes; Crosses, Genetic; Disease Progression; Genetic Linkage; Genetic Markers; Genetic Predisposition to Disease; Incidence; Keratins; Mice; Mice, Inbred SENCAR; Papilloma; Skin Neoplasms | 2002 |
Microcystic adnexal carcinoma of the breast: a very rare breast skin tumor.
Microcystic adnexal carcinoma is a rare, slowly progressing, malignant tumor of sweat gland origin.. A case of microcystic adnexal carcinoma of the breast with a history of 20 years is presented.. On initial examination, the ulcerative cutaneous mass was fixed to the underlying breast tissue and chest wall. Both the macroscopic appearance of the tumor and its location suggested a glandular breast carcinoma. However, an incisional biopsy revealed the nature of the tumor as microcystic adnexal carcinoma of the breast skin. Following the diagnosis, a wide excision of the tumor was carried out for the final treatment.. To our knowledge this is the first case of microcystic adnexal carcinoma arising in the breast skin presented in the literature.. This case demonstrates that microcystic adnexal carcinoma can occur on the breast skin and should be treated with wide excision due to its locally aggressive behavior. Topics: Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma, Skin Appendage; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Skin Neoplasms; Sweat Gland Neoplasms | 2002 |
Immunohistochemical analysis of cytokeratin and human milk fat globulin expression in mucinous carcinoma of the skin.
Mucinous carcinoma of the skin (MCS) is a rare epithelial tumor which arises primarily in the skin. Metastatic MC from extracutaneous sites, especially breast or colon, mimics MCS and cannot be differentiated from MCS by routine histology alone.. Nine cases of MCS were analyzed immunohistochemically using monoclonal antibodies against cytokeratins (CKs) and human milk fat globulin 1 (HMFG) in order to clarify their nature and compare the immunophenotypes with those of other MCs studied in the literature.. Expression of simple epithelial CKs in most of the tumor cells of all cases studied and co-expression of simple and stratified epithelial CKs in some tumor cells of two cases were recognized. CK 20 expression could not detected in any tumor cells. Focal HMFG expression in the luminal or outer surface of the nests was observed in three cases.. From CKs expression, MCS was speculated to differentiated mainly toward the secretory cells of the sweat glands, and some tumor cells toward the transient portion between the dermal duct and the secretory portion. Focal HMFG expression suggested either a consequence of malignant transformation or apocrine differentiation. No expression of CK 20 in MCS suggests that we may exclude the diagnosis of metastatic colorectal MC which expressed CK 20. Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Lactoglobulins; Male; Middle Aged; Skin Neoplasms | 2002 |
Overexpression of a constitutively active form of c-src in skin epidermis increases sensitivity to tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.
Transgenic mice were developed to study the role of c-src in epithelial tumorigenesis through targeted expression of a constitutively active form of murine c-src (src(529)). Src(529) was targeted to the interfollicular epidermis with the human keratin 1 (HK1) promoter. The skin phenotype of these mice was characterized by exaggerated epidermal hyperplasia and hyperkeratosis within the first week after birth. The severity of this phenotype correlated with overall src kinase activity, both of which subsided with age. Treatment of adult HK1.src(529) transgenic mice with the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate resulted in an increase in epidermal hyperplasia and labeling index significantly greater than that seen in nontransgenic littermates. In addition, HK1.src(529) transgenic mice developed papillomas earlier and in significantly greater numbers compared with nontransgenic littermates in a standard initiation-promotion experiment. The data support the hypothesis that activation of c-src kinase plays a role in skin tumor promotion. Topics: Animals; Carcinogens; Epidermis; Hyperplasia; Keratins; Kinetics; Mice; Mice, Transgenic; Mutation; Promoter Regions, Genetic; Proto-Oncogene Proteins pp60(c-src); Skin Neoplasms; Tetradecanoylphorbol Acetate | 2002 |
Targeted expression of spermidine/spermine N1-acetyltransferase increases susceptibility to chemically induced skin carcinogenesis.
The bovine keratin 6 gene promoter was used to target expression of spermidine/spermine N1-acetyltransferase (SSAT) to epidermal keratinocytes in the hair follicle of transgenic mice. K6-SSAT transgenic mice appeared to be phenotypically normal and were indistinguishable from normal littermates until subjected to a two-stage tumorigenesis protocol. For such tumorigenesis studies, mice were bred for six generations onto a tumor promoter resistant C57BL/6 background strain. K6-SSAT transgenic mice showed a 10-fold increase in the number of epidermal tumors that developed in response to a single application of 400 nmol of the tumor initiator 7,12-dimethylbenz[a]anthracene followed by twice weekly applications of 17 nmol of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate for 19 weeks. Tumor samples from transgenic animals showed marked elevations in SSAT enzyme activity and SSAT protein levels compared with tumors from non-transgenic littermates, and the accompanying changes in putrescine and N1-acetylspermidine pools indicated activation of SSAT-mediated polyamine catabolism in transgenic animals. An unusually high number of tumors were shown both grossly and histologically to have progressed to carcinomas in this model and these occurred with an early latency and only in mice carrying the K6-SSAT transgene. These results suggest that activation of polyamine catabolism leading to increases in putrescine and N1-acetylspermidine may play a key role in chemically induced mouse skin neoplasia. Topics: 9,10-Dimethyl-1,2-benzanthracene; Acetyltransferases; Animals; Animals, Genetically Modified; Carcinogens; Cattle; Genetic Predisposition to Disease; Immunohistochemistry; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasms, Experimental; Plasmids; Promoter Regions, Genetic; Putrescine; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors | 2002 |
The expression of keratin k10 in the basal layer of the epidermis inhibits cell proliferation and prevents skin tumorigenesis.
Forced expression of K10, a keratin normally expressed in postmitotic, terminally differentiating epidermal keratinocytes, inhibits the progression of the cell cycle in cultured cells (Paramio, J. M., Casanova, M. Ll., Segrelles, C., Mittnacht, S., Lane, E. B., and Jorcano, J. L. (1999) Mol. Cell. Biol. 19, 3086-3094). This process requires a functional retinoblastoma (pRb) gene product and is mediated by K10-induced inhibition of Akt and PKCzeta, two signaling intermediates belonging to the phosphoinositide (PI) 3-kinase signal transduction pathway (Paramio, J. M., Segrelles, C., Ruiz, S., and Jorcano, J. L. (2001) Mol. Cell. Biol. 21, 7449-7459). Extending earlier in vitro studies to the in vivo situation, this work analyzes the alterations found in transgenic mice that ectopically express K10 in the proliferative basal cells of the epidermis. Increased expression of K10 led to a hypoplastic and hyperkeratotic epidermis due to a dramatic decrease in skin keratinocyte proliferation in association with the inhibition of Akt and PKCzeta activities. The inhibition of cell proliferation and Akt and PKCzeta activities was also observed although to a minor extent in low hK10-expressing mice. These animals displayed no overt epidermal phenotype nor overexpression of K10. In these non-phenotypic mice, ectopic K10 expression also resulted in decreased skin tumorigenesis. Collectively, these data demonstrate that keratin K10 in vivo functions include the control of epithelial proliferation in skin epidermis. Topics: Animals; Cell Division; Epidermal Cells; Epidermis; Keratins; Mice; Mice, Transgenic; Protein Kinases; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Skin Neoplasms | 2002 |
[Recurrence of an epithelioid sarcoma of the scalp].
Epithelioid sarcoma is a rare soft tissue tumor that, due to its clinically unspecific features, is frequently mistaken for other benign and malignant entities. We report on a 63-year-old male presenting with a relapse of an epithelioid sarcoma. At clinical inspection, the tumor presented as an erythematous nodule with ulceration in the center. Despite its slow growth, epithelioid sarcoma should be regarded as an aggressive neoplasm exhibiting frequent local recurrences and subsequent lymphatic and visceral spreading in about half of the patients. Histopathological findings are the presence of large epithelioid and spindle cells with immunoreactivity for cytokeratin and vimentin. Topics: Biomarkers, Tumor; Diagnosis, Differential; Humans; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Reoperation; Sarcoma; Scalp; Skin Neoplasms; Vimentin | 2002 |
Tricholemmal carcinoma in continuity with trichoblastoma within nevus sebaceus.
A nodule arising within the nevus sebaceus on the vertex of the scalp of a 68-year-old woman was histopathologically and immunohistochemically investigated. We also used immunohistochemistry to investigate the cytokeratin (CK) distribution of the outer root sheaths of normal terminal hair follicles. The nodule consisted of two parts, a main exophytic part with a lobular proliferation and a small peripheral part with the features of trichoblastoma. The main exophytic lesion consisted of lobular aggregations composed of both or either basaloid cells and clear cells with the silhouette and cytology of malignancy. The columnar clear cells were aligned in a palisade at the periphery of the aggregations of clear cells, and the aggregations located in the superficial dermis were connected to the follicular infundibular structures. Almost all of the neoplastic aggregations were diffusely positive for CK7 (OV/TLR/30), and the innermost or inner cells of the neoplastic aggregations were positive for CK17; a similar staining pattern to that in the lower portion of the outer root sheath between the A and B fringes in normal terminal hair follicles. The exophytic part of the lesion was a malignant neoplasm with differentiation mainly toward the lower segment of the outer sheath between the A and B fringes of the terminal hair follicle, namely tricholemmal carcinoma. Our case may represent a collision of two distinctive neoplasms (tricholemmal carcinoma and trichoblastoma), however, an intimate relationship between these two neoplasms also should be considered. Topics: Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Hair Follicle; Hamartoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasms, Second Primary; Nevus; Scalp; Sebaceous Gland Neoplasms; Skin Diseases; Skin Neoplasms | 2002 |
Large expansion of morphologically heterogeneous mammary epithelial cells, including the luminal phenotype, from human breast tumours.
Regular expansion of heterogeneous populations of epithelial cells, including the luminal phenotype, was achieved from small biopsies of human breast tumours and cutaneous metastases by optimized feeder layer technique based on irradiated NIH 3T3 cells. Forty-one out of 47 primary tumour specimens and all three cutaneous metastases grew successfully for two to 10 passages in vitro. The main phenotypes of cultured cells and their changes in subcultures were characterized using immunocytochemistry and phase contrast microscopy (in few cases also time-lapse recording). In the majority of cultured cell populations a fraction of cells positive for keratin 19 (K19+), typical for the luminal phenotype, was detected. This is the cell type from which breast carcinoma is supposed to arise. While in cultures derived from benign lesions only basic phenotypes of luminal and myoepithelial cells were found, in cultures derived from malignant tumours unusual phenotypes of epithelial cells, in their majority K19+, were detected. The growth properties of cells from six benign and seven malignant samples were analyzed in detail. In the analyzed cell populations the culture lifetime - related to the number of colony-forming cells varied for cells from malignant tumours between 21 and 51 and from benign tumours between 22 and 40 cell generations. The total number of passages achieved was three to seven for malignant or four to nine for benign cultures. In spite of negative results of tumourigenicity testing in immunologically compromised Nu/nu mice the potential to culture apparently neoplastic cells was indicated by positive immunostaining for the p53 oncoprotein (seven of 23 tested malignant cases), the src oncoprotein (five of eight), and overexpression of the c-erbB-2 protein (five of 26). This was further confirmed by successful cultivation of malignant cells from cutaneous metastases. Two of the three metastasis-derived cultures were nearly homogeneously positive for K19 while the third was almost negative. The results proved the optimized feeder layer technique to be useful for regular yielding of large amounts of epithelial cells from small tumour biopsies and for supporting the majority of cell phenotypes present in the original tumour. Therefore, it appeared to be a promising tool for further analysis of interactions between luminal and myoepithelial cells in the development of human breast carcinoma and for the study of individual tumours. Topics: 3T3 Cells; Adult; Aged; Animals; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Case-Control Studies; Cell Count; Cell Transformation, Neoplastic; Cells, Cultured; Coculture Techniques; Female; Humans; Immunohistochemistry; Keratins; Mice; Microscopy, Phase-Contrast; Middle Aged; Phenotype; Skin Neoplasms; Tumor Cells, Cultured | 2002 |
Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel cell carcinoma in sentinel lymph nodes.
Sentinel lymph node biopsy (SLNBx) can identify Merkel cell carcinoma (MCC) micrometastasis.. We attempted to examine the effectiveness of immunostaining and identify antibodies most appropriate for evaluation of SLNBxs for MCC.. Histopathologic material from 10 patients with MCC who had SLNBx was reviewed.. Twenty-three SLNBxs from 10 patients appeared tumor-free in routine hematoxylin-eosin (H&E)-stained sections. However, tumor cells were detected in immunostained sections from 5 (22%) of 23 SLNBxs in 4 (40%) of 10 patients. Immunostains with pancytokeratin (panCK), cytokeratin-20 (CK-20), neurofilament protein, and chromogranin A were used for all primary and SLNBx specimens. All 5 (100%) micrometastatic foci stained strongly for CK-20 and panCK. Background normal lymph node tissue also stained for panCK but not for CK-20.. Examination of H&E sections alone is insufficient for excluding micrometastatic MCC in sentinel lymph nodes. We observed the greatest sensitivity and specificity with anti-CK-20 antibody in identifying micrometastatic MCC in sentinel lymph nodes. Topics: Aged; Aged, 80 and over; Carcinoma, Merkel Cell; Culture Techniques; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Registries; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Skin Neoplasms | 2002 |
Pathologic quiz case: cutaneous nodule of 3-year duration. Epithelioid sarcoma.
Topics: Adult; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Sarcoma; Skin Neoplasms; Vimentin | 2002 |
Spitz nevus of the tongue with pseudoepitheliomatous hyperplasia: report of three cases of a pseudomalignant condition.
Three cases of Spitz nevus of the tongue associated with pseudoepitheliomatous hyperplasia are reported: two occurring in children and one in an adult. The location at an unusual site and the complex pattern resulting from the intimate admixture of the neoplastic melanocytic component and the hyperplastic keratinocytic component led in each case to consider diagnoses such as malignant melanoma and invasive squamous cell carcinoma. Staining for S-100 protein and keratin was useful to identify and separate the two components. Spitz nevus of the tongue carries some intriguing similarities with granular cell tumor, suggesting a possible histogenetic and pathogenetic relationship. Topics: Adult; Biomarkers, Tumor; Child; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Neoplasm Proteins; Nevus, Epithelioid and Spindle Cell; S100 Proteins; Skin Neoplasms; Tongue Neoplasms | 2002 |
Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours.
Proteins of the Rho family control signalling pathways that regulate the actin cytoskeleton and gene transcription. In vitro studies have implicated Rho-like GTP-hydrolysing enzymes (GTPases) in cell migration, cell-cycle progression, and Ras-induced focus formation, suggesting a role for these GTPases in the formation and progression of tumours in vivo. To study this, we have generated mice lacking the Rac-specific activator Tiam1, a T-lymphoma invasion and metastasis inducing protein. Here we show that such Tiam1(-/-) mice are resistant to the development of Ras-induced skin tumours initiated with 7,12-dimethylbenzanthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate. Moreover, the few tumours produced in Tiam1(-/-) mice grew much slower than did tumours in wild-type mice. Tiam1-deficient primary embryonic fibroblasts were also resistant to Ras(V12)-induced focus formation. Analysis of Tiam1 heterozygotes indicated that both tumour initiation and promotion were dependent on the Tiam1 gene dose. Tiam1 deficiency was associated with increased apoptosis during initiation, and with impeded proliferation during promotion. Although the number of tumours in Tiam1(-/-) mice was small, a greater proportion progressed to malignancy, suggesting that Tiam1 deficiency promotes malignant conversion. Our studies identify the Rac activator Tiam1 as a critical regulator of different aspects of Ras-induced tumour formation. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Cell Division; Disease Progression; Gene Dosage; Genotype; Guanine Nucleotide Exchange Factors; Immunohistochemistry; Keratins; Mice; Mice, Knockout; Proteins; ras Proteins; Skin Neoplasms; T-Lymphoma Invasion and Metastasis-inducing Protein 1; Tetradecanoylphorbol Acetate | 2002 |
Differentiation-dependent glycosylation of cells in squamous cell epithelia detected by a mammalian lectin.
The squamous stratified epithelia contain a proliferative (harboring mitotic activity) and a differentiating compartment. Due to the potential of protein-carbohydrate interactions to regulate cellular activities we introduced a mammalian lectin to cyto- and histochemical analysis. We answer the questions of whether and to what extent this new probe can pinpoint differentiation-dependent glycosylation changes in sections and in culture of keratinocytes.. Purification and labeling enabled monitoring of galectin-3 reactivity in frozen sections of human and pig epidermis and basal cell carcinomas as well as in culture of keratinocytes. The staining pattern of the lectin was correlated with the staining profile of other cell markers including desmosomal proteins, beta(1) integrin, and the proliferation marker Ki-67. The Dolichos biflorus agglutinin (DBA) sharing binding reactivity of galectin-3 to the A type histoblood group epitope was used for comparison.. Both lectins exhibit suprabasal binding. However, their profiles were not identical, substantiated by lack of coinhibition. Strong DBA reactivity was also observed in a limited number of basal layer cells, namely in cells without the expression of the proliferation marker Ki-67. Cultured mitotic epidermal cells have no reactivity for DBA. Presence of ligands for this plant lectin was connected with decreased positivity of nuclei for Ki-67 and the occurrence of ring-shaped nucleoli, micronucleoli or absence of nucleoli. Considering colocalization the pattern of galectin-3-binding sites coincided with the presence of desmosomal proteins such as desmoplakin-1 and desmoglein but not beta(1) integrin, a potential ligand. Interestingly, studied basal cell carcinomas expressed no binding sites for galectin-3, while a limited number of cells were DBA-reactive.. The expression of galectin-3-binding sites and also DBA-reactive glycoligands correlates with an increased level of differentiation and/or cessation of proliferation in the examined squamous stratified epithelia. Further application of tissue lectins for characterizing ligand expression and its modulation is an important step to reveal functional relevance. Topics: Animals; Binding Sites; Carcinoma, Basal Cell; Cell Differentiation; Cells, Cultured; Cytoskeletal Proteins; Desmogleins; Desmoplakins; Epithelial Cells; Epithelium; Galectin 3; Glycosylation; Humans; Immunohistochemistry; Integrin beta1; Keratinocytes; Keratins; Ki-67 Antigen; Mice; Plant Lectins; Protein Binding; Skin Neoplasms; Swine | 2002 |
Basal cell carcinomas are populated by melanocytes and Langerhans [correction of Langerhan's] cells.
Several reports have documented the coexistence of basal cell carcinoma (BCC) with other lesions, including melanoma. This study was performed to determine whether nests of BCC contain benign melanocytes and Langerhans [corrected] cells. Ten cases of BCC were investigated to determine whether benign melanocytes and Langerhans [corrected] cells populate tumor nests. The BCCs were stained with antibodies to cytokeratin AEI/AE3, S-100, HMB-45, Melan-A, and CD1a proteins. We report that all 10 BCCs were populated by dendritic melanocytes distributed at the periphery (5/10 cases) or evenly throughout tumor nests (5/10 cases). Clusters of melanocytes were not identified in any of the BCCs. A total of 9 of 10 tumors showed staining of dendritic Langerhans cells with CD1a. A total of 8 of 10 tumors stained with cytokeratin AEI/AE3; in 6 of the 8 tumors, the staining was focal. We compared these findings with a single example of a BCC and melanoma in situ (MIS) collision tumor in which the cytokeratin AE1/AE3-positive epithelial nests of BCC were populated by a high density of malignant melanocytes that stained with S-100 and HMB-45. Melanocytes were disposed singly and in clusters of two or more cells within BCC tumor nests. We conclude from this study that BCCs are regularly populated by benign melanocytes and Langerhans [corrected] cells. Furthermore, when BCC is infiltrated with malignant melanocytes of MIS, the melanocyte density is higher and clusters of melanocytes can be observed. The significance of these two findings is unclear, as additional cases of BCC MIS collision tumor need to be studied. Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Basal Cell; Humans; Immunoenzyme Techniques; Keratins; Langerhans Cells; Melanocytes; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins; Neoplasms, Multiple Primary; S100 Proteins; Skin Neoplasms | 2001 |
Bax gene disruption alters the epidermal response to ultraviolet irradiation and in vivo induced skin carcinogenesis.
Bcl-2 family member proteins are differentially expressed in skin and in non-melanoma skin cancer (NMSC). To elucidate the contribution of bcl-2 and bax proteins to epidermal differentiation and skin carcinogenesis, we investigated keratinocyte proliferation, differentiation and tumourigenesis in bcl-2(-/-) and bax(-/-) mice. The rate and pattern of proliferation and spontaneous cell death in the bcl-2(-/-) and bax(-/-) mice were not different from control mice. The epidermis of bcl-2(-/-) and bax(-/-) expressed sightly higher levels of cytokeratin 1 and loricrin compared to control littermates. The apoptotic response to ultraviolet-induced genotoxic stress was assessed by quantitating TUNEL positive cells. Bax(-/-) keratinocytes showed a significant resistance to UV-induced cell death compared to control mice. The life-span of bcl-2(-/-) mice precluded an assessment of bcl-2 gene disruption on in vivo tumourigenesis. A significant increase in tumour incidence was observed in bax(-/-) mice compared to control mice in two-step chemical carcinogenesis studies. These findings suggest that bcl-2 and bax gene products may be important determinants of normal keratinocyte differentiation and response to genotoxic stress in vivo, and indicate that bax may provide a tumour suppressor effect during skin carcinogenesis. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; bcl-2-Associated X Protein; Carcinogens; Cell Differentiation; Epidermal Cells; Epidermis; Genes, bcl-2; Immunoblotting; Immunohistochemistry; In Situ Nick-End Labeling; Keratinocytes; Keratins; Membrane Proteins; Mice; Mice, Knockout; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Skin Neoplasms; Tetradecanoylphorbol Acetate; Ultraviolet Rays | 2001 |
Lectin and proteoglycan histochemistry of Merkel cell carcinomas.
Changes in carbohydrate residue expression and in proteoglycan distribution occur during different stages of tumor development and progression. However, few data concerning carbohydrate residue analysis as performed by lectin histochemistry and proteoglycan distribution of Merkel cell carcinoma, a rare malignant tumor of the skin, have been reported. Hence, lectin- and proteoglycan immunohistochemistry was performed on paraffin wax material of 9 cases of Merkel cell carcinomas characterized by cytokeratin and neurofilament immunohistochemistry. The lectin binding pattern of tumor cells varied between lectins with different sugar binding specificities, while within a given nominal sugar specificity intensities were remarkably similar between tumors from different patients. The most intensive reaction was observed using Con A (mannose/glucose-specific) followed by LCA with the same specificity and the N-Acetyl glucosamine-specific lectins (WGA, UDA, CMA), while no fucose binding sites were detected (UEA-I). In addition, N-Acetyl galactosamine residues were only occasionally detected. The lectin binding pattern of Merkel cell carcinoma cells indicated that predominantly N-linked glycans and not O-linked glycans, typical for mucins of most epithelia, were present. Hence these tumor cells were relatively undifferentiated and resembled stem cells more closely than differentiated epithelia. The tumor stroma was especially evaluated in this study and showed a lectin reaction, which was intermediate between the tumor cells and extra-tumoral stroma. For example, the reactions of N-Acetyl galactosamine-specific lectins were intensive in the extra-tumoral stroma but nearly negative in tumor cells, while the lectin reaction of the intra-tumoral stroma was similar to the cellular reaction. These results indicated an influence of tumor cells on the stromal constituents. Antibodies against chondroitin type glycosaminoglycans reacted with the tumor stroma and the pericellular substance around the tumor cells most intensely in - and around the major tumor septae which, in general, were well vascularized. The most intensive immunoreactivity was detected using the chondroitin-6-sulfate antibody. The cellular and membrane-associated reaction for heparan sulfate was less intensive in comparison to epidermal cells. In conclusion the pattern of lectin-binding sites, the high chondroitin(sulfate) specific reactivity and the relatively low intensity of heparan sulfate immunohistoc Topics: Biomarkers, Tumor; Carbohydrates; Carcinoma, Merkel Cell; Glycoconjugates; Humans; Keratins; Lectins; Membrane Glycoproteins; Neoplasm Proteins; Neurofilament Proteins; Phenotype; Proteoglycans; Skin Neoplasms; Stromal Cells | 2001 |
Up- and down-regulation of granulocyte/macrophage-colony stimulating factor activity in murine skin increase susceptibility to skin carcinogenesis by independent mechanisms.
The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in tumorigenesis is complex. On the one hand, GM-CSF can promote tumor cell growth, survival, and even metastasis. On the other hand, it can stimulate tumor cell rejection. In skin, it is early expressed after topic application of tumor-promoting agents and therefore may be responsible for changes that correlate with skin tumor promotion (e.g., epidermal hyperproliferation and inflammation). To analyze GM-CSF function in skin tumorigenesis, we generated transgenic mice epidermally overexpressing either GM-CSF or a GM-CSF antagonist. Both types of transgenic mice exhibited significantly increased numbers of benign tumors in a two-step skin carcinogenesis experiment using 7',12'-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-CSF displayed a significantly elevated carcinoma burden following a single-step carcinogenesis protocol consisting of tumor initiation only. Therefore, endogenous promotion is responsible for elevated tumor development in GM-CSF-overexpressing mice. In antagonist transgenic animals, an increased tumorigenicity of modified B16 tumor cells after cutaneous transplantation as compared with nontransgenic or GM-CSF transgenic mice was observed. Thus, the antitumor activity leading to the repression of tumor cell growth in control mice is GM-CSF dependent and is compromised in mice expressing the antagonist. We suggest that both, up-regulation and down-regulation of GM-CSF activity in skin, increase the incidence and growth of tumors via two independent mechanisms: endogenous tumor promotion in the case of increased GM-CSF activity and compromised tumor cell rejection in the case of decreased GM-CSF activity. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Down-Regulation; Granulocyte-Macrophage Colony-Stimulating Factor; Keratin-10; Keratins; Melanoma, Experimental; Mice; Mice, Transgenic; Neoplasm Transplantation; Phenotype; Skin; Skin Neoplasms; Skin Physiological Phenomena; Tetradecanoylphorbol Acetate; Transgenes; Up-Regulation | 2001 |
Proliferation and differentiation of the keratinocytes in hyperplastic epidermis overlying dermatofibroma: immunohistochemical characterization.
Epidermal changes overlying dermatofibromas (DFs) have been described as ranging from psoriasiform simple hyperplasia to basaloid hyperplasia sometimes morphologically indistinguishable from superficial basal cell carcinoma (BCC). To characterize epidermal hyperplasia overlying DFs and to determine its association with the disease process, we examined 30 cases of DF showing hyperplastic epidermis. We used nine immunohistochemical markers associated with keratinocyte proliferation or differentiation. In DFs, the dermal metallothionein (MT) expression and immunophenotypic changes with regard to epidermal differentiation varied depending on the stage of lesional evolution of the DFs. Immunostaining for epidermal growth factor receptor (EGFR), MT, and keratin 6 (K6) increased in simple hyperplastic epidermis (SHE) overlying DFs (n = 11), whereas it gradually diminished in basaloid hyperplastic epidermis (BHE) overlying DFs (n = 19). In SHE, there was a significant increase in K14 expression. Among 19 BHE cases, 12 showed premature expression of involucrin and delayed appearance of K1 along with aberrant expression of K14. Conversely, the remaining 7 BHE cases showed a pattern of involucrin and K1 similar to that of normal skin coinciding with decreased or absent dermal MT expression. Loricrin and filaggrin expression in all DFs was the same as that of normal skin. Based on the sparse positivity of Ki-67 in the hyperplastic epidermis overlying DFs, we found that the biologic ability of BHE and SHE was not apparent in the hyperproliferative state observed in psoriasis and BCC. These results suggest that the dermal fibrohistiocytic process may trigger the induction of SHE overlying DFs by an unknown mechanism and then mediate both the abnormal keratinocyte differentiation and the transformation of SHE to BHE through the evolution of the dermal lesions. Topics: Biomarkers; Carcinoma, Basal Cell; Cell Differentiation; Cell Division; Epidermis; ErbB Receptors; Filaggrin Proteins; Histiocytoma, Benign Fibrous; Humans; Hyperplasia; Immunoenzyme Techniques; Keratinocytes; Keratins; Metallothionein; Precancerous Conditions; Psoriasis; Skin Neoplasms | 2001 |
Growth and characterization of a cell line from a human primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma) in culture and as xenograft.
The primary neuroendocrine carcinoma of the skin or Merkel cell carcinoma (MCC) is a skin tumor with aggressive biological behaviour. Experimental models for investigating the biological properties of the tumor are prerequisite for developing new therapeutic approaches. In this study, we report the establishment and characterisation of a cell line derived from the lymph-node metastasis of a patient with highly aggressive MCC. Merkel carcinoma cells (MCC-1) grew as floating aggregates in suspension cultures for more than two years and over 70 subcultures. The proliferation rate in suspension cultures was rather moderate with a population doubling time of 69 h. The immunocytochemical pattern of the cultured MCC-1 was similar to that of the original tumor with expression of cytokeratin 18, neuron-specific enolase, neurofilaments, and synaptophysin. In addition, reverse transcriptase polymerase chain reaction (RT-PCR) revealed presence of chromogranin A mRNA in the MCC-1 cell line. Furthermore, electron microscopy yielded the rare finding of neuroendocrine granules in the cytoplasm of the cultured cells. The cell line MCC-1 was able to form colonies in soft agar. Nude mice developed solid tumors with similar histology to the original tumor after subcutaneous and intravenous injections of cultured MCC-1, and malignant ascites was seen after intraperitoneal injection. Also, two MCC-1 sublines were established by reculturing cells from the xenografts grown in vivo and immunocytochemistry confirmed their neuroendocrine origin. The MCC-1 line may thus serve as a model for studying the biology and the metastatic potential of Merkel cell carcinoma. Topics: Aged; Aged, 80 and over; Animals; Antigens, Differentiation; Carcinoma, Merkel Cell; Cell Division; Chromogranin A; Chromogranins; Humans; Keratins; Male; Mice; Mice, Nude; Neoplasm Transplantation; Phosphopyruvate Hydratase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Secretory Vesicles; Skin Neoplasms; Synaptophysin; Transplantation, Heterologous; Tumor Cells, Cultured | 2001 |
Expression of type I hair keratins in follicular tumours.
Hair keratins are specifically expressed in hair and nails. We previously demonstrated the expression of hair keratin basic 1 mRNA in pilomatrixomas. We recently developed a method for immunohistochemical staining of the group of acidic keratins, which have not yet been investigated in human tumours.. To study the expression of eight members of the type I hair keratin subfamily in pilomatrixomas and other skin tumours of follicular origin.. We performed immunohistochemistry on paraffin sections of formalin-fixed pilomatrixomas (40), trichoepitheliomas (10), trichoblastomas (10), desmoplastic trichoepitheliomas (10) and basal cell carcinomas (10), using antibodies against type I hair keratins hHa1, hHa2, hHa3-II, hHa4, hHa5, hHa6, hHa7 and hHa8 as well as cytokeratin CK17.. While CK17 was found in almost all tumours investigated, hair keratins were exclusively expressed in pilomatrixomas. Their expression was restricted to areas of transitional cells, located between outer basophilic matricial cells and an inner zone of eosinophilic shadow cells. The most frequently and most strongly expressed hair keratins were hHa1, hHa2, hHa5 and hHa8, whereas hHa4 and hHa6 were only weakly expressed. No positive staining was observed with anti-hHa3-II and anti-hHa7 antibodies. Hair keratin expression in intermediate maturation stage pilomatrixomas resembled that of normal hair follicles, with early matricial and cuticular keratins hHa5 and hHa2 being expressed in lower transitional cells, followed by expression of early cortex keratins hHa1 and hHa8 in intermediate transitional cells and the late cortex keratins hHa4 and hHa6 in upper transitional cells. The latter were, however, seen only in a few intermediate maturation stage pilomatrixomas and were generally absent in late-stage pilomatrixomas.. These changes in hair keratin expression patterns indicate that the maturation of pilomatrixomas towards large areas of shadow cells is associated with a gradual loss of differentiation-specific hair keratins. The complex hair keratin expression in pilomatrixomas is a further argument in favour of a hair matrix origin of this tumour. Topics: Carcinoma, Basal Cell; Hair Diseases; Hair Follicle; Humans; Keratins; Neoplasm Proteins; Neoplasms, Basal Cell; Pilomatrixoma; Skin Neoplasms | 2001 |
Squamous cell carcinoma detected by high-molecular-weight cytokeratin immunostaining mimicking atypical fibroxanthoma.
Atypical fibroxanthoma can mimic other tumors, particularly spindle cell squamous cell carcinoma and spindle cell or desmoplastic melanoma. We describe a patient with chronic lymphocytic leukemia who developed acantholytic squamous cell carcinoma on the face, which recurred and metastasized to a cervical lymph node. This tumor was at first diagnosed as atypical fibroxanthoma because of its histologic and immunostaining similarity. It showed weak or negative keratin cocktail staining and strong vimentin staining. However, a recurrent tumor was immunostained for high-molecular-weight keratin and showed strong positivity. Aggressive behavior of this squamous cell carcinoma may be due to altered immune response secondary to chronic lymphocytic leukemia. Topics: Aged; Carcinoma, Squamous Cell; Diagnosis, Differential; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Skin Neoplasms; Vimentin | 2001 |
Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes.
Telomerase transgenics are an important tool to assess the role of telomerase in cancer, as well as to evaluate the potential use of telomerase for gene therapy of age-associated diseases. Here, we have targeted the expression of the catalytic component of mouse telomerase, mTERT, to basal keratinocytes using the bovine keratin 5 promoter. These telomerase-transgenic mice are viable and show histologically normal stratified epithelia with high levels of telomerase activity and normal telomere length. Interestingly, the epidermis of these mice is highly responsive to the mitogenic effects of phorbol esters, and it is more susceptible than that of wild-type littermates to the development skin tumors upon chemical carcinogenesis. The epidermis of telomerase-transgenic mice also shows an increased wound-healing rate compared with wild-type littermates. These results suggest that, contrary to the general assumption, telomerase actively promotes proliferation in cells that have sufficiently long telomeres and unravel potential risks of gene therapy for age-associated diseases based on telomerase upregulation. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Catalytic Domain; Cattle; DNA-Binding Proteins; Female; Gastric Mucosa; Genes, p53; Genetic Therapy; Hyperplasia; Keratinocytes; Keratins; Mice; Mice, Knockout; Mice, Transgenic; Mouth Mucosa; Neoplasms, Experimental; Papilloma; Protein Subunits; RNA; Skin; Skin Neoplasms; Stomach; Telomerase; Telomere; Tetradecanoylphorbol Acetate; Vagina; Wound Healing | 2001 |
Cutaneous B-cell lymphoma with signet ring-cell morphology: a clinicopathologic and immunohistochemical study of three cases.
Three cases of primary cutaneous B-cell lymphoma with prominent signet ring-cell features are presented. The patients were three men between the ages of 37 years and 74 years (average, 55.5 years). Clinically, the three patients presented with multiple skin nodules. In one patient, the nodules had been present for approximately 5 weeks, although in the two other patients, the nodules were of unknown duration. The lesions were located in the upper extremities (forearm) and measured from 2 cm to 3 cm in diameter. No evidence of lymphadenopathy was observed in any of the patients. Surgical excision of the nodules was performed. Histologically, in two cases, the superficial and deep dermis was replaced by a diffuse cellular proliferation, and in one patient, the tumor cell population adopted a nodular pattern of growth involving adnexal structures and infiltrating the subcutaneous fat. In all cases, the tumors were composed of cells showing signet ring-cell features, with striking indentation of the nuclei toward the periphery of the cell. Immunohistochemical studies using antibodies for B-cell and T-cell markers (L-26 and UCHL) as well as antibodies for leukocyte common antigen, keratin, and kappa and lambda light chains were performed in all cases. The tumor cells showed a positive reaction for leukocyte common antigen, L-26, and lambda light chain restriction. Follow-up information was only available in one patient, who has remained alive and well 2 years after diagnosis without evidence of progression of the disease. The present cases highlight the importance of recognizing this unusual morphologic type of lymphoma so as to arrive at a correct diagnosis. Topics: Adult; Aged; Antigens, CD20; Cell Nucleus; Dermis; Humans; Immunoglobulin lambda-Chains; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma, B-Cell; Male; Middle Aged; Skin Neoplasms | 2001 |
Pseudoepitheliomatous hyperplasia of follicular origin and malignant melanoma.
Topics: Carcinoembryonic Antigen; Epithelial Cells; Hair Follicle; Humans; Hyperplasia; Keratins; Keratoacanthoma; Melanoma; Mouth Mucosa; Skin; Skin Neoplasms | 2001 |
[Pigmented Paget's disease of the male nipple].
Mammary Paget's disease unfrequently occurs in males, and may be pigmented in rare instances. Differential diagnosis with malignant melanoma relies on immunohistochemical studies.. A case of Paget's disease of the nipple in a 76 year-old male is reported, clinically mimicking a malignant melanoma because of massive pigmentation. Histologically, large Paget's clear cells were intermingled with numerous melanin-rich dendritic melanocytes. An underlying ductal carcinoma was found. After differential immunohistochemical staining, diagnosis of Paget's disease could be unequivocally substantiated since Paget's cells stained for epithelial markers, c-erbB-2 and hormonal receptors, whereas protein S100 and HMB45 were negative.. Pigmentation in mammary Paget's disease occurs preferentially in males. Pigmentation results from numerous melanocytes with abundant melanin in close contact with Paget's cells. An increased number of melanocytes may also be observed in cutaneous metastatic breast carcinomas. It could result from a chemotactic factor produced by neoplastic cells. Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms, Male; Diagnosis, Differential; Genes, erbB-2; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins; Nipples; Paget's Disease, Mammary; S100 Proteins; Skin Neoplasms | 2001 |
Deregulated expression of DP1 induces epidermal proliferation and enhances skin carcinogenesis.
E2F transcription factors have been implicated in several cellular processes, including proliferation, apoptosis, and oncogenic transformation. A functional E2F factor consists of a heterodimer containing an E2F polypeptide (E2F1-E2F6) and a DRTF1-polypeptide (DRTF1-polypeptide-1 (DP1) or DRTF1-polypeptide-2). It is the E2F subunit that supplies the transcriptional activation domain and the motif involved in binding to members of the retinoblastoma tumor suppressor family. The role of the DP subunit in regulating E2F-dependent activities is not completely understood. To examine the properties of DP1 in vivo, we generated transgenic mouse lines expressing DP1 under the control of a keratin 5 (K5) promoter. Overexpression of DP1 in basal layer keratinocytes caused mild hyperplasia and hyperproliferation of the epidermis but did not result in increased apoptosis or spontaneous tumor development. Coexpression of DP1 with E2F1 or E2F4 in the epidermis of bigenic mice modestly enhanced proliferation and apoptosis over the levels induced by E2F1 or E2F4 expression alone. In a two-stage chemical carcinogenesis assay, more and larger skin tumors developed in K5 DP1 transgenic mice than in nontransgenic mice. These findings show that in this in vivo model, deregulated expression of DP1 on its own induced proliferation and enhanced carcinogenesis. Topics: Animals; Apoptosis; Blotting, Northern; Blotting, Western; Bromodeoxyuridine; Cell Cycle Proteins; Cell Division; Cell Nucleus; Epidermal Cells; Epidermis; Immunohistochemistry; In Situ Nick-End Labeling; Keratins; Mice; Mice, Transgenic; Promoter Regions, Genetic; Protein Structure, Tertiary; Skin; Skin Neoplasms; Time Factors; Transcription Factor DP1; Transcription Factors; Transcriptional Activation; Transgenes | 2001 |
Clinical picture: eyelid metastasis.
Topics: Adenocarcinoma; Biopsy; Breast Neoplasms; Carcinoembryonic Antigen; Eyelid Neoplasms; Fatal Outcome; Female; Humans; Keratins; Middle Aged; Mucin-1; Skin Neoplasms | 2001 |
Targeted antizyme expression in the skin of transgenic mice reduces tumor promoter induction of ornithine decarboxylase and decreases sensitivity to chemical carcinogenesis.
To directly evaluate the role of increased ornithine decarboxylase (ODC) and polyamines in mouse skin carcinogenesis, we used bovine keratin 5 (K5) and keratin 6 (K6) promoter elements to direct the expression of antizyme (AZ) to specific skin cell populations. AZ is a multifunctional regulator of polyamine metabolism that inhibits ODC activity, stimulates ODC degradation, and suppresses polyamine uptake. K5-AZ mice treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) at 0 and 24 h exhibit increases in epidermal and dermal ODC activity that are reduced in magnitude. K6-AZ mice treated similarly do not show any increased ODC activity or protein after a second application due to TPA-induced expression of AZ protein. Epidermal and dermal polyamine content, particularly spermidine, is reduced in untreated K5-AZ mice and TPA-treated K5-AZ and K6-AZ mice. Susceptibility to 7,12-dimethylbenz(a)anthracene/TPA carcinogenesis was also investigated for two K6-AZ transgenic lines [K6-AZ(52) and K6-AZ(18)] and a single K5-AZ line. K6-AZ(52) mice had a substantial delay in tumor onset and a >80% reduction in tumor multiplicity compared with normal littermates. K6-AZ(18) and K5-AZ mice also developed fewer papillomas than littermate controls (35% and 50%, respectively), and the combination of these lines to produce double transgenic animals yielded an additive decrease (70%) in tumor multiplicity. These mice demonstrate for the first time that AZ suppresses tumor growth in an animal cancer model and provide a valuable model system to evaluate the role of ODC and polyamines in skin tumorigenesis. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Biogenic Polyamines; Carcinogens; Cattle; Enzyme Induction; Enzyme Inhibitors; Keratin-15; Keratin-5; Keratins; Mice; Mice, Transgenic; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Promoter Regions, Genetic; Protein Biosynthesis; Proteins; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate | 2001 |
Comparative histochemical study of Bowen's disease and actinic keratosis: preserved normal basal cells in Bowen's disease.
The degree of DNA-instability as revealed by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test) has been recently used as a marker of malignancy. This technique was applied to examine 17 skin tissue samples of Bowen's disease, 47 of actinic keratosis, 15 of squamous cell carcinoma, 5 of seborrheic keratosis, and 10 of normal skin. All benign neoplastic cells of seborrheic keratosis and normal epidermal cells were negative. On the other hand, all cancer cells were positive with the DNA-instability test, indicating their malignancy, but all basal cells in Bowen's disease were completely negative. Compatible with this result, the basal cells in Bowen's disease were characteristically normal as evident in other histochemical examinations. Thus, they were negative with p53 immunohistochemistry, with normal signals of chromosome 17 in situ hybridisation and argyrophilic nucleolar organiser region, and showed slightly enhanced proliferative activity as revealed by proliferating cell nuclear antigen immunohistochemistry. Immunohistochemical staining with 34 beta E12 (monoclonal antibody against cytokeratins 1, 5, 10, and 14), which stains all normal epidermal keratinocytes including basal cells, showed that only the basal cells of Bowen's disease stained strongly and homogeneously, while all cancer cells in the upper layers of Bowen's disease and all layers of actinic keratosis were only sporadically or weakly stained. Staining with 34 beta B4 (monoclonal antibody against cytokeratin 1), which recognises the whole epidermis except for the basal layer in the normal epidermis, showed that the basal cells in the Bowen's disease were completely negative, and lower layer cells in the actinic keratosis and upper layer cells in Bowen's disease were only sporadically stained positive, although the superficial layer cells in actinic keratosis stained strongly and homogeneously. Our findings clearly indicate that the basal cells in Bowen's disease are normal. In support of this conclusion, the same cells showed normal morphology on electron microscopy with preserved basement membrane, although the latter was often damaged in actinic keratosis. Topics: Actins; Bowen's Disease; DNA, Neoplasm; Humans; Immunoenzyme Techniques; Interphase; Keratins; Keratosis; Microscopy, Electron; Proliferating Cell Nuclear Antigen; Reticulin; Silver Nitrate; Skin; Skin Neoplasms; Staining and Labeling; Tumor Suppressor Protein p53 | 2001 |
Patterns of basal cell keratin 14 expression in Bowen's disease: a possible marker for tumour progression.
Bowen's disease is a well-established in situ malignancy of the epidermis. The keratin expression in Bowen's disease has been studied in many reports. However, the patterns of keratin (K) 14 expression in each case have not been closely examined.. To investigate if the pattern of expression of K14 has a relationship with tumour progression, we analysed the expression patterns of K14 in relation to the nature of tumour cells, comparing tumour cells in direct contact with the dermis, tumour cells separated from the dermis, and tumour cells invading into the dermis.. Twenty-seven tissue sections from 22 patients were stained with anti-K14 antibody, as well as with antilaminin and periodic acid-Schiff (PAS) staining to evaluate the conditions of the basement membrane. Staining patterns of K10 and integrin beta1, and their relationships with proliferating cell nuclear antigen (PCNA) and Ki-67 staining patterns, were also examined.. Tumour cells with no, or with obscured, basement membranes always showed positive staining for K14, while those with continuous (intact) basement membranes usually did not. Of 10 sections showing dermal involvement of Bowen's disease, five were K14 positive and five were K14 negative. All of these K14-positive sections with dermal involvement showed negative or obscured laminin and PAS staining. Most of the sections having K14-negative tumour cells with dermal involvement showed K14-positive lining cells with continuous staining with laminin and PAS-positive basement membranes. K10 was reciprocally expressed with K14 in most of the sections. Integrin beta1 was expressed in the basal layers of non-tumour epidermal cells, but not in tumour cells. Ki-67 and PCNA were expressed at high frequencies in tumour cells, clearly demarcating tumour cells from non-tumour cells.. Tumour cells separated from the dermis by lining cells were K14 negative with PAS- and laminin-positive basement membranes around them; tumour cells without lining cells were K14 positive with or without continuous basement membranes. K14 expression may be a marker of tumour progression in Bowen's disease. Topics: Basement Membrane; Biomarkers, Tumor; Bowen's Disease; Disease Progression; Humans; Keratin-14; Keratins; Ki-67 Antigen; Laminin; Periodic Acid-Schiff Reaction; Proliferating Cell Nuclear Antigen; Skin Neoplasms | 2001 |
Myc lacks E2F1's ability to suppress skin carcinogenesis.
Myc and E2F1 can each stimulate proliferation, induce apoptosis, and contribute to oncogenic transformation. However, only E2F1 has been shown to have a tumor suppressive activity under some conditions. To examine the potential of Myc to suppress tumorigenesis under one of the conditions in which E2F1 functions to suppress tumorigenesis, transgenic mice expressing Myc under the control of a keratin 5 (K5) promoter were generated. Like K5 E2F1 transgenic mice, K5 Myc transgenic mice have hyperplastic and hyperproliferative epidermis and develop spontaneous tumors in the skin and oral epithelium. In addition, K5 Myc and K5 E2F1 transgenic mice both display aberrant, p53-dependent apoptosis in the epidermis. It has been demonstrated that deregulated expression of E2F1 in the epidermis of transgenic mice inhibits tumorigenesis in a two-stage skin carcinogenesis assay. In sharp contrast to those results, deregulated expression of Myc in the epidermis of transgenic mice resulted in an enhanced response to two-stage skin carcinogenesis. We conclude that while Myc and E2F1 have similar proliferative, apoptotic and oncogenic properties in mouse epidermis, Myc lacks E2F1's tumor suppressive property. This suggests that E2F1's unique ability to inhibit skin carcinogenesis is not simply a consequence of promoting p53-dependent apoptosis. Topics: Age Factors; Animals; Apoptosis; Blotting, Northern; Bromodeoxyuridine; Cell Cycle Proteins; Cell Division; DNA-Binding Proteins; E2F Transcription Factors; E2F1 Transcription Factor; Epidermis; Exons; Genes, p53; In Situ Nick-End Labeling; Keratin-15; Keratin-5; Keratins; Mice; Mice, Transgenic; Phenotype; Promoter Regions, Genetic; Proto-Oncogene Proteins c-myc; Skin Neoplasms; Time Factors; Transcription Factors; Transgenes | 2001 |
[The evaluation of the relationship between malignancy grade and cytokeratin-10 accumulation in human skin squamous cell carcinoma].
The aim of the study was analysis of CK-10 expression in human skin squamous cell carcinoma (SCC) basing on immunohistochemical procedure. The study was carried out on 43 samples of skin SCC which were evaluated histopathologically with regard to 3-grade scale (G) of malignancy. In each case immunohistochemical reactions by use of ABC method were carried out in order to detect CK-10 within cancer cells. The expression of CK-10 was evaluated in accordance with arbitrary 3 grade scale: from +++ to +. The obtained results revealed affection of CK-10 expression in cancer cells. In G1 and G2 skin SCC a moderate expression of CK-10 was found and this occurred in cells grouped in nests. In G3 SCC the expression of CK-10 was very low and this was noted in single cells only. The use of immunohistochemical methods in evaluation of CK-10 expression can be a useful tool in routine histopathologic examination of tumors of epithelial origin. Topics: Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Neoplasm Staging; Skin Neoplasms | 2001 |
Lymphoepithelioma-like cholangiocarcinoma (LELC) not associated with Epstein-Barr virus.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Squamous Cell; Cholangiocarcinoma; Diagnosis, Differential; Epstein-Barr Virus Infections; Germinoma; Herpesvirus 4, Human; Humans; Immunohistochemistry; Keratins; Lymphoma; Male; Melanoma; Middle Aged; Mucin-1; Skin Neoplasms | 2001 |
Telomerase activity of Merkel cell carcinomas and Merkel cell carcinoma-derived cell cultures.
Merkel cell carcinomas are rare malignant tumors of the skin, which are predominantly observed in elderly patients (mean age 65-70 years). It is believed but not yet proven that these tumors are derived from the Merkel cells of the epidermis and hair follicles. The Merkel cells themselves probably originate from an asymmetric cell division of basal keratinocytes and the resulting differentiated Merkel cells have presumably, at least in humans, lost their growth potential. The capability of indefinite cell division in germ line cells and in the great majority of malignant tumors as well as an increased growth potential in certain somatic cells (such as basal cells of renewable tissues) is correlated with cellular telomerase activity, which is absent in differentiated somatic cells. In this study the telomerase activity in cryostat sections of frozen Merkel cell tumor biopsies and in in vitro cultivated Merkel cell carcinoma cells was analyzed. We detected telomerase activity in four tumors and three of four cell cultures. These results show that despite their pronounced neuroendocrine differentiation and their occurrence in patients of advanced age, Merkel cell carcinomas possess telomerase activity similar to that of common carcinoma types. Topics: Aged; Aged, 80 and over; Biopsy; Carcinoma, Merkel Cell; Dissection; Female; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Male; Middle Aged; Skin Neoplasms; Staining and Labeling; Telomerase; Tumor Cells, Cultured | 2001 |
Benign glandular schwannoma.
Glandular schwannoma is a rare variant of schwannoma characterized by the presence of glands in an otherwise typical schwannoma. We report a patient with benign glandular schwannoma occurring on the scalp, a site not previously reported. Histologically, a well-defined, encapsulated oval nodule was observed in the subcutaneous tissue. The nodule was composed of a spindle cell component and glandular structures. The spindle cell component stained positively for S-100 protein. All of the glandular epithelium stained with CAM 5.2 and epithelial membrane antigen but not with S-100 protein. The glandular epithelium was focally positive for carcinoembryonic antigen. The histogenesis of the glandular elements in these tumours is still debated. The variable size of the glandular structures in our case was evidence against an entrapped normal sweat gland origin. The glandular epithelium did not stain with S-100 protein at all, but stained with CAM 5.2, which did not support a direct metaplastic origin of the epithelial elements from the schwannian component. A few scattered CAM 5.2-positive cells and microglandular structures in our case may be the initial differentiating epithelial elements possibly derived from pluripotential neural crest cells. Topics: Adult; Biomarkers; Biomarkers, Tumor; Female; Head and Neck Neoplasms; Humans; Keratins; Neoplasm Proteins; Neurilemmoma; Scalp; Skin Neoplasms | 2001 |
The utility of cytokeratin 5/6 in the recognition of cutaneous spindle cell squamous cell carcinoma.
Cutaneous spindle cell squamous cell carcinoma (SSCC) is a challenging diagnosis since it may be difficult to distinguish from spindle cell melanoma, leiomyosarcoma and atypical fibroxanthoma. Furthermore, it may be difficult to demonstrate epithelial differentiation by a traditional immunohistochemical panel. We performed an expanded immunohistochemical evaluation of ultrastructurally documented SSCC to assess its utility in diagnosing this entity.. We identified 16 cases of SSCC that were composed predominantly of spindle-shaped cells and with ultrastructural evidence of epithelial differentiation (i.e. at least rudimentary cell junctions). Immunohistochemical analysis using antibodies to a variety of cytokeratins (AE1/3, K903, CK5/6) and S-100 protein was performed. The extent of immunostaining was graded on a scale of 0 to 4+ (0: no staining; 1+: < or =25%; 2+: 26-50%; 3+: 51-75%; 4+: >75%).. Of the 16 cases, 6 expressed AE1/3 (38%), 8 expressed K903 (50%) and 11 (69%) expressed CK5/6. Six cases were positive for all three CK markers and two cases were positive for both K903 and CK5/6 but negative for AE1/3. Three cases (19%) stained for CK5/6 without any staining for AE1/3 or K903. Five cases (31%) were negative for all epithelial markers. The extent of CK5/6 staining was either similar to or greater than K903 staining in 7 of 8 cases that stained with both markers. All 16 cases were negative for S-100 protein.. Including CK5/6 in the initial battery of immunostains performed on a cutaneous spindle cell neoplasm can help demonstrate epithelial differentiation in SSCC, even in the absence of AE1/3 or K903 staining. However, some cases of cutaneous SSCC can only be confirmed ultrastructurally, as up to one-third may not show evidence of epithelial differentiation using an expanded immunohistochemical panel. Topics: Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratin-5; Keratins; Predictive Value of Tests; Skin Neoplasms | 2001 |
Sebaceous carcinoma, trichoblastoma, and sebaceoma with features of trichoblastoma in nevus sebaceus.
A 73-year-old woman had a linear yellowish plaque on the upper part of her right ear since birth. She presented because of the sudden growth of a nodule within the plaque. The plaque was waxy and yellowish, arching around the upper part of the ear. A reddish to yellowish large nodule was seen within the central part of the arc-shaped plaque; in addition, a small pigmented nodule, a small skin-colored nodule, and a few pigmented papules were observed in the anterior half of the arched plaque. Histopathologic examination revealed the large nodule to be sebaceous carcinoma, the small pigmented nodule to be trichoblastoma, the small skin-colored nodule to be sebaceoma with the features of trichoblastoma, a few pigmented papules to be superficial trichoblastomas due to primitive follicular induction, and the linear yellowish plaque to be nevus sebaceus. Although our literature search revealed scanty reports of definite cases of sebaceous carcinoma in nevus sebaceus, the presented case demonstrated the occurrence of sebaceous carcinoma in nevus sebaceus. Malignant neoplasms occurring in nevus sebaceous seem to be extremely rare, but care should be taken when a large nodule suddenly grows in a lesion of nevus sebaceus, especially in older adults. The presented case also suggested a close relation between trichoblastoma and sebaceoma. The cytokeratin staining pattern could not distinguish between sebaceous and follicular neoplasms in our case. Topics: Aged; Carcinoma; Carcinoma, Skin Appendage; Ear Neoplasms; Ear, External; Female; Hamartoma; Humans; Immunohistochemistry; Keratins; Sebaceous Gland Neoplasms; Skin Diseases; Skin Neoplasms | 2001 |
Hemangioblastoma arising in the skin.
Hemangioblastomas are intracranial and intraspinal tumors arising sporadically or in patients with von Hippel-Lindau disease. To date, hemangioblastomas have not been described in the skin. Proliferating clear cells with a variable vascular component are found histologically. These clear cells stain for neuron-specific enolase but not cytokeratin or epithelial membrane antigen, allowing them to be differentiated from metastatic renal cell carcinoma. Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma, Renal Cell; Diagnosis, Differential; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Nose Neoplasms; Phosphopyruvate Hydratase; Skin Neoplasms | 2001 |
Cytokeratins as markers of follicular differentiation: an immunohistochemical study of trichoblastoma and basal cell carcinoma.
Trichoblastoma(s) (TB) are benign neoplasms of follicular differentiation frequently found in nevus sebaceus. Many morphologic features are shared with nodular basal cell carcinoma(s) (BCC), sometimes rendering the differential diagnosis difficult. Because both neoplasms can simulate components of mature hair follicles histologically, we attempted to corroborate this by immunohistochemical examination of cytokeratins and hair keratins differentially expressed in the hair follicle. Trichoblastoma(s) and BCC showed homogenous expression of CK14 and CK17. The innermost cells of the tumor nodules in all TB and in 72% of BCC were positive for CK6hf. Using a specific CK15 antibody, 38% of TB showed a focal labeling and all BCC remained negative; 70% of TB and 22% of BCC expressed CK19. CK8 was expressed by numerous Merkel cells present in all TB but in none of the BCC examined. All type I and II hair keratins tested, (especially hHa1, hHa5, and hHa8) remained negative in all tumors examined. Trichoblastoma(s) and BCC show consistent expression of CK6hf, CK14, and CK17; variable expression of CK15 and CK19; and absence of hair keratins. This indicates a differentiation toward the outer root sheath epithelium or the companion layer and not toward the inner root sheath, matrix, or cortex. Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Diagnosis, Differential; Hair; Humans; Immunohistochemistry; Keratins; Skin; Skin Neoplasms | 2001 |
Pigmented squamous cell carcinoma.
Pigmented squamous cell carcinomas have been reported in the oral and ocular mucosae, but rarely in the skin. We present a case of pigmented squamous cell carcinoma of the forehead and review the current English literature. Pigmented squamous cell carcinoma can be confused with pigmented basal cell carcinomas and melanoma, especially those melanomas associated with pseudoepitheliomatous hyperplasia and should be included in the differential diagnosis of atypical pigmented lesions. Topics: Carcinoma, Squamous Cell; Cell Differentiation; Diagnosis, Differential; Forehead; Humans; Keratins; Male; Melanins; Melanocytes; Melanoma; Melanosis; Middle Aged; Skin Neoplasms | 2000 |
Immunohistochemical detection of cytokeratin and epithelial membrane antigen in leiomyosarcoma: a systematic study of 100 cases.
Although 'aberrant' expression of the epithelial markers, cytokeratin (CK) and epithelial membrane antigen (EMA), in leiomyosarcoma has been described previously, there has not been a study of this phenomenon with clinicopathological correlation in a large series of lesions at different anatomical sites. We investigated systematically the immunohistochemical reactivity for CK and EMA in 100 cases of leiomyosarcoma. CK and EMA were positive in 38% and 44% of the cases, respectively. Although staining was usually focal, extensive immunoreactivity was observed in 11% with CK and 6% with EMA. There was no correlation between immunoreactivity for CK and EMA in leiomyosarcomas and non-neoplastic smooth muscle at the same location. Immunoreactivity for CK and EMA was not correlated with the location, age, sex, histological grade, or histological features, except for more frequent EMA positivity in vascular and uterine tumors than in soft tissue cases. These results indicate that CK and/or EMA-positive leiomyosarcomas do not have distinctive clinicopathological features differing from those of negative cases. However, the considerable frequency of immunoreactivity for these epithelial markers in leiomyosarcoma, occasionally with diffuse and strong immunopositivity, should be recognized as a potentially serious diagnostic pitfall in the differential diagnosis of other malignant spindle cell neoplasms. Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Immunoenzyme Techniques; Keratins; Leiomyosarcoma; Male; Middle Aged; Mucin-1; Muscle, Smooth; Skin Neoplasms; Soft Tissue Neoplasms; Uterine Neoplasms; Vascular Neoplasms | 2000 |
Intraepidermal Merkel cell carcinoma with no dermal involvement.
Cutaneous Merkel cell carcinoma (MCC) typically involves the dermis. Less than 10% of MCC have epidermal involvement. Only one MCC confined exclusively to the epidermis has been previously reported but was not recognized until the lesion recurred with typical MCC in the dermis. We present a case of a wholly intraepidermal pagetoid MCC without dermal involvement in a 74-year-old man with a 2.0-cm solitary verrucous papule on the left index finger. The initial biopsy and complete excision specimens showed marked epidermal hyperplasia, focal prominent squamous cell atypia, and MCC with florid pagetoid spread through the epidermis. There was no evidence of tumor within the dermis. The pagetoid MCC tumor cells showed diffuse cytoplasmic staining with antibodies to cytokeratin 20, and negative staining for chromogranin, neurofilament, S-100, vimentin, HMB45, leukocyte common antigen, and CD3. The cell of origin of MCC is still debated. The existence of an entirely intraepidermal variant of MCC would lend support to the view that MCC is a neoplastic expression of Merkel cells in at least some cases. Dermal-based MCC is a high-grade primary cutaneous neoplasm, but MCC confined exclusively to the epidermis may have a better prognosis. Topics: Aged; Carcinoma, Merkel Cell; Dermis; Epidermis; Fingers; Humans; Immunohistochemistry; Keratins; Male; Skin Neoplasms | 2000 |
Basal cell carcinomas in mice overexpressing Gli2 in skin.
Topics: Animals; Carcinoma, Basal Cell; Cattle; Cell Transformation, Neoplastic; Epidermis; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Hedgehog Proteins; Keratinocytes; Keratins; Kruppel-Like Transcription Factors; Mice; Mice, Transgenic; Neoplasm Proteins; Neoplasms, Multiple Primary; Promoter Regions, Genetic; Proteins; RNA, Messenger; RNA, Neoplasm; Signal Transduction; Skin Neoplasms; Trans-Activators; Transcription Factors; Zinc Finger Protein Gli2 | 2000 |
Pagetoid bowen disease: a report of 2 cases that express cytokeratin 7.
Bowen disease is a variant of squamous cell carcinoma in situ. In some cases a pagetoid growth pattern can be observed with cytologically atypical clear cells arranged singly and in nests. The differential diagnosis of pagetoid Bowen disease includes primarily Paget disease and malignant melanoma in situ, as well as other less common entities. Two cases of pagetoid Bowen disease are described, one in a 65-year-old man with a thigh lesion and the other in a 25-year-old man with a lesion in the penile/scrotal region. Neither patient had clinical evidence of an internal malignant neoplasm. In both cases, the neoplastic cells were positive for cytokeratin (CK) 7 and CK 19 and were negative for CK 18, CK 20, carcinoembryonic antigen, GCDFP-15, c-erbB2, S100, and HMB-45. In aggregate, these findings support the diagnosis of pagetoid Bowen disease. Previously, others have shown that CK 7 is an almost invariable marker of Paget disease. Thus, we report these two cases to illustrate that CK 7 can be expressed by pagetoid Bowen disease and should not be a cause of confusion in the differential diagnosis. Topics: Adult; Aged; Biomarkers, Tumor; Bowen's Disease; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Neoplasm Proteins; Paget Disease, Extramammary; Skin Neoplasms | 2000 |
Cutaneous malignant melanoma associated with extensive pseudoepitheliomatous hyperplasia. Report of a case and discussion of the origin of pseudoepitheliomatous hyperplasia.
We report a case of cutaneous malignant melanoma associated with extensive pseudoepitheliomatous hyperplasia. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and may complicate the diagnosis of cutaneous melanoma. This diagnostic pitfall is important to both recognize and be cognizant of, so as to avoid diagnostic errors. The observation of the pseudoepitheliomatous hyperplasia, in this case with an extensive proliferation of eccrine ducts, provides further evidence that cutaneous pseudoepitheliomatous hyperplasia arises within the eccrine apparatus. Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Diagnosis, Differential; Eccrine Glands; Epithelial Cells; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Melanoma; Skin; Skin Neoplasms | 2000 |
Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion.
Transgenic mice overexpressing insulin-like growth factor-1 (IGF-1) in the basal layer of skin epidermis were generated using the bovine keratin 5 promoter (BK5). Neonatal transgenic mice were slightly smaller at birth and exhibited early ear unfolding, wrinkled and thickened skin, and slightly enlarged ears compared with nontransgenic littermates. Morphological evaluation of the skin revealed that persistent overexpression of IGF-1 in the basal layer of the epidermis resulted in epidermal hyperplasia, hyperkeratosis, and an increased labeling index that persisted in adult mice. Phenotypic changes observed in skin were associated with transgene expression in the basal layer of the epidermis and activation of the IGF-1 receptor. Squamous papillomas (some of which converted to carcinomas) developed in a significant proportion (approximately 50%) of older BK5.IGF-1 mice. Treatment of BK5.IGF-1 transgenic mice with multiple topical applications of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, in the absence of tumor initiation led to the development of additional skin papillomas. Furthermore, treatment of BK5.IGF-1 transgenic mice with an initiating dose of 7,12-dimethylbenz[a]anthracene only led to the formation of additional papillomas in the absence of promotion. In two-stage carcinogenesis experiments, BK5.IGF-1 transgenic mice developed 7-fold more papillomas than nontransgenic littermates. Phosphatidylinositol-3-kinase and protein kinase B (Akt) activities were elevated (3-4-fold), and mitogen-activated protein kinase activity was elevated approximately 1.7-fold in the epidermis of transgenic mice compared with nontransgenic mice. In addition, UV light-induced epidermal apoptosis was significantly suppressed in BK5.IGF-1 transgenic mice. These data suggest that persistent activation of IGF-1 receptor signaling pathways in basal epithelial cells leads to spontaneous tumor promotion and that up-regulation of both mitogenic and cell survival signaling pathways may play an important role in the action of IGF-1 in this model system. Topics: Animals; Cattle; Epidermal Cells; Epidermis; Female; Gene Expression Regulation; Humans; Insulin-Like Growth Factor I; Keratins; Male; Mice; Mice, Transgenic; Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Promoter Regions, Genetic; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptor, IGF Type 1; Recombinant Fusion Proteins; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transgenes | 2000 |
Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently expresses androgen receptor.
Extramammary Paget disease (EPD) is an uncommon cutaneous malignant neoplasm that arises in areas rich in apocrine glands (perineum, vulva, and axilla). Apocrine gland origin or apocrine differentiation of cells of EPD has been suggested. Estrongen, progesterone, and androgen hormone receptors have been reported to exhibit a characteristic pattern of expression in mammary apocrine type carcinomas; however, their expression in EPD has not been elucidated fully. By using immunohistochemical methods, we studied the expression of steroid receptors in EPD on formalin-fixed paraffin-embedded tissue samples from 28 patients with EPD without associated visceral malignant neoplasms or adnexal carcinoma. Androgen receptor (AR) was identified in 15 of 28 cases. The proportion of AR-positive cells varied from 1% to more than 75%; 8 cases expressed AR in more than 10% of cells. Strong AR expression also was seen in the invasive carcinoma arising from 1 case of EPD. All cases lacked immunohistochemically detectable estrogen and progesterone receptors. The immunophenotype characteristic of apocrine carcinomas (AR-positive, estrogen receptor-negative, progesterone receptor-negative) was seen in a substantial proportion of EPD cases. Results suggest that AR expression is a factor in pathogenesis of EPD. This may be important for the therapy of recurrent or invasive disease. Topics: Adult; Aged; Apocrine Glands; Cell Count; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Skin Neoplasms | 2000 |
Spontaneous keratinocyte cell lines representing early and advanced stages of malignant transformation of the epidermis.
A unique series of epidermal cell lines representing different stages of malignant transformation were spontaneously derived from a single adult immunosuppressed individual. Four keratinocyte lines (PM1-4) established from forehead skin are here compared with 4 squamous cell carcinoma (SCC) lines (MET1-4) derived respectively from a primary cutaneous tumour, two local recurrences and a distant metastasis of invasive SCC. Despite altered growth properties, the PM lines retained many features of normal keratinocytes including keratin phenotype, differentiation capacity and non-tumorigenicity in athymic mice. In contrast, from early passage, the MET lines displayed markedly reduced growth requirements, abnormal differentiation, aberrant K18 expression and tumorigenicity in athymic mice. The abnormal keratin profile of individual MET lines closely reflected the keratin phenotype of the tumour of origin. Although unusual HPV types were identified in the original tissue, there was no evidence of persistent virus within any cell line and it appears that HPV is not critical for maintenance of the immortal phenotype. The PM lines were distinctly different from invasive SCC lines and are likely to be useful for studies of mutations important early in neoplastic progression. The SCC series represent primary, recurrent and metastatic carcinoma. Availability of such a series from the same individual will facilitate genetic analysis of the malignant process. Topics: Adaptation, Physiological; Adult; Animals; Carcinogenicity Tests; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cell Line; Cell Transformation, Neoplastic; Epidermis; Face; Humans; Keratinocytes; Keratins; Male; Mice; Mice, Nude; Neoplasm Staging; Neoplasm Transplantation; Papillomaviridae; Skin Neoplasms | 2000 |
Immunohistochemical analysis of cytokeratin expression in reactive eccrine syringofibroadenoma-like lesion: a comparative study with eccrine syringofibroadenoma.
In addition to solitary eccrine syringofibroadenoma (ESFA), there is another type of ESFA which is associated with underlying dermatoses (reactive ESFA-like lesion). Five lesions in 4 patients of reactive ESFA-like lesion were analyzed by an immunohistochemical method using 13 kinds of anti-cytokeratin (CK) antibodies. Two cases of solitary ESFA were also studied by the same procedure for comparison. Suprabasal staining pattern of AE1 and MNF116, which stain CKs 6, 16 and 17, markers of hyperproliferative state, was observed diffusely in 5 lesions of reactive ESFA-like lesions except for focal negative staining in one case, and was observed focally in one case of solitary ESFA. Furthermore, differentiation-specific cytokeratin expression was reduced in 3 of 5 lesions of reactive ESFA-like lesions. Both ESFA and reactive ESFA showed basically similar immunoreactivity suggesting differentiation toward the dermal duct. The above slight difference in immunoreactivity between both lesions may be explained due to inflammatory infiltrates associated with underlying dermatoses. Topics: Adenoma, Sweat Gland; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Immunophenotyping; Keratins; Skin Neoplasms; Sweat Gland Neoplasms | 2000 |
A cytokeratin profile of canine epithelial skin tumours.
The reactions of a number of epithelial skin tumours in dogs to a panel of monoclonal antibodies against different human cytokeratins (CKs) were examined immunohistochemically, the purpose being to detect a specific CK profile. CK 6 was present in all epithelial skin tumours with the exception of pilomatrixoma. CK 14 was found in basal cell-derived neoplasias and in sebaceous and perianal gland tumours. CK 10/11 was restricted to spinous cell-derived tumours and CK 8/18 was limited to sweat gland tumours. Topics: Animals; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Humans; Immunohistochemistry; Keratins; Skin; Skin Neoplasms | 2000 |
Immunohistopathologic characterization of a dermal melanocytoma-acanthoma in a German Shepherd Dog.
A cutaneous melanocytoma-acanthoma in a 2-year-old female German Shepherd Dog was characterized by the presence of two populations of neoplastic cells: epithelial and melanocytic. The epithelial component consisted of nests of well-differentiated stratified squamous epithelium closely associated with neoplastic melanocytes. The epithelial cells immunoreacted with both monoclonal and polyclonal anti-cytokeratin antibodies, and immunoreaction to S-100 protein and vimentin was observed in the melanocytic cells. This rare pigmented skin neoplasm of the dog apparently has a benign behavior. Topics: Animals; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Female; Keratins; Neoplasms, Glandular and Epithelial; Nevus, Blue; Skin Neoplasms | 2000 |
Primary mucinous carcinoma of the scalp.
Primary cutaneous mucinous carcinoma (MC) is a rare epithelial neoplasm derived from the sweat glands. Herein, we report a case of MC located on the head. A 66-year-old woman underwent excision of a nodular tumor with a reddish brown surface on the left parietal region. Histopathology revealed a neoplasm extending from the reticular dermis into the subcutaneous fat. The tumor cell aggregates showed cribriform and solid lobules and were embedded in lakes of mucin, separated by thin, fibrous septae. Focally single neoplastic cells were arranged in an Indian-file pattern. The tumor cells displayed an eosinophilic cytoplasm, large basophilic nuclei and some discrete nuclear atypia. Vascular spaces, filled by densely packed erythrocytes between the septae, were also observed. We compared the mucinous component with the tumor cell and the stromal component by light microscopy. Analyzing the tumor by an image analysis system in Alcian-blue-stained serial sections, we found the averaged total tumor area measuring 99.7 mm(2). The area of the mucinous component measured 92.4 mm(2), that of the tumor cells 3.7 mm(2) and that of the stromal component 3.6 mm(2). The extensive checkup of the patient disclosed no evidence for a further malignant neoplasm. After excision of the tumor an adjuvant radiotherapy was performed. The patient was free of recurrence and metastatic spread of the mucinous carcinoma during a 4-year follow-up. Topics: Adenocarcinoma, Mucinous; Aged; Female; Humans; Immunohistochemistry; Keratins; Mucin-1; Scalp; Skin; Skin Neoplasms | 2000 |
Primary cutaneous carcinoid tumour.
Topics: Carcinoid Tumor; Chromogranin A; Chromogranins; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Serotonin; Skin Neoplasms | 2000 |
Brown bullhead (Ameiurus nebulosus) skin carcinogenesis.
Alternative models using fish species have been tested in liver toxicity and carcinogenesis bioassays. Similar models have not been developed for skin. The brown bullhead (Ameiurus nebulosus) has shown potential as a model for skin carcinogenesis studies due to its sensitivity to environmental chemical pollutants. The present study is an initial morphologic and biochemical characterization of the normal and neoplastic brown bullhead skin to assess its suitability as a model of skin carcinogenesis. Brown bullhead were removed from Back River in the Chesapeake Bay region, an area historically polluted with heavy metals and polycyclic aromatic hydrocarbons. Histology, histochemistry, and electron microscopy were used to stage the morphologic development and progression of neoplasia in skin. The distribution of keratin, a family of structural proteins with altered expression in mammalian tumorigenesis, was analyzed with one and two dimensional gel electrophoresis and nitrocellulose blots of extracts from normal skin. Keratin expression in skin and other organs was also assessed with immunohistochemistry using AE1, AE3, and PCK 26 antibodies, and the proliferation index in skin and neoplasms with PCNA antibody. Skin lesions appeared to progress from hyperplasia through carcinoma, and the proliferation index was increased in papilloma. Also in papilloma, intercellular interdigitations appeared increased and desmosomes decreased which may in future studies correlate with changes in expression of other molecular markers of neoplastic progression. Both Type I and Type II keratin subfamilies were detected in skin using gel electrophoresis with the complimentary keratin blot-binding assay. For further development of the brown bullhead model, future studies can compare and relate these baseline data to alterations in expression of keratin and other markers in fish neoplasms and to molecular events which occur in man. Topics: Animals; Carcinogenicity Tests; Electrophoresis, Polyacrylamide Gel; Epithelium; Fishes; Histocytochemistry; Hydrocarbons, Aromatic; Hyperplasia; Keratins; Lip; Metals, Heavy; Microscopy, Electron; Papilloma; Proliferating Cell Nuclear Antigen; Skin Neoplasms; Water Pollutants, Chemical | 2000 |
Benign transport of breast epithelium?
Topics: Axilla; Biopsy; Breast; Breast Neoplasms; Carcinoma; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Melanoma; Neoplasm Seeding; Skin Neoplasms | 2000 |
Pagetoid dyskeratosis of the prepuce. An incidental histologic finding resembling extramammary Paget's disease.
Pale cells resembling those of paget's disease have been seen as an incidental finding within the epidermis in a variety of benign papules most commonly located in intertriginous areas. This lesion, called pagetoid dyskeratosis, is considered a reactive process in which a small part of the normal population of keratinocytes is induced to proliferate. Among the inductors friction is suspected. As far as we know, these cells have not been reported in the penis.. Here we describe the location of the lesion in the foreskin and the incidence of this lesion in a group of 281 unselected patients surgically treated for phimosis. In selected cases histochemical staining and immunohistochemical studies were performed.. Pagetoid dyskeratosis was found in 105 cases (37.4%) but only in 5 cases (1.8%) the lesion was conspicuous. The cells of pagetoid dyskeratosis show an immunohistochemical profile different from the surrounding keratinocytes characterized by premature keratinization. Pagetoid dyskeratosis cells must be distinguished from the artefactual clear cells of the epidermis, from reactive melanocytes, and from pale-cell acanthosis. In cases in which pagetoid dyskeratosis shows a florid expression there is a hazard of overdiagnosis to the patient. The main differential diagnosis includes extramammary Paget's disease, pagetoid squamous cell carcinoma in situ, epidermotropic metastasis, superficial spreading malignant melanoma, clear cell papulosis, and penile koilocytoses.. The pathologist should be familiar with the histologic features of pagetoid dyskeratosis in the foreskin in order to avoid misdiagnosis and unnecessary treatment. Routine histologic study is usually sufficient to identify the lesion. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Division; Child; Child, Preschool; Diagnosis, Differential; Humans; Infant; Infant, Newborn; Keratinocytes; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Penis; Phimosis; Skin Neoplasms | 2000 |
Ber EP4 and epithelial membrane antigen aid distinction of basal cell, squamous cell and basosquamous carcinomas of the skin.
Seventy-five skin tumours were studied to investigate the value of immunohistochemistry in differentiating basal cell, squamous cell and basosquamous carcinomas of the skin.. Archived paraffin-embedded tissue samples of basal cell carcinomas (n = 39), squamous cell carcinomas (n = 23) and basosquamous carcinomas (n = 13) were stained immunohistochemically using a panel of antibodies. All of the basal cell carcinomas stained positively for Ber EP4, in contrast to the group of squamous cell carcinomas, that showed no staining. Basosquamous carcinomas all showed at least some areas of Ber EP4 positivity. None of the basal cell carcinomas, but most of the squamous cell carcinomas (22 of 23) expressed epithelial membrane antigen (EMA). Only one of the basosquamous carcinomas expressed EMA positivity focally. CAM 5.2, carcinoembryonic antigen (CEA) and 34betaE12 antibodies lacked specificity in relation to the different tumour types.. Distinction of basal and squamous cell carcinomas of the skin can be readily achieved with routine immunohistochemistry using Ber EP4 and EMA. Identification of basosquamous carcinoma is also facilitated with this method. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Surface; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Skin Neoplasms | 2000 |
Constitutive expression of erbB2 in epidermis of transgenic mice results in epidermal hyperproliferation and spontaneous skin tumor development.
The erbB family of receptor tyrosine kinases, which consists of the epidermal growth factor receptor (EGFr/erbB1), erbB2 (neu), erbB3 and erbB4, has been shown to be important for both normal development as well as neoplasia. The expression of rat erbB2 was targeted to the basal layer of mouse epidermis with the bovine keratin 5 promoter. Overexpression of wild type rat erbB2 in the basal layer of epidermis led to alopecia, follicular hyperplasia and sebaceous gland enlargement as well as hyperplasia of the interfollicular epidermis. Spontaneous papillomas, some of which converted to squamous cell carcinomas, arose in homozygous erbB2 transgenic mice as early as 6 weeks of age with >90% incidence by 6 months. Analysis of several proliferation/differentiation markers indicated that erbB2 overexpression led to epidermal hyperproliferation and a possible delay in epidermal differentiation. Transgenic mice were also hypersensitive to the proliferative effects of the skin tumor promoter, 12-0-tetradecanoylphorbol-13-acetate (TPA) and were more sensitive to two-stage carcinogenesis. Elevations in EGFr and erbB2 protein as well as erbB2:EGFr and erbB2:erbB3 heterodimers were observed in skin of the erbB2 transgenic mice. Phosphotyrosine levels of the EGFr, erbB2 and erbB3 proteins were also elevated. These results indicate an important role for erbB2 signaling in epidermal growth, development and neoplasia. Oncogene (2000) 19, 4243 - 4254 Topics: Animals; Carcinogens; Carcinoma, Squamous Cell; Cattle; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Cocarcinogenesis; Dimerization; Disease Progression; Epidermis; ErbB Receptors; Female; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Genes, ras; Genes, Synthetic; Hyperplasia; Keratins; Male; Mice; Mice, Inbred ICR; Mice, Transgenic; Neoplasm Proteins; Papilloma; Phosphorylation; Promoter Regions, Genetic; Protein Processing, Post-Translational; Rats; Receptor, ErbB-2; Receptor, ErbB-3; Recombinant Fusion Proteins; Signal Transduction; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transgenes | 2000 |
A rippled-pattern trichoblastoma: an immunohistochemical study.
Since the first description by Hashimoto et al., there have been only a few case reports of rippled-pattern tricogenic tumor. In addition, there are no reports on detailed immunohistochemical analyses of this rare neoplasm. We describe here an additional case of rippled-pattern trichogenic tumor with a special reference to its immunohistochemical features.. A nodule arising on the occipital area of a 62-year-old Japanese woman was histologically and immunohistochemically investigated.. Histopathologically, the lesion contained various-sized lobular nests, which consisted of oval to elliptical shaped basaloid cells without any atypia and were embedded in the collagenous stroma. Some elongated basaloid cells were arranged in a palisading fashion forming parallel rows of epithelial ribbons in a rippled-pattern. Cytokeratin (CK) immunohistochemistry showed constant expressions of CK1/5/ 10/14, CK5/8, CK14 and CK7, and focal expressions of CK17 and CK19 in the basaloid cells, suggesting a keratin phenotypical similarity to the cells in small nodular type trichoblastoma.. The present tumor is a variant of trichoblastoma, and considered to be in close association with the outer root sheath and/ or follicular germinative cells. Topics: Biomarkers, Tumor; Female; Hair Diseases; Hair Follicle; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Neoplasm Proteins; Neoplasms, Basal Cell; Skin Neoplasms | 2000 |
Differentiation between merkel cell carcinoma and malignant melanoma: An immunohistochemical study.
Although Merkel cell carcinoma (MCC) exhibits specific clinical and histologic features, differentiation from other cutaneous neoplasms, such as lymphoma, metastatic oat cell carcinoma and malignant melanoma (MM), may sometimes be difficult.. The aim of our study was to immunohistochemically differentiate MCC from MM.. Paraffin sections from 6 cases of primary MCC and 6 cases of primary MM were investigated. For immunostaining, the APAAP method was used.. Neuron-specific enolase was positive in all cases of MCC, as well as in 2 cases of MM. Marked positivity for cytokeratins 18, 20 and chromogranin A was observed in the MCC group, whereas a complete absence of expression of these three markers was noted in the MM group. Immunostaining with HMB45 and NKI/C3 was positive in all cases of MM and negative in all cases of MCC. S-100 protein was positive in all but 1 case of MM. In contrast, only 1 case of MCC reacted with S-100 protein.. Our results underline the role of immunohistochemistry in the diagnosis and differential diagnosis of MCC. In particular, the combination of neuron-specific enolase, cytokeratins 18, 20 and chromogranin A positivity for MCC and HMB45, NKI/C3 and S-100 protein positivity for MM is of great value in the distinction between these two cutaneous neoplasms. Topics: Antigens, Neoplasm; Carcinoma, Merkel Cell; Chromogranin A; Chromogranins; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins; Phosphopyruvate Hydratase; S100 Proteins; Skin Neoplasms | 2000 |
Cooperation between Ha-ras and fos or transforming growth factor alpha overcomes a paradoxic tumor-inhibitory effect of p53 loss in transgenic mouse epidermis.
To investigate the role of loss of the p53 tumor suppressor gene in skin carcinogenesis, p53 knockout (p53(-/-)) mice were mated with transgenic mice coexpressing v-Ha-ras, v-fos, or human transforming growth factor alpha (TGFalpha) exclusively in the epidermis by using human keratin 1 (HK1)-based vectors (HK1.ras/fos, HK1.ras/alpha, and HK1.fos/alpha). HK1.ras/fos and HK1.ras/alpha mice displayed epidermal hyperplasia and autonomous benign papillomas to an identical degree between p53(+/+) and p53(+/-) genotypes. However, HK1.ras/fos mice with the p53(-/-) genotype were born with papillomatous skin and died soon after birth. HK1.ras/alpha-p53(-/-) mice also exhibited an increased epidermal hyperplasia, and, similar to HK1.ras/alpha mice with p53(+/+) and p53(+/-) genotypes, these mice rapidly developed spontaneous and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced papillomas. These results are in contrast to our previous observation that, HK1.ras, HK1.fos, and HK1.TGFalpha transgenic mice with the p53(-/-) genotype display an unexpected delay in both spontaneous and TPA-promoted papilloma formation compared with mice with p53(+/+) and p53(+/-) genotypes. Taken collectively, our mating experiments between HK1 oncogenic transgenic mice and p53 knockout mice may identify a backup system that effectively compensates for p53 loss. Activation of multiple oncogenes not only partly overcomes such compensation but also synergizes with p53 loss. However, HK1.fos/alpha-p53(-/-) mice failed to exhibit either an increased newborn epidermal hyperplasia or an accelerated spontaneous or TPA-induced papillomas, suggesting that certain combinations of oncogenes, such as with activated Ha-ras, are required for this process. Because neither spontaneous nor TPA-elicited papillomas in p53(-/-) mice progressed to malignancy, additional genetic insults appear to be required for malignant progression. Topics: Animals; Carcinogens; Epidermis; Female; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genes, fos; Genes, p53; Genes, ras; Keratins; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Transgenic; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transforming Growth Factor alpha | 2000 |
Trisomy 6 in Merkel cell carcinoma: a recurrent chromosomal aberration.
We retrospectively investigated 17 cases of primary and metastasizing Merkel cell carcinomas (MCC) from 14 patients using chromosomal in-situ hybridization (CISH) to study the occurrence of trisomy 6 in these lesions.. Histological diagnosis on all tumour samples was obtained on haematoxylin and eosin stained sections. Immunohistochemistry was performed with antibodies against pancytokeratin (CAM 5.2), cytokeratin 20 (CK20), MIC2 antigen (CD99), neuron-specific enolase (NSE), and chromogranin A (chrA). Sections (4 microm) of the paraffin-embedded tumours were analysed with alpha-satellite centromeric probes for chromosome 6 or 17 using CISH. The signal was amplified by the Tyramide Signal Amplification (TSA) assay. Immunohistochemically, the tumours showed the same general epithelial neuro-endocrine pattern: 11/13 expressed cytokeratin 20, and 47% exhibited trisomy 6, with no significant difference between primary and metastatic lesions. Incomplete follow-up data did not allow us to establish a prognostic value of trisomy 6, however, this aberration might be an additional diagnostic tool in distinguishing MCC from other small round blue cell tumours.. CISH seems to be a promising adjunctive method to diagnose Merkel cell carcinoma. Trisomy 6 should be investigated more closely in these cases, as has been done for chromosomes 1 and 11. Of particular interest would be identification of modifications in proto-oncogene(s) located on chromosome 6. Topics: Aged; Aged, 80 and over; Biomarkers; Carcinoma, Merkel Cell; Chromogranin A; Chromogranins; Chromosomes, Human, Pair 6; Cytogenetics; Female; Humans; In Situ Hybridization, Fluorescence; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Proto-Oncogene Mas; Skin Neoplasms; Trisomy | 2000 |
Cytokeratin staining in Merkel cell carcinoma: an immunohistochemical study of cytokeratins 5/6, 7, 17, and 20.
Merkel cell carcinoma is an aggressive cutaneous neoplasm with neuroendocrine differentiation that carries a poor prognosis. Its homogeneous morphology is easily confused with lymphoma, leukemia, metastatic small cell carcinoma, and poorly differentiated cutaneous malignancies. Histopathologic diagnosis frequently requires support by immunohistochemistry. The authors investigated cytokeratins (CKs) 5/6, 7, 17, and 20 staining in paraffin sections of 26 Merkel cell carcinomas to expand the knowledge of the CK staining profile of this entity. Reactivity with anti-CK 20 was demonstrated in 23 of 26 Merkel cell carcinomas (88%). All three CK 20-negative tumors showed punctate staining with anti-keratin CAM5.2. Six of 26 tumors (23%) were positive for CK 7, a finding not previously reported. The staining patterns for both CKs 20 and 7 ranged from punctate (perinuclear) to localized (confined to half of the cytoplasm) to diffuse. Punctate CK 20 staining was seen in 17 of 26 cases but was the predominant pattern in only 10 cases. Antibodies to CKs 5/6 and 17 were each negative in the 13 cases for which these stains were performed. Both the positive and negative elements of the CK profile of this distinctive neoplasm provide additional useful diagnostic information for the differential diagnosis between Merkel cell carcinoma and other carcinomas that may simulate it. The authors note that the classically described perinuclear dotlike keratin staining pattern is not universally seen with CK 20 and that CK 7 staining may be seen in a subset of Merkel cell carcinomas. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Merkel Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Skin Neoplasms | 2000 |
Malignant basal cell tumor in a Djungarian hamster.
A malignant basal cell tumor was found in the skin of the abdomen of a female Djungarian hamster of unknown age and weighing 40 g. Histologically, the tumor mass was composed of cells resembling the basal cells of the epidermis, and these cells exhibited solid type proliferation. In the tumor tissue and necrotic foci, horn cysts were observed. Immunohistochemically, cytokeratin was present in the tumor cells and horncysts. By electron microscopic examination, the tumor cells had scanty cell organelles and a few desmozomes. This paper describes a rare malignant basal cell tumor in a Djungarian hamster. Topics: Animals; Cell Division; Cricetinae; Female; Keratins; Microscopy, Electron; Neoplasms, Basal Cell; Phodopus; Rodent Diseases; Skin Neoplasms | 1999 |
Cytokeratin expression in trichoblastic fibroma (small nodular type trichoblastoma), trichoepithelioma and basal cell carcinoma.
Classical trichoblastic fibroma or small nodular type trichoblastoma (Ackerman) is a rare tumour. This tumour, trichoepithelioma and basal cell carcinoma (BCC) have some overlapping histopathological features. There are only a few reports on immunohistochemical studies in large series of these three neoplasms. We investigated immunostaining patterns of 10 different anticytokeratin (CK) antibodies and several other markers in these neoplasms, comparing them with the patterns in normal adult and fetal skin. In trichoblastic fibroma (three cases), CK1/5/10/14, CK7, CK8/18, CK10/11, CK14, CK17 and CK19 were expressed in the basaloid nests, and CK6 and involucrin were detected in the inner layers of keratinous cysts. Trichoepithelioma (seven cases) expressed CK1/5/10/14, CK8/18, CK14, CK17 and CK19 in the basaloid nests, and CK6, CK10, CK10/11 and involucrin were positive in the keratinous cysts. However, no CK7 expression was observed. Solid and keratotic types of BCC (29 cases) expressed CK1/5/10/14, CK7, CK8/18, CK14, CK17 and CK19 in the basaloid nests. The keratinous cysts in BCC were stained with anti-CK6, CK10, CK10/11 and involucrin antibodies. Coupled with the expression of CK8/18, CK17 and CK19 in the outer root sheath of the adult hair follicle, these three neoplasms shared a keratin phenotype characteristic of the outer root sheath. Judging from our immunohistochemical results, trichoblastic fibroma and BCC cannot be differentiated by their patterns of CK expression. The expression of CK7, which is noted in fetal hair follicles, trichoblastic fibroma and BCC, suggests the presence of subpopulations that retain fetal phenotypic characteristics in these two neoplasms. Although the current concept regards trichoepithelioma and trichoblastic fibroma as a single tumour group, the lack of CK7 expression in trichoepithelioma supports the notion that the two are different. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin; Skin Neoplasms | 1999 |
Electron microscopic in situ DNA nick end-labeling in combination with immunoelectron microscopy.
We describe an in situ DNA nick end-labeling method that can be performed at the electron microscopic level and can also be combined with immunoelectron microscopy. As the materials, we used skin tissues from normal skin and from Bowen's disease that had been cryofixed, freeze-substituted, and embedded in Lowicryl K11M resin. Ultrathin sections were cut and incubated with a reaction buffer containing digoxigenin-dUTP and terminal deoxynucleotidyl transferase. Digoxigenin nucleotides were labeled with anti-digoxigenin antibodies conjugated with colloidal gold. Specific signals were detected in the condensed chromatin of differentiated epidermal cells and hair follicles in normal skin and of dyskeratotic cells in Bowen's disease. The labeling density over chromosomal areas of apoptotic cells was significantly higher than that over chromosomal areas of mitotic cells or cytoplasmic areas. Ultrastructure was well preserved and double staining with an anti-keratin antibody was also successfully performed. This simple method has a wide range of applications to identify the nature of apoptotic cells and explore the mechanisms of apoptosis. Topics: Adult; Apoptosis; Bowen's Disease; Fetus; Humans; In Situ Nick-End Labeling; Keratins; Microscopy, Electron; Microscopy, Immunoelectron; Skin; Skin Neoplasms | 1999 |
Expression of human hair keratin basic 1 in pilomatrixoma. A study of 128 cases.
Hard keratins are expressed in normal hair and nails, and are characterized by a higher cysteine content than cytokeratins. Previous studies have suggested a coexpression of hard keratins and cytokeratins in pilomatrixoma, a benign follicular tumour which could originate from the hair matrix. Human hair keratin basic 1 (hHb1) is a newly characterized hair keratin which is expressed specifically by cortical cells of the normal hair shaft. A preliminary study has suggested that hHb1 could be expressed in pilomatrixoma. In order to confirm this hypothesis, we have studied a series of 128 pilomatrixomas by in situ hybridization, using a 35S-labelled hHb1-specific probe. The anti-sense probe was used as a negative control. Among these pilomatrixomas, six were early cases, 60 were classified into the intermediate stage (either fully developed or early regressive cases) and 62 were late regressive tumours made of shadow cells only. Forty-seven tumours showed hHb1 expression (37%), all being intermediate stage pilomatrixomas. The areas positively stained by the probe were band-like structures made of transitional cells only, which were very close to cells showing tricholemmal keratinization features. Neither the basophilic matrix cells nor the shadow cells expressed hHb1. Our results suggest that pilomatrixomas can differentiate towards cortical cells during their maturation process, as this keratin is specifically expressed in the cortex of the normal hair shaft. These data are consistent with previous studies which showed the expression of a hard keratin group in transitional cells by immunohistochemistry. The histogenesis of basophilic cells of pilomatrixoma is controversial, but it is likely that transitional cells represent an equivalent of the hair cortex. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Child; Child, Preschool; Female; Hair Diseases; Humans; In Situ Hybridization; Infant; Keratins; Male; Middle Aged; Pilomatrixoma; Skin Neoplasms | 1999 |
Expression of interferon-beta is associated with growth arrest of murine and human epidermal cells.
The cytokine interferon-beta is a regulator of cell replication and function, including invasion and induction of angiogenesis. The goal of this study was to determine whether the expression of interferon-beta by cells in the epidermis correlated with terminal differentiation. In situ hybridization analysis and immunohistochemical staining of formalin-fixed, paraffin-embedded specimens of normal human and murine epidermis and human and murine skin tumors of epithelial origin revealed that only differentiated, nondividing cells of the epidermis expressed interferon-beta protein. Keratinocyte cultures established from the epidermis of 3 d old mice were maintained under conditions permitting continuous cell division or induction of differentiation. Continuously dividing cells did not produce interferon-beta whereas nondividing differentiated cells expressing keratin 1 did. Growth-arrested, undifferentiated keratinocytes also expressed interferon-beta protein. Neutralizing interferon-beta in the culture medium inhibited differentiation, but the addition of exogenous interferon-beta did not stimulate differentiation. These data indicate that interferon-beta is produced by growth-arrested, terminally differentiated keratinocytes. Topics: Animals; Antibodies; Calcium; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cells, Cultured; Epidermal Cells; Epidermis; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Interferon-beta; Keratin-14; Keratinocytes; Keratins; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Transgenic; Skin Neoplasms; Time Factors | 1999 |
Cytokeratin 15 expression in trichoepitheliomas and a subset of basal cell carcinomas suggests they originate from hair follicle stem cells.
Trichoepitheliomas and many basal cell carcinomas appear to arise from the hair follicle, and in particular from the hair follicle bulge. This histogenesis is suggested from both morphological and immunohistochemical studies on tumor cells and stroma. Epithelial stem cells are thought to be important in tumorigenesis, and we previously localized a population of stem cells to the bulge area of the outer root sheath. We recently identified an anti-CD8 monoclonal antibody (DAKO clone C8/144B) that cross-reacts with cytokeratin 15 (K15), and serves as a specific marker for the bulge. In this study, we screened a series of trichoepitheliomas (n=13), basal cell carcinomas (n=37) and a variety of other skin tumors with this antibody. All trichoepitheliomas (100%) showed keratin 15 expression, while only a subset of basal cell carcinomas (27%) was K15-positive. Epidermal tumors, including squamous cell carcinomas, were K15-negative. Tumors of follicular derivation such as proliferating trichilemmal cysts were also K15-positive, while others such as pilomatricoma were K15-negative. Expression of K15 in trichoepitheliomas, some basal cell carcinomas and other follicular tumors suggests that these tumors are related to hair follicle stem cells in the bulge. Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Basal Cell; Hair Follicle; Humans; Immunoenzyme Techniques; Keratin-15; Keratins; Neoplasms, Basal Cell; Skin Neoplasms; Stem Cells | 1999 |
Dermal squamo-melanocytic tumor: a unique biphenotypic neoplasm of uncertain biological potential.
We report four cases of an unusual cutaneous squamo-melanocytic neoplasm with histological features of malignancy and uncertain biological potential. These tumors developed on the face of middle-aged and older adults. Clinically, a purple-black nodule ranged in size from 3 to 10 mm in maximum diameter. After complete excision, neither recurrence nor metastasis has been observed (mean follow-up time, 3.25 years). Histologically, a discrete dermal nodule surrounded by a fibroblastic stroma was composed of large islands of mitotically active atypical epithelioid cells. The nodule was not connected to the epidermis in three of four cases. Two types of cells were either diffusely admixed or clustered in small groups within the nodule. Small, atypical, epithelioid cells containing finely granular brown pigment, proven to be melanin, constituted the first cell type. The second type consisted of atypical squamoid cells, some with abundant pink cytoplasm, giving rise to squamous pearls. A lentigo maligna was present in one case. The remaining three cases had neither significant intraepidermal melanocytic nor keratinocytic atypia. Immunohistochemical studies indicated that the melanin-containing epithelioid cells expressed S-100 antigens, and the squamoid cells expressed cytokeratins. A small population of tumor cells did not label with either of the antibodies. These four tumors (along with a previously reported, apparently identical tumor arising in the setting of lentigo maligna) represent a unique biphasic dermal neoplasm with histological features of malignancy but, at this time, uncertain biological behavior. Although none have recurred or metastasized, the follow-up time is too short in our estimation to guarantee a benign course. These neoplasms are easily recognized by their characteristic features. Further follow-up evaluations should allow determination of their biologic potential. Topics: Adult; Aged; Antigens, Neoplasm; Carcinoma, Squamous Cell; Face; Female; Humans; Hutchinson's Melanotic Freckle; Immunohistochemistry; Keratins; Male; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; S100 Proteins; Skin Neoplasms | 1999 |
Basal cell carcinoma possibly originates from the outer root sheath and/or the bulge region of the vellus hair follicle.
In the present study, the immunophenotype of basal cell carcinoma was analysed in comparison with human vellus hair follicular keratinocytes. We also established the lectin binding profile of basal cell carcinoma and human vellus hair follicles (VHF), using several lectins with different sugar specificities. Our findings showed an almost identical immunohistochemical profile for basal cell carcinoma and the suprabulbar region of the outer root sheath of VHF, whereas other follicular compartments such as the bulbar, the isthmus or the supraseboglandular regions did not correlate. In particular, homogeneous and constant expression of the basal differentiation markers CK 5 and CK 14 were found in both specimen, with no expression of the simple epithelium type keratin CK 8 and the suprabasal differentiation markers CK 1 and CK 10. CK 19 showed variable expression in basal cell carcinoma, with constant expression in the outer root sheath and the follicular bulge regions, but was always absent in interfollicular epidermal keratinocytes. In addition, the lectin binding profiles of basal cell carcinoma and the outer root sheath in the suprabulbar region of human VHF were comparable, with the presence of binding sites for PNA, Con A and WGA. These findings provide evidence for a histochemical relationship between basal cell carcinoma and the follicular epithelium of VHF which is closer than that with the epidermis, and suggest its possible origin from or possibly its differentiation pattern towards the cells of the outer root sheath and/or the follicular bulge region of the VHF. Topics: Carcinoma, Basal Cell; Hair Follicle; Histocytochemistry; Humans; Keratinocytes; Keratins; Lectins; Neoplasm Proteins; Skin Neoplasms | 1999 |
The correlation of the metastatic ability with keratin expression in cultured murine melanoma cell lines, B16-F1 and-F10.
Keratin is an intermediate filament that is a major structural protein of epithelial cells. Until now, the expression of keratin in melanoma cells has not been well understood. Recently, it has been reported that keratin expression is correlated with invasive and metastatic behavior in a variety of cell types. We report keratin expression in cultured murine melanoma cell lines B16-F1 (low incidence of lung colonization) and F10 (high incidence of lung colonization) using an aqueous solution (10 mM Tris-HCl (pH 7.4)/10 mM EDTA/phenylmethyl sulphonyl fluoride (PMSF, 10 micrograms/ml). By comparing these two cell lines, we investigated whether differences in keratin expression can influence the metastatic ability of tumor cell lines in vitro. However, no remarkable differences in keratin expression were found in these cell lines. Topics: Animals; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Gene Expression Regulation, Neoplastic; Keratins; Melanoma, Experimental; Mice; Skin Neoplasms; Tumor Cells, Cultured | 1999 |
Myoepitheliomas of the skin and soft tissues. Report of 12 cases.
We describe 12 cutaneous and soft tissue myoepitheliomas, most of them in elderly patients. Morphologically the cutaneous and soft tissue myoepitheliomas revealed the same spectrum as their salivary gland counterparts. They were composed of a mixture of spindle, epithelioid and clear myoepithelial cells. Immunohistochemically they were positive to keratins and S-100 protein and reacted inconsistently with antibodies to smooth muscle actin. Morphologically they lacked any folliculo-sebaceous or apocrine differentiation. We believe that they are related to the eccrine type of cutaneous mixed tumours. Most cases had a benign behaviour, but 1 tumour metastasized, and the patient died of the tumour. Myoepitheliomas of soft tissues should be distinguished from other neoplasms with epithelial differentiation and from ossifying fibromyxoid tumour of soft parts, parachordoma and extraskeletal myxoid chondrosarcoma. Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myoepithelioma; S100 Proteins; Skin Neoplasms; Soft Tissue Neoplasms | 1999 |
An immunohistochemical study of the apocrine type of cutaneous mixed tumors with special reference to their follicular and sebaceous differentiation.
An immunohistochemical analysis of 8 cases of the apocrine type of cutaneous mixed tumor is reported. Histologically, 7 cases of the tumor were suggested to have follicular and/or sebaceous differentiation. Carcinoembryonic antigen (CEA), epithelial membrane antigen and gross cystic disease fluid protein-15 were present in the inner surface and/or in the luminal cell bodies of the tubular structures. CEA and non-specific cross-reacting antigen were also detected in the keratinous cysts. Positive reactions for S-100 protein and vimentin were observed in the solid nests, the outer layer of the tubular structures and some stromal cells. However, smooth muscle actin was only focally expressed in the outer cells of the tubular nests in one case. Involucrin was positive in the inner layers of the keratinous cysts. Various staining patterns were observed in the keratin immunohistochemistry. The solid nests showed heterogeneous expressions of CK1/5/10/14, CK7, CK10/11, CK14, CK8/18 and CK19. The inner cells of the tubular structures were constantly positive for CK7, CK8/18 and CK19, and heterogeneously for CK1/5/10/14, CK10/11 and CK14. The outer cells were heterogeneously positive for CK1/5/10/14 and CK14. The keratinous cysts showed positive reactions for CK1/5/10/14 throughout the whole cell layers, and for CK14 in the basal layer. The inner layers in some keratinous cysts expressed CK6, CK10/11 and CK17, but only CK10 in others. CK13 was positively stained in the transitional portion between the matricial structure and the column of shadow cells in the cyst wall in only one case. When compared with the immunohistochemistry of the normal skin, the apocrine type of cutaneous mixed tumor can show various immunophenotypical patterns similar to those of entire structures of hair follicles, sebaceous glands and all components of apocrine glands, that is to say, the folliculosebaceous-apocrine unit. Topics: Adenoma, Pleomorphic; Adipocytes; Adult; Aged; Aged, 80 and over; Apocrine Glands; Biomarkers, Tumor; Cell Differentiation; Epidermis; Female; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Melanocytes; Middle Aged; Sebaceous Glands; Skin Neoplasms; Stromal Cells; Sweat Gland Neoplasms | 1999 |
The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin.
Gene knockout technology has provided a powerful tool for functional analyses of genes expressed preferentially in a particular tissue. Given marked similarities between human and mouse skin, such studies with epidermally expressed genes have often provided valuable insights into human genetic skin disorders. Efficient silencing of a specified gene in a temporally regulated and epidermal-specific fashion could extend functional analyses to broadly expressed genes and increase the categories of human skin disorders to which parallels could be drawn. We have generated transgenic mice expressing Cre and a fusion protein between Cre recombinase and the tamoxifen responsive hormone-binding domain of the estrogen receptor (CreER(tam)) under the control of the human keratin 14 (K14) promoter. This promoter is strongly active in dividing cells of epidermis and some other stratified squamous epithelia. With K14-Cre, transgenic embryos recombine genetically introduced loxP sequences efficiently and selectively in the genomes of keratinocytes that reside in embryonic day 14.5 skin, tongue, and esophagus. With K14-CreER(tam), postnatal transgenic mice show no Cre activity until tamoxifen is administered. If orally administered, tamoxifen activates keratinocyte-specific CreER(tam), allowing recombination of loxP sequences in epidermis, tongue, and esophagus. If topically administered, tamoxifen allows recombination in the area of skin where tamoxifen was applied. Finally, we show that epidermal cells harboring a Cre-dependent rearranged genome persist for many months after tamoxifen application, indicating that the epidermal stem cell population has been targeted efficiently. These tools now pave the way for testing the functional role of different somatic mutations that may exist in mosaic disorders of the skin, including squamous and basal cell carcinomas. Topics: Animals; Epidermis; Gene Expression Regulation; Gene Targeting; Histocytochemistry; Integrases; Keratin-14; Keratinocytes; Keratins; Mice; Mice, Transgenic; Promoter Regions, Genetic; Receptors, Estrogen; Recombinant Fusion Proteins; Recombination, Genetic; Skin Neoplasms; Stem Cells; Tamoxifen; Viral Proteins | 1999 |
Tongue metastasis from a malignant diffuse mesothelioma of the pleura: report of a case.
Topics: Epithelial Cells; Facial Neoplasms; Follow-Up Studies; Humans; Keratins; Male; Mesothelioma; Middle Aged; Pleural Neoplasms; Skin Neoplasms; Tongue Neoplasms; Vimentin | 1999 |
Immunohistochemical analysis of cytokeratin expression in various trichogenic tumors.
The immunophenotypes, especially expression of cytokeratins, in 13 cases of trichogenic tumors were examined to investigate their histogenesis. Four cases of multiple trichoepithelioma, five cases of classical solitary trichoepithelioma, one case of desmoplastic trichoepithelioma, one case of trichogenic trichoblastoma, one case of trichoblastic fibroma, and one case of giant solitary trichoepithelioma were retrieved. The immunoreactivities of the epithelial nests and the keratinous cysts in these tumors were similar to those of the outer root sheath and the infundibulum of normal hair follicles, respectively. From the comparative studies of the immunophenotypes with those of normal hair follicles, we speculated that all trichogenic tumors differentiate mainly toward the outermost layer of the outer root sheath between the lower part of the permanent portion and the upper part of the transient portion and some parts of them differentiate toward various other parts of the follicles. Although differentiation toward the other follicular structures can vary from case to case, there is no particular staining pattern specific for each kind of trichogenic tumor and no significant differences in immunoreactivity among them. Our observations support a recent notion that all neoplasms of follicular germinative cells should be grouped as a single entity. Topics: Adult; Aged; Biomarkers, Tumor; Child; Female; Hair Follicle; Humans; Immunoenzyme Techniques; Immunophenotyping; Keratins; Male; Middle Aged; Neoplasms, Basal Cell; Protein Precursors; Skin Neoplasms | 1999 |
Melanocytic matricoma: a report of two cases of a new entity.
Many reports exist of pigmented adnexal tumors containing dendritic melanocytes such as pigmented basal cell carcinomas and pigmented pilomatricomas. Correspondingly, melanocytes are a known component of the bulbs of anagen follicles. The phenomenon of melanization of adnexal tumors highlights the interrelationship between melanocytes and adnexal epithelium and may represent normal melanocytes colonizing a neoplastic proliferation. We report on two cases of a unique tumor composed of neoplastic matrical cells with a significant component of melanocytes. Both cases presented as pigmented papules in older men (66 and 80 years, forearm and pectoral region, respectively). Histologically, these were well-defined nodular proliferations composed of variably melanized, pleomorphic, and mitotically active matrical and supramatrical cells forming clusters of "shadow cells." Admixed with the epithelial cells were numerous melanized dendritic melanocytes. Shadow cells expressed keratin 13, and a subpopulation of S-100 protein-positive dendritic cells were evident. No recurrence of any type was found after reexcisions 4 months and 2 years later. We propose the name of melanocytic matricoma for these two heretofore unreported cases of a unique neoplasm composed of matrical cells and melanocytes recapitulating epithelial-melanocyte interaction in the follicular anagen bulb. Although their small size, circumscription and clinical course suggest a benign nature, melanocytic matricomas' cytologic atypia disclose the potential for malignant behavior. Topics: Aged; Aged, 80 and over; Diagnosis, Differential; Hair Diseases; Hair Follicle; Humans; Keratins; Male; Melanocytes; Neoplasms, Adnexal and Skin Appendage; Pilomatrixoma; S100 Proteins; Skin Neoplasms; Treatment Outcome | 1999 |
Difluoromethylornithine chemoprevention of epidermal carcinogenesis in K14-HPV16 transgenic mice.
To be informative for chemoprevention, animal models must both closely emulate human disease and possess surrogate endpoint biomarkers that facilitate rapid drug screening. This study elucidated site-specific histopathological and biochemical surrogate endpoint biomarkers of spontaneous epidermal carcinogenesis in K14-HPV16 transgenic mice and demonstrated that the incidence and severity of these markers were decreased by the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO). The cumulative incidence of visible epidermal cancers in 127 untreated transgenic mice was 42% by 52 weeks of age, most frequently affecting the chest as flat lesions in association with chronic ulcers, or in the ear as protuberant masses. Microscopic malignancies were detected in 39% of 32-week-old transgenic mice and were found to emerge from precursor lesions that were of two distinct types: dysplastic sessile ear papillomas and hyperproliferative follicular/interfollicular chest dysplasias. ODC activity and tissue polyamine contents were differentially elevated in ear and chest skin during carcinogenesis, such that there was a marked elevation of both parameters of polyamine metabolism as early as 4 weeks of age in the ear, whereas in the chest, polyamine metabolism was increased significantly only in the late stages of neoplastic progression and in epidermal cancers. Administration of 1.0% DFMO in the drinking water from 4 to 32 weeks of age prevented both visible and microscopic malignancies and significantly decreased the incidence of chest and ear precursor lesions. ODC activity and tissue putrescine content were markedly diminished by DFMO chemoprevention in ear skin, whereas there was a more modest decline of these parameters in chest skin. DFMO treatment of transgenic mice from 28 to 32 weeks of age was associated with an absence of ear cancer and a marked regression of dysplastic papillomas. In contrast, the results in chest skin were complex in that the severity of chest precursors diminished, but their incidence was unchanged, and microscopic cancers were still detectable within these lesions. Collectively, this study highlights the utility of multistage epidermal carcinogenesis in K14-HPV16 transgenic mice both for the study of the biology of, and as a screening tool for, novel drugs and chemopreventive regimens. Topics: Administration, Oral; Animals; Anticarcinogenic Agents; Carcinoma, Squamous Cell; Disease Progression; DNA Replication; Ear; Eflornithine; Epidermis; Gene Expression Regulation; Genes, Viral; Keratin-14; Keratins; Mice; Mice, Transgenic; Neoplasm Proteins; Organ Specificity; Ornithine Decarboxylase Inhibitors; Papilloma; Papillomaviridae; Precancerous Conditions; Putrescine; Skin Diseases; Skin Neoplasms; Thorax; Transgenes | 1999 |
A multihit, multistage model of chemical carcinogenesis.
Carcinogenesis involves the accumulation of genetic changes within a single cell. Tumor promotion functions in the initial clonal expansion of an initiated cell but is generally not considered to influence later stages. To investigate whether tumor promotion can influence later stages of carcinogenesis we developed a two-hit 7, 12-dimethylbenz[a]anthracene (D) protocol designed to enrich for keratinocytes that contain at least two D-induced genetic alterations. FVB/N mice were initiated with D and promoted with 12-O-tetradecanoylphorbol-13-acetate (T) or treated with acetone (A) vehicle for 6 weeks. At 7 weeks after the start of promotion, but before visible papilloma development, groups of mice were treated with a second dose of D or A and 1 week later T promotion was resumed. D/T/A/T mice developed 2.8 papillomas/mouse and D/A/D/T mice demonstrated an additive tumor response and developed 5.8 papillomas/mouse. Importantly, D/T/D/T mice developed 12.4 papillomas/mouse, thereby demonstrating a synergistic tumor response compared with D/A/D/T and D/T/A/T mice. D/T/D/T papillomas exhibited increases in suprabasal S phase cells and keratin 13 expression when compared with D/T/A/T papillomas. D/T/D/T mice developed squamous cell carcinomas (SCCs) 10 weeks earlier than D/T/A/T mice and demonstrated a 96% malignancy incidence and 1.71 SCC/mouse compared with D/T/A/T mice, which demonstrated a 28% malignancy incidence and 0.32 SCC/mouse. Greater than 90% of D/T/A/T and D/T/D/T papillomas and SCCs contained mutant Ha-ras, while a normal Ha-ras allele persisted in all cases, indicating that a gene other than the remaining normal allele of Ha-ras was a target gene for the second D hit. These data demonstrate that: (i) promotion between the first and second hits has a profound outcome on carcinogenesis, presumably by increasing the probability that a second hit will occur in a previously initiated cell; (ii) continued promotion after the second hit is required for full expression of malignancy; (iii) the classic initiation-promotion protocol can be extended to a multihit, multistage model. Topics: 9,10-Dimethyl-1,2-benzanthracene; Acetone; Animals; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cocarcinogenesis; DNA Mutational Analysis; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Genes, ras; Keratinocytes; Keratins; Mice; Models, Biological; Neoplasm Proteins; Papilloma; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; S Phase; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1999 |
Malignant rhabdoid tumor of the vulva. Case report.
The poor prognosis of malignant rhabdoid tumor is emphasized and histopathological criteria for distinction from epithelial sarcoma of the vulva are discussed. Immunohistochemical analyses were performed by using nine different antigens including vimentin, cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, desmin, muscle-specific actin, S-100 protein, AP-15, neuron specific enolase. This is the sixth reported case of a malignant rhabdoid tumor of the vulva. The patient died eight months after the initial diagnosis in spite of a combination of surgery, adjuvant chemotherapy and external radiotherapy. Topics: Adult; Biomarkers, Tumor; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Recurrence, Local; Rhabdoid Tumor; Skin Neoplasms; Vimentin; Vulvar Neoplasms | 1999 |
Retiform/racemiform neoplasm with features of clear cell hidradenoma.
We report a case of a 78-year-old woman with a tumor of the left cheek. The tumor was a well-circumscribed cystic/solid nodule with a racemiform and reticulated pattern of growth of its epithelial cells, and mucinous and fibrocytic stroma. The epithelial cords and strands were continuous with the apocrine lining of large cystic structures. The main bulk of the epithelial component was formed by the proliferation of clear cells. This tumor is an example of an unusual benign neoplasm with racemiform and retiform patterns having a histogenetical link with the folliculo-sebaceous-apocrine unit. Topics: Adenoma, Sweat Gland; Aged; Female; Humans; Immunohistochemistry; Keratins; Skin; Skin Neoplasms | 1999 |
Transgenic mice overexpressing protein kinase Cdelta in the epidermis are resistant to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.
To determine the role of protein kinase Cdelta in mouse skin carcinogenesis, we have developed transgenic FVB/N mouse lines expressing in the epidermis an epitope-tagged protein kinase Cdelta (T7-PKCdelta) regulated by the human keratin 14 promoter. The untreated T7-PKCdelta mice displayed excessive dryness in the skin of the tail with a variable penetrance over time. Histologically, the tail skin showed hyperplasia with evidence of hyperkeratosis. The epidermis of the rest of the T7-PKCdelta mouse was unremarkable. Despite this mild phenotype, the effects of PKCdelta overexpression on mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) were dramatic. Two independent lines of T7-PKCdelta mice (16 and 37) expressing the T7-PKCdelta transgene were examined for responsiveness to skin tumor promotion by 7,12-dimethylbenz[a]anthracene and TPA. By immunoblot analysis, the T7-PKCdelta-16 and T7-PKCdelta-37 mice showed an 8- and 2-fold increase of PKCdelta protein. The T7-PKCdelta-16 mice averaged 300% more T7-PKCdelta activity than the T7-PKCdelta-37 mice did. The T7-PKCdelta-37 mice did not manifest any difference in tumor burden or incidence. However, the reduction in papilloma burden at 25 weeks of promotion for the T7-PKCdelta-16 mice relative to wild-type mice averaged 72 and 74% for males and females, respectively. The T7-PKCdelta-16 mice reached 50% papilloma incidence between 12 and 13 weeks of promotion compared with 8 weeks for wild-type mice. Furthermore, the carcinoma incidence was also reduced in T7-PKCdelta-16 mice. Carcinoma incidence at 25 weeks of promotion treatment was: wild-type females, 78%; T7-PKCdelta16 females, 37%; wild-type males, 45%; and T7- PKCdelta-16 males, 7%. Thus, PKCdelta when expressed at sufficient levels can suppress skin tumor promotion by TPA. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Female; Humans; Isoenzymes; Keratin-14; Keratins; Keratosis; Male; Mice; Mice, Transgenic; Neoplasm Proteins; Papilloma; Protein Kinase C; Protein Kinase C-delta; Sex Factors; Signal Transduction; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1999 |
Establishment of a new murine-phenotypic angiosarcoma cell line (ISOS-1).
A cell line, designated ISOS-1, was established from a tumor formed by transplantation of a human angiosarcoma into mice with severe combined immunodeficiency (SCID). The cells showed endothelial properties, based on the uptake of Dil-Ac-LDL and binding of UEA-I/GSA-I lectins, but were negative for CD11b and Pan Cytokeratin. However, the cells lost differentiated characteristics such as expression of von Willebrand factor, contact inhibition growth and tube formation activity. These findings indicate that ISOS-1 is a poorly-differentiated endothelial cell line. At the 81st passage, all of the cells were positive for H-2Dd in various intensity, but not HLA-ABC. The metaphase chromosomes consistently showed a characteristic mouse, but not human, telocentric form. Furthermore, this cell line produced fatal tumor growth in SCID mice and also in BALB/c mice. These results suggest that ISOS-1 is a murine-phenotypic angiosarcoma cell line. Topics: Animals; CD11 Antigens; Cell Division; Cell Transformation, Neoplastic; Chromosomes; Female; H-2 Antigens; Hemangiosarcoma; Histocompatibility Antigens Class I; Humans; Immunohistochemistry; Keratins; Lectins; Lipoproteins, LDL; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mice, Inbred Strains; Mice, SCID; Neoplasm Transplantation; Phenotype; Skin Neoplasms; Tumor Cells, Cultured; von Willebrand Factor | 1998 |
Severe follicular hyperplasia and spontaneous papilloma formation in transgenic mice expressing the neu oncogene under the control of the bovine keratin 5 promoter.
Transgenic mice were developed to explore the role of the erbB2 during epithelial homeostasis and tumorigenesis, through targeted expression of the neu oncogene (neu*). Expression of a neu* cDNA was targeted to the basal layer of skin epidermis as well as other epithelial tissues of transgenic mice via the bovine keratin 5 promoter. Two transgenic founders were obtained that were morphologically distinguishable from non-transgenic littermates by their visibly thickened skin and patchy hair growth by day 3 after birth. The presence of the transgene was confirmed by polymerase chain reaction analysis of tail DNA and immunofluorescence analysis of neu* protein in skin sections. Histological evaluation revealed significant hyperplasia of the follicular and interfollicular epidermis, the abnormal presence of horny material in the dermis and hypodermis, and a dramatic increase in epidermal proliferation. Many areas of the dermis involving this abnormal epithelial proliferation exhibited a squamous cell carcinoma-like appearance. In addition, there was unusual proliferation of the sebaceous glands. One founder died at day 14 and the other at day 20. The latter founder had two papillomas at the time of death. Additional phenotypic changes resulting from the expression of neu* in other tissues included hyperkeratosis in the forestomach and esophagus. In addition, there was a lack of distinction of the cortical-medullary boundaries and an increased rate of cell death in lymphocytes in the thymus. The phenotypic changes in these other tissues correlated with transgene expression. The data suggest that erbB2 signaling has an important role in epidermal proliferation. In addition, the data provide strong support for a role for erbB2 signaling during epidermal carcinogenesis in mouse skin. Topics: Animals; Female; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Hair Follicle; Homeostasis; Hyperplasia; Keratins; Male; Mice; Mice, Inbred ICR; Mice, Transgenic; Neoplasm Proteins; Papilloma; Promoter Regions, Genetic; Skin Neoplasms; Stomach; Thymus Gland; Transgenes | 1998 |
Human keratin-1.bcl-2 transgenic mice aberrantly express keratin 6, exhibit reduced sensitivity to keratinocyte cell death induction, and are susceptible to skin tumor formation.
Nonmelanoma skin cancers (NMSC) are among the most common malignancies in the world. Typically, these neoplasms grow slowly and are comparatively indolent in their clinical behavior. The most frequent molecular alterations implicated in the pathogenesis of these neoplasms involve genes known to be regulators of cell death including p53, Ha-ras and bcl-2. In order to evaluate the significance cell death deregulation during skin carcinogenesis, we generated a transgenic mouse model (HK1.bcl-2) using the human keratin 1 promoter to target the expression of a human bcl-2 minigene to the epidermis. Transgenic HK1.bcl-2 protein was expressed at high levels specifically in the epidermis extending from the stratum basale through the stratum granulosum. The epidermis of HK1.bcl-2 mice exhibited multifocal hyperplasia without associated hyperkeratosis and aberrant expression of keratin 6. The rate of proliferation was similar in HK1.bcl-2 and control epidermis although suprabasal BrdUrd incorporating cells were present only in HK1.bcl-2 skin. Keratinocytes from the HK1.bcl-2 mice were significantly more resistant to cell death induction by U.V.-B, DMBA, and TPA, compared to control keratinocytes. Furthermore, papillomas developed at a significantly greater frequency and shorter latency in the HK1.bcl-2 mice compared to control littermates following initiation with DMBA and promotion with TPA. Together these results support a role for bcl-2 in the pathogenesis of NMSC. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Cell Division; DNA Fragmentation; Gene Expression Regulation, Developmental; Genes, bcl-2; Humans; Keratinocytes; Keratins; Mice; Mice, Transgenic; Promoter Regions, Genetic; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Ultraviolet Rays | 1998 |
Cutaneous epithelioid schwannomas: a rare variant of a benign peripheral nerve sheath tumor.
Although benign epithelioid peripheral nerve sheath tumors have been described, they are rare, and benign epithelioid schwannomas have not yet been established as a specific histologic variant. We present four cases of tumors which we believe would meet criteria to be classified as benign epithelioid schwannomas. Biopsy specimens obtained from four different patients were examined with routine and immunohistochemical staining. All the tumors were well-circumscribed lesions that were surrounded by a capsule containing EMA-positive cells. The cellular component was composed of epithelioid cells, in which there was a lack of mitotic activity. Immunohistochemical studies showed the tumor cells were S-100 protein and Leu 7 positive and HMB-45 negative. In addition, type IV collagen encircled individual cells within the tumor, indicating a continuous basal lamina. We report a group of cutaneous epithelioid schwannomas. Although the presence of such tumors is not unexpected, this diagnosis may not be initially considered because of this rare cytologic feature. Topics: Adult; Antigens, Neoplasm; Collagen; Female; Humans; Immunohistochemistry; Keratins; Male; Melanoma-Specific Antigens; Mucin-1; Neoplasm Proteins; Nerve Sheath Neoplasms; Neurilemmoma; Peripheral Nervous System Neoplasms; S100 Proteins; Schwann Cells; Skin Neoplasms; Vimentin | 1998 |
Expression of Hras-p21 and keratin K13 in UVR-induced skin tumors in Sencar mice.
An ultraviolet radiation (UVR)-induced Sencar mouse skin carcinogenesis model was established to investigate the expression of Hras-p21 and keratin K13 in different stages of carcinogenesis, including UV-exposed nontumor skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). Expression of Hras-p21 and K13 was examined in paraffin-embedded tumor sections by using immunohistochemical, immunofluorescent, and double staining techniques with specific antibodies. Positive Hras-p21 staining was detected in 1/3 (33%) papillomas, 24/36 (67%) of SCCs, but not in UVR-exposed nontumor skin or SCTs. Positive staining of the malignant progression marker K13 was found in 22/36 (61%) of SCCs only. Coexpression of Hras-p21 and K13 was found in 17/36(47%) SCCs. H-ras exons 1 and 2 were amplified from skin/tumor sections by using nested polymerase chain reaction (PCR). PCR-based single-strand conformation polymorphism (SSCP) analysis and gene sequencing revealed three point mutations, one in UVR-exposed nontumor skin (codon 56), and two in SCCs (codons 13 and 21). There were no clear relationships between point mutations of H-ras and the positive staining of Hras-p21 and K13. These results indicate that overexpression of ras-p21 in conjunction with aberrant expression of K13 is a frequent event in UVR-induced SCCs in Sencar mouse skin. Point mutation of the H-ras gene appeared to be a rare event in UVR skin carcinogenesis and not to be responsible for overexpression of Hras-p21. Topics: Animals; Female; Keratins; Mice; Mice, Inbred SENCAR; Mutation; Neoplasms, Radiation-Induced; Proto-Oncogene Proteins p21(ras); Skin Neoplasms; Ultraviolet Rays | 1998 |
Deregulated expression of E2F1 induces hyperplasia and cooperates with ras in skin tumor development.
In cell culture studies, overexpression of the E2F1 transcription factor has been shown to stimulate proliferation, induce apoptosis, and cooperate with an activated ras gene to oncogenically transform primary rodent cells. To study the effect of increased E2F1 activity on epithelial growth and tumorigenesis in vivo, transgenic mice expressing E2F1 under the control of a keratin 5 (K5) promoter were generated. Expression of E2F1 in the epidermis results in hyperplasia but does not inhibit terminal differentiation. In a transgenic line expressing high levels of E2F1, mice have decreased hair growth likely as a result of aberrant apoptosis in developing hair follicles. Coexpression of a cyclin D1 transgene with E2F1 augments epidermal hyperplasia and further disrupts hair follicle development suggesting that hypophosphorylated Rb antagonizes the proliferative and apoptotic-promoting activities of E2F1. Finally, the E2F1 transgene is found to cooperate with a v-Ha-ras transgene to induce skin tumors in double transgenic animals. These findings confirm that many of the activities ascribed to E2F1 through in vitro studies can be reproduced in vivo and demonstrate for the first time that deregulated E2F activity can contribute to tumor development. Topics: Animals; Animals, Newborn; Apoptosis; Carrier Proteins; Cell Cycle Proteins; Cell Division; Crosses, Genetic; DNA-Binding Proteins; E2F Transcription Factors; E2F1 Transcription Factor; Epidermis; Gene Expression Regulation; Genes, ras; Hair; Humans; Hyperplasia; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Transgenic; Retinoblastoma-Binding Protein 1; Skin; Skin Neoplasms; Transcription Factor DP1; Transcription Factors; Transfection | 1998 |
Detection of the SYT-SSX chimeric RNA of synovial sarcoma in paraffin-embedded tissue and its application in problematic cases.
We report the development of a reverse-transcriptase polymerase chain reaction assay that detects (in paraffin-embedded, formalin-fixed tissue) the SYT-SSXchimeric RNA transcript resulting from the t(X;18) of synovial sarcoma. The primers chosen detect both of the SSX1 and SSX2 partners, and the target sequence is small enough (87 base pairs) to be reliably detected in archival and variably processed consultation material. To demonstrate its usefulness, we applied it to 14 problematic cases, including spindle cell tumors of the thoracic region, of the neck, and of subcutaneous tissue. For instance, we show that, depending on the location, synovial sarcoma can mimic malignant solitary fibrous tumor, the spindle epithelial tumor with thymus-like differentiation, or skin adnexal tumors. Molecular detection of the SYT-SSX chimeric RNA should allow the reclassification of difficult cases in which the morphologic features overlap different entities or in which tumor nosology is still evolving. Topics: Adult; Aged; Chromosomes, Human, Pair 18; Diagnosis, Differential; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Molecular Probe Techniques; Neoplasm Proteins; Paraffin Embedding; Polymerase Chain Reaction; Proteins; Proto-Oncogene Proteins; Recombinant Fusion Proteins; Repressor Proteins; RNA, Neoplasm; Sarcoma, Synovial; Skin Neoplasms; Thoracic Neoplasms; Transcription, Genetic; Translocation, Genetic; X Chromosome | 1998 |
Nodular melanosis due to epithelial neoplasms: a finding not restricted to regressed melanomas.
Nodular or tumoral melanosis consists of nodular or sheetlike deposits of melanophages in the dermis. When nodular melanosis is present, a completely regressed malignant melanoma is a major diagnostic consideration. We present a case of nodular melanosis due to regression of a pigmented basal cell carcinoma with pilar differentiation. In addition to this case, we present five additional cases of epithelial neoplasms with melanin deposition in the stroma. In each case, the source of the melanin was non-neoplastic dendritic melanocytes intermingled among the tumor cells. Therefore, if nodular melanosis is found, pigmented epithelial neoplasms should also be considered in the differential diagnosis. Topics: Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Carcinoma, Basal Cell; Humans; Immunohistochemistry; Iron; Keratins; Male; Melanins; Melanoma-Specific Antigens; Melanosis; Middle Aged; Neoplasm Proteins; S100 Proteins; Skin Neoplasms; Vimentin | 1998 |
Benign myoepithelioma of the skin.
A case of cutaneous myoepithelioma is reported. The tumor was composed of spindle-shaped, epithelioid, and plasmacytoid (hyaline) cells. It exhibited a widespread immunoreactivity for low molecular weight keratins and protein S-100, being irregularly positive for smooth muscle actin. Ultrastructural studies of tumor cells showed a variable content of intermediate filaments, with focal densities resembling smooth muscle dense bodies. A well-developed basal lamina, pinocytotic vesicles, and some desmosomes were also observed. In spite of being accepted as an individual entity, myoepitheliomas probably belong to a family of lesions that include mixed tumors. Therefore, this case can be considered as a salivary-gland-type tumor, probably originating from myoepithelial cells of sweat glands. The existence of this unique neoplasm provides further support to the debated role of myoepithelial cells in the development of mixed tumors. Topics: Actins; Aged; Biomarkers; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Myoepithelioma; Skin Neoplasms | 1998 |
The malignant capacity of skin tumours induced by expression of a mutant H-ras transgene depends on the cell type targeted.
. Pinpointing the cells from which tumours arise is a major challenge n tumour biology. Previous work has shown that the targeted expression of a mutant ras gene within the interfollicular cell compartment of mouse skin induces the formation of benign papillomas, but these do not spontaneously progress to malignancy. We have investigated the carcinogenic effects of expressing the same oncogene in a different population of epidermal cells.. Expression of mutant ras from a truncated keratin 5 gene promoter, which directs expression to the follicular and interfollicular cells of newborn mice and the hair follicle cells of adults, stimulated the development of acanthotic areas in newborn mice. Within one week of birth, the acanthotic skin developed areas of carcinoma in situ and adult mice developed papillomas and keratoacanthomas, the latter having a high frequency of spontaneous malignant transformation to squamous and occasionally spindle carcinomas. The benign tumours that arose had several hallmarks of tumours at a high risk of malignant progression, including suprabasal cell proliferation and heterogeneous expression of keratin 13. In contrast to tumours induced by expressing mutant ras under the control of the keratin 10 or keratin 1 gene promoters, the formation of these lesions was not dependent on wounding or a tumour promoter.. Benign tumours that are at a risk of malignant conversion are primarily derived from cells located within the hair follicle, and the nature of the cell in which tumour initiation occurs is a major determinant of malignant potential. Topics: Animals; Animals, Newborn; Gene Expression Regulation, Neoplastic; Genes, ras; Hair Follicle; Keratins; Lac Operon; Mice; Mice, Transgenic; Mutation; Promoter Regions, Genetic; Recombinant Fusion Proteins; Skin Abnormalities; Skin Neoplasms | 1998 |
Eccrine syringofibroadenoma: report of a case and analysis of cytokeratin expression.
Eccrine syringofibroadenoma (ESFA) is a rare disorder which shows differentiation toward the eccrine sweat apparatus. There is a controversy concerning the pathogenesis and precise differentiation of this tumor. We report a case of ESFA and its differentiation pattern by an analysis of cytokeratin expression. Using paraffin-embedded materials, histopathological and immunohistochemical studies were performed. Staining patterns of the luminal, peripheral, and inner cells of the tumor strands closely matched or mimicked those of the luminal, outer and intermediate cells of the normal eccrine dermal duct, respectively. The case of ESFA reported revealed a pattern of differentiation suggestive of an eccrine duct origin. Topics: Adenoma, Sweat Gland; Aged; Aged, 80 and over; Eccrine Glands; Fibroadenoma; Humans; Immunohistochemistry; Keratins; Male; Skin Neoplasms; Sweat Gland Neoplasms; Syringoma | 1998 |
Sebaceous neoplasm with reticulated and cribriform features: a rare variant of sebaceoma.
Troy and Ackerman defined the term sebaceoma (Am J Dermatopathol 1984: 6: 7-13) as benign neoplasm of basaloid cells with varying numbers of mature sebocytes. Steffen and Ackerman (Neoplasms with sebaceous differentiation. Philadelphia: Lee and Febiger, 1994: 401-425) illustrated many examples of sebaceoma, two of which had a reticulated and cribriform pattern. We report a case of sebaceoma from the scalp of a 52-year-old white female. Histologically, it displayed reticulated and cribriform basaloid epithelial islands. This is the third reported case of sebaceoma, to our knowledge, with these unusual features. Topics: Biomarkers, Tumor; Carcinoma, Transitional Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Scalp; Sebaceous Gland Neoplasms; Skin Neoplasms | 1998 |
Biochemical and immunohistochemical analyses of keratin expression in basal cell carcinoma.
Recently we demonstrated that the keratin 17 (K17) content exceeded the K16 content in most follicular tumors, in comparison with non-follicular epithelial skin tumours by two-dimensional gel electrophoresis (2-DE), densitometry and immunohistochemistry. At present the origin of basal cell carcinoma (BCC) is unknown. So, based on the above results, we studied keratin expression in eight cases of BCC, in order to analyze tumor differentiation by both biochemical and immunohistochemical methods. Biochemically, using 2-DE and immunoblotting, stratified epithelial keratins K5/K14 and large amounts of K17 were present in all cases. Simple epithelial keratins K8 and K19 were expressed in all and half of the cases, respectively. However, hyperproliferative associated keratins (K6/K16) and keratinized keratins (K1/K10) were detected in only a few cases. Immunohistochemical studies using frozen sections with chain-specific antikeratin monoclonal antibodies against K1, K7, K8, K10, K14, K16, K17, K18 and K19 showed that BCC tumor cells reacted positively with antibodies against K8, K14, K17 and K19, but did not react, or were rarely positive with K1, K7, K10, K16 and K18 antibodies. Predominant expression of K17 and the frequent expression of K8 and K19, with little K6/K16 and K1/K10 expression are the characteristic features of BCC, suggesting that BCC is differentiated towards undifferentiated follicular epithelia, most probably hair bulge cells. Topics: Aged; Carcinoma, Basal Cell; Electrophoresis, Gel, Two-Dimensional; Female; Humans; Immunoblotting; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms | 1998 |
Expression of a p53 mutant in the epidermis of transgenic mice accelerates chemical carcinogenesis.
To develop an in vivo model for studying the role of the p53 tumor suppressor in skin carcinogenesis, a murine p53(172H) mutant (equivalent to human p53(175H)) was expressed in the epidermis of transgenic mice, utilizing a targeting vector based on the human keratin 1 gene (HK1.p53m). HK1.p53m mice developed normally and did not exhibit an obvious epidermal phenotype or develop spontaneous tumors. However, these mice demonstrated an increased susceptibility to a two-stage chemical carcinogenesis protocol, with the rate of formation and number of papillomas being dramatically increased as compared to non-transgenic controls. The majority of papillomas in control mice regressed after termination of 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, whereas p53m papillomas progressed to carcinomas and metastases. In addition, more advanced malignancy, i.e., undifferentiated spindle cell carcinomas, were exclusively observed in p53m mice. Increased bromodeoxyuridine (BrdU) labeling, accompanied by decreased expression of p21, was observed in HK1.p53m papillomas. In situ examination of centrosomes in HK1.p53m papillomas also revealed marked abnormalities, with 75% of the cells containing > or = 3 centrosomes/cell, whereas centrosome numbers in papillomas from control animals remained normal. These data suggest that the accelerated tumorigenesis observed in chemically-treated p53m mice is most likely due to increased genomic instability resulting from an inhibition of G1 arrest and abnormal amplification of centrosomes. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Bromodeoxyuridine; Carcinogens; Centrosome; Disease Susceptibility; Epidermis; Female; Gene Amplification; Humans; Keratins; Male; Mice; Mice, Transgenic; Mutagenesis, Site-Directed; Papilloma; Promoter Regions, Genetic; Proto-Oncogene Proteins p21(ras); ras Proteins; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transgenes; Tumor Suppressor Protein p53 | 1998 |
Skin tumor development and keratin expression in different experimental models. Relation to inducing agent and target tissue structure.
The applicability of the experimental skin carcinogenesis model for studies of tumor development was examined by exposing the skin of various mouse strains to different chemical carcinogens and UV radiation regimens, in order to analyze the development and progression of the neoplastic process and the role of differentiation markers such as keratins. In tumor-sensitive hairy NMRI mouse skin, the chemical carcinogen, 7,12-dimethylbenz(a)-anthracene (DMBA) induced an abnormal epidermal cell differentiation and structural irregularities associated with an altered keratin expression, as well as numerous papillomas and squamous cell carcinomas. A suboptimal dose of UVB irradiation increased the number of DMBA-induced benign squamous neoplasms. Low doses of benzo(a)pyrene resulted in mild epidermal alterations, but only in one tumor. High doses of UVB induced a large number of undifferentiated spindle cell tumors with few keratinpositive cells in NMRI mice, similar though fewer tumors in hairy, heavily pigmented C57BL/6 mice, numerous papillomas and squamous cell carcinomas in hairless hr/hr mice but only two papillomas in hairy, moderately pigmented DBA/2 mice while UVA exposure produced only two papillomas in hairless SKH-1 mice. In conclusion, the extent and type of skin tumor development depended upon the induction regimen: physical, chemical, dose and duration, as well as on the skin structure: pigmentation and adnexal development, all of which have to be taken into account when relating experimental results to human conditions. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Biomarkers, Tumor; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Disease Models, Animal; Female; Keratins; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred Strains; Skin Neoplasms | 1998 |
VEGF/VPF overexpression in skin of transgenic mice induces angiogenesis, vascular hyperpermeability and accelerated tumor development.
Upregulation of keratinocyte-derived VEGF-A expression has recently been established in non-neoplastic processes of skin such as wound healing, blistering diseases and psoriasis, as well as in skin neoplasia. To further characterize the effects of VEGF-A in skin in vivo, we have developed transgenic mice expressing the mouse VEGF120 under the control of a 2.4 kb 5' fragment of keratin K6 gene regulatory sequences that confers transgene inducibility upon hyperproliferative stimuli. As expected from the inducible nature of the transgene, two of the three founder mice obtained (V27 and V208), showed no apparent phenotype. However, one founder (V2), mosaic for transgene integration, developed scattered red spots throughout the skin at birth. The transgenic offspring derived from this founder developed a striking phenotype characterized by swelling and erythema, resulting in early postnatal lethality. Histological examination of the skin of these transgenics demonstrated highly increased vascularization and edema leading to disruption of skin architecture. Expression of the transgene was silent in adult animals of lines derived from founders V27 and V208. Phorbol ester-induced hyperplasia resulted in transgene induction and increased cutaneous vascularization in adult transgenic mice of these lines. Skin carcinogenesis experiments performed on hemizygous crosses of V208 mice with activated H-ras-carrying transgenic mice (TG.AC) resulted in accelerated papilloma development and increased tumor burden. Previous results from our laboratory showed that VEGF upregulation is a major angiogenic stimulus in mouse epidermal carcinogenesis. By overexpressing VEGF in the skin of transgenic mice we now move a step further toward showing that VEGF-mediated angiogenesis is a rate-limiting step in the genesis of premalignant lesions, such as mouse skin papilloma. Our transgenic mice constitute an interesting model system for in vivo study of the cutaneous angiogenic process and its relevance in tumorigenesis and other skin diseases. Topics: Animals; Capillary Permeability; Endothelial Growth Factors; Genes, ras; Hyperplasia; Keratins; Lymphokines; Mice; Mice, Transgenic; Neovascularization, Pathologic; Neovascularization, Physiologic; Papilloma; Precancerous Conditions; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; Regulatory Sequences, Nucleic Acid; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors | 1998 |
Cytokeratin and neurofilament protein staining in Merkel cell carcinoma of the small cell type and small cell carcinoma of the lung.
Merkel cell carcinoma (MCC) has a small cell variant, indistinguishable in hematoxylin-eosin sections from metastatic small cell carcinoma of the lung (SCCL). To investigate whether intermediate filament expression is helpful in this distinction, 17 MCCs of the small cell type were examined for cytokeratin, as well as neurofilament protein immunostaining, and compared with 59 intermediate-type MCCs and 22 SCCL. With a pan-cytokeratin cocktail (cytokeratin 1-8, 10, 13-16, 19), most (39 of 55) intermediate-type tumors and, more important, 11 of 16 cases of the small cell variant exhibited focal paranuclear staining with dot-like positivity, crescentic positivity, or both. A combined focal (dot-like/crescentic) and diffuse cytoplasmic pan-cytokeratin staining was seen in additional 8 of 55 intermediate and 4 of 16 small cell MCCs. Cytokeratin 20 also evoked focal cytoplasmic staining and occasionally focal and diffuse positivity in the MCCs, irrespective of the subtype. Exclusively diffuse cytokeratin 20 patterns did not occur. Conversely, most SCCL showed a diffuse expression of pancytokeratin, and all cases remained cytokeratin 20 negative. When neurofilament protein was applied, approximately half of the MCCs (25 of 40), including 7 of 11 of the small cell variant, were positive, whereas all SCCL were negative. In conclusion, the cytokeratin and neurofilament protein patterns of small cell MCCs are identical to the pattern of intermediate MCCs but differ from the profile of SCCL, which may help in the differential diagnosis. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Merkel Cell; Carcinoma, Small Cell; Diagnosis, Differential; Female; Genetic Variation; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Lung Neoplasms; Male; Middle Aged; Neurofilament Proteins; Phenotype; Skin; Skin Neoplasms | 1998 |
Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin.
Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell. Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Elastic Tissue; Erythema; Female; Humans; Infrared Rays; Keratins; Keratosis; Male; Mitosis; Neoplasms, Multiple Primary; Skin Aging; Skin Neoplasms; Ultraviolet Rays | 1998 |
Cultured human sole-derived keratinocyte grafts re-express site-specific differentiation after transplantation.
Cultured epithelial autografts (CEA) derived from sole skin were transplanted to full-thickness wounds excised to muscle fascia over a variety of diverse body sites in 12 pediatric patients treated for acute burns or giant congenital nevi. The skin regenerated from the grafts was biopsied from 7 days to 6 years after grafting. The resultant epidermal phenotype was analyzed histologically and by immunohistochemical localization of keratin 9 (K9) as objective evidence of sole-type site-specific differentiation. Expression of K9 was also verified by one-dimensional gel electrophoresis of epidermal cytoskeletal extracts and K9 immunoblot analysis. Grafts prepared from epidermis of axilla; groin or foreskin and transplanted to wounds of comparable depth in an identical manner in the same patients served as controls of postgrafting differentiation. Biopsies of sole skin from amputation specimens from patients of comparable age served as normal positive controls, and biopsies of nonsole skin from patients of comparable age served as normal negative controls. As early as 2 weeks postgrafting, the histologic appearance of sole-derived CEA differed substantively from that of axilla- or groin-derived CEA controls and displayed a phenotype characteristic of sole skin with a thick compact stratum corneum, a thick stratum granulosum, and a distinct stratum lucidum. In sole-derived grafts rete ridges regenerated within 2 months postgrafting, whereas nonsole-derived grafts required 4-6 months for rete ridge regeneration. Once acquired, the sole skin phenotype was maintained long-term by all sole-derived CEA. In vitro, sole-derived keratinocytes synthesized little, if any, K9. However, within 7 days after grafting, K9 synthesis by multiple suprabasal keratinocytes was seen within the epidermis regenerated from sole-derived CEA. Protein of K9 appeared progressively more diffuse throughout the suprabasal layers, attaining a confluent pattern of expression comparable to normal controls of sole skin by 6 to 12 months postgrafting, and the confluent pattern of suprabasal K9 synthesis was maintained long-term. The results demonstrate that site-specific differentiation is an intrinsic property of postnatal human keratinocytes and can be expressed and maintained in a permissive environment in the absence of dermal tissue. Topics: Adolescent; Biomarkers; Burns; Cell Differentiation; Cells, Cultured; Child; Child, Preschool; Epidermal Cells; Female; Foot; Humans; Infant; Keratinocytes; Keratins; Male; Nevus; Phenotype; Protein Isoforms; Skin Neoplasms; Transplantation, Autologous | 1998 |
[Cytokeratins 7 and 20: aid to diagnosis of skin tumors].
Topics: Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Skin Neoplasms | 1998 |
The distribution of the desmosomal protein, plakophilin 1, in human skin and skin tumors.
Desmosomes are predominant among the types of plaque-bearing adhering junctions found in human skin. These structures contain a set of desmosomal cadherins and cytoplasmic plaque proteins, the synthesis of which is differentiation dependent. As plakophilin 1, a member of the armadillo gene family, is an important accessory desmosomal plaque protein, we raised several monoclonal antibodies specific for this protein and applied immunohistochemical and immunoblotting procedures to study the distribution of plakophilin 1 in desmosomes in adult and fetal skin, psoriatic epidermis, various epithelial skin tumors, and keratinocyte sheets grown in culture. In epidermis, the spinous layers were prominently immunostained by plakophilin 1 antibodies, whereas the basal cell layer was only weakly stained and the stratum corneum was entirely unstained. The staining observed in psoriatic epidermis was somewhat heterogeneous. In hair follicles, the outer root sheath (ORS) was delineated in its suprabasal cell layers, with variable staining in its upper and lower parts. All basal cells of the ORS remained unstained, as did upper inner root sheath (IRS) and matrix cells of lower bulb. In eccrine sweat glands, the reaction was confined to inner dermal ductal cells, with the acini remaining unstained. The desmosomal immunostaining observed in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) was very heterogeneous: In general, junctions in well-differentiated stratified tumor regions were more intensely stained than sections of poorly differentiated and invasively growing BCCs and SCCs. Plakophilin 1 was also prominent in the desmosomes of keratinocyte sheets grown in culture. The cell type-specific, i.e., differentiation-dependent, distribution of desmosomal plakophilin 1 is discussed in relation both to the stratification of the cutaneous epithelia and to tumor differentiation and growth. Topics: Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Desmosomes; Fetus; Foot; Humans; Immunohistochemistry; Keratinocytes; Keratins; Plakophilins; Proteins; Psoriasis; Skin; Skin Neoplasms | 1997 |
Histogenesis of clear cell hidradenoma: immunohistochemical study of keratin expression.
The expression of cytokeratins in 10 cases of clear cell hidradenoma, including 3 cases of solid cystic hidradenoma, were examined using 21 kinds of monoclonal antibodies. We divided them into three histologic patterns: massive nests with a few lumina (M nests), nests with some tubular lumina (L nests), and nests in solid cystic hidradenomas (S nests). All hidradenomas showed similar immunoreactivities to those in the lower dermal ducts or secretory cells of normal eccrine glands. With antibodies against simple epithelial cytokeratins (CKs 7, 8, 18, and 19), however, different immunostaining was noted among the three histologic patterns. Namely, the M nests failed to react to them, although some luminal cells in the L nests revealed a positive staining. Furthermore, a majority of luminal cells in the S nests revealed a positive staining with them. Therefore, we think that the luminal cells in solid cystic hidradenoma mainly differentiate toward the secretory cells, and that the M nests mainly differentiate toward the dermal duct. Those in the L nests are thought to differentiate toward the dermal duct and the secretory cells. The proportion of the differentiation toward luminal cells of dermal ducts to the differentiation toward secretory cells was the main difference among the three nests. In addition, there was no difference in immunophenotypes between clear cells and epidermoid cells in the two kinds of hidradenomas. Topics: Acrospiroma; Humans; Immunohistochemistry; Keratins; Retrospective Studies; Skin Neoplasms | 1997 |
Lymphoepithelioma-like carcinoma of the skin.
We report a case of lymphoepithelioma-like carcinoma of the skin on the right cheek of a 67-year-old man. Histologically, the entire dermis was occupied by multiple lobules of atypical epithelial tumor cell nests surrounded by inflammatory cells. Immunohistochemical examination showed that the epithelial tumor cells were positive for cytokeratin and epithelial membrane antigen. The inflammatory cells were positive for leukocyte common antigen and T-cell marker. Among the tumor nests, small ductal structures were positive for carcinoembryonic antigen. Ultrastructurally, these epithelial tumor cells had well-developed desmosomes and were joined to each other; no tonofilaments were observed in the cytoplasm. These findings strongly suggest that these tumor cells tended to differentiate to the adnexa of the skin. Topics: Aged; Antigens, Differentiation, T-Lymphocyte; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cheek; Cytoplasm; Desmosomes; Epithelium; Facial Neoplasms; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Leukocyte Common Antigens; Male; Mucin-1; Skin Neoplasms | 1997 |
Cutaneous mixed tumor containing ossification, hair matrix, and sebaceous ductal differentiation.
A 58-year-old Japanese male presented with a cutaneous mixed tumor containing ossification and hair matrix differentiation on the left side of the chin. Histologically, the tumor consisted almost exclusively of apocrine-type epithelial ductal structures and chondroid stroma. Strands and aggregation of basaloid cells which contained keratinous cystic structures with a column of shadow cells arising from basophilic basaloid cells, sebaceous duct-like structures, and ossification in the stroma were also evident. These findings suggest that cutaneous mixed tumors with ossification and hair matrix differentiation are related to both the whole hair follicle and the sweat apparatus. Topics: Adenoma, Pleomorphic; Apocrine Glands; Cell Differentiation; Chin; Epithelium; Facial Neoplasms; Hair; Hair Follicle; Humans; Keratins; Male; Middle Aged; Ossification, Heterotopic; Sebaceous Glands; Skin Neoplasms | 1997 |
Malignant melanoma and squamous cell carcinoma forming one tumour on a burn scar.
Malignant melanoma occurring in burn scars is rare and cases of malignant melanoma and squamous cell carcinoma arising in a burn scar are extremely rare. We report a case of malignant melanoma and squamous cell carcinoma arising in one tumour on a stable thermal burn scar on the right leg of a 55-year-old man after a long latent period of about 50 years. The case was unique in that the malignant melanoma and squamous cell carcinoma occurred synchronously next to each other and produced one tumour. Immunohistochemical stainings with keratin, S-100 protein and HMB 45 clearly distinguished the two kinds of atypical tumour cells. Following the total resection of the original tumour, metastasis of malignant melanoma in the inguinal lymph node was found. This case underlines the possibility that another tumour may co-exist even if pathological observation reveals one kind of tumour. Topics: Antigens, Neoplasm; Antigens, Surface; Burns; Carcinoma, Squamous Cell; Cicatrix; Humans; Immunohistochemistry; Keratins; Leg; Lymphatic Metastasis; Male; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Neoplasms, Multiple Primary; S100 Proteins; Skin Neoplasms | 1997 |
Spiradenoma and dermal cylindroma: comparative immunohistochemical analysis and histogenetic considerations.
We carried out an immunohistochemical analysis of nine spiradenomas and seven cylindromas. Our findings underscore the histomorphological similarities of the two adnexal neoplasms-namely, the expression of S-100 protein ascribed to eccrine differentiation within the tubular and large, pale-staining cells of both entities. Human milk fat globulin (HMFG) and lysozyme, two markers associated with apocrine differentiation, are expressed by tubular cells in spiradenomas and cylindromas. Lysozyme is also expressed in cylindromas by large, pale-staining cells. In addition, antibodies to alpha-smooth muscle actin strongly characterized the small basaloid cells of both types of neoplasm. Both spiradenomas and cylindromas expressed identical cytokeratin patterns. As with the various regions of eccrine and apocrine units, the expression by spiradenomas and cylindromas of keratins 7, 8, and 18 indicates differentiation toward the secretory tissue, whereas the expression of keratin 14 in some of the neoplastic cells points toward ductal differentiation. Malformed ductal and glandular structures in continuity with evolving spiradenomas and cylindromas in two of our cases also suggest that these tumors might arise from abortive adenxal anlagen. Topics: Actins; Adenoma; Adenoma, Sweat Gland; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carcinoembryonic Antigen; Carrier Proteins; Cell Differentiation; Cell Lineage; Eccrine Glands; Gene Expression Regulation, Neoplastic; Glycoproteins; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Membrane Transport Proteins; Morphogenesis; Mucin-1; Muramidase; Neoplasm Proteins; S100 Proteins; Skin Neoplasms; Sweat Gland Neoplasms; Vimentin | 1997 |
Overexpression of insulin-like growth factor-1 induces hyperplasia, dermal abnormalities, and spontaneous tumor formation in transgenic mice.
Transgenic animals were developed to assess the role of insulin-like growth factor 1 (IGF-1) in skin growth, differentiation and organization, as well as its importance in tumor formation. Expression of a human IGF-1 cDNA was targeted to the interfollicular epidermis of transgenic mice using a human keratin 1 promoter construct (HK1). Transgenic animals (HK1.IGF-1 mice) could be identified at birth by early ear unfolding and excessive ear and skin growth compared to non-transgenic littermates. Further examination of the skin from these mice showed epidermal hyperplasia and hyperkeratosis, marked thickening of the dermis and hypodermis, and early hair follicle generation in newborns. The severity of this phenotype correlated with transgene expression both of which subsided with age. Adult HK1.IGF-1 mice developed spontaneous tumors following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) alone and exhibited an exaggerated epidermal proliferative response following treatment with the tumor promoter compared to non transgenic littermates. Additionally, HK1.IGF-1 transgenic mice developed papillomas faster and in markedly greater numbers compared to non-transgenic littermates in standard initiation-promotion experiments. The data presented suggest an important role for IGF-1 in the process of multistage carcinogenesis in mouse skin. Topics: Animals; Carcinogens; Epidermis; Fluorescent Antibody Technique, Indirect; Humans; Hyperplasia; Insulin-Like Growth Factor I; Keratins; Mice; Mice, Transgenic; Neoplasms, Experimental; Skin Abnormalities; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1997 |
The immunohistochemical characteristics of the basosquamous cell carcinoma.
The basosquamous cell carcinoma (BSCC) is a poorly defined and often misunderstood cutaneous malignancy.. The purpose of this study was to compare, using immunohistochemical techniques, the BSCC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC).. BSCC occurring at Pennsylvania State University over the past 10 years were identified. Choosing seven BCC, and nine SCC as controls, all specimens were stained for keratin, lack of apoptosis, glycoproteins, and altered gene products using the avidin/biotin and strep-avidin immunoperoxidase techniques. Each malignancy was then graded for the percentage of cells stained with each marker.. Of the markers studied, all stained to varying degrees the malignant aspects of the specimens. There were similar patterns between tumors, with the BSCC showing a transition zone between typical BCC and SCC. This was most striking for Ber-EP4, where over two-thirds of the BCC stained, none of the SCC, and half of the BSCC showed reactivity.. BSCC has staining patterns similar to both the BCC and SCC. The presence of a transition zone does not support the concept that all BSCC are collision tumors, but rather a differentiation of one tumor into another. We confirm earlier reports that Ber-EP4 could be used to distinguish between classic BCC and SCC. AE1/AE3, bcl-2, TGF-alpha, and p53 were not helpful in separating the tumors. Topics: Carcinoma, Basal Cell; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Diagnosis, Differential; ErbB Receptors; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Proto-Oncogene Proteins c-bcl-2; Skin Neoplasms; Tumor Suppressor Protein p53 | 1997 |
Evaluation of laminin and cytokeratin-10 expression in squamous cell carcinoma of the skin.
Topics: Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Laminin; Neoplasm Staging; Skin Neoplasms | 1997 |
A unique case of squamous cell carcinoma showing adenocarcinomatous features with focal apocrine differentiation.
We report an 85-year-old man with squamous cell carcinoma on the right pinna. Two years after the excision of the lesion, metastatic foci were found extending from the right retromandibular to the mastoid region and into the parapharyngeal space. Histopathologically, the primary tumor showed interconnecting nests of atypical cells invading into the dermis from multiple epidermal and infundibular foci. The tumor had both squamous and glandular differentiation. A peculiar finding was the presence of decapitation secretion in the glandular foci. To our knowledge, definite apocrine differentiation in squamous cell carcinoma has not previously been reported. Topics: Adenocarcinoma; Aged; Aged, 80 and over; Apocrine Glands; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Differentiation; Ear Neoplasms; Ear, External; Head and Neck Neoplasms; Humans; Keratins; Male; Mastoid; Neoplasm Invasiveness; Pharyngeal Neoplasms; Skin Neoplasms; Skull Neoplasms | 1997 |
Epidermolytic acanthomas: clinical characteristics and immunohistochemical features.
Epidermolytic hyperkeratosis in bullous congenital ichthyosiform erythroderma results from mutations in the K1 and K10 genes. Epidermolytic acanthomas are solitary or multiple lesions with microscopic features that are identical to those in bullous congenital ichthyosiform erythroderma. In this study, the clinical and epidemiologic characteristics of epidermolytic acanthomas were summarized, and the expression of keratins (using antibodies to K1, K6, K10, K14, K16, and K19) in five solitary epidermolytic acanthomas was determined using immunohistochemistry techniques. The intensity of staining for K1 and K10 was (a) less in the altered granular layer, as compared to the adjacent nonaltered granular layer of the lesional skin, and (b) less in the lesional skin as compared to the perilesional, histologically normal-appearing skin. Expression of K6 and K16 was noted not only in the basal layer and suprabasal layers of the lesions, but also in the corresponding layers of the adjacent normal skin. Staining for K14 was also observed in the basal layers and suprabasal layers of the lesional and adjacent normal epidermis; within the lesional and perilesional normal skin, the intensity of positive staining for K14 was greater in the basal layers than in the suprabasal layers of the epidermis. The specimens did not stain for K19. In conclusion, using immunohistochemistry techniques on solitary epidermolytic acanthomas, we were able to demonstrate (1) an abnormality in K1 and K10 expression in the lesional skin as compared to the adjacent, histologically normal-appearing skin and (b) the expression of hyperproliferative keratins not only with the lesional skin, but also in the perilesional normal skin. We hypothesize that the pathogenesis of epidermolytic hyperkeratosis in lesions of solitary epidermolytic acanthomas results from mutations in the K1 and K10 genes. Topics: Adult; Aged; Child, Preschool; Female; Humans; Hyperkeratosis, Epidermolytic; Immunohistochemistry; Keratins; Male; Neoplasms, Glandular and Epithelial; Skin Neoplasms | 1997 |
Malignant mesothelioma metastatic to the skin, presenting as inflammatory carcinoma.
We report a 50-year-old man with a history of malignant pleural mesothelioma diagnosed 1 year previously and treated with pneumonectomy and radiotherapy who presented with an erythematous eruption on the left chest wall. A skin biopsy showed a proliferation of malignant epithelioid cells lining irregular clefts in the dermis. Some groups of cells were observed filling vascular lumina. Immunohistochemically, the tumor cells expressed cytokeratins (with antibodies AE1/AE3, MNF 116, and CAM 5.2), and epithelial membrane antigen (EMA), and were negative with Ulex europaeus (UE) and for carcinoembryonic antigen (CEA), CD34, CD15 (with LeuM1 antibody), and factor VIII-related antigen (FVIIIra). The histologic features and immunohistochemical profile were comparable to those observed in the primary pleural mesothelioma. This is the first reported case in which malignant mesothelioma metastatic to the skin presented as "inflammatory carcinoma." Although a very uncommon presentation, mesothelioma should be considered in the differential diagnosis of erythematous eruptions on the chest. Topics: Adenocarcinoma; Antigens, CD34; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Mesothelioma; Middle Aged; Mucin-1; Pleural Neoplasms; Skin Neoplasms; Thorax; von Willebrand Factor | 1997 |
Expression pattern of human hair keratin basic 1 (hHb1) in hair follicle and pilomatricoma.
Using in situ hybridization, human hair keratin basic 1 (hHb1) gene expression was investigated in human normal scalp. hHb1 transcripts were specifically detected in the cortical cells of hair shaft but neither in the outer and inner root sheaths, nor in the hair cuticle or the medulla. hHb1 expression was detected strongly in cortical cells located from the beginning of the keratogenous zone up to the isthmus. These data specify the localization of hHb1 expression. Furthermore, neoplasms with follicular differentiation, including trichoblastoma, trichoepithelioma, pilomatricoma, pilar carcinoma and basal-cell carcinoma, were analysed for hHb1 gene expression. One of the 4 pilomatricoma specimens examined exhibited a very high level of hHb1 transcripts. Interestingly, this labeling was specifically associated to a transitional cell layer en route to trichocytic differentiation, providing evidence that in pilomatricoma, epithelial germ cells can differentiate towards hair shaft keratinocytes before evolving in ghost cells. Topics: Carcinoma, Basal Cell; Cell Differentiation; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Keratinocytes; Keratins; Neoplasm Proteins; Pilomatrixoma; RNA, Messenger; RNA, Neoplasm; Skin Neoplasms | 1997 |
Trichoblastoma and basal cell carcinoma are neoplasms with follicular differentiation sharing the same profile of cytokeratin intermediate filaments.
Trichoblastoma and nodular basal cell carcinoma are generally held to be distinctive epithelial neoplasms with some overlapping features. We investigated 30 trichoblastomas in which the basaloid cells expressed cytokeratins (CK) CK5/6, CK14, CK17, CK19, and, in a few cells, vimentin. The cells of the periphery of small and large cysts showed the same profile. Cells lining the lumen of small cysts expressed CK14, CK17, and involucrin, and those in larger cysts showed a positivity for CK1, CK4, CK10, CK14, CK17, and involucrin. The remaining tested antibodies (CK7, CK8, CK13, CK18, CK20, alpha-smooth-muscle actin) were negative in all cases. The cells of the stroma expressed vimentin and in 22 cases, the CD34 antigen. Seventeen nodular basal cell carcinomas showed exactly the same staining pattern. Furthermore, there are striking immunohistochemical similarities between the neoplastic basaloid cells of both neoplasms and the cells of the hair germ. Therefore, trichoblastoma and nodular basal cell carcinoma cannot be distinguished by their pattern of cytokeratin expression in paraffin sections. The virtually identical cytokeratin pattern seen in trichoblastoma, basal cell carcinoma, and the developing fetal hair follicle is compelling evidence for common differentiation pathway. Topics: Actins; Adult; Aged; Aged, 80 and over; Antigens, CD34; Carcinoma, Basal Cell; Cell Differentiation; Cysts; Epithelium; Female; Fetus; Gene Expression Regulation, Neoplastic; Hair Follicle; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Melanocytes; Middle Aged; Neoplasms, Basal Cell; Paraffin Embedding; Protein Precursors; Skin Neoplasms; Vimentin | 1997 |
Microcystic adnexal carcinoma with extensive sebaceous differentiation.
We report two cases of microcystic adnexal carcinoma showing extensive sebaceous differentiation. Multiple cellular nests and strands within a moderately sclerotic stroma involving the full thickness of the dermis were observed. Clusters of basaloid cells with extensive sebaceous differentiation were present. Foci of sebaceous ductal differentiation were observed in the more superficial areas. Neither strikingly atypical cells nor mitotic figures were present. Perineural invasion was present in the deep areas of both tumors. Clinically, the lesions were solitary whitish-pink papules with a central dell on the faces of 2 men (aged 78 and 73 years old). We propose a relationship between these tumors and other cytologically bland but locally aggressive adnexal carcinomas. Sebaceous differentiation itself in a poorly circumscribed neoplasm does not indicate conventional extraocular sebaceous carcinoma. We propose a simple classification of locally aggressive adnexal carcinomas that takes into account the full range of adnexal differentiation that can occur in such lesions. Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Skin Appendage; Cell Differentiation; Elastic Tissue; Epidermis; Facial Neoplasms; Follow-Up Studies; Glycosaminoglycans; Humans; Keratins; Male; Mitosis; Neoplasm Invasiveness; Neurons; S100 Proteins; Sclerosis; Sebaceous Glands; Skin Diseases; Skin Neoplasms | 1997 |
Multiple malignant cylindromas of skin in association with basal cell adenocarcinoma with adenoid cystic features of minor salivary gland.
This unusual case is that of a middle-aged man exhibiting a tumor diathesis including a basal cell adenocarcinoma with features of adenoid cystic carcinoma arising in minor salivary gland of lip in association with multiple primary malignant cylindromas of skin. The labial lesion showed invasive tubules, solid epithelial sheets and cribriform structures. It did not exhibit PAS positive juxta-tubular basement membrane material. The skin lesions all showed features of a highly infiltrative cylindromatous carcinoma with two cell types, peripheral palisading and prominent PAS positive juxta-tubular basement membrane material. Immunocytochemical studies of the lip lesion and one of the skin lesions showed similarities, including positive staining for high and low molecular weight keratins and S-100 with negative staining for CEA. The precious descriptions of tumor diatheses involving dermal cylindromas and dermal analogue tumors of salivary glands and the distinctions with the present study are noted. If benign and even malignant cylindromas were described in the literature to be associated with basal cell adenocarcinoma of the major salivary glands, our case is unique by its association with this rare malignant tumor in a minor salivary gland. Topics: Adenocarcinoma; Adult; Carcinoma, Adenoid Cystic; Disease Susceptibility; Humans; Keratins; Lip; Male; S100 Proteins; Salivary Gland Neoplasms; Scalp; Skin Neoplasms | 1997 |
Cutaneous leiomyosarcoma.
We report the clinical, histopathologic, immunohistologic, and prognostic findings in 19 patients with cutaneous leiomyosarcoma, eight males and 11 females (mean age, 66 years; age range, 41-93 years). The tumors presented mainly as solitary lesions and were located on the head and neck (eight lesions), trunk (four lesions), upper extremities (three lesions), and lower extremities (four lesions). Histopathologically, two predominant growth patterns were observed: nodular (12 cases) and diffuse (seven cases). Neoplasms with a nodular growth pattern were characterized by high cellularity and prominent nuclear atypia, and they showed conspicuous mitoses, several necrotic cells, and sometimes extensive necrotic areas. By contrast, most cutaneous leiomyosarcomas with a diffuse growth pattern revealed low cellularity, well-differentiated smooth muscle cells, inconspicuous mitotic figures, and few or no necrotic cells. Immunohistologic investigations revealed all cutaneous leiomyosarcomas to express vimentin and smooth muscle actin. Pan-muscle actin (HHF-35) was also expressed in most cases (15 lesions). However, only 12 lesions showed positive staining for desmin. Remarkable was the expression of cytokeratins in five lesions. Clinical follow-up revealed local recurrences in five patients (three cases with nodular pattern and two lesions with a diffuse pattern) after a period ranging from 8 months to 3 years after surgical excision. No distant metastases have been observed in our series. We conclude that cutaneous leiomyosarcoma with a diffuse growth pattern may constitute a pitfall in histopathologic diagnosis because of the presence of only subtle criteria for malignancy. Cutaneous leiomyosarcoma may show different immunophenotypes, thus emphasizing the importance of using a large panel of antibodies (smooth muscle actin, HHF-35, desmin, vimentin, cytokeratins, and S-100 protein) in immunohistologic diagnosis. Cutaneous leiomyosarcoma sometimes reveals local recurrences, but it has negligible potential for distant metastases. Topics: Actins; Adult; Aged; Aged, 80 and over; Desmin; Female; Follow-Up Studies; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Leiomyosarcoma; Male; Middle Aged; Mitotic Index; Necrosis; Prognosis; Retrospective Studies; Skin Neoplasms; Vimentin | 1997 |
The actinic comedonal plaque.
A case of actinic comedonal plaque is reported. We comment on the case as well as describe the skin surface microscopic features. Topics: Acne Vulgaris; Aged; Carcinoma, Basal Cell; Diagnosis, Differential; Facial Dermatoses; Humans; Keratins; Male; Photosensitivity Disorders; Skin; Skin Neoplasms | 1997 |
Delays in malignant tumor development in transgenic mice by forced epidermal keratin 10 expression in mouse skin carcinomas.
The keratin cytoskeleton is formed in different epidermal compartments by distinct polypeptides. Basal, proliferative keratinocytes express keratin (K) 5 and K14, whereas, suprabasal, post-mitotic keratinocytes express K1 and K10. Changes in this keratin pattern have been found to occur in hyperproliferative skin disorders and, in particular, throughout mouse epidermal carcinogenesis. Whereas some keratins not found in normal epidermis (K6, K16, K13, and K8) are induced at different stages of tumor development, K1 and K10 expression is lost. To determine whether K1 and K10 loss is just a consequence of the altered differentiation program or an event required for tumor progression, we generated transgenic mice carrying the human keratin 10 gene (hK10) under the control of a bovine keratin 6 gene regulatory region, which is silent in normal skin but is induced and drives transgene expression in hyperproliferative skin keratinocytes and, therefore, in skin tumors. Transgenic animals subjected to a complete carcinogenesis protocol developed tumors that contained various amounts of transgenic hK10. Although no significant difference was found in tumor number or malignancy, tumor onset was significantly delayed in transgenic mice, indicating that the presence of K10 actually impairs tumor development. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Squamous Cell; Cattle; Cell Division; Cocarcinogenesis; Gene Expression; Humans; Keratin-10; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Skin; Skin Neoplasms; Skin Physiological Phenomena; Transgenes | 1997 |
Changes in protein expression during multistage mouse skin carcinogenesis.
To directly compare the expression patterns of different proteins known to be altered during mouse skin carcinogenesis, serial sections of normal and hyperplastic skin and tumors from various stages of 7,12-dimethylbenz[a]anthracene-initiated, 12-O-tetradecanoylphorbol-13-acetate-promoted female SENCAR mice were examined by immunohistochemistry. In untreated, normal mouse skin, keratin 1 (K1) and transforming growth factor-beta1 (TGFbeta1) were strongly expressed in the suprabasal layers, whereas integrin alpha6beta4 was expressed only in basal cells and only moderate staining for transforming growth factor-alpha (TGFalpha) was seen. In hyperplastic skin, TGFalpha expression became stronger, whereas expression of another epidermal growth factor (EGF) receptor ligand, heparin-binding EGF-like growth factor (HB-EGF), was strongly induced in all epidermal layers from no expression in normal skin. Likewise, the gap-junctional protein connexin 26 (Cx26) became highly expressed in the differentiated granular layers of hyperplastic skin relative to undetectable expression in normal skin. Expression of cyclin D1 in the proliferative cell compartment was seen in all benign and malignant tumors but not in hyperplastic skin. Beginning with very early papillomas (after 10 wk of promotion), expression of alpha6beta4 in suprabasal cells and small, focal staining for keratin 13 (K13) were seen in some tumors. Later (after 20-30 wk), focal areas of gamma-glutamyl transpeptidase (GGT) activity appeared in a few papillomas, whereas TGFbeta1 expression began to decrease. Cx26 and TGFalpha staining became patchier in some late-stage papillomas (30-40 wk), whereas suprabasal alpha6beta4, K13, and GGT expression progressively increased and K1 expression decreased. Finally, in squamous cell carcinomas (SCCs), there was an almost complete loss of K1 and a further decline in TGFalpha, HB-EGF, TGFbeta1, and Cx26 expression. On the other hand, almost all SCCs showed suprabasal staining for alpha6beta4 and widespread cyclin D1 and K13 expression, whereas only about half showed positive focal staining for GGT activity. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antigens, Surface; Carcinogens; Connexin 26; Connexins; Cyclin D1; Cyclins; Epidermal Growth Factor; Female; gamma-Glutamyltransferase; Heparin-binding EGF-like Growth Factor; Integrin alpha6beta4; Integrins; Intercellular Signaling Peptides and Proteins; Keratins; Mice; Mice, Inbred SENCAR; Neoplasm Proteins; Oncogene Proteins; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transforming Growth Factor alpha | 1997 |
Merkel cell hyperplasia in chronic radiation-damaged skin: its possible relationship to fibroepithelioma of Pinkus.
Moderate hyperplasia of Merkel cells (MC) in chronic sun-damaged skin and hypertrophic actinic keratoses is well known. In the present study we investigated the number of MC in 24 samples of chronic radiation dermatitis and 19 cases of fibroepithelioma of Pinkus (FP), which is known to arise preferably in radiation-damaged skin. Using antibodies against the low molecular weight cytokeratins 8, 18, and 20 and chromogranin A to visualize MC, we found hyperplasia of MC in chronic radiation dermatitis. Additionally, in all FPs we could detect many MC, especially in areas with a pronounced fenestrated pattern. Recently, regulative functions of MC on the growth of follicular epithelium under various conditions were discussed. Thus, MC hyperplasia suggests a causal role also in the development of FP. In this context, hyperplasia of MC in chronic radiation dermatitis could explain the frequent occurrence of FP due to radiation exposure. As we recently found MC also in trichoblastomas but not in basal-cell carcinomas, the MC in FP may indicate its relationship to the benign trichoblastoma rather than to the basal-cell carcinoma. It is possible that regulative influences of the MC are important for the clinically rather benign course of FP. Topics: Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Chromogranin A; Chromogranins; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Merkel Cells; Radiodermatitis; Skin Neoplasms | 1997 |
Histogenesis of mixed tumor of the skin, apocrine type: immunohistochemical study of keratin expression.
To investigate the histogenesis of mixed tumor of the skin, apocrine type, the immunophenotypes of 10 cases were examined using 19 different monoclonal anti-keratin antibodies and antibodies against carcinoembryonic antigen (CEA) and involucrin. By using light microscopy, four epithelial elements in this tumor were characterized: tubular branching structures with lumina lined by cuboidal epithelium and those with lumina lined by columnar epithelium, keratinous cysts, and solid aggregates of epithelial cells. The immunohistochemical patterns of cytokeratin expression suggested that cuboidal and columnar cells differentiated, respectively, toward the ductal and secretory cells of apocrine glands, whereas keratinous cysts revealed follicular infundibular differentiation. Furthermore, CEA expression, a marker for sweat-gland differentiation, was present not only on tubules' luminal surfaces but also on the inner surfaces of keratinous cysts. The simultaneous coexpression of CEA and cytokeratins specific for follicular infundibulum in the keratinous cysts, although perplexing, suggested that keratinous cysts may contain some cells differentiating toward the intrafollicular portion of apocrine ducts that enter infundibulae rather than eccrine ducts that have no infundibular association. We conclude that apocrine type of mixed tumors of the skin demonstrate differentiation toward all components of apocrine units. Topics: Adenoma, Pleomorphic; Apocrine Glands; Carcinoembryonic Antigen; Cell Differentiation; Cell Lineage; Cysts; Eccrine Glands; Epithelial Cells; Epithelium; Gene Expression Regulation, Neoplastic; Hair Follicle; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Middle Aged; Protein Precursors; Skin Neoplasms; Sweat Glands | 1997 |
Solitary fibrous tumor of the skin.
Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that most commonly involves the pleura, but is increasingly more often observed in extrapleural locations. A 37-year-old woman presented with an SFT involving the skin and subcutaneous tissue of the scalp. Histologically, SFT is well circumscribed and composed of uniform spindle cells arranged in interlacing fascicles. It exhibits alternating hypercellular and hypocellular areas with abundant thick, often keloid-like, hyalinized collagen. Hemangiopericytoma-like areas are frequently prominent. Immunohistochemical markers for smooth muscle, neural, and epithelial differentiation are negative, but generalized positivity for CD-34 is characteristic. Because of the expanding spectrum of anatomic involvement of SFT, it is not surprising that on rare occasions this tumor may involve the skin. Topics: Actins; Adult; Antigens, CD; Antigens, CD34; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Collagen; Desmin; Female; Hemangiopericytoma; Humans; Hyalin; Immunohistochemistry; Keloid; Keratins; Mesoderm; Mucin-1; Neoplasms, Fibrous Tissue; Pleural Neoplasms; S100 Proteins; Scalp; Skin Neoplasms; Vimentin | 1997 |
Syringoid eccrine carcinoma: a case report.
We report a case of syringoid eccrine carcinoma, a rare syringomatous tumor of the skin, occurring in a 70-year-old woman. Histological and immunohistochemical criteria are given to differentiate this neoplasm from other primary carcinomas of the skin as well as from skin metastases of internal malignancies. Topics: Aged; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Carrier Proteins; Cell Nucleus; Chromatin; Coloring Agents; Cytoplasm; Eccrine Glands; Female; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Membrane Transport Proteins; Neoplasm Proteins; Periodic Acid-Schiff Reaction; S100 Proteins; Skin Neoplasms; Sweat Gland Neoplasms; Syringoma; Vimentin | 1997 |
Combined neuroendocrine carcinoma of the skin (Merkel cell tumor) and trichilemmal cyst.
We report a case of neuroendocrine (Merkel cell) carcinoma (NC) of the skin, associated with a trichilemmal cyst, showing pagetoid spread into the trichilemmal epithelium. The association of the two lesions may strengthen the hypothesis that NC originates from pluripotent stem cells of adnexal epithelium. Topics: Aged; Biomarkers, Tumor; Carcinoma, Merkel Cell; Cell Nucleolus; Cell Nucleus; Chromatin; Cytoplasm; Epidermal Cyst; Epithelium; Female; Humans; Keratins; Neoplastic Stem Cells; Neurofilament Proteins; Phosphopyruvate Hydratase; Skin; Skin Diseases; Skin Neoplasms | 1997 |
Expression of the human erythrocyte glucose transporter Glut1 in cutaneous neoplasia.
The increased glucose uptake seen in cancer cells correlates with the expression of human erythrocyte glucose transporter (Glut1) protein in certain human malignancies.. Our purpose was to determine Glut1 expression in cutaneous neoplasms.. A polyclonal anti-Glut1 antibody (MYM) and a standard ABC immunoperoxidase technique were used to determine Glut1 expression in invasive squamous cell carcinomas (SCCs), SCC in situ, basal cell carcinomas (BCCs), melanomas, actinic keratoses (AKs), seborrheic keratoses, common acquired nevi, and scars with regenerative epidermal hyperplasia.. All of the cases of SCC in situ, 14 of 15 (93%) of the SCC, and 13 of 15 AKs (87%) showed intense membranous staining for Glut1. Glut1 staining was present in the epidermis of 8 of 15 scars (53%) but was not detected in any BCC, even in areas of focal keratinization and squamous metaplasia. Glut1 reactivity was absent in the melanomas and seborrheic keratoses.. Glut1 expression in a cutaneous lesion strongly suggests a proliferative lesion of the squamous cell type. Topics: Antibodies; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Division; Cicatrix; Dermatitis, Seborrheic; Epidermis; Epithelial Cells; Gene Expression Regulation, Neoplastic; Glucose; Glucose Transporter Type 1; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Keratosis; Melanoma; Monosaccharide Transport Proteins; Neoplasm Invasiveness; Nevus; Regeneration; Skin Neoplasms | 1997 |
Clear cell acanthoma developing in epidermal nevus.
A 33-year-old Japanese woman presented with a black papule on a pigmented lesion which had been on her right thigh since her early childhood. A hematoxylin-eosin-stained section revealed a sharply demarcated, acanthotic epidermis composed of enlarged clear cells, which stained positively for epithelial membrane antigen and negatively for carcinoembryonic antigen. With antikeratin antibodies, the tumor cells stained for AE1 and AE3, but did not stain for CAM5.2. They contained abundant glycogen. Histologically, we diagnosed the case as a clear cell acanthoma which developed in the pre-existing epidermal nevus. This is the second such case in the literature. Topics: Adult; Female; Glycogen; Humans; Hyperplasia; Keratins; Mucin-1; Nevus, Pigmented; Skin Neoplasms | 1997 |
Epithelioid sarcoma of the tongue.
A case of epithelioid sarcoma in the tongue is reported. The patient, a 35 year old woman, presented with a non-ulcerated painful lesion of the tongue. Microscopically, the tumour was characterised by multiple coalescent nodules with central geographic necrosis infiltrating the lingual muscle. The tumour cells were epithelioid with abundant eosinophilic cytoplasm and atypical nuclei. Immunohistochemically, the tumour cells stained for vimentin, keratin, and epithelial membrane antigen. These morphological and immunohistochemical appearances led to the diagnosis of epithelioid sarcoma of the tongue. Seven years later, the patient died with metastatic dissemination to the scalp, lungs, and brain. No case of epithelioid sarcoma arising in the tongue has been described previously. Topics: Adult; Brain Neoplasms; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Sarcoma; Scalp; Skin Neoplasms; Tongue Neoplasms | 1997 |
Trichogenic trichoblastoma arising on the supraclavicular fossa with an immunohistochemical study of cytokeratin expression.
We report a 52-year-old female with trichogenic trichoblastoma arising on the supraclavicular fossa. Clinical and histological examinations revealed a thumbnail-sized, elastic, hard, subcutaneous nodule which consisted of keratinous cysts and epithelial cords of basaloid cells with focally follicular differentiation. Based on histological observations, a diagnosis of trichogenic trichoblastoma was made. An immunohistochemical study using a panel of monoclonal antibodies against cytokeratins was performed to investigate the nature and differentiation of this tumour. The most characteristic findings of the immunohistochemistry were CK 8 and 19 expression in the epithelial cords and the outer cells of the cystic structures. These immunoreactivities were similar to those of the outermost layer of the outer root sheath between the lower permanent portion and the upper transient portion, and immunostaining with the other antibodies confirmed this similarity. We can speculate that trichogenic trichoblastoma differentiates mainly toward the outermost layer of the outer root sheath between the lower permanent portion and the upper transient portion, and then into follicular structures. Topics: Female; Hair Follicle; Humans; Keratins; Middle Aged; Neoplasm Proteins; Skin Neoplasms | 1997 |
Carcinogenesis in human skin grafted to SCID mice.
To directly examine a multistage carcinogenesis model and the role of UV light in human tissues, we grafted human skin onto mice with severe combined immunodeficiency disease. We found that the maximum dose of UV radiation in the B range (UVB; 280-320 nm) tolerated by these grafts was 500 J/m2 three times weekly. One hundred fifty-one grafted mice were then randomized and observed for a median of 9 months in five groups: no treatment, chemical initiation alone, UVB as a complete carcinogen, initiation plus UVB promotion, and initiation plus UVB and phorbol ester promotion. Actinic damage and squamous atypia were found in grafts of all groups receiving UV treatment; unequivocal human squamous carcinomas developed in two of these. Species origin was verified by human-specific bisbenzimide staining and in situ hybridization for human-specific Alu segment. Overall basal proliferation, measured immunohistologically, was reduced in UV-treated grafts, but foci of hyperproliferation were seen in conjunction with the dedifferentiated expression of cytokeratins 1, 10 and 5, 8. Murine tumors also developed frequently, confirming the biological relevance of the carcinogenic strategies tested. These findings demonstrate that development of malignant human tumors can be experimentally accelerated in human tissue. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antigens, Neoplasm; Carcinogens; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Humans; Keratins; Ki-67 Antigen; Mice; Mice, SCID; Neoplasm Proteins; Nuclear Proteins; Papilloma; Skin Neoplasms; Skin Transplantation; Tetradecanoylphorbol Acetate; Transplantation, Heterologous; Ultraviolet Rays | 1996 |
Atypical fibroxanthoma in a renal graft recipient.
Topics: Facial Neoplasms; Histiocytoma, Benign Fibrous; Humans; Keratins; Kidney Transplantation; Male; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms; Vimentin | 1996 |
Immunohistochemical study of primary and recurrent basal cell and metatypical carcinomas of the skin.
We investigated cell proliferation and expression of cytoskeletal proteins in 32 cases of primary basal cell carcinomas (BCC), 10 cases of recurrent BCC, and 10 cases of metatypical carcinomas (MTC). Paraffin-embedded biopsies were evaluated immunohistochemically with a battery of antibodies. Antibodies to proliferating cell nuclear antigen (PCNA) demonstrated comparatively low numbers of proliferating cells in 25 of 32 cases of primary BCC. In contrast, both recurrent BCC and MTC exhibited three to four times higher levels of proliferating cells than primary BCC. PCNA-positive cells were usually distributed uniformly throughout the lobules; at times, however, they were localized to the outer areas of those neoplasms, with a comparatively low level of proliferation index. Antibodies to keratin 17 strongly stained cells of all BCC cases, and antibodies to keratin 8 reacted with most of them. In contrast, the staining intensity of both types of keratin in MTC was decreased six to eight times as compared with all BCC. In addition, cells of eight BCC and three MTC reacted with antibodies to smooth muscle alpha-actin and myosin, neoplasms that did not differ by the number of PCNA-positive nuclei from carcinomas without contractile proteins. The differences in cell proliferation and keratin expression between BCC and MTC may be useful criteria for further distinguishing these carcinomas. The appearance of contractile proteins in some BCC and MTC may be the result of, or implies, myoepithelial differentiation. Topics: Actins; Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Basosquamous; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myosins; Neoplasm Recurrence, Local; Skin Neoplasms | 1996 |
Differentiation-associated localization of small proline-rich protein in normal and diseased human skin.
The expression of SPRR (small proline-rich protein) was investigated in normal human skin and in diseased skin from patients with psoriasis, squamous cell carcinoma, basal cell epithelioma, naevus pigmentosus, ichthyosis vulgaris and several inflammatory skin diseases, by immunohistochemical staining. A polyclonal antibody was raised against a synthetic peptide for a C-terminal common region for SPRR1 and SPRR3. In immunoblot analysis, a positive band of 18 kDa was detected, which showed the presence of SPRR1 in human epidermal keratinocytes. In normal epidermis, positive staining for SPRR was observed in keratinocytes in the granular layer and the uppermost or two spinous cell layers, with no staining of the other spinous or basal layers. The staining was obvious at the cell periphery, weak at the cytoplasm, and absent in the nucleus. Staining was observed in several outer layers of the follicular infundibulum to the isthmus. No staining was detected in the inner root sheath of the hair follicles, hair matrix, sebaceous gland, eccrine gland, eccrine duct, melanocytes, Langerhans cells or fibroblasts. The arrectores pilorum, striated muscles, muscle layers of vessels, and myoepithelia of eccrine gland, were weakly stained. In psoriatic skin, stained keratinocytes were distributed in the spinous cell layers except for the basal layer. In ichthyosis vulgaris, SPRR was barely expressed in the uppermost living cell layers of the epidermis. In epidermolytic hyperkeratosis, degenerated squamous cells widely expressed SPRR. In Darier's disease, dyskeratotic cells were clearly stained. In squamous cell carcinoma, staining was observed in keratotic cells around horny pearls. In basal cell epithelioma, naevus pigmentosus, and malignant melanoma, the tumour cells or naevus cells were not stained. The distribution of SPRR was similar to that of involucrin in normal and several diseased skin, except for ichthyosis vulgaris. We conclude that SPRR is expressed in close association with epidermal differentiation in normal skin and skin diseases. The alteration of the expression of the proteins correlated to terminal differentiation, and differs from disease to disease. Topics: Adult; Aged; Amino Acid Sequence; Cell Differentiation; Cornified Envelope Proline-Rich Proteins; Dermatitis; Epidermis; Female; Humans; Immunoblotting; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Molecular Sequence Data; Proteins; Psoriasis; Skin; Skin Diseases; Skin Neoplasms | 1996 |
Trichohyalin expression in skin tumors: retrieval of trichohyalin antigenicity in tissues by microwave irradiation.
The antitrichohyalin antibody AE 15 is effective for identifying the cell lineage that undergoes the pathway of inner root sheath-type differentiation. Unfortunately, the AE 15 does not react with trichohyalin in tissue that is formalin-fixed and embedded in paraffin according to routine procedures.. We attempted to retrieve the trichohyalin antigenicity in formalin-fixed, paraffin-embedded biopsy specimens that included normal skin as well as skin tumors such as trichofolliculoma and pilotricoma.. We found that the use of a metal solution in combination with microwave oven heating improves the trichohyalin immunoreactivity substantially. Further, trichohyalin was found to be expressed not only in the secondary hair structure in trichofolliculoma but also in a certain cell lineage that differentiates to squamoid cells in pilomatricoma.. Our findings established that surgical specimens processed under routine procedures can be successfully investigated with AE 15 using the microwave irradiation method. Studies of epidermal diseases expressing trichohyalin should provide valuable insights into our understanding the functional significance of trichohyalin during abnormal keratinization. Topics: Adjuvants, Immunologic; Cell Lineage; Epidermis; Epithelium; Epitopes; Fixatives; Formaldehyde; Gene Expression Regulation, Neoplastic; Hair Follicle; Hot Temperature; Humans; Intermediate Filament Proteins; Keratins; Microwaves; Neoplasms, Basal Cell; Paraffin Embedding; Pilomatrixoma; Protein Precursors; Skin; Skin Neoplasms; Sulfates; Tissue Fixation; Zinc Compounds; Zinc Sulfate | 1996 |
Nodular trichoblastoma with adamantinoid features.
We report a cutaneous tumor characterized by follicular differentiation and adamantinoid features that we consider to be part of the histopathologic spectrum of trichoblastoma. Previously, similar lesions have been reported in the medical literature as cutaneous lymphadenoma or lymphoepithelial tumor of the skin. Topics: Antigens, Neoplasm; Carcinoembryonic Antigen; Cell Differentiation; Facial Neoplasms; Humans; Keratins; Lymphoma; Male; Middle Aged; Mucin-1; Neoplasms, Basal Cell; Neoplasms, Glandular and Epithelial; Skin Neoplasms | 1996 |
Metastatic renal carcinoma in an African grey parrot (Psittacus erithacus erithacus).
Topics: Animals; Biopsy; Bird Diseases; Female; Keratins; Kidney Neoplasms; Liver Neoplasms; Parrots; Radiography; Skin Neoplasms | 1996 |
TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice.
TGFbeta1 has been implicated in cell cycle control and carcinogenesis. To address the exact function of TGFbeta1 in skin carcinogenesis in vivo, mice with TGFbeta1 expression targeted to keratinocytes were subjected to long-term chemical carcinogenesis treatment. TGFbeta1 showed biphasic action during multistage skin carcinogenesis, acting early as a tumor suppressor but later enhancing the malignant phenotype. The transgenics were more resistant to induction of benign skin tumors than controls, but the malignant conversion rate was vastly increased. There was also a higher incidence of spindle cell carcinomas, which expressed high levels of endogenous TGFbeta3, suggesting that TGFbeta1 elicits an epithelial-mesenchymal transition in vivo and that TGFbeta3 might be involved in maintenance of the spindle cell phenotype. The action of TGFbeta1 in enhancing malignant progression may mimic its proposed function in modulating epithelial cell plasticity during embryonic development. Topics: Animals; Carcinoma; Carcinoma, Squamous Cell; Cells, Cultured; Female; Immunologic Techniques; Integrins; Keratins; Mice; Mice, Transgenic; Papilloma; Skin Neoplasms; Transforming Growth Factor beta | 1996 |
Targeted expression of human O(6)-methylguanine-DNA methyltransferase (MGMT) in transgenic mice protects against tumor initiation in two-stage skin carcinogenesis.
Carcinogenesis proceeds in discrete steps involving initiation and promotion. There is ample evidence that the underlying cause of initiation is mutation, whereas for tumor promotion different hypotheses exist postulating the involvement of both epigenetic and genetic changes. DNA repair protects against tumor formation, but it has not been proven whether protection occurs at the level of tumor initiation or promotion. Since the most advanced experimental system for studying multistep carcinogenesis is the mouse skin, we generated transgenic mice that overexpress the human DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in their epidermal cells by virtue of cytokeratin (Ck) promoters. Total cellular methyltransferase activity was found to be significantly higher in skin protein extracts of transgenic as compared to nontransgenic mice. CkMGMT transgenic mice along with nontransgenic controls were treated according to the multistage skin carcinogenesis protocol. For initiation, a single subthreshold dose of N-nitroso-N-methylurea (MNU) or 7,12-dimethylbenz(a)anthracene (DMBA) was topically applied to the dorsal skin of the mice. Tumor promotion was carried out by repeated 12-O-tetradecanoylphorbol-13-acetate application. Our results clearly show that CkMGMT transgenic mice are strongly protected against MNU- but not DMBA-initiated skin tumor formation. As compared to nontransgenic controls, transgenic mice exhibited an approximately 6-fold reduction of skin tumor incidence after treatment with 20 micromol or 50 micromol MNU followed by 12-O-tetradecanoylphorbol-13-acetate. These results provide direct and the most compelling evidence to date that the DNA lesion O6-methylguanine is of decisive importance in tumor initiation, and that the protective effect of the repair protein MGMT in carcinogenesis is due to prevention of initiation without affecting tumor promotion. Topics: Animals; DNA Repair; Gene Expression Regulation, Enzymologic; Humans; Keratins; Methylnitrosourea; Methyltransferases; Mice; Mice, Transgenic; Neoplasms, Experimental; O(6)-Methylguanine-DNA Methyltransferase; Papilloma; Promoter Regions, Genetic; RNA, Messenger; Skin Neoplasms; Transgenes | 1996 |
Chromosome 6 trisomy as sole anomaly in a primary Merkel cell carcinoma.
We present a case of Merkel cell carcinoma of the thigh diagnosed by conventional histology, immunohistochemistry, electron microscopy and cytogenetics. A unique chromosome 6 trisomy characterized this primary neoplasm, as confirmed by FISH study. The role of chromosome analysis and interphase cytogenetics is emphasized as an adjunct in the subtyping of tumours and their prognostic evaluation. Topics: Aged; Aged, 80 and over; Carcinoma, Merkel Cell; Chromosomes, Human, Pair 6; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Karyotyping; Keratins; Male; Microscopy, Electron; Skin Neoplasms; Trisomy | 1996 |
Trichilemmal carcinoma developing in a burn scar: a report of two cases.
Two cases of trichilemmal carcinoma (TLC) developing in burn scars are reported. In Case 1, a 73-year-old man developed a TLC on his left lower leg five years after a burn. In Case 2, a 43-year-old man developed a cauliflower-like mass on his head 42 years after a burn. Histologically, tumor cells showed a lobular proliferation in continuity with the epidermis. Tumor nests were mostly composed of large atypical cells with clear cytoplasms containing PAS-positive, diastase sensitive materials. Some of the nests showed trichilemmal-type keratinization. These cases were treated only with surgical excision, and there has been no evidence since of local recurrence or metastasis. Topics: Adult; Aged; Burns; Cicatrix; Cytoplasm; Epidermis; Humans; Keratins; Leg Injuries; Male; Neoplasms, Basal Cell; Scalp; Skin Neoplasms | 1996 |
Lymphoepithelioma-like carcinoma of the skin.
Lymphoepithelioma-like carcinoma of the skin is a rare tumor with a microscopic resemblance to lymphoepitheliomatous tumors of the nasopharynx. A 62-year-old woman exhibited such a tumor on the nose together with regional lymph node metastases. Histologically, irregular islands of atypical epithelial cells unconnected to the overlying epidermis were surrounded by or mixed with numerous lymphocytes in the primary tumor. No squamous or glandular differentiation was present. Metastases to the submandibular lymph nodes appeared as glassy squamous cells that resembled trichilemmal keratinization. Staining of the tumor tissues with S-100 protein antibody revealed the presence of numerous short dendritic cells in clusters of epithelial cells. Total resection and adjunctive radiotherapy have led to a 6-year period free of recurrence. This is the second case report of this condition in Japan. Topics: Carcinoma, Squamous Cell; Cell Differentiation; Dendritic Cells; Epidermis; Epithelium; Female; Humans; Keratins; Lymphatic Metastasis; Lymphocytes; Middle Aged; Nose Neoplasms; Radiotherapy, Adjuvant; S100 Proteins; Skin Neoplasms | 1996 |
Intermediate- and low-molecular-weight keratin detection with the monoclonal antibody MNF116. An immunohistochemical study on 232 paraffin-embedded cutaneous lesions.
Immunohistochemical detection of certain low to intermediate molecular weight keratins often is impaired in routinely processed specimens due to masking of these antigens by formalin fixation. Despite standard enzymatic digestion, AE1:AE3 and CAM 5.2, two of the most currently utilized antikeratin antibody preparations, either stain weakly or fail to stain basal keratinocytes and tumors composed of basaloid keratinocytes in paraffin sections of formalin-fixed tissue. We present here our experience with the monoclonal antibody MNF116 which detects keratins 5, 6, 8, 17, and 19 (DAKO, Carpinteria, CA). We have studied 232 routinely-processed skin lesions with MNF116 and compared the staining with that of AE1:AE3 mixture or CAM 5.2. In normal skin, the staining achieved with MNF116 was particularly strong on the basal cells of the epidermis and adnexae. MNF116 was positive in all 154 epithelial tumors and negative in all but one (a leiomyosarcoma) of 78 mesenchymal and melanocytic tumors. AE1:AE3 mixture was positive in all but four poorly-differentiated squamous cell carcinomas and it was only weakly positive in most basal cell carcinomas. CAM 5.2 was positive in tumors of the sweat apparatus, Merkel cell carcinomas, metastatic carcinomas, and 5/15 basal cell carcinomas. We consider that, in routinely processed specimens, MNF116 is very useful and convenient for detection of cytokeratin expression in cutaneous lesions, and therefore helpful in the evaluation of tumors with small cells and other poorly differentiated neoplasms of the skin. Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Melanoma; Molecular Weight; Paraffin Embedding; Prospective Studies; Retrospective Studies; Skin Diseases; Skin Neoplasms | 1996 |
Trichoblastic fibroma. A case report and an immunohistochemical study of cytokeratin expression.
A 47-year-old woman noticed a nodule on her right shoulder that had been gradually increasing in size without symptoms. Histologic features of the biopsied nodule included round to irregularly shaped epithelial lobules demarcated by abundant sclerotic stroma located within the lower dermis and extending to the subcutis. The epithelial lobules consisted of cuboidal to columnar basaloid cells and were frequently arranged in narrow strands with many bifurcations and branching. Cystic structures containing lamellar keratinous material were occasionally found in connection with the lobules. The histologic findings were interpreted as trichoblastic fibroma. Immunohistochemical studies with antibodies directed against cytokeratins (CK) and involucrin revealed positive staining in most of the tumor cells with RCK102 and 34 beta E12 antikeratin antibodies, whereas the epithelial cords and the peripheral cells of the cystic structures stained with 170.2.14, 4.1.18, and CAM 5.2 antikeratin antibodies. However, CK1 or simple epithelial cytokeratins were not detected in any neoplastic elements. Based on comparative immunohistochemical findings in normal hair follicles, we propose that trichoblastic fibroma may first differentiate toward the outermost cell layer of the outer root sheath between the lower permanent portion and the upper transient portion and then into various other parts of the hair follicle. Topics: Epithelium; Female; Fibroma; Gene Expression Regulation, Neoplastic; Hair Follicle; Humans; Immunohistochemistry; Keratins; Middle Aged; Protein Precursors; Sclerosis; Shoulder; Skin; Skin Neoplasms | 1996 |
Gingival metastasis of merkel cell carcinoma: a case report.
An 82-year-old Caucasian man developed an ulcerated mass on the anterior mandibular gingiva. Five years previously he had been treated for a Merkel cell carcinoma (MCC) on his right cheek. Histopathologic examination showed small tumor cells with scanty cytoplasm, suggestive of malignancy. Immunohistochemical studies were performed with the use of nine antibodies. S-100 protein and leukocyte common antigen were helpful in ruling out melanoma and lymphoma. Pronounced reaction was shown for cytokeratin 20, a new histodiagnostic marker whose expression is almost entirely confined to Merkel cells, the gastric epithelium, and urothelium. The tentative diagnosis of metastasis of MCC was confirmed. Immunohistochemical studies are useful diagnostic aids in the establishment of the diagnosis of Merkel cell carcinoma. Topics: Aged; Aged, 80 and over; Carcinoma, Merkel Cell; Cheek; Cytoplasm; Diagnosis, Differential; Facial Neoplasms; Gingival Neoplasms; Humans; Keratins; Lymphoma; Male; Mandibular Neoplasms; Melanoma; Skin Neoplasms | 1996 |
Nodular basal cell carcinoma in vivo vs in vitro. Establishment of pure cell cultures, cytomorphologic characteristics, ultrastructure, immunophenotype, biosynthetic activities, and generation of antisera.
In this study we developed an in vitro model of nodular basal cell carcinoma (BCC). We obtained pure cultures of BCC cells and compared the morphologic characteristics, ultrastructure, immunophenotype, and behavior of cultured tumor cells with those of their in vivo counterparts. Tumors were excised from patients undergoing Mohs micrographic surgery. We established 69 primary cell cultures from 32 patients with nodular BCC.. Three cell types grew in primary cultures: fibroblasts, normal-appearing keratinocytes, and cells with dual (spindle and epithelioid) morphologic characteristics. Contaminating fibroblasts were removed using 0.125% trypsin-0.02% edetic acid, and normal-appearing keratinocytes were cornified and eliminated by temporarily increasing the concentration of calcium in the growth medium. The cells with dual morphologic characteristics remained intact and exhibited relentless growth in pure cultures. That these seemingly immortal cell strains represent true nodular BCC was demonstrated by (1) their biphasic morphologic characteristics and very slow cell growth rate, (2) their capability for anchorage-independent growth in soft agar, (3) their ultrastructural similarities to freshly excised nodular BCC, (4) their ability to generate antibodies selectively labeling nodular BCC tumor nests in vivo, and (5) their immunophenotypic similarities to BCC in vivo on more than 20 different cell markers.. This study provides a simple technique for establishing pure cell cultures of nodular BCC and describes extensively the in vitro parameters of tumor cell growth. The striking differences in behavior of cultured tumor cells in the presence or absence of normal-appearing keratinocytes suggest that normal human epidermal keratinocytes can suppress the growth of BCC cells. Topics: Adult; Aged; Animals; Antibodies, Neoplasm; Antigens, Neoplasm; Carcinoma, Basal Cell; Cell Division; Female; Filaggrin Proteins; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Rabbits; Skin Neoplasms; Tumor Cells, Cultured | 1996 |
Epidermotropically metastatic breast carcinomas. Rare histopathologic variants mimicking melanoma and Paget's disease.
Epidermotropic metastases from internal malignancies are exceedingly rare. We report two examples of epidermotropic metastatic breast carcinoma with striking intraepidermal involvement. The first case mimicked melanoma because the neoplastic cells contained melanin and were disposed both as single units and as nests at the dermoepidermal junction and throughout the epidermis. In the second case, the neoplastic cells were seen as isolated neoplastic cells with large, pale cytoplasm scattered throughout the epidermis, closely resembling extramammary Paget's disease. Immunohistochemical studies in both cases demonstrated the epithelial nature of intraepidermal neoplastic cells, which showed an immunophenotype identical to the neoplastic cells present in the dermis: positive staining with anti-cytokeratins, CEA, EMA, and GCDFP-15 and negative with anti-S-100 protein and HMB-45. These findings ruled out the possibility of a collision lesion, or simultaneous occurrence of melanoma and metastatic breast carcinoma. Pagetoid intraepidermal spread of metastatic breast carcinoma, as in our two cases, is exceptional. We also discuss the histogenetic similarities between our findings and those of mammary and extramammary Paget's disease, as well as the differential diagnosis of other cutaneous disorders characterized by pagetoid intraepidermal spread of neoplastic cells. Topics: Aged; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Diagnosis, Differential; Epidermis; Female; Humans; Immunohistochemistry; Keratins; Melanins; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Paget Disease, Extramammary; Paget's Disease, Mammary; S100 Proteins; Skin Neoplasms | 1996 |
[Panfolliculoma. Clinical and immunohistochemical findings in 4 cases].
Panfolliculoma is a rare benign neoplasm showing morphological similarities to the trichogenic trichoblastoma of Headington and the trichoblastoma of Ackerman. Eight patients have been previously reported; we add four additional patients. Their ages ranged from the 2nd to the 6th decade. The neoplasms were primarily situated on the head and the trunk. Clinical examination revealed a skin colored or red, dermal cystic nodule. The histological appearance of the panfolliculoma was characterized by symmetry, sharp circumscription and regular aggregations of cells, which were in parts solid or cystic. Additionally, follicular germs and papillae, matrical, inner and outer rooth sheath differentiation were identified. These varied forms of follicular differentiation were confirmed by the immunohistochemical expression of cytokeratins in different epithelial cells. Panfolliculoma is a benign neoplasm with proven morphological and immunhistochemical follicular differentiation. Topics: Antigens, CD34; Biomarkers, Tumor; Biopsy; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Neoplasms, Basal Cell; Skin; Skin Neoplasms | 1996 |
Primary neuroendocrine carcinoma of the skin with an unusual follicular lymphocytic infiltrate of the dermis.
Primary neuroendocrine carcinoma of the skin (PNECS) is a rare cutaneous tumor occurring predominantly on sun-exposed skin of elderly people. This histomorphological appearance of this aggressive tumor can be highly variable depending on the predominating growth pattern. We present an unusual case of PNECS: the tumor masked by a dense lymphoid infiltrate with a well-formed follicular growth pattern. In these cases of PNECS, the differential diagnosis must be extended to lymphoid neoplasms as well as lymphoepithelial neoplasms. Topics: Aged; B-Lymphocytes; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Cell Nucleus; Chromogranin A; Chromogranins; Cytoplasm; Diagnosis, Differential; Facial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymphocytes; Lymphoid Tissue; Neurofilament Proteins; Phosphopyruvate Hydratase; Skin; Skin Neoplasms | 1996 |
Lymphoepithelioma-like carcinoma of the skin.
The histopathological findings of two cases of primary lymphoepithelioma-like carcinoma (LELC) of the skin occurring in two elderly Chinese individuals are presented. Microscopically, they were well circumscribed and were composed of irregular nests of malignant epithelial cells in a background of reactive lymphoid cells including mature plasma cells. A focus of epithelial dysplasia was noted in the adjacent epidermis in one case, suggesting that the LELC might have originated from the overlying epidermis. The epithelial nature of the tumors was confirmed by cytokeratin staining. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed that the tumor cells were uniformly negative, although positive signals were detected in scattered background lymphocytes in case 1. Our results confirm the previous observation that LELC of skin is not related to Epstein-Barr virus, even in Chinese subjects. Nevertheless, such negative findings may prove to be of diagnostic value in excluding the alternative more common diagnosis of metastatic nasopharyngeal carcinoma, which is uniformly positive for EBER. Topics: Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; China; Epidermis; Epithelium; Female; Herpesvirus 4, Human; Humans; In Situ Hybridization; Keratins; Lymphocytes; Lymphoid Tissue; Male; Nasopharyngeal Neoplasms; Plasma Cells; RNA, Viral; Skin Neoplasms | 1996 |
[Tumor of the follicular infundibulum. Study of determining follicular differentiation].
Tumor of the follicular infundibulum is a rare proliferation of cells and its histogenesis or differentiation at the morphological level has been the subject of some controversy. In recent years cytokeratins have been recognized as important markers of epithelial differentiation, and of late new retrieval methods have meant it is possible to detect them in formalin-fixed and paraffin-embedded tissue. Four patients were studied, the ages ranging between the 2nd and 7th decade. The tumors were all located in the head and neck and in one case the lesion developed in a pre-existing sebaceous nevus. The morphological investigation revealed a flat, proliferation of polygonal, pale eosinophilic cells connected to epidermis or follicular infundibulum and with a centrally located nucleus. In addition, a few ductal structures resembling sebaceous ducts were seen and in one case a hair germ papilla and a follicular papilla was noted. Immunohistochemical investigations with antibodies against cytokeratins revealed differentiation comparable to that in the fetal follicular isthmus and, in one case, also differentiation in keeping with the fetal follicular infundibulum. Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Cytoplasm; Female; Hair Follicle; Hamartoma; Head and Neck Neoplasms; Humans; Keratinocytes; Keratins; Male; Middle Aged; Precancerous Conditions; Sebaceous Glands; Skin Neoplasms | 1996 |
TGF alpha and v-fos cooperation in transgenic mouse epidermis induces aberrant keratinocyte differentiation and stable, autonomous papillomas.
To assess the synergistic effect of growth and transcription factor deregulation on carcinogenesis in vivo, mating experiments were performed between transgenic mice expressing human TGF alpha or v-fos exclusively in the epidermis by means of a human keratin K1-based targeting vector (HK1.fos, HK1.TGF alpha and HK1.fos/alpha). While HK1.TGF alpha mice exhibited mild epidermal hyperplasia resulting in a wrinkled appearance, this hyperplasia was significantly increased in HK1.fos/alpha mice which also exhibited a novel opalescent and peeling skin phenotype. HK1.fos/alpha keratinocyte differentiation was considerably deregulated with cornified cells appearing in the granular layer, granular cells in the spinous layer and a sixfold increase in BrdU labeling over normal. In addition, hyperplastic HK1.fos/alpha epidermis exhibited aberrant loricrin, filaggrin and novel K13 expression associated with v-fos expression. Unlike adult HK1.TGF alpha controls, hyperplasia persisted in HK1.fos/alpha adults which also rapidly developed autonomous squamous cell papillomas. These results demonstrate that v-fos and TGF alpha over-expression can cooperate to reprogram keratinocyte differentiation and elicit the early stages of neoplasia. Moreover, TGF alpha over-expression appeared to play an early, initiating role in HK1.fos/alpha papilloma etiology, and a promotion role in the accelerated appearance of v-fos wound-associated preneoplastic phenotypes. However, the stable persistence of HK1.fos/alpha papillomas for up to 12 months, suggests that additional events are required for malignant conversion. Topics: Animals; Base Sequence; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Filaggrin Proteins; Genetic Vectors; Keratins; Mice; Mice, Transgenic; Microscopy, Electron; Molecular Sequence Data; Oncogene Proteins v-fos; Papilloma; Skin; Skin Neoplasms; Transforming Growth Factor alpha | 1995 |
Relative amounts of keratin 17 are higher than those of keratin 16 in hair-follicle-derived tumors in comparison with nonfollicular epithelial skin tumors.
Specimens of trichilemmal cyst, malignant trichilemmoma, keratoacanthoma, and epidermal cyst were examined to characterize keratin peptides in hair-follicle-derived tumors. Keratins were extracted from the specimens and analyzed by two-dimensional gel electrophoresis and densitometry; the results were then compared with those for normal epidermis, the outer root sheath of hair follicles, psoriatic epidermis, and various nonfollicular cutaneous epithelial tumors. The specific nonfollicular tumors examined were squamous cell carcinoma, Bowen disease, actinic keratosis, eccrine porocarcinoma, and sebaceous carcinoma. Immunohistochemistry also was performed with a few anti-keratin monoclonal antibodies. As a general rule, K6 and K16 were expressed in hyperproliferative conditions, such as epidermal tumors, and K17 was coexpressed in the same lesions. The ratio of K16 to K17 in many epithelial skin tumors has been unclear until now. K17 content exceeded K16 content in most follicular tumors, whereas in almost all the nonfollicular tumors and the psoriatic epidermis, K17 levels were less than or about equal to K16 levels. There was a significant difference in the ratio of K16 to K17 between follicular and nonfollicular skin tumors. These results indicate that alterations in the content of these keratins may be associated with follicular differentiation. Topics: Epidermis; Hair; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Neoplasms, Basal Cell; Psoriasis; Skin Neoplasms | 1995 |
Lymphoepithelioma-like carcinoma of the skin treated with Mohs micrographic surgery in combination with immune staining for cytokeratins.
Lymphoepithelioma-like carcinoma of the skin (LLCS) is a rare cutaneous neoplasm that histologically resembles nasopharyngeal lymphoepithelioma. Conventional surgical excision carries a considerable rate of recurrence (three of 11 reported cases with such treatment, with one patient dying of metastatic disease). We report the first case of lymphoepithelioma-like carcinoma of the skin treated with Mohs micrographic surgery. Because of its tendency to occur on the face and its potential for recurrence after incomplete removal, this tumor is a good candidate for treatment with Mohs micrographic surgery. Immunohistochemical staining of frozen sections for cytokeratins may help to detect neoplastic cells that may be obscured by the dense lymphoplasmacytic infiltrate associated with this tumor. Topics: Aged; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Male; Mohs Surgery; Nose Neoplasms; Skin Neoplasms | 1995 |
So-called mixed tumor of the skin on the wrist: an immunohistochemical study.
A case of so-called mixed tumor of the skin arising on the wrist was reported. Immunohistochemical staining of keratins of several molecular weights (AE1/AE3, RCK102, NCL-5D3 and 35 beta H11), carcinoembryonic antigen (CEA), S-100 protein, and desmin was performed. AE1/AE3 and RCK102 were positive in all the tumor cells; CEA, NCL-5D3 and 35 beta H11 were positive mainly in luminal cells of the tubuloalveolar structures. S-100 protein was positive in peripheral cells of the tubular lumina and in scattered cells in the mucous stroma. Desmin was negative in all the tumor cells. Immunohistochemical findings lent further support to the hypothesis that so-called mixed tumor of the skin differentiates into the secretory and ductal portions of the sweat gland. Topics: Adenoma, Pleomorphic; Carcinoembryonic Antigen; Desmin; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; S100 Proteins; Skin Neoplasms | 1995 |
[Multiple palmoplantar keratoses, basaliomas and porocarcinomas after arsenic therapy].
Topics: Acrospiroma; Aged; Arsenites; Biomarkers, Tumor; Biopsy; Carcinoma, Basal Cell; Diagnosis, Differential; Humans; Keratins; Keratoderma, Palmoplantar; Male; Neoplasms, Multiple Primary; Potassium Compounds; Precancerous Conditions; Skin; Skin Neoplasms | 1995 |
Changes of cytokeratin and involucrin expression in squamous cell carcinomas of the skin during progression to malignancy.
The detection of cytokeratins in neoplastic tissues by immunohistochemical methods has numerous diagnostic and investigative applications, because cytokeratins are usually conserved in tumour cells during malignant transformation. Recently, however, it has been reported that progression to malignancy is associated with commencement of expression of low-molecular-weight cytokeratins. In the present study, 42 specimens from 35 cases of squamous cell carcinoma (SCC) of the skin were analysed by immunohistochemical techniques, using polyclonal anti-involucrin antibody and a panel of monoclonal antikeratin antibodies, in order to investigate the nature and differentiation of SCCs. The expression of cytokeratins and involucrin in well-differentiated SCCs was similar to that in normal epidermis. In contrast with well-differentiated SCCs, the expression of differentiation-specific cytokeratins and involucrin was diminished in the immature tumour cells in proportion to the malignancy of the SCCs. Some antibodies, however, stained all tumour cells, irrespective of the degree of malignancy. Furthermore, expression of simple epithelial and non-cornifying stratified squamous epithelial cytokeratins was observed in atypical tumour cells of poorly differentiated SCCs. It is of interest that similar expression was noted in many tumour cells in the lymph node metastases and in some tumour cells in the primary cutaneous lesions. Cytokeratin expression similar to that in normal epidermal keratinocytes was conserved in well-differentiated SCCs, but the expression of cytokeratins changed during progression to malignant transformation. The expression of simple epithelial or non-cornifying stratified squamous epithelial cytokeratins in cutaneous SCCs may be a marker for their capability of invasion and metastatic potential. Topics: Antibody Specificity; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Protein Precursors; Skin Neoplasms | 1995 |
Birthmark due to cutaneous mosaicism for keratin 10 mutation.
Topics: Child, Preschool; Female; Humans; Keratins; Mosaicism; Nevus; Point Mutation; Skin Neoplasms | 1995 |
Sweat gland carcinoma in a human immunodeficiency virus-infected patient.
Eccrine (sweat gland) carcinoma is a rare form of skin cancer that may be locally destructive. It is known to recur after resection and can metastasize to regional or distant lymph nodes. There have been two reported cases in association with patients immunocompromised as the result of organ transplantation (I. Penn: Prog Allergy. 37: 259, 1986). We report here the first case of sweat gland carcinoma in a patient infected with the human immunodeficiency virus. Topics: Acquired Immunodeficiency Syndrome; Adenocarcinoma; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin Neoplasms | 1995 |
Mouse skin tumor progression results in differential expression of retinoic acid and retinoid X receptors.
Retinoids are powerful regulators of epidermal cell growth and differentiation and are widely used in the prevention and treatment of skin disorders and cancers in humans. Since many of the effects of retinoids on cell growth and differentiation are mediated by nuclear retinoid receptors (RARs and RXRs), we were interested in determining RAR and RXR gene expression during mouse skin tumor progression. The two-stage system of mouse skin carcinogenesis was used to generate papillomas and carcinomas, and the different stages of malignant progression (papillomas, differentiated squamous cell carcinomas, undifferentiated squamous cell carcinomas, and spindle cell carcinomas) were characterized in each tumor by specific keratin expression prior to receptor characterization. Using in situ hybridization analysis, we show that the two major RAR isoforms (alpha 1 and gamma 1), which account for most of RARs in the skin, were expressed in both the basal and suprabasal layers in mouse epidermis. In contrast, RXR alpha transcripts were compartmentalized to the basal cell layers and concentrated in hair follicles. During skin tumor progression, RAR (alpha 1 and gamma 1) transcripts were down-modulated in malignant tumor cells, whereas RXR (alpha and beta) transcript expression was expanded in papillomas and carcinomas as the number of undifferentiated cells also increased. RXR gamma was not detected in the skin or at any stage during skin tumor progression. Spindle cell tumors lacked markers of the keratinocyte phenotype and lost RAR expression, yet retained expression of RXR alpha and beta. The increased abundance of transcripts for RXRs and decreased presence of RARs in skin tumor progression may favor other nuclear signal transduction pathways requiring RXR for heterodimer formation and contribute to phenotypic progression of cancer cells. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma; Cell Compartmentation; Epidermis; In Situ Hybridization; Keratins; Mice; Papilloma; Receptors, Retinoic Acid; Retinoid X Receptors; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transcription Factors | 1995 |
Basal cell carcinoma with hyaline inclusions.
A 69 yr old man had a 4 mm basal cell carcinoma completely excised from the chin. Numerous hyaline cytoplasmic inclusions were contained within the tumor cells. The inclusions stained intensely red with Masson's trichrome, and immunocytochemically there was prominent rim labelling for keratins (bovine, callus and AE1/3) and muscle-specific actin, the latter more faintly decorating the centre of some inclusions. The inclusions were negative for antibodies to cytokeratin Cam5.2, epithelial membrane antigen (EMA), vimentin, S100, neurofilaments, glial fibrillary acidic protein (GFAP) and carcinoembryonic antigen (CEA) and there was no post Congo red apple green birefringence to indicate amyloid. Ultrastructure indicated the inclusions were composed of proteinaceous material surrounded by a defined rim of tonofilaments in cells showing no degenerative features. The findings suggested aberrant tumor cell keratinization. Familiarization with this rare variant of a common cutaneous carcinoma will alleviate diagnostic difficulties that may arise, particularly in superficial tumor curettage. Topics: Aged; Carcinoma, Basal Cell; Chin; Humans; Hyalin; Immunohistochemistry; Inclusion Bodies; Keratins; Male; Microscopy, Electron; Skin Neoplasms | 1995 |
c-fos is required for malignant progression of skin tumors.
The proto-oncogene c-fos is a major nuclear target for signal transduction pathways involved in the regulation of cell growth, differentiation, and transformation. Using the multistep skin carcinogenesis model, we have directly tested the ability of c-fos-deficient mice to develop cancer. Upon treatment with a tumor promoter, c-fos knockout mice carrying a v-H-ras transgene were able to develop benign tumors with similar kinetics and relative incidence as wild-type animals. However, c-fos-deficient papillomas quickly became very dry and hyperkeratinized, taking on an elongated, horny appearance. While wild-type papillomas eventually progressed into malignant tumors, c-fos-deficient tumors failed to undergo malignant conversion. Experiments in which v-H-ras-expressing keratinocytes were grafted onto nude mice suggest that c-fos-deficient cells have an intrinsic defect that hinders tumorigenesis. These results demonstrate that a member of the AP-1 family of transcription factors is required for the development of a malignant tumor. Topics: Animals; Cell Differentiation; Cell Transformation, Neoplastic; Epidermal Cells; Gene Expression; Genes, fos; Genes, ras; Keratinocytes; Keratins; Mice; Mice, Nude; Mice, Transgenic; Mutation; Neoplasm Transplantation; Oncogene Protein p21(ras); Papilloma; Skin Neoplasms; Time Factors; Transcription Factor AP-1 | 1995 |
Immunohistochemical and flow cytometric study of neuroendocrine carcinoma of the skin.
Immunohistochemical and flow cytometric analysis using formalin-fixed, paraffin-embedded sections was performed on 10 neuroendocrine carcinomas of the skin (NCS). Grimelius staining was positive in seven tumors. All tumors showed coexpression of CAM 5.2 and neuron-specific enolase with paranuclear dot-like or diffuse cytoplasmic reactivity. Neurofilament was positive in five cases, chromogranin in six, calcitonin and carcinoembryonic antigen in two each, and somatostatin and S-100 protein in one each. Eight primary lesions were diploid and the remaining two were aneuploid; however, two diploid NCS presented as aneuploid metastatic tumors. The follow-up periods ranged from 3 to 66 months (mean 13.6). Six patients died of metastatic diseases between 3 and 33 months (mean 9.2) after the diagnosis. There were no significant correlations among histologic features, DNA ploidy, S-phase fraction, and clinical outcome of the patients with NCS. These results indicate that a panel of antibodies may be required for immunohistochemical confirmation of neuroendocrine differentiation and that a flow cytometric analysis is not a good tool to predict the biologic behavior of NCS. Topics: Aged; Aged, 80 and over; Aneuploidy; Calcitonin; Carcinoma, Neuroendocrine; Chromogranins; Female; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Ploidies; S100 Proteins; Skin Neoplasms; Somatostatin | 1995 |
Differentiation and tumor response to retinobenzoic acid RE-80 in a malignant conversion model.
The synthetic retinobenzoic acid RE-80 was evaluated for its potential as an inductor of tumor cell differentiation and as a chemopreventive agent. A minimally toxic dose of RE-80 in vitro produced morphologic changes typical differentiation in epidermal tumor cell colonies. Indirect immunofluorescence indicated induction of a differentiation-associated keratin of internal stratified epithelia, K13, and inhibition of the differentiation-associated epidermal keratin K1. Cultured cells were skin-grafted to athymic nu/nu mice to evaluate RE-80 effects on early stage malignant progression in vivo. When tumors had grown to 3 to 4 mm in diameter, mice were treated by intraperitoneal injection with RE-80 (67 micrograms, 170 mmol, i.p., two times per week) or vehicle (100 microliters 20% ethanol). Papillomas (benign) and moderately differentiated squamous cell carcinomas were reduced in volume about 4-fold by RE-80 treatment. Larger, poorly differentiated squamous cell carcinomas were unaffected. RE-80 resulted in a lower proportion of proliferative cells (detectable by bromodeoxyuridine incorporation) and a higher proportion of moderately to well differentiated tumors after 40 days of treatment compared with control tumors, which were mainly poorly differentiated squamous cell carcinomas. K13 induction in vitro was correlated with response to retinoid in vivo. Induction of differentiation may be mechanism of the response to RE-80 in vivo since carcinoma cells expressing K13 did not incorporate bromodeoxyuridine and were on a terminal pathway. Topics: Animals; Antineoplastic Agents; Benzoates; Carcinoma, Squamous Cell; Cell Differentiation; Disease Models, Animal; Keratins; Mice; Mice, Nude; Papilloma; Skin Neoplasms; Tetrahydronaphthalenes; Tumor Cells, Cultured | 1995 |
Merkel cell tumor: report of case.
Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Merkel Cell; Cheek; Facial Neoplasms; Fatal Outcome; Female; Humans; Keratins; Membrane Glycoproteins; Mucin-1; Mucins; Phosphopyruvate Hydratase; Skin Neoplasms | 1995 |
Basal cell carcinoma associated with a giant comedone.
Topics: Aged; Carcinoma, Basal Cell; Cysts; Humans; Keratins; Male; Skin Diseases; Skin Neoplasms | 1995 |
Cutaneous epithelioid angiosarcoma exhibiting cytokeratin positivity.
Topics: Buttocks; Epithelium; Hemangiosarcoma; Humans; Keratins; Male; Middle Aged; Skin Neoplasms | 1995 |
Basal cell carcinoma: rapid techniques using cytokeratin markers to assist treatment by micrographic (Mohs') surgery.
In micrographic (Mohs') surgery, routine haematoxylin and eosin stains may present difficulties in interpretation of infiltrative (morphoeic) basal cell carcinoma. To supplement these routine stains rapid immunoperoxidase and immunofluorescence techniques are described using cytokeratin markers Dako LP34, MNF 116 or Novocastra NCL-Pan CK on frozen sections to help in the histological evaluation of these tumours. Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Mohs Surgery; Skin Neoplasms | 1995 |
Tricoadenoma of Nikolowski.
The patient, aged 50 years, with no relevant clinical history, complained of a symptomless, soft tumor of the right buttock that had been present for many years. On examination, it was found to be pediculate, oval, somewhat erythematous, firm on palpation, and with a central keratin plug. The greatest diameter of the lesion was 1.2 cm (Fig. 1). On surgical removal of the lesion, it was seen to be composed of a symmetric intradermal proliferation of cystic formations, uniformly distributed throughout and made up of flat, pluristratified epithelium with laminated keratin. There was little difference in the thickness of the walls of the cysts (Fig. 2). Some cysts were attached to a short tadpole-shaped, epithelial cord and surrounded by a scanty fibroblastic stroma. No hairmatrix-like differentiation nor basaloid structures were seen, nor were atypical cells present. There was hardly any inflammatory infiltration. Topics: Buttocks; Cysts; Epithelium; Fibroblasts; Humans; Keratins; Middle Aged; Neoplasms, Basal Cell; Skin Neoplasms | 1995 |
Triple cancers involving extramammary Paget's disease.
Topics: Carcinoembryonic Antigen; Carcinoma; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Follow-Up Studies; Humans; Hypopharyngeal Neoplasms; Keratins; Laryngeal Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Paget Disease, Extramammary; Penile Neoplasms; Skin Neoplasms | 1995 |
Immunohistochemical distribution pattern of intermediate filament proteins in 50 feline neoplasms.
Twenty-eight epithelial and 22 nonepithelial feline tumors were studied immunohistochemically. Epithelial tumors were 10 squamous cell carcinomas, two basal cell tumors, two sebaceous gland carcinomas, three apocrine gland carcinomas, three thyroid papillary carcinomas, one thyroid solid carcinoma, one renal clear cell carcinoma, one renal papillary carcinoma, one endometrial carcinoma, and four lung bronchioloalveolar carcinomas. Nonepithelial tumors were 10 fibrosarcomas, one liposarcoma, one leiomyosarcoma, one rhabdomyosarcoma, one hemangiosarcoma, two mast cell tumors, one osteosarcoma, three melanomas, and two lymphomas. Commercially available antibodies directed against high- and low-molecular-weight keratins (keratin, RCK-102, NCL-5D3), vimentin, desmin, glial fibrillary acidic protein (GFAP), and neurofilament intermediate filament (IF) proteins were used in the avidin-biotin-peroxidase complex technique on formalin-fixed, paraffin-embedded tumor tissue samples. All epithelial tumors except the endometrial carcinoma expressed some type of keratin protein. Squamous cell carcinomas expressed high-molecular-weight keratins exclusively. Coexpression of high- and low-molecular-weight keratins was observed in one basal cell tumor, sebaceous and apocrine adenocarcinomas, and thyroid, renal, and lung carcinomas. In addition to keratins, vimentin immunoreactivity was found in all basal cell tumors, all sebaceous gland, thyroid papillary, renal, and lung adenocarcinomas, and one of the apocrine gland adenocarcinomas. Immunoreactivity with GFAP antibody was found in one basal cell tumor and one sebaceous gland adenocarcinoma. The endometrial carcinoma did not react with any of the antibodies applied. Nonepithelial tumors analyzed expressed either vimentin (fibrosarcomas, liposarcoma, haemangiosarcoma, mast cell tumors, osteosarcomas, melanomas) or vimentin and desmin (leiomyosarcoma, rhabdomyosarcoma, one fibrosarcoma) IF proteins exclusively. Lymphomas did not react with any of the antibodies employed. These findings indicate that IF proteins antibodies can be included in diagnostic panels of antibodies for immunocharacterization of feline tumors. In addition, they can be used as a basis for the diagnoses of poorly differentiated or undifferentiated feline neoplasms. Topics: Animals; Cat Diseases; Cats; Desmin; Glial Fibrillary Acidic Protein; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Kidney; Kidney Neoplasms; Lung Neoplasms; Neoplasms; Neoplasms, Glandular and Epithelial; Neurofilament Proteins; Skin Neoplasms; Thyroid Gland; Thyroid Neoplasms; Vimentin | 1995 |
Merkel cells are integral constituents of desmoplastic trichoepithelioma: an immunohistochemical and electron microscopic study.
The incidence of Merkel cells has previously been investigated in a number of inflammatory and tumorous lesions of the skin. Special attention was given to tumors with follicular differentiation. In the present study we examined the localization of Merkel cells in another adnexal tumor, the desmoplastic trichoepithelioma (n = 15), as well as in its main differential diagnosis, the morpheiform basal-cell carcinoma (n = 30). Using immunohistochemical methods, we found Merkel cells as a stable constituent in desmoplastic trichoepitheliomas, but failed to detect them in morpheiform basal-cell carcinomas. These findings might therefore be an important tool in the sometimes very difficult but clinically imperative distinction between these two conditions. Furthermore, our study may be of interest in the discussion about the origin of desmoplastic trichoepitheliomas. High numbers of Merkel cells in desmoplastic trichoepitheliomas indicate a bulge-derived origin of this adnexal tumor, since high numbers of Merkel cells, especially in the bulge, were recently discovered. Although the significance of Merkel cell hyperplasia in desmoplastic trichoepithelioma is not presently understood, a regulatory role of the Merkel cell in growth and development of this adnexal tumor is suggested. Topics: Carcinoma, Basal Cell; Chromogranin A; Chromogranins; Epidermis; Hair Follicle; Humans; Immunohistochemistry; Keratins; Merkel Cells; Microscopy, Electron; Neoplasms, Basal Cell; Skin Neoplasms | 1995 |
Mucinous carcinoma of the eyelid. An immunohistochemical study.
Mucinous carcinoma is a rare primary eyelid malignancy. It is, however, more common in other sites and may metastasize to the eye. Thus, it is important to consider a distant primary when diagnosing mucinous carcinoma of the eyelid. We studied various immunohistochemical markers that may be useful. Two cases of mucinous carcinoma from the eyelid were reacted with antibodies to cytokeratins (35-beta-H11), carcinoembryonic antigen, S-100 protein, gross cystic disease fluid protein-15, alpha-lactalbumin, estrogen receptor, and progesterone receptor. All antigens were positive in both cases. This study shows that immunohistochemistry may help exclude metastatic mucinous carcinoma to the eyelid from many sites, except the breast, which the eyelid primary closely resembles. Thus, a breast primary should be specifically sought and excluded clinically. Topics: Adenocarcinoma, Mucinous; Aged; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carcinoembryonic Antigen; Carrier Proteins; Eyelid Neoplasms; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Lactalbumin; Male; Membrane Transport Proteins; Middle Aged; Neoplasm Proteins; Receptors, Estrogen; Receptors, Progesterone; S100 Proteins; Skin Neoplasms | 1995 |
Tubular apocrine adenoma with eccrine and apocrine immunophenotypes or papillary tubular adenoma?
A case of papillary tubular adenoma is reported. On microscopic examination the lesion, located on the scalp, showed a tubular-branching pattern, opening on the skin surface, and features of decapitation secretion. Immunohistochemical evidence of both eccrine and apocrine differentiation was found. This case, which on a clinicopathological basis alone could be classified as tubular apocrine adenoma, illustrates the difficulties in contrasting the latter to its eccrine counterpart (papillary eccrine adenoma) and suggests that the terms papillary tubular adenoma or tubulopapillary hidradenoma more accurately describe these lesions. Topics: Adenoma; Adenoma, Sweat Gland; Adenoma, Villous; Adult; Antigens, Neoplasm; Apocrine Glands; Carcinoembryonic Antigen; Cell Differentiation; Diagnosis, Differential; Eccrine Glands; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Mucin-1; Neoplasm Proteins; Scalp; Skin Neoplasms; Sweat Gland Neoplasms | 1995 |
Cutaneous squamoproliferative lesions in renal transplant recipients. Differentiation from lesions in immunocompetent patients.
Of 291 immunosuppressed renal transplant recipients (RTRs) with surviving allografts attending the Royal London Hospital, 171 patients (59%) were found to have warty keratoses. On histological analysis, the lesions in 50 patients (17%) showed partial-thickness dysplasia, and 34 (12%) had one or more invasive squamous cell carcinoma (SCC) and/or one or more in situ SCC or full-thickness dysplasia. We examined the claim that squamoproliferative lesions in RTRs possess distinctive histopathological features that differ from those of similar lesions occurring sporadically in the nonimmunosuppressed population. We compared 40 squamoproliferative lesions from RTRs with 40 matched squamoproliferative lesions from nonimmunosuppressed patients; lesions were coded and their source was unknown to the assessors. Two dermatopathologists independently assessed the cases and gave scores for 11 histological features that have been reported to be characteristic of such lesions in the immunosuppressed population. These included a warty architecture, koilocytes, and multinucleate giant cells. Using these criteria, it was not possible to distinguish lesions of immunosuppressed patients from those of immunocompetent people. Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Cytoplasmic Granules; Diagnosis, Differential; Epithelium; Female; Giant Cells; Graft Survival; Humans; Hyalin; Immunocompetence; Immunosuppression Therapy; Keratins; Keratosis; Kidney Transplantation; Male; Neoplasm Invasiveness; Papilloma; Skin Neoplasms; Transplantation, Homologous; Warts | 1995 |
Merkel cells in nevus sebaceus. An immunohistochemical study.
Nevus sebaceus, considered to be a hamartoma, is known to develop several secondary hyperplastic and neoplastic proliferations. By the use of immunohistochemical studies, we were able to describe a sometimes very striking increase of Merkel cells in nine of 19 nevi sebacei. Only nevi sebacei that formed follicular germ structures and trichoblastomas showed a Merkel cell hyperplasia. In the hyperplastic epidermis of some cases a slight hyperplasia of singular Merkel cells was observed. In foci with follicular germs and trichoblastomas, however, the Merkel cells were much more abundant and sometimes arranged in clusters. Merkel cell hyperplasia is likely to represent another facet of hamartomatous hyperplasia in nevi sebacei. Our observation that trichoblastomas in nevus sebaceus possess, as a rule, hyperplasia of Merkel cells, might be an additional aid to distinguish these tumors from basal cell carcinomas, which are usually devoid of Merkel cells. Furthermore, our findings are a hint that development of follicular germs and trichoblastomas in nevi sebacei may be promoted by Merkel cells. Topics: Adolescent; Carcinoma, Basal Cell; Cell Count; Child; Chromogranin A; Chromogranins; Coloring Agents; Diagnosis, Differential; Epidermis; Hair Follicle; Hamartoma; Humans; Hyperplasia; Immunohistochemistry; Keratins; Merkel Cells; Neoplasms, Basal Cell; Skin; Skin Abnormalities; Skin Neoplasms | 1995 |
Cutaneous metastasis of CNS chordoma.
A rare case of cutaneous skin metastasis from an intracranial chordoma is presented. A large nodule developed in the left thigh of a 22-year-old woman who had been previously diagnosed to have a chordoma at the base of her skull. Sections from the biopsied specimens of the nodule showed proliferations of physaliphorous cells and stellate cells in cords and in nests in a myxoid stroma. Immunohistochemically, neoplastic cells were stained positively with antibodies to S-100 protein and cytokeratin. The results of the histopathological and immunohistochemical studies of the nodule were interpreted as pointing to a diagnosis of metastatic chordoma based on their similarity to the results of studies of the primary neoplasm in the cranial region. Based on the number of cases of skin metastasis from chordoma reported in the literature, skin should be kept in mind as one of the target organs, although such metastases are still rare. Topics: Adult; Brain Neoplasms; Cell Nucleus; Chordoma; Cytoplasm; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Neoplasm Recurrence, Local; S100 Proteins; Skin Neoplasms; Thigh; Vacuoles | 1995 |
Cutaneous metastasis of chordoma.
A chordoma metastatic to the skin of the nose is reported. The patient (a 40-year-old man) had undergone excision of a sacral chordoma 16 months previously. In patients whose clinical histories are unknown, cutaneous metastases of chordoma can be confused with mixed tumors of sweat glands. Cytological features, including the presence of physaliphorous cells, and immunohistochemical coexpression of low molecular weight keratins and S-100 protein are helpful features that lead to a correct diagnosis. Topics: Adult; Chordoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Nose Neoplasms; S100 Proteins; Sacrum; Skin Neoplasms; Spinal Neoplasms; Sweat Gland Neoplasms; Vimentin | 1995 |
Immunohistochemical localization of keratins and involucrin in solar keratosis and Bowen's disease.
The present study was conducted to determine the patterns of immunohistochemical characterization of keratin (K) and involucrin in solar keratosis and Bowen's disease in order to clarify the abnormal differentiation or maturation of the tumor cells in these precancerous epithelial dermatoses. Seventeen human anti-cytokeratin antibodies and an anti-involucrin antibody were used to examine 15 cases of solar keratosis and 18 cases of Bowen's disease. Formalin-fixed and paraffin-embedded sections were stained with these antibodies by the avidin-biotin-peroxidase technique. In solar keratosis, keratin and involucrin distribution was similar to that in normal epidermis, whereas in Bowen's disease the keratin distribution varied among individual cases. The dyskeratotic cells in Bowen's disease showed a reduction or loss of staining with these antibodies, and they were occasionally positive for keratin 19. These observations suggest that there is a difference in keratin and involucrin expression between solar keratosis and Bowen's disease and that the atypical cells of Bowen's disease exhibit a diversity of differentiation. Topics: Aged; Aged, 80 and over; Bowen's Disease; Cell Differentiation; Cellular Senescence; Epidermis; Female; Fixatives; Formaldehyde; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Keratosis; Male; Middle Aged; Paraffin Embedding; Precancerous Conditions; Protein Precursors; Skin Neoplasms; Sunlight | 1995 |
Is keratoacanthoma a variant of squamous cell carcinoma. New insights into an old controversy ... soon?
Topics: Antigens, Neoplasm; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Epidermis; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Keratins; Keratoacanthoma; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins; Precancerous Conditions; Skin Neoplasms; Tumor Suppressor Protein p53 | 1995 |
Quantitative image analysis of p53 protein accumulation in keratoacanthomas.
Keratoacanthomas are benign skin tumors that grow rapidly but eventually regress. They occur most commonly in sun-exposed skin and are histologically remarkably similar to squamous cancers. Since mutations of the p53 tumor suppressor gene are found frequently in cutaneous squamous cell carcinomas, we hypothesized that p53 mutations might contribute to the development of keratoacanthomas. To address this question, we did p53 immunohistochemistry with a polyclonal rabbit antiserum, CM-1, that binds both mutant and wild-type p53 proteins. Although wild-type p53 protein degrades rapidly and is generally undetected by immunohistochemistry, mutant p53 protein has a longer half-life and accumulates to detectable levels. We tested 26 formalin-fixed keratoacanthomas and 4 normal skin biopsies. Positive nuclear staining was detected in 20 of 26 (77%) of the keratoacanthomas and in none of the normal skin samples. Nuclear staining occurred in the outermost layer of the neoplasms and not in the keratin-filled central cores. Since nuclear p53 protein within a cutaneous squamous cell carcinoma usually correlates with missense mutation, these data suggest that p53 mutations contribute to the development of this benign neoplasm. The histologic similarity to squamous cell carcinoma and the accumulation of p53 protein suggest progression toward malignancy, but the invariable regression of these tumors suggests an arrest at some point in multistage carcinogenesis. If this model is correct, then genetic analysis of keratoacanthomas may provide clues to the later stages of squamous carcinogenesis including local invasion and metastasis. Topics: Animals; Carcinoma, Squamous Cell; Cell Nucleus; Coloring Agents; Disease Progression; Fixatives; Formaldehyde; Genes, p53; Half-Life; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Keratoacanthoma; Mutation; Neoplasm Regression, Spontaneous; Rabbits; Remission, Spontaneous; Skin; Skin Neoplasms; Sunlight; Tumor Suppressor Protein p53 | 1995 |
Epithelial markers and differentiation in adnexal neoplasms of the skin: an immunohistochemical study including individual cytokeratins.
Applying immunohistochemical procedures for the detection of eight different cytokeratin (CK) polypeptides and other differentiation markers, we compared the staining patterns of normal cutaneous structures with those of benign adnexal tumors (n = 65). Syringomas exhibited a marker pattern highly reminiscent of that seen in normal dermal eccrine ducts (EMA in peripheral cells, CK 10 in intermediate cells, and CK 6, CK 19, and CEA in luminal cells). Nodular hidradenomas exhibited complex patterns suggesting relationship between tumor cells, including clear cells, and normal secretory coil cells (CK 7, CK 8, CK 19, and EMA); however, dermal-duct and epidermoid differentiation were also detectable. In both cylindromas and spiradenomas, zonal staining patterns were apparent: modified myoepithelial cells were positive for smooth-muscle-type actin, while the luminal cells mainly expressed ductal markers (CK 6 and CK 19) and, less prominently, secretory-coil markers including CK 7. Eccrine poromas exhibited a widespread reaction for CK 5/6 and EMA, analogous to peripheral dermal duct cells, but focal maturation toward inner-ductal and secretory-coil cells was also demonstrable. The staining pattern observed in trichoepitheliomas resembled that of the outer but not the inner root sheath. In conclusion, the detailed marker profiles obtained in the present study have broadened our understanding of the differentiation and nature of these highly singular tumor types. Topics: Adenoma; Adenoma, Sweat Gland; Antibodies, Monoclonal; Binding, Competitive; Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Cell Differentiation; Epidermal Cells; Epidermis; Humans; Immunohistochemistry; Keratins; Neoplasms, Basal Cell; Reference Values; Skin Neoplasms; Sweat Glands; Syringoma | 1995 |
A nevoid plaque with histological changes of trichoepithelioma and cylindroma in Brooke-Spiegler syndrome. An immunohistochemical study with cytokeratins.
Brooke-Spiegler syndrome is characterized by the development of multiple trichoepitheliomas and cylindromas. In addition, multiple spiradenomas have been observed in this autosomal-dominant inherited disease. We report a 53-year-old woman with multiple cylindromas on the head and neck and multiple trichoepitheliomas on the face. Additionally, she had had since birth a plaque on the right side of her neck containing two nodules with features of both cylindroma and trichoepithelioma. Immunohistochemical investigations revealed in the basaloid cells of trichoepithelioma an expression of CK 5/6, CK 14, CK 17, CK 19 and vimentin. The cells of the cylindroma lacked vimentin but expressed additionally CK 7, CK 8 and CK 18. The occurrence of cylindroma and trichoepithelioma in a single nevoid plaque from a patient with Brooke-Spiegler syndrome implies an alteration in the stem cells of the folliculosebaceous-apocrine unit and could be characteristic of the disorder. Topics: Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Eyebrows; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neck; Neoplasms, Basal Cell; Neoplasms, Multiple Primary; Scalp; Skin Neoplasms; Syndrome | 1995 |
Ornithine decarboxylase expression in cutaneous papillomas in SENCAR mice is associated with altered expression of keratins 1 and 10.
The patterns of expression of ornithine decarboxylase (ODC) and a number of keratinocyte differentiation products were examined in early papillomas by immunocytochemistry as an initial effort to develop phenotypic markers of the early stages of mouse skin tumorigenesis. Tumors were induced in SENCAR mice by initiation with 7,12-dimethylbenzanthracene, followed by once or twice weekly promotion treatments with 12-O-tetradecanoylphorbol-13-acetate. The patterns of immunocytochemical staining observed in early papillomas, collected after 7 weeks of promotion, were compared to those obtained with control skin and large, hyperkeratotic papillomas, collected after 23 weeks of promotion. In groups receiving 12-O-tetradecanoylphorbol-13-acetate, constitutive and induced ODC expression were evaluated either several days or 4.5 h after the last treatment, respectively. The major differentiation products in suprabasal keratinocytes are keratins, K1 and K10. These keratins were normally expressed in mildly hyperplastic epidermis, but staining became patchy in markedly hyperplastic epidermis. In early papillomas, K1 staining was patchy, and K10 staining occurred in very limited focal areas or was negative, such that the absence of staining delineated the lesions. Antibodies to the basal cell keratins, K5 and K14, stained both basal and suprabasal cells in hyperplastic epidermis and papillomas. Similarly, an antibody to keratin K6, which is expressed under conditions of hyperproliferation, uniformly stained the basal and suprabasal layers of hyperplastic epidermis and papillomas, demonstrating that the staining patterns observed with the antibodies to K1 and K10 were specific. Expression of ODC in the histologically normal skin of control mice was detected only in the hair follicles and depended on the hair cycle. Staining for induced ODC in mice treated with 12-O-tetradecanoylphorbol-13-acetate once weekly for 7 weeks was intense and diffuse throughout the suprabasal layers of the epidermis. In early and large papillomas, staining for constitutively expressed ODC was intense and diffuse in suprabasal cells. This intense staining for ODC occurred consistently in areas with decreased K1 and K10 expression, and, therefore, was associated with an altered pattern of differentiation. High constitutive ODC expression and decreased K1 and K10 expression will be useful phenotypic markers for studying the early stages of tumorigenesis in mouse skin. Topics: 9,10-Dimethyl-1,2-benzanthracene; Acetone; Animals; Cell Differentiation; Female; Filaggrin Proteins; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Membrane Proteins; Mice; Ornithine Decarboxylase; Papilloma; Skin Neoplasms | 1994 |
Neuroendocrine carcinoma of the skin (Merkel cell carcinoma). An immunoelectron-microscopic case study.
An unusual tumor with a controversial name as well as histogenesis, the neuroendocrine carcinoma of the skin (also known as "Merkel cell carcinoma," "trabecular carcinoma of the skin") has previously been extensively studied by immunohistochemical methods at the light-microscopic level. Ultrastructural descriptions of this tumor have also been extensive, although immunocytochemical study of this neoplasm at the electron-microscopic level has been limited. In this report, we have used postembedding protein A-gold immunocytochemistry on thin sections from tumor embedded in Lowicryl K4M to investigate the expression and ultrastructural localization of a panel of commercially available, diagnostically useful antibodies. Antibodies associated with epithelial derivation included anti-keratin monoclonal antibody AE1/AE3, polyclonal anti-keratin, and monoclonal anti-cytokeratin cocktail (MAK-6), as well as a monoclonal antibody against epithelial membrane antigen (EMA). Antibodies associated with neuroendocrine derivation included monoclonal anti-chromogranin A and monoclonal anti-synaptophysin. Although staining with a polyclonal antibody directed against neuron-specific enolase (NSE) was equivocal, there was no labeling with a monoclonal anti-neurofilament antibody. The finding of positive keratin labeling of filaments arranged in paranuclear aggregates correlates well with the previously described immunohistochemical staining pattern at the light-microscopic level. Moreover, the presence of cytoplasmic synaptophysin and chromogranin positivity over dense-core granules exemplifies the neuroendocrine differentiation present in this fascinating tumor of the skin. Topics: Aged; Antigens, Neoplasm; Carcinoma, Merkel Cell; Cell Nucleolus; Cell Nucleus; Chromatin; Chromogranin A; Chromogranins; Connective Tissue; Cytoplasmic Granules; Desmosomes; Epidermis; Female; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Membrane Glycoproteins; Microscopy, Immunoelectron; Mucin-1; Phosphopyruvate Hydratase; Skin Neoplasms | 1994 |
Three subtypes of poroid neoplasia in a single lesion: eccrine poroma, hidroacanthoma simplex, and dermal duct tumor. Histologic, histochemical, and ultrastructural findings.
A single poroid neoplasm composed of three histologically distinct lesions (hidroacanthomas simplex, eccrine poroma, and dermal duct tumor) is reported. Comparative histologic, histochemical, and electron-microscopic studies revealed that each tumor subtype contained varying proportions of poroid cells, clear cells, and cuticular cells. The major component of all three neoplasms was poroid cells, which, under the electron microscope, were characterized by a few, small, poorly developed desmosomes, and were histochemically characterized by a positive succinic dehydrogenase reaction. The dermal duct tumor was cultured, and showed similar histochemical findings to the in vivo poroid cells. These results suggest that poroid cells play the most important role in the histogenesis of these three neoplasms. Topics: Acrospiroma; Aged; Cytoplasm; Cytoplasmic Granules; Epidermis; Glycogen; Humans; Keratins; Male; Microscopy, Electron; Neoplasms, Glandular and Epithelial; Neoplasms, Multiple Primary; Skin Neoplasms; Sweat Gland Neoplasms; Tumor Cells, Cultured | 1994 |
Primary rhabdoid tumour of the skin in a 14-month-old child.
We report on a primary cutaneous rhabdoid tumour in a 14-month-old child, to the best of our knowledge, the second case in the literature. The tumour showed a multipolypoid gross appearance and classical histological features. The neoplastic cells were positive for keratin and vimentin and most were positive for proliferating cell nuclear antigen. The ultrastructural examination revealed typical intracytoplasmic aggregates of intermediate filaments. The tumour showed a very aggressive course, and the child died 5 months after the diagnosis of cerebral metastasis. Topics: Brain Neoplasms; Cell Nucleolus; Cell Nucleus; Cytoplasm; Fatal Outcome; Humans; Hyalin; Immunohistochemistry; Inclusion Bodies; Infant; Intermediate Filaments; Keratins; Male; Organelles; Rhabdoid Tumor; Skin Neoplasms; Vimentin | 1994 |
Analysis of HPV16 E6 and mutant p53-transfected keratinocytes in reconstituted epidermis suggests that wild-type p53 inhibits cytokeratin 19 expression.
Using a reconstituted skin culture model we have analysed the effects of oncogenic human papillomavirus (HPV) and mutant TP53 genes on the proliferation and differentiation of human keratinocytes. Immortal cell lines generated by transfection of early passage normal human keratinocytes with HPV16 E7 plus mutant human TP53 (KN #1), HPV16 E7/E6 (KN #2), or HPV16 E7 plus murine p53 (KN #3) were examined. KN #1 and KN #2 behaved identically, reconstructing a tumor-like epidermis characterized by the lack of differentiation and the presence of an aberrant epidermal architecture. In contrast, KN #3 reconstructed an epidermis that was more similar to that obtained with normal keratinocytes. KN #1 and KN #2 were further characterized by the inversion of the proliferative compartment and the abnormal expression of cytokeratin 19 (CK19). Because p53 function is reduced in these cells, either by heterocomplex formation between endogenous wild-type p53 and transfected mutant p53 or by E6-induced degradation of wild-type p53, we hypothesized that CK19 expression may be normally repressed by wild-type p53. This hypothesis was supported by the strict correlation observed between TP53 mutation and CK19 expression in a set of human skin tumors. CK19 was detected in all eight carcinomas containing a mutated TP53 gene but in none of the 16 carcinomas containing only wild-type TP53. These results illustrate the utility of the in vitro reconstituted skin model for investigating the consequences of genetic alterations in human keratinocytes. Topics: Cell Differentiation; Cell Division; Cell Line; Culture Techniques; Gene Expression; Genes, p53; Genes, Viral; Humans; Keratinocytes; Keratins; Mutation; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; Phenotype; Repressor Proteins; Skin; Skin Neoplasms; Transfection | 1994 |
Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice.
To model human papillomavirus-induced neoplastic progression, expression of the early region of human papillomavirus type 16 (HPV16) was targeted to the basal cells of the squamous epithelium in transgenic mice, using a human keratin 14 (K14) enhancer/promoter. Twenty-one transgenic founder mice were produced, and eight lines carrying either wild-type or mutant HPV16 early regions that did not express the E1 or E2 genes were established. As is characteristic of human cancers, the E6 and E7 genes remained intact in these mutants. The absence of E1 or E2 function did not influence the severity of the phenotype that eventually developed in the transgenic mice. Hyperplasia, papillomatosis, and dysplasia appeared at multiple epidermal and squamous mucosal sites, including ear and truncal skin, face, snout and eyelids, and anus. The ears were the most consistently affected site, with pathology being present in all lines with 100% penetrance. This phenotype also progressed through discernible stages. An initial mild hyperplasia was followed by hyperplasia, which further progressed to dysplasia and papillomatosis. During histopathological progression, there was an incremental increase in cellular DNA synthesis, determined by 5-bromo-2'-deoxyuridine incorporation, and a profound perturbation in keratinocyte terminal differentiation, as revealed by immunohistochemistry to K5, K14, and K10 and filaggrin. These K14-HPV16 transgenic mice present an opportunity to study the role of the HPV16 oncogenes in the neoplastic progression of squamous epithelium and provide a model with which to identify genetic and epigenetic factors necessary for carcinogenesis. Topics: Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Ear; Filaggrin Proteins; Keratins; Mice; Mice, Transgenic; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; Phenotype; Precancerous Conditions; Promoter Regions, Genetic; RNA, Viral; Skin; Skin Neoplasms | 1994 |
Fine-needle aspiration cytology of metastatic basal cell carcinoma of the skin to the lung.
Metastatic basal cell carcinomas of the skin are rare. We present the cytologic features of a metastatic basal cell carcinoma to the lung diagnosed by fine-needle aspiration biopsy. Cytologic examination revealed syncytial groups of relatively small cells with hyperchromatic, oval to spindle-shaped nuclei having high nuclear to cytoplasmic ratios. Immunocytochemical studies performed on the cell block sections revealed the malignant cells to be positive for cytokeratin (AE1/3) and negative for neuroendocrine markers, [neuron specific enolase (NSE) and chromogranin (Phe-5)]. We reviewed the literature related to metastatic basal cell carcinoma of the skin and discuss risk factors and mechanisms of metastatic spread. In addition, a discussion of the other entities that can enter into the differential diagnosis is presented along with the role of ancillary studies. To the best of our knowledge, we believe this is the first case report of the fine-needle aspiration (FNA) cytology of a basal cell carcinoma metastatic to the lung. Topics: Biopsy, Needle; Carcinoma, Basal Cell; Female; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Middle Aged; Skin Neoplasms | 1994 |
[The Merkel cell].
Topics: Biomarkers, Tumor; Carcinoma, Merkel Cell; Cytoplasmic Granules; Humans; Intermediate Filaments; Keratins; Microscopy, Electron; Skin; Skin Neoplasms | 1994 |
Rapid cytokeratin stains enhance the sensitivity of Mohs micrographic surgery for squamous cell carcinoma.
Recurrence of squamous cell carcinoma (SCC) following Mohs micrographic surgery is uncommon. However, such cases do exist, presumably because of incomplete excision. Identification of single cells or small clumps of SCC tumor may be extremely difficult and can be compromised by inflammatory reaction.. The purpose of this study was to evaluate the benefits of incorporating rapid cytokeratin (CK) stains into Mohs technique.. Simple modification of standard immunoenzyme techniques allows keratin-specific staining to be achieved in less than 90 minutes on Mohs cryostat sections. We used the rapid labeled streptavidin biotin anticytokeratin method at the stage when no tumor was apparent by hematoxylin and eosin staining in 20 patients with large, aggressive, or recurrent invasive SCCs.. In eight cases, single cells or small clumps of SCC tumor were identified utilizing AE-1 monoclonal antibody. These patients subsequently underwent further surgery, including wider tumor resection, superficial parotidectomy, or postoperative radiation therapy.. The rapid CK antibody staining technique enhances the sensitivity of tumor identification in Mohs micrographic surgery, and should reduce tumor recurrence rates. Topics: Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Mohs Surgery; Skin Neoplasms; Staining and Labeling | 1994 |
Expression of keratin 20 in malignant eccrine poromas.
Eight cases of malignant eccrine poromas were studied immunohistochemically with a broad panel of antibodies in order to better characterise the spectrum of their differentiating pathways. Special attention was paid to the expression of cytokeratins, mainly the newly recognised keratin 20. In general, the pattern of staining agreed to previous studies. Anyway, a non-expected positivity with keratin 20 was seen in two cases. The usefulness of the immunohistochemistry to discover areas with masked differentiation in adnexal tumours of the skin was once more confirmed. Topics: Acrospiroma; Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Middle Aged; Skin Neoplasms; Staining and Labeling | 1994 |
Epithelial markers in malignant melanoma. A study of primary lesions and their metastases.
In order to determine epithelial markers in malignant melanoma in routinely processed paraffin sections and to compare the staining of primary (cutaneous) malignant melanomas and their metastases, we stained formalin-fixed paraffin sections of 13 primary and 18 metastatic malignant melanomas using the streptavidin-biotin peroxidase method by antibodies to S-100, vimentin, HMB-45, polyclonal carcinoembryonic antigen (CEA), monoclonal CEA, cytokeratins (CAM 5.2 and broad-spectrum CKKES), and epithelial membrane antigen (EMA). All primary and most metastatic malignant melanomas showed positive staining with anti-S-100, HMB-45, and anti-vimentin. Reactivity with polyclonal CEA was observed in 15 (48%) of the 31 lesions; 14 of them were metastatic. No lesion was reactive with monoclonal CEA. Significant cytokeratin (CK) staining was evident in only three (9.7%) lesions (all metastatic), which also stained specifically with anti-CK 18. EMA was observed only focally in two (6.5%) lesions. There was no correlation between epithelial markers staining of the primary tumours and their metastases. All lesions with CK or EMA staining showed concomitant extensive staining for S-100, HMB-45, and vimentin. We conclude that (a) polyclonal CEA staining in malignant melanoma is not rare and is probably due to CEA-related molecules; (b) significant CK reactivity is rare and related to simple CK, such as CK 18; (c) epithelial marker reactivity is more common in metastases of malignant melanomas and is not correlated to the reactivity in their primary tumors. Considering our results and reports of positive S-100, vimentin, and HMB-45 in epithelial tumors, a wide panel of antibodies is recommended for the study of undifferentiated tumors. Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Melanoma-Specific Antigens; Membrane Glycoproteins; Mucin-1; Mucins; Neoplasm Proteins; S100 Proteins; Skin Neoplasms; Vimentin | 1994 |
Immunohistochemical localization of cytokeratins and involucrin in calcifying epithelioma: comparative studies with normal skin.
The expression of cytokeratins and involucrin varies greatly in different epithelia, and this raises the possibility that detailed analysis of these epidermal proteins might provide a means of identifying various skin tumours. The present study was conducted to determine the immunohistochemical distribution of cytokeratins and involucrin in calcifying epithelioma of Malherbe, in order to elucidate the nature and differentiation of this tumour. To correlate the immunohistochemical profile with the most frequent histological patterns, we categorized the basophilic, transitional, shadow, and squamoid cells, and the shreds of keratin. Comparative studies with normal skin showed that the shadow and transitional cells corresponded to hair cortex cells, the squamoid cells to the outer root sheath, the basophilic cells adjacent to the stroma to the outermost cell layer of the outer root sheath between the lower permanent portion and upper transient portion of the follicles, and the basophilic cells adjacent to the transitional cells to the hair matrix. The expression of cytokeratins in most shreds of keratin was similar to that in squamoid cells. Calcifying epithelioma was, therefore, shown to be composed of tumour cells differentiating into both the hair cortex and outer root sheath. These tumour cells were differentiated from basophilic cells, which showed the same staining patterns as the outermost cell layer of the outer root sheath between the lower permanent portion and upper transient portion of the hair follicles, supporting the hypothesis that the keratinocytes in the outermost cell layer can differentiate into the transitional portion of the follicle and anagen hair. Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Hair Diseases; Humans; Immunohistochemistry; Infant; Keratins; Middle Aged; Pilomatrixoma; Protein Precursors; Skin; Skin Neoplasms | 1994 |
An immunohistochemical study of sebaceous carcinoma with anti-keratin monoclonal antibodies: comparison with other skin cancers.
Formalin-fixed and paraffin-embedded tissue specimens of six cases of extraocular sebaceous carcinoma were studied immunohistochemically with eight anti-keratin monoclonal antibodies, 34 beta B4, 35 beta H11, Ks13.1, Ks19.1, PKK1, LP34, KL1 and AE1. The staining patterns of sebaceous carcinoma were compared with those of normal sebaceous glands and other skin cancers which should be distinguished from sebaceous carcinoma histopathologically. The other skin cancers compared were eccrine porocarcinoma, malignant clear cell hidradenoma, extramammary Paget's disease with underlying adenocarcinoma, malignant trichilemmoma, and squamous cell carcinoma. Most cases of sebaceous carcinoma were stained with 35 beta H11, Ks19.1, LP34, KL1 and AE1, while normal sebaceous glands were positive only with 35 beta H11, LP34, KL1 and AE1. By immunostaining, sebaceous carcinoma was distinguishable from extramammary Paget's disease with underlying adenocarcinoma, squamous cell carcinoma, malignant trichilemmoma, and eccrine porocarcinoma, but was not clearly distinguishable from malignant clear cell hidradenoma. These findings demonstrate that sebaceous carcinoma shows positive reactions with antibodies to simple epithelial keratin, probably as a result of neoplastic transformation, and that immunohistochemical examination using anti-keratin monoclonal antibodies is useful in distinguishing sebaceous carcinoma from several other skin cancers. Topics: Acrospiroma; Adenocarcinoma, Sebaceous; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Neoplasms, Basal Cell; Paget Disease, Extramammary; Sebaceous Gland Neoplasms; Skin Neoplasms; Sweat Gland Neoplasms | 1994 |
Genetic and clinical mosaicism in a type of epidermal nevus.
Many skin disorders are characterized by a mosaic pattern, often with alternating stripes of affected and unaffected skin that follow the lines of Blaschko. These nonrandom patterns may be caused by a postzygotic mutation during embryogenesis. We studied the genetic basis of one such disorder, epidermal nevus of the epidermolytic hyperkeratotic type. Epidermolytic hyperkeratosis is an autosomal dominant blistering skin disease arising from mutations in the genes for keratin (K) 1 and 10. The offspring of patients with epidermal nevi may have generalized epidermolytic hyperkeratosis.. We studied the K1 and K10 genes in blood and in the keratinocytes and fibroblasts of lesional and nonlesional skin from three patients with epidermal nevi and four of their offspring with epidermolytic hyperkeratosis.. In the patients with epidermal nevi, point mutations in 50 percent of the K10 alleles of epidermal cells were found in keratinocytes from lesional skin; no mutations were detected in normal skin. This mutation was absent or underrepresented in blood and skin fibroblasts. In the offspring with epidermolytic hyperkeratosis, the same mutations as those in the parents were found in 50 percent of the K10 alleles from all cell types examined.. Epidermal nevus of the epidermolytic hyperkeratotic type is a mosaic genetic disorder of suprabasal keratin. The correlation of mutations in the K10 gene with lesional skin and the correlation of the normal gene with normal skin provide evidence that genetic mosaicism can cause clinical mosaicism. Topics: Alleles; DNA; Epidermis; Female; Humans; Keratins; Male; Mosaicism; Nevus; Point Mutation; Skin Neoplasms | 1994 |
Development of transgenic mouse models of skin carcinogenesis: potential applications.
Topics: Animals; Carcinogens; Cocarcinogenesis; Crosses, Genetic; DNA-Binding Proteins; Gene Expression Regulation; Genes, ras; Genetic Vectors; Keratinocytes; Keratins; Mice; Mice, Transgenic; Oncogene Protein p21(ras); Oncogene Proteins, Viral; Organ Specificity; Proto-Oncogene Proteins c-fos; Recombinant Fusion Proteins; Skin Neoplasms | 1994 |
Merkel cells in neurofibromas and neurilemomas.
Merkel cells are an integral component of the cutaneous nervous system. They are commonly associated with dermal nerves under normal physiological conditions. We postulated that Merkel cells may be present in increased numbers within the epidermis overlying benign peripheral nerve sheath tumours such as neurilemomas and neurofibromas. Paraffin-embedded skin biopsy specimens from 21 patients with neurilemomas and 26 with neurofibromas, were analysed for the presence of Merkel cells using a standard immunohistochemical assay (avidin-biotin-peroxidase complex system) with an antibody to cytokeratin 8 (CAM 5.2). Ten cases of leiomyomas were examined as controls. Merkel cells were identified in the interfollicular area of the basal cell layer overlying 14 of 21 (67%) neurilemomas and nine of 26 (35%) neurofibromas. Merkel cells were more frequently observed in increased numbers in a linear array within the basal cell layer in neurilemomas than in neurofibromas, where they were found as individual cells. No Merkel cells were found in the epidermis overlying leiomyomas. The results of this study suggest that Merkel cells are quantitatively increased in the basal cell layer of the epidermis overlying benign peripheral nerve sheath tumours, particularly neurilemomas. Topics: Humans; Keratins; Neurilemmoma; Neurofibroma; Skin; Skin Neoplasms | 1994 |
Tricholemmal carcinoma. A clinicopathologic study of 13 cases.
We describe 13 cases of tricholemmal carcinoma, a rarely recognized cutaneous adnexal neoplasm. The patients were nine men and four women. In general, the tumors presented as slow-growing epidermal papules, indurated plaques, or nodules showing predilection for sun-exposed, hair-bearing skin. The lesions were most frequently misdiagnosed clinically as basal cell carcinoma. Histologically, they showed a variegation of growth patterns including solid, lobular, and trabecular; they were characterized by a proliferation of epithelial cells with features of outer root sheath differentiation, including abundant glycogen-rich, clear cytoplasm, foci of pilar-type keratinization, and peripheral palisading of cells with subnuclear vacuolization. Because of their variable growth pattern, overt cytologic atypia, abundant clear cytoplasm, occasional pagetoid intraepidermal spread, and brisk mitotic activity, these tumors may pose difficulties for diagnosis and be confused with other malignant skin tumors with clear cell changes. Despite the seemingly malignant cytological appearance of these lesions, clinical follow-up in 10 cases showed no recurrence or metastasis over a period of 2-8 years. Thus, conservative surgical excision with clear margins appears to be the treatment of choice for these neoplasms. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoplasm; Diagnosis, Differential; Epidermal Cyst; Epithelium; Female; Follow-Up Studies; Glycogen; Hair Diseases; Humans; Keratins; Male; Middle Aged; Mitosis; Neoplasms, Basal Cell; Skin Diseases; Skin Neoplasms; Vacuoles | 1994 |
Collagenous spherulosis in a schwannoma.
"Collagenous spherulosis" is the term used to describe striking concentric and radiating formations of collagen in tumors. It was originally used for these formations in epithelial tumors of the breast and subsequently in tumors of salivary glands. Recently, the histologic, immunohistochemical, and ultrastructural features were described in a chondroid syringoma. We report a case of collagenous spherulosis in a schwannoma. Routine histologic sections showed a circumscribed tumor in which the predominant feature was radiating fibrillar structures that tended to compress the cellular component of the tumor. Immunohistochemical studies showed that the cells were positive for glial fibrillary acidic protein (GFAP) and S-100 protein but negative for keratin. EMA showed a positive reaction in a thin band of cells around the periphery of the tumor consistent with perineurial cells. Type IV collagen stained around the periphery of the collagen formations. Electron microscopy revealed that the material was consistent with collagen. Our findings were essentially identical to those reported in the chondroid syringoma. This case confirms the findings of the previous study and shows that these unusual formations are not confined to tumors of epithelial origin. Because the architecture of the tumor is distorted, special stains may be required for correct diagnosis. Topics: Adenoma, Pleomorphic; Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; CD57 Antigens; Cell Nucleus; Collagen; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Mucins; Neoplasm Proteins; Neurilemmoma; Phosphopyruvate Hydratase; S100 Proteins; Skin Neoplasms; Staining and Labeling | 1994 |
[Expression of various keratins in basal cell, metastatic, and squamous cell skin cancer].
Topics: Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Neoplasm Metastasis; Skin Neoplasms | 1994 |
Cutaneous lymphadenoma.
Topics: Adenoma; B-Lymphocytes; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Lip Neoplasms; Male; Middle Aged; Skin Neoplasms; T-Lymphocytes | 1994 |
Evidence that regression in keratoacanthoma is immunologically mediated: a comparison with squamous cell carcinoma.
Recent research observations suggest that the keratoacanthoma (KA) is a form of resolving squamous cell carcinoma (SCC). The mechanism by which this resolution takes place has not been fully explored, although it may have an immunological basis. To investigate this, we compared 15 clinically and histologically diagnosed KAs and 15 SCCs with regard to cellular infiltrate and keratin expression. We found that KAs have significantly higher numbers of CD3+ and CD4+ cells invading their epidermal component than SCCs. The T lymphocytes infiltrating KAs were more immunologically active, as greater numbers expressed the interleukin-2 receptor (IL-2R) than those in SCCs. It is of interest that CD36 was expressed by a significantly greater proportion of tumour cells within KAs than SCCs. This was also the case for the intercellular adhesion molecule ICAM-1, and the differentiation marker keratin 10. Overall, these findings suggest that KA regression is immunologically mediated, with activated (IL-2R+) CD4+ T lymphocytes and adhesion molecules playing a pivotal role in the immune response. Topics: Aged; Aged, 80 and over; Antigens, CD; Carcinoma, Squamous Cell; CD3 Complex; CD36 Antigens; CD4 Antigens; Epidermis; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Keratins; Keratoacanthoma; Lymphocyte Activation; Middle Aged; Platelet Membrane Glycoproteins; Receptors, Interleukin-2; Remission, Spontaneous; Skin Diseases; Skin Neoplasms; T-Lymphocytes | 1994 |
Sclerosing B-cell lymphoma involving the skin.
We report a case of sclerosing B-cell lymphoma involving the skin. The patient is a 43-year-old man who came to our institution with a 4-year history of multinodular masses in the back. A thoracic CT scan demonstrated subcutaneous masses with extension to the posterior parietal pleura and compression of several epidural spaces. An incisional biopsy was performed and demonstrated an infiltrative process in the lower dermis composed of interconnected thick sclerosing bands forming compartments around groups of large neoplastic cells. These neoplastic cells were shown to be B lymphocytes using immunohistochemical stains. A diagnosis of diffuse sclerosing B-cell lymphoma, large cell type, was made. Our case is reported to alert dermatologists and dermatopathologists to the occurrence of this neoplasm in the skin which could be confused with a deep inflammatory process or other neoplastic conditions. Topics: Adult; Antigens, CD; Humans; Keratins; Lymphoma, B-Cell; Male; S100 Proteins; Sclerosis; Skin Neoplasms | 1994 |
Immunohistochemical demonstration of the expression of neurofilament proteins in Merkel cells.
The presence of immunoreactive neurofilament proteins has previously been reported in Merkel cell carcinomas but not in normal human epidermal and dermal Merkel cells. We have studied the immunoreactivity of epidermal Merkel cells for neurofilament triplet proteins (68 KD, 70 KD, 160 KD, 200 KD), using epidermal sheets prepared from the plantar skin of human adults, which enabled us to survey large numbers of Merkel cells. Neurofilament protein 200 KD-positive cells were readily identified, while neurofilament protein 68 KD-, 70 KD- and 160 KD-positive cells were largely absent. 200 KD-positive cells in the epidermis were confirmed to represent Merkel cells by a sequential immunoenzyme labeling for the simple epithelial type cytokeratin (No. 8). 200 KD-positive cells were 5.9% of the total number of epidermal Merkel cells. Despite a heterogeneous expression of neurofilament protein subspecies between the normal and transformed Merkel cells, the presence of neurofilament proteins in epidermal Merkel cells may link them to Merkel cell carcinomas. Topics: Adult; Carcinoma, Merkel Cell; Cell Transformation, Neoplastic; Dendrites; Epidermis; Epithelium; Gene Expression; Humans; Immunohistochemistry; Keratins; Mechanoreceptors; Melanoma; Nerve Tissue Proteins; Neurofilament Proteins; Nevus, Pigmented; Skin; Skin Neoplasms | 1994 |
Keratin 17 expression as a marker for epithelial transformation in viral warts.
The profile of keratin expression in benign warts from various cutaneous and mucosal sites along with dysplastic warts and squamous cell carcinomas has been examined using a panel of monospecific antibodies to epithelial keratins. Viral warts and verrucous keratoses from immunosuppressed renal transplant recipients show a spectrum of squamous atypia from benign lesions, from minimal changes to full thickness dysplasia. Changes associated with malignancy include loss of differentiation-specific keratins 1 and 10 together with expansion of basal cell epitopes and inappropriate expression of simple epithelial keratins 8, 18, and 19 in advanced squamous cell carcinoma. This late expression of keratins 8 and 18 contrasts with early expression of keratin 17 in all dysplastic lesions examined. Keratin 17 is found suprabasally in hyperproliferative lesions, including benign warts, but marked basal plus suprabasal expression is seen increasingly in malignantly transformed epidermis. These findings were not specific to immunosuppression, as shown by identical findings in control squamous cell carcinoma from nonimmunosuppressed individuals. Keratin 17 expression may prove prognostically helpful when assessing dysplasia in epidermal tumors. Topics: Biomarkers; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cell Transformation, Viral; Condylomata Acuminata; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Skin; Skin Diseases; Skin Neoplasms; Warts | 1993 |
Differential modulation of epidermal keratinization in immortalized (HaCaT) and tumorigenic human skin keratinocytes (HaCaT-ras) by retinoic acid and extracellular Ca2+.
The growth and differentiation response to retinoic acid (RA) was studied in the human keratinocyte line HaCaT and tumorigenic clones transfected with c-Ha-ras oncogene (HaCaT-ras). Differentiation (mainly keratin synthesis) was evaluated and correlated to cell proliferation in vitro but also growth behaviour in vivo (tumorigenicity). Comparable to normal keratinocytes, HaCaT cells and ras clones showed increased expression of the epidermal suprabasal keratins K1 and K10 upon RA depletion of the media (delipidized serum), while simple epithelial type keratins K7, K8 and K18 as well as K19 and K13 (typical of internal stratified epithelia) were almost completely suppressed. The cell density-dependent increase of K1 and K10 at intermediate RA levels (as in regular media with untreated serum) was also observed at Ca2+ levels below 0.1 mM, thus being clearly unrelated to stratification, whereas K13 synthesis was Ca(2+)-dependent and initiated with stratification. The effects on keratins were fully reversed by increasing RA concentrations. There was only mild stimulation of proliferation at RA doses (10(-10) to 10(-8) M) not directly corresponding to suppression of keratinization. Thus, the negative RA influence on K1 and K10, opposed to the effect on simple keratins, substantiates the preserved regulatory capacity rendering these cells appropriate models for biological testing. Among the various tumorigenic HaCaT-ras clones highly and moderately differentiating ones could be distinguished, accordingly induction in vitro led to a comparable spectrum of differentiation markers (K1 and K10 appearing early, and filaggrin late) as growth in vivo. These in vitro results demonstrate that, in spite of some differences in RA sensitivity, virtually all clones possess the epidermal differentiation repertoir which is regulated according to the same principles. Finally, this confirms our in vivo data that differentiation potential is not inversely related to the state of transformation or tumorigenicity. Topics: Calcium; Cell Division; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Epidermal Cells; Epidermis; Filaggrin Proteins; Fluorescent Antibody Technique; Humans; Keratinocytes; Keratins; Precipitin Tests; Proto-Oncogene Proteins p21(ras); Skin Neoplasms; Tretinoin; Tumor Cells, Cultured | 1993 |
Solid basal cell epithelioma (BCE) possibly originates from the outer root sheath of the hair follicle.
The presence and distribution of several cytokeratins (CKs) in 20 solid basal cell epitheliomas (BCEs) were investigated and compared with the pattern of CKs in normal epidermis, perilesional skin and in the outer root sheath (ORS) of the human hair follicle. Tissue samples were stained with monoclonal antibodies (MoAbs) against human CKs, using the APAAP technique. Additionally, CK profiles were assessed by gel electrophoresis and immunoblot technique. Cells of BCE and ORS were positively stained with the MoAb KL1, whereas the basal layer of normal epidermis remained negative. Six out of 20 BCEs were partially stained with the MoAb RPN1165, which also stained the lower ORS, but not the epidermal basal layer. Using SDS-PAGE and immunoblot, the CK profiles of BCE and ORS were almost identical, showing the presence of CKs 5, 6, 14, 16 and 17; the CK pattern of normal epidermis, however, showed the presence of CKs 1, 5, 10 and 14. Perilesional skin (< 5 mm) showed keratin changes similar to the BCE pattern; the basal layer was stained with the MoAb KL1 and the suprabasal layer was negative to MoAb CK1, in contrast to normal epidermis. Keratin analysis revealed a CK pattern of perilesional skin different from that of normal epidermis (CKs 1, 5, 6, 10, 14, 16 and 17). Our immunohistochemical and biochemical investigations underline the possible role of the lower ORS as a cellular pool for the generation of BCE. Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Hair; Humans; Keratins; Scalp; Skin Neoplasms; Staining and Labeling | 1993 |
Cutaneous plexiform schwannoma in a pig.
A plexiform schwannoma (PFS) observed as a solitary mass in the dermis of a 6-month-old pig consisted of schwannoma cells of Antoni A type and B type. Neoplastic cells in Antoni A type areas sometimes showed cord-like outgrowths or a neurofibromatous pattern. Neoplastic cells in Antoni B type areas showed erythrophagocytosis, some encircling the microvasculature. Immunohistochemically, neoplastic cells were strongly positive for S-100 protein and vimentin. Peripheral parts of the nodules were cytokeratin (clone AE1/AE3)-positive, as in normal swine perineurial cells. Double immunostaining clearly demonstrated neoplastic cells doubly positive for both S-100 protein and cytokeratin, suggesting that S-100-positive Schwann cells and cytokeratin-positive perineurial cells are functional variants of the same cell type. Ultrastructurally, neoplastic cells in Antoni A type areas possessed characteristics of Schwann cells, such as cytoplasmic interdigitation, external laminae and intercellular junctions. At the periphery of the nodules, features of perineurial cells were detected. Neoplastic cells in Antoni B type areas seemed to be undergoing degenerative processes similar to those in Antoni A type regions and they contained many lysosomes. The neoplasm was generally similar in both location and histology to that seen in man, but there were some histological, immunohistochemical and ultrastructural differences. This is the first reported case of PFS in domestic animals. Topics: Animals; Epidermis; Female; Immunohistochemistry; Keratins; Neurilemmoma; S100 Proteins; Skin Neoplasms; Swine; Swine Diseases; Vimentin | 1993 |
The diagnostic use of low molecular weight keratin expression in sebaceous carcinoma.
Sebaceous carcinoma is an infrequent skin tumor and its histological features sometimes closely resemble those of squamous cell carcinoma (SCC) and basal cell epithelioma (BCE), which often leads to a misdiagnosis. In the present immunohistochemical study, however, sebaceous carcinoma exhibited quite a different expression of keratins from SCC and BCE. We immunohistochemically examined 26 excised specimens of sebaceous carcinoma, 10 of SCC and 12 of BCE of the eyelids, using two monoclonal antibodies against high molecular weight keratins, 34 beta B4 (68kd) and 34 beta E12 (56kd, 56.5kd, 58kd), and two monoclonal antibodies against low molecular weight keratins, 35 beta H11 (54kd) and CAM5.2 (39kd, 43kd, 50kd). The cases of sebaceous carcinoma were positive with 34 beta B4 (23%), 34 beta E12 (54%), 35 beta H11 (81%) and CAM5.2 (73%). Of the four anti-keratin antibodies used in this study, 35 beta H11 was negative in all cases of SCC or BCE. These findings indicate that when sebaceous carcinoma is suspected, but no fat staining appropriate materials are available, a monoclonal antibody against low molecular weight keratin, 35 beta H11 (54kd), can be a useful tool to immunohistochemically rule out both SCC and BCE. Topics: Adenocarcinoma, Sebaceous; Adenoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Molecular Weight; Sebaceous Gland Neoplasms; Skin Neoplasms | 1993 |
Plexiform schwannoma. Immunohistochemistry of Schwann cell markers, intermediate filaments and extracellular matrix components.
An immunohistochemical study using a comprehensive panel of antibodies to Schwann cell markers, intermediate filaments and extracellular matrix components has been performed on three cases of plexiform schwannoma. All tumour cells expressed S 100 protein, Leu 7-HNK 1 antigen and vimentin; glial fibrillary acidic protein was detected in many tumour cells. In addition, expression of cytokeratin was also demonstrated in one case. The associated extracellular matrix was found to be reactive with antibodies to laminin, heparan sulfate proteoglycan, fibronectin, type I, III, IV and VI collagen. It is concluded that Schwann cells producing their own extracellular matrix are the main components of these tumours. The significance of the cytokeratin expression and the possible role of the extracellular matrix in regulating Schwann cells' proliferation in peripheral nerve tumours are discussed. Topics: Adult; Antigens, Differentiation; Biomarkers, Tumor; Cell Division; Child, Preschool; Collagen; Extracellular Matrix Proteins; Fibronectins; Glial Fibrillary Acidic Protein; Heparitin Sulfate; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Laminin; Male; Neurilemmoma; S100 Proteins; Schwann Cells; Skin Neoplasms; Vimentin | 1993 |
Immunohistochemical characterization of transplantable rat squamous cell carcinoma (FF-6) in skin and thymus.
FF-6 is a transplantable squamous cell carcinoma which originally arose in the facial skin of a DA rat. It was established after maintaining the tumor in the subcutaneous tissue or peritoneal cavity of DA rats conventionally for over 30 generations. When the soybean-sized original FF-6 tumor was transplanted subcutaneously, it became an oval, hard, whitish, solitary and thumb-head-sized nodule within one month. After intraperitoneal transplantation of FF-6, it formed many nodules ranging from miliary to thumb-head size, which adhered and/or metastasized to many abdominal organs. When FF-6, cut into small pieces, was injected into the lower lip, the tumor grew bigger in situ, and metastasized to regional lymph nodes. Histologically, FF-6 was characterized as a well-differentiated squamous cell carcinoma, showing positive staining with anti-keratin, anti-laminin, anti-collagen type IV, anti-fibronectin and UB-14 antibodies. This transplantable tumor may be useful for analyzing the mechanisms of proliferation and metastasis of squamous cell carcinoma in vivo, and the host defence mechanism in rats, as well as being a suitable model of human squamous cell carcinoma. Topics: Animals; Carcinoma, Squamous Cell; Cell Division; Cell Line; Collagen; Fibronectins; Humans; Immunohistochemistry; Keratins; Laminin; Lymphatic Metastasis; Neoplasm Metastasis; Neoplasm Transplantation; Rats; Rats, Inbred Strains; Skin Neoplasms; Thymus Neoplasms | 1993 |
Cutaneous meningioma: histochemical, immunohistochemical and ultrastructural investigation.
Topics: Adolescent; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Male; Meningioma; Skin Neoplasms; Vimentin | 1993 |
Progressive alterations of cytokeratin expressions in the process of chronic arsenism.
Recent studies of an endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan are focusing on its cytokeratin analysis in hopes of tracing the disease's biochemical expression. Specimens were obtained from uninvolved skin and arsenical cancers including Bowen's disease, basal cell carcinoma, and squamous cell carcinoma. In this study, we used two-dimensional polyacrylamide gel electrophoresis to analyse cytokeratin expression. Progressive alterations in cytokeratin expression were found in various skin lesions. These include an expression of K16 in the uninvolved skin; K16 and K6 in Bowen's disease; and K16, K6 and K17 in squamous cell carcinoma and basal cell carcinoma. In addition, we found that the K1 isoelectric variants shifted to more acidic forms with the complete absence of K1 in basal cell carcinoma. K16 expression in uninvolved skin indicates that it is nevertheless in a hyperproliferative status. K17 was expressed in squamous cell carcinoma and basal cell carcinoma, but not in Bowen's disease. The progressive impairment of phosphorylation of K1 and K2 in the process of chronic arsenism provides us with a suitable model for studying the biological significance of phosphorylation in intermediate filaments during chemical carcinogenesis. Topics: Arsenic Poisoning; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chronic Disease; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Poisoning; Skin; Skin Neoplasms; Taiwan | 1993 |
[Analysis of keratin filament structural transformation in human epithelial cells].
Upon 2-3 hours cold treatment (0 degrees C), the keratin filaments of some PcaSE-1 cells and BEL-7404 cells are partly transformed into granular aggregates. But such structural transformation does not occur in HeLa cells and CNE cells. By rewarming (37 degrees C) cells within 15-30 minutes, this structural changes of keratin filaments in PcaSE-1 cells and BEL-7404 cells are readily reversed. In contrast, in HeLa cells and CNE cells, keratin filaments are transformed into granula aggregates during mitosis, but the keratin filament network in PcaSE-1 cells and BEL-7404 cells remained intact and encircled the developing mitotic spindle as the cells entered mitosis. Results suggest that the above two types of keratin filament structural transformation might be induced by different factors. Our results also indicate that: (1) PcaSE-1 cells treated with colchicine alone or with combination of colchicine and cytochalasin D does not cause granular aggregates of keratin filaments. However, after depolymerization of microtubules with colchicine, the response of the cells to cold treatment is intensified. (2) The aggregate formation during cold treatment is unrelated to whether epithelial cells contain two different type intermediate filaments or not. (3) Epithelial cells preextracted with Triton X-100 do not induce granular aggregate formation of keratin filaments upon cold treatment. (4) The structural transformation upon cold treatment may be a characteristic of keratin filaments of certain epithelial cell lines. Topics: Cold Temperature; Cytoplasmic Granules; Epithelium; HeLa Cells; Humans; Intermediate Filaments; Keratins; Liver Neoplasms; Nasopharyngeal Neoplasms; Skin Neoplasms; Tumor Cells, Cultured | 1993 |
Monospecific monoclonal antibodies to keratin 1 carboxy terminal (synthetic peptide) and to keratin 10 as markers of epidermal differentiation.
Monospecific antibodies to individual keratin polypeptides can be used to examine the tissue and cellular coexpression of members of keratin pairs. Monospecific monoclonal and polyclonal antibodies have been raised to keratins 1 and 10 using both crude cytoskeletal extracts and synthetic peptides. The tissue distribution of these keratins has been determined against a panel of freshly frozen normal tissues from humans, rodents and pigs. Epidermal expression has been examined in psoriatic plaques, and healing wounds, as examples of epidermal hyperproliferation. Cultured keratinocytes in monolayer (low calcium), stratified (high calcium), and complex cultures, transformed keratinocytes, and tumour cell lines, have been examined for the in vitro expression of these keratins. The sensitivity and precise localization of reactivity with these monospecific antibodies gives a highly accurate picture of individual cell expression. There is confirmation of coexpression of keratins 1 and 10 in epidermal and mucosal sites, and with keratin 16 in hyperproliferative states. These monospecific antibodies provide an important means of examining keratin expression in epidermal tumours and keratinizing disorders, and of seeking keratin mutations in cell lines and in skin diseases. Topics: Adult; Animals; Antibodies, Monoclonal; Biomarkers; Cell Differentiation; Cell Division; Cell Line; Cells, Cultured; Epidermal Cells; Epidermis; Gene Expression Regulation; Humans; Infant, Newborn; Keratinocytes; Keratins; Keratosis; Mice; Mice, Inbred BALB C; Mucous Membrane; Psoriasis; Skin; Skin Neoplasms; Swine; Wound Healing | 1993 |
Changes in keratin expression during malignant progression of transformed mouse epidermal keratinocytes.
We have studied in this report the expression of keratins in mouse epidermal keratinocytes transformed in culture by a chemical carcinogen (PDV) and in cell lines (PDVCM1, PDVCM2, PDVCV1, and PDVC57) derived by tumor transplantation of PDV cells in syngeneic C57Bl/6 mice. PDV, PDVCM1, PDVCM2, and PDVCV1 cell lines are weakly to moderately tumorigenic, giving rise to squamous cell carcinomas, although not at all injection points, whereas PDVC57 cells are more malignant, inducing highly anaplastic carcinomas at 100% of injection sites. All the cell lines synthesize anomalously simple epithelial keratins, substantial amounts of K8, and minor quantities of K18 and K19, but the level of expression is increased in PDVC57. We have found that in PDVC57 cells upregulation of K8 is linked to down-regulation of the normal keratins produced by epidermal keratinocytes in culture (i.e., K5, K6, K14, and K17). On the other hand, K8 does not generally colocalize with K13, a keratin also aberrantly expressed by epidermal cell cultures when induced to differentiate by high Ca2+ medium. K13, normally synthesized in internal stratified epithelia, is anomalously induced in mouse epidermal tumors and has been used as an early marker of carcinoma progression. In tumors induced by the cell lines upon injection in mice, K8 is found in the less differentiated regions as opposite to K13, restricted to the differentiating areas of the tumors. In PDV, PDVCM1, PDVCM2, and PDVCV1 carcinomas the overall expression of K13 is higher than that of K8. However, this relation is inverted in tumors induced by PDVC57 cells, in a good correlation with the tumoral phenotypes produced by the cell lines. Our results suggest that upregulation of the simple epithelial keratin K8, as found in transformed epidermal cell lines and tumors, is a late marker of malignant progression and is associated with the loss of the differentiated phenotype. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Line, Transformed; Cell Transformation, Neoplastic; Genes, ras; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Skin Neoplasms; Up-Regulation | 1993 |
Expression patterns of epithelial differentiation antigens and lectin-binding sites in ameloblastomas: a comparison with basal cell carcinomas.
Whether the peripheral ameloblastoma (PA) and intraoral basal cell carcinoma (BCC) are two different clinical entities or essentially the same lesion still remains unresolved. The immunophenotypes of neoplastic cells of peripheral and intraosseous ameloblastomas, ameloblastic carcinomas, and BCCs were studied using a panel of monoclonal/polyclonal antibodies and lectins. The major cytokeratins (CKs) of neoplastic cells of ameloblastomas were CKs 5 and 14, whereas co-expression of CKs 8, 18, and 19 was observed in the cells of the stellate reticulum-like areas. Metaplastic squamous and keratinizing cells found in follicular and acanthomatous variants of ameloblastomas expressed CKs 1 and 10, involucrin, and binding sites for the lectins Ulex europeaus agglutinin I and Helix pomatia agglutinin. beta 2-Microglobulin was uniformly negative in all cases of ameloblastomas and ameloblastic carcinomas studied. Cutaneous BCCs also demonstrated similar reactive patterns with the above-mentioned antigens. The most striking feature is the presence of a peritumorous band-like peanut agglutinin staining found in both BCCs and PAs but not in intraosseous ameloblastomas. This unique peanut agglutinin staining pattern of PA may be diagnostically useful for its histopathologic distinction from an intraosseous ameloblastoma that has infiltrated the soft tissue. The neoplastic cells of ameloblastomas express markers of less-differentiated epithelial cells. Despite differences in epithelial origins, PAs are tumors analogous to cutaneous BCCs. Topics: Adolescent; Adult; Aged; Ameloblastoma; Antigens, Differentiation; beta 2-Microglobulin; Bone Neoplasms; Carcinoma, Basal Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lectins; Male; Middle Aged; Protein Precursors; Receptors, Mitogen; Skin Neoplasms; Soft Tissue Neoplasms | 1993 |
Neurofilament immunoreactivity in Merkel-cell tumors: a differentiating feature from small-cell carcinoma.
To differentiate Merkel-cell tumor (MCT) from other neuroendocrine (NE) carcinomas, we immunostained (using avidin-biotin-peroxidase method) nine MCT and 37 NE (including 28 small-cell) carcinomas for NE markers (neuron-specific enolase and chromogranin), cytokeratin, neurofilament, vimentin, and a number of other markers. Cytokeratin was positive in 100% of MCT and in 85% of small-cell carcinomas; neurofilament and vimentin were positive in respectively 100% and 22% of MCT and 0% of NE carcinomas. Our data suggest that the coexpression of cytokeratin and neurofilament by an undifferentiated dermal or visceral tumor is of significant help in diagnosing MCT and differentiating it from small-cell carcinomas. The vimentin reactivity is a weak and insignificant discriminant. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Merkel Cell; Carcinoma, Small Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neurofilament Proteins; Phosphopyruvate Hydratase; Skin Neoplasms | 1993 |
Peripherin, a neuronal intermediate protein, is stably expressed by neuroendocrine carcinomas of the skin, their xenograft on nude mice, and the corresponding primary cultures.
The histogenesis of neuroendocrine carcinomas of the skin is still controversial. To determine the degree of neural differentiation of these neoplasias, we studied the expression of intermediate filament proteins in tumoral tissues. Expressions of peripherin, the neurofilament protein NF-L, vimentin, and cytokeratin 8 were analyzed by immunohistochemical methods on 12 human primary tumors and 3 tumor xenografts on nude mice. Peripherin was detected in 10 primary tumors by immunofluorescence. The protein and the corresponding messenger RNA were identified by two-dimensional gel electrophoresis and Northern analysis in extracts of an immunofluorescence-negative tumor. Peripherin, NF-L, and cytokeratin 8 were detected in tumoral cells, whereas vimentin was found exclusively in the stroma. The histological and ultrastructural properties of the original cells of neuroendocrine carcinomas of the skin, as well as coexpression of peripherin, cytokeratin 8, and neurofilament polypeptides, were preserved in tumor xenografts and their primary cultures in vitro. These results bring new elements to the knowledge of the biology of neuroendocrine carcinomas of the skin and indicate that peripherin constitutes a marker for tumor identification. Topics: Animals; Carcinoma, Merkel Cell; Humans; Intermediate Filament Proteins; Keratins; Membrane Glycoproteins; Mice; Mice, Nude; Neoplasm Transplantation; Nerve Tissue Proteins; Neuropeptides; Peripherins; Skin Neoplasms; Transplantation, Heterologous; Tumor Cells, Cultured; Vimentin | 1993 |
Low frequency of codon 61 Ha-ras mutations and lack of keratin 13 expression in 7,12-dimethylbenz[a]-anthracene-induced hamster skin tumors.
Alterations in the pattern of keratin expression are a common feature of skin-tumor development. In this study, we investigated whether the loss of epidermal keratin 1 (K1) and its replacement by mucosal keratin 13 (K13) is unique to mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA), since it has been reported that human epidermal tumors do not exhibit aberrant expression of K13. With that purpose, we analyzed the keratin profiles of 16 DMBA-induced hamster skin tumors using monospecific antibodies against K1 and K13. Although all the tumors expressed K1, they also showed an overall tendency towards loss of this keratin; furthermore, none of the tumors expressed K13. Previous studies have suggested that the induction of K13 in mouse skin is related to the mutation of the Ha-ras gene by the initiating agent DMBA, a mutation consistently found in murine DMBA/TPA-induced tumors and rarely found in human skin tumors. Therefore, we also evaluated the tumors for the presence of codon-61 mutations by direct sequencing of DNA extracted from paraffin-embedded tissue sections. Only three tumors showed an A-->T transversion in the second nucleotide of Ha-ras codon 61. However, presence of the mutation did not correlate with K1 staining. Although hamster skin tumors were induced by the same initiator as were mouse skin tumors, hamster skin tumors did not show the same keratin profile. Moreover, their immunohistochemical expression of K1 and K13 and their codon 61 sequences resembled that of their human counterparts. These results suggest that the aberrant expression of K13 may be unique to murine skin. Furthermore, although codon 61 Ha-ras mutation appears to be related to keratin alterations in the mouse model, this mutation is not sufficient to produce the same biochemical changes in other species. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Base Sequence; Carcinoma, Squamous Cell; Cheek; Cricetinae; DNA, Neoplasm; Genes, ras; Immunoenzyme Techniques; Keratins; Male; Mesocricetus; Molecular Sequence Data; Papilloma; Point Mutation; Polymerase Chain Reaction; Sequence Analysis, DNA; Skin Neoplasms; Species Specificity | 1993 |
Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by a targeted v-Ha-ras oncogene.
The regulatory elements of the human keratin K1 gene have been used to target expression of the v-Ha-ras oncogene exclusively in the epidermis of transgenic mice. We developed 12 transgenic mouse lines that express the HK1.ras transgene, producing epidermal hyperplasia in neonates and hyperkeratosis in juveniles. Eventually this skin phenotype diminished but with time adult animals developed papillomas that could persist or regress. The rate and frequency of tumorigenesis appeared to be limited, which suggests that v-Ha-ras requires a second or even third event to elicit and maintain a benign phenotype in transgenic mice. Since in certain transgenic lines papillomas appeared at wound sites, it appears that the promotion stimulus from wounding may be a second event. We envision that such transgenic mice that express v-Ha-ras in the epidermis will become a powerful model for assessing how environmental and molecular factors affect the process of multistage skin carcinogenesis in vivo, as well as a model for evaluating novel therapeutic protocols. Topics: Aging; Animals; Bacteriophage lambda; Base Sequence; Cell Transformation, Neoplastic; Disease Models, Animal; Female; Fluorescent Antibody Technique; Gene Expression; Gene Expression Regulation, Neoplastic; Genes, ras; Genetic Techniques; Hyperplasia; Keratins; Keratosis; Male; Mice; Mice, Transgenic; Molecular Sequence Data; Papilloma; Polymerase Chain Reaction; Regulatory Sequences, Nucleic Acid; RNA, Neoplasm; Skin Neoplasms | 1993 |
Granular cell basal cell carcinoma. Light microscopy, immunohistochemical and ultrastructural study.
Granular cell basal cell carcinoma (BCC) is a rare histological variant of BCC. In this, the fifth reported case, a 67-year-old male with BCC located on the nose, light microscopy examination showed a tumour with the classical configuration of nodular BCC, in which most cells had finely granular eosinophilic cytoplasm. Ultrastructural observation showed numerous lysosome-like granules filling the cytoplasm of tumour cells, along with numerous well-formed pentalaminate desmosomes. Immunohistochemical profile (including positivity for keratins C 5.2 and AE 1 and for Leu-M1), together with the presence of cytoplasmic tonofilament bundles and desmosomes, are consistent with the proposed epithelial origin of granular cells in this tumour. Topics: Aged; Carcinoma, Basal Cell; Cytoplasm; Desmosomes; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Skin Neoplasms | 1993 |
Retinoid-dependent transcriptional suppression of cytokeratin gene expression in human epidermal squamous cell carcinoma cells.
We have previously demonstrated that cytokeratin levels are coordinately regulated in normal cultured human keratinocytes. In the present study we examine the mechanism of this regulation using human squamous cell carcinoma (SCC) cells. Treatment of SCC-13 cells with 20 or 200 nM trans-retinoic acid results in nearly complete suppression of cytokeratin K5 and K6 expression. This change is accompanied by a simultaneous reduction (> 20-fold) in the level of the mRNAs encoding K5 and K6. Transcriptional analysis indicates that the transcription rate of the K5 and K6 genes drops by approximately four to fivefold in retinoid treated nuclei. Retinol (2000 nM) also promotes this change. In contrast, cytokeratin K19 does not increase in the presence of retinoic acid, thus the normal coordinate regulation of keratin gene expression by retinoids appears to be uncoupled in SCC-13 cells. However, this does not represent a general defect in positive regulation of gene expression by retinoids, since in a transient transfection assay trans-retinoic acid positively regulates a reporter plasmid containing the retinoid response element from the retinoic acid receptor-beta gene. The synthetic retinoids Ro 13-6298 (ethyl ester) and its metabolic derivative Ro 13-7410 (free acid) are both active in modulating the differentiation of normal keratinocytes. In contrast, only Ro 13-7410 is active in SCC-13 cells. As Ro 13-6298 binds poorly to the retinoic acid receptors, this suggests that SCC-13 cells, unlike normal keratinocytes, lack the ability to convert Ro 13-6298 to the active Ro 13-7410.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Base Sequence; Carcinoma, Squamous Cell; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Keratins; Molecular Sequence Data; Retinoids; Skin Neoplasms; Transcription, Genetic; Transfection; Tumor Cells, Cultured | 1993 |
Adenoid cystic carcinoma of the skin--an immunohistochemical and ultrastructural study.
Adenoid cystic carcinoma of the skin was studied. Histologically, tumor cells were arranged in a tubular and a cribriform pattern, mainly int he reticular dermis. Immunohistochemically, epithelial membrane antigen was reactive with the tumor cells, but S-100 protein, vimentin, and carcino-embryonic antigen were not. On electron microscopy, we confirmed the findings of previous reports; tumor cells were arranged to form luminal structures; most of them were pseudolumina containing fine mucin granules, basal laminae, and collagen fibers, but some were true lumina with numerous microvilli and junctional complexes. New findings of this study were bizarre-shaped, electron-dense, net-like structures within the true lumina which were considered to be a type of mucin. Topics: Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Collagen; Cytoplasm; Cytoplasmic Granules; Facial Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microvilli; Mucin-1; S100 Proteins; Skin Neoplasms; Vimentin | 1993 |
Spiradenomas in Brooke-Spiegler syndrome.
Brooke-Spiegler syndrome is an autosomal dominantly inherited disease characterized by the development of multiple trichoepitheliomas and cylindromas. Among other neoplasms that may also occur in Brooke-Spiegler syndrome are basal cell carcinomas and spiradenomas. Spiradenomas and cylindromas have so many features in common that they have been regarded as variants of the same neoplasm. This assumption was supported by the occurrence of both types of lesions in Brooke-Spiegler syndrome. We report a case of Brooke-Spiegler syndrome in which spiradenomas were found in the immediate vicinity of trichoepitheliomas and in continuity with follicles. Because of the embryonic relationship between follicles and apocrine glands, these features indicate that spiradenomas are apocrine neoplasms. We conclude that Brooke-Spiegler syndrome is an inherited disease that affects the folliculosebaceous apocrine unit. Topics: Adenoma, Sweat Gland; Adult; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Cell Nucleus; Cytoplasm; Facial Neoplasms; Female; Humans; Keratins; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; S100 Proteins; Skin Neoplasms | 1993 |
Spindle-cell non-pleomorphic atypical fibroxanthoma: analysis of a series and delineation of a distinctive variant.
Atypical fibroxanthoma is a bizarre, cytologically malignant but usually clinically benign, lesion which typically arises in sun-damaged skin of the head and neck region in the elderly. Classically, its morphology is said to represent the dermal counterpart of pleomorphic malignant fibrous histiocytoma. We have identified 10 cases of a more monomorphic spindle-celled, fascicular variant which, paradoxically, was often mistaken for a clinically malignant lesion because it lacked the pleomorphism of conventional atypical fibroxanthoma. These tumours all arose in the head and neck region as polypoid lesions in the elderly. The tumours were confined to the dermis, often had an epidermal collarette, showed an eosinophilic fascicular morphology and were highly mitotic. All 10 were vimentin positive and five showed very focal actin positivity. Desmin, keratin and S-100 protein were negative in all cases. The clinical course was benign in all cases, justifying their accurate recognition. The principal differential diagnoses are spindle cell squamous carcinoma, spindle cell melanoma and leiomyosarcoma. Immunohistochemistry plays a key role in this distinction. Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Desmin; Diagnosis, Differential; Female; Fibrosarcoma; Humans; Immunohistochemistry; Keratins; Leiomyosarcoma; Male; Melanoma; Middle Aged; Mitosis; S100 Proteins; Skin Neoplasms; Vimentin | 1993 |
Morphological characterization of a new human epithelioid sarcoma cell line, ES020488, in vitro and in vivo.
A new human epithelioid sarcoma cell line (ES020488) was established from a cutaneous metastasis in 26-year-old man, and was morphologically characterized in vitro and in vivo by comparison with the original tumor. The ES020488 cells showed a male karyotype ranging from 39 to 83 chromosomes, with various abnormalities but no specific pattern. The cells were round, polygonal or spindle-shaped with abundant cytoplasm and round nuclei containing prominent nucleoli; they proliferated in a sheet-like pattern. Tumors transplanted into nude mice revealed essentially the same features as the original tumor. Both in vitro and in vivo, the cells immunohistochemically expressed vimentin, cytokeratin, and EMA, but not desmin and S-100 protein. Ultrastructural study revealed irregular or round nuclei containing abundant euchromatin and prominent nucleoli, many intermediate filaments running irregularly or around the nucleus, and a number of filopodia-like processes. ES020488 cells were thus proven to retain and exhibit the unique morphological characteristics of an epithelioid sarcoma both in vitro and in vivo. These cells are possibly derived from synovioblastic mesenchyme. Topics: Adult; Animals; Cell Division; Cell Nucleolus; Cell Nucleus; Cytoplasm; Humans; Immunohistochemistry; Karyotyping; Keratins; Male; Mice; Mice, Nude; Microscopy, Electron; Neoplasm Transplantation; Sarcoma; Skin Neoplasms; Tumor Cells, Cultured; Vimentin | 1993 |
Chordoma cutis: a report of nineteen patients with cutaneous involvement of chordoma.
Chordoma, an uncommon tumor originating from remnants of the notochord, with cutaneous involvement has rarely been reported.. Our purpose was to document clinical manifestations, histopathologic features, immunohistochemical findings, treatment, and course of chordoma with cutaneous involvement.. Pathologically proven cases of chordoma were reviewed retrospectively for cutaneous involvement. Detailed clinical data and histopathologic changes were studied. Skin biopsy specimens were stained for immunohistochemical phenotyping.. Of 207 cases of chordoma, 19 had skin involvement: as local recurrences or metastasis in 12, as direct extension of primary tumor in 6, and as a result of distant metastasis from sacrococcygeal chordoma in 1. Local recurrences were frequent, but distant metastasis to various organs, including skin, occurred.. We propose the term chordoma cutis to describe this condition. In seven patients, cutaneous lesions were detected when the diagnosis of primary chordoma was made. Topics: Adult; Aged; Cause of Death; Cell Nucleus; Chordoma; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Sacrococcygeal Region; Skin Neoplasms; Survival Rate; Vacuoles; Vimentin | 1993 |
The nature of ghost cells in calcifying odontogenic cyst: an immunohistochemical study.
Two solid and two cystic forms of calcifying odontogenic cysts were stained immunohistochemically to study keratin, carcinoembryonic antigen, epithelial membrane antigen, and S-100 protein expression in ghost cells. The patterns of immunoreactivity were compared with those of dentigerous cysts, odontogenic keratocysts, ameloblastomas, calcifying epitheliomas of Malherbe, and control samples. Immunostaining patterns of calcifying odontogenic cysts were found to be similar to the odontogenic lesions and different from calcifying epithelioma. It is concluded that ghost cells are "keratinizing" odontogenic cells showing aberrant differentiation. These cells should not be regarded as metaplastic. The similarity of the immunostaining patterns of cystic and solid calcifying odontogenic cysts supports the view that these lesions are two morphologic variants of the same entity. Topics: Ameloblastoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Dentigerous Cyst; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mouth Mucosa; Mucin-1; Odontogenic Cysts; Odontogenic Tumors; S100 Proteins; Skin; Skin Neoplasms | 1993 |
Loss of expression of transforming growth factor beta in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion.
Mouse skin carcinomas arise from a small subpopulation of benign papillomas with an increased risk of malignant conversion. These papillomas arise with limited stimulation by tumor promoters, appear rapidly, and do not regress, suggesting that they differ in growth properties from the majority of benign tumors. The transforming growth factor beta (TGF-beta) proteins are expressed in the epidermis and are growth inhibitors for mouse keratinocytes in vitro; altered TGF-beta expression could influence the growth properties of high-risk papillomas. Normal epidermis, tumor promoter-treated epidermis, and skin papillomas at low risk for malignant conversion express TGF-beta 1 in the basal cell compartment and TGF-beta 2 in the suprabasal strata. In low-risk tumors, 90% of the proliferating cells are confined to the basal compartment. In contrast, the majority of high-risk papillomas are devoid of both TGF-beta 1 and TGF-beta 2 as soon as they arise; these tumors have up to 40% of the proliferating cells in the suprabasal layers. Squamous cell carcinomas are also devoid of TGF-beta, suggesting that they arise from the TGF-beta-deficient high-risk papillomas. In some high-risk papillomas, TGF-beta 1 loss can occur first and correlates with basal cell hyperproliferation, while TGF-beta 2 loss correlates with suprabasal hyperproliferation. Similarly, TGF-beta 1-null transgenic mice, which express wild-type levels of TGF-beta 2 in epidermis but no TGF-beta 1 in the basal layer, have a hyperproliferative basal cell layer without suprabasal proliferation. In tumors, loss of TGF-beta is controlled at the posttranscriptional level and is associated with expression of keratin 13, a documented marker of malignant progression. These results show that TGF-beta expression and function are compartmentalized in epidermis and epidermal tumors and that loss of TGF-beta is an early, biologically relevant risk factor for malignant progression. Topics: Animals; Base Sequence; Carcinoma, Squamous Cell; Cell Division; Cell Transformation, Neoplastic; Epidermal Cells; Epidermis; Female; Keratins; Mice; Mice, Transgenic; Molecular Sequence Data; Papilloma; Risk; Skin Neoplasms; Transforming Growth Factor beta | 1993 |
Avian keratoacanthoma (dermal squamous cell carcinoma) in broiler chicken carcasses.
Multiple lesions of dermal squamous cell carcinoma are found at a low frequency (0.04%) in the carcasses of young meat-type chickens at slaughter. For this study, affected carcasses (n = 308) were removed from the processing line, and lesions were characterized by size, distribution, and morphology. Carcasses were also sexed and examined for evidence of metastasis. Nodular (n = 297) and ulcerative (n = 1,707) lesions were counted and examined. Most lesions were present in the pectoral, dorsopelvic, and femoral feather tracts. Few lesions (n = 11) were found in wing tracts. Mean diameter was 5.4 mm for ulcerative lesions and 3.1 mm for nodular lesions. Histologic sections of ulcerative (n = 579) and nodular (n = 113) lesions were examined. Small nodular lesions originated from hyperplastic feather follicle epithelium. Nodules contained keratin-filled cysts lined by squamous epithelium that were associated with isolated islands and infiltrating cords of dermal keratinocytes. Loss of surface epithelium resulted in noduloulcerative and ulcerative lesions. Invasion of underlying skeletal muscle and evidence of visceral metastasis were not present, but invasion through elastic laminae and into the subcutis was present in 20.5% (134/654) of the lesions examined. The nodular lesions in these carcasses were morphologically similar to early nodular lesions previously described in live chickens as avian keratoacanthomas. A retrospective study compared selected production parameters and disease condemnations to the prevalence of squamous cell carcinoma in 665 flocks of broiler chickens. There was a positive correlation (P < 0.0001) with the occurrence of airsacculitis but a negative correlation with increased age and condemnations for leukosis (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Animals; Carcinoma, Squamous Cell; Keratinocytes; Keratins; Poultry; Poultry Diseases; Prevalence; Retrospective Studies; Skin Neoplasms | 1993 |
Hyperplasia, hyperkeratosis and benign tumor production in transgenic mice by a targeted v-fos oncogene suggest a role for fos in epidermal differentiation and neoplasia.
A vector, derived from the human K1 keratin gene, has been employed to target v-fos expression exclusively in the epidermis of transgenic mice. Adult transgenic mice expressors (3-4 months) displayed hyperplasia and hyperkeratosis, initially in wounded (tagged) ears, which later became bilateral. This phenotype appeared at other epidermal sites, most notably in the axilla and inguinal areas. This indicates that a second promoting event, such as wounding or friction, is required to elicit these pathological changes. Highly keratotic benign ear lesions and benign squamous papillomas appeared after long latency at sites of phenotypic epidermis. These data suggest that v-fos may be interfering with c-fos function in normal keratinocyte differentiation, but by itself is insufficient to elicit overt benign lesions. Topics: Alopecia; Animals; Base Sequence; Cell Differentiation; Epidermis; Gene Expression Regulation, Neoplastic; Genes, fos; Hyperplasia; Keratins; Keratosis; Mice; Mice, Transgenic; Molecular Sequence Data; Oncogene Proteins v-fos; Proto-Oncogene Proteins c-fos; Skin Neoplasms | 1993 |
Meningioma-like tumor of the skin. An ultrastructural and immunohistochemical study.
Three unusual cutaneous tumors are described along with ultrastructural and immunohistochemical studies. All lesions were asymptomatic red-brown papulonodules. Light microscopic examination revealed a whorled configuration of spindle-shaped cells, some concentrically arranged around blood vessels. Immunohistochemical panels exhibited positive staining only with antibody to vimentin and negative staining with antibodies against S-100 protein, muscle markers, cytokeratin, epithelial membrane antigen, Leu 7, type IV collagen, and factor XIIIa, ruling out obvious nevomelanocytic, nerve sheath, meningothelial, smooth muscle, and perithelial differentiation. Electron microscopic examination demonstrated cells producing poorly formed collagen fibrils, sparse collagen fibers, and possessing occasional ill-defined intercellular junctions between their elongated cell processes. This rare tumor is considered to be either an immature fibrohistiocytic or possibly a nerve sheath neoplasm with striking similarities to so-called canine hemangiopericytoma. Because the prominent whorled pattern was reminiscent of meningioma, the lesion was referred to as meningioma-like tumor of the skin. Topics: Actins; Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; CD57 Antigens; Collagen; Desmin; Female; Hemangiopericytoma; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Meningioma; Microscopy, Electron; Middle Aged; Mucin-1; S100 Proteins; Skin Neoplasms; Vimentin | 1993 |
Immunohistochemical evaluation of epidermis overlying basal cell carcinomas.
We have examined the character and carcinogenic properties of the normal-appearing epidermis overlying basal cell carcinomas by immunohistochemical methods, employing a series of monoclonal antibodies. The labelling index was significantly increased in the atrophic epidermis overlying basal cell carcinomas (solid type, n = 20), compared with the epidermis overlying or adjacent to squamous cell carcinoma (n = 20), keratoacanthoma (n = 10), dermatofibroma (n = 10), neurofibroma (n = 10), soft fibroma (n = 10), pyogenic granuloma (n = 10) and cutaneous leiomyoma (n = 5). Cells which expressed epidermal growth factor (EGF) receptor were detected in all layers of the epidermis over the basal cell carcinomas, but not the other tumours. Basement membrane-related antigens, including bullous pemphigoid antigen and GB3 antigen, were decreased in the epidermis. AE1, the monoclonal antibody against basal cell keratin, reacted with the uppermost layers of the normal-appearing epidermis overlying the basal cell carcinomas. ICAM-1 expression was very weak in the overlying epidermis. The dermis subjacent to the proliferating epidermis showed staining for transforming growth factor-alpha (TGF-alpha), strong positive PECAM-1 staining of endothelium, and numerous HLA-DR-positive cells. From these results, we suggest that the proliferative activity in the epidermis overlying basal cell carcinomas is not a state induced by the dermal infiltrate, but represents carcinogenic activity of the epidermis. Topics: Antibodies, Monoclonal; Antigens, CD; Autoantigens; Basement Membrane; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Adhesion Molecules; DNA; Epidermis; ErbB Receptors; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Keratins; Skin Neoplasms; Transforming Growth Factor alpha | 1993 |
Immortalization of rabbit corneal epithelial cells by a recombinant SV40-adenovirus vector.
Cultured corneal epithelial cell is detrimental because of its short life span and its heterogeneity. We have tried to establish an immortalized epithelial cell line.. Primary cultured rabbit corneal epithelial cells were infected with a recombinant SV40-adenovirus vector and were cloned three times.. The immortalized cell continued to grow by more than 400 generations through 100 passages. SV40-associated large T antigen was demonstrable on the nuclear membrane of these immortalized cells by immunofluorescence technique. This cell line exhibited a similar cobblestone-like appearance as normal corneal epithelial cells. Transmission electron microscopy showed a line of evidence for stratification, including desmosome formation and microvilli development at the superficial cell layer. As the culture grew, these cells began to express cornea-specific 64 kD cytokeratins. In contrast to cultured normal corneal epithelial cells, this cell line had a good proliferative ability after a long-term storage in liquid nitrogen.. Because this particular cell line shares properties consistent with normal corneal epithelial cells and is easy to handle in vitro, it may serve as a useful tool in corneal epithelial research. Topics: Animals; Antigens, Polyomavirus Transforming; Cell Division; Cell Line; Cell Transformation, Viral; Cells, Cultured; Cornea; Electrophoresis, Polyacrylamide Gel; Epithelial Cells; Epithelium; Fluorescent Antibody Technique; Keratins; Male; Mice; Mice, SCID; Rabbits; Recombinant Proteins; Severe Combined Immunodeficiency; Simian virus 40; Skin Neoplasms | 1993 |
ras gene activation and aberrant expression of keratin K13 in ultraviolet B radiation-induced epidermal neoplasias of mouse skin.
Both papillomas and squamous cell carcinomas (SCC) induced in mouse epidermis by initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) exhibit aberrant expression of a type I keratin, K13, that is normally characteristic of terminal differentiation of internal stratified epithelia. There is evidence that the aberrant expression of K13 depends on the presence of an activated ras gene in mouse epidermal keratinocytes (Sutter et al., Mol Carcinog 4:467-476, 1991). To assess the general validity of this hypothesis, we investigated both aberrant K13 expression and activation of each of the three members of the ras gene family in epidermal tumors induced in four different mouse strains (SKH-1 hr, SENCAR, BALB/c, and C3H/He) by chronic irradiation with ultraviolet (UV) B. The tumor collection comprised nine papillomas and 30 well or poorly differentiated SCC. Aberrant K13 expression occurred in only five of 39 tumors and was restricted to SCC of both types. This indicates that aberrant K13 expression in UV-induced epidermal tumors was intrinsically different from that in chemically induced tumors. Polymerase chain reaction analysis of the tumors for different point mutations in codons 12, 13, and 61 of the Ha-ras and Ki-ras genes and in codon 61 of the N-ras gene revealed that only one of the well differentiated tumors from a SKH-1 hr mouse exhibited a GGA-->GAA mutation in codon 12 of the Ha-ras gene. Although this tumor was also positive for aberrant K13 expression, such a correlation could not be made for the remaining K13-expressing tumors. This indicates that the activation of one of the members of the ras gene family is not a general prerequisite for the aberrant expression of K13 in mouse epidermal keratinocytes. Topics: Animals; Base Sequence; Carcinoma, Squamous Cell; Gene Expression Regulation, Neoplastic; Genes, ras; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Molecular Sequence Data; Neoplasms, Radiation-Induced; Papilloma; Point Mutation; Skin Neoplasms; Transcriptional Activation; Ultraviolet Rays | 1993 |
The conversion of mouse skin squamous cell carcinomas to spindle cell carcinomas is a recessive event.
Squamous carcinomas of both human and rodent origin can undergo a transition to a more invasive, metastatic phenotype involving reorganization of the cytoskeleton, loss of cell adhesion molecules such as E-cadherin and acquisition of a fibroblastoid or spindle cell morphology. We have developed a series of cell lines from mouse skin tumors which represent different stages of carcinogenesis, including benign papillomas, and clonally related squamous and spindle carcinomas derived from the same primary tumor. Some spindle cells continue to express keratins, but with a poorly organized keratin filament network, whereas in others no keratin expression is detectable. All of the spindle cells lack expression of the cell adhesion molecule E-cadherin and the desmosomal component desmoplakin. Loss of these cell surface proteins therefore appears to precede the destabilization of the keratin network. At the genetic level, it is not known whether such changes involve activation of dominantly acting oncogenes or loss of a suppressor function which controls epithelial differentiation. To examine this question, we have carried out a series of fusion experiments between a highly malignant mouse skin spindle cell carcinoma and cell lines derived from premalignant or malignant mouse skin tumors, including both squamous and spindle carcinoma variants. The results show that the spindle cell phenotype as determined by cell morphology and lack of expression of keratin, E-cadherin, and desmoplakin proteins, is recessive in all hybrids with squamous cells. The hybrids expressed all of these differentiation markers, and showed suppression of tumorigenicity to a variable level dependent upon the tumorigenic properties of the less malignant fusion partner. Our results suggest that acquisition of the spindle cell phenotype involves functional loss of a gene(s) which controls epithelial differentiation. Topics: Animals; Antigens, Differentiation; Cadherins; Carcinoma; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cytoskeletal Proteins; Cytoskeleton; Desmoplakins; Epidermis; Fluorescent Antibody Technique; Gene Expression Regulation; Genes, Recessive; Genes, Suppressor; Hybrid Cells; Immunohistochemistry; Keratins; Mice; Phenotype; Skin Neoplasms; Tumor Cells, Cultured | 1993 |
Squamous cell carcinomas. An immunohistochemical study of cytokeratins and involucrin in primary and metastatic tumours.
The expression of cytokeratins (CK) 1, 4, 5/6, 8, 13, 18, 19 and 20 and involucrin in 42 cases of squamous cell carcinomas from various locations was examined. The tumours expressed CK5/6 in 55%, CK8 in 76%, CK13 in 43% and CK19 in 95% of cases. The CK5/6-positive primary tumours were from uterine cervix, head and neck, lung, skin, oesophagus and urinary bladder, and the CK13-positive primary tumours were from uterine cervix, lung and vulva. Metastatic squamous cell carcinomas from head and neck more frequently expressed CK5/6 and 13, 7/7 (100%) and 6/7 (86%) compared with 3/5 (60%) and 0/5 (0%) in the primary squamous cell carcinomas. Few cases were CK1, CK4 and CK18 immunoreactive. CK20 immunoreactivity was not observed. Involucrin was expressed in 71% of tumours, and most of the involucrin-positive cells were located at the central parts of tumour cell clusters except for one case in which the peripheral cells around tumour cell clusters were positive. Thus, expression of the so-called simple epithelial markers CK8 and CK19 occurs in the majority of squamous cell carcinomas. The absence of CK20 immunoreactivity may be helpful in differential diagnosis. Topics: Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphatic Metastasis; Mouth Neoplasms; Protein Precursors; Skin Neoplasms; Urinary Bladder Neoplasms; Uterine Neoplasms | 1993 |
Primary cutaneous CD30-positive anaplastic large cell lymphoma. Report of 27 cases.
The clinical, morphological and immunohistochemical features of 27 patients with anaplastic large cell lymphoma (ALCL) of CD30-positive type, with cutaneous lesions as the sole initial clinical manifestation, were analyzed. The neoplasm presented as solitary or multiple, usually ulcerated skin lesions, affecting predominantly elderly patients (median age: 67 years) with a male preponderance (male to female ratio of 6:1). In most patients, there was an excellent response to chemotherapy. The cardinal histological features included diffuse dermal and subcutaneous infiltration by large, anaplastic tumor cells, all or nearly all of which showed diffuse, strong membrane staining and frequently a paranuclear, dot-like reaction with the CD30 marker (Ber-H2). Epidermal ulceration, pseudo-epitheliomatous hyperplasia and dermal vascular proliferation were also observed. Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Neoplasm; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Lymphoma, Large B-Cell, Diffuse; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Skin Neoplasms | 1993 |
Schwannoma with sweat duct differentiation.
We report a schwannoma with well differentiated ducts resembling cutaneous sweat ducts. The tumor presented as a painless mass near the left knee of a 41-year-old female. The mass had been present for many years. Some increase in size had been noticed over the previous 2 to 3 yr. The bulk of the tumor was composed of spindle cells with the appearance of Antoni A and Antoni B tissue. Rare mitotic figures were noted. In several areas of the tumor, numerous well-differentiated ducts were present. Most resembled normal cutaneous sweat ducts. In some areas, cystic dilatation of the ducts was present. Focal areas demonstrated poorly formed ducts and single cells with prominent nuclei and ample cytoplasm. Well formed ducts, poorly formed ducts, and single cells marked with AE 1/3 (keratin) and epithelial membrane antigen. The spindle cell proliferation marked for S 100 protein and vimentin. Sweat duct differentiation has not been reported previously in either benign or malignant schwannoma. Light and electron microscopic features of this tumor are presented. Topics: Adult; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Neurilemmoma; S100 Proteins; Skin Neoplasms; Sweat Glands; Vimentin | 1993 |
Cutaneous lymphadenoma. A basal cell carcinoma with unusual inflammatory reaction pattern?
Two additional cases of cutaneous lymphadenoma (CL) are reported. The lesions presented as single nodules of many years' duration on the face. Histologically, the neoplasms consisted of irregularly shaped lobules immersed in a dense fibroblastic stroma involving the whole dermis and extending into the subcutaneous fat. Duct-like structures suggesting an eccrine differentiation were recognized. The lobules were composed of a rim of basaloid cells surrounding large epithelioid cells and lymphocytes. In some areas the basaloid lobules were only partly replaced by the inflammatory cells. Immunohistochemically, the intralobular inflammatory component was composed of a mixed B- and T-cell population and S-100-positive dendritic cells. The observation of these cases suggests that CL is not a distinct entity but may represent a basal cell carcinoma, possibly with pilar or eccrine differentiation, in which an immune host reaction pattern is exceedingly unusual. Topics: B-Lymphocytes; Carcinoma, Basal Cell; Cheek; Diagnosis, Differential; Epithelium; Facial Neoplasms; Female; Fibroblasts; Humans; Keratins; Lymphoma; Male; Middle Aged; S100 Proteins; Skin Neoplasms; T-Lymphocytes | 1993 |
Cooperation between v-fos and v-rasHA induces autonomous papillomas in transgenic epidermis but not malignant conversion.
Transgenic mice have been previously established that express v-rasHa or v-fos exclusively in the epidermis by means of a targeting vector based on the human keratin 1 gene (HK1). Epidermal expression of v-rasHa (HK1.ras) or v-fos (HK1.fos) resulted in hyperplasia, hyperkeratosis, and later, in benign tumors. To assess the potential for oncogene cooperation in vivo mating experiments were performed. Resultant HK1.fos/ras mice exhibited an obvious increase in the severity of neonatal and juvenile preneoplastic phenotypes, together with the immediate onset of tumorigenesis as compared to single oncogene sibling controls. The HK1.fos/ras tumors grew aggressively and often compromised the animals by 10-12 weeks. However, tumors remained benign as determined by histotype and specific keratin markers. These data indicate that v-fos can cooperate with an initiating v-rasHa phenotype to generate autonomous papillomas, but additional events are required for malignant conversion. Topics: Animals; Animals, Newborn; Base Sequence; Cell Transformation, Neoplastic; DNA Primers; Fluorescent Antibody Technique; Genes, fos; Genes, ras; Genetic Vectors; Humans; Hyperplasia; Introns; Keratins; Mice; Mice, Transgenic; Molecular Sequence Data; Papilloma; Polymerase Chain Reaction; Skin; Skin Neoplasms; TATA Box | 1993 |
[Nevoid acquired perforating dermatosis of vellus hair follicles--a new entity? Case report with immunohistochemical studies].
We report on a 45-year-old male patient with a 15-years history of partly excoriated and inflamed lesions of verruccous-papular character, arranged in a linear naevoid fashion on the extensor side of the right arm and shoulder. The lesions were not related to a dermatoma but seemed to be located in the Blaschko's lines. On histology an epidermal invagination was found, conspicuously arranged over proliferating vellus hair follicles, which were increased in number as in a hamartoma. The rete ridges were directed towards early anagens of the vellus hairs with consecutive crateriform invagination of the epidermis with parakeratosis and basophilic debris on the innermost layer of the invagination. Serial sections allowed demonstration of incomplete and complete perforation with accumulation of neutrophils. Immunohistochemistry revealed marked staining of basal cells of the proliferating epidermal keratinocytes with cytokeratins 14 and 18 within the lesion. No association with diabetes or renal insufficiency and no familial background could be found. Topics: Adult; Arm; Basement Membrane; Biopsy; Cell Division; Darier Disease; Humans; Immunoenzyme Techniques; Keratins; Male; Nevus, Pigmented; Skin; Skin Neoplasms | 1993 |
Histologic spectrum of carcinomas with eccrine ductal differentiation (sweat-gland ductal carcinomas).
Seven cases of sweat-gland carcinomas showing eccrine ductal differentiation (ductal carcinomas) are presented. The tumors had a variable histological appearance, but were basically characterized by the following histological elements: (a) tubular structures, sometimes cystic or having a "tadpole" appearance; (b) solid islands of squamous, basaloid, or clear cells; (c) periodic acid-Schiff-positive endoluminal and/or intracellular material; and (d) infiltrating growth. Immunocytochemically, tumor cells were positive for keratin and negative for actin. Endoluminal material contained carcinoembryonic antigen in five of seven cases. Although it is not yet clear whether carcinomas exhibiting eccrine ductal differentiation may represent a specific histotype or a group encompassing several distinct clinicopathological entities, the histological analysis of the cases suggested that the wide spectrum of their histological appearances may be due to variable grades of differentiation. Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Eccrine Glands; Facial Neoplasms; Female; Humans; Keratins; Lip Neoplasms; Male; Middle Aged; Scalp; Skin Neoplasms; Sweat Gland Neoplasms; Thoracic Neoplasms | 1993 |
Trichogerminoma. Report of 14 cases.
We report 14 cases of trichogerminoma, a rare form of cutaneous adnexal neoplasm, derived from hair germ epithelium. The neoplasms occurred in 9 men and 5 women. Their ages ranged from 16 to 73 years (median 53 years). The tumors were slow growing, asymptomatic dermal or subcutaneous nodules, located on the head and neck (6), trunk (4), extremities (2) and hip (1), with no distinguishing clinical features. Histologically, trichogerminomas were characterized by sharply circumscribed, pseudoencapsulated dermal and subcutaneous nodules, ranging in size from 0.4 to 4.0 cm in diameter (mean 1.9 cm). The nodules were subdivided into lobules separated by variable amounts of stroma that demonstrated varying cellularity and mucin content. The lobules were composed of basaloid cells that formed densely packed, round nests or "cell balls" resembling hair bulbs. The basaloid cells demonstrated peripheral palisading, keratinization and differentiation towards various pilosebaceous structures. Retraction spaces, well developed hair follicles and hair shafts were not observed. These distinctive histologic features separated these neoplasms from other tumors of pilar origin and from basal cell carcinoma. The trichogerminomas behaved in a benign fashion with one exception. Complete excision of the lesions is the treatment of choice. Topics: Adolescent; Adult; Aged; Epidermis; Epithelium; Female; Hair Diseases; Humans; Keratins; Male; Middle Aged; Skin Neoplasms | 1992 |
Meningothelial hamartoma of the scalp. A case report with immunohistochemical studies.
An unusual and, apparently, hitherto undescribed congenital lesion of the scalp which proved to be heterotopic meningothelial tissue is reported, and its clinical, morphological, and theoretical implications are reviewed. A 14-month-old male infant exhibited a soft tissue lesion on the midline of the parietal scalp since birth. The lesion had grown in size since birth. Histological examination showed an admixture of mature adipose tissue, bands consisting of bundles and small nodules of dense collagen, both enclosed and bordered by rests and strands of meningothelial cells. A network of vessel-like channels lined by plump hyperchromatic cells with spindle-shaped nuclei and occasionally multinucleated giant cells was one of the prominent features. Immunohistochemically, these cells were positive for vimentin, but staining was negative for EMA and all other antibodies tested. A fibrocollagenous stalk via bony defect showed no arachnoid cell rests. The authors believe that the herein described lesion and the hamartoma of the scalp described by Suster and Rosai (1990) may represent varying morphological expressions of a pathogenetically related process. Precautions appropriate to the possibility of intracranial extension must be taken at the time of surgery. Topics: Antigens, Neoplasm; Collagen; Hamartoma; Humans; Immunohistochemistry; Infant; Keratins; Male; Meninges; Scalp; Skin Neoplasms; Soft Tissue Neoplasms | 1992 |
Keratin expression in normal skin and epidermal neoplasms demonstrated by a panel of monoclonal antibodies.
The tissue labelling of a panel of monoclonal antikeratin antibodies (LL001, LL002, LL003, LP2K, BA17, LP34, CAM5.2, and LH1) recognising keratins 1, 5, 8, 10, 14, 18, and 19 were investigated in frozen and formalin-fixed normal skin. Antibodies LL001, LL003, BA17, LP34, CAM5.2, and LH1 were found to be reactive in formalin-fixed material and were used to study 23 basal cell carcinomas, 8 squamous cell carcinomas, 5 keratoacanthomas, 5 Bowen's disease, and 6 clear cell acanthomas. All these tumours demonstrated a loss of keratin 10 expression as demonstrated by loss of labelling with LH1. Keratin 14 expression, as demonstrated by LL001, was reduced but present in all the tumours except squamous cell carcinomas and keratoacanthomas where increased labelling was observed in the more differentiated areas of these tumours. Simple epithelial keratin expression was demonstrated by positive labelling with CAM5.2 and keratin 19 by BA17 in a third of basal cell carcinomas and squamous cell carcinomas. Three of the five keratoacanthomas labelled with BA17, indicating the presence of keratin 19 in these lesions. These results support the concept that keratin expression is a phenotypic marker of the state of differentiation or malignant transformation and that patterns of keratin expression are not specific to any particular premalignant or malignant disorder. Topics: Antibodies, Monoclonal; Axilla; Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Freezing; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Reference Values; Skin; Skin Neoplasms; Tissue Fixation | 1992 |
Malignant pilomatricoma. An immunohistochemical study with antihair keratin antibody.
A case is reported of malignant pilomatricoma confirmed by immunohistochemistry using anti-human hair keratin (anti-HHK) antibody prepared by the authors. The tumor occurred in the soft tissue of the inguinal region of an 88-year-old woman, with later invasion of the epidermis. No other possible primary lesion was found at autopsy. Histologically, the tumor was squamous cell carcinoma with nests of tumor cells and shadow cell-like necrotic cells showing central keratinization and focal calcification. Immunohistochemically, the hair keratin was positive in this tumor and in benign pilomatricomas exclusively. All other skin lesions and various squamous cell carcinomas examined were negative for this antigen. The staining patterns of commercial antiepidermal keratin and antiinvolucrin antibodies were significantly different from that of anti-HHK in normal skin and in these lesions. To the authors' knowledge, this is the first case of malignant pilomatricoma tested with anti-HHK staining. Malignant pilomatricoma is generally a low-grade malignant tumor, but it can metastasize and be fatal as it was in this case. Topics: Aged; Aged, 80 and over; Biomarkers; Blotting, Western; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Female; Hair; Humans; Immunoenzyme Techniques; Keratins; Scalp; Skin Neoplasms | 1992 |
Keratin expression in basal cell carcinomas.
The keratin phenotype of 15 cases of basal cell carcinoma was assayed immunohistochemically using a panel of monospecific antibodies to single keratin polypeptides. Whilst tumour tissue strongly expressed primary keratins 5 and 14 (normally synthesized in basal keratinocytes) no expression of secondary keratins 1 and 10 (characteristic of skin-type differentiation) was detected. Keratin 17, characteristic of the outer hair root sheath, was strongly expressed in all tumours. Keratin 19 was also normally expressed in parts of the hair follicle and was detected in four cases. The 'high cell turnover' keratin 16 was frequently induced in the overlying epidermis, but was rare within tumour tissue. No expression of simple epithelial keratins 8 and 18 was detected. Whilst the keratin phenotype of tumour cells is similar to that of basal cells within part of the hair root sheath, in keeping with suggestions of a follicular origin for basal cell carcinomas, the findings are also compatible with an origin from interfollicular pluripotent stem cells differentiating towards follicular structures. Topics: Animals; Antibodies, Monoclonal; Carcinoma, Basal Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mice; Rabbits; Skin Neoplasms | 1992 |
The fibroma-like variant of epithelioid sarcoma. A fibrohistiocytic/myoid cell lesion often confused with benign and malignant spindle cell tumors.
Five cases of a previously undescribed variant of epithelioid sarcoma are presented. This variant differs from the usual lesion in its absence of the typical necrobiotic nodular epithelioid pattern. It is instead composed of deceptively bland fibrohistiocytic and myoid cells arranged in a fibroma-like or dermatofibroma-like pattern with an affinity for osseous involvement. The clinical presentation, ultrastructural features, and presence of vimentin and low molecular weight keratin within the tumor cells justifies their designation as an epithelioid sarcoma variant. Topics: Adolescent; Adult; Bone Neoplasms; Calcaneus; Diagnosis, Differential; Female; Femoral Neoplasms; Fibroma; Fingers; Histiocytoma, Benign Fibrous; Humans; Humerus; Keratins; Male; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms; Thigh; Tibia; Toes; Ulna; Vimentin | 1992 |
Poorly differentiated squamous cell carcinomas of the skin can express vimentin.
Thirty cases of poorly differentiated carcinomas of the skin were examined for the expression of vimentin. All cases expressed cytokeratins; in addition, 12 cases were positive for vimentin. These were all non-reactive with antibodies to S100 protein, HMB45 and desmin. The finding of vimentin in poorly differentiated squamous cell carcinomas underscores the need for caution in the use of immunohistochemical stains for tumor typing. Cutaneous squamous cell carcinomas are an addition to the list of epithelial tumors which are known to coexpress vimentin intermediate filaments. Other carcinomas which consistently express vimentin include those of renal, endometrial, thyroid, pulmonary, ovarian, salivary gland, adrenal and more recently, those of breast and prostatic origin. Topics: Actin Cytoskeleton; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Skin Neoplasms; Vimentin | 1992 |
Desmoplastic trichilemmoma.
Seven cases of desmoplastic trichilemmoma (DT), a recently described pseudomalignant variant of trichilemmoma, are reviewed. The tumor generally occurs in men after the fifth decade of life and presents as a small solitary nodule on the face. It is frequently misdiagnosed clinically as a basal cell carcinoma or a papilloma. Histologically DT displays a superficial lobular growth arranged about a central prominent desmoplastic stroma. At the periphery, the tumor lobules show the typical features of trichilemmoma. In contrast, at the center the cells assume a more random pattern of cords and strands traversed by the hyaline stroma, mimicking invasive carcinoma. The tumor's architectural pattern, in particular the perilobular hyaline mantle, enables DT to be differentiated from basal cell carcinoma and malignant trichilemmoma. Immunohistochemical analysis failed to demonstrate human papilloma virus (HPV), epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and alpha-lactalbumin in tumor epithelium. Keratin was expressed by the central pseudoinvasive epithelial cords. Neither factor XIIIa nor keratin expression was found in the stromal cells, which stained only for vimentin. These findings suggest that DT is not an HPV-induced epithelial proliferation and that the stroma is not the result of degenerative changes in tumor epithelium. Instead, there appears to be a fibroblast-mediated, dendrocyte-independent, stromal reaction producing this appearance. Topics: Aged; Antigens, Neoplasm; Antigens, Viral; Carcinoembryonic Antigen; Cell Nucleus; Child; Cytoplasm; Facial Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Lactalbumin; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Papillomaviridae; Skin Neoplasms; Transglutaminases; Vimentin | 1992 |
Cystic giant solitary trichoepithelioma.
A case of a giant solitary trichoepithelioma is reported. The tumor was located on the thigh, extending from the deep dermis to the subcutaneous tissue with no epidermal contact, and showed a large central cystic cavity that measured 9 cm x 4 cm. We review the cases published under this and other names. Topics: Adipose Tissue; Cell Nucleus; Chromatin; Cysts; Cytoplasm; Epithelium; Fibroblasts; Humans; Keratins; Male; Middle Aged; Skin; Skin Neoplasms; Thigh | 1992 |
CD8+ cutaneous anaplastic large-cell lymphoma: report of two cases with immunophenotyping, T-cell-receptor gene rearrangement and electron microscopic studies.
Two cases are reported of cutaneous anaplastic large-cell lymphoma with the suppressor/cytotoxic (CD8) phenotype. In both cases there was a solitary skin tumour in which there was a dense infiltrate with large irregularly shaped cells which on immunophenotyping expressed CD8. DNA hybridization analysis showed rearrangements of the T-cell-receptor gene in both cases. Topics: Aged; Antigens, CD; Antigens, CD1; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; CD3 Complex; CD8 Antigens; Female; Gene Rearrangement, T-Lymphocyte; Humans; Immunophenotyping; Keratins; Ki-1 Antigen; Lymphoma, Large B-Cell, Diffuse; Molecular Probe Techniques; Receptors, Antigen, T-Cell; Skin Neoplasms | 1992 |
Dermal granulomatous inflammation to cornified cells. Significance near cutaneous squamous cell carcinoma.
Discrimination of benign from malignant is fundamental to accurate histologic diagnosis. This article describes a series of nine patients with cutaneous squamous cell carcinoma who were noted to have in the vicinity of their neoplasm seemingly benign but biologically significant dermal granulomatous inflammation to cornified cells (GRC).. Two patients were reported as having this finding alone on incisional biopsy specimens only to have subsequent biopsy specimens demonstrate bona fide malignant neoplasms. On Mohs' frozen sections, four patients were noted to have GRC without concomitant tumor and four patients had GRC admixed with tumor. Two patients who demonstrated GRC but no neoplasm on final Mohs' sections had development of recurrent neoplasm after the initial procedure.. In the setting of suspected or proved cutaneous squamous cell carcinoma, GRC signifies the presence of viable neoplasm and warrants additional tissue resection. Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cells; Female; Granuloma, Foreign-Body; Humans; Inflammation; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms | 1992 |
Development of an in vitro model to study carcinogen-induced neoplastic progression of initiated mouse epidermal cells.
Initiation and promotion in mouse skin carcinogenesis produce multiple benign tumors, squamous papillomas, but only a few squamous cell carcinomas. The spontaneous conversion from the benign to the malignant phenotype occurs over many months and in stages, but induced malignant conversion can be accomplished more rapidly by exposure of papilloma-bearing mice to mutagens or by transfection of papilloma cell lines with specific oncogenes. The analysis of genetic targets responsible for carcinogen-induced neoplastic progression would be facilitated by the development of in vitro models where the process is rapid, focal, and quantitative. To this end, primary newborn mouse keratinocytes were initiated in vitro by the introduction of the v-rasHa oncogene via a defective retrovirus. Recipient cells produce squamous papillomas and have a high proliferation rate in culture medium with 0.05 mM Ca2+, but fail to grow in medium with 0.5 mM Ca2+ which is permissive for growth of malignant keratinocytes. When v-rasHa-keratinocytes were exposed to mutagens in vitro, proliferative foci emerged after culture in 0.5 mM Ca2+ for 4 weeks. These foci stained intensely red with rhodamine stain, could be easily quantitated, and readily incorporated bromodeoxyuridine. Dose-response studies with several mutagens indicated that the number of foci increased with concentration to the point where excessive cytotoxicity developed. Mutagens varied in potency for producing foci in the following order: cis-diamminedichloroplatinum greater than or equal to benzo(a)pyrene diolexpoxide I greater than N-methyl-N'-nitro-N-nitrosoguanidine greater than or equal to 4-nitroquinoline-N-oxide greater than N-acetoxy-acetyl- aminofluorene. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate was inactive in the assay. A subset of cell lines derived from foci produced malignant tumors in vivo, while others were not tumorigenic. Analysis of DNA from cell lines and tumors revealed that most tumorigenic cell lines maintained the v-rasHa genome, whereas the viral sequences were deleted in nontumorigenic cell lines. Immunohistochemical analysis indicated that proliferative foci and quiescent v-rasHa keratinocytes expressed keratin 8, a marker of v-rasHa expression in cultured keratinocytes. Cells in foci, but not v-rasHa control cells, expressed keratin 13, a marker which is strongly associated with the malignant progression of skin tumors in vivo. This in vitro assay provides a quantitative model to Topics: Animals; Animals, Newborn; Base Sequence; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cells, Cultured; Epidermal Cells; Epidermis; Genes, ras; Keratinocytes; Keratins; Methylnitronitrosoguanidine; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Oligodeoxyribonucleotides; Papilloma; Polymerase Chain Reaction; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transfection | 1992 |
Dissociation of sensitivities to tumor promotion and progression in outbred and inbred SENCAR mice.
The sensitivity of outbred SENCAR mice and inbred SENCAR (SSIN) mice to multistage carcinogenesis was studied. Tumors were induced using either 7,12-dimethylbenz[a]anthracene or N-methyl-N'-nitro-N-nitrosoguanidine as initiators and 12-O-tetradecanoylphorbol-13-acetate or benzoyl peroxide as promoting agents. Although the number of papillomas per mouse was higher in SSIN than in outbred SENCAR mice, the number of carcinomas observed in the SSIN strain was significantly lower regardless of the initiator or promoter used. It was also observed that the expression of markers of premalignant progression (i.e., dysplasia, expression of keratin K13, and loss of keratin K1 expression) was markedly suppressed in SSIN papillomas. After 50 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate, the pattern of expression of K13 and K1 in SSIN mice was comparable to the pattern observed in outbred SENCAR mice after 10 to 20 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate. It was also observed that 67% of the tumors induced in SSIN mice by initiation with 7,12-dimethylbenz[a]anthracene exhibited a mutation in codon 61 of the Ha-ras-1 gene. This latter finding suggests that the differences observed in tumor progression between the inbred strain and the outbred stock are not related to a genetic alteration in the Ha-ras-1 gene but rather to an independent event that we have postulated to involve a putative suppressor gene. The data reported here suggest that the putative gene(s) that confers susceptibility to tumor promotion was segregated from the gene(s) involved in tumor progression during selection and inbreeding of the SENCAR mouse stock. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benzoyl Peroxide; Carcinoma, Squamous Cell; Female; Genes, ras; Keratins; Methylnitronitrosoguanidine; Mice; Mutation; Papilloma; Skin Neoplasms; Species Specificity; Tetradecanoylphorbol Acetate | 1992 |
[Immunohistologic characterization of skin metastases in a patient with simultaneous cancers of the rectum and cervix].
A patient with skin metastases several years after surgical treatment of carcinoma of the cervix and the rectum is presented. Comparative histology and immunohistochemical analysis with anti-cytokeratin antibodies implicated the carcinoma of the cervix as the source of the skin infiltrates. Based on this patient's case record, the use of anti-cytokeratin antibodies for identification and subtyping of epithelial or carcinoma cells is discussed with special reference to cytokeratin 7. Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Combined Modality Therapy; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Staging; Neoplasms, Second Primary; Rectal Neoplasms; Skin; Skin Neoplasms; Uterine Cervical Neoplasms | 1992 |
Immunohistochemistry in the differential diagnosis of nodular hidradenoma and glomus tumor.
The histologic distinction between nodular hidradenoma and glomus tumor is an occasional difficult diagnostic problem. Both tumors may show circumscribed aggregates of uniform epithelioid cells, a myxoid stroma, and variable numbers of blood vessels. Especially troublesome are solid cellular hidradenomas without duct-like structures and glomus tumors without a vascular pattern. To develop an immunohistochemical profile useful in this differential diagnosis, 25 selected skin tumors and four normal glomus bodies were studied with antibodies against low molecular-weight cytokeratin (CAM 5.2), epithelial membrane antigen (EMA), carcino-embryonic antigen (CEA), S-100, and vimentin (VIM). The tumors included eight unequivocal hidradenomas, seven unequivocal glomus tumors, and 10 histologically equivocal cases, originally diagnosed as glomus tumors. In all unequivocal glomus tumors and glomus bodies, only VIM was positive. Of the eight unequivocal hidradenomas, three were positive for CAM 5.2, EMA, CEA, S-100, and VIM; two for CAM 5.2 only; one for CAM 5.2, EMA, and S-100; one for CAM 5.2, EMA, and CEA; and one for CEA only. In the histologically equivocal cases, eight were positive for VIM only, characteristic of glomus tumor; and two were positive for CAM 5.2, EMA, CEA, S-100, and VIM, and were reclassified as hidradenomas. The study suggests that morphologic criteria may not always accurately differentiate between hidradenoma and glomus tumor and that in equivocal cases immunohistochemistry may be useful in the differential diagnosis. Topics: Adenoma, Sweat Gland; Adolescent; Adult; Aged; Antigens, Neoplasm; Arteriovenous Anastomosis; Carcinoembryonic Antigen; Child; Diagnosis, Differential; Foot Diseases; Glomus Tumor; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Skin Neoplasms; Vimentin | 1992 |
Porokeratotic eccrine ostial and dermal duct nevus. An abnormally keratinizing epidermal invagination or a dilated, porokeratotically plugged acrosyringium and dermal duct?
Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) has been said to represent a widely dilated, keratin-plugged acrosyringium and dermal duct. We have observed in a case of congenital PEODDN a normal-appearing, acrosyringium-like duct that traverses vertically the entire length of the parakeratotic column. Also, in its lower course, it stained positively for carcinoembryonic antigen, while the inner borders of the invagination from which the parakeratotic column arose stained negatively. This leads us to suggest that the epithelial structure in PEODDN is an abnormally keratinizing epidermal invagination through which an acrosyringium-like duct traverses, rather than an abnormally dilated, parakeratotically plugged acrosyringium and dermal duct. Topics: Adult; Carcinoembryonic Antigen; Eccrine Glands; Epidermis; Epithelium; Hand; Humans; Immunoenzyme Techniques; Keratinocytes; Keratins; Keratosis; Male; Nevus, Pigmented; Skin Neoplasms | 1992 |
Relationship between the expression of differentiation-specific keratins 1 and 10 and cell proliferation in epidermal tumors.
In normal epidermis, the expression of keratins 1 and 10 is associated with the loss of proliferative capacity and the onset of terminal differentiation. Keratins 1 (K1) and 10 (K10) are commonly expressed in the differentiating layer of benign tumors, but are lost during progression from the benign to the malignant state in skin carcinogenesis. Active gene constructs of mouse K1 and K10 were introduced into papilloma and carcinoma cell lines derived from keratinocytes to analyze the consequences of the expression of these keratins on the organization of the endogenous cytoskeletal network and on the mitotic activity of the recipient cells. Exogenous K1 integrated into the preexisting keratin K5/K14 network of both SLC-1 carcinoma and 308 papilloma cells. The formation of a recombinant cytoskeleton was more restricted for K10 than for K1 and appeared to be related to a requirement for cessation of cell division before K10 could integrate. The integration of exogenous K1 filaments into the endogenous keratin network was compatible with sustained proliferation of SLC-1 carcinoma cells in vitro. However, the exogenous gene was not expressed in tumor grafts in vivo. In contrast, stable K1 or K10 transfectants could not be selected in 308 cells, suggesting that benign tumor cells expressing suprabasal keratins cannot sustain proliferation. Topics: Animals; Blotting, Northern; Blotting, Western; Carcinoma, Squamous Cell; Cell Division; Cell Line; Cytoskeleton; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Papilloma; RNA, Neoplasm; Skin Neoplasms; Transfection | 1992 |
Cytokeratin expression in mucinous sweat gland carcinomas: an immunohistochemical analysis of four cases.
Four mucinous sweat gland carcinomas were examined for the distribution of cytokeratin (CK) polypeptides using immunohistochemical techniques on paraffin-embedded sections. All the tumour specimens reacted with monoclonal antibodies to CK 7, CK 8, CK 18 and CK 19. Antibodies to CK 1, CK 1/2/10/14, CK 1/5/10/11, CK 13, CK 14 and CK 20 did not stain any of the carcinomas. The results add additional support to the notion that mucinous sweat gland carcinoma represents a tumour histogenetically related to the eccrine secretory coil. Furthermore, the absence of CK 20 might significantly contribute to the differentiation of this tumour from cutaneous metastases from gastrointestinal carcinomas. Topics: Adenocarcinoma, Mucinous; Aged; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Skin Neoplasms; Sweat Gland Neoplasms | 1992 |
Expression of Ulex europaeus agglutinin I lectin-binding sites in squamous cell carcinomas and their absence in basal cell carcinomas. Indicator of tumor type and differentiation.
Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in lectin binding have been reported to accompany epidermal cell differentiation, marking alterations in membrane sugars during this process. The presence of UEA I (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been used as a marker for terminally differentiated (committed) keratinocytes. In this article, we report the presence of UEA-I-binding sites on squamous keratinocytes of well-differentiated squamous cell carcinomas, with patchy loss of UEA I positivity on poorly differentiated cells of squamous cell carcinomas, suggesting a possible use for this technique in the rapid assessment of less differentiated areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal cell carcinomas may be related to an inability of cells comprising this tumor to convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting in an inability of basal cell carcinoma cell to undergo terminal differentiation into a committed keratinocyte. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Endothelium, Vascular; Epidermis; Epithelium; Fucose; Humans; Keratinocytes; Keratins; Lectins; Plant Lectins; Receptors, Cell Surface; Receptors, Mitogen; Skin Neoplasms | 1992 |
Aberrant expression of the simple epithelial type II keratin 8 by mouse skin carcinomas but not papillomas.
Keratins have been demonstrated to be suitable markers of changes taking place during epithelial neoplasia. Therefore, we analyzed 18 mouse skin tumors (nine papillomas and nine squamous cell carcinomas), induced either by two-stage carcinogenesis with 7,12-dimethylbenz[a]anthracene(DMBA)/12-O-tetradecanoylphorbol-13-acetat e or complete carcinogenesis with DMBA, by immunofluorescence with a monoclonal antibody to keratin (K) 8 (TROMA-1). Immunoperoxidase staining and immunoblotting were also used on selected tumor samples to further explore for the presence of K8. All of the papillomas tested were negative for the presence of K8, whereas the carcinomas were positive. The level of K8 expression in carcinomas showed a positive correlation with the degree of malignancy. Northern blot analysis using a K8 cDNA probe suggested that control of K8 expression in mouse skin tumors occurs at the transcriptional level. Double-label immunofluorescence staining using TROMA-1 and RK13 antibodies demonstrated that K8 did not generally colocalize with K13, a keratin normally found in internal stratified epithelial but aberrantly expressed in mouse epidermal tumors. Furthermore, tumors expressing high levels of K8 showed a reduced expression of K13. Histological examination of immunoperoxidase-stained tumors demonstrated that K8-positive cells were mainly found in anaplastic areas, whereas K13 foci were restricted to well-differentiated regions. Our results demonstrate that K8 expression is a marker of late stages of carcinoma progression in the mouse skin carcinogenesis model. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Blotting, Northern; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Epithelium; Female; Fluorescent Antibody Technique; Gene Expression; Genes, ras; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mutation; Papilloma; RNA; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1992 |
Expression of simple epithelial keratins in epidermal neoplasia is not directly and exclusively related to malignancy.
Topics: Humans; Keratins; Skin; Skin Neoplasms | 1992 |
Malignant eccrine spiradenoma. A clinicopathologic study.
Malignant eccrine spiradenomas (MES) are exceedingly rare and their immunohistochemical and ultrastructural features have not been fully characterized. We studied two cases, one of them immunohistochemically and electron microscopically. Patient 1 had a 25-year history of multiple exophytic tumors involving the scalp, the skin of the face, and the torso. Of the lesions removed, ten were spiradenomas, two with malignant changes, and three were cylindromas. The malignant areas showed loss of tubular and nesting patterns, lack of two cell populations, and contained anaplastic cells with high mitotic rate. The immunohistochemical findings were consistent with eccrine differentiation. Patient 2 had a cystlike mass of long duration in the right groin. Histologically, the mass consisted of nodules of benign eccrine spiradenomas adjacent to a ductal-cystic mass lined by anaplastic cells, but areas of squamous and glandular differentiation were also present.. (a) Case 1 is probably the first reported MES associated with multiple spiradenomas and cylindromas. (b) Cytodifferentiation in MES is variable, sometimes with almost complete loss of eccrine differentiation. (c) Identification of adjacent spiradenomas may be required for definite diagnosis of MES. (d) Clinical history of longstanding lesions with recent fast growth warrants tissue diagnosis. Topics: Adenoma, Sweat Gland; Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, CD34; Antigens, Neoplasm; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carcinoembryonic Antigen; Carrier Proteins; Female; Glycoproteins; Humans; Keratins; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Mucin-1; S100 Proteins; Skin Neoplasms; Sweat Gland Neoplasms | 1992 |
Lymphoepitheliomalike carcinoma of the skin. A case report with immunophenotypic analysis and in situ hybridization for Epstein-Barr viral genome.
Lymphoepithelioma is a malignant epithelial neoplasm of the nasopharynx. Similar malignancies--lymphoepitheliomalike carcinomas--of salivary glands, thymus, larynx, lung, stomach, and uterus have been described. We present here a case of lymphoepitheliomalike carcinoma of the skin in an 84-year-old woman. Histologically this neoplasm presented as a fairly discrete dermal aggregate of syncytial nests of epithelioid-appearing cells that displayed no squamous or glandular differentiation, surrounded by a dense lymphocytic infiltrate. Results of immunophenotypic studies showed expression of high molecular weight cytokeratins and increased density of dermal dendrocytes within and adjacent to the tumor. No Epstein-Barr viral genomic sequences were detected by in situ hybridization, which suggests that cutaneous neoplasms may have different etiologic agents compared with similar tumors, found to be associated with this DNA-containing virus, arising in extracutaneous sites. The combined light microscopic and immunohistochemical assessment of this rate cutaneous neoplasm permits distinction of lymphoepitheliomalike carcinoma from benign/malignant lymphoproliferative disorders or neuroendocrine carcinomas. Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA, Viral; Female; Herpesvirus 4, Human; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Nucleic Acid Hybridization; Skin Neoplasms | 1992 |
Immunohistochemical stains in extramammary Paget's disease.
The histologic and immunohistochemical characteristics of 49 skin biopsy specimens from 49 patients with extramammary Paget's disease were studied. Patients with extramammary Paget's disease with and without underlying malignant disease were identified. Associated malignant lesions, present in 16 patients (33%), were transitional cell carcinoma of the bladder (n = 8), adenocarcinoma underlying the skin (n = 3), adenocarcinoma of the anus (n = 1), adenocarcinoma of the vulva (n = 1), apocrine carcinoma (n = 1), prostate carcinoma (n = 1), and carcinoma metastatic to the lung (n = 1). The main histologic feature was the presence of Paget's cells, predominantly at the base of the epidermis. In 6% of the cases, well-defined nests of large Paget's cells mimicked melanocytic nests. Carcinoembryonic antigen and Cam 5.2 (a monoclonal antibody that stains 40-kDa, 45-kDa, and 52.5-kDa low molecular weight keratins) were localized to the Paget's cells in 42 of 45 (93%) and 29 of 41 cases (71%), respectively. Forty-four of 46 lesions (96%) were mucin positive, as determined by Hale's colloidal iron stain. Absence of staining for colloidal iron and carcinoembryonic antigen occurred somewhat more frequently in patients with underlying malignant disease than in patients without tumors (13% vs. 0% mucin negative and 13% vs. 3% carcinoembryonic antigen negative, respectively). Although immunohistochemical staining for low molecular weight keratin may be used to confirm the diagnosis of extramammary Paget's disease, Cam 5.2 is not as sensitive as the colloidal iron or carcinoembryonic antigen stain. Topics: Aged; Aged, 80 and over; Anus Neoplasms; Carcinoembryonic Antigen; Female; Genital Neoplasms, Male; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Paget Disease, Extramammary; S100 Proteins; Skin Neoplasms; Vulvar Neoplasms | 1992 |
Marjolin's ulcer: immunohistochemical study of 17 cases and comparison with common squamous cell carcinoma and basal cell carcinoma.
Formalin-fixed, paraffin-embedded biopsy specimens of 17 cases of squamous cell carcinoma of Marjolin's ulcer (SCC-MU), 6 cases of common SCC (SCC), and 5 cases of basal cell carcinoma (BCC) were stained with three monoclonal antikeratin antibodies (CAM 5.2, MAK-6, and MA-903), a monoclonal antivimentin antibody (V9), and a polyclonal anticarcinoembryonic antigen antiserum (A115). Neoplastic cells of SCC-MU, SCC, and BCC showed consistently negative staining for CAM 5.2. A wide range of reactivity, from negative to diffuse strong positivity, among neoplastic cells of SCC-MU and SCC was noted with MAK-6. Alternatively, neoplastic cells of SCC-MU, SCC, and BCC consistently showed diffuse moderate to strong reactivity with MA-903. These findings imply that SCC-MU has largely high-molecular-weight keratins. They also showed a wide range of reactivity with V9. However, neoplastic cells of five of the six SCC and five cases of BCC were negative for V9. These findings suggest that neoplastic cells of SCC-MU contain vimentin in higher frequency than in the more usual SCC. Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biopsy; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cicatrix; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Skin; Skin Neoplasms; Ulcer; Vimentin | 1992 |
Spindle cell neoplasms coexpressing cytokeratin and vimentin (metaplastic squamous cell carcinoma).
Spindle cell squamous carcinoma (SCSC) and atypical fibroxanthoma (AFX) are both spindle cell neoplasms (SCN) that usually arise in areas of solar or ionizing radiation of elderly patients. Both lesions have a similar biologic behavior. In addition, the morphologic and ultrastructural similarities found in AFX and the spindle cell component of SCSC, have led some investigators to conclude that these tumors have a similar cell of origin. We studied 15 SCNs with no evidence of epithelial origin and no morphologic epithelial component, that showed immunohistochemical and ultrastructural evidence that would support metaplastic changes of a squamous cell carcinoma to a neoplasm with mesenchymal characteristics. Topics: Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Skin Neoplasms; Vimentin | 1992 |
A comparative immunohistochemical study of adenoid cystic carcinoma of the skin and salivary glands.
We performed an immunohistochemical study that compared a primary adenoid cystic carcinoma (ACC) of the skin with two salivary gland ACC. All three tumors stained positively and in identical fashion for epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), broad-spectrum keratins, and low-molecular-weight keratins. Both EMA and CEA were localized to the luminal surfaces and the secreted contents of the tubular structures and the ductlike structures of the cribriform formations. The staining reactions for both types of keratin were more intense in the cells lining the tubular structures and the ductlike structures of the cribriform formations. One of the two salivary ACCs stained positively for S-100 protein; the other was positive for vimentin. The cutaneous ACC was negative for both antigens. Leu-7 antigen was not detected in either type of ACC. These results show that primary cutaneous ACC and salivary ACC have similar immunohistochemical staining patterns for a number of antigens. We believe this similarity is due to the fact that these antigens are shared by the sweat glands and salivary glands, which are considered to be the respective sites of origin for these two types of tumors. Topics: Adult; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Female; Humans; Immunoenzyme Techniques; Keratins; Killer Cells, Natural; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Salivary Gland Neoplasms; Skin Neoplasms; Staining and Labeling; Vimentin | 1991 |
[Expression of intermediate filaments in cutaneous cylindroma].
Using different monoclonal anti-cytokeratin antibodies (broad spectrum, cytokeratin 7, 8, 18, 19) and the antibody A55-A/A9 until now characterized only by immunohistology the staining of ductal structures and some cells within the lobulae of dermal cylindromata was demonstrated. In regard to the cytokeratin polypeptide patterns of the adnexes in uninvolved skin an exact histogenetic correlation by our findings is not possible, but the pattern is consistent with the conception of the glandular origin of the tumours. Topics: Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Humans; Intermediate Filaments; Keratins; Skin Neoplasms | 1991 |
Immunohistochemical demonstration of keratins 8 and 14 in benign tumours of the skin appendage.
The expression of keratins 8 and 14 was investigated immunohistochemically by the avidin-biotin-peroxidase (ABC) method using formalin-fixed paraffin-embedded specimens from 42 tumours of human skin appendages. Results were compared with the staining of 34 specimens from normal skin and skin appendages adjacent to the tumours. Keratin 14 was detected by the monoclonal antibody (mAb) 312C8-1, and was found in the basal cells of the epidermis, the outer root sheaths of hair follicles, and the peripheral cells of sebaceous glands. It was also detected in the inner and outer layers of cells in the ductal portion and the myoepithelial cells in the secretory portion of apocrine and eccrine sweat glands. Keratin 8 was detected by mAb 35BH11, and was present in the secretory cells of eccrine and apocrine sweat glands but not in myoepithelial or ductal cells. The pilosebaceous apparatus and the epidermis were uniformly negative. In benign skin appendage tumours, the staining patterns for both keratins generally resembled their distribution in the corresponding normal tissues. The demonstration of keratins 8 and 14 may be useful in the recognition, classification and diagnosis of skin appendage tumours. Topics: Antibodies, Monoclonal; Hair; Humans; Immunohistochemistry; Keratins; Sebaceous Glands; Skin; Skin Neoplasms; Sweat Glands | 1991 |
The expression of skin-specific gene K51 in the epidermal layer of human skin and in basal cell carcinoma cells.
Gene K51 probe isolated previously from the rat genomic library has been used to study the expression of its human counterpart by in situ hybridization and Northern blot analysis. A polyA-containing transcript of human gene K51 of 3 kb size has been detected in embryonic skin. The gene is also expressed in the epidermis of newborn humans and adults, but not in the adjacent mesenchymal tissues. Immunostaining with keratin antisera revealed predominantly earlier stage expression of K51 than cytokeratin markers. Sebaceous and sweat glands also contain cells expressing K51 gene. K51 expression was found in the cells of eight individual basal cell carcinomas tested, with the level of expression lower than in keratinocytes from normal human epidermis. We propose that K51 gene expression could serve as a convenient marker for the study of the process of skin keratinocyte development and the changes in this process associated with skin cancers and dysplasia. Topics: Blotting, Northern; Carcinoma, Basal Cell; Epidermal Cells; Epidermis; Gene Expression Regulation, Neoplastic; Genes; Humans; Immunohistochemistry; Keratinocytes; Keratins; Skin Neoplasms | 1991 |
Abnormal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines.
We have analyzed the expression of the three retinoic acid receptor (RAR) (alpha, beta, gamma) mRNAs and the intermediate filament protein keratin 19 (K19) mRNA in cell lines cultured from oral and epidermal human squamous cell carcinoma (SCC) and from benign, hyperplastic, and hyperkeratotic (leukoplakia) lesions arising in various regions of the oral cavity. Seven of the SCC lines were derived from tumors arising in regions of the oral cavity in which the normal epithelial cells (keratinocytes) express RAR beta transcripts. Seven of the nine SCC lines tested did not exhibit detectable RAR beta mRNA levels, even in response to addition of retinoic acid (RA). The RAR beta gene did not appear to be rearranged or deleted in the five nonexpressing SCC lines examined by Southern analysis. The steady-state RAR gamma mRNA levels were 2- to 4-fold lower in 6 of the 9 SCC lines than in their normal counterparts, whereas the RAR alpha message levels in SCC lines were similar to those of the normal cell strains. The expression of keratin 19 message, which is RA inducible in normal keratinocytes, was also abnormal in many of the SCC cell lines. Some SCC lines, e.g., those derived form tumors of the soft palate epithelium, did not express high levels of K19 message even though normal soft palate keratinocytes expressed high levels of K19 mRNA. Two of the nine SCC lines expressed higher than normal levels of K19 mRNA, and this expression was RA independent. Cells cultured from four oral leukoplakia lesions were also examined and found to express RAR beta mRNA at relatively normal levels, but they expressed RAR gamma message at half the level of epithelial cells cultured from normal tissue. These results show that the correlation between RAR beta gene expression and K19 gene expression that we have observed in the various normal keratinocyte subtypes of the oral cavity (D.L. Crowe et al., manuscript in preparation) is not present in transformed keratinocytes (SCC cells). The lack of apparent RA regulation of the K19 gene in SCC lines may be associated with other aberrations in differentiation which have been identified in SCC cells. Abnormally low expression of the RAR beta receptor may contribute to neoplastic progression in stratified squamous epithelia. It may also determine whether a tumor is responsive to RA as a chemotherapeutic agent. Topics: Blotting, Southern; Carcinoma, Squamous Cell; Carrier Proteins; DNA; Genomic Library; Humans; Keratinocytes; Keratins; Leukoplakia; Mouth Neoplasms; Receptors, Retinoic Acid; RNA, Messenger; Skin Neoplasms; Transcription, Genetic; Tumor Cells, Cultured | 1991 |
Identification of a cloned sequence activated during multi-stage carcinogenesis in mouse skin.
Differential screening of cDNA libraries made from chemically induced malignant mouse skin squamous cell carcinomas (SCC) identified three sequences, including one called mal2, that were upregulated in their expression at both the benign papilloma and malignant SCC stages. The mal2 plasmid cDNA clone (containing a 350 bp insert) was used to screen lambda phage cDNA libraries made from chemically induced SCCs. Two of the largest mal2-related cDNA inserts obtained from the phage libraries were sequenced. In addition a mal2-related genomic clone was obtained by hybridization probing of a mouse spleen genomic DNA library. The sequence of the genomic clone overlapped and was identical with both the mal2 plasmid and lambda cDNA clones. Identity was found between the mal2 cDNAs, the mal2 genomic sequence and the cDNA sequence for a mouse hyperproliferative keratin called K6. A synthetic oligonucleotide specific for the 3' untranslated region of the mal2 or keratin K6 gene was used in Northern analyses to demonstrate elevated steady-state levels of K6 keratin transcripts in SCCs induced by various protocols involving both chemical and ionizing radiation initiation of tumors as well as complete chemical and radiation carcinogenesis protocols. Metastatic lung lesions derived from SCCs generated by repeated doses of benzo[a]pyrene showed moderate levels of K6 keratin transcripts, whereas normal lung showed very low levels of K6 transcripts. The overexpression of the mal2 or keratin K6 gene in malignant SCCs was independent of the protocol, either chemical or radiation, that was used to induce the tumors. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Base Sequence; Carcinoma, Squamous Cell; Gene Expression Regulation, Neoplastic; Keratins; Mice; Molecular Sequence Data; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1991 |
Occult herpesvirus folliculitis clinically simulating pseudolymphoma.
Two cases of cutaneous herpesvirus infection are described that clinically masqueraded as pseudolymphoma. Light microscopy demonstrated typical viral changes involving pilosebaceous complexes with sparing of the surface epithelium. Dermal changes consisted of a dense perivascular and perifollicular inflammatory infiltrate. Multinucleated lymphoid cells were found in the dermis in one case and viral inclusions in fibroblasts were present in the other case. Immunoperoxidase stains with antisera to herpes simplex virus types I and II were positive in one case and negative in the other case. Ultrastructural examination demonstrated viral particles consistent with herpesvirus in both cases. Recognition of typical histologicl features of herpesvirus folliculitis will lead to an accurate diagnosis in these types of clinically unsuspected cases. Topics: Adult; Folliculitis; Herpesviridae; Herpesviridae Infections; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Male; Microscopy, Electron; Middle Aged; Necrosis; Skin Neoplasms | 1991 |
[Patterns of keratin protein expression in basal cell, metatypical and squamous cell carcinoma of human skin].
Comparative immunomorphological study of keratinous proteins was performed in 17 basaliomas, 4 metatypical (MT) and 1 squamous cell carcinomas by means of a spectrum of antibodies to the individual keratins. It is found that cells of MT carcinoma are distinguished from basalioma cells by the absence of keratins N8 and 17 and this may be used for the differential diagnosis of these two tumours. The spectrum of keratins expressed by basalioma cells coincides with that of early stages of hair follicles. Keratin N17 is locally induced in parabasal layers of the morphologically intact epidermis adjacent to the tumour. Topics: Aged; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Middle Aged; Neoplasm Proteins; Skin Neoplasms | 1991 |
Intermediate and fine cytofilaments in cutaneous and subcutaneous leiomyosarcomas.
The expression of fine and intermediate cytofilaments in 10 cutaneous and seven subcutaneous leiomyosarcomas was studied immunohistochemically. All the tumors contained tumor cells which showed a positive immunoreactivity for desmin in formaldehyde-fixed and paraffin-embedded sections, but none of the seven anti-desmin antibodies used alone produced a distinct positive staining in all the tumors. A lack of correspondence in terms of immunoreactivity between tumor cells and the supposed muscle of origin was observed, especially in the subcutaneous leiomyosarcomas. In all cases, antibodies to muscle-specific and smooth muscle-specific actin were found to produce a positive staining in both the tumors and the supposed muscle of origin. Vimentin was detected in 8/10 cutaneous and 4/7 subcutaneous leiomyosarcomas, while the supposed muscle of origin was positive in 3/10 and 7/7 cases, respectively. Four of the cutaneous and three of the subcutaneous leiomyosarcomas contained tumor cells which stained positively for cytokeratins, while the supposed muscle of origin showed no positivity. It thus appears that a phenotypic shift in terms of vimentin and cytokeratin expression occurs in the tumor cells of cutaneous and subcutaneous leiomyosarcomas compared with the supposed muscle of origin. It is recommended that more than one monoclonal anti-desmin antibody is used to characterize these tumor entities. It is also concluded that the immunoreactivity for muscle-specific actins in superficial leiomyosarcomas is more constant, although less specific, than that of desmin and that the demonstration of the simultaneous expression of muscle-specific actins and desmin is helpful. Topics: Actin Cytoskeleton; Actins; Aged; Antibodies; Antibodies, Monoclonal; Desmin; Female; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Leiomyosarcoma; Male; Middle Aged; Skin Neoplasms | 1991 |
Expression of simple epithelial keratins 8 and 18 in epidermal neoplasia.
A systematic study of keratin expression in epidermal lesions (six actinic keratoses, 10 Bowen's disease, seven squamous cell carcinomas) has been undertaken by using a large panel of monospecific monoclonal antibodies to individual keratins. Expression of differentiation-specific keratins was frequently delayed or lost from dysplastic regions. Novel expression of the embryonic, or simple epithelial, keratins 8 and 18 was widely observed in intradermal areas of poorly differentiated squamous cell carcinomas. In addition, the most proliferative of in situ malignancies (Bowen's disease) also contained small numbers of cells expressing simple epithelial keratins. These observations suggest that the expression of simple epithelial keratins may be of functional importance in malignancy of keratinocytes and could be related to tumor invasion and/or to changes in epithelial-mesenchymal interactions. Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Skin Neoplasms | 1991 |
Inflammatory linear verrucous epidermal naevus (ILVEN) versus linear psoriasis. A clinical, histological and immunohistochemical study.
Inflammatory Linear Verrucous Epidermal Nevus (ILVEN) has been suggested to be a separate disease entity. However, the distinction from linear psoriasis has been discussed in the literature over recent decades. The aim of the present study was to investigate, in addition to the clinical and histological criteria, the immunohistochemical aspects of inflammation, epidermal proliferation and keratinization. From a clinical and histological point of view, ILVEN and psoriasis, according to the established criteria, have been proved to overlap. The immunohistochemical study suggests that the following procedures have an additional diagnostic impact: assessment of elastase-positive cells, assessment of keratin 16 and of keratin 10. Topics: Adult; Aged; Antibodies, Monoclonal; Chromoblastomycosis; Diagnosis, Differential; Humans; Keratins; Keratosis; Male; Middle Aged; Nevus; Pancreatic Elastase; Psoriasis; Skin Neoplasms | 1991 |
Undifferentiated carcinoma of the vulva mimicking epithelioid sarcoma.
We report an undifferentiated sweat gland carcinoma of the vulva in an 80-year-old woman. The tumor, which was located in the right labium majus, resembled an epithelioid sarcoma histologically; it had a granulomatous appearance with multiple tumor nodules containing epithelioid tumor cells. The tumor also contained rhabdoid cells; a large cluster of them showed histological features indistinguishable from those of a malignant rhabdoid tumor. Immunohistochemically, the tumor cells reacted not only for epithelial markers such as cytokeratins, EMA, and CEA, which are known to be expressed by epithelioid sarcoma, but also for CA125 and with monoclonal antibodies recognizing sweat gland structures--namely, EKH5 and EKH6. For comparison, two epithelioid sarcomas and two extrarenal malignant rhabdoid tumors were also studied. Of these tumors, only one extrarenal rhabdoid tumor reacted with EKH5, and none reacted for CA125. Electron-microscopic examination of the present tumor showed the presence of discontinuous basal laminae and tonofibril-like structures as well as primitive cell junctions and interdigitating filopodia. From these findings, we conclude that the tumor was an undifferentiated sweat gland carcinoma mimicking an epithelioid sarcoma. Findings in this case support the idea of the diverse histogenesis of extrarenal malignant rhabdoid tumors and indicate that electron microscopy is important for differentiating epithelioid sarcoma from skin adnexal carcinoma. Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Carcinoma; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Sarcoma; Skin Neoplasms; Sweat Gland Neoplasms; Sweat Glands; Vulvar Neoplasms | 1991 |
Altered regulation of growth and expression of differentiation-associated keratins in benign mouse skin tumors.
Alterations in the pattern of epidermal cell differentiation and proliferation in mouse skin and benign skin tumors were studied by two-color immunofluorescence using monospecific antibodies. Replicating cells were identified by 5-bromo-deoxyuridine (BrdU) pulse-labeling and differentiating cells by keratins K1 and K10. In normal mouse skin, pulse-chase experiments for 120 h revealed that replication was restricted to a single layer of basal cells. Replicating cells did not express K1 or K10, but these keratins were sequentially expressed in post-mitotic basal cells 18 and 24 h following DNA synthesis respectively, and cells expressing these keratins migrated into the suprabasal layers. In phorbol-ester- or cantharidin-stimulated hyperplastic skin, replicating cells were also confined to the basal cell compartment and suprabasal cells expressed keratins 1 and 10. In papillomas induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate, replication occurred predominantly in cells in an expanded basal cell compartment (two to four layers above the basement membrane). Cells in these basal layers did not express K1 or K10, but more superficial cells did. After a 1 h pulse of BrdU, replication was also identified in suprabasal cells expressing the differentiation-associated keratins. These and other results suggest that benign tumor cells escape the obligatory growth arrest associated with differentiation. Replication of K1- and K10-expressing suprabasal cells may represent an early alteration during mouse skin carcinogenesis. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Cell Differentiation; Cell Division; Female; Gene Expression Regulation, Neoplastic; Keratinocytes; Keratins; Male; Mice; Mice, Hairless; Microscopy, Fluorescence; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1991 |
Adenosquamous carcinoma of the skin: a report of 10 cases.
Cutaneous squamous carcinoma with true glandular differentiation has only rarely been documented. Ten patients with such tumors are presented. There were six men and four women, aged 48 to 87 years. The tumors were located on the central face (eight), scalp (one), and hand (one) and consisted of minimally elevated, indurated, keratotic plaques, up to 6 cm in size. Microscopically, the neoplasms exhibited multifocal origin from the epidermis; deep, dispersed, infiltrative growth; perineural invasion; and stromal desmoplasia. Squamous differentiation was most marked superficially. Glandular differentiation was more obvious in deeper areas. Lumens typically developed within squamous nests and were often lined by cells with cytoplasmic vacuoles, some of which contained mucin. The neoplastic cells had obvious cytologic atypia and easily identified mitotic figures. Immunohistochemically, nine neoplasms studied contained carcinoembryonic antigen in glandular foci. Each patient had one or more surgical resections, and six also received radiation and/or chemotherapy. Five patients died with uncontrolled local recurrence, and two are alive with extensive disease and clinical evidence of regional lymph node involvement. Two individuals with small, superficial neoplasms that could be completely removed are disease free. One patient died of unrelated causes shortly after diagnosis. Cutaneous adenosquamous carcinoma is more aggressive than the usual carcinoma of the skin. It must be distinguished from the cytologically bland, microcystic adnexal (sclerosing sweat duct) carcinoma which is capable of recurring but rarely, if ever, proves fatal. The question of whether adenosquamous carcinoma is an epidermally derived squamous tumor with divergent differentiation or should be viewed as a newly recognized adnexal carcinoma remains to be resolved. Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; S100 Proteins; Skin Neoplasms | 1991 |
Recurrent malignant fibrous histiocytoma with expression of cytokeratin.
A case of locally recurrent malignant fibrous histiocytoma was documented in a 70-year-old man. He first noticed a subcutaneous nodule forty years previously. The tumor was surgically removed four times during the last four years with local recurrence on every occasion. In the recurrent tumors, the tumor cells almost completely replaced the whole dermis and invaded skeletal muscles. They were composed of pleomorphic spindle cells arranged in a storiform pattern and bizarre histiocytic cells, which were present principally in the deeper portions of the tumor. Both types of tumor cells showed marked nuclear atypicality. In the primary tumor, surrounding a large necrotic area, spindle-shaped cells were arranged in a storiform pattern. These tumor cells exhibited only mild nuclear atypia. The recurrent tumor was strongly positive for vimentin and alpha-1-antichymotrypsin. Most tumor cells were also weakly positive for KL1, a monoclonal antibody for keratin. A Western-blot analysis revealed the presence of two bands (62 and 69 Kd) reacting with KL1 in the fractions which were obtained from the tumor according to the method for keratin extraction. Topics: Aged; Blotting, Western; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Neoplasm Recurrence, Local; Skin Neoplasms | 1991 |
Myoepitheliomas in inbred laboratory mice.
Myoepitheliomas are subcutaneous tumors that arise from myoepithelial cells of various exocrine glands. In a retrospective study of 142 tumors observed over a period of 3 years, myoepitheliomas occurred spontaneously in A/HeJ, A/J, BALB/cJ, BALB/cByJ, LLC.A/Ckc, and NOD/Lt inbred strains of mice. Tumors presented primarily in the subcutaneous tissues of the ventral neck (74% of the myoepitheliomas evaluated) but were observed in several other subcutaneous locations, including the head, perineum, and ventral abdomen. These areas were adjacent to salivary, mammary, clitoral, preputial, and Harderian glands. Forty myoepitheliomas were tested by the avidin-biotin complex technique with a panel of antisera specific for mouse keratins, intermediate filaments, and other cytoskeletal proteins to determine the cell type from which this neoplasm originated. Antibodies directed against the specific mouse keratins K5, K6, and K14, and a broadly cross-reactive cytokeratin antibody stained acinar and ductal myoepithelial cells in normal mammary, salivary, and Harderian glands, and neoplastic cells in all cases. Antisera directed against a smooth muscle actin (anti-alpha-sm-1) stained acinar myoepithelial cells of the glands and vascular smooth muscle but neither ductular myoepithelial cells nor tumor cells. This supports the notion that these tumors originate from extraglandular ductular myoepithelial cells. Southern blots, prepared from DNA extracted from nine myoepitheliomas, did not show restriction fragment length polymorphisms when mouse mammary tumor virus (MMTV) cDNA or Int-1 genomic DNA probes were used; this implies that a retrovirus is not the etiologic agent. Topics: Age Factors; Animals; Blotting, Southern; DNA, Neoplasm; Female; Fluorescent Antibody Technique; Immunohistochemistry; Incidence; Keratins; Male; Mice; Mice, Inbred Strains; Microscopy, Electron; Myoepithelioma; Retrospective Studies; Rodent Diseases; Skin Neoplasms | 1991 |
Carcinogenesis in porokeratosis. Evidence for a role relating to chronic growth activation of keratinocytes.
Porokeratoses are known to give rise to squamous and basal cell carcinomas. In this study, we examined 15 lesions of porokeratosis immunohistochemically for evidence of aberrant keratinization using several markers of keratinocyte (KC) maturation and differentiation, including involucrin, filaggrin, cytokeratins, and the growth activation marker psi-3. The staining patterns obtained were compared with several non-premalignant parakeratotic skin lesions including psoriasis, pityriasis rosea, pityriasis rubra pilaris, irritated seborrheic keratosis, atopic dermatitis, seborrheic dermatitis, and verruca vulgaris. The centers of porokeratoses stained in a pattern identical to that observed in other premalignant keratinocytic lesions including actinic keratoses, recessive dystrophic epidermolysis bullosa, and nonhealing wounds. KCs beneath the cornoid lamella (CL) stained in a pattern similar to that observed in squamous cell carcinomas. KCs peripheral to the CL in the epidermis showed a normal staining pattern. The control non-premalignant parakeratotic lesions displayed a variety of staining patterns, but none showed a pattern identical to that observed in porokeratosis. The failure of KCs in porokeratoses to mature and differentiate normally may be related to the increased incidence of carcinomas associated with these lesions. Topics: Epidermis; Filaggrin Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratosis; Protein Precursors; Skin Neoplasms | 1991 |
[The use of monoclonal antibodies to cytokeratin peptides for the diagnosis of basal cell carcinoma of the skin].
25 skin basaliomas were studied immunohistochemically using 6 different monoclonal antibodies (MAB) to the low-molecular cytokeratins N 8, 18 (according to Moll's catalog) as well as to the cytokeratins N 1, 2, 9, 10, 11 and N 17. Prekeratin N 17 was found in all tumours while cytokeratin N 18 was found in no tumour. Prekeratin N 8 was expressed in 24% of tumours. MAB EE 21-06 to the cytokeratin N 1, 2, 9, 10, 11 are reactive with tumour cells in 20% of cases. Basalioma cells (apart from trichobasalioma) did not react with MAB G 36-19. These results suggest a dissimilar origin of basaliomas and may help in the differential diagnosis of the skin malignant tumours. Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Molecular Weight; Skin Neoplasms | 1991 |
Distribution of epithelial membrane antigen in eccrine poroma.
Using immunohistochemical methods, we investigated the distribution of epithelial membrane antigen (EMA) on the normal eccrine gland, eccrine poroma and hidroacanthoma simplex. Granular membrane-associated reaction of EMA was detected on the outer cells of both the intraepidermal and the upper portion of intradermal eccrine ducts, as well as on the luminal surfaces and intercellular canaliculi of eccrine glands. Clear immunolabeling was also present in the tumor cells of eccrine poroma and hidroacanthoma simplex. Thus, it is suggested that the constituent cells of these tumors originate from the outer cells of the intraepidermal and/or the upper portion of the intradermal eccrine ducts. There was no immunolabeling for EMA on the tumor cells of seborrheic keratosis and basal cell carcinoma. Immunohistochemical staining for EMA is a useful tool for the diagnosis of skin appendage tumors. Topics: Adenoma, Sweat Gland; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Cell Membrane; Cytoplasm; Dermatitis, Seborrheic; Eccrine Glands; Epithelium; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Reproducibility of Results; Skin Neoplasms | 1991 |
A pedunculated follicular hamartoma: a case showing a central trichofolliculoma-like tumor with multiple trichogenic tumors.
We report a rare case with a pedunculated nodule on the nasal septum, which seems a kind of follicular hamartoma with a pedunculated appearance. Our case was a 77-year-old Japanese male with an 11 x 11 x 10 mm sized, skin-to-pink colored, pedunculated nodule on the center of his nasal septum. Histopathological study revealed the nodule to be a well-formed dilated hair follicle at the central pore of the tumor, where keratin debris and vellus hairs were present. In addition, epithelial cells forming long thin strands or immature follicle-like structures had proliferated multifocally from the epidermis of the wall of the central follicle to the peripheral epidermis. One distinctive feature was the formation of a primary germinal bud with thick concentric collagen fibers and sparse elastic fibers. Although a combined tumor of trichofolliculoma with highly-graded desmoplasia, multiple trichogenic trichoblastomas, and perifollicular fibromas was suggested, calling it a pedunculated follicular hamartoma seemed more useful because the pathological features were basically similar to reported follicular hamartomas and the clinical feature was so distinctive. Topics: Aged; Cell Division; Collagen; Hair; Hamartoma; Humans; Immunoenzyme Techniques; Keratins; Male; Nasal Septum; Nose Neoplasms; Skin Neoplasms | 1991 |
Pseudohorn associated with basal cell carcinoma.
Cutaneous horns usually represent compacted keratin arising from an underlying pathologic process and are important to dermatologists because they may indicate an underlying malignancy. The differential diagnosis of cutaneous horns includes pseudohorns, which have the morphologic appearance of a cutaneous horn but consist entirely of benign or malignant tumor. We describe a second type of pseudohorn consisting of hair, dried serum, and inflammatory exudate that was associated with an underlying basal cell carcinoma. Topics: Carcinoma, Basal Cell; Diagnosis, Differential; Female; Humans; Keratins; Middle Aged; Skin; Skin Neoplasms; Staphylococcal Skin Infections | 1991 |
Merkel cell carcinoma of the head and neck associated with Bowen's disease.
The Merkel cell carcinoma occurs primarily in the skin of the head and neck, and develops in the dermis with a trabecular growth pattern. Immunohistochemistry reveals positive staining for neuron-specific enolase, neurofilaments, cytokeratin and chromogranin A. Electron microscopically, the tumor cells contain dense-core granules, spinous cytoplasmic processes, desmosomes, zonulae adherentes and paranuclear filament aggregates besides frequent mitoses, focal necroses and lymphocyte and plasma cell infiltrates. The Merkel cell carcinoma is often co-existent with other malignancies such as squamous cell carcinoma or, as in the present study, with Bowen's disease. The definite diagnosis of the Merkel cell carcinoma can be effected only by electron microscopic examination of the tumor. Topics: Aged; Bowen's Disease; Carcinoma, Merkel Cell; Chromogranin A; Chromogranins; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasms, Multiple Primary; Phosphopyruvate Hydratase; Skin Neoplasms | 1991 |
Histopathogenesis of inflammatory linear verrucose epidermal naevus: histochemistry, immunohistochemistry and ultrastructure.
Skin lesions of three patients with inflammatory linear verrucose epidermal naevus (ILVEN) were examined. Histologically, orthokeratosis and parakeratosis were alternately seen in the acanthotic epidermis. By N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide staining, the horny cells in the parakeratotic epidermis showed a cytoplasmic SH pattern and a weak membranous SS pattern. The orthokeratotic epidermis revealed an increased involucrin expression, whereas the parakeratotic epidermis showed almost no involucrin expression. Ultrastructurally, in the parakeratotic epidermis, the living keratinocytes had prominent Golgi apparatuses and vesicles in the cytoplasm. In the intercellular spaces in the upper spinous layer through to the lower horny layer, an electron dense, homogeneous substance was deposited. The cytoplasm of the horny cells was filled with keratin filaments and contained remnants of nucleus and cytoplasmic membrane structures, and some lipid droplets. The marginal band formation was incomplete. Most of these ultrastructural abnormalities were not found in the orthokeratotic epidermis. There are both similarities and differences in histopathogenesis of the parakeratotic epidermis between ILVEN and psoriasis. A unique finding was the lack of involucrin expression in the ILVEN parakeratotic epidermis. Topics: Adult; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Keratins; Male; Nevus; Protein Precursors; Skin; Skin Neoplasms | 1991 |
An immunohistochemical study of mixed tumor of the skin.
An asymptomatic tumor developed on the upper lip of a 63-year-old man. Histologically, the tumor contained glandular and cystic structures forming many branching lumina, and many scattered single cells in an abundant mucoid to chondroid stroma. The tumor was diagnosed as mixed tumor of the skin. Histochemically, the cells composing the tubular structures contained neutral mucopolysaccharides and the stroma, acid mucopolysaccharides. Immunohistochemically, the cells of the glandular and cystic structures showed epithelial and sweat gland differentiation (EMA-, CEA-, BRST-1- and BRST-2-positive), while the cells scattered in the stroma showed a tendency toward myoepithelial differentiation (S-100 protein- and vimentin-positive). Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Nucleus; Cytoplasm; Desmin; Glycoproteins; Humans; Immunohistochemistry; Keratins; Lip Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasms, Germ Cell and Embryonal; Neurofilament Proteins; S100 Proteins; Skin Neoplasms; Vimentin | 1991 |
v-Ha-ras-induced mouse skin papillomas exhibit aberrant expression of keratin K13 as do their 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate -induced analogues.
Introduction of the v-Ha-ras gene into primary epidermal keratinocytes, followed by grafting of these cells to animals, leads to the formation of benign epidermal tumors that resemble papillomas induced chemically by a two-stage carcinogenesis protocol. In this study, we investigated v-Ha-ras-induced papillomas for aberrant expression of type I keratin K13, previously described in 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13- acetate (DMBA/TPA)-induced mouse epidermal tumors. Papillomas produced from three independent infection series were removed 3 wk after grafting concomitant with control grafts originating from mock-, neo-, and v-fos-infected primary keratinocytes. Combined analysis of the grafts by western blotting of extracted keratins and immunofluorescence studies of frozen sections with a K13-monospecific antibody revealed K13 expression in all v-Ha-ras-induced papillomas and absence of this keratin in all control grafts. K13-positive cells in papillomas were restricted to the suprabasal cell layers of the lesions and, at this stage of papilloma development, occurred as foci of varying extensions. Analysis of genomic DNA from v-Ha-ras-induced papillomas for the methylation state of a CpG dinucleotide in the distant promoter region of the K13 gene revealed the occurrence of unmethylated DNA copies that were generated at the expense of methylated DNA copies ubiquitously present in normal epidermis. The ratio of unmethylated to methylated DNA copies correlated with the extent of suprabasal K13 protein expression. Thus, all features of aberrant K13 expression previously described in DMBA/TPA-induced papillomas were shared by v-Ha-ras-induced papillomas. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Base Sequence; Blotting, Western; Fluorescent Antibody Technique; Gene Expression; Genes, ras; Keratinocytes; Keratins; Methylation; Mice; Molecular Sequence Data; Oligonucleotides; Oncogene Protein p21(ras); Oncogene Proteins v-fos; Papilloma; RNA, Messenger; Skin Neoplasms; Skin Transplantation; Tetradecanoylphorbol Acetate | 1991 |
[Expression of keratin 16 in normal and lesional skin of solitary and multiple Bowen's disease using monoclonal antibody Ks 8.12 staining].
Bowen's disease is an intraepidermal squamous cell carcinoma usually consisting of a solitary lesion. However, multiple Bowen's lesions are one of the characteristics of arsenicalism in endemic areas where people drink deep well water containing high concentrations of arsenic along the southwest coast of Taiwan. This work seeks to clarify the differences between multiple Bowen's disease in the blackfoot disease endemic area, and solitary Bowen's disease in a non-endemic area by means of Ks 8.12 monoclonal cytokeratin antibody staining. Ks 8.12 may be regarded as a specific antibody for Keratin 16 in the skin and is used as a marker for hyperproliferation. Our results show that Ks 8.12 staining of normal skin in patients with a solitary Bowen's lesion is patchy and always restricted to the basal cell layer. By contrast, the normal skin of patients with multiple Bowen's lesions shows diffuse Ks 8.12 staining of the basal cell layer and various degrees of staining of the suprabasal layers. Similar results were observed in both solitary and multiple Bowen's lesions showing diffuse Ks 8.12 staining of the epidermis. Our results revealed clear differences in keratin expression between the clinically normal skin of patients with solitary Bowen's disease and that of patients with chronic arsenicalism. Finally the clinically normal skin of patients with multipole Bowen's disease showed characteristic changes in the expression of Keratin 16 in the suprabasal layers. Topics: Aged; Antibodies, Monoclonal; Bowen's Disease; Female; Humans; Keratins; Male; Middle Aged; Skin; Skin Neoplasms | 1991 |
Demonstration of changes in cytokeratin expression in condylomata accuminata in relation to the presence of human papilloma virus as shown by a combination of immunohistochemistry and in situ hybridization.
Human papillomavirus (HPV) can be detected in, and is probably involved in the etiology of, the majority of anogenital neoplasias. Infection with the virus induces a number of events in the infected epithelial cells that may lead to the development of benign or malignant tumors. One change that can be detected in the infected cells is in squamous differentiation, which is reflected by the pattern of cytokeratin polypeptide expression. By studying this pattern in relation to the presence of the virus, an indication may be obtained of the influence of the virus on the cellular differentiation in individual cells. By using a combination of DNA in situ hybridization and immunohistochemistry, for HPV and cytokeratin polypeptides, respectively, we studied the presence of HPV6 or HPV11 in condylomata accuminata derived from anogenital skin in relation to the cytokeratin polypeptides K1, 4, 8, 10, 14, and 18. We found that in many samples the presence of the skin-type cytokeratins K1 and K10 was decreased, whereas K13, and to a lesser degree K4, appeared. The cellular localization of these aberrations in cytokeratin expression could be related to the presence of HPV6 or 11 DNA in the tissue. Topics: Cell Differentiation; Condylomata Acuminata; DNA, Viral; Female; Humans; Immunohistochemistry; Keratins; Male; Nucleic Acid Hybridization; Papillomaviridae; Skin Neoplasms | 1991 |
Recessive dystrophic epidermolysis bullosa skin displays a chronic growth-activated immunophenotype. Implications for carcinogenesis.
Epidermolysis bullosa represents a grouping of inherited skin diseases characterized by epidermal fragility and frequently wounded skin. The recessive dystrophic subtype of epidermolysis bullosa (RDEB) is characterized by extensive dermal scarring after healing of repeated epidermal injuries and by an unusually high incidence of squamous cell carcinoma occurring in chronically wounded skin. In contrast, the simplex form of epidermolysis bullosa usually heals without scarring and does not predispose to malignant neoplasms of the skin. The differences in scarring and the neoplastic potential of these two forms of epidermolysis bullosa prompted us to investigate growth activation and differentiation characteristics in epidermal keratinocytes in individuals with these disorders. The expression of filaggrin, involucrin, cytokeratins, and the growth activation marker psi-3 was examined by immunohistochemistry in skin biopsy specimens from four individuals with epidermolysis bullosa simplex and six individuals with RDEB. Previous experiments using this technique have demonstrated that these antibodies are good markers for identifying growth-activated keratinocytes in wounded and hyperplastic epidermis. All biopsy specimens of healed wounds in skin from patients with RDEB showed epidermis that reacted with antibodies to filaggrin, involucrin, specific cytokeratins, and psi-3 in a growth-activated pattern. This growth-activated phenotype was maintained in keratinocytes from previously wounded skin that had been healed for more than 2 years. The RDEB growth-activated phenotype detected by immunohistochemistry was not associated with microscopically detectable epidermal hyperplasia. In contrast, all cases of epidermolysis bullosa simplex examined showed an epidermal phenotype similar to that of keratinocytes in normal skin. Thus, healing with dermal scar formation in RDEB is associated with a persistent growth-activated immunophenotype of epidermal keratinocytes. This chronic growth activation state or failure of cells to differentiate in a normal fashion may be directly linked to the high incidence of squamous cell cancers in individuals with RDEB. Topics: Adolescent; Adult; Antigens; Carcinoma, Squamous Cell; Epidermis; Epidermolysis Bullosa; Female; Filaggrin Proteins; Humans; Infant; Infant, Newborn; Intermediate Filament Proteins; Keratinocytes; Keratins; Male; Middle Aged; Protein Precursors; Retrospective Studies; Skin Neoplasms | 1990 |
Microcystic adnexal carcinoma. An immunohistochemical comparison with other cutaneous appendage tumors.
Since its initial description, microcystic adnexal carcinoma (MAC) of the skin has been controversial. In particular, it features keratin production of the type seen in some pilar neoplasms , and has been thought to pursue partial follicular differentiation. Diagnostically, MAC may be difficult to separate from desmoplastic trichoepithelioma (DTE) in superficial biopsy specimens. We studied 12 MACs, 22 malignant eccrine acrospiromas, 7 sudoriferous syringometaplasias, 6 syringomas, 5 DTEs, and 40 other benign pilar neoplasms immunohistochemically. Paraffin sections and antibodies to "hard" (pilar) keratins. epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Leu-M1, and S100 protein were employed. The MACs exhibited reactivity for hard keratin subclasses AE 13 and AE 14, EMA, CEA, and Leu-M1. Desmoplastic trichoepitheliomas expressed positivity for AE 14, EMA, and Leu-M1 focally, but lacked the other specified markers. Syringomas and malignant acrospiromas displayed EMA, CEA, and AE 14 reactivity, and 5 syringometaplastic lesions were AE 14-reactive. Benign pilar tumors aside from DTEs were reactive only for AE 13, AE 14, or both. These data indicate that MAC exhibits an immunophenotype that is a "hybrid" of those seen in pure sweat glandular and follicular neoplasms, and suggest that it may indeed show combined pilar and sudoriferous differentiation. Based on these results, it also appears that immunohistochemical analysis may be useful in the diagnostic separation of MAC and DTE. Topics: Adenoma, Sweat Gland; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Membrane Glycoproteins; Middle Aged; Mitosis; Mucin-1; Skin; Skin Neoplasms | 1990 |
Carcinoid tumor of skin: report of a possible primary case.
A case of a possible primary carcinoid tumor of the skin in a 40-year-old man is presented. The neoplasm was diagnosed as consistent with carcinoid tumor on the basis of conventional light microscopy, immunohistochemical studies, and electron microscopy. Workup revealed no evidence of carcinoid tumor elsewhere. Metastases to the skin from internal carcinoid tumors are uncommon, but presumed primary carcinoid tumors that arise in the skin are extremely rare; only three cases have been found in the English-language literature. Topics: Adult; Biopsy; Carcinoid Tumor; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Skin; Skin Neoplasms | 1990 |
Neuroendocrine (Merkel-cell) carcinoma of the skin: immunocytochemical and cytomorphologic analysis on fine-needle aspirates.
Cytomorphologic and immunocytochemical characteristics of tumor cells from fine-needle aspirates of four neuroendocrine (Merkel-cell) carcinomas of the skin are described. All aspirates were cellular with dispersed small to medium sized tumor cells with scanty cytoplasm. Many mitoses were observed. Careful scrutiny revealed a tendency of the tumor cells to form microacinar and pseudorosette formations as well as small clusters of molding cells. Immunocytochemical analysis of cytospin preparations showed a peculiar dot-like cytokeratin positivity, while neuron-specific enolase staining was more diffuse. A weak S-100 positivity was observed. This staining pattern is highly suggestive of Merkel-cell tumor. It can thus be concluded that immunocytochemical analysis in conjunction with cytomorphology on fine-needle aspirates will allow the identification of neuroendocrine carcinoma of the skin and its differentiation from other small-cell neoplasias of the skin. Topics: Aged; Aged, 80 and over; Biopsy, Needle; Carcinoma, Merkel Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Phosphopyruvate Hydratase; Skin Neoplasms | 1990 |
"Activated" keratinocyte phenotype is unifying feature in conditions which predispose to squamous cell carcinoma of the skin.
While some cutaneous squamous cell carcinomas (SCC) arise from predisposing conditions such as burn scars, draining sinuses, and chronic, nonhealing wounds, the vast majority of these tumors arise from actinically damaged epidermis. It has been shown previously that keratinocytes within healing wounds show an "activated" immunophenotype when stained with antibodies to psi-3, involucrin, filaggrin, and cytokeratins. A similar pattern has been seen in keratinocytes from patients with recessive dystrophic epidermolysis bullosa (RDEB), in whom the incidence of cutaneous SCC is markedly increased. We tested the hypothesis that actinic keratoses (AK), recognized as precursors in the development of the majority of SCC, would show a similar activated immunophenotype when stained with the antibody panel described above. We examined 10 AK, biopsied from the facies and extremities of ten patients, ages 60 to 80, with antibodies to psi-3, involucrin, filaggrin, and AE1. All lesions examined had an immunostaining pattern indistinguishable from that seen in keratinocytes from patients with RDEB or within healing wounds. There was suprabasilar staining of keratinocytes with antibodies to psi-3 and AE1. Involucrin and filaggrin was expressed by all keratinocytes above the midstratum spinosum. Within the acrosyringia and acrotrichia, the staining pattern was that of the normal epidermis, i.e., AE1 staining of basal keratinocytes, granular layer staining of involucrin and filaggrin, and absence of psi-3 expression. These data suggest that an activated keratinocyte phenotype is a unifying feature in conditions which predispose to development of cutaneous SCC. Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Epidermis; Female; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratosis; Male; Middle Aged; Phenotype; Precancerous Conditions; Protein Precursors; Skin Neoplasms; Sunburn | 1990 |
Cell differentiation in benign cutaneous fibrous histiocytomas. An immunohistochemical study with antibodies to histiomonocytic cells and intermediate filament proteins.
Seven benign cutaneous fibrous histiocytomas (BFHs) were investigated immunohistochemically by using a panel of antibodies to histiomonocytic cells and intermediate filament proteins. Immunoreactivity with antimacrophage antibodies was observed in all tumors in a significant but varying proportion of the tumor cells. All tumors were also positive for vimentin. In addition, two of the BFHs were positive for cytokeratin and one for desmin. The results suggest that BFHs either display a true histiomonocytic trait or, alternatively, contain a prominent histiomonocytic infiltration. Some BFHs may be related to smooth muscle cells as indicated by desmin positivity. The occasional occurrence of cytokeratin in BFHs could also be explained by smooth muscle cell differentiation. Topics: Adult; Antibodies, Monoclonal; Cell Differentiation; Desmin; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Monocytes; Skin Neoplasms; Vimentin | 1990 |
[Cytokeratin expression of tumor tissue in cutaneous merkeliomatosis (disseminated cutaneous Merkel cell carcinomas)].
In 2 patients suffering from cutaneous merkeliomatosis, we investigated the immunohistochemical expression of cytokeratin in cutaneous tumors, making use of 3 monoclonal antibodies. We observed a strong selective cytoplasmic fluorescence of the tumor cells in formalin-fixed tissue sections. Thus we were able to detect single intra-epidermal tumor cells. Both these findings and the intracorneal occurrence of tumor cells argue for a transepidermal elimination process. The reactivity patterns with monoclonal anticytokeratins revealed a cytokeratin expression of simple epithelial including cytokeratin 19. Topics: Antibodies, Monoclonal; Carcinoma, Merkel Cell; Cytoplasm; Fluorescent Antibody Technique; Humans; Keratins; Neoplasms, Multiple Primary; Skin; Skin Neoplasms | 1990 |
Human squamous cell carcinoma from skin: establishment and characterization of a new cell line (HSC-5).
A new cell line, designated as HSC-5 and derived from human skin squamous cell carcinoma (SCC), has been established in vitro and maintained proliferative in continuous tissue culture for over two years. The cells grow in a monolayer in vitro and have anaplastic epithelioid features. The doubling time was about 35 hr at the 30th passage. Chromosome analysis showed hypotetraploidy with a modal number of 76. A trial of transplantation of the cultured cells into nude mice was not successful. Analysis of cytokeratins from HSC-5 by two-dimensional gel electrophoresis revealed polypeptides No. 5, 8, 13, 18 and 19. The cell line is available to other investigators. Topics: Carcinoma, Squamous Cell; Cell Line; Humans; Keratins; Polyploidy; Skin Neoplasms; Tumor Cells, Cultured | 1990 |
Disseminated syringomas of the upper extremities. Case history and immunohistochemical and ultrastructural study.
A case of disseminated syringomas with unusual distribution and high age of onset is reported. The 66-year-old male patient presented with multiple lesions confined to dorsum of both hands and flexor side of both forearms. Morphological and immunohistochemical studies using keratin, S-100, carcinoembryonic antigen, and epithelial membrane antigen antibodies were performed both at light microscopical and ultrastructural level. These investigations revealed the presence of keratin filament containing colloid bodies near syringomatous epithelia. Reactivity for carcinoembryonic antigen could be demonstrated on the membranes of intracytoplasmic vesicles as well as within luminal debris. Absence of S-100 and epithelial membrane antigen in the tumor and ultrastructural features indicate ductal origin of syringoma. Topics: Adenoma, Sweat Gland; Age Factors; Aged; Arm; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Male; Protein Precursors; S100 Proteins; Skin; Skin Neoplasms | 1990 |
[Chondroid hidradenoma. Immunohistologic detection of cytokeratin and calmodulin].
The chondroid hidradenoma (chondroid syringoma, mixed tumor of skin) is a rare benign tumor with eccrine differentiation. It is composed of both adenoid structures surrounded by a mucoid stroma and "chondroid" single cells. Tumor cells with immunoreactive calmodulin were found predominantly in the centre of adenoid structures, whereas cells expressing cytokeratin were preferable located as the margins. Topics: Adenoma, Sweat Gland; Aged; Biomarkers, Tumor; Female; Fluorescent Antibody Technique; Humans; Keratins; Scalp; Skin Neoplasms | 1990 |
Keratin expression in equine normal epidermis and cutaneous papillomas using monoclonal antibodies.
Keratin expressions in normal equine epidermis and experimentally induced equine papillomas were studied by immunohistochemical methods with three different human cytokeratin monoclonal antibodies, 34 beta B4 (directed against component 1), 34 beta E12 (directed against components 1, 5, 10, 11) and 35 beta H11 (directed against component 8). Staining patterns with 34 beta B4 and 34 beta E12 in the normal equine epidermis did not differ from those in the normal human epidermis. In the early developing papilloma, keratinocytes showed an abnormal suprabasal staining pattern and expressed an additional 56 kD keratin protein detected by 34 beta E12. In the advanced papilloma, cytolytic cells in the outer spinous and the granular layers did not stain positively with any of the three antibodies used. In both early and advanced papillomas, the expression of high molecular weight keratin proteins, as detected by 34 beta B4 and 34 beta E12, did not correlate with the degree of keratinization. By electron microscopy, keratinocytes in the advanced papilloma showed a marked decrease of tonofibrils and desmosome-tonofilament complex. These alterations may result from an abnormality in both proliferation and functional terminal differentiation of keratinocytes in the papilloma. There were obvious differences in staining patterns with 35 beta H11 between the normal human and equine epidermis; 54 kD keratin protein was expressed in suprabasal layers of the equine normal and papillomatous epidermis. Thus, this keratin protein may be regarded as a "permanent" marker for the equine epidermis. Topics: Animals; Antibodies, Monoclonal; Epidermis; Head and Neck Neoplasms; Horse Diseases; Horses; Keratins; Microscopy, Electron; Molecular Weight; Neoplasm Proteins; Papilloma; Skin Neoplasms | 1990 |
Tissue-specific expression of murine keratin K13 in internal stratified squamous epithelia and its aberrant expression during two-stage mouse skin carcinogenesis is associated with the methylation state of a distinct CpG site in the remote 5'-flanking reg
Under normal conditions, the expression of the murine type-I keratin K13 is restricted to the suprabasal, differentiating cell layers of internal stratified squamous epithelia that line the oral cavity and the upper digestive tract. It is, however, also expressed aberrantly but constitutively in only the differentiating parts of 7,12-dimethylbenz[alpha]anthracene/12.0-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) induced malignant epidermal tumors of the back skin of mice, whereas its likewise suprabasal expression in papillomas is highly variable [27]. In an approach to unravel regulatory DNA sequence elements involved in the tissue-specific and aberrant K13 expression, the 5'-flanking region of the gene was analyzed with regard to potential methylation sites and DNase hypersensitive regions. We report on the identification of a CpG dinucleotide (designated M1; located about 2.3 kb upstream of the transcriptional start site), whose methylation state correlates with the differential gene activity in various epithelia and tumors. We show that in K13-nonexpressing integumental epidermis the M1 site is methylated in both suprabasal and basal cells. In contrast, internal stratified squamous epithelia (i.e. tongue, esophagus, forestomach) exhibit an unmethylated M1 site not only in their suprabasal. K13-expressing cells, but also in basal cells--in which, however, the keratin is not yet synthesized. The identical situation is encountered in DMBA TPA-induced moderately differentiating epidermal squamous cell carcinomas with compartmentalized K13 expression. In papillomas we observed a striking correlation between the extent of both suprabasally expressed K13 protein and demonstrable DNA copies carrying an unmethylated M1 site. Moreover we found that the sequence region around the M1 site was DNAseI hypersensitive in K13-expressing malignant tumors, but DNaseI insensitive in K13-nonexpressing epithelia and cells. DNAseI hypersensitivity in K13-expressing tissues was, however, independent of an active transcription of the gene in differentiating cells or transcriptional inertia in basal cells. These results strongly suggest that the sequence element around the demethylated M1 site is involved in a multi-level control mechanism mediating the selective expression of the K13 gene in internal squamous epithelia and in DMBA/TPA-induced epidermal tumors. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Base Sequence; Carcinoma, Squamous Cell; Deoxyribonuclease I; DNA, Neoplasm; Epithelial Cells; Epithelium; Female; Gene Expression Regulation, Neoplastic; Immunohistochemistry; Keratins; Methylation; Mice; Molecular Sequence Data; Nucleotides; Organ Specificity; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured | 1990 |
Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter.
The promoter region of the suprabasal keratin 10 gene has been used to direct expression of a mutant human Harvey-ras oncogene to the differentiating cells of the mouse epidermis. Transgenic animals develop hyperkeratosis of the skin and forestomach--the two sites known to express high levels of the keratin 10 polypeptide in vivo. Papillomas subsequently develop on the skin surface, initially at sites subject to biting or scratching such as the base of the tail or behind the ears. The results suggest that the "second event" involved in tumor development in these transgenic animals is the local induction of a mild wounding stimulus. Furthermore, because the H-ras transgene is expressed in suprabasal cells, it appears that cells which have left the stem cell compartment can be induced to form at least benign tumors in vivo. Topics: Animals; Chromosome Mapping; Cloning, Molecular; Epidermis; Gene Expression; Genes, ras; Keratins; Mice; Mice, Transgenic; Papilloma; Promoter Regions, Genetic; Skin; Skin Diseases; Skin Neoplasms; Stomach; Wound Healing | 1990 |
S100 immunophenotypes of uveal melanomas.
To determine whether ocular melanomas are immunophenotypically identical to cutaneous melanomas, 34 primary and metastatic choroidal melanomas representing all major histotypes defined by the Callender's classification, plus one melanoma of the iris and one conjunctival melanoma, were subjected to a panel of immunostains designed to distinguish anaplastic biopsies of cutaneous melanomas from carcinomas and lymphomas. All ocular melanomas were found to express the intermediate filament vimentin but not keratin, and all but 2 were melanotic by immunostaining. Thirty-three of 34 (97%) choroidal melanomas were strongly stained with a rabbit polyclonal antibody (P-S100) developed against the S100 protein family. In contrast, none of 14 spindle cell type primary lesions was stained with a monoclonal antibody (MAB-079) specific for both S100 alpha and S100 beta, the best-characterized S100 polypeptides. Furthermore, only 2 of 5 epithelioid and 3 of 10 mixed-cell-type melanomas were weakly reactive. Overall, 14.7% (5 of 29) were stained. In comparison, MAB079 stained 85% of all cutaneous melanomas. Five metastases of choroidal melanomas (spindle B, epithelioid, and mixed cell types) from different organ sites also were stained by P-S100 but not by MAB079. These findings were corroborated by immunostaining with another monoclonal antibody (MAB4D4) specific for S100 beta. Differential staining by the polyclonal but not the monoclonal antibodies suggests the possible presence of a variant S100 polypeptide(s) in choroidal melanomas. Since S100 alpha, S100 beta, and related proteins appear to be physiologically important, additional studies of these S100 proteins may shed light on the etiology or pathology of choroidal melanomas. Topics: Antibodies, Monoclonal; Chi-Square Distribution; Conjunctival Neoplasms; Humans; Immunoenzyme Techniques; Iris Neoplasms; Keratins; Melanoma; Phenotype; S100 Proteins; Skin Neoplasms; Uveal Neoplasms; Vimentin | 1990 |
Eccrine spiradenoma occurring in infancy mimicking mesenchymal tumor.
Eccrine spiradenoma (ES) rarely (less than 1%) occurs in infancy. These tumors differ from the conventional ES by the presence of superficial dermal nodules which display a less distinct two-cell pattern of immature adnexal epithelial cells and rarely ductule formation. These tumors may be mistaken for mesenchymal neoplasms involving the skin and subcutis of infants and young adults. Recognition of the histopathologic features and immunostains are required to make a definite diagnosis. We describe 2 cases of ES occurring in patients younger than one year. Detailed histopathologic and histochemical differential features of these tumors and mesenchymal neoplasms of the skin and subcutis commonly occurring in infants and young adults are discussed. The biologic behavior of infantile ES is benign, but complete excision is recommended to prevent recurrence. We speculate that these tumors may represent congenital hamartomatous growths. Topics: Adenoma, Sweat Gland; Carcinoembryonic Antigen; Child; Child, Preschool; Diagnosis, Differential; Ferritins; Humans; Immunohistochemistry; Infant; Keratins; Mesenchymoma; S100 Proteins; Skin Neoplasms | 1990 |
Nonrandom duplication of the chromosome bearing a mutated Ha-ras-1 allele in mouse skin tumors.
We analyzed the normal/mutated allelic ratio of the Ha-ras-1 gene in mouse skin squamous cell carcinomas induced by initiation with dimethylbenz[a]anthracene and promotion with phorbol 12-myristate 13-acetate. DNA for these studies was obtained from short-term tumor cultures (24-72 hr) to eliminate the contribution of stromal and inflammatory cells to the sample. The allelotypic analysis was performed in 25 squamous cell carcinomas by quantitative radio-analysis of the Xba I restriction fragment length polymorphism as detected by BS9, a v-Ha-ras probe, and rehybridization of the Southern blots with probes for chromosomes 7 and 8. Approximately 85% of the tumors presented overrepresentation of the mutated allele in the form of 1 normal/2 mutated (12 tumors), 0 normal/3 mutated (4 tumors), 0 normal/2 mutated (3 tumors), and gene amplification (3 tumors). No tumor was found with a 2 normal/1 mutated allelic ratio. These results support our previous cytogenetic studies, indicating that trisomy of chromosome 7 is present in the majority of these tumors and show that nonrandom duplication of the chromosome carrying the mutated Ha-ras-1 allele appears to be a major mechanism by which the mutated gene is overrepresented. Topics: 9,10-Dimethyl-1,2-benzanthracene; Alleles; Animals; Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Chromosome Mapping; Gene Amplification; Genes, ras; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred Strains; Models, Genetic; Mutation; Nucleic Acid Hybridization; Polymorphism, Restriction Fragment Length; Skin Neoplasms | 1990 |
Early expression of type I K13 keratin in the progression of mouse skin papillomas.
The premalignant evolution of chemically induced mouse skin papillomas is characterized by dysplastic changes, aneuploidy, induction of gamma-glutamyl transpeptidase (GGT), and changes in the expression of keratins, especially differentiation-associated K1. This keratin, which is expressed in normal epidermis and early papillomas, is no longer present in more advanced dysplastic and aneuploid papillomas and in fully invasive carcinomas. More recently, it has been shown that K13, a keratin normally present in internal epithelia but not in epidermis, is aberrantly expressed in epidermal tumors. In the present study, the timing of expression of K13 and its correlation with other markers of premalignant evolution were investigated. Papillomas were induced by SENCAR mice by a single initiating dose of 20 nmol of 7,12-dimethylbenz[a]-anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) (2 micrograms twice a week). Tumors were randomly harvested at 10, 20 and 35 weeks of promotion. K13 and K1 expression in papillomas was studied using immunoblotting and immunostaining of consecutive sections, as previously described. As expected from previous studies, the distribution of K1 in papillomas collected at 10 weeks of promotion was restricted to differentiated cells and was uniform throughout the section of the papilloma. Conversely, K13 was expressed only as small foci in 10 out of 21 papillomas (48%). Papillomas of 20 weeks were also positive for K1. Staining for K13 was positive in these papillomas with the exception of only one that was essentially negative, presenting only one small positive focus. Some of the papillomas collected at week 35 were negative for K1, but immunostaining with K13 showed uniform staining of suprabasal cells in all the papillomas studied. In all cases, immunohistochemical results were confirmed by immunoblotting with proteins extracted from 7 microns sections from each paraffin block. These results indicate that keratins K1 and K13 are coexpressed in most papillomas from 10 to 35 weeks of promotion. However, analysis of adjacent sections showed that K13 positive areas are topographically located in the K1 negative areas of the papillomas, suggesting a shift in the differentiation program from epidermal to mucosal types of keratinization. Based on these and previous studies from our laboratory, we conclude that K13 is an early marker of papillomas progression, which occurs before gross chromosomal abnormalities Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Keratins; Mice; Papilloma; Precancerous Conditions; Skin Neoplasms; Time Factors | 1990 |
Malignant melanoma with pseudocarcinomatous hyperplasia--an entity that can simulate squamous cell carcinoma. A light-microscopic and immunohistochemical study of four cases.
We report four unusual cases of malignant melanoma in which squamous cell carcinoma was strongly considered in the differential diagnosis on routine hematoxylin and eosin-stained sections due to the near absence of melanin and the presence of pseudocarcinomatous hyperplasia. Ultimately, immunohistochemical staining for S-100 protein and keratin established the correct diagnosis of malignant melanoma in all cases. Topics: Aged; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Male; Melanoma; Middle Aged; S100 Proteins; Skin; Skin Neoplasms | 1990 |
Proliferating trichilemmal cyst with spindle cell carcinoma.
We report a 58-year-old woman with proliferating trichilemmal cyst (PTC), from which a spindle cell carcinoma arose. The tumor on her scalp had been removed at another hospital. Histological examination had revealed almost typical features of PTC. However, the case showed a partial transformation to spindle cell carcinoma, and transition zones between squamous epithelium and spindle cells were present. Three months after histologic examination, the patient came to us for the treatment of recurrent tumor. Despite surgical resection, the patient died as a result of distant metastases. Histologically, the recurrent tumor was composed of only spindle-shaped tumor cells. We describe the first example of this uncommon condition. Topics: Carcinoma; Diagnosis, Differential; Epidermal Cyst; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Middle Aged; Skin Diseases; Skin Neoplasms | 1990 |
An investigation of cytokeratin expression in skin epithelial cysts and some uncommon types of cystic tumours using chain-specific antibodies.
The differentiation state of skin epithelial cysts and some uncommon types of epithelial skin tumours was investigated by immunohistochemical staining, mainly using cytokeratin (CK) polypeptide-specific monoclonal antibodies. Samples of interfollicular epidermis, hair follicles and eccrine sweat glands were included as reference tissues. The CK reactivity in epidermoid cysts and milia is not restricted to CKs involved in epidermal-type differentiation, i.e. CK1, 5, 10 and 14, but in addition CK16, a hyperproliferative keratinocyte marker is suprabasally expressed. CK1 and 10 are other prominent suprabasal markers, while CK14 seems to be preferentially expressed in the basal cell layer. Of the non-epidermal CKs, only CK4 was focally or more extensively detected in about 50% of the cases. In terms of CK reactivity, keratinization of trichilemmal cysts corresponds to the keratinization of the anagen-phase hair follicle in the isthmus. The CK reactivity is again restricted to CK1, 5, 10, 14 and 16. However, the CK1 as well as CK10 reactivity is subject to serious limitations, since both CKs were only convincingly observed in foci of terminal differentiation. Eccrine hydrocystoma obligatorily expresses a complex CK set, including CK7, 8, 14, 18 and 19. This CK set perfectly corresponds to the CK composition observed in acini of eccrine sweat glands. In addition, a discontinuous CK4 and 16 reactivity was seen in about 50% of the sites, while CK1 and 10 displayed a strictly focal appearance. On the other hand, syringoma produces in its distinct structures, a CK pattern reminiscent of the one observed in eccrine sweat gland ducts and includes CK1, 5, 10, 14, 16 and 19.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Antibodies, Monoclonal; Antibody Specificity; Cysts; Epidermal Cyst; Epithelium; Gene Expression; Humans; Immunohistochemistry; Keratins; Peptides; Skin; Skin Diseases; Skin Neoplasms | 1990 |
[Contribution of monoclonal antibody HMB45 in the histopathologic diagnosis of melanoma].
We have tested the diagnostic value in malignant melanoma of HMB45, a monoclonal antibody available for use on paraffin-embedded tissue. MATERIAL AND METHOD. Tissues tested. The following pathological tissues were tested: 10 intradermal and 11 compound naevi; 6 spitz naevi; 20 dysplastic naevi; 10 blue naevi; 2 Bednar's tumours; 6 Sutton naevi; 15 melanonychias; 21 cutaneous and 11 ocular malignant melanomas (MM), and 3 achromic metastases. Control tissues were: vitiligo (20), carcinoma (5), malignant schwannoma of the orbit (1), soft tissue sarcoma (5) and malignant lymphoma (5). Antibodies. The antibodies used were antiprotein S100, antivimentin, anticytokeratin (KL1), monoclonal antileucocyte (CD45) antibodies and HMB45, a monoclonal antibody of the IgG 1 type obtained from lymph node metastases from pigmented malignant melanomas. RESULTS. None of the control tissues were stained by the HMB Ab. Intradermal naevi did not react positively. Compound naevi: the juntional cells were stained by HMB45 in 2/10 cases. Dysplastic naevi: HMB45 showed heterogeneous reactivity of junctional cells in 15/20 cases, and this correlated with the degree of atypia. Blue naevi: HMB45 stained the superficial and deep cells in 3/10 cases. Bednar's tumour: no cell was stained by HMB45. Spitz naevi: HMB45 gave an intensely positive reaction of junctional cells in 4/5 cases and a weaker reaction of dermal cells. Sutton naevi: the naevus cells were not stained by HMB45 in 5/6 cases. In simple melanocytic hyperplasia of the nail bed, only a few atypical cells were stained. In superficially spreading melanoma (SSM) all neoplastic cells were stained by HMB45 in proportion to their degree of atypia. Residual naevus cells were negative. The anti S100 and the antivimentin antibodies stained all neoplastic and naevus cells. In nodular melanoma (NM), HMB45 stained all neoplastic cells in proportion to their degree of atypia. The antivimentin Ab stained the neoplastic cells, and so did the anti-S100 Ab which also stained inflammatory cells. In acral-lentiginous melanoma (ALM), HMB stained the dermal tumoral cells moderately and the junctional cells more strongly. In ocular melanoma, HMB45 strongly stained the fusiform cells and less strongly the epithelioid cells. In achromic metastases from cutaneous malignant melanomas, HMB45 strongly stained the neoplastic cells but did not stain the peritumoral cells. DISCUSSION. The purpose of this study was to compare the value of HMB45 with that o Topics: Antibodies, Monoclonal; Eye Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Leukocytes; Melanoma; Nevus, Pigmented; S100 Proteins; Skin Neoplasms; Vimentin | 1990 |
Clear cell basal cell carcinoma.
We describe a case of clear cell basal cell carcinoma of the superficial type, presenting as a crusted eruption on the abdomen. Histological examination showed a solid proliferation of clear cells attached to the under-surface of an atrophied epidermis. In addition, distinct pagetoid infiltration was seen within the overlying epidermis. A focal connection between the clear cell portion and a deeper lying nodular basal cell carcinoma was demonstrated, elucidating the true nature of the lesion. Immunohistochemical studies and electronmicroscopy confirmed the epithelial derivation of the tumour. The clear cell appearance was due to multiple cytoplasmic electronlucent vacuoles which were not surrounded by membranes. Topics: Abdomen; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Middle Aged; Organelles; S100 Proteins; Skin Neoplasms; Vimentin | 1990 |
TGF-beta and retinoic acid: regulators of growth and modifiers of differentiation in human epidermal cells.
In the epidermis of skin, a fine balance exists between proliferating progenitor cells and terminally differentiating cells. We examined the effects of TGF-beta s and retinoic acid (RA) on controlling this balance in normal and malignant human epidermal keratinocytes cultured under conditions where most morphological and biochemical features of epidermis in vivo are retained. Our results revealed marked and pleiotropic effects of both TGF-beta and RA on keratinocytes. In contrast to retinoids, TGF-beta s acted on mitotically active basal cells to retard cell proliferation. Although withdrawal from the cell cycle is a necessary prerequisite for commitment to terminal differentiation, TGF-beta s inhibited normal keratinization in suprabasal cells and promoted the type of differentiation commonly associated with wound-healing and epidermal hyperproliferation. The actions of TGF-beta s and RA on normal keratinization were synergistic, whereas those on abnormal differentiation associated with hyperproliferation were antagonistic. These observations underscore the notion that environmental changes can act separately on proliferating and differentiating cells within the population. Under the conditions used here, the action of TGF-beta s on human keratinocytes was dominant over RA, and TGF-beta s did not seem to be induced as a consequence of RA treatment. This finding is consistent with the fact that RA accelerated, rather than inhibited, proliferation in raft cultures. Collectively, our data suggest that the effects of both factors on epidermal growth and differentiation are multifaceted and the extent to which their action is coupled in keratinocytes may vary under different conditions and/or in different species. Topics: Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cell Line; Cells, Cultured; DNA Replication; Epidermal Cells; Humans; Keratinocytes; Keratins; Molecular Weight; Skin Neoplasms; Transforming Growth Factor beta; Tretinoin | 1990 |
Histologic alterations produced by chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone) in SENCAR mouse skin: relationship to skin tumor promoting activity.
Histologic changes induced in SENCAR skin following a single treatment with chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone) exhibited differences in time course from that observed with 12-O-tetradecanoylphorbol-13-acetate (TPA). Although not significantly different, maximum elevations in epidermal thickness, total number of nucleated epidermal cells, and dark basal keratinocytes (DCs) induced by 220 nmol chrysarobin occurred at 96 h after treatment, while those induced by 3.4 nmol TPA occurred at 48 h. Both compounds elicited comparable inflammatory responses. Twice-weekly applications of chrysarobin for 2.5 weeks induced a moderate hyperplasia, increase in total nucleated epidermal cells, and increased DCs at 48 and 96 h after the last treatment, with a higher value for these parameters occurring at 48 h. Interestingly, the magnitude of these changes was similar to that observed after a single application. In contrast, twice-weekly applications of TPA induced a dramatic, potentiated induction of epidermal hyperplasia and DCs. Once-weekly applications of chrysarobin led to a potentiated induction of both hyperplasia and DCs compared to the twice-weekly treatment regimen and also more effectively promoted epidermal papillomas in previously initiated SENCAR mice. Skin sections from mice treated with chrysarobin displayed overt signs of epidermal toxicity including altered basal cell morphology and a decreased number of basal cells per 125 micron of basement membrane. Hyperplasia induced by multiple but not single treatments with chrysarobin and TPA correlated quantitatively with their papilloma promoting activity. In addition, the data suggest that epidermal toxicity may play a role in tumor promotion by anthrones. Topics: Administration, Cutaneous; Animals; Anthracenes; Carcinogens; Female; Hyperplasia; Keratins; Mice; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors | 1989 |
Gap-junctional intercellular communication in epidermal cell lines from selected stages of SENCAR mouse skin carcinogenesis.
Homologous and heterologous gap-junctional intercellular communication (IC) was characterized in a panel of cell lines derived from selected stages of SENCAR mouse skin carcinogenesis. This panel included a "carcinogen-altered" cell line, 3PC, obtained from Ca2+-resistant primary adult keratinocytes after exposure to dimethylbenz(a)anthracene as well as cell lines obtained from early and late-stage papillomas and a squamous cell carcinoma (CA3/7) generated during standard in vivo initiation/promotion protocols (dimethylbenz(a)anthracene/12-O-tetradecanoyl-phorbol-13-acetate). Also studied was a cell line (B66BA) obtained from a metastatic lesion following benzo(a)pyrene-induced skin tumorigenesis. Intercellular communication was measured in low-calcium (0.05 mM) medium by quantitation of cell-cell transfer of microinjected fluorescent dye Lucifer Yellow CH. Homologous IC ability diminished progressively from 68 dye-coupled cells per injection for 3PC cultures, to between 21 and 54 dye-coupled cells per injection for three papilloma-derived cell lines, to six and three dye-coupled cells per injection for CA3/7 and B66BA cells, respectively. To test communication of these cells with their normal counterparts, heterologous IC was examined in cocultures with primary adult keratinocytes. Under the conditions used, normal cells established functional communication channels with each cell line tested, showing no selectivity. These results suggest that progressive loss of homologous but not heterologous IC capacity accompanies neoplastic development in mouse skin carcinogenesis. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benzo(a)pyrene; Calcium; Cell Communication; Cell Line; Epidermis; Intercellular Junctions; Keratins; Mice; Microinjections; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1989 |
[Primary neuroendocrine Merkel cell carcinoma of the skin].
A 78-year-old woman noticed a nodule on the dorsal aspect of the left lower leg which caused no symptoms but gradually increased in size. The raised, brown-red nodule, about 1.5 cm in diameter, was widely excised because malignancy was suspected. Light and electronmicroscopy revealed changes typical of Merkel-cell carcinoma. Immunohistochemistry demonstrated neuron-specific enolase and cytokeratin. No metastases were found. Together with Langerhans cells and melanocytes, Merkel cells belong to the three non-keratinocyte cell types of the epidermis. Topics: Aged; Carcinoma, Merkel Cell; Endoplasmic Reticulum; Female; Humans; Immunohistochemistry; Keratins; Mitochondria; Phosphopyruvate Hydratase; Skin; Skin Neoplasms | 1989 |
Correlation between cell-cell contact formation and activation of protein kinase C in a human squamous cell carcinoma cell line.
Formation of desmosomal cell-cell contact associated with reorganization of keratin intermediate filaments (KIFs) was observed when cultured cells of a cell line of human skin squamous cell carcinoma were transferred from low (0.07 mM) calcium to high (1.87 mM) calcium medium. At low calcium, cells were dispersed without desmosomal cell-cell contact and the KIFs were mostly concentrated around the nucleus. After 15 min of the transfer, cells contacted each other and formed small colonies and the KIFs initiated to show a radial arrangement. In addition to the cell-cell contact formation and rearrangement of KIFs, the transfer induced fourfold increase of particulate-associated protein kinase C (C-kinase) activity. When 12-O-tetradecanoyl phorbol-13-acetate (PMA), which specifically activates C-kinase, was added to the cells grown at low calcium medium, cell-cell contact formation and radial arrangement of KIF bundles almost identical to those induced by the transfer to high calcium medium were observed. These data suggest a correlation between an increase in C-kinase activity and formation of cell-cell contacts associated with rearrangements of KIFs. Topics: Calcium; Carcinoma, Squamous Cell; Cell Communication; Enzyme Activation; Humans; Intermediate Filaments; Keratins; Osmolar Concentration; Protein Kinase C; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured | 1989 |
[Skin metastases in prostatic cancer. Immunohistologic indications of the primary tumor].
Prostatic carcinoma accounts for about 1% of all cancers that metastasize to the skin. The regions most frequently involved are the genital region, the head and the trunk. Clinically the lesions present as nodules; less often diffuse infiltrates, red macules and papules or tumors of an angiomatous appearance occur. Histopathological examination of skin biopsy specimens can reveal gland-like, epithelial or anaplastic differentiation of tumor cells. Prostatic origin can be proven by the immunohistological demonstration of acid prostatic phosphatase or prostatic specific antigen in paraffin-embedded specimens taken for routine histological examination. Topics: Acid Phosphatase; Biomarkers, Tumor; Breast Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prostatic Neoplasms; Skin; Skin Neoplasms | 1989 |
Signet-ring squamous cell carcinoma.
Among carcinomas, signet-ring morphologic characteristics have been regarded as pathognomonic of adenocarcinoma. This report presents the case of a poorly differentiated cutaneous squamous cell carcinoma with a monodispersed, invasive signet-ring component. Kreyberg stains had negative results for mucin. Immunohistochemical analysis demonstrated that concentric rings in the signet-ring cells were composed of keratin. To the best of the authors' knowledge, this is the first report of signet-ring squamous cell carcinoma. Another feature that bears emphasis is that this squamous cell carcinoma led to the death of the patient, even though it originated in a field of actinic keratosis. Topics: Adenocarcinoma, Mucinous; Aged; Carcinoma, Squamous Cell; Forehead; Humans; Immunohistochemistry; Keratins; Keratoacanthoma; Keratosis; Neoplasm Recurrence, Local; Skin Neoplasms; Staining and Labeling | 1989 |
Reduced levels of UV-induced unscheduled DNA synthesis in epidermal keratinocytes of patients with xeroderma pigmentosum and correlation with development of skin neoplasms.
Primary epidermal keratinocytes obtained from 25 patients with xeroderma pigmentosum (XP) (nine with XP-A, one with XP-C, two with XP-D, five with XP-E, and eight with XP-variant) exhibited less UV-induced unscheduled DNA synthesis (UDS) than did those from 34 normal subjects. Levels of UDS depended greatly on the type of XP; i.e., 3-17% of the control in XP-A, 14% in XP-C, 33-53% in XP-D, 38-77% in XP-E and 58-98% in XP-variant. The extent of UDS in epidermal keratinocytes was almost the same as that in dermal fibroblasts in XP-C, D, and E, but in three out of eight of the XP-variant the level of UDS in epidermal keratinocytes was significantly lower than that in normal subjects. Clinically, three out of nine XP-A patients developed skin neoplasms before 20 years of age. Both patients with XP-D developed skin neoplasms around 40 years of age. In the five XP-E patients, two developed multiple basal cell epithelioma on sun-exposed areas during the forth decade, and one of them also developed squamous cell carcinoma at the age of 50. Four out of the eight patients with the XP-variant developed various skin neoplasms during their 20s and 30s. These results suggest that a defect in UV-induced UDS in epidermal keratinocytes of XP patients is responsible for skin carcinogenesis and the extent to which this defect occurs tends to relate to the age of onset of skin neoplasms. Topics: Adult; Age Factors; Child; DNA; DNA Repair; Epidermis; Female; Humans; Keratins; Male; Middle Aged; Skin Neoplasms; Ultraviolet Rays; Xeroderma Pigmentosum | 1989 |
Neuroendocrine carcinoma (Merkel cell tumor?) presenting as a subcutaneous tumor. An ultrastructural and immunohistochemical study of three cases.
The clinical and pathological features of three unusual soft tissue tumors are presented. They occurred in the groin of elderly patients in the subcutaneous tissue. In Case 1, the inguino-crural tumor coexisted with a second mass in the pelvis. The tumors had a tendency to recur locally and to invade the regional lymph nodes. Metastatic dissemination of the disease resulted in the death of the patient in Case 3. Histologically, the tumors appeared composed of small round cells with scanty cytoplasms, arranged in diffuse, poorly cohesive or solid sheets. In places, a trabecular pattern was noted. Mitotic figures were numerous. Some cells exhibited argyrophil granules. The ultrastructural study revealed compact whorls of intermediate filaments and neurosecretory granules. All three cases displayed a paranuclear dot-like positive reaction with antibodies to cytokeratins and neurofilaments. A diffuse cytoplasmic immunostaining for neuron-specific enolase was present in Cases 1 and 2. Protein S-100, vimentin and leucocyte common antigen could not be demonstrated. All these characteristics, except for the subcutaneous location, are shared with neuroendocrine (Merkel cell) tumors of the skin. Topics: Aged; Aged, 80 and over; Antigens, Differentiation; Carcinoma, Merkel Cell; Desmin; Diagnosis, Differential; Female; Histocompatibility Antigens; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Leukocyte Common Antigens; Male; Microscopy, Electron; Middle Aged; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Proteins; Skin Neoplasms; Vimentin | 1989 |
The influence of fixation on the relative amount of cytoplasmic ribosomes in mouse epidermal basal keratinocytes. A morphometric study of so-called "dark cells" and their putative role in epidermal carcinogenesis.
The nature and significance of so-called dark keratinocytes in the epidermis during chemical carcinogenesis is still a matter of concern and debate. Based on ultrastructural observations it has been suggested that dark cells most often are shrunken cells. Reports on skin carcinogenesis, however, claim that dark cells are a sign of ongoing tumor promotion and represent those stem cells in the epidermis from which the tumors originate. It is therefore important to find out whether these cells are simply injured and shrunken cells, or vital cells of great importance for carcinogenesis. Dark cells are assumed to be rich in ribosomes. There is evidence, however, that the observed number of dark cells is highly dependent on tissue fixation. In the present ultrastructural study, morphometric methods were used to compare the effects of two different fixation procedures on the amount of cytoplasmic ribosomes in dark cells from both untreated and carcinogen-treated hairless mouse epidermis. The results show that the ultrastructural features of both dark and clear cells vary considerably with different fixation procedures. In acetone-treated controls typical dark cells are only observed when the fixative has a lower osmotic activity than the plasma. With iso-osmolal fixation typical dark cells are not observed. After an abortive two-stage carcinogenesis treatment, in which a single application of 9,10-dimethyl-1,2-benzanthracene (DMBA) in acetone was followed by a single application of 12-O-tetradecanoyl-13-acetate (TPA) in acetone, signs of cell injury could be found after both fixation procedures. With DMBA/TPA and hypo-osmolal fixation the number of dark cells seemed to increase, whereas only signs of cell injury with occurrence of some heavily altered "clear cells" dominated the picture with iso-osmolal fixation. Morphometry showed that both the numerical and the volumetric densities of cytoplasmic ribosomes in basal keratinocytes varied most significantly with the fixation procedure used. The cytoplasmic volumes did not vary in a way that could explain these differences. One might therefore assume that the number of ribosomes depends on the fixative. Large swelling artifacts occurred when a fixative with low osmotic activity was used, leading to compression of neighboring cells. Hence, an increased ribosomal density reported previously in dark cells is probably related to such cell volume artifacts and does not reflect an actually increased quantity of ribosome Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Cytoplasm; Epidermal Cells; Epidermis; Female; Fixatives; Keratins; Male; Mice; Mice, Hairless; Microscopy, Electron; Ribosomes; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1989 |
[Disordered keratinocyte differentiation in epidermal tumors and mycosis fungoides].
The immunocytochemical method with monoclonal antibodies to human and murine epidermis basal-cell antigen (BCAg) has been used in studies on the disorders in keratinocyte differentiation in epidermal tumors and mycosis fungoides. The fluorescence intensity augmented and BCAg distribution in the cytoplasm grew more diffuse as the degree of the tumor cell differentiation lowered. In mycosis fungoides the BCAg reaction has been positive first in the suprabasal layers; as the disease progressed, the fluorescence has involved the entire epidermis. The BCAg test is a sensitive tool for estimating the epidermal cell maturity in processes associated with impaired differentiation of keratinocytes. Topics: Antibodies, Monoclonal; Antigens, Differentiation; Antigens, Neoplasm; Biopsy; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Epidermis; Humans; Immunohistochemistry; Keratins; Mycosis Fungoides; Skin Neoplasms | 1989 |
Different ultrastructural feature of keratinocytes in human malignant melanomas.
The ultrastructural feature of keratinocytes was investigated in human superficially spreading melanomas of type B. The tumor cells of these melanomas are characterized by spheroidal melanosomes and containing pheomelanins. Contrary to type A melanomas the keratinocytes show no striking transformation reaction neither in the nucleus nor in the cytoplasm although this part of the cell mostly contains abundant melanin granules surrounding the nucleus. Whether there exists a relation to the clinical course still has to be clarified. Topics: Epidermis; Histocytochemistry; Humans; Keratins; Melanocytes; Melanoma; Microscopy, Electron; Skin Neoplasms | 1989 |
Distribution of neu (c-erbB-2) protein in human skin.
The neu (c-erbB-2) gene encodes a transmembrane protein with tyrosine kinase activity that appears to be a growth factor receptor. Antibody was generated by immunization of rabbits with a synthetic polypeptide that was based on an internal sequence at the carboxy terminus of the molecule. This antibody was used to survey the expression of neu in human skin by immunohistochemistry. Significant protein was found in the squamous cell layer of the surface epidermis, in squamous cell carcinomas, in the external root sheath of hair follicles, and in eccrine gland secretory cells; it was poorly expressed in the basal cell layer and in a basal cell carcinomas. Increased neu expression appears to be associated with the differentiation of keratinocytes. Topics: Antibody Specificity; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Line, Transformed; Epidermal Cells; Humans; Immunoenzyme Techniques; Keratins; Precipitin Tests; Proto-Oncogene Proteins; Receptor, ErbB-2; Skin; Skin Neoplasms | 1989 |
Comparative stages of expression of human squamous carcinoma cells and carcinogen transformed keratinocytes.
The mouse monoclonal antibody OSU 22-3 was prepared using cells from a squamous cell carcinoma (SCC) as an immunogen. This antibody reacts with an antigen found on squamous cell carcinomas but does not react with normal keratinocytes. This antibody and two antibodies that react with normal keratinocytes were used as markers of malignant and normal phenotypes. These markers were used to evaluate several spontaneous and carcinogen initiated SCC tumors and to identify the expression of an antigen associated with a malignant phenotype. A variety of subpopulations in carcinogen initiated tumors and spontaneous SCC tumors were noted. The subpopulations that reacted only with MoAb OSU 22-3 exhibited features of anchorage independent growth and cellular invasiveness, and formed progressively growing tumors in nude mice. Other SCC spontaneous tumor cell subpopulations reacted with the antibodies associated with normal keratinocytes. These cells did not proliferate in vitro and did not form tumors in the nude mouse. There were other carcinogen transformed cells which reacted with MoAb OSU 22-3 but not with the antibodies associated with normal keratinocytes. These cells exhibited anchorage independent growth and cellular invasiveness but did not form tumors in nude mice. We conclude from this work that human SCC tumors contain multiple cell populations. These cell populations have varied growth properties and express surface antigens that may indicate their malignant vigor. Carcinogen transformed keratinocytes do exhibit some of the characteristics of SCC tumor phenotypes but not the property of malignant progressively growing cells on a routine and consistent basis. This feature is transiently and inconsistently expressed in a surrogate host by populations prepared from spontaneous SSC tumors. Topics: Animals; Antibodies, Monoclonal; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Dose-Response Relationship, Drug; Epidermal Cells; Epidermis; Humans; Keratins; Lethal Dose 50; Male; Methylnitronitrosoguanidine; Mice; Mice, Nude; Neoplasm Staging; Phenotype; Skin Neoplasms; Tumor Cells, Cultured | 1989 |
Cytologic and immunohistochemical diagnosis of neuroendocrine (Merkel cell) carcinoma in cerebrospinal fluid.
Neuroendocrine (Merkel cell) carcinoma of the skin is a rare entity. Often locally aggressive, this lesion may also metastasize to organ systems, including bone, liver, and brain. The authors report a case of a 64-year-old male who presented with hoarseness and dysphagia 17 months after resection of a primary Merkel cell carcinoma of the nose. Additional studies revealed bilateral vocal cord paralysis secondary to central nervous system dysfunction. Cytologic evaluation of the cerebrospinal fluid revealed malignant tumor cells consistent with metastatic Merkel cell carcinoma. Presented are the cytologic and immunohistochemical findings in a case of metastatic Merkel cell carcinoma involving the central nervous system. Topics: Carcinoma, Merkel Cell; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Nervous System Neoplasms; Nose Neoplasms; Phosphopyruvate Hydratase; Skin Neoplasms | 1989 |
Altered keratin expression in benign and malignant skin diseases revealed with monoclonal antibodies.
We studied keratin expression in benign epidermal skin diseases, and in Bowen's disease by using three monoclonal cytokeratin antibodies. In adult normal skin, these antibodies bind only to the follicular epithelium (PKK1), the basal keratinocytes (PKK2), or the suprabasal cells in interfollicular epidermis (KA5). Additionally, in fetal epidermis, the PKK1 antibody reacts with basal keratinocytes. In psoriasis and lichen planus, the PKK2 antibody distinctly revealed all epidermal cell layers by immunostaining. However, a negative basal cell-like layer was revealed in both lesions with the KA5 antibody. In pityriasis rubra pilaris, the basal cell layer was uniformly stained with the PKK2 antibody, but only some keratinocytes in upper cell layers showed fluorescence and, in chronic eczema, the 3-4 lowest epidermal cell layers were reactive. The PKK1 antibody did not stain interfollicular keratinocytes in any of the benign proliferative skin diseases studied. In Bowen's disease, a heterogeneous staining pattern with varying intensity among individual cells was seen with all of the antibodies used. Our results suggest different changes in keratin expression in chronic benign and malignant epidermal diseases that may reflect the mechanisms behind these changes. Topics: Antibodies, Monoclonal; Bowen's Disease; Carcinoma, Squamous Cell; Epidermal Cells; Fluorescent Antibody Technique; Humans; Keratins; Psoriasis; Skin Diseases; Skin Neoplasms | 1989 |
Microcystic adnexal carcinoma of the scalp.
Microcystic adnexal carcinoma (MAC) is a recently described rare adnexal neoplasm showing benign histologic features but a locally aggressive behavior. It has most commonly been reported to occur on the face but it has also been noted in the axilla and buttock. We describe a 41-year-old white male with a 5-year history of MAC on the scalp and treatment by Mohs micrographic surgery. To our knowledge, this is the first case of MAC reported to occur on the scalp. Topics: Adult; Carcinoma; Cysts; Epidermis; Humans; Keratins; Male; Scalp; Sclerosis; Skin Neoplasms | 1989 |
The ultrastructure of epithelioid sarcoma.
We have described clinical, histological immunohistochemical and ultrastructural features of four typical examples of epithelioid sarcoma. Smooth-muscle-type focal densities amid fine actin-like filaments in typical epithelioid cells often containing prominent rER have been observed, as well as a structure in the form of a densely granular cytoplasmic body. These features are suggestive of myofibroblastic differentiation. A tumour with light microscopy features typical of epithelioid sarcoma but of spindle-cell appearance is also described. Ultrastructurally this consists of myofibroblasts and it is suggested that this may be an unusual variant in which myofibroblastic differentiation is a major feature. Topics: Adult; Aged; Cell Transformation, Neoplastic; Female; Fibroblasts; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Muscle, Smooth; Sarcoma; Skin Neoplasms; Vimentin | 1989 |
Evidence for the metabolism of tumor promoter organic hydroperoxides into free radicals by human carcinoma skin keratinocytes: an ESR-spin trapping study.
Humans are exposed to various peroxy and hydroperoxy compounds which are in use in the cosmetic, pharmaceutical and polymer industries and which are also generated as a result of the peroxidative metabolic conversion of certain lipids. This study was designed to determine whether the organic hydroperoxides, tert-butyl hydroperoxide, cumene hydroperoxide and tert-butyl peroxybenzoate are metabolized by human carcinoma skin keratinocytes to free radicals. Incubation of keratinocytes prepared from cutaneous squamous cell carcinoma in phosphate-buffered saline (pH 7.4) containing desferrioxamine with tert-butyl hydroperoxide, cumene hydroperoxide and tert-butyl peroxybenzoate in the presence of spin trap (3,5-dibromonitrosobenzene sulfonic acid) resulted in the generation of corresponding methyl radical adducts. Prior heating of the cells to 100 degrees C abolished the generation of radical adducts. The addition of ethanol to the reaction mixture also inhibited formation of radical adducts. These data provide the first direct evidence that human carcinoma skin cells can generate free radicals from organic hydroperoxides. Since free radicals are suggested to be involved in the cascade of events occurring during tumor promotion this metabolic capacity may be an important determinant of human cancer risk for hydroperoxides. Topics: Benzene Derivatives; Benzenesulfonates; Benzoates; Carcinoma, Squamous Cell; Cell Line; Electron Spin Resonance Spectroscopy; Epidermal Cells; Epidermis; Free Radicals; Humans; Keratins; Kinetics; Nitroso Compounds; Peroxides; Skin Neoplasms; Spin Labels; tert-Butylhydroperoxide | 1989 |
Occurrence of Langerhans cells and expression of class II antigens on keratinocytes in malignant and benign epithelial tumors of the skin: an immunohistopathologic study with monoclonal antibodies.
We used an avidin-biotin complex immunoperoxidase technique with various monoclonal antibodies to determine Langerhans cell densities, class II antigen expression on keratinocytes, and phenotypes of other infiltrating cells in several malignant and benign epithelial tumors of the skin. Our observations indicate (1) there are few Langerhans cells in nests of basal cell carcinoma and squamous cell carcinoma; (2) there are increased Langerhans cell densities in seborrheic keratoses, verrucous epidermal nevus, and Bowen's disease; (3) there is an expression of class II molecules on the keratinocytes and cancer cells of basal cell carcinoma, squamous cell carcinoma, Bowen's disease, seborrheic keratosis, and verrucous epidermal nevus; and (4) there is a netlike staining of the keratinocyte surface with OKM5 in the epidermal lesion of seborrheic keratosis, verrucous epidermal nevus, and Bowen's disease, as well as in the epidermis adjacent to the basal cell carcinoma and squamous cell carcinoma nests. Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Bowen's Disease; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermal Cells; Female; Histocompatibility Antigens Class II; Humans; Keratins; Keratosis; Langerhans Cells; Male; Middle Aged; Skin Neoplasms | 1989 |
[Immunohistochemical study of the distribution of carcinoembryonic antigen and keratin in 2 cases of extramammary Paget disease].
Sweat gland origin of Paget disease is demonstrated by the presence of carcinoembryonic antigen (CEA). We studied the expression of CEA and keratin in two cases of extramammary Paget disease. Our results are commented. Topics: Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Paget Disease, Extramammary; Skin Neoplasms | 1989 |
[Immunohistochemical study of the distribution of carcinoembryonic antigen and keratin in tumors of epidermal origin. I: Squamous and basal cell epitheliomas].
Carcinoembryonic antigen (CEA) has been studied extensively, in association with visceral tumors and normal tissues. Although CEA has been demonstrated in sweat gland cutaneous tumors, little is known about its presence in skin and epithelial related tumors. We studied the presence of CEA and keratin in squamous cell and basal cell carcinoma using immunohistochemical techniques. Its distribution related with differentiation, proliferation and malignant potential is observed. The expression of both antigens is correlated. Topics: Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Skin Neoplasms | 1989 |
Keratinocyte expression of OKM5 antigen in inflammatory cutaneous disease.
Keratinocyte expression of the monocyte/macrophage surface antigens defined by OKM1 and OKM5 antibodies (Ortho Diagnostics) was examined using the peroxidase anti-peroxidase immunohistochemical technique. A range of inflammatory cutaneous disorders were investigated, including lichen planus, psoriasis and atopic dermatitis. Positive suprabasal keratinocyte expression of OKM5 antigen was observed in all disorders, while keratinocyte staining with OKMI antibody was consistently negative. These results provide further evidence that keratinocytes may play an important role in cutaneous immune responses. Furthermore, they are consistent with the recent observation that HLA-DR positive keratinocytes may modulate cutaneous immunological reactions by inducing T-cell unresponsiveness. Topics: Adult; Antigens, Differentiation; CD36 Antigens; Dermatitis, Atopic; Epidermis; Humans; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Lymphoma; Monocytes; Psoriasis; Skin Diseases; Skin Neoplasms | 1989 |
Rudimentary meningocele: a variant of "primary cutaneous meningioma".
We studied 5 primary cutaneous meningiomas. All were congenital. Four were nodules or plaques on the scalp, and one was a lumbar polyp. Two were alopecic. A skull defect was present deep to one lesion, and the lumbar polyp was attached to dura. The tumors were concentrated in the subcutis, where strands of meningocytes were embedded in dense collageous tissue. Meningocytes wrapped around collagenous fibers, producing "collagen bodies". These formed the nidus for calcification that included psammoma bodies. Meningocytes also dissected between collagenous fibers, creating anastomosing spaces that mimicked a vascular tumor. Meningothelial-lined clefts, several milimeters in length, were present in 4 cases. Two lesions extended through dermal defects into the superficial dermis, where adnexa were reduced or absent. The meningocytes contained vimentin and epithelial membrane antigen. They lacked cytokeratin, S100 protein, and endothelial markers. The meningothelial lesions described herein lack the nodular and sheet-like growth patterns that typify meningiomas of the central nervous system and most primary ectopic meningiomas, including some that develop within the skin. They appear closely related to meningoceles and should be viewed as developmental abnormalities rather than neoplasms. The term "rudimentary meningocele" seems appropriate for these lesions. Topics: Adolescent; Adult; Child; Child, Preschool; Female; Genetic Variation; Humans; Immunohistochemistry; Infant; Keratins; Male; Membrane Glycoproteins; Meningioma; Meningocele; Mucin-1; S100 Proteins; Skin Neoplasms; Vimentin | 1989 |
Atypical fibroxanthoma: two unusual variants.
Two unusual fibroxanthomas were studied by light microscopy. The first case contained numerous osteoclast-like cells and resembled malignant giant cell tumour of soft tissues, a variant of malignant fibrous histiocytoma. Osteoclast-like giant cells were negative for lysozyme and alpha-1-antitrypsin. The second case contained areas of chondroid differentiation which resembled chondrosarcoma. Tumour cells within the cartilaginous areas were positive for S100 protein. Topics: Aged; Aged, 80 and over; alpha 1-Antitrypsin; Chondrosarcoma; Female; Fibroma; Genetic Variation; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Muramidase; S100 Proteins; Skin Neoplasms | 1989 |
Epithelial markers in synovial sarcoma. An immunohistochemical study on paraffin embedded tissues.
Immunohistochemical studies on synovial sarcomas have proved the potentiality of these neoplasm for epithelial and mesenchymal differentiation and antibodies detecting epithelial cells have been found to be helpful in determining the histological types. In this study different epithelial markers directed against various cytokeratins, HMFG-2 and EMA were investigated on paraffin embedded tissues of 13 cases of synovial sarcomas, with regard to their reliability in unmasking the epithelial components demonstrable in this type of neoplasm. The results lead to three conclusions: firstly, synovial sarcomas possess the capacity for generating different epithelial cell types with uncommon compositions of intermediate filaments as well as of membrane proteins, secondly, these features may be expressed in a heterogenous pattern even within the same tumour and finally, the use of wide range anti-cytokeratin antibodies covering the spectrum of basic as well as acidic type proteins seems to be necessary for the detection of all epithelial components demonstrable in synovial sarcomas. Topics: Antibodies; Biomarkers, Tumor; Breast Neoplasms; Epithelium; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Sarcoma, Synovial; Skin Neoplasms; Stomach Neoplasms; Synovial Membrane | 1989 |
Expression of membrane glycoproteins in normal keratinocytes and squamous carcinoma cell lines.
Con A acceptor glycoproteins were analyzed by 2D-PAGE and 125I-Con A overlay in three squamous carcinoma cell lines and compared with those in the simian virus (SV40)-transformed keratinocyte cell line SVK-14 and in normal keratinocytes. The majority of the glycoproteins identified by this technique were expressed at similar levels in all of the cells examined, independent of the culture conditions used. A cell surface glycoprotein gp34 (MW 34 kDa, pI 5.1) was increased in the tumor cells compared with normal keratinocytes and expression varied with the culture density. Another glycoprotein, gp21 (MW 21 kDa, pI 6.3), was found to be increased in expression in normal keratinocytes and stratified hyperconfluent cultures of squamous carcinoma cell lines. This paper describes the potential of this technique to identify membrane glycoproteins which may be expressed as a function of proliferation or differentiation. Topics: Carcinoma, Squamous Cell; Cell Line; Concanavalin A; Electrophoresis, Gel, Two-Dimensional; Humans; Keratins; Membrane Glycoproteins; Molecular Weight; Reference Values; Skin; Skin Neoplasms; Tumor Cells, Cultured | 1989 |
Differentiation of cultured human keratinocytes: effect of culture conditions on lipid composition of normal vs. malignant cells.
Differentiation in keratinocytes can be experimentally modulated by changing the culture conditions. When cultured under conventional, submerged conditions, the extent of cellular differentiation is reduced in the presence of low calcium medium and is enhanced in medium containing physiologic calcium concentrations. Moreover, cultures grown at the air-medium interface or on a dermal substrate, or both, differentiate even further. Herein we report the effect of culture conditions on lipid composition in normal human keratinocytes and three squamous carcinoma cell (SCC) lines that vary in their capacity to differentiate as assessed by cornified envelope formation. Under submerged conditions, the total phospholipid content was lower, triglyceride content higher, and phospholipid:neutral lipid ratio lower in direct correlation to the degree of differentiation in these cultures. When grown at the air-medium interface on de-epidermized dermis, evidence of further morphologic differentiation was found only for well-differentiated SCC cells and normal keratinocytes. Similarly, the phospholipid content remained high in poorly differentiated SCC cells and it decreased modestly in well-differentiated SCC cells and markedly in normal keratinocytes. In all cell lines the triglyceride content was increased and cholesterol content decreased when compared to parallel submerged cultures, but these differences were most pronounced in well-differentiated cell lines. Acylceramides and acylglucosylceramides were found only in normal keratinocytes and only under the most differentiation-enhancing conditions. These studies demonstrate differentiation-related changes in the lipid content of both normal and neoplastic keratinocytes. Topics: Cell Differentiation; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Epidermal Cells; Epidermis; Humans; Infant; Keratins; Lipids; Male; Skin Neoplasms; Tumor Cells, Cultured | 1989 |
Immunocytochemical diagnosis of skin tumours of the dog with special reference to undifferentiated types.
Immunoperoxidase techniques for S-100 protein, keratin, cytokeratin, vimentin and desmin were applied to 65 canine skin tumours. These included eight squamous cell carcinomas, eight fibrosarcomas, eight melanomas, eight mastocytomas, eight haemangiosarcomas, eight leiomyosarcomas, five liposarcomas and 12 poorly differentiated tumours. Consistent results were obtained within each group. Cytokeratin and keratin immunoreactivity was detected only in squamous cell carcinomas. Vimentin was present in fibrosarcomas, melanomas, haemangiosarcomas, mastocytomas, leiomyosarcomas and liposarcomas. S-100 protein immunoreactivity was detected in melanomas, haemangiosarcomas, liposarcomas and leiomyosarcomas. Only leiomyosarcomas were positive for desmin. According to these results the 12 anaplastic tumours were diagnosed either as carcinomas, fibrosarcomas or malignant melanomas. Topics: Animals; Carcinoma, Squamous Cell; Desmin; Dog Diseases; Dogs; Fibrosarcoma; Hemangiosarcoma; Immunoenzyme Techniques; Keratins; Leiomyosarcoma; Liposarcoma; Mast-Cell Sarcoma; Melanoma; S100 Proteins; Skin Neoplasms; Vimentin | 1989 |
Expression of EGF receptor, involucrin, and cytokeratins in basal cell carcinomas and squamous cell carcinomas of the skin.
The distribution of several markers of keratinocyte differentiation was studied in normal epidermis, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs) using the immunoperoxidase technique on frozen sections of punch biopsy specimens. As markers a panel of chain-specific monoclonal antibodies (MoAbs) directed against cytokeratin (CK) 4, 8, 10, 13, 18 and 19, a polyclonal antiserum against involucrin, as well as a MoAb against the epidermal growth factor (EGF) receptor were used. In 15 out of 19 BCCs tested, expression of CK 8 was seen. Only a few individual cells in a limited number of BCCs showed positive staining for CK 4, 18, or 19. No expression of CK 10 was seen except for some foci of cell keratinization. Involucrin was not found in BCCs except for some squamous horn cysts. In all BCC cells expression of EGF receptor was found. In the suprabasal layers of normal epidermis from SCC patients, positive staining for CK 10 was seen. A few individual cells in a limited number of SCCs showed positive staining for CK 4, 8, or 18. Involucrin was expressed in the center of SCCs and in the upper layers of normal epidermis. Expression of EGF receptor was found in all SCC cells. These results demonstrate differences in cellular origin and differentiation between BCC and SCC. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermal Cells; Epidermis; ErbB Receptors; Humans; Immunoenzyme Techniques; Keratins; Protein Precursors; Skin Neoplasms | 1989 |
Basal cell carcinoma with hyaline inclusions.
A 67-year-old woman had a basal cell carcinoma of the forehead containing numerous hyaline cytoplasmic inclusions. Electron microscopic studies revealed that these inclusions were aggregates of cytoplasmic filaments. Immunohistochemical studies demonstrated reactivity for keratin, vimentin, and smooth-muscle myosin in these structures. Because of potential diagnostic difficulties, the pathologist should be aware of this unusual form of basal cell carcinoma. Topics: Aged; Carcinoma, Basal Cell; Female; Humans; Hyalin; Inclusion Bodies; Intermediate Filaments; Keratins; Neoplasm Recurrence, Local; Skin Neoplasms; Staining and Labeling | 1989 |
Neutrophil and eosinophil chemotactic factors released from human keratinocytic (hair follicular) tumor cells.
Topics: Cell Line; Cell Movement; Chemotactic Factors; Chemotactic Factors, Eosinophil; Epidermal Cells; Humans; Interleukin-8; Keratins; Neutrophils; Skin Neoplasms; Tumor Cells, Cultured | 1989 |
[Histochemical studies of transepidermal elimination of nevus cells in nevus cell nevi of the corium].
Dermal nevocytic nevi (NN) were histochemically studied with the help of FITC-conjugated lectins as well as antisera against keratin and plasminogen activators of the urokinase type. 3 out of 18 NN showed interpenetrating nevus cells in atrophic parts of the epidermis. These cells revealed strong lectin reactivity both with Con A (cytoplasmatic binding) and WGA/RCA II (membraneous binding). In addition we found membraneous reaction with anti-urokinase, whereas there was no anti-keratin staining. Our findings suggest active transepidermal elimination of nevus cells in dermal nevocytic nevi. Topics: Fluorescent Antibody Technique; Humans; Keratinocytes; Keratins; Nevus, Pigmented; Receptors, Mitogen; Skin; Skin Neoplasms | 1989 |
Multistage chemical carcinogenesis protocols produce spindle cell carcinomas of the mouse skin.
Spindle cell carcinomas were identified using polyacrylamide gel electrophoresis and immunoblotting of proteins extracted from paraffin-embedded tissue sections. Immunohistochemistry using rabbit monospecific antisera against the mouse 55 kd keratin polypeptide also identified these tumors. A group of 53 SENCAR mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) yielded, after one year, four spindle cell carcinomas (0.07/mouse), whereas another group of 31 mice treated with a three-stage carcinogenesis protocol (initiation with DMBA and promotion for 10 weeks with TPA followed by 10 weeks of benzoyl peroxide) gave rise to six spindle cell carcinomas (0.19/mouse). The number of keratin-positive tumor cells and the intensity of the immunostain varied markedly, but all tumors expressed the 55 kd polypeptide. Although other carcinogens, mainly UV radiation, have been able to induce spindle cell tumors, the present data indicate that chemical carcinogenesis protocols are able to induce the formation of this highly malignant variant of skin carcinoma. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Blotting, Western; Carcinoma; Drug Administration Schedule; Immunoenzyme Techniques; Keratins; Mice; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1989 |
Unusual patterns of keratin expression in the overlying epidermis of patients with dermatofibromas: biochemical alterations in the epidermis as a consequence of dermal tumors.
Dermatofibromas are frequently associated with acanthosis of the overlying epidermis. Using monospecific antisera and cRNA probes, we have examined the pattern of expression of keratin and keratin mRNA in the affected epidermis of patients with these dermal tumors. Our studies reveal several abnormalities in keratin expression within the thickened areas of overlying epidermis. In two of 15 patients, we detected K6 and K16, keratins which are frequently associated with epidermal diseases of hyperproliferation but are not present in normal epidermis. In both cases, K6 and K16 were found in suprabasal layers, similar to that seen for psoriasis and squamous cell carcinomas. Expression of K6 and K16 in skin samples from patients with dermatofibromas seemed to be dependent upon how near was the tumor to the overlying epidermis, and possibly upon the degree of cellularity within the tumor mass. A second aberration in keratin expression, and one which did not appear to be linked to K6/K16 expression, was the altered expression of the basal epidermal keratin K14. Expression of this keratin and its mRNA was variable, often extending into multiple suprabasal layers and including both basal-like and squamous-like cells. In contrast to the expression of K6/K16, aberrant expression of K14 was a relatively frequent event, occurring in greater than 70% of the dermatofibroma skin samples examined. These observations provide the first biochemical evidence in support of previous morphologic studies, indicating that alterations in epidermal differentiation can occur as a consequence of dermal skin tumors. Topics: Fibroma; Humans; Immunoblotting; Keratins; Skin; Skin Neoplasms | 1989 |
Vimentin-positive squamous cell carcinoma arising in a burn scar. A highly malignant neoplasm composed of acantholytic round keratinocytes.
Two patients had unusual squamous cell carcinoma (SCC) arising in a burn scar. The SCCs rapidly recurred and metastasized after radical operation, and the patients died of disseminated metastases. Histopathologically, the SCC was poorly differentiated and consisted of acantholytic round cells that diffusely proliferated into the deep dermis. However, small, solid nests composed of squamoid cells were focally observed. Immunohistochemical studies revealed that the acantholytic round neoplastic cells expressed not only keratin but also vimentin, and the coexpression was substantiated with double immunostaining. Vimentin-positive SCC composed of acantholytic round neoplastic cells may be a highly malignant subset of cutaneous SCC. Topics: Burns; Carcinoma, Squamous Cell; Cicatrix; Female; Humans; Keratins; Male; Middle Aged; Skin Neoplasms; Vimentin | 1989 |
Neuroendocrine (Merkel cell) carcinoma of the skin: a clinico-morphological study of 13 cases.
The clinico-morphological features in 13 patients (nine female) with neuroendocrine carcinoma of the skin are presented. The mean age was 64.9 years. The limbs were the most common site of primary tumour, followed by the face. The clinical course was characterized by a high incidence of regional lymph node metastases (69%) and recurrences (46%). Seven of the patients died of tumour, with a mean survival time of 13 months. Histologically, a solid pattern of tumour growth was most common. The cells were usually small and uniform. Squamous cell differentiation was found in one tumour. The cell of all tumours reacted positively for cytokeratins and neuron-specific enolase. The positive reaction frequently had a ball-like globular pattern, corresponding to inclusion-like bodies seen on light microscopy and to paranuclear whorls of intermediate filaments observed on electron microscopy. Neurosecretory granules were seen on electron microscopy in the 11 cases examined and in one case a 'Luse body' was found in the intercellular space. Topics: Aged; Carcinoma, Merkel Cell; Cytodiagnosis; Female; Humans; Immunohistochemistry; Inclusion Bodies; Keratins; Male; Microscopy, Electron; Middle Aged; Phosphopyruvate Hydratase; Skin Neoplasms | 1989 |
Immunohistochemical spectrum of malignant melanoma. The common presence of keratins.
Acetone-fixed frozen sections of 15 malignant melanomas of the skin with metastases were studied immunohistochemically for the presence of different types of intermediate filament proteins, synaptophysin, muscle cell actins, and desmoplakins. One of the melanomas was a primary toe tumor, and the others mainly regional lymph node metastases. The original diagnosis of melanoma was reconfirmed in each case, and the melanoma diagnosis of the metastases was verified by S100 protein immunostaining in all cases and by a monoclonal antibody to melanoma cells (NK1C3) in 7 cases. All melanomas were prominently vimentin-positive. In 10 of 15 cases, immunoreactive keratin could be demonstrated with antibody CAM 5.2. The presence of keratins was confirmed in selected cases with three other monoclonal antibodies including AE1, PKK1, and a monoclonal antibody specific for keratin number 18. Desmoplakin, another marker of epithelial differentiation, was not found in melanoma cells. Two melanomas contained neurofilament-positive tumor cells, which were however negative for synaptophysin. Desmin, muscle actins, and glial fibrillary acidic protein were not found in the neoplastic cells. On the basis of the present results one could conclude that the protein composition of the cytoskeleton of melanomas is more complex than has been previously thought and most importantly that melanomas may contain keratins. Topics: Adult; Aged; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Melanoma; Middle Aged; Skin Neoplasms | 1989 |
Immunohistochemical study on keratin expression in certain cutaneous epithelial neoplasms. Basal cell carcinoma, pilomatricoma, and seborrheic keratosis.
We investigated immunohistochemically 20 basal cell carcinomas (BCC), five pilomatricomas, and nine seborrheic keratoses using anti-BCC keratin monoclonal antibody (BKN-1) and anti-hair keratin monoclonal antibodies (HKN-2, HKN-4- -7). The neoplastic cells in all the cases of BCC were always uniformly stained by BKN-1, HKN-2, and HKN-4, indicating that the BCC cells display a constant antigenicity of keratin, which may be different from that of the normal epidermis. Although no fluorescence by HKN-6 or HKN-7 was seen in any cases of BCC, HKN-5 partially but strongly stained the neoplastic nests in most cases of BCC; BCC may have differentiation toward the lower part of hair follicular epithelium. In pilomatricoma, all the anti-keratin monoclonal antibodies showed a similar staining pattern; the differentiating neoplastic cells undergoing transition from basaloid to eosinophilic were positively stained by each antibody in all the cases. This finding of pilomatricoma corresponds to that of the differentiating cells in the inner hair layers, especially in the hair cortex. In seborrheic keratoses, no fluorescence was recognized with HKN-5- -7, which stain the lower follicular cells in the normal human skin. The staining patterns of seborrheic keratosis by BKN-1, HKN-2, and HKN-4 were similar to those of the normal interfollicular epidermis. These anti-keratin monoclonal antibodies seem to be useful for the investigation of the direction of differentiation of skin adnexal neoplasms. Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Dermatitis, Seborrheic; Humans; Immunohistochemistry; Keratins; Keratosis; Skin Neoplasms | 1989 |
[Cytokinetics and keratins of keratinocytes from skin of the elderly].
Regarding the keratin pattern of non-exposed skin, we found no significant qualitative or quantitative differences between 6 old persons (mean age 85 years) and 4 young adults (mean age 20 years). There was, however, a slight increase of proliferation keratins (K6, K16) in aged skin. In non-exposed skin taken from 6 old (mean age 70 years) and 5 young persons (mean age 37 years), longterm primary submersion cultures of keratinocytes did not show any significant differences as far as the classical parameters of growth behavior were concerned (i.e. plating efficiency, cell count, and labeled thymidine incorporation). In accordance with these findings, daily measurements of the thymidine kinase activity in the supernatants revealed discrete but not significant differences between keratinocytes in aged people and those in young persons. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Cell Division; DNA Replication; Female; Humans; Keratinocytes; Keratins; Male; Melanoma; Middle Aged; Skin Aging; Skin Neoplasms | 1989 |
Epithelial differentiation in synovial sarcoma. Correlation with histology and immunophenotypic expression.
The epithelial properties of the cells in six cases of synovial sarcoma, five biphasic and one monophasic, were examined. Epithelial cells formed well demarcated glandular nests with a multi- or single-layered lining, poorly defined nest-like clusters, or appeared as scattered single plump cells in a spindle-cell stroma. Keratinization was seen in multi-layered epithelia, and was suggested in single-layered epithelia from the presence of some enlarged eosinophilic cells. Immunohistochemically, epithelia lining glands showed reactivity for both low- and high-molecular-weight (MW) cytokeratins, and the reactions for both were strongest in keratinized cells. Clustered or single plump cells showed low-MW cytokeratin reactivity. All epithelial cells were negative for the largest cytokeratin (no. 1), and occasionally stained positively for vimentin. Spindle-shaped stromal cells usually stained positively for vimentin only. Type IV collagen was distributed linearly around well circumscribed epithelia, but not around poorly defined epithelia or plump cells. Epithelial membrane antigen was distributed linearly along glandular spaces and irregularly or granularly in clustered plump cells. The immunophenotypic epithelialization in synovial sarcoma was restricted, but showed considerable correlation with the histological grade of differentiation. Topics: Adult; Aged; Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Collagen; Desmin; Epithelium; Female; Humans; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Phenotype; S100 Proteins; Sarcoma, Synovial; Skin Neoplasms; Vimentin | 1989 |
Proliferating tricholemmal tumour with lymph node metastases.
A 42-year-old woman with a proliferating tricholemmal tumour (PTT) with regional lymph node metastases is reported. Histochemical studies showed evidence of tricholemmal keratinization. There was recurrence following excision and subsequently the patient developed lymph node metastases. Topics: Adult; Female; Humans; Keratins; Lymphatic Metastasis; Neoplasm Recurrence, Local; Scalp; Skin Neoplasms | 1989 |
Synthesis of cytokeratin 13, a component characteristic of internal stratified epithelia, is not induced in human epidermal tumors.
Human cytokeratin 13 is one of the most abundant intermediate filament (IF) proteins of many internal stratified epithelia and occurs, at least in certain cell cultures, in an O-glycosylated form binding the lectin, wheat germ agglutinin (WGA). As other groups have reported that, in the mouse, the synthesis of mRNA encoding the 47-kDa cytokeratin corresponding to human cytokeratin 13 is induced in epidermal keratinocytes during malignant transformation, we have examined the synthesis of cytokeratin 13 mRNA and protein in human epidermis and epidermal tumors, using specific cDNA probes and cytokeratin 13 antibodies. We isolated two different cDNA clones from the vulvar carcinoma cell line A-431, in which this protein is abundant: One clone seems to represent the entire mRNA, whereas the other is only a minor component and encodes a truncated cytokeratin 13 lacking most of the carboxy-terminal tail domain, probably a product of alternative, "incorrect" splicing. Comparison of the amino acid sequences with those of other cytokeratins revealed a high degree of conservation with respect to several other human type I cytokeratins, notably cytokeratin 15, and to the murine 47-kDa cytokeratin. When human epidermis and a series of benign and malignant epidermal tumors were examined with these cDNA probes and cytokeratin-13-specific antibodies we did not find an induction of expression in keratinocytes, normal or malignantly transformed, except for some scattered, sparse cytokeratin-13-positive cells and very low levels of cytokeratin 13 mRNA, detectable only with the highly sensitive polymerase chain reaction (PCR). We conclude that the gene(s) encoding cytokeratin 13 are not induced in human keratinocytes during epidermal carcinogenesis, in apparent contrast to reports of murine epidermal tumors, and we discuss possible explanations for this interspecies difference. Topics: Amino Acid Sequence; Base Sequence; Cell Line; DNA; Gene Expression Regulation; Humans; Immunohistochemistry; Keratins; Molecular Sequence Data; Nucleic Acid Hybridization; RNA, Messenger; Skin; Skin Neoplasms | 1989 |
Benign and malignant tumor stages in a mouse keratinocyte line treated with 7,12-dimethylbenz[a]anthracene in vitro.
Stable pre-tumorigenic, benign tumor and squamous cell carcinoma stages have been isolated after treatment of a cloned mouse keratinocyte line with 7,12-dimethylbenz[a]anthracene. Intraperitoneal injection and skin grafting of athymic nude mice were suitable for growth of these well-differentiated tumor cells, whereas subcutaneous injection was not. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma, Squamous Cell; Cell Line; Injections, Intraperitoneal; Keratins; Mice; Mice, Nude; Neoplasm Staging; Skin Neoplasms; Skin Transplantation | 1988 |
Recombinant gamma interferon increases the binding of peripheral blood mononuclear leukocytes and a Leu-3+ T lymphocyte clone to cultured keratinocytes and to a malignant cutaneous squamous carcinoma cell line that is blocked by antibody against the LFA-1
Because keratinocytes (KCs) express HLA-DR in a wide variety of skin diseases in which mononuclear leukocytes are observed in close apposition to KCs (i.e., graft-versus-host disease), and since gamma interferon (IFN-gamma) induces HLA-DR expression on KCs, we asked whether IFN-gamma treatment of KCs would influence the adherence of mononuclear leukocytes. When allogeneic peripheral blood mononuclear leukocytes (PBML) and a Leu-3+ T cell clone were coincubated with IFN-gamma-treated KCs (300 U/ml, 3 days), there was a marked increase in binding compared with nontreated KCs. Similar binding results were obtained using a cutaneous squamous carcinoma cell line (SCL-1) after IFN-gamma treatment. The IFN effect was relatively specific for IFN-gamma, as neither IFN-alpha nor -beta had any effect. Tumor necrosis factor exposure (500 U/ml, 3 days) increased the binding of the Leu-3+ T cell clone to both KCs and SCL-1 cells. Neutrophils displayed a less marked (but statistically significant) increase in binding to IFN-gamma-treated KCs. Using the Leu-3+ cell clone and SCL-1 cells, detailed kinetic analysis of the effect of IFN-gamma on binding was performed. The increased adherence between the cells began to appear after only 7 hours of treatment with r-IFN-gamma (300 U/ml) and reached a plateau at 48 hours, with significantly enhanced binding continuing for at least 48 hours after removal of IFN-gamma. The mechanism of binding was explored by preincubation of the PBML/Leu-3+ T cells with anti-LFA-1 (lymphocyte function-associated antigen) antibody (0.6-6.0 micrograms/ml), which totally inhibited the binding with no effect by anti-LFA-2 or -3 or class I or II antibodies despite documented binding of these antibodies to the cells. These results suggest that, after exposure to IFN-gamma, the ability of KCs to bind mononuclear leukocytes is strongly enhanced, and this adherence may be important in leukocyte trafficking in the skin as well as contributing to altered KC-leukocyte interaction, which may be of fundamental importance in a variety of skin disease. Topics: Antigens, Differentiation, T-Lymphocyte; Carcinoma, Squamous Cell; Cell Adhesion; Cells, Cultured; Clone Cells; Epidermal Cells; Humans; Interferon-gamma; Keratins; Leukocytes, Mononuclear; Neutrophils; Recombinant Proteins; Skin Neoplasms; Spectrometry, Fluorescence; T-Lymphocytes | 1988 |
Intraepidermal pilar epithelioma: a new dermatopathologic interpretation of a skin tumor.
An intraepidermally developed epithelial cell tumor, forming multiple nests, was examined to identify its cytologic characteristics. Histochemically, the tumor cells contained neither glycogen nor lipid substance. By N-(7-dimethylamino-3-methyl-4-coumarinyl)maleimide staining, the cytoplasm of the tumor cells in the periphery of each nest was rich in SH groups but not in SS linkages, whereas centrally located homogeneous tumor cells contained SS diffusely but no SH. The tumor cells showed no activity of phosphorylase and a weak activity of succinic dehydrogenase. Immunohistochemically, antihair keratin monoclonal antibodies specific for hair cells decorated the tumor cells, but carcinoembryonic antigen staining showed no positivity. Ultrastructurally, the tumor cells underwent a keratinization forming a fingerprint pattern of keratin filaments; however, membrane-coating granules and marginal bands were not formed. These intraepidermal tumor cells may have cytologic natures similar to those of hair cortical cells. The term intraepidermal pilar epithelioma is proposed as a diagnosis for this tumor. Topics: Cell Differentiation; Epidermis; Female; Hair; Humans; Immunohistochemistry; Keratins; Melanocytes; Middle Aged; Skin Neoplasms | 1988 |
Reaction of human keratinocytes with the monoclonal antibody anti-Leu-11: an immunohistologic study.
Biopsy specimens from skin of 99 patients with 26 different dermatoses and 17 specimens from normal skin were labeled with regard to the reactivity of keratinocytes with the monoclonal natural killer-associated antibody anti-Leu-11b by means of the avidin-biotin-peroxidase complex method. Reactivity occurred in 64.7% of the preparations from normal skin and in 84.8% of the preparations from diseased skin. The membranes of the subcorneal keratinocyte layers were labeled regularly. In some of the preparations cytoplasmic reactivity and labeling of the basement membrane zone occurred in addition. Most labeled preparations and the highest labeling intensities were shown in the skin tumors and in the infectious dermatoses. The biologic significance of this finding is discussed. Topics: Antibodies, Monoclonal; Antigens, Surface; Epidermal Cells; Epidermis; Humans; Immunohistochemistry; Keratins; Killer Cells, Natural; Lymphocyte Function-Associated Antigen-1; Skin Diseases; Skin Diseases, Infectious; Skin Neoplasms | 1988 |
Two cases of clear cell acanthoma: an immunohistochemical study.
Two cases of clear cell acanthoma are reported. The expression of carcinoembryonic antigen (CEA), involucrin and keratin proteins in the tumors was investigated immunohistochemically. In 1981, Penneys et al. reported that this tumor was not of sweat gland origin because of the absence of CEA. This study confirmed this, further, the pattern of positive reaction of involucrin also indicated that this tumor is not of sweat duct origin. Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Protein Precursors; Skin Neoplasms | 1988 |
Generation of multiple monoclonal antibodies for diagnostic use from a single hybridoma fusion.
BALB/c mice were exposed simultaneously to three nonrelated immunogens, myelin basic protein, uridyl-galactosyl transferase, and tissue obtained from a formalin-fixed, paraffin-embedded block containing a pilomatrixoma. Standard hybridoma techniques were used and antibody generation assayed using an unlabelled antibody biotin-avidin method with sections of human cerebellum, liver, and pilomatrixoma as the substrates. Using the above assay, clones were selected that secreted antibodies with selective specificities for each of the immunogens. By ELISA assay, the monoclonal antibodies reacting with cerebellum also reacted to the myelin basic protein preparation used as immunogen and the monoclonal antibody reacting to hepatocytes bound to the preparation of uridyl-galactosyl transferase used as immunogen. Our data suggests that the generation of monoclonal antibodies with a variety of diagnostic applications can be obtained from a single fusion following immunization with multiple nonrelated antigens, requiring considerably less laboratory cost and effort than would be required to obtain similar monoclonal antibodies in separate fusions. Topics: Animals; Antibodies, Monoclonal; Galactosyltransferases; Hybridomas; Keratins; Mice; Myelin Proteins; Skin Neoplasms | 1988 |
Transcriptional control of high molecular weight keratin gene expression in multistage mouse skin carcinogenesis.
Monospecific antikeratin antisera and specific complementary DNA probes were used to analyze expression of keratin genes in newborn mouse skin and skin papillomas and carcinomas by indirect immunofluorescence, immunoblotting, and in situ hybridization. Tumors were induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate. Type I epidermal keratin K14 protein (Mr 55,000) is found in all living layers of the newborn skin but is most abundant in the lower strata. K1 (Mr 67,000) and K10 (Mr 59,000) proteins are predominantly suprabasal and K1 is processed in the stratum corneum. Transcripts for K14 were confined largely to the basal cell layer by in situ hybridization. Transcripts for K1 and K10 were highly expressed in suprabasal cells including the granular cell layer. In benign tumors, distribution of K14 protein is similar to that in newborn skin, while the abundance of K1 and K10 appears to be somewhat reduced although the tissue distribution remains suprabasal. Transcription of K14 is aberrant in benign tumors and transcripts persist throughout much of the suprabasal cell layers. Transcripts of K1 and K10 are normally distributed in papillomas but grain density is less intense than in newborn epidermis. Keratin expression in carcinomas is highly disturbed. K14 protein and transcripts are highly expressed in all strata in carcinomas while protein and transcripts for K1 and K10 are essentially absent. These results suggest that papilloma cells fail to respond to or generate signals to regulate K14 expression in the differentiating suprabasal cell layers and may not fully express their suprabasal cell keratins. Carcinomas fail to express suprabasal cell keratins and this is regulated at the transcriptional level. The loss of suprabasal keratin expression may provide a marker for malignant conversion in the mouse skin carcinogenesis model. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Animals, Newborn; Carcinoma; Cell Transformation, Neoplastic; Female; Gene Expression Regulation; Genes; Keratins; Mice; Mice, Inbred Strains; Nucleic Acid Hybridization; Papilloma; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transcription, Genetic | 1988 |
Sequential development of aneuploidy, keratin modifications, and gamma-glutamyltransferase expression in mouse skin papillomas.
To elucidate the role and timing of expression of different premalignant and malignant markers in tumor promotion, we correlated alterations in keratin patterns and gamma-glutamyltransferase (GGT) expression with the chromosomal status of individual mouse skin papillomas. Papillomas were induced by 7,12-dimethylbenz[a]anthracene initiation and 12-O-tetradecanoylphorbol-13-acetate promotion. Individual tumors were randomly sampled at 20 and 35 weeks of promotion. Each tumor was cytogenetically analyzed and serial paraffin sections were used for GGT detection, immunoblotting, and immunohistochemistry studies. Monospecific antibodies elicited against keratins K1 (Mr 67,000) and K14 (Mr 55,000) were used to analyze keratin modifications. Most tumors at 20 weeks of promotion, although exhibiting aneuploidy, still presented high levels of the K1 differentiation-associated keratin. Later during promotion those tumors bearing the highest aneuploidy indexes were those that showed a marked decrease in or absence of the K1 protein. Furthermore, those same tumors with the highest levels of genomic alterations also exhibited foci of GGT activity. These results support the idea that the majority of papillomas under continuous promotion are progressing toward malignancy. Aneuploidy seems to precede detectable keratin modifications, and GGT activity appears to be the latest marker to be expressed. Topics: 9,10-Dimethyl-1,2-benzanthracene; Aneuploidy; Animals; gamma-Glutamyltransferase; Immunoenzyme Techniques; Keratins; Metaphase; Mice; Mice, Inbred Strains; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1988 |
Early signals for keratinocyte differentiation: role of Ca2+-mediated inositol lipid metabolism in normal and neoplastic epidermal cells.
Differentiation of cultured keratinocytes is regulated by the Ca2+ concentration of the culture medium. Below 0.1 mM Ca2+, a monolayer of basal cells is formed which fully differentiates in response to a rise in medium Ca2+. A role for protein kinase C in this differentiation program has been suggested because phorbol esters induce epidermal differentiation in cells grown in reduced Ca2+ medium, and exogenously added phospholipase C (which increases cellular diacylglycerol) mimics phorbol ester action. These findings suggested that the external Ca2+ signal may lead to protein kinase C activation via stimulation of cellular phospholipase C activity. The effect of the external Ca2+ signal on phospholipase C was studied in cultures prelabeled with [3H]-inositol. Within 2 min after addition of Ca2+ to 1 mM, an increase in inositol phosphates was measured. This correlated with a decrease in radiolabeled phosphoinositides, suggesting that these were the source of the increased inositol phosphates. After 3 h in 1 mM Ca2+ medium, each of the inositol phosphates remained increased to 130-140% of control levels. Inositol phosphate metabolism in neoplastic epidermal cells was quantitatively similar to normal cells in response to the Ca2+ signal. Stimulation of phosphatidylinositol (PIP) metabolism appears to be mediated by a rise in intracellular free Ca2+ because Ca2+ ionophores A23187 and ionomycin also cause a similar rise in inositol phosphate levels. Phorbol esters did not increase PIP turnover but instead stimulated phosphatidylcholine metabolism. The induction of epidermal differentiation by phorbol esters was enhanced by ionomycin, suggesting that both protein kinase C activation, elevation of intracellular calcium and PIP turnover were important components of the signal for epidermal differentiation. These results demonstrate that the second messenger system for Ca2+-mediated keratinocyte differentiation may be through a direct effect on phospholipase C activity. Topics: Animals; Calcimycin; Calcium; Cell Differentiation; Cells, Cultured; Choline; Epidermal Cells; Epidermis; Ethers; Inositol; Ionomycin; Keratins; Mice; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1988 |
Immunohistochemistry (S 100, KL 1) and human papillomavirus DNA hybridization on morbus Bowen and bowenoid papulosis.
In this study 55 paraffin embedded samples defined as Bowen's disease or bowenoid papulosis were investigated with antibodies against S 100 protein and keratins (KL 1). S 100-positive cells were quantified and related to defined section area of the epidermal compartment by computer-assisted image analysis. The density of S 100-positive cells was compared with normal skin and was particularly related to growth patterns and keratinization of the different lesions under study. S 100-positive dendritic cells were found to be reduced overall in bowenoid lesions when compared with normal skin. Lesions with high counts of S 100-positive dendritic cells most frequently showed a solitary growth pattern with highly conserved architecture and differentiation and no tendency to stromal invasion. In contrast, cases with low counts of S 100-positive cells very often showed multifocal development, a high degree of architectural disturbance and dedifferentiation. In this group, stromal invasion (cases of invasive carcinoma associated with Bowen's disease) was seen more often. Interestingly, this latter group of cases also revealed a peculiar keratin pattern. Frequently, the basal cell layer was decorated with KL 1 antibody, which usually recognizes only suprabasaly located keratinocytes. No differences between Bowen's disease and bowenoid papulosis were found in terms of densities of S 100-positive dendritic cells and keratin pattern. In our experience, extragenital Bowen's disease and genital Bowen's disease can not be distinguished on purely morphological grounds or with the immunocytochemical approach presented here. Interestingly, when employing in situ hybridization with HPV 16 probes three of seven samples of genital Bowen's disease harboured HPV 16 DNA, whereas six cases of extragenital disease were negative. Topics: Adult; Age Factors; Aged; Bowen's Disease; Carcinoma, Squamous Cell; DNA, Viral; Female; Genital Neoplasms, Female; Genital Neoplasms, Male; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Male; Middle Aged; Nucleic Acid Hybridization; Papillomaviridae; S100 Proteins; Skin Neoplasms | 1988 |
Immunologic characteristics of keratins in extramammary Paget's disease.
Six cases of extramammary Paget's disease were immunohistochemically investigated with several antikeratin monoclonal antibodies. Paget cells and surrounding epidermal keratinocytes were equally stained with an antikeratin monoclonal antibody, HKN-4, which recognizes a broad spectrum of keratins. However, Paget cells were clearly distinguished from the surrounding epidermal keratinocytes by HKN-2, which does not react with keratins of secretory cells but does react with keratins of ductal and myoepithelial cells of sweat glands and with epidermis and hair tissue of the normal skin. The HKN-2 did not bind to Paget cells, but the surrounding keratinocytes were positive. CK7, LE41, RGE53, and LP2K, which recognize simple epithelium-type keratins 7 (molecular weight [MW], 54,000; type II), 8 (MW, 52,500; type II), 18 (MW, 45,000; type I), and 19 (MW, 40,000; type I), respectively, stained Paget cells but not the surrounding keratinocytes. Two cases of Merkel cell carcinoma, examined as controls, showed positivity to LE41 and RGE53 but not to CK7 and LP2K. Since in the normal skin the secretory cells of sweat glands showed the same keratin expression as that of Paget cells, Paget cells of extramammary Paget's disease may be derived from or differentiate to the secretory cells of sweat glands. Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Penile Neoplasms; Skin Neoplasms; Sweat Glands; Vulvar Neoplasms | 1988 |
Cytokeratin analysis of pilomatrixoma: changes in cytokeratin-type expression during differentiation.
The various structural components of pilomatrixoma (calcifying epithelioma of Malherbe) were studied for the expression of hair-specific (trichocytic) cytokeratins as well as epithelial cytokeratins, using immunoperoxidase and immunofluorescence microscopy of frozen sections as well as two-dimensional gel electrophoresis and immunoblotting. Trichocyte-type cytokeratins were detected in only a minor subpopulation of basophilic cells but more prominently in most "transitional" cells as well as in "shadow" cells. In contrast, antibodies against certain epithelial cytokeratins (including antibody KA1 against cytokeratins of stratified squamous epithelia and antibodies against cytokeratin 19) revealed an extensive but heterogeneous staining of basophilic cells. In regions of squamoid cells, epithelial cytokeratins in an unusual pattern were found. An antibody against vimentin was negative on pilomatrixoma cells. An antibody against desmoplakins decorated true desmosomes in basophilic and transitional cells. Biochemically, trichocytic cytokeratin polypeptides as well as epithelial cytokeratins 5, 6, 14, 16, 17, and 19 were positively detected. These results provide evidence in support of the notion of a trichocytic differentiation and probably derivation of pilomatrixoma. According to the cytokeratin expression patterns the majority of pilomatrixoma cells resemble the normal hair cortex lineage but some enter a pathway of squamous cell differentiation. Topics: Adult; Aged; Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins; Male; Skin Neoplasms; Vimentin | 1988 |
Dyskeratosis and the dyskeratoses.
Darier first described dyskeratotic cells as infectious agents, but he later wrote that they were caused by abnormal keratinization. He grouped various inflammatory, infectious, and neoplastic skin diseases under the term "dyskeratoses." It is argued herein that the dyskeratotic cell and the so-called dyskeratoses have not been defined in a consistent manner because Darier's concepts were incorrect. Darier's dyskeratotic cell is classified here as one type of necrotic keratinocyte. Some conditions in which dyskeratotic and necrotic keratinocytes occur are described. Topics: Acantholysis; Cell Survival; Darier Disease; Epidermis; France; History, 19th Century; History, 20th Century; Keratins; Skin Diseases; Skin Neoplasms; Terminology as Topic | 1988 |
Use of monospecific antisera and cRNA probes to localize the major changes in keratin expression during normal and abnormal epidermal differentiation.
We report here the isolation and characterization of three antisera, each of which is specific for a single keratin from one of the three different pairs (K1/K10, K14/K5, K16/K6) that are differentially expressed in normal human epidermis and in epidermal diseases of hyperproliferation. We have used these antisera in conjunction with monospecific cRNA probes for epidermal keratin mRNAs to investigate pathways of differentiation in human epidermis and epidermal diseases in vivo and in epidermal cells cultured from normal skin and from squamous cell carcinomas in vitro. Specifically, our results suggest that: (a) the basal-specific keratin mRNAs are down-regulated upon commitment to terminal differentiation, but their encoded proteins are stable, and can be detected throughout the spinous layers; (b) the hyperproliferation-associated keratin mRNAs are expressed at a low level throughout normal epidermis when their encoded proteins are not expressed, but are synthesized at high levels in the suprabasal layers of hyperproliferating epidermis, coincident with the induced expression of the hyperproliferation-associated keratins in these cells; and (c) concomitantly with the induction of the hyperproliferation-associated keratins in the suprabasal layers of the epidermis is the down-regulation of the expression of the terminal differentiation-specific keratins. These data have important implications for our understanding of normal epidermal differentiation and the deviations from this process in the course of epidermal diseases of hyperproliferation. Topics: Amino Acid Sequence; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Cells, Cultured; Epidermal Cells; Epidermis; Humans; Immune Sera; Immunoassay; Immunohistochemistry; Keratins; Molecular Sequence Data; Nucleic Acid Hybridization; Psoriasis; RNA, Messenger; Skin Neoplasms; Tumor Cells, Cultured | 1988 |
A keratotic variant of malignant trichilemmoma.
Topics: Female; Histocytochemistry; Humans; Keratins; Middle Aged; Skin Neoplasms | 1988 |
Fibronectin gene expression by epithelial tumor cells in basal cell carcinoma: an immunocytochemical and in situ hybridization study.
Previous observations have demonstrated that fibronectin is deposited in high abundance in basal cell carcinoma stroma. In this study, the nature of fibronectin and the site of its synthesis were explored in 10 basal cell carcinomas of the nodulo-ulcerative type by immunocytochemistry and in situ hybridization. First, simultaneous localization of epithelial tumor cell islands and fibronectin epitopes was carried out by double immunofluorescence staining with monoclonal anti-cytokeratin antibodies and polyclonal fibronectin antibodies, the latter recognizing both the cellular and plasma types of the protein. Large amounts of fibronectin were deposited in the basal cell carcinoma stroma, with the highest concentration present in the immediate proximity of the epithelial cell islands. Immunofluorescence with a monoclonal anti-fibronectin antibody, which is directed against the ED-domain of cellular fibronectin and does not recognize the plasma type of fibronectin, revealed essentially the same staining pattern as that obtained with the polyclonal anti-fibronectin antibody. This observation suggested that fibronectin in BCC was predominantly of the cellular type. Second, in situ hybridizations, utilizing a human fibronectin specific cDNA, demonstrated that the highest concentration of fibronectin mRNA was found in the most peripheral cell layer of the epithelial tumor islands. The presence of fibronectin mRNAs in the tumor cells of the central regions of the islands, as well as within occasional stromal cells, was also noted. Thus, two lines of evidence suggest that the epithelial tumor cells are predominantly responsible for the synthesis and deposition of fibronectin in basal cell carcinoma. The presence of fibronectin may explain the characteristic biologic behavior of basal cell carcinomas, including low degree of metastatic potential and local destructive nature of the tumors. Topics: Autoradiography; Carcinoma, Basal Cell; Fibronectins; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Keratins; Nucleic Acid Hybridization; RNA, Messenger; Skin Neoplasms | 1988 |
Quantitation of primary in vitro clonogenic keratinocytes from normal adult murine epidermis, following initiation, and during promotion of epidermal tumors.
A quantitative in vitro assay for clonogenic epidermal cells from adult mice has been designed to focus on the cells from normal epidermis that are potential targets for carcinogens. Dorsal epidermal cells were isolated by trypsinization from groups of three to six CD-1 female mice with yields of 1.31 +/- 6.84 X 10(6) (average of n = 7; SD) viable epidermal cells per square centimeter of skin. Suspensions of single epidermal cells were plated at clonal density onto irradiated Swiss 3T3 cells. The cultures were maintained in high calcium SPRD-105 medium designed to support concomitant proliferation and terminal differentiation of keratinocytes from normal as well as carcinogen-exposed mice. Two weeks later, the dishes were fixed and stained with rhodanile blue, and epidermal colonies were counted. The average number of colonies from normal epidermis was 45 +/- 8.5 (n = 11; SD) per 10(4) cells plated for mice 9 to 69 weeks of age. To determine the effects of initiation on the number of clonogenic epidermal cells, groups of mice 8 weeks of age were treated topically with 200 nmol of 7,12-dimethylbenz(a)anthracene or acetone alone. The number of colonies in both treatment groups remained within the control (untreated) range at all intervals from 7 to 61 weeks after initiation. In contrast, the number of clonogenic cells from control as well as initiated epidermis remained elevated at 1 month following multiple in vivo treatments of skin with 12-O-tetradecanoylphorbol-13-acetate (TPA). The increase in the number of clonogens was always greater from initiated epidermis treated with TPA than from control epidermis treated with TPA. These results suggest that an increase in the clonogenic population was a consequence of promotion rather than initiation and are in agreement with a concomitant carcinogenesis experiment confirming the apparent irreversibility of initiation, the veritable absence of tumors in the absence of promotion, and the similarity of the tumor responses regardless of the age of the animal at initiation or the length of the delay interval between initiation and promotion. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Colony-Forming Units Assay; Epidermis; Female; Keratins; Mice; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tumor Stem Cell Assay | 1988 |
Systemic interferon-gamma therapy for cutaneous melanoma: subversive role of keratinocyte prostaglandin E production induced by interferon-gamma.
Topics: Epidermis; Humans; Interferon-gamma; Keratins; Melanoma; Prostaglandins E; Skin Neoplasms | 1988 |
Acantholytic acanthoma.
This article describes 31 examples of acantholytic acanthoma, a newly recognized, solitary, benign cutaneous tumor. Acantholytic acanthoma was typically an asymptomatic, keratotic papule or nodule. Patients ranged in age from 32 to 87 years (median 60 years); the ratio of men to women was 2:1; the most frequent clinical diagnosis was keratosis; and half of the growths were on the trunk of the body. Histologically, the lesions showed hyperkeratosis, papillomatosis, and acanthosis. Acantholysis was an outstanding finding in all cases; the patterns resembled pemphigus vulgaris, pemphigus vegetans, superficial pemphigus, or Hailey-Hailey disease, but no patient had evidence of any of these disorders. The term acantholytic is used because acantholysis is the outstanding histologic feature in these neoplasms; acanthoma was chosen because the growths are benign tumors of epidermal keratinocytes. The relationship of acantholytic acanthoma to acantholytic blistering disease is similar to that of solitary lichen planus-like keratosis to lichen planus and epidermolytic acanthoma to bullous congenital ichthyosiform erythroderma. Topics: Acantholysis; Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Epidermis; Female; Humans; Keratins; Male; Middle Aged; Papilloma; Skin Diseases; Skin Neoplasms | 1988 |
Pagetoid dyskeratosis: a selective keratinocytic response.
Pale cells that resemble those of Paget's disease have been found within apparently normal epidermis in a variety of benign papules. Although they have been considered an artifact, they show characteristic premature keratinization. In contrast to other dyskeratotic processes they mature into orthokeratotic squamae. The histopathologic, ultrastructural and immunocytochemical features of these cells are illustrated, and the differential diagnosis is reviewed. Topics: Adolescent; Adult; Child; Diagnosis, Differential; Epidermis; Female; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Paget Disease, Extramammary; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1988 |
Cellular differentiation and expression of matrix genes in type 1 neurofibromatosis.
The cellular heterogeneity of cutaneous tumors from nine patients with type 1 (von Recklinghausen's) neurofibromatosis was studied using several antigenic markers with special reference to focal heterotopic differentiation and interindividual variation. Furthermore, cells which actively express the genes for type I and III collagens and fibronectin, the major components of the abundant extracellular matrix of neurofibromas, were localized using in situ hybridizations. In eight of nine cases, the S-100 protein positive cells, i.e. Schwann-like cells, composed 60 to 80% of the total cell population. However, in one case, only about 40% of the cells were S-100 protein positive. The latter tumor was studied with respect to perineurial cell differentiation and stained with a mixture of two antibodies, directed against the S-100 protein and type IV collagen. In Schwann cells, the staining reaction for S-100 protein was observed in the nuclear region, whereas the staining reaction for type IV collagen was located peripherally, corresponding to the basement membrane zone covering the cells. The stromal cells which showed only the peripheral staining profile were considered to be neoplastic perineurial cells. Distinct structures with epithelial, endothelial, or smooth muscle cell differentiation were present within the benign tumors, as detected by immunostaining for cytokeratin, epithelial membrane antigen, factor VIII-related antigen and desmin, respectively. In situ hybridizations revealed a clearly detectable expression of type I procollagen genes in less than 10% and type III procollagen gene in less than 5% of the total cell population. Active synthesis of fibronectin was limited to the vascular walls, when examined by in situ hybridization, and antibodies to cellular fibronectin localized to the same areas. However, antibodies to plasma fibronectin produced a uniform staining reaction throughout the tumors suggesting that most of the fibronectin in neurofibromas is plasma-derived. The latter observation suggests that neurofibroma cells are freely accessible to various plasma proteins, including growth factors, which may influence the growth characteristics of these lesions. Topics: Antibodies, Monoclonal; Antigens; Antigens, Neoplasm; Cell Transformation, Neoplastic; Collagen; Desmin; DNA Probes; Endothelium; Epithelium; Epitopes; Extracellular Matrix; Factor VIII; Fibronectins; Gene Expression Regulation; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Mast Cells; Membrane Glycoproteins; Mucin-1; Muscles; Mutation; Neurofibromatosis 1; Nucleic Acid Hybridization; Phagocytes; Procollagen; RNA, Messenger; S100 Proteins; Schwann Cells; Skin Neoplasms; von Willebrand Factor | 1988 |
The characterization of squamous cell carcinoma induced by ultraviolet irradiation in hairless mice.
Squamous cell carcinomas (SCCs) induced by ultraviolet irradiation in hairless mice were characterized according to their growth, gross appearance and light and transmission electron microscopic features. SCCs arose directly from irradiated skin (ab initio) or progressed from pre-existing epidermal tumours and lesions. SCCs could be graded using guidelines established for human tumours. SCCs comprised 60.8% of the tumours examined. Of these, 35.6% were designated as grade 1, 27.7% as grade 2, 7.9% as grade 3 and 28.7% as grade 4. Spindle cell tumours suspected of being SCCs were included in grade 4. Grades 1, 2 and 3 could not be distinguished on the basis of growth and gross appearance. Those arising ab initio presented as either red, ulcerated lesions or as raised, white, verrucose lesions. Grade 4 SCCs that arose ab initio presented as rapidly growing, red, spherical lesions. Those that arose from pre-existing tumours or lesions had no characteristic appearance, and variable growth. Light microscopically, grade 4 SCCs with an obvious point of origin from epidermis or other epidermal tumours, and putative grade 4 SCCs without such a point of origin, were characterized commonly by spindle cells, pleomorphic giant or multinucleated cells and individual cell reticular fibres. Ultrastructurally, spindle cells, although poorly differentiated, were distinct from flibroblastic proliferations and had few tonofilaments or desmosomes, and were inconsistently surrounded by basal lamina-like material. On the basis of these characteristics, and despite inconclusive positivity with immunoperoxidase staining for keratin and prekeratin, it was concluded that these spindle cell tumours were most probably of identical squamous cell origin.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Animals; Antibodies; Carcinoma, Squamous Cell; Immunoenzyme Techniques; Keratins; Mice; Mice, Hairless; Microscopy, Electron; Neoplasms, Radiation-Induced; Protein Precursors; Skin Neoplasms; Ultraviolet Rays | 1988 |
Defective expression of a desmosome-related keratinocyte membrane antigen in squamous cell carcinoma.
Topics: Antibodies, Monoclonal; Antigens, Differentiation; Antigens, Neoplasm; Carcinoma, Squamous Cell; Desmosomes; Epidermal Cells; Epidermis; Fluorescent Antibody Technique; Gold; Humans; Immunohistochemistry; Keratins; Skin Neoplasms | 1988 |
Intermediate filament staining in the cytologic and histologic diagnosis of canine skin and soft tissue tumors.
Formalin-fixed histologic and acetone-fixed cytologic preparations from 87 surgically removed subcutaneous and soft tissue canine tumors were examined for immunoreactivity to cytokeratin, desmin, and vimentin. The avidin-biotin complex (ABC) technique demonstrated immunoreactivity in both preparations, but the intensity and specificity of the reactions were dependent on the primary antibody. Polyclonal antibodies to cytokeratin were more consistent in immunoreactivity than were polyclonal desmin or vimentin antibodies. The monoclonal antibody proved more satisfactory for demonstrating vimentin than the polyclonal antibody. Greater dilutions of primary antibodies may be used on cytologic preparations than on histologic sections. Evaluation of cytologic preparations may be inconclusive due to background staining, scant cellularity, or poor cytoplasmic preservation. Topics: Animals; Antibody Specificity; Avidin; Biotin; Desmin; Dog Diseases; Dogs; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Predictive Value of Tests; Prospective Studies; Skin Neoplasms; Soft Tissue Neoplasms; Vimentin | 1988 |
Growth and antigenic characteristics of basal cell carcinoma in culture.
Basal cell carcinomas (BCCs) were cultured using an explant method and compared with normal cultured skin. Immunohistochemical staining revealed reduced beta 2 microglobulin uptake by BCCs in frozen section, but normal staining of the tumours in culture. In culture, fibronectin was detected on the cell surface of normal keratinocytes but not on BCCs. The above differences may explain some of the behaviour of BCCs in vivo. Topics: Antigens, Neoplasm; beta 2-Microglobulin; Carcinoma, Basal Cell; Cell Division; Fibronectins; Humans; Immunoenzyme Techniques; Keratins; Skin Neoplasms; Tumor Cells, Cultured | 1988 |
Immunofluorescent localization of cytokeratin intermediate filaments as a means of defining the presence of recurrent basal cell carcinoma.
Intermediate filament subunits are reliable markers of cytogenetic origin for both normal and neoplastic cells. Immunohistochemical localization of cytokeratin filaments offers a sensitive and specific means of identifying basal or reserve cells when studying histologic sections of skin biopsy specimens. We have applied this technique on eighteen cases in which unequivocal diagnosis or recurrent basal cell carcinoma could not be rendered by conventional histologic techniques. In three of the cases studied, microscopic islands of basal cell carcinoma could be demonstrated by positive staining with cytokeratin antibodies. In the remaining fifteen cases, the possibility of recurrent basal cell carcinoma could be conclusively eliminated on the basis of negative staining with this antibody. Immunolabeling with tissue specific cytokeratin antibodies by indirect immunofluorescent examination may thus constitute a reliable and relatively simple technique that may serve to establish a definitive diagnosis in equivocal cases of suspected recurrent basal cell carcinoma. Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cytoskeleton; Diagnosis, Differential; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Neoplasm Recurrence, Local; Skin; Skin Neoplasms | 1988 |
[Neuroendocrine cancer of the skin (Merkel cell carcinoma) in childhood].
Topics: Adolescent; Biomarkers, Tumor; Carcinoma, Merkel Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Phosphopyruvate Hydratase; Skin; Skin Neoplasms | 1988 |
Keratinocyte- and tumor-derived inducers of collagenase.
Topics: Carcinoma, Basal Cell; Culture Media; Enzyme Induction; Enzyme Inhibitors; Epidermal Cells; Epidermis; Fibroblasts; Humans; Keratins; Microbial Collagenase; Skin Neoplasms; Tissue Extracts; Tissue Inhibitor of Metalloproteinases | 1988 |
Malignant progression of papilloma-derived keratinocytes: differential effects of the ras, neu, and p53 oncogenes.
The p117 keratinocyte cell line was derived in culture from chemically induced mouse papillomas. The benignly transformed nature of these cells was demonstrated by their ability to re-form benign papillomas when grafted back onto the animal. Retroviral vectors were used to introduce into the p117 cells three distinct oncogenes: v-Ha-ras, p53, and neu. All three oncogenes were able to induce tumorigenic conversion of the p117 keratinocytes when assayed by subcutaneous injection into nude mice. However, grafting the oncogene-transformed cells onto the back of the mouse revealed important differences in the ability of the three oncogenes to induce a fully malignant phenotype. While the ras-transformed papilloma cells formed aggressive carcinomas, p53 and neu transformation yielded an intermediate phenotype, with formation of large exophytic tumors, not yet invasive but with highly dysplastic features remarkably similar to those of in situ carcinomas. These findings establish a homologous, genetically modifiable cell system in which various stages of malignant transformation can be directly compared. Topics: Animals; Carcinogenicity Tests; Cell Line, Transformed; Cell Transformation, Neoplastic; Epidermal Cells; Epidermis; Genes, ras; Keratins; Mice; Mice, Nude; Oncogenes; Papilloma; Skin Neoplasms; Skin Transplantation | 1988 |
Molecular cloning of mouse epidermal cystatin A and detection of regulated expression in differentiation and tumorigenesis.
A gamma gt 11 cDNA expression library representing mouse epidermis mRNA was screened with polyclonal rabbit antiserum directed against 10-13 kDa epidermal antigens that had previously been shown to be regulated during epidermal differentiation. A cDNA clone was detected and isolated and its identity as the coding sequence for one of the antigens was confirmed by translation of hybrid-selected mRNA from mouse epidermis. The cDNA sequence predicted a peptide homologous to the reported sequence of rat epidermis cystatin A, a thiol proteinase inhibitor. This identification was confirmed by cross-reactivity of the gamma clone fusion protein with authentic antiserum to rat epidermis cystatin A. Southern gel analysis showed that mouse DNA may contain several closely related genes homologous to the cystatin probe. An mRNA of about 0.6 kb from epidermis and cultured mouse epidermal cells hybridized with the cystatin probe on northern analysis. The abundance of the message was high in cultured basal cells and was selectively diminished by inducing terminal differentiation in culture with an elevated Ca2+ concentration in the medium. Cystatin message was abundant in chemically induced mouse skin papillomas but reduced in carcinomas. In epidermis, mRNA was localized to the less differentiated basal and lower spinous layers by in situ hybridization. Regulation of expression of cystatin A in epidermis and tumors suggests that it may be important in the control of normal keratinocyte proliferation and differentiation and in malignant conversion. Topics: Amino Acid Sequence; Animals; Base Sequence; Blotting, Southern; Cell Differentiation; Cloning, Molecular; Cross Reactions; Cysteine Proteinase Inhibitors; Epidermal Cells; Gene Expression Regulation; Keratins; Mice; Mice, Inbred Strains; Nucleic Acid Hybridization; Protease Inhibitors; RNA, Messenger; Skin Neoplasms | 1988 |
TGF alpha stimulates growth of skin papillomas by autocrine and paracrine mechanisms but does not cause neoplastic progression.
To investigate the role of transforming growth factor alpha (TGF alpha) in tumor development, we introduced the human TGF alpha (hTGF alpha) cDNA into cultured primary mouse epidermal cells or papilloma cells using a replication-defective retroviral vector and analyzed skin grafts constructed with such cells. Expression of the exogenous gene was confirmed by detection of hTGF alpha mRNA by northern RNA blot analysis, and the secreted hTGF alpha was measured by ELISA of culture supernatants. Tumor cells expressing hTGF alpha produced benign tumors (papillomas), which were 1.5- to 2-fold larger than tumors of parental cells when tested as skin grafts on nude mice. Grafts of normal cells that expressed hTGF alpha produced normal skin. When mixtures of parental tumor cells and normal mouse keratinocytes were grafted to nude mice, papilloma formation was suppressed and tumors that did form were small. Grafts of hTGF alpha-producing papilloma cells combined with either normal epidermal cells or hTGF alpha-producing epidermal cells yielded large tumors. Mixed grafts containing keratinocytes expressing hTGF alpha and parental papilloma cells also produced large tumors. While the tumor size was substantially increased by hTGF alpha expression, the tumors that developed in all groups were histologically benign and reached a stable size 4-5 wk after grafting. These results indicate that expression of hTGF alpha by either tumor cells (autocrine) or adjoining normal cells (paracrine) can stimulate tumor growth, particularly when tumor growth is suppressed by normal tissue. However, expression of this growth factor did not appear to influence tumor progression directly. Topics: Animals; Blotting, Northern; Blotting, Southern; Cell Line; Disease Models, Animal; Keratins; Mice; Mice, Nude; Neoplasm Transplantation; Papilloma; RNA, Messenger; Skin; Skin Neoplasms; Transfection; Transforming Growth Factors | 1988 |
Enhanced G2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture.
A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containing the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation. Topics: Animals; Carcinogens; Cell Transformation, Neoplastic; Cells, Cultured; Chromatids; Chromosome Aberrations; DNA Repair; Humans; Interphase; Keratins; Mice; Oncogenes; Radiation Tolerance; Skin Neoplasms; Transfection | 1987 |
Cytokeratin distribution in Merkel cell tumor of the skin.
Topics: Cytoskeleton; Humans; Keratins; Skin Neoplasms | 1987 |
Expression of keratin proteins in deeply invasive basal and squamous cell carcinoma: an immunohistochemical study.
The expression of certain classes of keratin is associated with cell maturation and differentiation. During cell transformation and tumor development, the cell specificity of intermediate filament, keratin, is largely conserved. Taking advantage of this, we utilized monoclonal antikeratin immunohistochemical techniques to examine basal and squamous cell carcinomas as they became deeply invasive. Dyskeratotic keratinocytes and keratin pearls in squamous cell carcinomas (SCCs) stain with antikeratin antisera to larger keratins (65-67 Kd). At the deep tumor margins, SCCs no longer express larger keratins but retain expression of 50, 58 Kd, which are markers of keratinocytes derived from stratified squamous epithelial cells. This selective loss of expression of keratin polypeptide markers of differentiation in SCC is associated with progressively more aggressive biologic behavior as the tumor invades deeper structures such as muscle and bone. Recurrent basal cell carcinoma (BCC) which was of the nodular type when first excised, shows features of morphea-like BCC and of aggressive growth patterns at the deep invasive margin. At these deep margins, some tumors express markers of keratinization (65-67 Kd). While tumor cells retain the specificity of the intermediate filament, keratin, the individual cells express products of differentiation as measured by keratin expression independently of their cytologic atypia. At the deeper invasive margin of the tumor, the neoplastic cells synthesize keratin proteins in an unpredictable fashion. Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Invasiveness; Skin Neoplasms | 1987 |
Immunohistochemical demonstration of simple epithelia-type keratin intermediate filament in a case of Merkel cell carcinoma.
A case of Merkel cell carcinoma that developed on the right cheek of a 77-year-old woman is reported. The diagnosis was ultrastructurally made by demonstrating dense-core granules in the cytoplasm of the tumor cells. Immunohistochemically, the tumor cells were shown to possess simple epithelia-type keratin intermediate filaments, but no neurofilaments. This finding was in accordance with that obtained on normal Merkel cells. No bioactive peptides examined could be detected in the tumor cells. Typing of intermediate filaments in tumor cells may be one of the important markers, along with the ultrastructural findings, in diagnosing Merkel cell carcinoma. Topics: Adenocarcinoma; Aged; Cheek; Cytoskeleton; Epithelium; Female; Fluorescent Antibody Technique; Histocytochemistry; Humans; Intermediate Filaments; Keratins; Skin Neoplasms | 1987 |
Diversity of cytokeratins in carcinomas.
Topics: Adenocarcinoma; Breast Neoplasms; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cytoskeleton; Diagnosis, Differential; Epithelium; Female; Gastrointestinal Neoplasms; Humans; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Lung Neoplasms; Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms | 1987 |
Recombinant gamma interferon induces HLA-DR expression on squamous cell carcinoma, trichilemmoma, adenocarcinoma cell lines, and cultured human keratinocytes.
We investigated the effects of recombinant human gamma interferon on the induction of HLA-DR expression by two human squamous cell carcinoma, three trichilemmoma, one eccrine carcinoma, two adenocarcinoma cell lines, and cultured human keratinocytes in vitro. None of eight epithelial cell lines or keratinocytes expressed HLA-DR without gamma interferon treatment. In contrast, pure gamma interferon (500 IU/ml, 72-h treatment) induced HLA-DR expression on 1/2 squamous cell carcinoma, 3/3 trichilemmoma, 2/2 adenocarcinoma cell lines, and 4/4 keratinocyte cell lines, as determined using a fluorescence-activated cell sorter. A maxillary squamous cell carcinoma line and an eccrine carcinoma cell line failed to express HLA-DR with gamma interferon treatment; however, the growth of cells was inhibited by gamma interferon treatment. By indirect immunoperoxidase techniques, tumor cells such as Bowen's disease and squamous cell carcinoma were found to express HLA-DR. Since HLA-DR expression has been shown to be important for various immune responses, these findings suggest that gamma interferon plays important roles in various immune-related skin diseases. Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Division; Cell Line; Epidermis; Hair; Histocytochemistry; HLA-D Antigens; HLA-DR Antigens; Humans; Immunochemistry; Interferon-gamma; Keratins; Recombinant Proteins; Skin Neoplasms | 1987 |
Cell proliferation kinetics of cultured human keratinocytes and fibroblasts measured using a monoclonal antibody.
Measurements of cell cycle kinetics using an immunoperoxidase method employing monoclonal anti-bromodeoxyuridine (BrdU) antibody were compared with an autoradiographic method using [3H]-thymidine. The methods were applied to epithelial cells grown from explants of normal skin and basal cell carcinoma (BCC), and to fibroblasts from normal skin, hypertrophic scar and keloid. In normal keratinocytes the number of peroxidase-positive cells was higher than the number incorporating [3H]-thymidine, because of the presence of labelled cells in the centre of the explants in the former. The epithelial cells from BCC gave a mean (+/- SD) of 4.9 +/- 1.2% peroxidase-positive cells, while no cells were labelled with [3H]-thymidine. In dermal fibroblasts from normal skin and hypertrophic scar the percentages of peroxidase-positive cells did not differ significantly from the [3H]-thymidine labelling indices. The immunological method has advantages over [3H]-thymidine autoradiography in that it avoids radioactive material and the proportion of cells labelled by the two methods is the same. Topics: Antibodies, Monoclonal; Autoradiography; Bromodeoxyuridine; Carcinoma, Basal Cell; Cell Division; Culture Techniques; Epidermis; Fibroblasts; Humans; Immunoenzyme Techniques; Keratins; Kinetics; Skin Neoplasms | 1987 |
Differential expression of class II alloantigens by keratinocytes in disease.
The purpose of this study was to determine whether keratinocytes in certain disease states such as cutaneous T-cell lymphoma and lichen planus, express HLA-DR antigens (corresponding to the murine I-E antigens) only or whether they are also capable of expressing HLA-DQ antigens (analogues of the murine I-A antigens). Cryostat sections from 11 biopsies from cutaneous T-cell lymphoma and from 11 lichen planus biopsy specimens were submitted to indirect immunofluorescence and a 4-step immunoperoxidase method. This consists of applying monoclonal antibodies recognizing HLA-DR and HLA-DQ molecules and the intracytoplasmic invariant chain of the class II molecules. In 8 of the 11 cutaneous T-cell lymphoma specimens and in 3 of the 11 lichen planus biopsies concomitant expression of HLA-DR and HLA-DQ molecules by keratinocytes was detectable with the immunoperoxidase method. However, with the indirect immunofluorescence technique HLA-DQ antigens on keratinocytes could not be detected. The simultaneous expression of surface-bound HLA-DR antigens and intracytoplasmic gamma-chains was demonstrable in all cases investigated and with both the immunohistologic methods applied. Topics: Epidermis; Histocytochemistry; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunochemistry; Isoantigens; Keratins; Lichen Planus; Lymphoma; Skin Neoplasms; T-Lymphocytes | 1987 |
Merkel cell tumor coexpressing cytokeratin and neurofilament proteins.
Whorled filaments 10 nm in width were identified by anti-intermediate filaments antibodies in a Merkel cell tumor from a 52-year-old man. Immunohistochemical tests revealed that the tumor was stained with anti-keratin antibody and antibodies against the 68-kd and 200-kd subunits of neurofilament proteins but not antibody against the 150-kd subunit. This is the first reported case of Merkel cell tumor expressing a 200-kd subunit of neurofilament proteins. Topics: Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Male; Microscopy, Electron; Middle Aged; Neurofilament Proteins; Skin Neoplasms | 1987 |
Cytokeratin expression in smooth muscle and smooth muscle tumours.
The expression of cytokeratin intermediate filaments by a tumour has been accepted as evidence of an epithelial origin. Although there have been anecdotal reports of cytokeratin expression within tissues and neoplasms of non-epithelial origin, particularly muscle, there have been no comprehensive studies of its frequency and distribution. In order to investigate this we have studied 51 cases of normal smooth muscle and benign and malignant smooth muscle tumours using a panel of monoclonal antibodies against a range of intermediate filaments (cytokeratins, desmin and vimentin). Cytokeratin expression was noted overall in 50% of normal, benign and malignant smooth muscle tissues. Such expression tended to have a focal or patchy distribution. No case expressed cytokeratins in the absence of both desmin and vimentin. The implication of these findings for diagnostic immunocytochemistry is that intermediate filaments alone are not completely reliable markers of tumour histogenesis and should be used as part of a larger panel of monoclonal antibodies. Topics: Desmin; Female; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Keratins; Leiomyoma; Leiomyosarcoma; Muscle, Smooth; Myometrium; Neoplasms, Muscle Tissue; Skin Neoplasms; Uterine Neoplasms; Vimentin | 1987 |
Calcifying epithelioma of Malherbe with ossification. Special reference to lectin binding and immunohistochemistry of ossified sites.
Lectin binding sites and immunohistochemically detectable fibronectin and carbonic anhydrase II (CA II) were examined in induced bone structure of calcifying epithelioma of Malherbe. Pathological features of ossification were particularly evident in the border zone between tumor epithelium and stroma, and epithelial foci adjacent to sites of bone formation were conspicuously basophilic. The use of lectin binding in these foci coincided with the basophilic epithelial zones: Con A, RCA-1, PNA, SBA, and WGA bound strongly, indicating the presence of glucose (Glu), mannose (Man), galactose (Gal), N-acetyl-D-galactosamine (GalNAC), and N-acetyl-D-glucosamine (GlcNAC). Fibronectin was also detected in the same epithelial-mesenchymal interacting layers as the positive lectin-binding sites. Staining for CA II was strongly positive in giant cells and in epithelial zones in the bone-inducing areas. The bond induction mechanism in the stromal tissue of calcifying epithelioma of Malherbe may initially involve the action CA II in the epithelial-mesenchymal interacting zone, which then brings about ossification of the matrix which is fibronectin-positive and rich in lectin-binding sites. Topics: Adult; Binding Sites; Carbonic Anhydrases; Fibronectins; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lectins; Male; Middle Aged; Ossification, Heterotopic; Receptors, Mitogen; Skin Neoplasms | 1987 |
Immunohistochemical localization of ornithine decarboxylase in human skin.
Topics: Animals; Cell Division; Cells, Cultured; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Ornithine Decarboxylase; Psoriasis; Skin; Skin Neoplasms; Ultraviolet Rays | 1987 |
Chondroid syringoma (mixed tumor of the skin). A clinicopathological study of 13 cases.
The clinicopathology of 13 cases of chondroid syringoma were examined. The ages of the patients ranged from 26 to 86 years, with an average of 48 years. There were eight males and five females. Ten tumors out of the thirteen appeared on the face. Only one patient out of ten was suspected of recurrence in follow-up information. Histologically, all tumors consisted of epithelial cells, chondroid or myxoid matrix, and other strumal elements. The tumors were histologically classified into two types; twelve tumors had tubular and cystic lumina lined by two layers of epithelial cells, and only one case had small lumina lined by only a single layer. By an immunohistochemical study with a PAP method, positive stainings of keratin were observed in all cases, and S-100 protein in all but one. Ultrastructurally, the tumor cells showed features of an epithelial cell. Some ultrastructural differences were noted between two types of chondroid syringoma. Type I tumor cells had many tonofilaments in cytoplasm, but cytoplasmic filaments in type II were of the intermediate-type. Topics: Adenoma, Sweat Gland; Adult; Aged; Aged, 80 and over; Cell Nucleus; Cytoskeleton; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged; Organoids; Recurrence; S100 Proteins; Skin Neoplasms | 1987 |
The cellular composition of adenoid cystic carcinoma. An immunohistochemical study.
To investigate the cellular differentiation of adenoid cystic carcinomas (ACC), a comparative immunohistochemical study of 12 normal salivary glands and eight specimens of ACC was performed. Antibodies were used against S100 protein (S), keratins (K) of various molecular weights, vimentin (V), muscle-specific actin (A), epithelial-membrane antigen, human milk fat globules, and collagen type IV. A panel of four of these antibodies (SKVA) was identified as the most helpful in characterizing cells in normal salivary glands and ACC. The immunophenotypes depended on the histologic patterns of ACC. Cells in morphologically recognizable duct structures in the cribriform and trabecular areas expressed a phenotype similar to that of the intercalated duct. Cell layers around pseudocysts and occasional cellular islands had an immunophenotype suggesting myoepithelial-cell differentiation. The most clear cut epithelial/myoepithelial bilaminar differentiation was present in areas with a trabecular pattern, in which the layers facing the stroma and the central ductal elements had SKVA phenotypes of myoepithelial and ductal differentiation, respectively. In areas with a reticular pattern, most of the cells showed ductal differentiation. Many of the cells in the cribriform and basaloid regions were immunophenotypically undifferentiated. These results indicate that ACC consists of undifferentiated cells and of cells that are differentiating toward ducts, predominantly intercalated ducts, and toward myoepithelium. These findings support previous observations by electron microscope. Topics: Actins; Antibodies; Breast Neoplasms; Bronchial Neoplasms; Carcinoma, Adenoid Cystic; Cell Differentiation; Collagen; Histocytochemistry; Keratins; Lymphatic Metastasis; Membrane Proteins; Molecular Weight; Mucin-1; Phenotype; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Skin Neoplasms; Submandibular Gland Neoplasms; Vimentin | 1987 |
Specific alterations in keratin biosynthesis in mouse epidermis in vivo and in explant culture following a single exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate.
Treatment of mouse skin with a single dose of the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) causes dramatic alterations in the biosynthesis of specific epidermal keratins. TPA was applied either topically to the skin of mice or added to the culture medium of skin explants maintained in vitro. Twenty-four h after exposure, skin samples were pulse labeled with [35S]methionine, and epidermal proteins were extracted and resolved by two-dimensional gel electrophoresis. In whole animals, TPA caused a marked decrease in the biosynthesis of the Mr 67,000 (basic) and 59,000 (acidic) keratins, specific markers for suprabasal differentiation in the epidermis. In addition, the synthesis of an acidic keratin of Mr 48,000 and a basic keratin of Mr 62,000 was also decreased. Concomitantly, TPA caused an increase in the synthesis of a basic keratin of Mr 60,000 and acidic keratins of Mr 52,000 and 49,000, markers for proliferating cells and primary epidermal cell cultures. The normal pattern of keratin synthesis observed in explants from normal skin was similar to that observed in skin samples from animals treated with TPA, except that synthesis of the Mr 67,000 basic keratin subunit was maintained. The addition of TPA to culture medium containing the skin explants resulted in a dose-dependent decrease in the synthesis of this keratin. Furthermore, resulting patterns of keratinization were identical to epidermis treated with TPA in vivo. These results suggest that a single acute exposure to TPA alters normal differentiation of mouse epidermal cells in vivo while causing a pronounced basal cell hyperproliferation. This response can be reproduced following TPA exposure to skin explants in culture, suggesting that the changes in keratinization observed are independent of the animal. Specific keratins modulated during TPA-induced hyperplasia may serve as marker proteins for aberrant epidermal cell growth and differentiation leading to the development of neoplasia. Topics: Animals; Cell Differentiation; Cell Division; Electrophoresis, Polyacrylamide Gel; Epidermis; Female; Keratins; Mice; Molecular Weight; Organ Culture Techniques; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1987 |
[An immunohistochemical study on basal cell epithelioma using anti-keratin monoclonal antibodies].
Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Fluorescent Antibody Technique; Humans; Keratins; Microscopy, Electron; Skin; Skin Neoplasms | 1987 |
[Neuroendocrine carcinoma (Merkel cell tumor) in the head and neck area].
The neuroendocrine carcinoma of the skin has its histogenetic origin in Merkel cells and a preference in head and neck area in the seventh decade of life. The definitive diagnosis can be made with a combination of electron microscopy and immunohistochemistry. Merkel cell carcinoma is a primary cutaneous neoplasma and is rarely found on the lips or gingiva. Operation and radiation are the therapy of choice. The value of an additional antineoplastic chemotherapy in the treatment of Merkel cell carcinoma is still controversial. Although long survival times had been described in literature the occurrence of local relapses and metastases demands for frequent controls. Topics: Aged; Biopsy; Female; Head and Neck Neoplasms; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Lymph Node Excision; Lymphatic Metastasis; Microscopy, Electron; Neurofilament Proteins; Skin Neoplasms | 1987 |
Immunohistochemical study of epidermal Langerhans cells and dermal dendritic cells in benign and malignant skin lesions characterized by a dermal lymphoid infiltrate consisting either of B-cells or T-cells.
Skin biopsies from 43 patients with a rather dense dermal lymphoid infiltrate of either inflammatory or neoplastic nature have been investigated. We studied the number, distribution and immunophenotype of epidermal Langerhans cells and dermal dendritic cells. As previously reported, differences in epidermal Langerhans cell and dermal dendritic cell numbers between skin biopsies with a B-cell infiltrate and skin biopsies with a T-cell infiltrate were found, dendritic cells being more numerous in the latter. The main finding of this study was an uneven distribution of epidermal Langerhans cells and dermal dendritic cells in skin biopsies with a T-cell infiltrate: in skin lesions with an inflammatory lymphoid infiltrate, small clusters of epidermal and dermal dendritic cells admixed with T-lymphocytes (predominantly T-helper/inducer cells) and small blood vessels were present at areas of exocytosis. In skin lesions with a neoplastic lymphoid infiltrate larger, more loosely arranged aggregates of dendritic cells and T-cells were seen. These cell aggregations composed of activated (inflammatory or neoplastic) T-cells and dendritic cells may represent the cutaneous homologue of the secondary T-nodule in the lymph node. Both types of cell aggregates may correspond to the dendritic cell-T cell clusters observed in in vitro induced immune responses. Topics: B-Lymphocytes; Dendritic Cells; Histocytochemistry; HLA-DR Antigens; Humans; Immunochemistry; Keratins; Langerhans Cells; Lymphocytes; Skin; Skin Diseases; Skin Neoplasms; T-Lymphocytes | 1987 |
Basal cell tumour with eccrine differentiation (eccrine epithelioma)--a histochemical and immunocytochemical analysis of a case.
Topics: Adult; Antibodies, Neoplasm; Carcinoma, Basal Cell; Female; Humans; Keratins; Skin Neoplasms | 1987 |
Mouse keratinocytes derived from initiated skin or papillomas are resistant to DNA strand breakage by benzoyl peroxide: a possible mechanism for tumor promotion mediated by benzoyl peroxide.
Alkaline elution was used to examine DNA single-strand breaks in cultured normal and carcinogen-altered mouse keratinocytes exposed to 12-O-tetradecanoyl phorbol-13-acetate and benzoyl peroxide. Seven cell lines derived from carcinogen-induced mouse skin papillomas and three cell lines derived from N-methyl-N'-nitro-N-nitrosoguanidine-treated non-tumor bearing mouse skin were resistant to phorbol ester-mediated DNA strand breaks after 6 or 24 h. Normal keratinocytes sustained strand breaks after 24 h but not after 6 h. Benzoyl peroxide induced extensive strand breaks in normal keratinocytes at both 6 and 24 h, and this was associated with marked cytotoxicity. In contrast, 9 of 10 cell lines showed complete or partial resistance to strand breaks following benzoyl peroxide exposure. It is proposed that differential resistance to DNA strand breaks and cytotoxicity among normal and carcinogen-altered keratinocytes provides the biological basis for the promoting action of benzoyl peroxide. Furthermore, sublethal DNA damage in preneoplastic or neoplastic keratinocytes may account for the potency of benzoyl peroxide in causing malignant conversion. Topics: Animals; Benzoyl Peroxide; DNA Damage; Keratins; Methylnitronitrosoguanidine; Mice; Mice, Inbred BALB C; Papilloma; Peroxides; Skin; Skin Neoplasms | 1987 |
Immunohistochemical distinction of Paget's disease from Bowen's disease and superficial spreading melanoma with the use of monoclonal cytokeratin antibodies.
The differentiation of Paget's disease from Bowen's disease and Pagetoid superficial spreading melanoma may represent diagnostic difficulties. The special stains used in their differential diagnosis are nonspecific and not always sensitive. Therefore, the expression of cytokeratins of different molecular weights (54, 57, and 66 kilodaltons [kD]) was studied in 26 intraepithelial neoplasms in formalin-fixed paraffin-embedded tissues with the use of an avidin-biotin complex (ABC) method with monoclonal cytokeratin antibodies. These included 9 cases of Paget's disease, 11 cases of Bowen's disease, and 6 cases of Pagetoid superficial spreading melanoma. Paget cells from vulva and breast were always positive for 54-kD cytokeratin, variable for 57-kD cytokeratin, and negative for 66-kD cytokeratin. The neoplastic cells in all 11 cases of Bowen's disease were stained for 57-kD and 66-kD cytokeratins but not for 54-kD cytokeratin. The neoplastic cells in all cases of melanoma did not express any of the cytokeratins studied. The results indicate that antibodies to cytokeratins of different molecular weights may be used as a diagnostic tool in the distinction of Paget's disease from Bowen's disease and melanoma. Topics: Antibodies, Monoclonal; Bowen's Disease; Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Squamous Cell; Female; Humans; Keratins; Melanoma; Paget Disease, Extramammary; Paget's Disease, Mammary; Skin; Skin Neoplasms; Vulvar Neoplasms | 1987 |
Multiple clear cell acanthomas. A clinical, histological, and ultrastructural report.
A case of multiple clear cell acanthomas in a 64-year-old woman is reported. The clinical and histological findings of this rare entity are consistent with the hypothesis that clear cell acanthomas are benign epidermal tumors. An ultrastructural study was performed with special emphasis on the melanocytic-keratinocytic interaction. Topics: Epidermis; Female; Histocytochemistry; Humans; Keratins; Leg; Melanocytes; Microscopy, Electron; Middle Aged; Neoplasms, Multiple Primary; Papilloma; Skin; Skin Neoplasms | 1987 |
Anti-keratin monoclonal antibody against basal cell epithelioma keratin: BKN-1.
Topics: Antibodies, Monoclonal; Carcinoma, Basal Cell; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Skin Neoplasms | 1987 |
Immunohistochemical observations on binding of monoclonal antibody to epithelial membrane antigen in epithelial tumors of the oral cavity and skin.
A total of 211 cases of benign and malignant tumors of epithelial origin were studied by the immunoperoxidase method to determine the distribution profile of epithelial membrane antigen (EMA) with the use of monoclonal antibody. Normal epithelial cells in the oral mucosa and skin were usually negative for EMA staining, as were epithelial cells in hyperplastic lesions and papillomas. Paget cells and tumor cells of Bowen's disease (carcinoma in situ) demonstrated a high incidence of EMA positivity, whereas the frequency in basal cell carcinoma was unexpectedly low. Squamous cell carcinomas revealed positive EMA staining of cytoplasmic membranes, and the antigen was also present in keratinized areas. EMA expression in squamous cell carcinoma generally showed a high incidence (85%) and was higher in keratinized lesions than in unkeratinized or less well-differentiated neoplasms. EMA distribution could be classified into two forms: one in which the cytoplasmic membranes demonstrate positivity and in which a positive cytoplasmic pattern is found in parakeratinized cells in malignant foci. Topics: Antibodies, Monoclonal; Antigens; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mouth Mucosa; Mouth Neoplasms; Mucin-1; Protein Precursors; Skin Neoplasms | 1987 |
Malignant progression of an SV40-transformed human epidermal keratinocyte cell line.
Human foetal keratinocytes were transfected with a recombinant plasmid (pSV6-1) which contained an origin defective SV40 genome. The resulting transformed cell line had many properties in common with previously described SV40-transformed keratinocytes, including expression of simple epithelial-type keratins. It was non-tumourigenic in nude mice at early passages, forming small benign cysts, however, after approximately 46 in vitro passages, these transformed keratinocytes formed invasive squamous cell carcinomas in athymic nude mice. Several in vitro changes were associated with this acquisition of tumourigenicity (a) an alteration in cellular morphology, (b) development of a cytogenetically marked clone and (c) loss of cell surface fibronectin. The loss of fibronectin was also observed in vivo; cysts formed by SV6-1 Bam/HFK produced human fibronectin whereas tumours did not, although both tumours and cysts were laminin- and keratin-positive. These results indicate that the spontaneous development of secondary events in immortalised human cells may lead to the acquisition of a malignant phenotype. Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Transformed; Cell Transformation, Neoplastic; Cell Transformation, Viral; Epidermis; Fibronectins; Fluorescent Antibody Technique; Humans; Karyotyping; Keratins; Male; Mice; Mice, Nude; Neoplasm Transplantation; Simian virus 40; Skin Neoplasms; Transfection | 1987 |
Keratinocyte T6 antigen expression after PUVA therapy.
We report T6 antigen expression on keratinocytes in 11 cutaneous T lymphomas treated by PUVA therapy. This staining was absent before treatment. T6 reactivity was strictly limited to cell membrane. The nature of this expression is discussed, and it is suggested that it could be attributed to a passive diffusion from Langerhans's cells. Topics: Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Epidermal Cells; Epidermis; HLA-DR Antigens; Humans; Keratins; Leukocyte Count; Lymphoma; PUVA Therapy; Skin Neoplasms; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory | 1987 |
[Study of cell surface protein in normal and abnormal cultured keratinocytes].
Topics: Autoradiography; Carcinoma, Squamous Cell; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Epidermal Cells; Humans; Keratins; Male; Membrane Proteins; Skin Neoplasms; Trypsin | 1987 |
A new marker of terminal differentiation in keratinizing epithelia.
Using the well-differentiated human squamous carcinoma cell line LICR-LON-HN-5 as an immunogen we have produced a monoclonal antibody (32a) that reacts with the keratohyalin granular layer of the normal epidermis. We present here results showing the distribution of the epitope recognized by this antibody in human tissues in vivo and in vitro, as demonstrated using immuno cytochemical staining techniques at the light and ultrastructural levels. Expression of the determinant first appears at 18 weeks of fetal development, localized in cells associated with the hair germ. In hyperplastic epidermis the staining pattern is altered, apparently linked with a switch from orthokeratotic to parakeratotic keratinization. In primary squamous cell carcinomas and in xenografts formed by the squamous carcinoma cell line LICR-LON-HN-5 the keratinized elements are stained. Poorly differentiated tumours are not stained, indicating that antibody may be useful as a marker of terminal differentiation in vivo. When grown on collagen gels both human epidermal keratinocytes and the squamous carcinoma cell line show staining of the more differentiated cells which appears to be associated with the keratinohyalin granules, indicating that this antibody may be of value in studies aimed at the control of squamous differentiation. Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Epidermal Cells; Epitopes; Humans; Keratins; Skin; Skin Neoplasms | 1986 |
Immunologic detection of markers of keratinocyte differentiation. Its use in neoplastic and preneoplastic lesions of skin.
We examined seven invasive squamous cell carcinomas, five squamous cell carcinomas in situ, four keratoacanthomas, two actinic keratoses, and two seborrheic keratoses by indirect immunofluorescence. We used a panel of three antibodies: one directed against filaggrin, one against involucrin, and one against peptidylarginine deiminase. Anti-involucrin stained all the lesions studied, but the pattern within a given category of lesions was variable and consistent differences between the categories were not observed. Similarly, the antibodies against peptidylarginine deiminase and filaggrin were not able to distinguish differences between the various types of tumors. We conclude that in tumors of epidermis, benign or malignant, products of differentiation are expressed independently of histologic atypia or clinical aggressiveness. Therefore, markers of differentiation do not appear to be reliable indexes for distinguishing benign from malignant lesions. Topics: Carcinoma, Squamous Cell; Filaggrin Proteins; Fluorescent Antibody Technique; Humans; Hydrolases; Intermediate Filament Proteins; Keratins; Keratoacanthoma; Precancerous Conditions; Protein Precursors; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases; Skin; Skin Neoplasms | 1986 |
Merkel cell tumor of the skin: an immunohistochemical study.
Skin biopsy specimens from 12 elderly patients with Merkel cell tumors were investigated. Conventional light microscopy and immunohistochemical techniques were used. All of the tumors had similar morphologic features. Immunoreactivity for neuronspecific enolase, gastrin, calcitonin, and epithelial membrane-like antigen was demonstrated, and both neurofilaments and keratin filaments were observed. The immunohistochemical findings supported a Merkel cell origin for these Merkel cell tumors. The co-expression of neuroendocrine and epithelial markers in Merkel cell carcinomas is suggestive of neuroendocrine differentiation in a neoplasm of epithelial origin. Merkel cell carcinomas share many characteristics with neuroendocrine tumors of the bronchopulmonary and gastrointestinal tracts. All of these neoplasms may originate from cells of similar types that are present in several organs. Topics: Aged; Female; Frozen Sections; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; S100 Proteins; Skin Neoplasms | 1986 |
Keratoacanthoma and squamous cell carcinoma of the skin: immunohistochemical localization of involucrin and keratin proteins.
Fifteen keratoacanthomas and fifteen squamous cell carcinomas of the skin were examined by immunoperoxidase methods for involucrin and both 45- and 63-kilodalton keratins. Keratoacanthomas showed a relatively homogeneous staining pattern for involucrin; all cells except basal cells stained with mild to moderate intensity. Squamous cell carcinomas disclosed a highly irregular involucrin staining pattern with marked variation in staining intensity from cell to cell. Staining patterns for keratin proteins did not appear to distinguish between keratoacanthomas and squamous cell carcinomas. The 45-kilodalton keratin pattern showed diffuse staining within both keratoacanthomas and squamous cell carcinomas, and the 63-kilodalton keratin pattern consisted of focal staining, mostly of dyskeratotic cells. These results suggest that involucrin may serve as a diagnostic aid in differentiating between squamous cell carcinomas and keratoacanthomas. In addition, other lesions in the differential diagnosis of keratoacanthoma and squamous cell carcinoma were also examined for involucrin. Topics: Adult; Aged; Carcinoma, Squamous Cell; Epidermis; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Keratoacanthoma; Middle Aged; Neoplasm Proteins; Protein Precursors; Sebaceous Glands; Skin Diseases; Skin Neoplasms; Sweat Glands | 1986 |
Neoplastic conversion of human keratinocytes by adenovirus 12-SV40 virus and chemical carcinogens.
Efforts to investigate the progression of events that lead human cells of epithelial origin to become neoplastic in response to carcinogenic agents have been aided by the development of tissue culture systems for propagation of epithelial cells. In the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus 12 and simian virus 40 (Ad 12-SV40) were transformed by treatment with the chemical carcinogens N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide. Such transformants showed morphological alterations and induced carcinomas when transplanted into nude mice, whereas primary human epidermal keratinocytes treated with these chemical carcinogens failed to show any evidence of transformation. This in vitro system may be useful in assessing environmental carcinogens for human epithelial cells and in detecting new human oncogenes. Topics: 4-Nitroquinoline-1-oxide; Adenoviruses, Human; Animals; Cell Line; Cell Transformation, Neoplastic; Cell Transformation, Viral; Epidermal Cells; Humans; Keratins; Methylnitronitrosoguanidine; Mice; Mice, Nude; Neoplasm Transplantation; Nitroquinolines; Oncogenes; Simian virus 40; Skin Neoplasms | 1986 |
Intermediate filaments in Merkel cell tumor.
Topics: Humans; Intermediate Filament Proteins; Keratins; Skin Neoplasms | 1986 |
The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on phospholipid metabolism of human epidermal keratinocytes in culture.
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated the release of [3H]choline from prelabelled membrane phospholipids of cultured keratinocytes obtained from normal human skin. In contrast, TPA in the concentration range of 10(-12) to 10(-6) g/ml failed to induce deacylation of [3H]arachidonic acid or stimulate [3H]prostaglandin production in prelabelled keratinocytes. In addition, TPA did not induce [3H]choline incorporation into the membrane phospholipids of these cells. The previously reported inability of TPA to stimulate a proliferative response in these cell cultures may be related to the resistance of these cells to TPA-induced alterations of arachidonate metabolism. Topics: Arachidonic Acid; Arachidonic Acids; Cell Differentiation; Cells, Cultured; Choline; Enzyme Activation; Epidermal Cells; Epidermis; Fetal Blood; Humans; Hydrocortisone; Keratins; Phospholipases; Phospholipids; Prostaglandins; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tritium | 1986 |
Heterogeneity of ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin and in epidermal tumors.
One of the earliest events after treatment of mouse skin with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is the induction of ornithine decarboxylase (ODC). Using an immunoperoxidase technique with a rabbit antiserum specific for ODC, the localization of cells containing high levels of ODC following TPA treatment was determined. CD-1 female mice treated with multiple topical applications of TPA and killed 4.5 h after the last TPA treatment exhibited a heterogeneous localization of ODC in this hyperplastic epidermis. The cells which exhibited intense immunostaining were found predominantly in the suprabasal cells lining the hair follicles. This specific ODC staining in cells surrounding hair follicles was inhibited by pretreatment of mice with either retinoic acid or cycloheximide 1 h before TPA treatment. The induction of ODC-specific staining after TPA treatment in hyperplastic mouse skin was transient, since no staining was observed 16 or 24 h after TPA treatment. In contrast, benign papillomas produced by two-stage tumorigenesis contained some cells demonstrating high levels of ODC a week after the last TPA application. These results indicate that both normal mouse epidermal cells as well as tumor tissue display cellular heterogeneity of ODC expression. Topics: Animals; Enzyme Induction; Epidermal Cells; Epidermis; Female; Keratins; Mice; Mice, Inbred Strains; Ornithine Decarboxylase; Papilloma; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tretinoin | 1986 |
Immunocytochemical study of a trabecular carcinoma of the skin (Merkel cell tumor). Case report.
The existence of different neuroendocrine markers was investigated by immunocytochemistry in a case of Merkel cells tumor. Neuroplastic cells contain NSE,NF,CK and chromogranin A i.r. On the basis of the results the neuroendocrine nature of this uncommon neoplasm of the skin is confirmed and it is suggested that chromogranin A could represent an additional marker for Merkel cells tumors. Topics: Adenocarcinoma; Aged; Chromogranin A; Chromogranins; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Lymphatic Metastasis; Male; Phosphopyruvate Hydratase; Skin Neoplasms; Staining and Labeling | 1986 |
Diagnosing tumours on routine surgical sections by immunohistochemistry: use of cytokeratin, common leucocyte, and other markers.
Tumours of uncertain tissue of origin were investigated by immunohistochemistry on formalin fixed paraffin embedded sections. Two antibodies--PD7/26, an anti common leucocyte antigen, and CAM5.2, an anticytokeratin--recognised most lymphomas and carcinomas, respectively: 88% of these tumours were identified by the two antibodies alone. These antibodies permitted the separation of the cases into groups: positive with CAM5.2, positive with PD7/26, and a third comprising those negative with both. The negative group contained other tumours and a small number of carcinomas and lymphomas; many of the lymphomas were, apparently, of histiocytic origin. Comparison of CAM5.2 with other epithelial markers showed that it was the most effective. Some further classification of the tumours was carried out with a panel of organ and cell specific antibodies: mesotheliomas were recognised by their pattern of reactivity with epithelial markers. Overall, the tumour type was determined in 90% of cases. Immunohistochemistry performed as described can be a potent aid to the diagnostic histopathology of tumours. Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Histocompatibility Antigens; Humans; Keratins; Leukocyte Common Antigens; Lymphoma; Mesothelioma; Neoplasms; Sarcoma; Skin Neoplasms; Thyroid Neoplasms | 1986 |
Reactivity of T lymphotropic retrovirus antibody (12/1-2) in man: comparison of epidermis with other epithelial cells.
The reactivity of a monoclonal antibody against human T lymphotropic retrovirus (antibody 12/1-2, recognising the HTLV-1 p19 internal core viral protein) with benign and malignant cutaneous biopsy specimens was examined and compared with results obtained on normal skin, on various other human cells and tissues, and on immunoblotted extracts of tonsil squamous epithelium. In keeping with previous studies, 12/1-2 labelled a proportion of the thymic epithelial stroma and the entire layer of basal cells in stratified non-keratinized and keratinized epithelium. Furthermore, antibody 12/1-2 reacted with basal cell carcinomas and showed an essentially identical staining pattern in normal skin, cutaneous T cell lymphomas, and a range of benign dermatoses. The dot blot preparations showed that 12/1-2 recognised an antigen associated with keratin intermediate filaments. These data indicate that antibody 12/1-2 forms a useful marker for subsets of epithelial cells, which presumably participate in T cell education, and that a range of cutaneous disorders of widely different aetiology show no abnormalities in epithelial expression of this antigen. Topics: Antibodies, Monoclonal; Antibodies, Viral; Antigens; Carcinoma, Basal Cell; Deltaretrovirus; Epithelium; Humans; Keratins; Lymphoma; Palatine Tonsil; Skin; Skin Diseases; Skin Neoplasms; T-Lymphocytes; Thymus Gland | 1986 |
Role of immunohistochemistry in the diagnosis of undifferentiated tumors involving the skin.
Twenty undifferentiated skin tumors were examined by immunostaining in an attempt to achieve more precise identification. Light microscopy yielded only a differential diagnosis, whereas immunostaining of formalin-fixed, paraffin-embedded tissue sections with a panel of antibodies to intermediate filaments and other cell components led to a definitive diagnosis. Four cytokeratin-positive epithelial tumors were subtyped into squamous cell carcinomas and adenocarcinomas with the use of antibodies to different cytokeratin polypeptides. Fifteen vimentin-positive tumors were subdivided into malignant melanomas with the use of antibody to S-100 protein, lymphomas with the use of antibody to immunoglobulin, and mesenchymal tumors (angiosarcomas, atypical fibroxanthomas, dermatofibrosarcoma protuberans, and meningiomas) with the use of antibody to S-100 protein, factor VIII, and lysozyme. One desmin-positive tumor was diagnosed as a leiomyosarcoma of the skin. A scheme is presented for using immunohistochemistry to facilitate the diagnosis of undifferentiated tumors involving the skin. Topics: Antibodies; Desmin; Diagnosis, Differential; Epidermis; Histocytochemistry; Humans; Immunologic Techniques; Intermediate Filament Proteins; Keratins; S100 Proteins; Skin Neoplasms; Vimentin | 1986 |
Cell surface carbohydrates in proliferative epidermal lesions. II. Masking of peanut agglutinin (PNA) binding sites in solar keratoses, Bowen's disease, and squamous cell carcinoma by neuraminic acid.
Seventy-six skin biopsies of proliferative lesions were studied by using 4 different lectins and an avidin-biotin-peroxidase complex. In solar keratosis, Bowen's disease and squamous cell carcinoma, malignant-appearing keratinocytes exhibited loss of membrane staining with Concanavalia ensiformis agglutinin (Con A), but revealed cytoplasmic staining. When incubated with peanut agglutinin (PNA), the malignant keratinocytes did not stain. However, the PNA binding sites were not absent, but masked by sialic acid. Following cleavage of the sialic acid with neuraminidase, free PNA binding sites could be demonstrated in the plasma membranes. In contrast, the keratinocytes in keratoacanthomas showed membrane staining with Con A and also contained free PNA binding sites. These histochemical findings confirm and extend our earlier observations regarding cell surface carbohydrates in premalignant and malignant epidermal lesions. Topics: ABO Blood-Group System; Binding Sites; Bowen's Disease; Carbohydrate Metabolism; Carcinoma, Squamous Cell; Cell Membrane; Concanavalin A; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Keratosis; Lectins; Neuraminic Acids; Peanut Agglutinin; Plant Lectins; Skin; Skin Neoplasms; Sunlight; Wheat Germ Agglutinins | 1986 |
Colloid keratosis. Morphologic characterization of a nonspecific reaction pattern of squamous epithelium.
Colloid keratosis is characterized by homogeneous eosinophilic masses of variable size and number within the upper layers of squamous epithelia, including epidermis. It has been observed as the characteristic feature of many onychoses and inflammatory conditions of oral epithelium, and as an incidental finding in neoplastic and nonneoplastic lesions in the skin and respiratory tract. Its nature remains obscure, but knowledge at present suggests that it may represent a disorder of an early phase of keratinization. Current evidence supports the hypothesis that colloid keratosis represents a nonspecific cellular reaction pattern of squamous epithelium. Topics: Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Colloids; Eosinophilia; Epithelium; Female; Humans; Keratins; Keratosis; Male; Middle Aged; Necrosis; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1986 |
The use of antikeratin antibodies in the immunohistochemical distinction between neuroendocrine (Merkel cell) carcinoma of the skin, lymphoma, and oat cell carcinoma.
Paraffin sections of formalin-fixed tumor samples from 26 patients with neuroendocrine (Merkel cell) carcinoma of the skin (NECS) were studied immunohistochemically with three monoclonal antibodies to low molecular weight keratin (MAB-K) and with antibodies to leukocyte common antigen (LCA), neurofilament (NF), neuron-specific enolase (NSE), S100 protein (S100), and chromogranin (CGN), to investigate the relative diagnostic value of these antibodies. Samples from 20 lymphomas, 10 non-oat cell undifferentiated carcinomas, 10 oat cell carcinomas, and 10 melanomas served as controls. Keratin was found in 25 of the 26 NECS and in all undifferentiated and oat cell carcinomas. A ball-like immunostaining for keratins, resembling an inclusion body was seen only in cases of NECS and some carcinoids. Neurofilament, NSE, and CGN were expressed by fewer NECS than was keratin and all NECS were negative for LCA and S100. None of the lymphomas and melanomas contained detectable keratin, NF, NSE, or CGN. Only the lymphomas stained with LCA. Only the melanomas were S100-positive. It is concluded that keratin is the most useful single discriminating marker in the separation of neuroendocrine (Merkel cell) carcinoma of the skin from lymphoma, melanoma and, when the characteristic inclusion-like pattern is seen, from metastatic oat cell carcinoma. Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoid Tumor; Carcinoma; Carcinoma, Small Cell; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunochemistry; Keratins; Lung Neoplasms; Lymphoma; Male; Melanoma; Microscopy, Electron; Middle Aged; Nerve Tissue Proteins; Skin Neoplasms | 1986 |
Immunohistochemical studies on epithelial cells in mixed tumor of the skin.
We performed studies on the lectin-binding pattern in epithelial tumor cell components of 4 cases of mixed tumor of the skin developing on the face in addition to identification of keratin and carcinoembryonic antigen (CEA), compared with those of normal sweat glands. Normal eccrine glands showed specific labelling with Dolichos biflorus agglutinin (DBA) and soybean agglutinin (SBA), whereas none of the studied lectins reacted specifically with normal apocrine glands. In mixed tumors the dark cells, which form the inner layer of the tubuloalveolar and ductal structure, showed the presence of keratin and CEA, as well as of specific sugar structures that bind to DBA and SBA. On the other hand the light cells that form the outer layer of the tubular structures or the solid epithelial cell nests gave only a faint to moderate staining of keratin, and no staining of CEA or lectins. It is probable that the inner dark cells differentiate toward the cells that have the same sugar structures on the cell surface as those of the normal eccrine gland cells, while the outer light cells appear to be immature or in a less differentiated state. Topics: Adult; Aged; Carcinoembryonic Antigen; Epithelium; Facial Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Lectins; Male; Neoplasms, Germ Cell and Embryonal; Skin Neoplasms | 1986 |
[Expression of HLA-DR antigen in cutaneous malignant lymphomas and recombinant gamma interferon induces HLA-DR antigen on cultured human keratinocytes].
Topics: Adult; Aged; Cells, Cultured; Epidermal Cells; Female; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Interferon-gamma; Keratins; Lymphoma; Male; Middle Aged; Skin Neoplasms | 1986 |
GP37 expression in normal and diseased human epidermis: a marker for keratinocyte differentiation.
An antiserum prepared against a glycoprotein (GP37) extracted from the upper epidermal layers, was used to stain frozen sections of human oral mucosa, normal and abnormal skin by an indirect immunofluorescence technique. On normal human epidermis, this antiserum mainly reacted with the cytoplasm of granular cells, whereas on buccal mucosa the recognized antigen was observed as scattered dots limited to the upper epithelial layers. In epidermal diseases, alterations in the staining pattern were observed. In psoriasis, the labelling was markedly diminished; in contrast, in lichen planus it was intense and present on the 3-6 uppermost cellular layers. Basal cell epitheliomas were almost negative, except around horn cysts. In Bowen's disease dyskeratotic cells were strongly labelled. In squamous cell carcinomas a clear-cut staining was observed in squamous nests. On cultures, GP37 expression could be induced by growing epidermal cells in vitamin A-depleted medium. The biological significance of the observed staining patterns remains to be precised. Nevertheless, GP37 represents a sensitive marker of epidermal differentiation and may be useful in skin pathology and in in vitro studies. Topics: Animals; Carcinoma, Squamous Cell; Epidermal Cells; Fluorescent Antibody Technique; Glycoproteins; Humans; In Vitro Techniques; Keratins; Lichen Planus; Macaca; Mice; Psoriasis; Rabbits; Skin Diseases; Skin Neoplasms | 1986 |
Merkel cell (small cell) carcinoma of the skin: immunohistochemical and ultrastructural demonstration of distinctive perinuclear cytokeratin aggregates and a possible association with B cell neoplasms.
Three cases of Merkel cell (small cell) carcinoma of the skin are presented with immunohistochemistry for epithelial and neuroendocrine antigens. All three cases showed distinctive punctate perinuclear cytoplasmic positivity for cytokeratin which corresponded to aggregates of intermediate filaments, seen ultrastructurally in two cases. Epithelial membrane antigen was also identified in two cases. Only one case showed cytoplasmic positivity for neuron specific enolase, and immunostaining for a battery of polypeptide hormones was negative. The demonstration of cytokeratin perinuclear inclusions provides a distinctive immunohistochemical feature to aid in their diagnosis. Two of the three patients had chronic lymphocytic leukaemia years before the diagnosis of Merkel cell carcinoma. The possible association of lymphoproliferative disorders, particularly B cell tumours, and Merkel cell carcinoma is discussed. Topics: Aged; Antigens, Neoplasm; Carcinoma, Small Cell; Cell Nucleus; Cytoplasm; Epithelium; Female; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Male; Microscopy, Electron; Middle Aged; Phosphopyruvate Hydratase; Skin Neoplasms | 1986 |
Coexpression of neurofilament and keratin proteins in cutaneous neuroendocrine carcinoma cells.
Four cases of neuroendocrine carcinomas (NECA) of the skin were studied by indirect immunofluorescence, using a monoclonal antikeratin antibody and a polyclonal antineurofilament antibody. Fifty to ninety percent and 80 to greater than 95% of the NECA cells stained with the antineurofilament antibody and the antikeratin antibody, respectively. Using double-labeling indirect immunofluorescence we could also demonstrate that, in 3 cases studied, some of the NECA cells, but not all, stained with both antikeratin and antineurofilament antibodies. These results, together with the recent knowledge of the intermediate filament protein type of normal Merkel cells (MC), tend to support the hypothesis that NECA cells do not originate from epithelial MC but from dermal neuroendocrine cells. A dual concept of intraepithelial MC and extraepithelial intradermal neuroendocrine cells, "from possible distinct origin," is proposed. Such a system has already been suggested for the neuroendocrine cells of the appendix and bronchial mucosae. Topics: Adenocarcinoma; Aged; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Neoplasm Proteins; Neurofilament Proteins; Skin Neoplasms | 1986 |
[Immunohistochemical and ultrastructural studies of mixed tumor of the skin].
Topics: Adenoma, Sweat Gland; Adult; Aged; Carcinoembryonic Antigen; Female; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; S100 Proteins; Skin Neoplasms | 1986 |
Involucrin expression in epithelial tumors of oral and pharyngeal mucosa and skin.
Involucrin has been recognized recently as a marker of terminal differentiation of squamous epithelial cells and also as a useful marker for keratinization; its expression in epithelial tumors of oral and pharyngeal mucosa and skin was examined. Involucrin in normal oral mucosa and skin was restricted to the granular and upper spinous layers and was absent in the basal layer. Hyperkeratosis was characterized by strong positive staining for involucrum in spinous and granular cell layers. A similar pattern was noted in seborrheic keratosis and verruca vulgaris. Condyloma acuminatum specimens revealed slight staining, whereas Paget cells were negative. Calcifying epitheliomas of Malherbe were usually unreactive. Papillomas exhibited the regular distribution of involucrin, as found in normal squamous epithelium. Basal cell carcinomas were generally negative, whereas squamous cell carcinomas showed an irregular distribution of involucrin. Immunohistochemical staining for involucrin may be useful for identification of keratinizing cells in epithelial tumor foci, just as is the use of monoclonal antibody to keratin KL1. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Papilloma; Pharyngeal Neoplasms; Protein Precursors; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1986 |
The differential diagnosis of intraepidermal malignant lesions using immunohistochemistry.
The malignant intraepithelial proliferations--malignant melanoma level I, bowenoid epithelial dysplasia, and mammary as well as extramammary Paget's disease--may cause differential diagnostic difficulties. We have examined 12 cases of malignant melanoma level I, nine cases of bowenoid epithelial dysplasia, 17 cases of extramammary and five cases of mammary Paget's disease for S100 protein, carcinoembryonic antigen (CEA), cytokeratin, and keratin to evaluate the sensitivity and specificity of these reactions with regard to their differential diagnostic value. Antibodies against S100 reacted specifically with the tumor cells in intraepithelial malignant melanomas; antibodies against CEA reacted specifically with the tumor cells in Paget's disease; and cytokeratin and keratin antibodies reacted with the epithelial tumor cells in Paget's disease as well as in bowenoid epithelial dysplasia. However, only antibodies to CEA and keratin showed 100% sensitivity. We conclude that the investigated antibodies may be of differential diagnostic value in cases of intraepidermal neoplasias, but that a negative reaction does not exclude diagnosis of these diseases. Topics: Bowen's Disease; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Immunologic Techniques; Keratins; Melanoma; Paget Disease, Extramammary; Paget's Disease, Mammary; Retrospective Studies; S100 Proteins; Skin Neoplasms | 1986 |
Epithelioid sarcoma and isolated necrobiotic granuloma: a comparative immunocytochemical study.
Epithelioid sarcoma (ES) occasionally may be confused, both clinically and histologically, with isolated necrobiotic granulomas (ING), leading to misdiagnosis and potential mismanagement of these conditions. We studied 11 cases of ES and 11 of ING (6 examples of deep granuloma annulare and 5 of rheumatoid nodule) immunohistochemically, in an attempt to determine whether they could be diagnostically separated by such means. Monoclonal antibodies to cytokeratin polypeptides (CK), epithelial membrane antigen (EMA), and leukocyte common antigen (LCA) were applied to formalin-fixed, paraffin-embedded sections in each case, using the avidin-biotin-peroxidase complex technique. All ES cases stained positively for CK, and 6 expressed EMA, while examples of ING were non-reactive for these antigens. Conversely, the large epithelioid histiocytic cells in cases of ING were immunoreactive with anti-LCA, whereas no case of ES displayed this determinant in tumor cells. In the latter lesions, reactive peritumoral inflammatory cells were LCA-positive, but were readily distinguished from neoplastic cells on morphological grounds, as well as by their negativity with anti-CK and anti-EMA. Based on these data, it is concluded that immunohistologic stains for epithelial and hematopoietic antigens are valuable in the conclusive diagnostic separation of epithelioid sarcoma and necrobiotic granulomas. Topics: Adolescent; Adult; Aged; Antigens, Surface; Child; Child, Preschool; Diagnosis, Differential; Epithelium; Female; Granuloma; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Male; Middle Aged; Sarcoma; Skin Diseases; Skin Neoplasms | 1986 |
Neuroendocrine carcinoma of the skin: an immunohistochemical study of tumor markers and neuroendocrine products.
Fifteen neuroendocrine carcinomas of the skin (Merkel cell tumors) were stained within the constraints of tissue availability by the Grimelius method and immunohistochemically for keratin, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), S-100, common leukocyte antigen (CLA), met-enkephalin, bombesin, calcitonin, ACTH, gastrin, and somatostatin. Focal argyrophilia was present in 5 of 12 tumors. All tumors tested demonstrated immunoreactivity for NSE and 5 tumors were positive for keratin. One tumors appeared to demonstrate focal ACTH-like immunoreactivity, but otherwise no immunoreactivity for the above mentioned polypeptide hormones was noted in 11 completely studied tumors. One tumor contained histologically obvious areas of squamous differentiation in addition to areas of Merkel cell tumor. In various tumors, keratin immunoreactivity was present either in areas of histologically obvious squamous differentiation, in randomly scattered single cells not histologically identifiable as squamous, or in a paranuclear dot-like distribution. Immunoreactivity for CEA, S-100 and CLA was not present in any tumors. The lack of met-enkephalin and the presence of squamous differentiation in these tumors indicates multidirectional differentiation in a fashion not phenotypically typical of Merkel cells. Topics: Adenocarcinoma; Adrenocorticotropic Hormone; Bombesin; Calcitonin; Carcinoembryonic Antigen; Enkephalin, Methionine; Gastrins; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Phosphopyruvate Hydratase; Skin Neoplasms; Somatostatin | 1986 |
UV radiation-induced tumors in haired mice: identification as squamous cell carcinomas.
The most common tumor induced by UV radiation in haired mice is considered to be a fibrosarcoma on the basis of its presentation as a nodule in the skin and on the basis of a spindled appearance upon light microscopic examination. A squamous cell carcinoma is thought to be a much less common tumor. In the present report this concept was reevaluated in mammary tumor virus-free C3H/HeNCr (C3H-) mice. From first appearance, almost all lesions upon gross morphologic examination have an epidermal component and initially are similar to solar keratoses in humans. The lesions then become nodular and eventually develop central ulceration, often with a rolled border characteristic of squamous cell carcinomas. The morphology upon light microscopic examination ranged from well-differentiated squamous cell carcinoma to a poorly differentiated spindle cell neoplasm. Occasionally, variable patterns of squamous differentiation were seen in the same lesion. Immunoperoxidase examination with a polyclonal antikeratin serum demonstrated the presence of keratin in 84 of 87 tumors. Frequent, poorly formed desmosomes were found on ultrastructural examination. These tumors usually had a regressor phenotype upon transplantation into recipients. In conclusion, almost all UV radiation-induced tumors in C3H- mice are squamous cell carcinomas, and these tumors are usually antigenic. Topics: Animals; Carcinoma, Squamous Cell; Desmosomes; Epidermis; Keratins; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Neoplasms, Radiation-Induced; Sarcoma, Experimental; Skin Neoplasms; Ultraviolet Rays | 1986 |
Cytochemical expression of epidermal peroxidase and cytochrome oxidase activities in pathological skin conditions of man.
The cytochemical expression of epidermal peroxidase and cytochrome oxidase activity was recently well documented in normal human skin. We report here its expression in basal and squamous cell carcinomas, actinic keratoses, psoriasis, allergic contact dermatitis, seborrheic keratoses, and autosomal dominant ichthyosis vulgaris. The two enzyme activities were evaluated using the diaminobenzidine method. If present, the two enzymes were always localized in the same organelles as in normal epidermis: endogenous peroxidase in the nuclear envelope and endoplasmic reticulum, and cytochrome oxidase in mitochondria. In basal and squamous carcinomas, actinic keratoses and psoriasis, the keratinocytes lost their peroxidase activity, but maintained their cytochrome oxidase activity. In seborrheic keratoses, allergic contact dermatitis and ichthyosis vulgaris, the cytochrome oxidase activity was greatly reduced or abolished in keratinocytes, Langerhans' cells, and melanocytes, whereas the peroxidase activity was present as in normal epidermis. These results indicate that the two peroxidatic enzymes studied are not interrelated and alternatively suppressed by different cellular dysfunctions. Topics: 3,3'-Diaminobenzidine; Biopsy; Electron Transport Complex IV; Epidermal Cells; Humans; Keratins; Langerhans Cells; Peroxidases; Skin; Skin Diseases; Skin Neoplasms | 1986 |
[Epidermal cell cultures--significance for wound coverage in the human].
Epithelial sheets can be cultivated from isolated epidermal cells; in this way, it is possible to increase the cell number considerably. H. Green and co-workers were the first to make use of such epithelia for the autologous covering of burn wounds. We modified this method and report on our experiences with this technique in a patient with small skin defects. Topics: Adult; Burns; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Melanoma; Skin Neoplasms; Skin Transplantation; Vimentin; Wound Healing | 1986 |
Cytokeratin and laminin immunostaining in the diagnosis of cutaneous neuro-endocrine (Merkel cell) tumours.
Nine cutaneous neuro-endocrine tumours have been immunostained with monoclonal antibodies to low molecular weight cytokeratin (CAM 5.2) and neurofilament. Polyclonal antisera to neurone-specific enolase, calcitonin and laminin were also used. All nine cases showed paranuclear, dot-like positive staining with CAM 5.2 and diffuse cytoplasmic staining for neurone-specific enolase. Neurofilament and calcitonin immunoreactivity could not be demonstrated. All tumours were negative for laminin immunoreactivity. The limitations of staining for neurone-specific enolase are discussed and the value of CAM 5.2 in the differential diagnosis of cutaneous neuro-endocrine tumours is emphasized. The histogenetic implications of the absence of laminin staining are considered. Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Cytoplasm; Diagnosis, Differential; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Laminin; Male; Middle Aged; Nervous System Neoplasms; Neurosecretory Systems; Phosphopyruvate Hydratase; Skin Neoplasms | 1986 |
[Immunohistochemical and electron microscopic study of so-called mixed tumor of the skin].
Topics: Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged; Myosins; Neoplasms, Germ Cell and Embryonal; S100 Proteins; Secretory Component; Skin Neoplasms | 1986 |
Immunohistochemical studies of basal cell carcinomas transplanted into nude mice.
Xenografting into nude mice forms a system for analysis of human tissues under experimental conditions. In this study, normal skin samples and basal cell carcinomas were investigated, prior to and after transplantation, using immunofluorescence methods with antibodies against keratins, laminin, and collagen type IV. Three groups of transplants were studied: intact tissue samples, human epithelium (either normal or neoplastic) recombined with normal human dermis and, human epithelium recombined with normal mouse dermis. Transplants recovered after 3 weeks showed the following characteristics. The xenograft system was satisfactory in terms of host survival and rate of successful tissue recovery except for recombinants between human epithelium and mouse dermis. Intact and recombined samples of normal skin retained their preexisting patterns of architecture, cytodifferentiation, and basement membrane staining. Solid nonfibrosing basal cell carcinomas showed altered architecture and differentiation of both the epithelium and the basement membrane zone after transplantation: the solid tumor pattern changed towards spreading of tumor cells, a more squamous differentiation pattern was apparent and was confirmed by reactivity with antibodies against large keratins. Discontinuities of the basement membrane zone were detected with antibodies against laminin and collagen type IV. These changes were seen in both intact and recombined tumor transplants. Topics: Animals; Basement Membrane; Carcinoma, Basal Cell; Collagen; Fluorescent Antibody Technique; Humans; Keratins; Laminin; Mice; Mice, Nude; Neoplasm Transplantation; Skin; Skin Neoplasms | 1986 |
Criteria for the diagnosis of primary endocrine carcinoma of the skin (Merkel cell carcinoma). A histological, immunohistochemical and ultrastructural study of 13 cases.
Thirteen cases of primary endocrine carcinoma of the skin (Merkel cell carcinoma) were reviewed with the aim of defining the morphological, immunohistochemical and ultrastructural criteria for diagnosis. The tumour cells were characterized by their scanty cytoplasm, generally small uniform nuclei with finely dispersed chromatin and multiple small nucleoli. Nuclear shapes varied from round to spindle, with larger and pleomorphic forms predominating in 2 tumours. A striking feature seen in 12 tumours was the occurrence of a "ball-in-mitt" pattern represented by 1 or 2 crescentic tumour cells closely wrapped around an oval cell. Staining for neuron-specific enolase was the most consistent marker of the tumour and the characteristic juxtanuclear globular staining for keratin and cytokeratin and the occasional coexpression of neurofilament set this tumour apart from other cutaneous neoplasms, in particular, metastatic carcinoid tumours and oat cell carcinoma from the lung. The fine structural features of note were striking paranuclear or juxtanuclear whorls of intermediate filaments, seen in 7 cases, the presence of variable numbers of membrane-bound dense core granules of 80-150 nm diameter in all cases and cytoplasmic spinous or microvillous projections containing microfilaments in 4 cases. Less consistent characteristics of primary endocrine carcinomas of the skin included cell moulding, argyrophilia and immunohistochemical staining for ACTH, VIP and calcitonin. The high frequency of vessel invasion in this series is in keeping with the high rate of local recurrence, lymph node metastases and visceral dissemination reported. The distinction from other similar appearing tumours in the skin is discussed. Topics: Adult; Aged; Aged, 80 and over; Cytoplasm; Female; Histocytochemistry; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Phosphopyruvate Hydratase; Skin Neoplasms | 1986 |
Variability of expression and arrangement of cytokeratin and neurofilaments in cutaneous neuroendocrine carcinomas (Merkel cell tumors): immunocytochemical and biochemical analysis of twelve cases.
Twelve specimens of cutaneous neuroendocrine carcinomas (Merkel cell tumors) available as fresh tissue were analyzed for intermediate filament (IF) expression by immunocytochemical and biochemical methods. In immunofluorescence microscopy, most cases were positive for both simple-epithelium-type cytokeratins and the neurofilament L- and M-polypeptides. Several different IF staining patterns ranging from presence of plaque-like structures (fibrous bodies) only to nearly exclusive expression of delicate cytokeratin fibrils could be distinguished. In immunoelectron microscopy the labeling for both cytokeratin and neurofilament polypeptides seemed evenly distributed among the IFs of the fibrous bodies. In primary culture, tumor cells maintained the coexpression of both IF types. Desmoplakin-positive true desmosomes were found in 5 specimens. Biochemically, cytokeratins nos. 8, 18 and, variably, 19, as well as IT protein and, in many specimens, the neurofilament L-protein and a putative neurofilament M-protein were detected. Only traces of the neurofilament H-polypeptide were found. Our results show that a coexpression of cytokeratin IFs and neurofilaments in variable patterns is a characteristic feature of cutaneous neoendocrine carcinomas; occasionally, however, neurofilaments may be very scarce. The biological, histogenetic and diagnostic implications are discussed. Topics: Adult; Aged; Aged, 80 and over; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Female; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Male; Microscopy, Electron; Microscopy, Fluorescence; Middle Aged; Neurosecretory Systems; Skin Neoplasms | 1986 |
[A clinicopathological study of extramammary Paget's disease].
Topics: Aged; Aged, 80 and over; Female; Genitalia; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged; Paget Disease, Extramammary; Skin Neoplasms | 1986 |
Basement membrane components and keratin in the dominantly inherited form of cylindroma.
Specific antibodies against basement membrane associated, connective tissue components: type IV and V collagens, laminin, fibronectin and heparan sulphate proteoglycan were used to study the basement membrane-like structures in cylindroma lesions. All these components were immunohistochemically demonstrated as a band surrounding islands of epithelial cells and all except fibronectin also inside the islands. Antibodies to keratin filaments stained most of the cells inside the epithelial islands confirming the epithelial origin of the cells. Topics: Basement Membrane; Carcinoma, Adenoid Cystic; Chondroitin Sulfate Proteoglycans; Collagen; Female; Fibronectins; Fluorescent Antibody Technique; Genes, Dominant; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Keratins; Laminin; Middle Aged; Skin Neoplasms | 1985 |
Immunodiagnosis in dermatopathology.
Topics: Antibodies, Monoclonal; Dermatitis; Histiocytosis, Langerhans-Cell; Histocytochemistry; Humans; Hypersensitivity, Delayed; Immunochemistry; Keratins; Skin Diseases; Skin Neoplasms; T-Lymphocytes | 1985 |
Antibodies to intermediate filament proteins. The differential diagnosis of cutaneous tumors.
One hundred cutaneous tumors were investigated immunohistopathologically for the expression of intermediate filament (IF) proteins. Epithelial tumors, such as basocellular and squamous cell carcinomas, cutaneous adnexal tumors, and metastatic carcinomas showed keratin positivity in a varying number of tumor cells with two keratin antibodies with different specificities. Neoplastic cells of fibrohistiocytic tumors, pigmented nevi, melanomas, hemangiomas, glomus tumors, and lymphomas were positive for vimentin, but not for keratin or desmin. Cutaneous leiomyomas and leiomyosarcomas, on the other hand, were positive for desmin. The results show that the typing of IFs enables the differential diagnosis between carcinomas and sarcomas or melanomas, epidermal appendage tumors, and mesenchymal tumors, and between fibrohistiocytic and leiomyocytic tumors, and therefore are of diagnostic value in histopathologic problems of the skin. Topics: Adenocarcinoma; Adenoma, Sweat Gland; Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Desmin; Diagnosis, Differential; Fluorescent Antibody Technique; Hemangioma; Histiocytoma, Benign Fibrous; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Leiomyoma; Melanoma; Neoplasm Metastasis; Nevus, Pigmented; Skin Neoplasms; Vimentin | 1985 |
Extramammary Paget's disease of the perianal and perineal regions. Evidence of apocrine derivation.
A case of perianal and perineal extramammary Paget's disease in a male is reported. The presence of gross cystic disease fluid protein--a new marker of apocrine epithelia--in Paget's cells provides additional insight into the histopathogenesis of this condition. This marker may be a valuable diagnostic adjunct in evaluating intra-epithelial malignancies at a variety of anatomic sites. Topics: Aged; Anal Canal; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Carcinoembryonic Antigen; Carrier Proteins; Glycoproteins; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Transport Proteins; Neoplasm Proteins; Paget Disease, Extramammary; Perineum; Skin Neoplasms; Sweat Glands | 1985 |
Two Shope papillomavirus-associated VX2 carcinoma cell lines with different levels of keratinocyte differentiation and transplantability.
Two cell lines, named VX2T and VX2R, were isolated from the transplantable VX2 carcinoma, a wholly anaplastic tumor established from a carcinoma induced by the Shope cottontail rabbit papillomavirus (CRPV) (J.G. Kidd and P. Rous, J. Exp. Med. 71:813-838, 1940). The CRPV genome was found to be maintained and transcribed in both cell lines, as in the VX2 carcinoma. The VX2T cells retained the tumor-producing capacity in the rabbit and the low expression of epidermal keratinocyte differentiation of the VX2 tumor cells. The VX2R cells, although tumorigenic for nude mice, were no longer serially transplantable in the rabbit and expressed differentiated functions of keratinocytes. These data indicate that the anaplastic characteristic and the transplantability of VX2 carcinoma cells to immune competent allogenic hosts may be lost without any detectable modification of the physical state and transcription of the CRPV genome. Topics: Animals; Carcinoma; Cell Differentiation; Cell Line; Cytoskeletal Proteins; DNA, Neoplasm; DNA, Viral; Keratins; Neoplasm Transplantation; Papillomaviridae; Rabbits; Skin Neoplasms; Tumor Virus Infections | 1985 |
[Kaposi's sarcoma: comparative immunohistochemical study and histogenic significance of endothelial markers].
The origin of spindle-shaped cells in Kaposi's sarcoma (KS) remains controversial. Non-specific histochemical reactions, electron microscopic examinations and immunostainings using antibody against factor VIII-related antigen (F VIII-RAG) and Ulex europaeus agglutinin I (UEAI) lectin as endothelial markers have given contradictory results. Immunohistochemical techniques were applied to 7 frozen skin biopsy specimen of KS from 5 elderly Mediterranean people and 1 renal allograft recipient, and a group of 27 other frozen cutaneous tumours including haemangio and lymphangiosarcomas, benign vascular lesions and various epithelial, melanocytic, fibrohistiocytic, fibrosarcomatous and muscular tumours. Using UEAI and antibodies against F VIII-RAG, HLA-DR and vimentin, a large proportion of positive KS spindle cells was found in all cases whereas cells were negative for keratin. Among the various immunoreactivity patterns observed in this study, a unique immunohistochemical profile was demonstrated for KS, angiosarcoma and endothelial cell, which strongly supports the endothelial origin of spindle cells in KS. Whereas F VIII-RAG, HLA-DR, vimentin and UEAI were sensitive endothelial markers, only F VIII-RAG appeared specific for endothelial cells since UEAI stained 2 squamous cell carcinomas and HLA-DR and vimentin were present in various mesenchymal and melanocytic tumours. Topics: Adult; Aged; Antigens; Endothelium; Factor VIII; Hemangiosarcoma; Histocompatibility Antigens Class II; Histocytochemistry; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Lectins; Middle Aged; Plant Lectins; Sarcoma, Kaposi; Skin Neoplasms; Vimentin; von Willebrand Factor | 1985 |
PUVA--lentigo.
Topics: Cell Nucleus; Dose-Response Relationship, Radiation; Epidermis; Humans; Hyperplasia; Keratins; Lentigo; Melanocytes; Melanosis; Photochemotherapy; Psoriasis; PUVA Therapy; Skin Neoplasms | 1985 |
Immunohistochemical and ultrastructural study on pilomatrixoma.
Topics: Cell Nucleus; Cytoplasm; Hair; Humans; Keratins; Scalp; Skin Neoplasms; Staining and Labeling | 1985 |
An ultrastructural study of a sclerosing epithelial hamartoma.
The histological and ultrastructural features of a sclerosing epithelial hamartoma are described. By electron microscopy, epithelial cords formed by basal-like cells and epithelial cysts with a pattern of keratinization similar to that of normal epidermis or of follicular infundibula were seen. By conventional light microscopy, continuities were found between the epithelial cords and the overlying epidermis. The stroma was found to be fibrous and contained some fibroblasts or possibly myofibroblasts with bundles of microfilaments. The data are interpreted with respect to the origin of the neoplasm, its line of differentiation, and its sclerosing behavior. Topics: Actin Cytoskeleton; Adult; Biopsy; Cheek; Facial Neoplasms; Female; Fibroblasts; Hamartoma; Humans; Keratins; Sclerosis; Skin; Skin Neoplasms | 1985 |
Keratin gene expression in mouse skin tumors and in mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate.
Alterations in the pattern of epidermal differentiation and proliferation occur during mouse skin carcinogenesis. We have used cDNA clones corresponding to the major keratin subunits synthesized in differentiating epidermal cells (Mr 67,000 and 59,000) and in proliferating epidermal cells (Mr 60,000, 55,000, and 50,000) to study changes in keratin gene transcript levels in mouse epidermis exposed to tumor promoters. The same probes were used to characterize the keratin expression patterns in benign and malignant skin tumors. A single topical treatment with 12-O-tetradecanoylphorbol-13-acetate caused a rapid initial decrease in the epidermal transcript levels corresponding to the Mr 67,000 and 59,000 keratin subunits. By 48 h the transcript level for the Mr 67,000 keratin subunit was restored to control values, whereas the transcript levels for the Mr 59,000 subunit returned to control at a slower rate. In contrast, the transcript level for the Mr 55,000 subunit was increased substantially 12- 48 h after treatment, the Mr 50,000 subunit transcript increased to a lesser extent, and the Mr 60,000 subunit message was transiently decreased at 12 h but returned to the level of solvent-treated skin by 24 h. Single exposure to the incomplete tumor promoters 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate, the ionophore A23187, and mezerein induced changes in keratin gene transcripts similar to those of 12-O-tetradecanoylphorbol-13-acetate. The antipromoter fluocinolone acetonide, administered with 12-O-tetradecanoylphorbol-13-acetate, partially inhibited the decrease in the Mr 59,000 and 67,000 transcripts and completely inhibited the increase in the Mr 55,000 transcript. In skin papillomas produced by initiation and promotion, keratin gene expression was similar to normal skin, with the exception of a two-fold increase in the transcript levels for the Mr 55,000 keratin subunit. However, in carcinomas, the transcript levels for the Mr 67,000 and 59,000 subunits were only 1-3% of those observed in untreated mouse epidermis. In concert with other data, the rapid and selective loss of transcripts for differentiation-related keratins after exposure to both complete and incomplete tumor promoters is most consistent with an accelerated rate of maturation in differentiating keratinocytes, resulting in the rapid production of transcript-depleted fully mature squames. The enhanced level of Mr 55,000 transcripts suggests a concomitant increase in the number of all cells or Topics: Animals; Carcinoma; Female; Fluocinolone Acetonide; Gene Expression Regulation; Keratins; Mice; Molecular Weight; Papilloma; Phorbols; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transcription, Genetic | 1985 |
Phenotypic and cytogenetic characteristics of different stages during spontaneous transformation of mouse keratinocytes in vitro.
Topics: Animals; Calcium; Cell Differentiation; Cell Transformation, Neoplastic; Cells, Cultured; Chromosome Aberrations; Keratins; Mice; Neoplasm Transplantation; Phenotype; Precancerous Conditions; Skin Neoplasms | 1985 |
Significant decreases in the intensity of staining for proteins and protein thiols in basal-cell epitheliomas (basaliomas) as compared to normal skin.
Microphotometric measurements of fast reacting protein thiols (PSHr) and proteins were performed on freshly frozen sections of samples from normal skin (26 cases as controls) and from 45 basal cell epitheliomas (basalioma; BCE). The intensity of the staining (E/micron2) for both proteins and PSHr was significantly higher in normal epidermis than in the adjacent dermis. The values of QE (quotient of values observed in the epidermis divided by those observed in the dermis) were calculated to be 3.48 for proteins (QE, Prot) and 4.62 for PSHr (QE, PSHr). In cases of BCE, significantly lower QE values were found: QE, Prot = 2.16 and QE, PSHr = 1.72. The decrease of QE, PSHr was due to a decrease in the staining intensity observed in the BCEs, whereas practically no changes occurred in the adjacent dermis. The decrease of QE, Prot was mainly caused by a decrease in the staining intensity in the BCE (by 68%) as well as in the adjacent dermis (by 36%). By dividing the mean extinction value (E/micron2) for PSHr by the E/micron2 for proteins, a new quotient, PSHr/Prot, is obtained which can serve as a quantitative measure of the content of the tissue proteins of PSHr. The proteins of normal epidermis contained more PSHr than dermal proteins. The proteins of BCEs also contained more PSHr than those of the adjacent dermis, but the PSHr/Prot values of both tissues were 1.5 to 1.6 times greater than the corresponding values for normal epidermis and dermis, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Carcinoma, Basal Cell; Female; Humans; Keratins; Male; Proteins; Skin; Skin Neoplasms; Staining and Labeling; Sulfhydryl Compounds | 1985 |
Neuroendocrine skin carcinoma coexpressing cytokeratin and neurofilament proteins.
Neuroendocrine (Merkel cell) carcinomas of the skin have been recognized as such for several years. Given the reported wide variability in the morphology and clinical evolution of these tumors, the notion that may they comprise several variants rather than a single type has been advocated. Electron microscopy has played a key role in the early recognition of these tumors while immunohistochemical studies for various neuroendocrine markers have facilitated their subsequent diagnosis and improved our understanding as to their complexity by the demonstration of immunoreactivity for NSE (neuron specific enolase) and a number of neuropeptides. There has also been considerable interest in the study of the cytoskeletal intermediate filament complement of neuroendocrine neoplasms in general and of those of the skin in particular. Early reports indicated that neuroendocrine skin carcinomas had neurofilaments while subsequent investigations determined that they had cytokeratin. However, more recent studies have indicated that at least some neuroendocrine skin carcinomas could in fact coexpress both aforementioned classes of intermediate filament proteins. This brief report is presented to confirm the latter investigations. Topics: Carcinoma; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Male; Microscopy, Electron; Middle Aged; Neurofilament Proteins; Nose Neoplasms; Skin Neoplasms | 1985 |
Coexpression of keratin and vimentin in epithelioid sarcoma.
Topics: Adolescent; Adult; Antibodies, Monoclonal; Epithelium; Female; Humans; Keratins; Male; Sarcoma; Skin Neoplasms; Vimentin | 1985 |
Characterization of UV induced keratoacanthoma-like lesions in HRA/Skh-1 mice and their comparison with keratoacanthomas in man.
UV induced keratoacanthoma-like lesions in mice were studied grossly, light microscopically and electron microscopically. The tumours varied in their degree of cell organization and keratinization but all exhibited downward growth and had a continuous basement membrane. Ultrastructurally, the keratinocytes displayed villous distortion of their plasma membranes, and at times the basal lamina of the epidermal-dermal junction showed focal discontinuation. The keratoacanthoma-like lesions in mice had similarities of appearance to keratoacanthoma in man but showed no regression and regularly progressed to squamous cell carcinoma. This clinical course is dissimilar to that of keratoacanthoma in man which suggests that the use of the term is inappropriate for these UV induced tumours. Moreover, in the context of our experimental system and a dynamic picture of tumour development where tumour types can be seen as stably arising and continuing entities or, a progressive sequence for which squamous cell carcinoma represents an end stage, it is not appropriate to view the keratoacanthoma-like lesion in mice as an entity distinct from the spectrum of UV induced tumours progressing from benignity to malignancy. Topics: Animals; Carcinoma, Squamous Cell; Epidermis; Humans; Keratins; Keratoacanthoma; Mice; Mice, Hairless; Microscopy, Electron; Neoplasms, Radiation-Induced; Skin; Skin Diseases; Skin Neoplasms; Ultraviolet Rays | 1985 |
Alterations in the expression of two epidermal differentiation antigens in human epidermal disorders.
The expression of an epidermal keratin subunit and a specific antigen of the keratinocyte membrane, two differentiation antigens in normal human epidermis, was studied in benign and malignant epidermal lesions by use of monoclonal antibodies KL1 (anti 55-57 Kd keratins) and KL3 (anti keratinocyte membrane antigen). In normal human epidermis, KL1 labelled all keratinocytes from the suprabasal layers, KL3 stained the intercellular spaces in all epidermal layers with a fluorescence intensity increasing from the basal to the more upper layers and recognized a keratinocyte membrane antigen as demonstrated in electron microscopy. Frozen or deparaffinized sections of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) malignant melanomas, warts, and skin biopsies from benign lesions (psoriasis, lichen planus, bullous pemphigoid, lupus erythematodes, pemphigus, vasculitis) were tested with either KL1 or KL3 by indirect immunofluorescence and/or immunoperoxidase. Benign and malignant lesions in which modifications of the keratinization process and cell differentiation are known to occur (BCC, SCC, warts, psoriasis) showed the most severe alterations as compared to normal epidermis. With KL1 we observed an irregular staining of basal cells; a reorganization of keratin filaments and variable staining intensities within tumoral cells which did not express high MW keratins. With KL3 drastic alterations in the epidermal intercellular patterns and loss of reactivity of tumoral cells were noted. Conversely, the positivity of epidermal basal cells with KL1, in some cases, was the only modification noted in other skin lesions. Topics: Antibodies, Monoclonal; Antigens, Surface; Cell Differentiation; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Skin; Skin Diseases; Skin Neoplasms | 1985 |
[Oncologic and related topics].
Topics: Antibodies, Monoclonal; Antibody Specificity; Antineoplastic Agents; Combined Modality Therapy; Debrisoquin; HLA Antigens; Humans; Hydroxylation; Keratins; Lymphatic Metastasis; Melanoma; Otorhinolaryngologic Neoplasms; Polymorphism, Genetic; Protease Inhibitors; Risk; Skin Neoplasms; Tumor Stem Cell Assay | 1985 |
[Basocellular epithelioma. Considerations on its histogenesis].
Twenty-nine cases of basal cell carcinoma were studied with immunoperoxidase techniques for the detection of carcinoembryonic antigen. Results presented in the text would indicate that a high percentage of basal cell carcinomas have sweat gland histogenetic origins and that this is independent of its morphologic features. The use of immunohistochemical techniques in the detection of biological markers demonstrates once again their value not only in identifying a disease but also in determining its histogenetic origins. Topics: Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Cell Differentiation; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Skin Neoplasms; Sweat Gland Neoplasms | 1985 |
Immunofluorescent localization of intermediate filament subunits for the differential diagnosis of malignant melanoma.
Intermediate filament subunits in normal cells and in their malignant derivatives can be used as specific markers for their histogenetic origins. We have studied five neoplasms of the skin in which positive identification of vimentin containing intermediate filaments by indirect immunofluorescence microscopy helped to establish the diagnosis of malignant melanoma. All of the neoplasms included in this study posed problems in differential diagnosis by conventional light microscopy and yielded equivocal results by conventional histochemistry. Thus, definitive distinction between poorly differentiated carcinoma and poorly differentiated melanoma could not be made by conventional microscopy. In all of the neoplasms described here, immunolabeling with antibodies against different intermediate filaments demonstrated positive staining for vimentin only. This intermediate filament subunit is present in melanocytes (as well as in many mesenchymal cells) but not in epithelial cells. Our study indicates that this technique may be valuable in differential diagnosis of malignant melanoma, particularly in instances where cells lack melanin or show other atypical morphologic features. Topics: Aged; Aged, 80 and over; Cell Nucleus; Cytoplasm; Desmin; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Male; Melanins; Melanoma; Middle Aged; Skin Neoplasms; Vimentin | 1985 |
Atypical fibroxanthoma distinguishable from spindle cell carcinoma in sarcoma-like skin lesions. A clinicopathologic and immunohistochemical study of 21 cases.
A clinicopathologic study was done of 21 cutaneous, sarcoma-like lesions previously diagnosed as atypical fibroxanthoma, spindle cell carcinoma, or dermal sarcoma. These lesions were most commonly presented as a solitary, often ulcerated nodule, occurring on exposed skin of the face in the elderly or, occasionally, on roentgen-damaged or burnt skin of the head, leg, or hand. Microscopic features of the 21 lesions were, however, not alike, thereby implying that such sarcoma-like lesions had derived from heterogeneous origins. The immunohistochemical staining in a comparative study with two other cases of unequivocal spindle cell squamous carcinoma suggested that these lesions could be histogenetically divided into two different groups: (1) the major group of true atypical fibroxanthoma, consisting of 19 cases, and (2) the minor group of probable spindle cell squamous carcinoma, consisting of 2 cases. Despite a wide histologic spectrum and of heterogeneity of these lesions, there was a benign clinical course in the majority, due in part to the small size and superficial location of the lesions. Topics: Adult; Aged; Carcinoma; Diagnosis, Differential; Female; Fibroma; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Skin Neoplasms | 1985 |
Cytokeratin typing of cutaneous tumors: a new immunochemical probe for cellular differentiation and malignant transformation.
Topics: Cell Transformation, Neoplastic; Humans; Immunologic Techniques; Keratins; Peptides; Skin; Skin Neoplasms | 1985 |
Cells of extramammary Paget's disease express cytokeratins different from those of epidermal cells.
The patterns of expression of cytokeratin polypeptides which are closely correlated to routes of differentiation of epithelial cells were studied in extramammary Paget's disease. Cytokeratins of uninvolved and involved epidermis were analyzed by two-dimensional gel electrophoresis of microdissected tissue preparations as well as by immunofluorescence microscopy using cytokeratin antibodies with different specificities. In uninvolved epidermis, cytokeratins Nos. 1, 5, 6, 10, 11, 14, and 16, characteristic of keratinocytes, were found. Epidermis infiltrated by Paget's cells contained the same components and, in addition, cytokeratins Nos. 7, 8, 18, and 19, the latter being characteristic of simple and glandular epithelia, including apocrine and eccrine skin glands. By immunohistochemistry, broad-spectrum antibodies to cytokeratins decorated both keratinocytes and Paget's cells. Antibodies selective for cytokeratins Nos. 1, 10, and 11 stained suprabasal keratinocytes but not Paget's cells. In contrast, antibodies to cytokeratin No. 18 were negative on keratinocytes but the Paget's cells were selectively stained, as were the secretory cells but not the ductal cells in apocrine and eccrine glands. The results show that the cytoskeleton of Paget's cells is different from that of keratinocytes and ductal cells of skin glands and suggest that these tumor cells express the glandular type cytokeratins Nos. 7, 8, 18, and 19. This provides cell biologic support for a relationship of cells of Paget's disease to secretory cells of apocrine and eccrine glands. The histogenesis of extramammary Paget's cells is discussed in relation to these findings. Topics: Aged; Fluorescent Antibody Technique; Humans; Immunoelectrophoresis, Two-Dimensional; Keratins; Male; Paget Disease, Extramammary; Peptides; Skin; Skin Neoplasms; Staining and Labeling | 1985 |
Malignant transformation of a cloned, nontumorigenic mouse epidermal keratinocyte cell line, MSK-C3H-NU, by 7,12-dimethylbenz(a)anthracene.
MSK-C3H-NU, a cloned mouse epidermal keratinocyte cell line, was established from the epidermis of C3H/HeN mammary tumor virus-positive nude mice. Although it has lost its diploid chromosome number, the cell line is nontumorigenic, has been stable during serial subcultivations for over 2 years, and has retained some differentiated biological characteristics of normal keratinocytes. MSK-C3H-NU cells were cultured in growth medium containing 7,12-dimethylbenz(a)anthracene. After 2 months, colonies exhibited marked changes in cell morphology, cell arrangement, and keratinization pattern that appeared. The transformation frequency per 10(5) survivors in 7,12-dimethylbenz(a)anthracene-treated (10, 100, and 500 ng/ml) subgroups was 0, 119, and 1370 for Experiment I and 3.9, 238, and 2500 for Experiment II, respectively. Most of these transformed cells became malignant and formed tumors in nude mice. Histologically, the tumors were well-differentiated, keratinizing, squamous cell carcinomas showing papillary growths. In 7,12-dimethylbenz(a)anthracene-treated subgroups, cells from colonies that retained the original morphological characteristics did not form tumors in animals, and in control groups, no cell population showed tumorigenicity. In the MSK-C3H-NU cell system, the morphological alterations seem to be strongly associated with malignant conversion. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma, Squamous Cell; Cell Line; Cell Transformation, Neoplastic; Chromosomes; Clone Cells; Keratins; Mice; Mice, Inbred C3H; Mice, Nude; Skin Neoplasms | 1985 |
Histologic distribution of staining by a monoclonal antibody (psi-3) in psoriasis and occurrence of psi-3 antigen in other cutaneous diseases.
psi-3 is a monoclonal antibody that recognizes a 135,000 molecular weight structural component of maturing keratinocytes in psoriasis (the psi-3 antigen) but fails to bind to any constituent of keratinocytes in normal epidermis. This paper describes the occurrence of the psi-3 antigen in a variety of dermatopathologic conditions using immunoperoxidase (biotin-avidin-peroxidase) and immunofluorescence methods which show excellent concordance. In 35 of 36 specimens of psoriasis vulgaris, psi-3 antibody consistently immunolabels the cytoplasm of keratinocytes above the basal layer. At the edges of psoriatic plaques, psi-3 antibody staining extends for a variable distance into lesion-free epidermis. A similar pattern has been found in a certain number of other conditions described in the paper, including squamous cell carcinoma and condyloma acuminatum, but not Darier's disease, basal cell carcinoma, nor lamellar ichthyosis. In all but one condition, the outermost or basal layer of cells is never stained. The only disease in which the lowermost cell layer is stained is a lichen planus-like lesion. The occurrence of psi-3 antigen cannot be correlated with any histologic feature of psoriasis such as acanthosis, loss of the granular layer, or hyperproliferation. The antigen appears to be a unique keratinocyte constituent which is expressed in certain pathologic conditions and which is not detected by any other histologic or immunophenotyping method. It is a potentially valuable addition to the panel of antibodies available for characterizing epithelial cells. Topics: Antibodies, Monoclonal; Antigens; Biopsy; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Psoriasis; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1985 |
A monoclonal antibody labelling the keratinocyte membrane: a marker of epidermal differentiation.
A murine hybridoma secreting an IgM monoclonal antibody (KL3) was produced by cell fusion of mouse myeloma cells with spleen cells from mice immunized with human epidermal keratins. On normal human epidermis KL3 stained the intercellular spaces from the stratum germinatum to the stratum granulosum with a fluorescence intensity increasing from the basal layer to the upper layers. Basal cells were not stained on the side facing the basement membrane. About 90% of free keratinocytes isolated after trypsinization were labelled by KL3 in a punctate staining. Immunoelectron microscopy allowed us to show that the antigen recognized by KL3 was exclusively localized on the keratinocyte membrane especially in the desmosomal plaques. KL3 reactivity was not modified by preincubation of skin sections with lectins showing a selective intercellular labelling of upper layers of epidermis or pemphigus antisera, nor by adsorption of the antibody on NP40 soluble proteins of the epidermis. Though KL3 reactivity was completely abolished after adsorption of purified keratins, no immunological reactivity of KL3 was detected with epidermal keratin polypeptides blotted on nitrocellulose paper. In psoriatic epidemis and epidermal tumors KL3 reactivity was drastically modified. These results suggest that KL3 recognized a keratinocyte membrane antigen implied in the epidermal differentiation process. Topics: Animals; Antibodies, Monoclonal; Antigens, Surface; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Membrane; Epidermal Cells; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Macaca fascicularis; Mice; Psoriasis; Rabbits; Skin; Skin Diseases; Skin Neoplasms; Warts | 1985 |
Paget cells express cytokeratins typical of glandular epithelia.
The expression of cytokeratins in Paget cells in mammary and extramammary Paget's disease was studied using different keratin antibodies and immunofluorescence microscopy. Antibodies to epidermal keratin did not react with the Paget cells but stained the surrounding epidermis. Two monoclonal cytokeratin antibodies (PKKI and RGE 53), which reacted typically with simple glandular epithelia in normal tissues, brightly stained the Paget cells and left the surrounding epidermal cells unstained. The results indicate that Paget cells are derived from mammary or sweat duct epithelium rather than from epidermal cells. Topics: Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Epithelium; Female; Fluorescent Antibody Technique; Humans; Keratins; Paget Disease, Extramammary; Paget's Disease, Mammary; Skin Neoplasms; Sweat Glands | 1985 |
Development of phorbol ester responsiveness in neonatal mouse epidermis: correlation between hyperplastic response and sensitivity to first-stage tumor promotion.
As compared with the adult state, neonatal mouse skin (strain NMRI) has a hyperplastic appearance which gradually changes into the mature type between postnatal day 3 and 10. Concomitantly, the late fetal and neonatal keratin polypeptide pattern is replaced by the mature pattern. As long as the adult type of epidermal differentiation is not sufficiently developed (i.e., prior to postnatal day 5), topical application of the phorbol ester tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) causes neither morphological alterations nor a measurable induction of cellular proliferation and ornithine decarboxylase activity. TPA application at day 7 evokes, however, (i) a hyperplastic reaction followed by a massive 'psoriasis-like' hyperkeratosis, (ii) an increase of ornithine decarboxylase activity and (iii) a restoration of the neonatal keratin polypeptide pattern. Multistage tumorigenesis experiments carried out with prenatally initiated mice show that during the early period of development (prior to postnatal day 5) mouse skin is also resistant to the effects of TPA as a stage I tumor promoter. Since both the hyperplastic response and the sensitivity to tumor promotion develops in a strictly parallel manner, reactions involved in the induction of epidermal hyperplasia are assumed to provide an important condition of stage I skin tumor promotion. Topics: Animals; DNA; Female; Hyperplasia; Keratins; Mice; Mice, Inbred Strains; Mitosis; Ornithine Decarboxylase; Phorbols; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1985 |
Hypopharyngeal squamous cell carcinoma metastatic to skin.
Multiple cutaneous nodules developed in a patient with squamous cell carcinoma of the hypopharynx. Biopsy revealed poorly differentiated squamous cell carcinoma metastatic to the skin. A keratin stain confirmed the presence of keratin in the cutaneous tumor cells. Cutaneous metastases from carcinoma of the hypopharynx are very rare. Topics: Biopsy; Carcinoma, Squamous Cell; Humans; Keratins; Male; Middle Aged; Pharyngeal Neoplasms; Skin; Skin Neoplasms | 1985 |
A study of intermediate filaments (cytokeratin, vimentin, neurofilament) in two cases of Merkel cell tumor.
In two cases of Merkel cell tumor, the study of intermediate filaments, using monoclonal antibodies (vimentin, cytokeratin, neurofilaments), confirmed the double differentiation (neuroendocrine and epithelial) of this tumor as previously observed in histological, electron microscopical and histochemical analyses. Labelling of the tumor cells was positive with monoclonal antibodies against neurofilament proteins and cytokeratin. Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Cytoplasmic Granules; Cytoskeleton; Female; Humans; Intermediate Filament Proteins; Keratins; Skin Neoplasms; Vimentin | 1985 |
Distribution of keratin proteins in neoplastic and tumorlike lesions of squamous epithelium. An immunohistochemical study.
Seventy-six cases of tumorlike and neoplastic lesions from epidermis and oral epithelium were analyzed by a histochemical technique for the demonstration of keratin. Formalin-fixed paraffin sections were reacted with rabbit antihuman keratin antiserum (dilution of 1:40). The types of distribution of keratin in cells of lesions were classified into five categories: (1) regional, as found in normal squamous epithelia and benign hyperkeratinized lesions, and papilloma, and keratinized squamous cell carcinoma; (2) total, as seen in intensely keratinized lesions, such as verruca vulgaris and highly keratinized squamous cell carcinoma; (3) negative, as displayed by basal cell carcinoma; (4) scattered, as in the most poorly differentiated squamous cell carcinomas; and (5) mixed cellular, as found in both poorly and moderately differentiated squamous cell carcinomas. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dermatitis, Seborrheic; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Keratosis; Lectins; Mouth Neoplasms; Papilloma; Protein Binding; Skin Neoplasms; Warts | 1985 |
Primary neuroendocrine (Merkel cell?) carcinoma of the skin. II. An immunocytochemical study of 21 cases.
Twenty-one examples of neuroendocrine carcinoma of the skin were examined by the unlabeled antibody enzyme method for several neural hormones and peptides, carcinoembryonic antigen, S-100 protein, neuron-specific enolase, and three intermediate filaments: neurofilament, glial fibrillary acidic protein, and cytokeratin. Vasoactive intestinal polypeptide from two sources reacted with the neoplastic cells of four (18%) and seven (32%) of the cases, and pancreatic polypeptide reacted with scattered cells of one case. Neuron-specific enolase reactivity occurred in 50% of the cases. Neurofilament (70, 150, 200 kilodaltons) was strongly positive in 40% of the tumors whereas neurofilament (200 kilodaltons) was negative. Two monoclonal anticytokeratin antibodies of 54 kilodaltons and 44-54 kilodaltons reacted in 77% and 64% of the cases, respectively, in a distribution similar to the neurofilament. Sections reacted with antisera against cytokeratins of higher molecular weight were negative. The demonstration of vasoactive intestinal polypeptide, pancreatic polypeptide, neurofilament, and neuron-specific enolase is evidence of the neuroendocrine nature of this neoplasm. Topics: Carcinoma; Epidermal Cells; Epidermis; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Neurofilament Proteins; Pancreatic Polypeptide; Phosphopyruvate Hydratase; Skin Neoplasms; Vasoactive Intestinal Peptide | 1985 |
The first stage and complete promoting activity of retinoic acid but not the analog RO-10-9359.
Retinoic acid has the ability to act as either a weak first stage promoter or a weak complete promoter in the initiation-promotion protocol for skin carcinogenesis in the SENCAR mouse. The retinoid analog RO-10-9359 lacks this tumor promoting activity. Both retinoids however inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. Additional comparisons revealed that retinoic acid alone can induce dark keratinocytes, a characteristic of tumor promoters, while RO-10-9359 cannot. Retinoic acid but not RO-10-9359 can induce an immediate chemiluminescence response in human polymorphonuclear cells. Both retinoids, however, inhibit a TPA-induced response. Since the chemiluminescence response is believed to be due to oxygen free radical generation, the data suggest that the ability of retinoic acid but not RO-10-9359 to promote tumors and induce dark cells may be due to initial oxidative reactions at the cell membrane. Topics: Animals; Etretinate; Female; Keratins; Luminescent Measurements; Mice; Neutrophils; Ornithine Decarboxylase; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tretinoin | 1985 |
The cutaneous pathology of Cowden's disease: new findings.
Histological, histochemical and immunohistochemical findings were studied in 40 cutaneous biopsies from 7 patients with Cowden's disease. Most facial biopsies showed a spectrum of trichilemmomas and related follicular malformations, including cylindrical trichilemmomas, lobulate trichilemmomas (14 lesions), and a keratinizing type sharing features with inverted follicular keratosis. One facial growth showed trichilemmomal changes without apparent follicular origin. Studies for common papilloma virus structural antigens were negative, apart from a typical common wart in one patient. Immunohistochemical studies in 6 facial trichilemmomas and acral keratoses, using a panel of anti-keratin antibodies, disclosed only abnormal differentiation with lack of large keratins in the lobulate trichilemmomas. Nine biopsies revealed a distinctive type of fibroma characterized by an organized pattern of interwoven fascicles of collagen bundles with a laminated or tortuous appearance, embedded in abundant mucin. A number of fibromas showed striking hyalinization; these may represent a second microscopic hallmark of Cowden's disease in addition to facial trichilemmomas. Topics: Antigens, Viral; Biopsy; Facial Neoplasms; Fibroma; Hamartoma; Humans; Keratins; Skin; Skin Neoplasms; Staining and Labeling; Syndrome | 1985 |
Monoclonal antibodies specific for subsets of epidermal keratins: biochemical and immunocytochemical characterization--applications in pathology and cell culture.
Keratin composition has been widely used as a biochemical marker of differentiation in normal epithelia, cell culture systems and tumours of epithelial tissues. We have been developing a model system for the study of human squamous epithelial cell differentiation, and among a panel of monoclonal antibodies we have generated for analysing this system are two antibodies recognizing subsets of epidermal keratins. The two antibodies, designated LICR-LON-16a and LICR-LON-29b, were raised to the human squamous carcinoma cell line LICR-LON-HN-5, and we describe here their biochemical and immunocytochemical characterization. Antibody 16a reacts with only epidermal basal cells in normal human skin and shows specificity for the 45 and 46 kdalton keratins. Antibody 29b stains all living layers of the epidermis, and reacts with a broad range of ketain polypeptides, (45-56 kdaltons) in immunoblotting analyses. We have investigated the alterations of cellular staining that occur in chronic hyperproliferative skin diseases and carcinomas and compared this with the staining of multilayered cultures of normal keratinocytes and the HN-5 cell line. We show that in squamous cell carcinomas and in HN-5 cell xenografts 16a and 29b stain only the well-differentiated cell types. Furthermore we found that the basal cell specificity of 16a was lost in all of the hyperproliferative skin lesions examined including psoriasis and eczema. This transition to suprabasal staining pattern was also seen in the cultures of normal keratinocytes and HN-5 cells. We conclude that aberrant keratin synthesis or abnormal post-translational processing of keratins associated with an increased rate of cell turnover could account for the altered expression of the epitope recognized by antibody 16a. Topics: Antibodies, Monoclonal; Antibody Specificity; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Epitopes; Humans; Keratins; Skin; Skin Neoplasms | 1985 |
Differences of expression of cytokeratin polypeptides in various epithelial skin tumors.
In normal skin, cytokeratin polypeptides are expressed in different cell-type-specific patterns, in the keratinocytes of the different epidermal cell strata as well as in different lateral epithelial domains. Using light microscopically controlled microdissection of defined regions from frozen sections of biopsies, we have prepared cytoskeletons of various benign and malignant keratinocyte-derived tumors of human skin and analyzed their cytokeratin polypeptide patterns by two-dimensional gel electrophoresis. Premalignant fibroepitheliomas and basal cell epitheliomas display a relatively simple cytokeratin pattern (cytokeratins nos. 5, 14, 15, and 17). Pseudocarcinomatous hyperplasia, some squamous cell carcinomas, and a certain subtype of condylomata acuminata present a hair-follicle-like pattern (nos. 5, 6, 14, 16, 17). In addition to these components, variable, mostly low amounts of cytokeratins nos. 1 (Mr 68,000), and 11 are detected in most squamous cell carcinomas, in keratoacanthomas, verruca vulgaris, and another type of condylomata acuminata. In molluscum contagiosum, verruca plana, solar keratosis, and seborrheic keratosis, the cytokeratin expression is shifted more towards the normal epidermal pattern (polypeptides nos. 1, 2, 5, 10, 11, 14, 15 and traces of nos. 6 and 16 in the latter two tumors). No tumor-specific cytokeratins have been found. We conclude that keratinocyte-derived skin tumors contain various combinations of cytokeratins of the subset typical for normal keratinocytes of skin, but no cytokeratins typical for internal, simple epithelia. Different groups of tumors can be distinguished by their specific cytokeratin patterns. Possible applications of cytokeratin typing in clinical diagnosis are discussed. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Condylomata Acuminata; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Keratoacanthoma; Keratosis; Molecular Weight; Molluscum Contagiosum; Papilloma; Peptides; Skin; Skin Neoplasms; Warts | 1984 |
Cellular differentiation of basal cell carcinoma studied with fluorescent lectins and cytokeratin antibodies.
The expression of cellular glycoconjugates and cytokeratin polypeptides in 8 basal cell carcinomas (BCC) was studied using fluorochrome-coupled lectins and different keratin-antibodies. Peanut agglutinin and Wistaria floribunda agglutinin, binding to all layers of normal human epidermis, also stained all cells in the basal cell carcinomas. Dolichos biflorus agglutinin, which in normal epidermis binds only to the basal cells, gave a mottled staining pattern in most of the tumors. Instead, Ulex europaeus I agglutinin and soybean agglutinin, which in normal epidermis only bind to the spinous and granular cell layers, did not stain tumor cells in basal cell carcinomas. Rabbit antibodies to human 43-50kD epidermal keratin polypeptides and 2 monoclonal cytokeratin antibodies, PKK1 reacting only with follicular epithelium, and PKK2 reacting also with the basal epidermal cells, brightly stained all cells of the basal cell carcinomas studied, whereas antibodies to human 60-67kD epidermal keratin polypeptides did not bind to the carcinoma cells. The results suggest that the cells in basal cell carcinomas resemble epidermal basal cells both by their glycoconjugate pattern and keratin expression. However, the tumor cells also express cytokeratins, which can be found only in the follicular epithelium, but not in normal interfollicular epidermis. Topics: Adult; Aged; Antibodies; Carcinoma, Basal Cell; Cell Differentiation; Fluorescent Dyes; Humans; Keratins; Lectins; Middle Aged; Skin Neoplasms | 1984 |
Merkel cell tumor of the skin. Ultrastructural and immunohistochemical studies.
A skin tumor of a 66-year-old female was investigated morphologically and immunohistochemically. The tumor was located within the dermis and comprised of rounded cells with scanty cytoplasm, which proliferated forming a small nest or trabecular arrangement. Electron microscopic observation indicated the presence of dense-core granules within the tumor cell cytoplasm suggesting that the tumor was derived from Merkel cells. Occasionally clusters or bundles of the intermediate filaments were found in the perinuclear cytoplasm of the tumor cells. Each tumor cell was connected with desmosomes. Immunohistochemical staining with anti-keratin antiserum showed positive reaction at the perinuclear cytoplasm of the tumor cells indicating that the cluster of the microfilaments presumably contains keratin. Conversely S-100 protein was negative in the tumor cells. The results obtained strongly suggest that the tumor or Merkel cell was considered to be derived from the epidermal immature cells rather than from the neural crest. Topics: Aged; Cytoplasmic Granules; Female; Humans; Keratins; Microscopy, Electron; S100 Proteins; Skin; Skin Neoplasms; Staining and Labeling | 1984 |
New immunocytochemical observations with diagnostic significance in cutaneous neuroendocrine carcinoma.
The presence and distribution of cytokeratins, actin, neurofilament protein, neuron-specific enolase, S-100 protein, and different neuropeptides were studied immunohistochemically by the peroxidase-antiperoxidase immunoenzyme method or the avidin-biotin-peroxidase technique in 10 patients with primary cutaneous neuroendocrine carcinoma. In all cases of cutaneous neuroendocrine carcinoma, immunoreactivity for neuron-specific enolase, cytokeratin, and neurofilament was identified. No staining was found after incubation with antibodies to S-100 protein, actin, and other tested neuropeptides. The cytoplasmic cytokeratin and neurofilament immunoreactivity was particularly strong in perinuclear areas, sometimes showing an annular pattern or displaying a discoid profile. The diagnosis of cutaneous neuroendocrine carcinoma may be reliably made by the immunocytochemical demonstration of neuron-specific enolase and intermediate filaments (cytokeratin, neurofilament protein) by conventional microscopy. Cutaneous neuroendocrine carcinoma has morphological, immunological, and histogenetic similarities to carcinoid neoplasms of the gut. We favor the concept that cutaneous neuroendocrine carcinoma is derived from, or differentiates toward, dermal neuroendocrine cells. Topics: Apudoma; Diagnosis, Differential; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Neurofilament Proteins; Phosphopyruvate Hydratase; Skin Neoplasms | 1984 |
Profiles of keratin proteins in basal and squamous cell carcinomas of the skin. An immunohistochemical study.
Profiles of immunohistochemical staining for different molecular weight keratin proteins (45, 46, 55, and 63 kilodalton (kd] were evaluated in basal and squamous cell carcinomas of the skin and surrounding epidermis. Basal cell carcinomas predominantly stained with antisera to low molecular weight keratins (45 and 46 kd). Staining with antisera to higher molecular weight keratins (55 and 63 kd) was focal and restricted to areas of squamous differentiation. Invasive squamous cell carcinomas in addition to staining with antisera to low molecular weight keratins (45 and 46 kd) showed diffuse staining for 55-kd keratin and foci of staining for 63-kd keratin most prominent in keratinized regions of the tumors. In situ squamous cell carcinomas (Bowen's disease) differed from invasive squamous cell carcinoma in showing increased staining for high molecular weight keratin (63 kd). Abnormal keratin profiles were identified adjacent to and overlying basal and squamous cell carcinomas, with antisera to low molecular weight keratins (45 and 46 kd) staining all layers of the epidermis, and decreased intensity of staining for high molecular weight keratin (63 kd). Keratin profiles may help define abnormal squamous maturation in epidermis adjacent to tumors. Immunohistochemical staining for different molecular weight keratin proteins may also be helpful in the differential diagnosis of skin lesions. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Humans; Immunoenzyme Techniques; Keratins; Molecular Weight; Skin; Skin Neoplasms | 1984 |
Extramammary Paget's disease--evidence for an apocrine origin. An immunoperoxidase study of gross cystic disease fluid protein-15, carcinoembryonic antigen, and keratin proteins.
The histogenesis of extramammary Paget's disease has long remained unresolved and controversial. In an attempt to delineate the origin of the neoplastic cells in this disease, the immunoperoxidase localization of gross cystic disease fluid protein (GCDFP-15), a marker of apocrine epithelium, carcinoembryonic antigen (CEA), and keratin proteins, was determined for seven cases of extramammary Paget's disease (five vulvar, one anogenital, and one axillary). Immunoreactivity for GCDFP-15 was localized within Paget cells in six of our seven cases, including five cases from the vulva and one case from the axilla. CEA was present in the Paget cells in all seven cases. None of the Paget cells exhibited immunoreactivity for keratin proteins. Within normal skin, eccrine glands were immunoreactive for both keratin and CEA, whereas GCDFP-15 localized only to apocrine ducts and glands. Our findings strongly support an apocrine cell derivation for extramammary Paget's disease. Topics: Aged; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Axilla; Carcinoembryonic Antigen; Carrier Proteins; Female; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Membrane Transport Proteins; Middle Aged; Paget Disease, Extramammary; Skin Neoplasms; Sweat Glands; Vulvar Neoplasms | 1984 |
Immunofluorescent and immunoperoxidase staining of antibodies to fibrous keratin. Improved sensitivity for detecting epidermal cancer cells.
Microscopically controlled surgery (Mohs' surgery) is a widely accepted technique because it provides total extirpation of skin tumors with maximum conservation of tissue. However, in poorly differentiated tumors it is often difficult microscopically to recognize individual tumor cells in the midst of an inflammatory cell infiltrate, in fibrotic tissue, in connective tissue around blood vessels, in nerve sheaths, and in fascial planes. We have developed techniques to differentiate tumor cells, derived from the epidermis, from the normal nonkeratinizing tissue of mesodermal origin or the inflammatory cell infiltrate. In frozen sections, indirect immunofluorescence techniques with polyclonal antibodies to fibrous keratin allowed rapid identification of tumor cells of basal and squamous cell carcinoma. Immunoperoxidase staining proved to be a remarkably sensitive method for the identification of such carcinoma cells in both frozen and paraffin-embedded sections. When used in combination with the precise mapping techniques of Mohs' surgery, these reliable and specific stains permitted greater accuracy in assessing the total resection of an invasive tumor. Topics: Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermis; Fluorescent Antibody Technique; Frozen Sections; Humans; Immunoenzyme Techniques; Keratins; Rabbits; Skin Neoplasms | 1984 |
Opposing effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and hydrocortisone on growth and differentiation of cultured malignant human keratinocytes.
The human keratinocyte line SCC-13, derived from a squamous cell carcinoma of epidermis, was examined for effects on growth and differentiation upon treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Inhibition of growth was observable at 0.1 nM and maximal in the concentration range of 1-100 nM TCDD, but was completely antagonized by addition of hydrocortisone to the growth medium. TCDD was found to inhibit several aspects of keratinocyte differentiation that are stimulated by hydrocortisone. In confluent cultures, accumulation of keratin protein and transglutaminase activity were suppressed as well as spontaneous envelope formation and envelope competence. This phenomenon occurred without significant effect of TCDD on depletion of hydrocortisone from the medium. We conclude that the response of SCC-13 cells to TCDD depends upon hormonal conditions in culture and that this agent can interfere with cellular responses to normal physiological conditions, thereby altering the differentiation program ordinarily observed. Topics: Acyltransferases; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cell Line; Dioxins; Humans; Hydrocortisone; Keratins; Polychlorinated Dibenzodioxins; Skin Neoplasms; Transglutaminases | 1984 |
Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes.
The polypeptide composition of epidermal keratin varies in disease. To better understand the biological meaning of these variations, we have analyzed keratins from a number of human epidermal diseases by the immunoblot technique using AE1 and AE3 monoclonal antikeratin antibodies. The results reveal a continuous spectrum of keratin expression ranging from one closely resembling the normal in vivo pattern to one almost identical to cultured epidermal keratinocytes. Specifically, a 50-kilodalton (kd) (AE1-positive) and a 58-kd (AE3-positive) keratin are present in all diseases, supporting the concept that they represent "permanent" markers for keratinocytes. A 56.5-kd (AE1) and a 65-67-kd (AE3) keratin, previously shown to be markers for keratinization, are expressed only by lesions retaining a keratinized morphology. A 48-kd (AE1) and a 56-kd (AE3) keratin are present in all hyperproliferative (para- or nonkeratinized) disorders, but not in normal abdominal epidermis or in ichthyosis vulgaris which is a nonhyperproliferative disease. These two keratins have previously been found in various nonepidermal keratinocytes undergoing hyperproliferation, suggesting that these keratins are not epidermis-specific and may represent markers for hyperproliferative keratinocytes in general. In various epidermal diseases, there is a reciprocal expression of the (keratin) markers for hyperproliferation and keratinization, supporting the mutual exclusiveness of the two cellular events. Moreover, our results indicate that, as far as keratin expression is concerned, cultured human epidermal cells resemble and thus may be regarded as a model for epidermal hyperplasia. Finally, the apparent lack of any major, disease-specific keratin changes in the epidermal disorders studied so far implies that keratin abnormalities probably represent the consequence, rather than the cause, of these diseases. Topics: Antibodies, Monoclonal; Antigen-Antibody Complex; Cells, Cultured; Humans; Keratins; Molecular Weight; Skin; Skin Diseases; Skin Neoplasms | 1984 |
The ultrastructure of chondroid syringoma (mixed tumor of skin).
The ultrastructural features of a chondroid syringoma (mixed tumor of skin) are presented. The tumor consisted of groups of epithelial cells, ductal structures, and cells lying individually within a cartilaginous matrix. Many of these latter cells were indistinguishable morphologically from true chondrocytes. Some of these chondroid cells showed positive staining for cytokeratin using the immunoperoxidase technique. Transitional cells with characteristics intermediate between epithelial and chondroid cells are noted. Topics: Biopsy; Cytoskeleton; Facial Neoplasms; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasms, Germ Cell and Embryonal; Skin; Skin Neoplasms | 1984 |
Neuroendocrine carcinoma of skin with simultaneous cytokeratin expression.
An unusual tumor of the skin was removed from the thigh of a 52-year-old white male. By light microscopy, the tumor was composed of intermediate and small cells in sheets and clusters. Ultrastructural study of the tumor cells showed numerous dense core granules and dendritic cell processes as well as intermediate filaments and cell junctions frequently within the same cells. Most of the tumor cells were stained intensely by antibodies to neurone-specific enolase (NSE), a marker of cells of the central and peripheral nervous system. The neuropeptides met-enkephalin and vasoactive intestinal peptide (VIP) were also found in tumor cells. Immunohistochemistry furthermore demonstrated cytokeratin. Both the ultrastructural appearance and keratin content of this tumor set it apart from conventional Merkel cell (or trabecular) carcinoma of the skin in a manner analogous to bipartite (i.e., epidermoid and small cell) carcinoma of lung. The production of neuropeptides simultaneously with the production of keratin establishes this as a bipartite skin tumor (i.e., ectodermal and neuroectodermal phenotype). We suggest that at least some primary neuroendocrine tumors of the skin arise from multipotential ectodermal cells not of neural crest origin, as has been proposed for small cell carcinoma of lung. Topics: Apudoma; Cytoplasmic Granules; Enkephalin, Methionine; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Phosphopyruvate Hydratase; Skin; Skin Neoplasms; Vasoactive Intestinal Peptide | 1984 |
Infrared spectroscopic analysis of materials from calcified epithelioma.
An infrared spectrum of the calcified epithelioma excised from the eyelid of a three-year old girl was observed. Main absorption peaks were assigned as proteins and calcium phosphate. The crystallinity of calcium phosphate was 41%. The relative content of proteins and calcium phosphate was monitored as 7.4:1, reproducing the spectrum of the calcified epithelioma with a mixture of keratin and calcium phosphate. An epithelioma taken from the trunk of a 41-year-old man showed no calcification and the infrared spectrum of this epithelioma showed no absorption peaks of calcium phosphate. Topics: Adult; Calcinosis; Calcium Phosphates; Carcinoma; Child, Preschool; Eyelid Neoplasms; Female; Humans; Keratins; Male; Neoplasm Proteins; Skin Neoplasms; Spectrophotometry, Infrared | 1984 |
Differential staining of cytoid bodies and skin-limited amyloids with monoclonal anti-keratin antibodies.
The authors have used 5 different monoclonal antikeratin antibodies to study the antigenic profiles of cytoid bodies and skin-limited amyloids. Monoclonal antibodies AE1 (which stains the basal cell layer in normal human epidermis), AE2 (suprabasal layers), AE3 (whole epidermis), EKH4 (lower 2-3 layers), and EKH1 (recognizes all classes of intermediate filaments) were used to stain frozen skin sections by the indirect immunofluorescent or indirect immunoperoxidase technique. Cytoid bodies in lichen planus (LP) and discoid lupus erythematosus (DLE) were strongly stained with AE1, AE3, EKH4, and EKH1 antibodies but were negative with AE2. In contrast, amyloids in lichen amyloidosus and macular amyloidosis were stained strongly with EKH4 but only weakly or not at all with AE1, AE2, AE3, and EKH1. Amyloid associated with epithelial tumors showed closer immunologic profiles to cytoid body. These findings suggest that epidermal keratins are the major precursor substance of skin-limited amyloids as well as cytoid bodies in LP and DLE. Sequential changes in antigenic profiles from basal cells to amyloids through cytoid bodies further suggest that cytoid bodies may represent one of the precursor substances of skin-limited amyloids. Topics: Amyloid; Amyloidosis; Antibodies, Monoclonal; Carcinoma, Basal Cell; Fluorescent Antibody Technique; Humans; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1984 |
Melittin-stimulated arachidonic acid metabolism by cultured malignant human epidermal keratinocytes.
Upon melittin stimulation, cultured SCC-13 keratinocytes release prostaglandins E2, F2 alpha, 6-keto-F1 alpha, thromboxane B2, leukotriene B4, and 6-sulfido-peptide-containing leukotrienes (SRS) into serum free medium. Release of prostaglandins E2, F2 alpha, and SRS, normalized to cell protein, is 3- to 10-fold higher from rapidly growing than confluent cultures. Cells growing with hydrocortisone in the medium produce approximately twice the level of the cyclooxygenase-mediated metabolites PGE2 and PGF2 alpha as those without hydrocortisone, but similar levels of the lipoxygenase-mediated metabolite SRS. The results demonstrate the potential utility of squamous carcinoma lines for investigating biochemical pathways of arachidonic acid metabolism in keratinocytes. Topics: Arachidonic Acid; Arachidonic Acids; Bee Venoms; Cell Line; Humans; Keratins; Kinetics; Melitten; Prostaglandins; Skin Neoplasms; SRS-A | 1984 |
Defective low-density lipoprotein metabolism in cultured, normal, transformed, and malignant keratinocytes.
To obtain more information on differences in cellular behavior during the differentiation process, a number of types of epithelial cells with and without a defect in cornified envelope formation were compared as to the regulation of intracellular cholesterol synthesis by low-density lipoprotein (LDL) and the uptake and degradation of [125I]LDL. The following cells were cultured: normal skin fibroblasts (F), normal (K) and SV 40 transformed (SVK14) keratinocytes, and a number of squamous carcinoma cell (SCC) lines in which the defective terminal differentiation was found to occur in the following order of intensity: SCC-12F2 less than SCC-25 approximately equal to SCC-15 less than SCC-12B2 less than SCC-4. Compared with normal human fibroblasts, most of the cells under study showed a defective response to changes of the extracellular serum LDL concentration. The degree of inducibility of cholesterol synthesis after the cells were deprived of extracellular sources of cholesterol as well as the degree of the LDL-induced suppression of the intracellular cholesterol synthesis in cells preincubated in medium supplemented with lipoprotein-deficient serum decreased in the following order: F greater than SCC-4 greater than SCC-15 approximately equal to SCC-25 greater than SCC-12B2 congruent to SCC-12F2 greater than SVK14 approximately equal to K. A defect in LDL metabolism was found to be responsible for the partial or complete failure of LDL to regulate the cholesterol metabolism, because when sterol was delivered to all cell types in artificial nonlipoprotein form (i.e., as 25-hydroxycholesterol) a marked suppression of cholesterol synthesis was observed. For all SCC lines tested except SCC-12B2 good correlation was found between the degree of LDL-induced suppression of cholesterol synthesis and the decreasing ability of cells to differentiate into squames or cornified envelope-forming cells. The transformation of keratinocytes by SV 40 virus did not lead to any change in the response of the cells to changes in the extracellular LDL concentration since both the normal and the transformed keratinocytes showed the same response to LDL (i.e., no response). Topics: Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Cell Transformation, Viral; Cells, Cultured; Cholesterol; Culture Media; Epidermal Cells; Epidermis; Fibroblasts; Humans; Hydroxycholesterols; Keratins; Lipoproteins, LDL; Simian virus 40; Skin Neoplasms | 1984 |
Spindle cell tumours of the skin of debatable origin. An immunocytochemical study.
Twelve cases of malignant spindle-cell and sarcomatoid tumours of the skin of debatable nature were studied by immunocytochemical methods, using four antisera which might help contribute to resolution of the problems. The initial diagnosis made on structural grounds was confirmed by immunocytochemistry in six of eight cases in which a specific diagnosis had been made (one melanoma, three squamous carcinomas and two atypical fibroxanthomas). One case, initially regarded as AFX was reclassified as a squamous carcinoma, while a further case of possible AFX could not be confirmed by immunocytochemical study. Of the four cases in which structural examination was inconclusive, two were identified as squamous carcinomas and one as a melanoma by virtue of tumour markers. The fourth case was an intriguing actin-rich tumour of uncertain nature. Immunocytochemistry, despite certain limitations, has a valuable role to play in the analysis of the problematic spindle-cell malignant and pseudomalignant tumours of the skin. Topics: Actins; Aged; Carcinoma, Squamous Cell; Female; Fibroma; Humans; Immunoenzyme Techniques; Keratins; Male; Melanoma; Middle Aged; Muramidase; S100 Proteins; Skin; Skin Neoplasms | 1984 |
Retinoids in superficial bladder tumours update.
Topics: Animals; Cell Transformation, Neoplastic; Etretinate; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Papilloma; Skin Neoplasms; Tretinoin; Urinary Bladder Neoplasms | 1984 |
Involucrin in squamous and basal cell carcinomas of the skin: an immunohistochemical study.
Involucrin is a precursor of cross-linked protein of human stratum corneum, and its appearance in the upper layers of the epidermis is a function of the normal differentiation of the keratinocyte. Cases of basal cell and squamous cell carcinoma were evaluated for the presence of involucrin using immunoperoxidase techniques on paraffin sections. Basal cell carcinomas were negative for involucrin with staining restricted to squamous horn cysts, while squamous cell carcinomas stained strongly, particularly in large keratinized cells. Cases of squamous cell carcinoma in situ (Bowen's disease) revealed increased staining for involucrin with staining of dyskeratotic cells at all levels in the epithelium. Abnormal patterns of staining were also noted in non-neoplastic epidermis adjacent to carcinomas. Immunohistochemical staining for involucrin identifying abnormal or premature keratinization is a sensitive marker for dyskeratosis in squamous epithelia and may have applications in the histopathologic evaluation of skin specimens. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermis; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Protein Precursors; Skin Neoplasms | 1984 |
Simultaneous appearance of keratin modifications and gamma-glutamyltransferase activity as indicators of tumor progression in mouse skin papillomas.
gamma-Glutamyltransferase (GGT), an enzyme not found in normal adult epidermis, was detected in most skin papillomas larger than 13 mm in diameter and in all squamous carcinomas induced by 7,12-dimethylbenz[a]anthracene initiation and 12-O-tetradecanoylphorbol 13-acetate promotion in noninbred Sencar mice. Furthermore, these GGT-positive lesions were also characterized by a marked decrease or absence of high-molecular-weight components of epidermal keratin. Since these characteristics are common to both carcinomas and large papillomas but are practically undetectable in normal epidermis and small papillomas, GGT activity and lack of high-molecular-weight keratin components seem to be good indicators of tumor progression, i.e., from papilloma to squamous carcinoma. Topics: 9,10-Dimethyl-1,2-benzanthracene; Acyltransferases; Animals; Carcinoma, Squamous Cell; Female; Histocytochemistry; Keratins; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate; Transglutaminases | 1983 |
The use of antikeratin antibodies in the diagnosis of human neoplasms.
The presence of intracellular keratin was examined in 230 human neoplasms using indirect immunofluorescence on fresh frozen, acetone-fixed sections. The use of antikeratin antibodies raised in rabbits against human callus and purified by affinity chromatography proved to be a rapid, sensitive, and reliable method of demonstrating keratin. Epithelial tissues and epithelial-derived neoplasms were found to contain keratin, whereas tissues and neoplasms of mesenchymal, lymphoreticular, or neural crest origin did not contain intracellular keratin. This technic is a useful adjunct for the surgical pathologist in the diagnosis of poorly differentiated neoplasms. Its application either confirmed, modified, or in several instances, changed the original light microscopic impression. The modified or changed diagnoses were confirmed by transmission electron microscopy. Topics: Adult; Aged; Antibodies; Breast Neoplasms; Carcinoma, Basal Cell; Female; Fluorescent Antibody Technique; Humans; Keratins; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Middle Aged; Neoplasms; Skin Neoplasms; Thymoma | 1983 |
Trichilemmal keratosis (horn): a light and electron microscopic study.
Three cases of trichilemmal keratosis (horn) were light microscopically examined and all showed numbers of U- or V-shaped epidermal proliferations which keratinized in a fashion either identical or similar to trichilemmal keratinization. Electron microscopy revealed both uneven and linear borders between the keratinized and the keratinizing cells with a few keratohyalin droplets, remnants of desmosomes, no marginal band in the horny layer, perinuclear vacuolation, few spherical bodies in the intercellular spaces (ICS) of the upper epidermis, and widening of the ICS of the lower epidermis. A number of electron dense spherical particles, 40-50 nm in diameter, were observed in nuclei of the upper epidermis. This suggests that ultrastructure of trichilemmal keratosis is similar rather to viral warts than to trichilemmal cysts, although there are close similarities between trichilemmal keratosis and cyst. Topics: Adult; Aged; Cysts; Desmosomes; Diagnosis, Differential; Epidermis; Epithelium; Humans; Keratins; Keratosis; Male; Middle Aged; Skin; Skin Diseases; Skin Neoplasms | 1983 |
Keratin polypeptide composition as a biochemical tool for the discrimination of benign and malignant epithelial lesions in man.
An investigation was undertaken of the keratin polypeptides of various benign and malignant tumors of the human skin and vaginal epithelium by one and two dimensional gel electrophoresis. The keratin patterns of benign tumors were found to be similar to the patterns of normal epithelium or stratum corneum. The relative proportion of stratum-corneum associated keratin polypeptides to those polypeptides characteristic for the living layers corresponds to morphological features (e.g., hyperkeratosis, acanthosis). In contrast to benign tumors, epithelial carcinomas totally lack the group of high-molecular-weight keratins. This finding may be helpful in the diagnostic discrimination between benign and malignant epithelial lesions. Topics: Electrophoresis; Electrophoresis, Polyacrylamide Gel; Epithelium; Female; Humans; Keratins; Peptides; Skin Neoplasms; Vaginal Neoplasms | 1983 |
Recent advances in epidermal biology: relevance to epidermal malignancies.
Recent advances in the biology of the epidermis increase our understanding of skin cancer. Epidermal tissue culture demonstrates that cells from epidermal malignancies retain their malignant characteristics. Some epidermal tumors contain a low molecular weight keratin as a major structural protein; a low molecular weight keratin is a characteristic of fetal epidermis as well. Certain epidermal cell-surface antigens, such as the pemphigus antigen, may be absent in skin cancers. A population of long-lived skin cells may be the site for genetic alterations that eventually produces skin cancers. A population of basal "dark" cells is increased after treatment with tumor promoting agents such as phorbol esters. Two-stage (initiation, promotion) epidermal carcinogenesis can now be studied in tissue culture. Several components of the complex multilayered basement membrane zone are produced by epidermal cells. Malignancies of epidermal cells may extend beyond the basement membrane zone by disordered synthesis of the zone or by producing enzymes including collagenases that alter the zone. Topics: Animals; Antigens, Surface; Basement Membrane; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cells, Cultured; Epidermal Cells; Epidermis; Humans; Keratins; Langerhans Cells; Mice; Skin Neoplasms | 1983 |
Malignant melanomas contain only the vimentin type of intermediate filaments.
Six malignant melanomas have been examined for the type of intermediate filament they contain. All six cases showed positive staining of intermediate filaments with antibodies to vimentin, with cells containing large numbers of melanosomes being stained less strongly in general. The tumor cells did not react with antibodies to keratin, desmin, neurofilaments or glial fibrillary acidic protein. Thus typing of intermediate filaments can distinguish melanoma from undifferentiated carcinoma, but not from lymphoma or sarcoma. Since melanocytes are known to be vimentin positive, and since most of the samples we studied were from metastases, these results are a further indication that the intermediate filament type typical of the parental cell is retained in the metastases, as well as in the primaries of solid tumours. The implications of vimentin positivity for the histiogenesis of the melanocyte are also discussed. Topics: Cytoskeleton; Desmin; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Immunologic Techniques; Intermediate Filament Proteins; Keratins; Lymphatic Metastasis; Melanoma; Skin Neoplasms; Vimentin | 1983 |
Prekeratin in spindle cell tumors of the skin.
A variety of benign and malignant skin lesions was stained for the presence of prekeratin using an unlabeled antibody peroxidase-antiperoxidase method and an antibody raised against human prekeratin protein. No prekeratin could be detected in benign or malignant lesions derived from melanocytes, and prekeratin could not be found in atypical fibroxanthoma, Kaposi's sarcoma, angiosarcoma, dermatofibrosarcoma protruberans, and leiomyosarcoma. Paget's cells did not contain prekeratin. Varying staining intensities were observed in keratinocytic atypical hyperplasias. Of particular interest is the observation that many spindle cell lesions that were difficult to identify with 100% assurance from routine stains could be positively identified as squamous cell carcinoma after prekeratin was found in the atypical cells. Topics: Animals; Carcinoma, Squamous Cell; Immunoenzyme Techniques; Keratins; Protein Precursors; Rabbits; Skin Neoplasms | 1983 |
Presence of fibroblast-type intermediate filaments (vimentin) and absence of neurofilaments in pigmented nevi and malignant melanomas.
The cytoskeletal intermediate filaments of pigmented nevi and malignant melanomas (nine cases of each) were evaluated using monospecific antibodies against intermediate filament proteins and immunofluorescence microscopy. Both pigmented nevi and cutaneous malignant melanomas showed only vimentin-type intermediate filaments, but not keratin, neurofilaments, desmin or glial fibrillary acidic protein. Thus, nevi and melanomas do not show neural characteristics in the cytoskeletal intermediate filament pattern although they appear to show other neural markers. Vimentin - content in melanomas versus keratin - content in carcinomas may be used as a differential diagnostic feature. Topics: Desmin; Fluorescent Antibody Technique; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Melanoma; Neurofilament Proteins; Nevus, Pigmented; Skin Neoplasms; Vimentin | 1983 |
The distribution of keratin type intermediate-sized filaments in so-called mixed tumour of the skin.
Epithelial cells can be distinguished from various non-epithelial cells by the presence of keratin-type intermediate-sized filaments, which can be detected by immunofluorescence microscopy, using antibodies to alpha-keratin. In the present study, two types of antibodies were obtained. One of them was specific for alpha-keratin (mol. wt. 49,000 to 69,000 daltons) in whole epidermis, and the other for alpha-keratin (mol. wt. 62,000 and 69,000 daltons) in prickle and granular cells but not in basal cells. Four cases of so-called mixed tumour of the skin were studied by immunofluorescence microscopy using these antibodies. Tumour cells nests of cuboidal and polygonal cells, tubular structures and keratinous cysts reacted with these antibodies, as did individually-dispersed tumour cells within the myxoid and chondroid matrix. These results indicate that all the tumour cells of the so-called mixed tumour of the skin are of epithelial origin. Differences in staining intensity between these tumor cells and their specificity for these two antibodies are discussed with reference to keratin differentiation in tumour cells. Topics: Adult; Cytoskeleton; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Microscopy, Fluorescence; Middle Aged; Neoplasms, Germ Cell and Embryonal; Skin; Skin Neoplasms | 1983 |
Preservation of morphological, functional, and karyotypic traits during long-term culture and in vivo passage of two human skin squamous cell carcinomas.
Two cell lines (SCL-I and SCL-II) derived from squamous cell carcinomas of human skin were investigated during 4 years in culture. Both lines were tumorigenic in nude mice, and cells could be recultivated from xenografts. Growth in agar remained poor, but both cell lines developed abnormal stratified epithelial structures in organotypical cultures. The morphological and particularly ultrastructural characteristics remained typical in both cultures and xenografts. Keratinization slightly decreased, but nude mouse tumors differentiated as the original tumors, and this was reflected in keratin expression. Six major polypeptides (Mr 61,000, 57,000, 54,000, 51,000, 49,000, and 45,000) were similarly identified in both tumors and cell lines, also after animal passage, which was further substantiated by two-dimensional gel electrophoresis, but quantitative variations were found with different growth conditions. A distinct keratin cytoskeletal network was visualized in both lines by immunofluorescence, but only a few cells in SCL-II also expressed vimentin. Flow cytometry demonstrated 2c DNA stem lines for original tumors and derived lines. Early passages were hypodiploid by cytogenetic analysis of banded chromosomes. In SCL-I, a shift to tetraploidy occurred before passage 20 and remained stable throughout. In SCL-II, an incomplete shift to near tetraploidy and a stem line deviation were apparent, but later passages, nude mouse tumors, and cells recultured therefrom were hypodiploid (2c) again. Chromosome studies further revealed distinct stable marker chromosomes which showed additional structural aberrations with time in culture and after animal passage. Thus, phenotypically and genotypically, each squamous cell carcinoma and its derived cell line were distinct, and characteristics were preserved over long time periods in vitro and through in vivo passage. Topics: Animals; Carcinoma, Squamous Cell; Cell Division; Cell Line; Chromosome Banding; DNA, Neoplasm; Flow Cytometry; Humans; Karyotyping; Keratins; Kinetics; Mice; Mice, Nude; Neoplasm Transplantation; Skin Neoplasms; Transplantation, Heterologous | 1983 |
Properties of carcinogen altered mouse epidermal cells resistant to calcium-induced terminal differentiation.
Eight cell lines exhibiting resistance to Ca2+ induced terminal differentiation were derived from primary mouse epidermal cultures and their properties analyzed. The lines developed either spontaneously (2 lines) or after exposure of primary cultures to carcinogens or carcinogens and tumor promoter. All but one of the lines were of epithelial or epitheloid morphology but 3 of the 8 lines lacked desmosomes, keratin filaments and immunoprecipitable keratin proteins, and thus could not be defined as keratinocytes. Two of the 5 keratinocyte lines were tumorigenic in syngeneic Balb/c newborns after 4 months in medium containing 1.2 mM Ca2+, and 3 lines remained non-tumorigenic even after 11 months in 1.2 mM Ca2+. All three of the non-keratinizing lines were tumorigenic. Tumorigenic potential of the 5 keratinocyte lines did not correlate with ploidy (as determined by DNA content), transglutaminase activity or growth in soft agar. However, the 2 tumorigenic keratinocyte lines contained cells which stained intensely red for gamma glutamyl transpeptidase activity, while the non-tumorigenic keratinocyte lines did not. Only those lines lacking desmosomes and keratin filaments grew in soft agar, but these lines were negative for gamma glutamyl transpeptidase activity. Ploidy and transglutaminase activity did not correlate with tumorigenicity in these non-keratinizing lines. These results show that cell lines derived from cultured mouse epidermal cells and selected on the basis of their resistance to Ca2+ induced terminal differentiation may be preneoplastic. Furthermore the association of additional markers with malignant change in these cell lines depended on whether or not the cells were keratinizing. Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benz(a)Anthracenes; Calcium; Cell Differentiation; Cell Line; Cell Transformation, Neoplastic; Drug Resistance; Keratins; Methylnitronitrosoguanidine; Mice; Microscopy, Electron, Scanning; Skin; Skin Neoplasms; Skin Physiological Phenomena | 1983 |
Immunofluorescence studies on epidermal keratinization in some skin disorders with keratin antisera.
The immunofluorescence technique using antisera against human plantar stratum corneum fibrous protein (total keratin) and 64K M.W. keratin subunit isolated from total keratin by SDS polyacrylamide gel electrophoresis (PAGE) was used to examine epidermal keratinization in some skin disorders. In normal skin, total keratin was distributed throughout the epidermis, while 64K keratin was localized at the suprabasal layers. In the case of squamous cell carcinoma (SCC), the tumor cells were uniformly stained positive with total keratin antiserum, whereas diminished or negatively stained cells were observed with 64K keratin antiserum (64K antiserum), suggesting that the tumor included cells in various stages of differentiation. In basal cell epithelioma (BCE), most of the tumor cells were negatively stained with 64K antiserum being consistent with the histologic observation that BCE is originated from the basal cells. However, some of the tumor cells were stained positive with 64K antiserum, indicating that individual cell keratinization might occur in BCE. In lichen planus, an inflammatory disease demonstrating so-called lichnoid tissue reaction, positively stained colloid bodies in the upper dermis were observed either with total keratin antiserum or with 64K antiserum. It was suggested that colloid bodies resulted from individual keratinization of damaged keratinocytes during inflammation. Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epidermis; Fluorescent Antibody Technique; Humans; Keratins; Lichen Planus; Skin Neoplasms | 1983 |
Cytoplasmic fine network and mitochondria in normal and abnormal cultured keratinocytes: an electron microscopic study using whole-cell observation technique.
The cytoplasmic fine structures of both normal human cultured keratinocytes (NHK) and squamous cell carcinoma cells (HSC) were examined by electron microscopy using the whole-cell preparation method and stereo-viewing techniques. The presence of cytoplasmic fine network (CFN) was confirmed in both NHK and HSC, but the structures of the two were found to be radically different. In particular, the mitochondria showed a number of distinct morphological differences. The introduction of cytochalasin B and colchicine into HSC partially destroyed the CFN, and, as a result, the morphology of the HSC mitochondria changed to become similar to those of NHK. It seems that the CFN may have an important role in determining the shape of the cell organelles, such as mitochondria, and that the shape of the mitochondria may perhaps be used as an indication of cell malignancy. Topics: Carcinoma, Squamous Cell; Cells, Cultured; Colchicine; Cytochalasin B; Cytoskeleton; Epidermis; Humans; Keratins; Mitochondria; Skin Neoplasms | 1983 |
Anti-keratin monoclonal antibodies: production, specificities and applications.
Topics: Animals; Antibodies, Monoclonal; Fluorescent Antibody Technique; Humans; Hybridomas; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred BALB C; Microscopy, Electron; Rats; Skin; Skin Neoplasms; Sweat Gland Neoplasms | 1983 |
Changes in regional keratin polypeptide patterns during phorbol ester-mediated reversible and permanently sustained hyperplasia of mouse epidermis.
Topics: Animals; Back; Ear; Hyperplasia; Keratins; Mice; Neoplasms, Experimental; Phorbol Esters; Phorbols; Skin; Skin Neoplasms; Tail | 1982 |
Hypopigmented mycosis fungoides: report of five cases with ultrastructural observations.
Five dark-skinned individuals presented with widespread well-demarcated hypopigmented lesions, biopsy of which revealed the histopathological features of mycosis fungoides. Ultrastructural studies showed focal invasion of the epidermis by mycosis cells with degenerative changes in adjacent melanocytes and keratinocytes. The majority of melanocytes exhibited swelling of cytoplasmic organelles and disordered melanogenesis with production of spherical incompletely melanized melanosomes. In addition disintegrating melanocytes were occasionally seen. Perifollicular repigmentation within hypopigmented areas occurred in two patients following clearing of the epidermal infiltrate with PUVA therapy. Mycosis fungoides may present with areas of cutaneous hypopigmentation. Topics: Adolescent; Adult; Humans; Keratins; Male; Melanocytes; Microscopy, Electron; Middle Aged; Mycosis Fungoides; Pigmentation Disorders; Skin Neoplasms | 1982 |
Keratin modifications in epidermis, papillomas, and carcinomas during two-stage carcinogenesis in the SENCAR mouse.
To elucidate the role of keratin modification in tumor promotion, we investigated the keratin polypeptide patterns of mouse epidermis, papillomas, and carcinomas throughout an initiation-promotion experiment. The epidermal keratin modifications induced by repetitive 12-O-tetradecanoylphorbol-13-acetate treatments in both initiated and noninitiated mouse skin were essentially identical to those observed with a single 12-O-tetradecanoylphorbol-13-acetate application. These changes were even more pronounced in epidermal papillomas. In addition, the keratins of the papillomas displayed greater charge heterogeneity, particularly among the high-molecular-weight keratins (Mr 60,000 to 62,000). As the experiment progressed, there appeared to be a selective loss of one group of high-molecular-weight keratins (Mr 62,000) in some of the papillomas. Interestingly, the carcinomas that appeared at this time had significant reduction in both groups of high-molecular-weight keratins. In fact, the keratin profiles of carcinomas were very similar to the patterns observed in basal cells after a single 12-O-tetradecanoylphorbol-13-acetate treatment of adult epidermis. This may indicate that the program of keratin expression of a carcinoma becomes permanently fixed at a basal cell pattern. Changes in keratin patterns may serve as a biochemical marker of malignant progression in mouse epidermis. Topics: Animals; Carcinogens; Carcinoma; Female; Keratins; Mice; Mice, Inbred Strains; Molecular Weight; Neoplasms, Experimental; Papilloma; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1982 |
Immunohistochemical localization of keratin-type proteins in epithelial neoplasms. Correlation with electron microscopic findings.
A rabbit antiserum prepared against human keratins isolated from calluses was applied to sections of 108 neoplasms using indirect immunofluorescence and immunoperoxidase technics. The vast majority of epithelial neoplasms were strongly positive for keratin-type proteins, even in the absence of obvious keratinization or squamous differentiation as revealed by light microscopy. This keratin-positivity was invariably correlated with the identification of intermediate-sized filaments arranged in loose or dense bundles in the cytoplasm of neoplastic epithelial cells. Keratin-negative neoplasms included nevi, malignant melanomas, carcinoid tumors, malignant lymphomas, and a variety of connective-tissue tumors. Immunologic identification of keratin-type proteins was particularly helpful in establishing the epithelial nature of "undifferentiated" malignant tumors, including oat cell carcinomas. Topics: Adenocarcinoma; Animals; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Humans; Immunoenzyme Techniques; Keratins; Rabbits; Skin Neoplasms; Urinary Bladder Neoplasms | 1982 |
Retinoids. Therapeutic use in dermatology.
Topics: Acne Vulgaris; Humans; Isotretinoin; Keratins; Psoriasis; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A | 1982 |
[Structural changes of keratohyalin granules in papilloma tissue following cryogenic surgery].
Topics: Cryosurgery; Humans; Keratins; Microscopy, Electron; Papilloma; Papillomaviridae; Postoperative Period; Skin Neoplasms | 1982 |
Antibodies to intermediate filament proteins as molecular markers in clinical tumor pathology. Differentiation of carcinomas by their reaction with different cytokeratin antibodies.
Antibodies to human and bovine epidermal prekeratin and antibodies to mouse liver cytokeratin component D (Mr 49 000) have been applied in indirect immunofluorescence microscopy on sections of human tumors of mammary gland and liver. In non-neoplastic mammary gland all epithelial cells were stained with these antibodies. In pre-invasive and invasive ductal and lobular carcinomas a cell population was observed which was not significantly stained with antibodies to epidermal prekeratin but did strongly react with antibodies to liver cytokeratin D. In the liver, the antibodies to epidermal prekeratin as well as those directed against liver cytokeratin D strongly decorated bile duct epithelia. In contrast, significant staining of the hepatocytes was only achieved with antibodies to liver cytokeratin D. This different staining reaction was maintained in liver tumors of hepatocellular and cholangiocellular origin. Antibodies to vimentin stained mesenchymal cells and tumors of mesenchymal derivation but reacted not significantly with any of the epithelial and carcinoma cells examined. The difference is of practical importance for the discrimination between anaplastic carcinomas and sarcomas of unknown origin. Cytokeratin could also be detected by antibody staining using the peroxidase-antiperoxidase (PAP) technique in formaldehyde-fixed and paraffin-embedded material of skin, gastrointestinal, respiratory, urinary and genital tract as well as various glands, liver and kidney. Examples of positive reactions were shown in a squamous cell carcinoma, a basalioma and a pleomorphic adenoma of the parotis. It is concluded that the immunohistochemical analysis of intermediate filament proteins has diagnostic potential in clinical pathology and may help to elucidate histogenesis and differentiation of tumors and possibly also prognosis of tumor growth. It is further suggested to use antibodies recognizing different subsets of proteins of the cytokeratin family in order to distinguish between different types of carcinomas. Topics: Adenoma, Pleomorphic; Breast Neoplasms; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Parotid Neoplasms; Protein Precursors; Sarcoma; Skin Neoplasms | 1982 |
Comparative investigation of keratin-filaments in normal tissues and tumours of skin, oral mucosa, salivary glands and thymus.
Antibodies against different fractions of keratins can be helpful in various fields of special pathology. Antibodies against "small" and "large" keratins permit to evaluate epithelial maturation in skin and oral mucosa. In addition, disturbances of keratinization during inflammatory processes and malignant transformation can be analyzed. The main application of antibodies against the entire fractions of keratins is the detection of the epithelial nature of a neoplasm. By this tool, particular problems in surgical pathology concerning differential diagnosis can be handled in an easier way. Among the different tissues and their neoplasms, examples of the analysis of thymus tumours and salivary gland tumours are presented. Immunoreactivity with keratin antibodies depends crucially on tissue processing. In the normal diagnostic procedure, good results are regularly obtained if cryostat or Bouin-fixed paraffin-embedded sections are used. Topics: Adenoma; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoskeleton; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Parakeratosis; Salivary Gland Neoplasms; Salivary Glands; Skin; Skin Neoplasms; Thymus Gland; Thymus Neoplasms | 1982 |
Effect of tumor promote phorbol esters on the in vitro keratinization of rat epidermal cells in normal, premalignant and malignant stages.
The effect of skin tumor promote, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and related phorbol esters on primary diploid and four established, i.e. two aneuploid premalignant and two malignant, lines of fetal rat epidermal cells wee analyzed. TPA quantitatively or qualitatively affected the keratinization processes of cultured epidermal cells in the concentration range of 10 - 1,000 ng/ml. Its inhibitory effect on keratinization was obvious in the lamellar keratinization processes of aneuploid premalignant epidermal cells. With a few exceptions, the inhibition was reversible. However, TPA lethally damaged the primary diploid epidermal cells in this range of concentration. TPA did not inhibit the keratinization of malignant epidermal cells but destroyed the polarity in their keratinization processes. Topics: Aneuploidy; Animals; Cell Differentiation; Cell Division; Cell Line; Diploidy; Embryo, Mammalian; Epidermal Cells; Epidermis; Keratins; Phorbol Esters; Phorbols; Precancerous Conditions; Rats; Skin Neoplasms; Tetradecanoylphorbol Acetate | 1981 |
Immunochemical identification of intermediate-sized filaments in human neoplastic cells. A diagnostic aid for the surgical pathologist.
Forty-three tumors were investigated by means of immunofluorescence with the use of antibodies against the following different classes of intermediate-sized (10 nm) filament proteins: 1) cytokeratins, 2) vimentin, and 3) desmin. In general, the immunologic features of tumor-cell intermediate filaments are those present in their tissue of origin. It can be seen, therefore, that, during neoplastic transformation, there are no major changes in the synthesis of the type of intermediate filament proteins when compared to normal tissues. Immunologic identification of these proteins furnishes the surgical pathologist with a quick and clear-cut way to differentiate tumors of mesenchymal origin from epithelial neoplasms, and in particular to distinguish between malignant lymphomas and lymph node metastases of undifferentiated carcinomas. Topics: Adult; Animals; Antibodies; Breast Neoplasms; Carcinoma; Cytoskeleton; Desmin; Female; Guinea Pigs; Humans; Keratins; Male; Mice; Microtubules; Middle Aged; Muscle Proteins; Neoplasms; Protein Precursors; Sarcoma; Skin Neoplasms; Vimentin | 1981 |
[A case of nevus systematicus accompanied by white macules: an ultrastructural study of granular degeneration (author's transl)].
Topics: Child, Preschool; Humans; Keratins; Male; Melanocytes; Nevus; Skin; Skin Neoplasms | 1981 |
Immunofluorescence studies on civatte bodies and dyskeratotic cells with anti-keratin antibody.
So-called Civatte bodies and dyskeratotic cells were investigated in some skin disorders by using indirect immunofluorescence techniques with anti-human keratin antibody. In the disorders with lichenoid tissue reaction such as lichen planus and DLE, Civatte bodies were observed in the lower epidermis and upper dermis and they reacted distinctly to the anti-keratin antibody. In malignant skin tumors which show dyskeratotic cells in the epidermis, such as basal cell epithelioma and Bowen's disease, dyskeratotic cells were more clearly reacted to the antibody than other keratinocytes. These observations present additional new evidence for the hypothesis that Civatte bodies are derived from tonofilaments of keratinocytes. Topics: Adolescent; Aged; Animals; Antibodies; Female; Fluorescent Antibody Technique; Guinea Pigs; Humans; Keratins; Male; Microbodies; Microscopy, Electron; Middle Aged; Molecular Weight; Organoids; Rats; Skin; Skin Diseases; Skin Neoplasms | 1981 |
Correlation of prekaratin peptides and ultrastructure in epithelial cells of human skin tumors in vivo and in vitro.
Prekeratin was reduced in human skin malignancies comparing Bowen's carcinoma (BC), basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) with normal epidermis. This observation correlated with ultrastructural appearance and frequency of tonofilaments. Gel electrophoresis of tumor extracts revealed the decrease or loss of larger prekeratin peptides (65 to 68 K daltons) prominent in the epidermis. Biopsies, particularly from BC, resembled normal keratinocytes in culture with respect to their prekeratin patterns (48 to 61 K daltons). The pattern was most different, and prekeratin lowest, in SCC and derived cultures. In BCC-cultures, however, prekeratin (almost identical to keratinocytes) and filament formation significantly exceeded the respective tumor levels. Topics: Bowen's Disease; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Line; Epidermis; Humans; Keratins; Protein Precursors; Skin Neoplasms | 1981 |
Lymphocyte-epidermis interactions in malignant epidermotropic lymphomas: I. Ultrastructural aspects.
The interactions between lymphocytes, Langerhals cells and keratinocytes, are described by electron microscopy in cutaneous lesions of malignant epidermotropic lymphomas (mycosis fungoides and Sézary's syndrome). Various contacts are observed between the different cells. During the degenerating process of keratinocytes, Langerhans cells disappear and histiocytic cells are bound to necrosing epidermal cells. The immunological process of Pautrier microabscess formation is discussed by comparison with ultrastructural aspects of cutaneous lecions of G.V.H. reaction in man. Topics: Adult; Aged; Cell Nucleus; Epidermis; Female; Humans; Intercellular Junctions; Keratins; Langerhans Cells; Lymphocytes; Lymphoma; Male; Microscopy, Electron; Middle Aged; Mycosis Fungoides; Organoids; Sezary Syndrome; Skin Neoplasms | 1980 |
Experimental production of antibodies against stratum corneum keratin polypeptides.
Anti-keratin polypeptide sera (K.P.S) were obtained by immunizing guinea pigs with fibrous proteins from stratum corneum, which were acquired from normal human epidermis by m eans of S.D.S. polyacrylamide gel electrophoresis. After absorption with red blood cells and liver powder the sera were tested by indirect immunofluorescence technique on different substrates. Antibodies against polypeptides P1 and P2 of M.W. 67,000 and 62,000 dalton, respectively, were directed toward cytoplasmic Ag of keratinocytes of spinous and graunular layer of normal human and rabbit epidermis. No labeling could be detected in the basal cell layer. This finding is in favor of various differentiation stages of the keratinizing cells. P3 of M.W. 53,000 dalton induced low titre anibodies which labelled the whole epidermis, including the basal cell layer. The fourth polypeptide of M.W. 49,000 dalton seemed not to be immunogenic in such experiences. In tumors, such as basal cell carcinom,a squamous cell carcinoma, and warts, the expression of keratin antigens is markedly diminished. No analogy could be drawn between experimental keratin polypeptide antibodies and the human epidermal cytoplasmic antibodies which were detected in some patient sera. Topics: Animals; Antibody Formation; Antibody Specificity; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoplasm; Epidermis; Female; Fluorescent Antibody Technique; Guinea Pigs; Humans; Keratins; Peptides; Rabbits; Skin; Skin Neoplasms; Warts | 1980 |
Rhodamin B stain for keratin: evaluation of its specificity and its application in dermal pathology.
We used Rhodamin B stain in sections of normal skin, benign and malignant epithelial tumors and dermatoses. Keratin staining was uneven and showed variation in different lesions. While trichohyalin of the anagen hair follicle stained with intensity, keratohyalin granules failed to show similar reaction. Topics: Humans; Keratins; Rhodamines; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling; Xanthenes | 1980 |
Keratin polypeptides distribution in normal and diseased human epidermis and oral mucosa. Immunohistochemical study on unaltered epithelium and inflammatory, premalignant and malignant lesions.
Topics: Animals; Cell Differentiation; Cell Transformation, Neoplastic; Female; Guinea Pigs; Histocytochemistry; Humans; Immune Sera; Immunologic Techniques; Keratins; Molecular Weight; Mouth Mucosa; Peptides; Skin; Skin Neoplasms | 1980 |
Nuclear inclusions of tonofilaments and keratohyalin granules in the condyloma acuminatum.
Electron-microscopic investigations of the condyloma acuminatum show different nuclear inclusions in keratinocytes of the granular layer or the layer immediately below. Fibrous structures were indentified as tonofilaments and irregularly shaped electron-dense substances as keratohyalin. However the question remains as to whether there is a connection between the viral infection and the occurrence of such intranuclear inclusions. Topics: Cell Nucleus; Chromatin; Condylomata Acuminata; Cytoplasmic Granules; Cytoskeleton; Humans; Hyalin; Keratins; Male; Microscopy, Electron; Penile Neoplasms; Skin Neoplasms | 1980 |
Ultrastructural characterization of the extramammary Paget cell plasma membrane: a freeze-fracture study.
The plasma membrane ultrastructure of the extramammary Paget cells was characterized by freeze-fracture electron microscopy, which was first employed for the study of Paget cells. The Paget cell plasma membrane revealed a flat fractured plane with much fewer and smaller desmosome-particle aggregations than those of the keratinocyte. No gap junctions were detected. Many intramembranous particle-free vesicles were seen in the intercellular spaces. Particle-free blebs projecting from the plasma membranes were seen on some cell surfaces. These features greatly differed from those of keratinocytes. On the other hand, an increase of gap junctions was noticed o the keratinocytes around or in the Paget's disease lesions. Topics: Aged; Cell Membrane; Freeze Fracturing; Humans; Intercellular Junctions; Keratins; Male; Microscopy, Electron; Paget Disease, Extramammary; Skin Neoplasms | 1980 |
Clear cell carcinoma of the skin. A variant of the squamous cell carcinoma that simulates sebaceous carcinoma.
Certain clear-cell carcinomas of the skin observed in elderly caucasian men with a history of excessive sun exposure and multiple skin neoplasms may be mistaken for sebaceous carcinomas or other cutaneous clear-cell tumors. These tumors are believed to be variants of squamous cell carcinoma undergoing extensive hydropic change which results in the clear-cell appearance. They are classified into three histologic types. Type I and type III tumors are either primary or recurrent squamous-cell carcinomas. The histogenesis of type II tumors is uncertain but they may represent recurrent metastatic tumors from the previously excised, adjacent epidermal squamous-cell carcinomas; however, the possibility that they are primary adnexal tumors of undetermined histogenesis remains to be determined. Various techniques of staining, as well as differences in histologic appearance, assist in the differential diagnosis of these and other cutaneous clear-cell neoplasms. Topics: Adenocarcinoma; Aged; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Male; Middle Aged; Sebaceous Gland Neoplasms; Skin Neoplasms | 1980 |
[Rhodamine B: a tracer of follicular keratinization (author's transl)].
The mixture at equal volumes of a 0.1 p. 100 solution of rhodamine B in distilled water and of a 0.25 p. 100 solution of toluidine blue in Walpole's pH 4.4 buffer dyes each pilar sheath differently. At the level of the medulla, the granules fix rhodamine B, so do the cortical cells at the level of the keratogenic zone. Once they are keratinized, however, cortical cells remain colorless. Concerning the cells of the inner root sheath, on the other hand, their trichohyaline granules are dyed by rhodamine B, whereas the keratinized cells turn dark blue under the effect of toluidine blue. The trichilemmal keratin both of the isthmus of the anagen hair and of the follicular sac becomes light red. This technique, which can be easily applied to the trichogram, allows us to identify more or less mature pilar anlages in in adnexal tumors, to differentiate keratinizing cysts and to trace various pathological keratins. Thanks to a chemical study, it was shown that the mixture rhodamine B-toluidine blue is only a mechanical mixture which works through its acide-bases properties. Topics: Carcinoma, Basal Cell; Cysts; Diagnosis, Differential; Epidermis; Hair; Hair Diseases; Histocytochemistry; Humans; Keratins; Rhodamines; Skin Neoplasms; Xanthenes | 1980 |
Keratins as markers of malignancy in mouse epidermal tumors.
A comparative study of the keratin composition of adult and neonatal mouse epidermis, benign and malignant tumors of mouse skin and murine epidermal cells grown in culture revealed striking differences in the keratin polypeptide patterns when analyzed by one-dimensional gel electrophoresis. Not only did the study confirm body-site specific alterations in the keratin patterns within one species, but it also demonstrated that similar to cultured epidermal cells, three malignant skin tumors investigated specifically lacked a group of keratin components with molecular weights larger than 61,000 daltons, which were invariably present in all normal and also in benign tissues. These findings offer the possibility of using keratins as molecular markers of the malignant state of epidermal cells. Two-dimensional gels of the keratin polypeptides of normal epidermis and of benign tumors exhibited spot patterns which could be divided at the 61,000 dalton level into an essentially basic subgroup, comprising the high molecular weight keratins, and an acidic subgroup including the low molecular weight components. The two uppermost proteins of cultured epidermal cells and carcinomas (molecular weights 61,000 and 58,000 daltons) belong to the acidic subgroup in normal tissues as well as in papillomas. However, in the case of malignant tumors and in vitro transformed epidermal cells they showed distinct alterations in charge in that they migrated into the more alkaline part of the gel. The number of spots appearing in the more basic region of the gel could be inversely related to the degree of differentiation exhibited by tumors or in vitro cells. Topics: Animals; Animals, Newborn; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Epidermis; Keratins; Mice; Neoplasms, Experimental; Skin Neoplasms | 1980 |
Two siblings with epidermodysplasia verruciformis with large clear cells in the epidermis: electron microscope and immunological findings.
In two Arab brothers presenting the characteristic clinical picture of epidermodysplasia verruciformis (EV), histological examination revealed large clear cells in the granular layer and uppermost part of the prickle cell layer of the epidermis. The report of this histological picture in two cases by other authors in the past had aroused considerable discussion as to the true diagnosis. The finding of large clear cells in our two confirmed cases of EV supports the opinion that this does not necessarily contradict the diagnosis of EV. Electron microscope investigation revealed groups of particles in the nuclei of a few keratinocytes in the granular layer which were compatible with papova virus particles. The changes seen in the clear cells support the theory of the viral etiology of EV. Ehe immunological studies showed intact humoral immunity but impaired cellular immunity. Topics: Adolescent; Epidermis; Humans; Keratins; Male; Papillomaviridae; Polyomaviridae; Precancerous Conditions; Skin Diseases; Skin Neoplasms; Syndrome | 1979 |
Trichilemmal horn: cutaneous horn showing trichilemmal keratinization.
A unique and distinctive clinicopathological entity occurred in nineteen patients who ranged in age from 16 to 72 (median 50) years. Clinically, these were solitary cutaneous horns. Nine were on the limbs, four on the back, two on the face, three on the scalp, and in one the site was not known; the median duration was 2 years. Histologically, there was a benign picture with a protrusion of massive horn and trichilemmal keratinization at the base. This tumour, which I have named trichilemmal horn, must be differentiated from other lesions that show trichilemmal keratinization (trichilemmal cyst, proliferating trichilemmal cyst, keratoacanthoma) and from other cutaneous horns, including trichilemmomal horn (cutaneous horn overlying trichilemmoma). Topics: Adolescent; Adult; Aged; Cysts; Diagnosis, Differential; Female; Humans; Keratins; Male; Middle Aged; Skin; Skin Diseases; Skin Neoplasms | 1979 |
Basal cell carcinoma--signet ring type. Ultrastructural study.
Light microscopic examination of a basalioma (basal cell carcinoma) revealed unusual keratinizing cells resembling signet ring cells with pink cytoplasmic inclusions. Ultrastructurally the inclusions consisted of filamentous masses encircled by abundant tonofilaments giving a striking picture of abnormal individual tumor cell keratinization. Topics: Aged; Carcinoma, Basal Cell; Cytoplasm; Humans; Keratins; Male; Skin Neoplasms | 1979 |
A tridimensional view of intradermal nevi as revealed by scanning electron microscopy.
When scanning electron microscopy (SEM) was applied to the study of intradermal nevi, interesting tridimensional features were recognized. The free surface of the lesions showed ruffled keratinized cells. "Normal" hairs as well as "corkscrew" hairs emerged from the follicular openings. Nevus cells were either round or elongated and surrounded by connective tissue fibers. Topics: Adult; Hair; Humans; Keratins; Microscopy, Electron, Scanning; Nevus, Pigmented; Skin; Skin Neoplasms | 1979 |
Qualitative changes in the biologic characteristics of cultured fetal rat keratinizing epidermal cells during the process of malignant transformation after benzo[a]pyrene treatment.
In vitro malignant transformation of fetal rat keratinizing epidermal cells from inbred SD rats after benzo[a]pyrene (BP) treatment was analyzed from various biologic viewpoints. BP treatment directly and indirectly effected changes in cell growth characteristics, i.e., temperature dependence for growth, in vitro keratinization, chromosome structure, and the ability to form colonies on plastic substrate, on 0.57% agar medium layer, and in 0.33% soft agar medium. BP-treated cells at 30 degrees C remained in the premalignant stages and showed shifts in chromosome structure toward the hypodiploid range and parakeratotic changes in their keratinization process. However, the cells failed to form colonies even on a plastic substrate. BP-treated cell lines that adapted to temperatures of 35 and 37.5 degrees C remained in the premalignant stages; however, they acquired the ability to form colonies on plastic substrates during subcultivation. Malignantly transformed colonies appeared in these cell lines. In vitro keratinization processes were classified into nearly normal (diffuse lamellar, focal lamellar, and parakeratotic), intermediate, and atypical subtypes (columnar, spherical, and single-cell type). Cells of atypical keratinization subtypes and some of the intermediate subtypes formed squamous cell carcinomas in syngeneic hosts. Malignantly transformed cells showed shifts in chromosome structure toward the hypotetraploid range and colony formation on the 0.57% agar medium layer. However, they failed to form colonies in 0.33% soft agar medium. With the use of changes in biologic characteristics of the cells as indicators, fetal rat keratinizing epidermal cells in culture were classified into five stages. The appearance of stage III cells seemed to be the first key step in their malignant transformation. Topics: Animals; Benzopyrenes; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Chromosome Aberrations; Clone Cells; Keratins; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Skin Neoplasms; Transplantation, Isogeneic | 1979 |
Scanning electron microscopy of dermatofibromas.
The three-dimensional morphology of six dermatofibromas was studied by scanning electron microscopy. Hypertrophic epidermal ridges covered with large keratinized cells overlay each dermal lesion. Small collagenous fibers in the tumors contrasted with the bundles of much larger collagenous fibers in the normal dermis peripheral to the lesions. Topics: Adult; Female; Fibroma; Humans; Keratins; Male; Microscopy, Electron, Scanning; Middle Aged; Skin; Skin Neoplasms | 1979 |
Trichilemmal tumor undergoing specific keratinization: "keratinizing trichilemmoma".
Numerous tumors with follicle-like direction of differentiation have been described. At least three of them connected to the overlying epidermis are related to the outer root sheath or trichilemma: the tumor of follicular infundibulum (Mehregan & Butler 1961) and the inverted follicular keratosis (Helwig 1955) or follicular poroma (Duperrat & Mascaro 1963) have been related to the infundibulum, the tricholemmoma (Headington & French 1961) to the lower outer root sheath. On the occasion of a case first diagnosed as proliferating trichilemmal cyst of the scalp, we think we have individualized a tumor exhibiting ability to undergo trichilemmal keratinization. We describe its histogenesis and stress its peculiarties compared with other lesions showing trichilemmal keratinization. Topics: Aged; Epidermis; Female; Hair; Humans; Keratins; Scalp; Skin Neoplasms | 1979 |
[Viral acanthomas and specialized forms of keratinosome "membrane coating granules" (author's transl)].
In the case of viral acanthomas, the stratum spinosum and granulosum presents ballooned cells which contain all transitional stages from multivesicular bodies (MVB) to keratinosomes. A particularity in condylomata acuminata are the "wagon-wheel" bodies. These structures are typical for the non keratinazed squamous epithelium. The participation of intercellular extruded "wagon-wheel" bodies, MVB and atypical keratinosomes on an irregular baso-apical diffusion-barrier in the epidermis of cases with viral acanthomas has been discussed. On the basis of the relation seen between MVB and the Golgi-apparatus, their transition to partially atypical keratinosomes in cases of viral acanthomas and their "expulsion" into the intercellular space could indicate that in keratinozytes the enzymatically regulated feed-back between the cellular surface and the capability to synthesize is changed by viral agents. The interference appears to manifest itself in the Golgi-apparatus and also appears to be "specified" by the terrain present. Topics: Animals; Condylomata Acuminata; Cytoplasmic Granules; Epithelium; Humans; Keratins; Laryngeal Neoplasms; Microscopy, Electron; Papilloma; Skin Diseases; Skin Neoplasms; Tumor Virus Infections; Warts | 1978 |
Cutaneous nevi.
Topics: Adolescent; Cell Transformation, Neoplastic; Humans; Ichthyosis; Infant, Newborn; Keratins; Melanoma; Nevus; Nevus, Pigmented; Skin Neoplasms; Warts | 1978 |
Inflammatory linear verrucose epidermal nevus. A pathologic study.
We saw three patients with inflammatory linear verrucose epidermal nevus (ILVEN). The purpose of this study is to better delineate the histopathologic features of this type of nevus. In fact, in all three cases very particular, specific histologic lesions have been noted that permit us to better distinguish this recently outlined entity. The histologic features were depressed, cup-like areas of hyper-granulosis with overlying orthokeratotic hyperkeratosis, alternating (with sharp dermacation) with raised, level areas of agranulosis with overlying parakeratotic hyperkeratosis. Topics: Adult; Child; Female; Humans; Infant; Keratins; Keratosis; Male; Nevus, Pigmented; Parakeratosis; Skin Neoplasms | 1977 |
["Pagetoid reticulosis" (Woringer and Kolopp disease). A disease of the Merkel cell (author's transl)].
A case of Woringer and Kolopp disease "Pagetoid reticulosis" is described. Clinical features include a ring of a target pattern of erythemato-squamous infiltrated skin lesion. The characteristic histological aspect of dense epidermal infiltrate by abnormal cells with a spared dermis has been observed. Ultrastructural findings include cytoplasmic granules with a found electron dense core and close relationship to neurites, two features of the Merkel cell of human normal epidermis. By comparing our patients with the already reported cases of Woringer and Kolopp disease it seems likely that this is a unique disease with no relationship with cutaneous lymphoma but which is defined by a Merkel cell proliferation. Topics: Aged; Cytoplasm; Humans; Keratins; Langerhans Cells; Lymphatic Diseases; Male; Melanocytes; Organoids; Skin Neoplasms | 1977 |
Tumors of the pilosebaceous unit induced in the rat by the intravenous administration of 7,12-dimethylbenz(A)anthracene.
Six of 70 female Sprague-Dawley rats given a single intravenous injection of 7,12-dimethylbenz[a]anthracene (DMBA) developed 7 pilosebaceous tumors. Two of the tumors showed differentiation toward the upper portion of the pilosebaceous unit while 5 showed differentiation toward the lower portion. Each tumor was examined histochemically for the presence of inner root sheath keratin of the hair follicle using the carbamido diacetyl reaction for citrulline and for hair shaft keratin using boiling ninhydrin reagent. The 2 tumors of the upper portion of the pilosebaceous unit were sebaceous adenomas which were accompained by a keratinizing epithelim like that of the sebaceous gland duct and upper pilosebaceous canal. Histochemically, the keratin was not like that of hair shaft nor inner root sheath. The 5 tumors showing differentiation toward components of the lower pilosebaceous unit were trichoepitheliomas. They were composed of structures which, to varying degrees, recapitulated the organization of the normal hair follicle. Within these follicular structures, both inner root sheath and hair shaft type keratins were found. The occurrence of skin tumors after the intravenous administration of DMBA was unexpected since it is uncommon for skin tumors to be produced by the systematic administration of chemical carcinogens and they have never been described after the oral administration of DMBA. That the route of administration may influence tumor production with this carcinogen is suggested by the fact that the only other reported tumors, which were squamous carcinomas, also followed intravenous injection of DMBA. Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenoma; Animals; Benz(a)Anthracenes; Female; Hair; Injections, Intravenous; Keratins; Neoplasms, Experimental; Rats; Sebaceous Gland Neoplasms; Skin Neoplasms | 1976 |
Cellular changes in the basaloid cell papilloma.
Electron microscopic analyses of basaloid cell papillomas of the solid and papillomatous types are reported. The submicroscopic organization is described. Some of the ultrastructural findings, e.g. an increased number of mitochondria, a certain mitochondrial polymorphismus, the occurrence of irregularly shaped intracytoplasmic vesicles, the abundance of endoplasmic reticulum hypertrophy and the remarkable presence of microtubule-like structures, an unusual finding in a material fixed at the temperature used, are indicating an altered metabolic activity. The alternating presence and absence of keratohyalin is found to be submicromorphologically related to the formation of A- respectively B-cells. This is compared with the formation of parakeratosis in psoriatic lesions without keratohyalin. A formation of orthokeratosis as seen by the light microscopical procedure seems possible without preceeding occurrence of keratohyalin. Topics: Carcinoma, Basal Cell; Cell Nucleus; Cytoplasm; Cytoplasmic Granules; Endoplasmic Reticulum; Humans; Hyalin; Keratins; Keratosis; Microscopy, Electron; Microtubules; Mitochondria; Parakeratosis; Ribosomes; Skin Neoplasms; Temperature | 1975 |
Second European Meeting on Electron Microscopy applied to Cutaneous Pathology.
Topics: Humans; Keratins; Microscopy, Electron; Pigmentation; Skin; Skin Diseases; Skin Diseases, Vesiculobullous; Skin Neoplasms | 1975 |
Congenital circumscribed hypomelanosis: a characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus, and piebaldism.
Subcellular defects of hypomelanosis in tuberous sclerosis (TS) (28 subjects) were compared by light and electron microscopy with oThere forms of congenital circumscribed hypomelanosis that occur in nevus depigmentosus (ND) (8 subjects) and in piebaldism (PB) (4 subjects), respectively. On the light microscopic level in both TS and ND, the population density of functioning melanocytes was normal but each perikaryon was small, and dopa activity was decreased. On the ultrastructural level, the hypomelanotic skin and hair of TS were associated with a decrease in the synthesis, melanization, and size of melanosomes; the decrease in the size of melanosomes resulted in the aggregation of melanosomes (i.e., a melanosome complex) in the keratinocytes in all the specimens examined. In ND, ther were no obvious changes in the size and melanocytes. the hypomelanosis of ND is related to the decreased synthesis and also, perhaps, abnormal transfer of melanosomes. In PB the hypomelanosis of the skin and hair results from the absence of functional melanocytes. The hypermelanotic areas of PB, however, characteristically contain melanocytes that synthesize abnormal (sperical and granular) as well as normal (ellipsoidal and lamellar) melanosomes. Topics: Adolescent; Adult; Albinism; Black People; Child; Child, Preschool; Dihydroxyphenylalanine; Female; Hair; Humans; Infant; Keratins; Male; Melanins; Melanocytes; Microscopy, Electron; Nevus; Organoids; Pigmentation Disorders; Skin; Skin Neoplasms; Tuberous Sclerosis; White People | 1975 |
Keratin granulomas in squamous cell carcinomas treated by irradiation.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Granuloma; Head and Neck Neoplasms; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Skin Neoplasms | 1975 |
[Occurrence of intracytoplasmic desmosomes in keratinocytes (author's transl)].
Topics: Biopsy; Cell Membrane; Cytoplasm; Desmosomes; Humans; Keratins; Keratoderma, Palmoplantar; Melanoma; Microscopy, Electron; Skin; Skin Neoplasms | 1974 |
Aspects of skin biology pertinent to pharmacology.
Topics: Animals; Cell Division; Connective Tissue; Disease Models, Animal; Epithelial Cells; Humans; Keratins; Melanocytes; Pigmentation Disorders; Psoriasis; Skin; Skin Diseases; Skin Neoplasms; Vitiligo | 1974 |
[Adhesive tape induced depigmentation. An ultrastructural study and comparison with vitiligo and vitiliginous depigmentation associated with melanoma (author's transl)].
Topics: Adhesiveness; Bandages; Basement Membrane; Biopsy; Diagnosis, Differential; Dihydroxyphenylalanine; Humans; Keratins; Langerhans Cells; Male; Melanocytes; Melanoma; Microscopy, Electron; Middle Aged; Pigmentation Disorders; Skin Neoplasms; Vitiligo | 1974 |
[Clear-cell acanthoma. Clinical, histological and ultrastructural observations (author's transl)].
Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasmic Granules; Diagnosis, Differential; Female; Humans; Keratins; Leg; Male; Middle Aged; Papilloma; Skin Neoplasms | 1974 |
Trichodiscoma. A benign tumor related to haarscheibe (hair disk).
Topics: Adult; Biopsy; Diagnosis, Differential; Female; Fibroma; Follow-Up Studies; Hair; Hamartoma; Humans; Keratins; Male; Melanins; Middle Aged; Mucins; Neurofibroma; Sensory Receptor Cells; Skin; Skin Neoplasms | 1974 |
Pilomatrixoma (epithelioma calcificans Malherbe). A clinical and histopathological survey of Danish material from 1954 to 1971.
Topics: Adolescent; Adult; Aged; Basophils; Calcinosis; Child; Child, Preschool; Citrulline; Epithelial Cells; Eyelid Neoplasms; Facial Neoplasms; Female; Granulation Tissue; Hair; Humans; Infant; Keratins; Male; Sex Factors; Skin Neoplasms; Staining and Labeling; Syndrome | 1973 |
The modulation in fasted hosts of a tumour's growth and the contrasting stability of its intrinsic grade of malignancy.
Topics: Animals; Cell Differentiation; Fasting; Keratins; Mice; Mitosis; Neoplasms, Experimental; Papilloma; Skin Neoplasms | 1973 |
[Solitary epidermolytic acanthoma].
Topics: Adult; Edema; Humans; Hyalin; Keratins; Keratoacanthoma; Male; Melanins; Melanocytes; Pigments, Biological; Skin Neoplasms | 1972 |
Syringocystadenoma papilliferum. An electron microscopic study.
Topics: Adenoma, Sweat Gland; Adolescent; Aged; Collagen; Cytoplasmic Granules; Desmosomes; Ear, External; Epithelial Cells; Female; Glycogen; Humans; Inclusion Bodies; Infant; Keratins; Leukocytes; Lipids; Lysosomes; Macrophages; Male; Melanocytes; Microscopy, Electron; Mitochondria; Mucus; Neutrophils; Skin Neoplasms | 1972 |
[Electron microscopy study on the morphology of Paget cells].
Topics: Desmosomes; Endoplasmic Reticulum; Epithelial Cells; Female; Glycogen; Golgi Apparatus; Humans; Keratins; Lysosomes; Microscopy, Electron; Microtubules; Middle Aged; Mitochondria; Mitosis; Paget Disease, Extramammary; Ribosomes; Skin Neoplasms | 1972 |
[Ultrastructural study of the skin in Xeroderma pigmentosum].
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Keratins; Macrophages; Male; Melanocytes; Microscopy, Electron; Skin Neoplasms; Xeroderma Pigmentosum | 1972 |
[Various forms of endoplasmic reticulum in dedifferenciated keratinocytes. Observations in squamous cell carcinoma].
Topics: Biopsy; Carcinoma, Squamous Cell; Endoplasmic Reticulum; Histocytochemistry; Humans; Keratins; Lipids; Microscopy, Electron; Ribosomes; Skin Neoplasms | 1972 |
Dyskeratosis in Bowen's disease: the ultrastructure and fate of keratinocytes with altered tonofilament-desmosome complexes.
Topics: Acantholysis; Carcinoma, Squamous Cell; Cell Membrane; Cytoplasm; Desmosomes; Epithelial Cells; Epithelium; Extracellular Space; Humans; Keratins; Langerhans Cells; Melanins; Mitochondria; Organoids; Ribosomes; Skin Neoplasms | 1971 |
The effect of keratinisation of the respiratory metabolism of epitheliomas in DMBA-treated mice skin.
Topics: Animals; Benz(a)Anthracenes; Carcinoma; Glycolysis; Keratins; Lactates; Male; Mice; Oxygen Consumption; Skin Neoplasms | 1971 |
The familial occurrence of multiple eruptive milia.
Topics: Adult; Bone Cysts; Carcinoma, Basal Cell; Diagnosis, Differential; Epidermal Cyst; Humans; Jaw Diseases; Keratins; Male; Ribs; Skin; Skin Neoplasms; Syndrome | 1971 |
The cutaneous amyloidoses. I. Localized forms.
Topics: Adult; Aged; Amyloid; Amyloidosis; Collagen; Diagnosis, Differential; Female; Forearm; Humans; Keratins; Leg Dermatoses; Lichen Planus; Lipidoses; Male; Melanins; Middle Aged; Pruritus; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling | 1970 |
[Practical significance of histochemistry].
Topics: Basement Membrane; Carcinoma; Dermatology; Diagnosis, Differential; Esterases; Fluorescent Antibody Technique; Glycogen; Histocytochemistry; Humans; Keratins; Keratoacanthoma; Keratosis; Lupus Erythematosus, Discoid; Mast-Cell Sarcoma; Psoriasis; Skin; Skin Diseases; Skin Neoplasms; Sweat Glands; Urticaria | 1970 |
Differentiating neoplasms of hair germ.
Differentiating neoplasms of hair germ are benign epithelial-mesenchymal tumours of skin in which hair follicle development may be partly or completely recapitulated. The epithelial component is equivalent to the hair germ. The mesenchymal component is equivalent to the dermal papilla. Epithelial-mesenchymal interaction results in the morphogenesis of hair follicles. In neoplasms showing stromal induction, there is centrifugal organizations: hair bulbs are found at the periphery of tumour lobules and hairs are projected centrally to lie within small keratinizing cysts. Neoplasms of hair germ without advanced morpho-differentiation are termed ;trichoblastomas', and those neoplasms in which hair follicle development is advanced are called ;trichogenic trichoblastomas'. Topics: Adult; Epithelium; Female; Hair; Humans; Keratins; Male; Middle Aged; Morphogenesis; Scalp; Skin; Skin Neoplasms | 1970 |
Papillomas (warts) in hairless mice. Mus musculus and Peromyscus maniculatus gambeli.
Topics: Animals; Dermoid Cyst; Epithelium; Female; Fibroblasts; Hair; Histiocytes; Keratins; Male; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Papilloma; Skin; Skin Neoplasms; Transplantation, Homologous; Warts | 1970 |
A cutaneous horn on the bovine teat.
Topics: Animals; Cattle; Cattle Diseases; Female; Horns; Keratins; Mammary Glands, Animal; Papilloma; Skin Neoplasms | 1970 |
Pilomatrixoma--calcifying epithelioma (Malherbe).
Topics: Basophils; Calcinosis; Hair; Humans; Keratins; Ossification, Heterotopic; Skin Neoplasms; Staining and Labeling | 1969 |
[Physiopathology of keratogenesis--electron microscopy study].
Topics: Carcinoma, Basal Cell; Humans; Ichthyosis; Keratins; Keratosis; Microscopy, Electron; Mitochondria; Psoriasis; Skin Neoplasms | 1969 |
[Verrucose nevus in a water jet with dystrophic cells ("acanthikeratolysis"). Histochemical study].
Topics: Adolescent; Histocytochemistry; Humans; Keratins; Male; Nevus; Skin; Skin Neoplasms | 1968 |
Inability to induce keratinization in basal cell tumors. Wounding and application of resin podophyllum.
Topics: Adolescent; Adult; Biopsy; Carcinoma; Humans; Keratins; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Podophyllum; Skin Neoplasms; Wound Healing | 1967 |
Keratin in normal and abnormal epidermis.
Topics: Aging; Birefringence; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemistry Techniques, Analytical; Humans; Keratins; Keratosis; Microscopy, Polarization; Skin; Skin Neoplasms; Staining and Labeling | 1966 |
An electron microscope study of squamous cell carcinoma in merino sheep associated with keratin-filled cysts of the skin.
Topics: Animals; Carcinoma, Squamous Cell; Cysts; Keratins; Sheep; Sheep Diseases; Skin Neoplasms | 1966 |
[LEUKOPLAKIC EPITHELIAL NEVI OF THE ORAL MUCOSA AND THEIR KERATINIZATION FORM].
Topics: Adolescent; Child; Humans; Keratins; Leukoplakia; Mouth Mucosa; Mouth Neoplasms; Nevus; Nevus, Pigmented; Pathology; Skin Neoplasms | 1965 |