bromochloroacetic-acid and Carcinoma--Merkel-Cell

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

Merkel cell carcinoma (MCC) is an uncommon primarily dermal malignancy of relatively aggressive biologic course. Several presentations in the mucosa of the head and neck region have been reported in the literature, and 3 such patients have recently been seen at our institution. We review this recent experience and present the first reported primary lingual MCC in a 57-year-old caucasian man. We provide a review of oral mucosal MCC and guidelines for histopathologic and immunohistochemical diagnosis. Merkel cell carcinoma should be included in the differential diagnosis of head and neck mucosal lesions, especially if the tumor is submucosal, and MCC may involve the tongue. Mucosal MCC is aggressive, and there is a high risk for local recurrence and regional and distant metastasis. Fulminating courses are often seen. We discuss our treatment policies based on the current literature.

Topics: Aged, 80 and over; Biomarkers; Carcinoma, Merkel Cell; Chromogranin A; Chromogranins; Fatal Outcome; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratin-20; Keratins; Lip Neoplasms; Male; Middle Aged; Mouth Mucosa; Phosphopyruvate Hydratase; Synaptophysin; Tongue Neoplasms

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

Merkel cell carcinoma (Mcc) is an uncommon and aggressive tumour with neuroendocrine features that occur predominantly in the head and neck region. The rarity of this tumour, especially when it arises in the oral mucosa, makes both early identification and standardisation of treatment difficult, particularly as regards complementary treatment. The availability of monoclonal antibodies with restricted specificity for some antigens thought to be related to neuroendocrine carcinomas, such as Merkel cell carcinoma, and ultrastructural studies offer some new leads to investigation. This has allowed, a greater number of these tumours to be discovered, thereby increasing the chances of effective management. A case of Mcc of the floor of the mouth is reported, together with the results of cytokeratin, neuron specific enolase and chromogranin immunohistochemistry.

Topics: Antibodies, Monoclonal; Carcinoma, Merkel Cell; Chromogranins; Fatal Outcome; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Mouth Floor; Mouth Neoplasms; Neoplasm Proteins; Phosphopyruvate Hydratase

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

Merkel cell carcinomas (MCC) were compared to small cell carcinomas of the lung (SCCL) and oesophagus (SCCO). Most MCC were of the intermediate cell type while SCCL and SCCO were usually of the small cell type. Only MCC of trabecular type could be separated from SCCL and SCCO by means of histopathological examination alone. All MCC (25) stained with cytokeratin CAM 5.2, 20 of which in a "paranuclear globular" or combined "paranuclear globular"/diffuse pattern while 17 MCC stained with cytokeratin AE1/AE3. Cytokeratin CAM 5.2 reacted with 60 percent of the SCCL and 86 percent of the SCCO, and cytokeratin AE1/AE3 with 33 and 28 percent respectively. Neurofilament stained 17 MCC in a "paranuclear globular" pattern but none of the SCCL and SCCO. All MCC with a diffuse staining pattern for cytokeratin CAM 5.2 were negative for neurofilament. The results of this study and review of the literature indicate that in most instances Merkel cell carcinoma can be separated from other SCC, pulmonary as well as extrapulmonary, by means of histopathological and, above all, immunohistochemical examinations.

Topics: Antigens, CD; Antigens, Differentiation; Carcinoma, Merkel Cell; Carcinoma, Small Cell; Esophageal Neoplasms; Histocompatibility Antigens; Humans; Intermediate Filament Proteins; Keratins; Leukocyte Common Antigens; Lung Neoplasms; Membrane Glycoproteins; Mucin-1; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Proteins

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

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Merkel Cell; Fibroblasts; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Skin Neoplasms

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

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

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

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

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

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

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

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

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

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

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

Merkel cell carcinoma (MCC) has only limited sensitivity to chemotherapeutic agents. The aim of the study was to determine if members of the anthraquinone family could be used as adjuncts to increase the growth inhibiting effect of anticancer agents in MCC. An adherent variant of MCC was derived from a previously established MCC cell line suspension. Cells were characterized by immunocytochemical methods using specific antibodies against epithelial (low molecular weight cytokeratins and cytokeratin 20) and neuroendocrine (neuron-specific enolase, neurofilament protein, chromogranin A and synaptophysin) antigens. Emodin and aloe-emodin, members of the anthraquinone family, inhibited proliferation of the adherent MCC cells, with a slight advantage of aloe-emodin over emodin. Aloin had no effect on cell proliferation. The chemotherapeutic agents, cis-platinol (abiplastin), doxorubicin (adriablastin), and 5-fluorouracil, and the tyrosine kinase inhibitor STI 571, all independently inhibited the proliferation of adherent MCC cells. The addition of aloe-emodin potentiated their inhibitory effect, especially when low concentrations of the anticancer compounds were used. The antiproliferative action of STI 571 may be associated with the presence of anti-c-kit antibodies. The combined use of anticancer agents, especially at low concentrations, and aloe-emodin may be considered a preferable means for treating MCC.

Topics: Antineoplastic Agents; Benzamides; Carcinoma, Merkel Cell; Cell Adhesion; Cell Division; Cell Line, Tumor; Chromogranin A; Chromogranins; Cisplatin; Dose-Response Relationship, Drug; Doxorubicin; Drug Synergism; Enzyme Inhibitors; Fluorouracil; Humans; Imatinib Mesylate; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Neurofilament Proteins; Phosphopyruvate Hydratase; Piperazines; Protein-Tyrosine Kinases; Pyrimidines; Synaptophysin

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

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

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

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

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

Lymphadenopathy in the human immunodeficiency virus (HIV) can be of diverse etiology, ranging from infection to cancer. A neoplasm of epithelial origin manifested as inguinal lymphadenopathy without a primary lesion is rare. We report a case of Merkel cell tumor confined only to a lymph node in a patient with the acquired immunodeficiency syndrome (AIDS). We believe this is the first report of primary nodal Merkel cell tumor in a patient with HIV. Because Merkel cell tumor is a rare skin neoplasm with features suggestive of high malignant potential, it is important to distinguish a primary nodal Merkel cell tumor from malignant metastatic processes on the one hand and relatively benign causes of adenopathy on the other.

Topics: Acquired Immunodeficiency Syndrome; Adult; Axilla; Carcinoma, Merkel Cell; Chromogranins; Follow-Up Studies; HIV Infections; Humans; Inguinal Canal; Keratins; Lymph Nodes; Lymphatic Diseases; Male; Phosphopyruvate Hydratase; Synaptophysin

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

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

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

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

Merkel cell carcinomas (MCC) not infrequently involve the periorbital region and the eyelids. Clinically, they are relatively characteristic but often unsuspected. Histologically, MCC are often misdiagnosed as lymphoma, melanoma, or metastatic small cell carcinoma of the lung (SCCL).. We present clinical, histological, and immunohistochemical data on six eyelid cases (all females; age 63-102 years; one with concomitant CLL) from our files of 77 MCC with special respect to differential diagnosis. For comparison, 22 SCCL were analyzed. Immunohistochemistry was done with antibodies against pan-cytokeratin (pan-CK), cytokeratin-20 (CK-20), neurofilament protein (NF), neuron-specific enolase (NSE), chromogranin (CHR), and S100 protein (S100).. Morphologically, five of six MCC were prototypic, one was of the small cell variant. Immunohistochemically, dot-like positivities for pan-CK and CK-20 were seen in all six MCC, and for NF in five tumors. None of the 22 SCCL stained positively for CK-20 or NF but 21/22 cases were positive for pan-CK. Only 1/21 SCCL showed dot-like patterns for pan-CK; 20/21 reacted diffusely. All MCC and 13/22 SCCL displayed CHR-positive cells. All MCC and all SCCL were positive for NSE and negative for S100.. Dot-like positivities for CK-20 or NF are important to prove MCC and to exclude SCCL in clinically and morphologically doubtful cases. Dot-like positivities for pan-CK favor MCC, but do not always exclude SCCL. NSE and CHR are of no value for the differential diagnosis of MCC and SCCL. Melanoma and lymphoma are ruled out by negativity for S100 and pan-CK, respectively.

Topics: Aged; Aged, 80 and over; Carcinoma, Merkel Cell; Carcinoma, Small Cell; Diagnosis, Differential; Eyelid Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Leukemia, Lymphocytic, Chronic, B-Cell; Lung Neoplasms; Middle Aged; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Proteins

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

The first case report of a merkel cell carcinoma arising from the palatal mucosa in a young adult is presented. The histopathological similarities of this tumour in skin and oral mucosa are also discussed. The patient was a 14-year-old female with a non-symptomatic painful swelling in the left molar region of the maxilla. Under the diagnosis of a malignant tumour, a partial maxillary resection was performed, but there was a recurrence, and finally the patient died of cerebral metastasis. The tumor was composed mainly of uniform small cells. Immunohistologically, a large number of the cells were reactive to neuron specific enolase (NSE) and cytokeratin CK19, and some of the cells were positive to CK8, CK13, CK20, PGP9.5 and CEA focally and slightly. Pseudo-rosette formation and squamous differentiation were frequently detected. The ultrastructure of the tumour cells showed abundant Golgi bodies associated with neurosecretory granules. We conclude that it is the first case of a Merkel cell tumour arising from palatal mucosa and invading underlying bone with reactive hyperplasia. These findings closely resemble those of the same tumour occurring in the skin

Topics: Adolescent; Carcinoma, Merkel Cell; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Palatal Neoplasms; Phosphopyruvate Hydratase

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

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

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

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

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

Topics: Biomarkers, Tumor; Carcinoma, Merkel Cell; Cytoplasmic Granules; Humans; Intermediate Filaments; Keratins; Microscopy, Electron; Skin; Skin Neoplasms

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

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

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

Merkel cell carcinoma of the eyelid is a rare malignant tumor. Immunohistochemical studies can be helpful in establishing the diagnosis of this tumor. We encountered a case of Merkel cell carcinoma of the eyelid and conducted an immunohistochemical analysis for clarification of its cell properties. The patient in this study was a 78-year-old man who noted a small mass on his right upper eyelid, which was subsequently removed. However, the lesion recurred and progressively enlarged. The results of a biopsy indicated the possibility of a highly malignant tumor. The lesion was removed by orbital exenteration. Merkel cell carcinoma was finally diagnosed by using light and electron microscopy. In immunohistochemical studies, the tumor cells showed both neuron-specific enolase and cytokeratin. Most of the cells were also labeled with antibodies against the protein gene product 9.5, endocrine granule constituent and chromogranin A. However, no neuropeptides were labeled. The properties of the tumor cells appeared virtually the same as those of normal human Merkel cells.

Topics: Aged; Carcinoma, Merkel Cell; Chromogranin A; Chromogranins; Eyelid Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Male; Neuropeptides; Phosphopyruvate Hydratase; Thiolester Hydrolases; Ubiquitin Thiolesterase

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

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

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

Primary neuroendocrine carcinomas of the skin were recognized as distinctive neoplasms and clinicopathologic information on their location on the eyelids have been reported. The authors present one case of primary neuroendocrine carcinoma occurring on the right lower lid in a 73-year-old woman. The clinical history, light and electron microscopic findings as well the results of an immunohistochemical study are described. The ultrastructural study demonstrated the characteristic membrane-bound dense-core neurosecretory granules. Immunoreactivity for neuron-specific enolase, keratin filaments, epithelial membrane antigen and calcitonin were observed and are strongly suggestive of a neuroendocrine differentiation in a neoplasm of epithelial origin. Various hypothesis concerning the origin of this tumor are discussed on the basis of the immunohistochemical findings. The authors also provide a brief review of the literature.

Topics: Aged; Antibodies, Monoclonal; Calcitonin; Carcinoma, Merkel Cell; Eyelid Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Phosphopyruvate Hydratase

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

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

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

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

Topics: Adolescent; Biomarkers, Tumor; Carcinoma, Merkel Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Phosphopyruvate Hydratase; Skin; Skin Neoplasms