bromochloroacetic-acid and Necrosis

Atypical teratoid/rhabdoid tumor of the central nervous system is a highly malignant neoplasm and that usually arises in the posterior fossa, survival from this is frequently poor. We present a unique case in a 21-month-old girl who had an atypical teratoid/rhabdoid tumor with cystic components located in the right fronto-parietal lobe. The patient underwent radical surgical intervention followed by chemotherapy. It consisted of five chemotherapeutic agents, but the patient did not receive any radiotherapy. The postoperative course was uneventful and the patient was followed-up by cranial magnetic resonance imaging every 3 months. Two years later at the last follow-up visit, there was no evidence of a tumor relapse on MRI, and the examination was symptom free. It is possible the favorable outcome of the patient resulted from a rapid diagnosis, prompt management, radical surgical intervention and aggressive chemotherapy.

Topics: Actins; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Combined Modality Therapy; Diagnosis, Differential; Female; Follow-Up Studies; Frontal Lobe; Glial Fibrillary Acidic Protein; Humans; Infant; Keratins; Magnetic Resonance Imaging; Microsurgery; Mitotic Index; Necrosis; Neurologic Examination; Parietal Lobe; Rhabdoid Tumor; Supratentorial Neoplasms; Teratoma; Vimentin

Cytokeratins have been extensively used as serum tumour markers for monitoring of disease progression in cancer patients. The source of cytokeratins in the circulation as well as the mechanisms of release from cells have long been unclear. Recent evidence suggests that cytokeratins present in the circulation of cancer patients are released from apoptotic or necrotic tumour cells. CK18 is cleaved by caspases during apoptosis and a monoclonal antibody (M30) specific to caspase-cleaved forms is available. The molecular form of CK18 released from cells (caspase-cleaved or not) can conveniently be determined by immunoassays (M30-Apoptosense and M65 ELISA assays; Peviva AB, Bromma, Sweden) to determine cell death mode--apoptosis or necrosis. Recent studies where these assays were used to evaluate the response to cytotoxic anticancer drugs using cancer patient serum have been encouraging. CK18 is attracting considerable interest as a response biomarker during clinical trials of anticancer drugs. Properties such as excellent antigen stability and the epithelial specificity of cytokeratins contribute to make this biomarker attractive.

Topics: Antibodies, Monoclonal; Apoptosis; Biomarkers, Tumor; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Humans; Immunoassay; Keratin-18; Keratins; Models, Biological; Necrosis; Neoplasms

We present a brief review of epithelioid trophoblastic tumor, a rare trophoblastic neoplasm derived from chorionic-type intermediate trophoblastic cells that typically presents in reproductive-age women between 1 and 18 years following a previous gestation. Histologic features include a nodular growth pattern of monomorphic, epithelioid cells within a hyaline matrix. Areas of necrosis and mitotic activity (0-9 mitoses per 10 high-power fields) are additional features of this neoplasm. Positive immunostaining for p63 and cytokeratin, frequent location in the lower uterine segment and endocervix, as well as the epithelioid appearance can lead to confusion with squamous cell carcinoma. Inhibin-alpha is typically expressed, as well as focal, more variable expression of other trophoblastic markers including beta-human chorionic gonadotropin, human placental lactogen, placental alkaline phosphate, and Mel-CAM (CD148). The clinical behavior of this rare form of gestational trophoblastic disease is difficult to predict. Although most cases follow a benign course following resection, there is a potential for metastatic disease.

Topics: Adult; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Epithelioid Cells; Female; Humans; Immunohistochemistry; Keratins; Membrane Proteins; Mitosis; Necrosis; Pregnancy; Trophoblastic Tumor, Placental Site; Uterine Neoplasms

Intracellular macromolecules are released from dying tumor cells and may subsequently be detected in patient blood. In this review, we will discuss the use of cytokeratin-18 as a serum biomarker for monitoring therapy-induced cell death. Cytokeratins are abundant intracellular proteins expressed by most types of carcinoma, but not by treatment-sensitive cells from bone marrow and other tissues. Release of cytokeratins into blood is therefore expected to show some specificity for tumor cell death. Cytokeratin-18 (CK18) is cleaved by caspases specifically during apoptosis, and the molecular form of this protein (caspase-cleaved vs. non-cleaved) released from dying tumor cells is therefore diagnostic as to the type of cell death (apoptosis vs. necrosis). Analyses of different CK18 forms in patient sera have suggested that tumor apoptosis may not necessarily be the dominating death mode in many tumors in vivo. Measurements of increased levels of CK18 in serum during therapy of prostate and breast cancer patients have been encouraging with regard to the possible future use of CK18 as a biomarker for monitoring therapy efficiency.

Topics: Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Endpoint Determination; Humans; Keratins; Necrosis; Neoplasms

Malignant mesenchymomas are uncommon tumors of soft tissues. Three such tumors involving the pleura have been reported in the literature. We report a case of malignant mesenchymoma of the pleura that had liposarcomatous, rhabdomyosarcomatous, chondrosarcomatous, and osteosarcomatous elements.

Topics: Adipose Tissue; Aged; Carcinoma, Large Cell; Diagnosis, Differential; Humans; Keratins; Lung Neoplasms; Male; Mesenchymoma; Necrosis; Pleural Neoplasms

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

The molecular mechanism of the local hypersensitivity reactions to wasp venom including dermal necrosis remains an enigma regardless of the numerosity of the reported cases. In this study, we discovered a new membrane disrupting toxin, VESCP-M2 responsible for tissue damage symptoms following Vespa mandarinia envenomation. Electrophysiological assays revealed a potent ability of VESCP-M2 to permeate the cell membrane whereas in vivo experiments demonstrated that VESCP-M2 induces edema, pain and dermal necrosis characterized by the presence of morphological and behavioral phenotypes, pro-inflammatory mediators, biomarkers as well as the disruption of dermal tissue. This study presents the molecular mechanism and symptom-related function of VESCP-M2 which may form a basis for prognosis as well as therapeutic interventions.

Topics: Amino Acid Sequence; Animals; Apolipoprotein A-I; Cell Membrane; CHO Cells; Cricetulus; Edema; HEK293 Cells; HeLa Cells; Human Umbilical Vein Endothelial Cells; Humans; Hypersensitivity; Keratins; Mice, Inbred BALB C; Mice, Nude; Necrosis; Pain; Peptides; Wasp Venoms; Wasps

During the preoperative diagnostics of an 80-year-old male patient prior to a planned endarterectomy, an unclear space-occupying lesion was detected in the right nasopharyngeal cavity. It proved to be a dense soft tissue space-occupying lesion of the right maxillary sinus. The histological investigations revealed a partially necrotically decomposed malignant tumor below normal respiratory mucosa free from dysplasia. This case demonstrates the difficulties in differential diagnostics, particularly involving (aberrant) expression of cytokeratin.

Topics: Aged; Biomarkers, Tumor; Carotid Stenosis; Cell Nucleus; Diagnosis, Differential; Endarterectomy, Carotid; Humans; Immunohistochemistry; Incidental Findings; Keratins; Male; Maxillary Sinus; Maxillary Sinus Neoplasms; Multiple Myeloma; Necrosis; Tomography, X-Ray Computed

Clearance of dead cells is critical for maintaining homeostasis and prevents autoimmunity and inflammation. When cells undergo apoptosis and necrosis, specific markers are exposed and recognized by the receptors on phagocytes. DEC205 (CD205) is an endocytotic receptor on dendritic cells with antigen presentation function and has been widely used in immune therapies for vaccine generation. It has been shown that human DEC205 recognizes apoptotic and necrotic cells in a pH-dependent fashion. However, the natural ligand(s) of DEC205 remains unknown. Here we find that keratins are the cellular ligands of human DEC205. DEC205 binds to keratins specifically at acidic, but not basic, pH through its N-terminal domains. Keratins form intermediate filaments and are important for maintaining the strength of cells and tissues. Our results suggest that keratins also function as cell markers of apoptotic and necrotic cells and mediate a pH-dependent pathway for the immune recognition of dead cells.

Topics: Animals; Antigens, CD; Apoptosis; Dendritic Cells; Glycoside Hydrolases; HEK293 Cells; Humans; Hydrogen-Ion Concentration; Jurkat Cells; Keratins; Lectins, C-Type; Ligands; Mice, Inbred C57BL; Minor Histocompatibility Antigens; Necrosis; Protein Binding; Receptors, Cell Surface

Primary cultures of human proximal tubular (hPT) cells are a useful experimental model to study transport, metabolism, cytotoxicity, and effects on gene expression of a diverse array of drugs and environmental chemicals because they are derived directly from the in vivo human kidney. To extend the model to investigate longer-term processes, primary cultures (P0) were passaged for up to four generations (P1-P4). hPT cells retained epithelial morphology and stained positively for cytokeratins through P4, although cell growth and proliferation successively slowed with each passage. Necrotic cell death due to the model oxidants tert-butyl hydroperoxide (tBH) and methyl vinyl ketone (MVK) increased with increasing passage number, whereas that due to the selective nephrotoxicant S-(1,2-dichlorovinyl)-l-cysteine (DCVC) was modest and did not change with passage number. Mitochondrial activity was lower in P2-P4 cells than in either P0 or P1 cells. P1 and P2 cells were most sensitive to DCVC-induced apoptosis. DCVC also increased cell proliferation most prominently in P1 and P2 cells. Modest differences with respect to passage number and response to DCVC exposure were observed in expression of three key proteins (Hsp27, GADD153, p53) involved in stress response. Hence, although there are some modest differences in function with passage, these results support the use of multiple generations of hPT cells as an experimental model.

Topics: Apoptosis; Cell Proliferation; Cells, Cultured; Cysteine; Epithelial Cells; Female; HSP27 Heat-Shock Proteins; Humans; Keratins; Kidney Tubules, Proximal; Male; Middle Aged; Mitochondria; Necrosis; Transcription Factor CHOP; Tumor Suppressor Protein p53

The cytopathologic diagnosis of basaloid squamous cell carcinoma can be problematic as there are several components of the differential diagnosis that share common cytomorphologic features. In this study, we report the fine-needle aspiration (FNA) findings of 16 basaloid squamous cell carcinoma cases and compare those cases to 16 cases of small cell carcinoma. To our knowledge, this is the largest series of basaloid squamous cell carcinoma FNA cases ever reported. The following cytomorphologic features were compared for both tumors: cohesive tissue fragments, single cells, adenoid cystic-like features (cribriform pseudoglandular lumina with hyaline materials), necrosis, nuclear size, nuclear molding, nucleoli, cytoplasm, and the presence of single keratinized cells. Adenoid cystic-like features and the presence of single keratinized cells were specific for basaloid squamous cell carcinoma (P < 0.05).

Topics: Aged; Biopsy, Fine-Needle; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasm; Female; Gastrointestinal Neoplasms; Humans; Keratins; Male; Middle Aged; Necrosis; Respiratory Tract Neoplasms

Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy of presumed intercalated duct origin comprising 1% of all salivary gland tumours. High grade transformation (HGT) in EMC is a recently recognised entity with only a few cases reported in the literature. The authors report an additional case of EMC with HGT involving the submandibular gland. The patient was a 60-year-old woman who requested examination of the rapid growth of a mass in the left submandibular area, which she had first noticed 20 years previously. Histologically, the tumour had two distinct carcinomatous components. One component had features of a low grade EMC. The second component consisted of polygonal cells, arranged in a solid and nested pattern, with marked nuclear pleomorphism, brisk mitotic activity, and frequent necrosis. The Ki-67 labelling index of the EMC component was 9%, and that of the high grade component was 40%. The patient developed multiple pulmonary metastases 15 months after surgery. The aggressive behaviour of EMC with HGT suggests that it is important to recognise this variant of EMC to avoid misdiagnosis and inappropriate treatment.

Topics: Calcium-Binding Proteins; Calmodulin-Binding Proteins; Calponins; Carcinoma; Cell Nucleus; Cell Transformation, Neoplastic; Cytoplasm; Diagnostic Errors; Female; Follow-Up Studies; Humans; Keratins; Ki-67 Antigen; Lung Neoplasms; Membrane Proteins; Microfilament Proteins; Middle Aged; Mitotic Index; Necrosis; Neoplasm Invasiveness; Submandibular Gland Neoplasms

Topics: Adult; Antigens, CD20; Carcinoma; Diagnosis, Differential; DNA Nucleotidylexotransferase; Female; Follow-Up Studies; Humans; Keratins; Lymphoma; Male; Middle Aged; Necrosis; Seminoma; Thymoma; Thymus Neoplasms; Tuberculosis

Classification of necrotic or degenerate thyroid nodules can be difficult. The aim of this study was to investigate the value of cytokeratins, thyroid-specific markers (TTF-1 and thyroglobulin) and HBME-1 antibodies in such thyroid lesions.. Twenty-eight necrotic or degenerate thyroid lesions, including four cervical cystic papillary carcinoma (CPC) metastases, were evaluated with immunohistochemistry for TTF-1, thyroglobulin, HBME-1, AE1&3, Cam5.2, MNF116 and cytokeratin (CK)19. There was loss of TTF-1 staining in all necrotic lesions, with positive staining in degenerate tumour cells of all four metastatic CPCs. Thyroglobulin was retained in 18 lesions. Dual CK19 and HBME-1 expression was seen only in six of seven necrotic papillary thyroid carcinomas and the four metastatic CPCs. Retained immunoreactivity for AE1&3 and Cam5.2 was seen in most necrotic papillary carcinomas (n = 11/11 and n = 10/11, respectively), poorly differentiated carcinomas (n = 2/3 and n = 3/3, respectively) and follicular-patterned areas of anaplastic carcinoma (n = 3/5 and n = 4/5, respectively). Cam5.2 showed spurious staining of macrophages in eight lesions.. Thyroglobulin is useful in establishing the thyroid origin of a necrotic lesion. TTF-1 may be useful for highlighting degenerate tumour cells within metastatic CPCs. Retained expression of CK19 and HBME-1 is seen in necrotic papillary carcinomas. AE1&3 is the most specific and Cam5.2 the most sensitive of the CK cocktails in non-viable thyroid lesions.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Necrosis; Thyroglobulin; Thyroid Nodule; Young Adult

High intensity focused ultrasound (HIFU) is an emerging alternative for the treatment of prostate adenocarcinoma. Alpha-methylacyl-CoA racemase (AMACR) has been shown to be a sensitive immunomarker for prostate cancer, however, there is no information available concerning its utility and that of other immunomarkers for the detection of malignancy after HIFU therapy.. AMACR expression was examined in 11 cases of prostatic carcinoma treated by HIFU, with histological evidence of residual carcinoma. In seven cases tumour was examined from thin core biopsies and in four cases from tissue fragments obtained by transurethral resection of prostate (TURP). In addition to AMACR, immunostaining was also undertaken for p63, cytokeratin 34betaE12, cytokeratin 5, cytokeratin 8-18, prostate specific alkaline phosphatase (PSAP), prostate specific antigen (PSA), chromogranin and CD56.. In two of the cases foci of tumour were cut out in serial sections. AMACR was expressed in eight of nine evaluable cases (4/5 biopsies and 4/4 TURP specimens). Cytokeratin 8-18 and PSAP were positive in all cases, whereas PSA was positive in five of nine cases. Cytokeratin 34betaE12, cytokeratin 5, and p63 marked the basal layer in normal prostatic glands, but were negative in neoplastic glands. In four cases we found tumour cells with positive staining for CD56 and chromogranin.. A panel with positive markers for AMACR, and negative markers for p63/cytokeratin 5/cytokeratin 34betaE12 confirms the neoplastic nature of the residual glands on biopsies or TURP fragments sampled after HIFU therapy.

Topics: Ablation Techniques; Adenocarcinoma; Biomarkers, Tumor; Combined Modality Therapy; Fluorescent Antibody Technique, Direct; Humans; Immunoenzyme Techniques; Keratin-5; Keratins; Male; Necrosis; Prostatic Neoplasms; Racemases and Epimerases; Transurethral Resection of Prostate; Ultrasonic Therapy; Ultrasonography

Neoadjuvant chemotherapy followed by resection has become the mainstay in the treatment of hepatoblastoma (HB). The changes after chemotherapy typically result in tumor necrosis and a fibrohistiocytic response. We have observed that treated HBs undergo additional morphologic changes that have not been described. Herein, we report a 15-year retrospective study of HBs in 22 children who received neoadjuvant chemotherapy according to the Children's Oncology Group protocols. The medical records, diagnostic imaging, and histopathology were reviewed. Besides treated HBs having characteristic necrosis and fibrohistiocytic response, two-thirds had areas of cytoarchitectural differentiation ("maturation") mimicking non-neoplastic liver, and a quarter had alterations mimicking hepatocellular carcinoma. Nuclear expression of beta-catenin and keratin profiles were useful in distinguishing residual tumor with "maturation" from non-neoplastic liver and therefore in the assessment of surgical margins. Statistical analysis revealed that larger pretreatment and posttreatment imaged tumor size, larger tumor size at pathologic examination, and vascular invasion were significant univariate predictors of metastatic disease, whereas pretreatment imaged tumor size and vascular invasion were also significant independent predictors (multivariate logistic regression analysis). Multifocality, greater posttreatment necrosis and hepatocellular carcinoma-like morphology were more often associated with metastatic disease, but did not reach statistical significance.

Topics: Antineoplastic Combined Chemotherapy Protocols; beta Catenin; Biomarkers, Tumor; Biopsy; Cell Nucleus; Chemotherapy, Adjuvant; Child, Preschool; Female; Hepatectomy; Hepatoblastoma; Humans; Immunohistochemistry; Infant; Kaplan-Meier Estimate; Keratins; Liver Neoplasms; Logistic Models; Male; Necrosis; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Neoplasm, Residual; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The erbium:yttrium-aluminum-garnet (Er:YAG) laser is used for surgical resurfacing. It has ablative properties with water as its main chromophore.. This study attempted to establish the cutaneous effect and cellular response to Er:YAG laser irradiation using different fluences (7.5 and 15 J/cm(2)).. Female nude mouse was used as the animal model in the study. Physiological parameters were examined and histology was evaluated at 4, 24 and 96 h after laser exposure. A proteomic analysis and immunoblotting were also used to determine the mechanisms of the laser's effect on the skin.. Both fluences were associated with a significant increase in transepidermal water loss (TEWL), erythema (a*), and the skin pH at 4 and 24h. In contrast, at 96 h, the levels of these parameters had generally decreased to the baseline. The histology examined by light microscopy and transmission electron microscopy (TEM) showed vacuolization, hydropic degeneration and epidermal necrosis of laser-irradiated skin. The higher fluence (15 J/cm(2)) exhibited more-severe disruption of the skin. Bulous and scarring were observed in skin treated with the higher fluence during the recovery period. p53 and p21 proteins were significantly activated in skin following exposure to the laser. However, proliferating cell nuclear antigen and cytokeratin expressions were downregulated by the low fluence (7.5 J/cm(2)).. Both proliferation and apoptosis occurred when the laser-irradiated the skin.

Topics: Animals; Antigens, Nuclear; Apoptosis; Cell Proliferation; Cicatrix; Cyclin-Dependent Kinase Inhibitor p21; Erythema; Female; Keratins; Lasers, Solid-State; Mice; Mice, Nude; Models, Animal; Necrosis; Proteomics; Skin; Tumor Suppressor Protein p53

Poroid neoplasms comprise classic poroma (P), hidroacanthoma simplex (HS), dermal duct tumor (DDT), and poroid hidradenoma (PH). The 3 latter are rarely reported. Poroid cells in P have recently been identified as keratinocytes of the lowermost acrosyringium and the sweat duct ridge.. To investigate a large cohort of poroid neoplasms to better define the clinical and pathologic aspects of HS, DDT, and PH. To analyze the expression of discriminatory keratins in all 4 poroid neoplasms.. 202 P, 11 HS, 17 DDT, 31 PH, and 5 composite tumors were examined under light microscopy, and 11, 9, 10, 15, and 2, respectively, by immunohistochemistry using anti-keratin antibodies, in particular, anti-K77, specific for luminal cells of the eccrine dermal sweat duct, and Ki-67 antibody.. HS appeared later in life (66.6 years old) than P, DDT, and PH. Whereas P, DDT, and PH displayed unspecific clinical aspects, HS had most frequently the aspect of a large seborrheic keratosis with well-defined borders. HS, DDT, and PH were absent on palms and soles, but were found on the trunk, the lower limbs, and the upper limbs. Similar pathologic features were observed in all tumors, that is, a majority of poroid cells expressing K14, islands of K10-positive and K77-negative large cells. K77 expression was limited to luminal cells of intact ductal structures within the tumors.. Our data demonstrate the common histogenesis of the 4 poroid neoplasms, which seem to derive from the basal keratinocytes of the sweat duct ridge and the lower acrosyringium. The variable length of the sweat duct ridge may account for the variety of poroid neoplasms, according to the site of tumor induction along this structure.

Topics: Acanthoma; Acrospiroma; Adolescent; Adult; Aged; Aged, 80 and over; Child; Dermis; Female; Humans; Immunohistochemistry; Keratinocytes; Keratins; Ki-67 Antigen; Male; Middle Aged; Necrosis; Retrospective Studies; Sweat Gland Neoplasms; Sweat Glands; Young Adult

To investigate the clinicopathological features and immunophenotype of centrally necrotizing carcinoma (CNC) of the breast to ascertain its relationship to basal-like phenotype and its prognosis.. The clinical and pathological characteristics of 33 CNCs were reviewed. Immunohistochemical study of oestrogen receptor, progesterone receptor, HER2, cytokeratin (CK) 8/18, high-molecular-weight CK (34betaE12), CK5/6, CK14, CK17, smooth muscle antigen, p63, vimentin and epidermal growth factor receptor was performed. The striking feature of CNC was a central, necrotic or acellular zone surrounded by a ring-like area of viable tumour cells. The central zone showed three morphological types: predominance of coagulative necrosis (21 cases), predominance of fibrosis and scar tissue (nine cases) and infarction (three cases). Tumour cells displayed invasive ductal carcinoma of high grade. The expression rate of basal-like markers was higher than that of myoepithelial markers (87.9% versus 46.2%). Basal-like subtype was shown by 63.6% of cases. The expression rate of CK5/6 (90.5%) was highest among basal-like markers. Follow-up data of 19 patients were available. Median progression-free survival was 15.5 months. In 12 patients (63.2%), local recurrence and/or distant metastasis developed (median time to recurrence and/or metastasis, 14.0 months).. CNC has distinctive morphological features, which mostly exhibit a basal-like immunophenotype and poor prognosis. CNC is a typical representative of basal-like breast cancer.

Topics: Actins; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; ErbB Receptors; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Necrosis; Neoplasms, Hormone-Dependent; Phenotype; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Vimentin

The purpose of this report is to present the clinical and histological features of a basaloid squamous cell carcinoma (BSCC) occurring in the retromolar trigone of a 59-year-old man and to relate its immunohistochemical characteristics.. BSCC is an aggressive distinct variant of squamous cell carcinoma (SCC) requiring recognition as a separate entity from SCC due to its peculiar behavior.. A clinical examination revealed a 12x07x07 mm nodular mass with a rubbery consistency, defined borders, covered by reddish mucosa and an absence of bleeding upon palpation. Histologically, nests and cords of closely packed, moderately pleomorphic basaloid cells with nuclear palisading along the periphery of the neoplastic nests surrounded by a fibrous stroma were found.. Since this tumor can mimic other neoplasms such as adenoid cystic carcinoma, neuroendocrine carcinoma, and basal cell adenocarcinoma, histological features are essential to differentiate between them. Furthermore, immunohistochemical testing can provide valuable diagnostic information that can have a profound impact on treatment options and the prognosis.. BSCC needs to be differentiated from other neoplasms as early as possible because of its adverse prognosis. Clinicians are advised to conduct a mucosal evaluation during oral examinations and take a thorough medical history which could ultimately save the life of a patient.

Topics: Adenocarcinoma; Carcinoma, Adenoid Cystic; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Nucleus; Diagnosis, Differential; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Laminin; Male; Middle Aged; Mitosis; Mouth Neoplasms; Necrosis; Tumor Suppressor Protein p53

Necrotic testicular tumors are relatively frequent and can present a significant diagnostic challenge. Because of differing treatments for seminomas versus nonseminomas, accurate diagnosis is critical. Eleven totally (n=9) or almost totally (n=2) necrotic testicular tumors were retrieved from our consult files. The submitting pathologists favored benign processes in 4 cases, Leydig cell tumor in 1, and lymphoma in 1. The cases were evaluated for histologic features and, when material was available, by immunostaining with 7 antibodies: keratin (AE1/AE3), OCT4, placental alkaline phosphatase, alpha-fetoprotein (AFP), CD117, CD30, and S100. Only distinct reactivity in a cellular distribution in the necrotic zone was considered positive; nuclear reactivity alone was scored for OCT4 and membrane reactivity for CD117 and CD30. Mean patient age was 35 years (range 16-63). Mean tumor size was 19 mm (range 7-53). All patients presented with unilateral testicular masses (6 right, 5 left); 2 also had acute pain. The combination of histologic features, immunostains and, in 1 case, serum AFP permitted classification of 8 tumors (4 seminomas, 3 embryonal carcinomas, 1 yolk sac tumor). Three were not classifiable. The necrotic seminomas lacked associated coarse intratubular calcifications and were positive for OCT4 (4/4) and CD117 (3/3) but negative for keratin (0/4) and CD30 (0/4). The necrotic embryonal carcinomas had associated coarse intratubular calcifications and were positive for keratin (2/3), OCT4 (2/2), and CD30 (3/3). OCT4 stained 1 unclassifiable tumor, which lacked other specific markers. We did not find placental alkaline phosphatase, AFP, and S100 stains useful, although S100 did highlight tumor "ghost" cells in 1 case. Other features in most cases included intratubular germ cell neoplasia (6/11), tubular atrophy/hyalinization (10/11), tumor "ghost" cells (10/11), scar (9/11), and inflammation (10/11). Of the 5 patients with available follow-up, 3 were free of disease at 1, 5, and 8 years after orchiectomy (2 necrotic seminomas and 1 germ cell tumor, unclassified). One patient with yolk sac tumor (age 63 y) developed widespread metastases after 15 months and died of disease. The final case was initially misinterpreted as "testicular infarction, no malignancy" and 16 months later the patient developed a large retroperitoneal seminoma. Most totally necrotic testicular tumors can be placed into clinically important groups by assessment for coarse intratubula

Topics: Adolescent; Adult; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Embryonal; Disease-Free Survival; Endodermal Sinus Tumor; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Male; Middle Aged; Necrosis; Octamer Transcription Factor-3; Orchiectomy; Proto-Oncogene Proteins c-kit; Seminoma; Testicular Neoplasms; Young Adult

Histological grade is one of the most important prognostic factors in breast carcinomas, but poorly differentiated neoplasms still have quite heterogeneous biological behaviour, since they can be genetically classified as basal-like, HER2+ or even luminal. The aim was to analyse the frequency of oestrogen receptor (ER), progesterone receptor (PR) and HER2 expression profiles among breast carcinomas with <10% tubular formation, and their correlation with classic prognostic factors.. One hundred and thirty-four samples of paraffin-embedded tumours were studied retrospectively. The tumours were classified in to four groups by their ER/PR/HER2 profile: (i) ER+ and/or PR+ but HER2-; (ii) ER+ and/or PR+ and HER2+; (iii) ER- and/or PR- but HER2+; and (iv) ER-, PR- and HER2- (triple-negative). The histological features of triple-negative and HER2+ carcinomas overlap. The only difference was the expression of basal cytokeratins (basal CK), which was more frequent among triple-negative carcinomas. Basal-CK expression defined a more aggressive group of tumours, according to the pathological features, regardless of the immunohistochemical profile.. Group 1 and 2 tumours (ER+ and/or PR+ tumours with or without HER2 expression) were not statistically different, suggesting that poorly differentiated carcinomas with hormone receptors correspond to the luminal B type of tumour. Among poorly differentiated breast carcinomas, the classic profile associated with basal-CK identifies distinct subtypes equivalent to those seen by genetic classification.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Cell Proliferation; Female; Fluorescent Antibody Technique, Direct; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Necrosis; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Tissue Array Analysis; Young Adult

Co-expression of cytokeratin and vimentin has been traditionally associated with a few select tumors. However, this phenomenon is being recognized in a wider range of tumors. Twenty-one canine primary pulmonary epithelial neoplasms were evaluated for the co-expression of cytokeratin and vimentin. The histologic pattern and grade, and an immunohistochemical grade for cytokeratin and vimentin staining, were determined for each neoplasm. Adenocarcinomas predominated, and histologically, most tumors were grade II. All of the neoplasms stained positive for cytokeratin, while only 8 (38%) stained positive for both vimentin and cytokeratin. Papillary adenocarcinomas were consistently vimentin negative. The anaplastic histologic pattern had significantly more vimentin staining than the other histologic patterns. There was no significant difference in histologic grade or grading criteria between those tumors that stained with vimentin and those that did not. The present study established that cytokeratin and vimentin co-expression occurs in canine primary pulmonary epithelial tumors at a similar frequency to human pulmonary neoplasms. Further investigation will be needed to characterize the significance of this finding, particularly with respect to prognosis.

Topics: Adenocarcinoma; Animals; Dog Diseases; Dogs; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Necrosis; Vimentin

To investigate the incidence of central nodal necrosis (CNN) in the cervical lymph nodes of patients with oral squamous cell carcinoma (SCC) and the factors that influence the formation of CNN.. Lymph nodes shown as CNN on computed tomography (CT) films in 107 lymph nodes from 27 patients with oral SCC were selected. Lymph nodes with CNN on CT films were compared with the pathological findings of lymph nodes on specimens. We compared many kinds of factors influencing the formation of CNN, including the differentiated type, with the incidence of CNN.. Significant relationships were found between the incidence of CNN in metastatic lymph nodes and the presence of well-differentiated SCC and the presence of keratinization in tumour cells.. The results indicated that if a patient had SCC with low-grade differentiation, CNN in small lymph nodes would be difficult to detect on CT scan. Therefore, noting changes in lymph node density in the absence of CNN on CT scans is necessary in case the primary tumour is low-grade SCC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neck; Neck Dissection; Necrosis; Neoplasm Staging; Tomography, X-Ray Computed

The aim of this study was to assess the morphological characteristics and immunohistochemical profile of breast carcinomas with basal and myoepithelial phenotypes to obtain a better understanding of their biological behaviour and nature. One thousand nine hundred and forty-four invasive breast carcinomas were examined, using tissue microarray (TMA) technology and immunohistochemistry, to identify those tumours that showed basal and myoepithelial phenotypes, and their immunophenotype profile was characterized using a variety of markers. In addition, haematoxylin and eosin-stained sections of these tumours were studied for several morphological parameters. The findings were correlated with patient and tumour characteristics and outcome data. Tumours were classified into two groups: (1) tumours with basal phenotype [expressing one or both basal markers (CK5/6 and/or CK14)] and (2) tumours with myoepithelial phenotype (expressing SMA and/or p63). Group 1 was further subdivided into two subgroups: (A) dominant basal pattern (more than 50% of cells positive) and (B) basal characteristics (10-50% of cells positive). Group 1 tumours constituted 18.6% (8.6% and 10% for groups 1A and 1B, respectively) and group 2 constituted 13.7% of the cases. In both groups, the most common histological types were ductal/no specific type, tubular mixed and medullary-like carcinomas; the majority of these tumours were grade 3. There were positive associations with adenoid cystic growth pattern, loss of tubule formation, marked cellular pleomorphism, poorer Nottingham prognostic index, and development of distant metastasis. In addition, associations were found with loss of expression of steroid hormone receptors and FHIT proteins and positive expression of p53 and EGFR. The most common characteristics in group 1 were larger size, high-grade comedo-type necrosis, development of tumour recurrence, and absence of lymph node disease. Group 2 tumours were more common in younger patients and were associated with central acellular zones, basaloid change, and positive E-cadherin protein expression. Group 1 characteristics were associated with both reduced overall survival (OS) [log rank (LR) = 22.5, p < 0.001] and reduced disease-free interval (DFI) (LR = 30.1, p < 0.001), while group 2 characteristics showed an association with OS (LR = 5, p = 0.02) but not with DFI. Multivariate analysis showed that basal, but not myoepithelial, phenotype has an independent value in predicting outcome. B

Topics: Actins; Adult; Age Factors; Aged; Biomarkers, Tumor; Breast Neoplasms; Cadherins; Carcinoma, Ductal, Breast; Cell Differentiation; Disease-Free Survival; ErbB Receptors; Female; Genes, p53; Humans; Immunohistochemistry; Keratins; Middle Aged; Multivariate Analysis; Myoepithelioma; Necrosis; Neoplasms, Basal Cell; Receptors, Androgen; Staining and Labeling; Survival Rate

The diagnosis of hidradenocarcinoma is difficult due to a combination of factors including inconsistent nomenclature/ classification, rarity of the neoplasm, and variable morphology of cells composing the neoplasm. Immunohistochemistry has not been previously performed on a series of hidradenocarcinomas. We evaluated six cases of hidradenocarcinoma histologically and immunohistochemically using antibodies to gross cystic disease fluid protein-15 (GCDFP-15), carcino-embryonic antigen (CEA), epithelial membrane antigen (EMA), S-100 protein, keratin AE1/3, cytokeratin 5/6, p53, bcl-1, bcl-2, and Ki67. Histology suggested concurrent eccrine and apocrine differentiation of the cases. Ki67 and p53 staining was strongly positive in five of six tumors. The neoplasms stained with antibodies to CEA, S-100 protein, GCDFP-15, EMA, bcl-1, and bcl-2 in no consistent pattern. All tumors studied stained positively for keratin AE1/3 and cytokeratin 5/6. In making the diagnosis of hidradenocarcinoma, it may be unnecessary to separate hidradenocarcinoma into eccrine and apocrine categories, and although Ki67 and p53 may be helpful, histological parameters remain paramount.

Topics: Adenoma, Sweat Gland; Adult; Aged; Carcinoembryonic Antigen; Cyclin D1; Gene Expression Regulation, Neoplastic; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Mitosis; Mucin-1; Necrosis; Proto-Oncogene Proteins c-bcl-2; S100 Proteins; Sweat Gland Neoplasms; Tumor Suppressor Protein p53

Lymph node infarction is a spontaneous coagulative necrosis of the affected lymph node and is frequently associated with concurrent and subsequent malignant lymphoma. However, this phenomenon appears to be rarely associated with metastatic carcinomas. Here, we report on the histopathologic and immunohistologic findings of three cases showing lymph node infarction in the regional lymph node associated with metastatic colorectal adenocarcinoma. Histologically, coagulative necrosis of metastatic carcinoma was surrounded by a thick rim of granuloma consisting of histiocytes with or without epithelioid features, foamy cells, and a small number of lymphocytes. The immunohistochemical study of the coagulative necrosis demonstrated that cytokeratins (AEI/AE3 and CAM5.2) and carcinoembryonic antigen (CEA) were well preserved in all three cases. However, compared with viable tumor tissues, only a few tumor cells were positive for epithelial membrane antigen. Using formalin-fixed and paraffin-embedded tissues, immunostaining for cytokeratins and CEA of the lymph node containing necrotic carcinoma may provide clinically valuable information.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Infarction; Keratins; Lymph Nodes; Lymphatic Diseases; Lymphatic Metastasis; Middle Aged; Necrosis

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

Cytokeratins are released from carcinoma cells by unclear mechanisms and are commonly used serum tumor markers (TPA, TPS, and CYFRA 21-1). We here report that soluble cytokeratin-18 (CK18) is released from human carcinoma cells during cell death. During necrosis, the cytosolic pool of soluble CK18 was released, whereas apoptosis was associated with significant release of caspase-cleaved CK18 fragments. These results suggested that assessments of different forms of CK18 in patient sera could be used to examine cell death modes. Therefore, CK18 was measured in local venous blood collected during operation of patients with endometrial tumors. In most patient sera, caspase-cleaved fragments constituted a minor fraction of total CK18, suggesting that tumor apoptosis is not the main mechanism for generation of circulating CK18. Monitoring of different CK18 forms in peripheral blood during chemotherapy of prostate cancer patients showed individual differences in the patterns of release. Importantly, several examples were observed where the increase of apoptosis-specific caspase-cleaved CK18 fragments constituted only a minor fraction of the total increase. These results suggest that cell death of epithelially derived tumors can be assessed in patient serum and suggest that tumor apoptosis may not necessarily be the dominating death mode in many tumors in vivo.

Topics: Apoptosis; Breast Neoplasms; Caspases; Cell Line, Tumor; Female; Humans; Keratins; Necrosis

In orthotopic liver transplantation, ischemic-reperfusion is one of the most important factors that cause the incidence of biliary compliance. The aim of this study was to investigate the effects of ischemia reperfusion on epithelial cells apoptosis and proliferation of intrahepatic bile duct (IBD) (>20 microm).. 30-minute warm ischemia was applied to rat livers respectively, and experiment was performed on days 2, 7, 14, 28 after reperfusion. Apoptosis was determined in situ by morphology and TUNEL, and cholangiocyte proliferation was evaluated in situ by morphometry of liver sections stained for cytokeratin-19 (CK-19) and by proliferating cellular nuclear antigen staining in liver sections.. Two days after ischemia reperfusion, apoptosis of cells was observed in large intrahepatic bile ducts (>20 microm) (5.6%+/-1.2%), but the number of large intrahepatic bile ducts reduced (0.32+/-0.06). Seven days after ischemia reperfusion, the apoptosis index of cholangiocytes decreased to 1.2%+/-0.3%, and the number of intrahepatic bile ducts began to proliferate and returned to nearly normal on day 28.. Ischemia reperfusion causes a decrease in the number of intrahepatic bile ducts (>20 microm) as a result of a higher rate of apoptosis and absence of initial proliferation.

Topics: Animals; Apoptosis; Bile Ducts, Intrahepatic; Cell Division; Epithelial Cells; Hepatocytes; Immunohistochemistry; In Situ Nick-End Labeling; Keratins; Male; Necrosis; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Reperfusion Injury

In cultured neuroblastoma cells, hypoxia induces a dedifferentiated phenotype. We tested whether hypoxia-induced dedifferentiation also occurs in vivo in mammary ductal carcinoma in situ with its well-defined lesions and distinct areas of necrosis. Ductal carcinoma in situ cells surrounding the central necrosis have high hypoxia inducible factor-1alpha protein levels, down-regulated estrogen receptor-alpha, and increased expression of the epithelial breast stem cell marker cytokeratin 19; lose their polarization; and acquire an increased nucleus/cytoplasm ratio, hallmarks of poor architectural and cellular differentiation. The hypoxia-induced changes were confirmed in cultured breast cancer cells. We propose that hypoxia-induced dedifferentiation is a mechanism that promotes tumor progression in breast cancer.

Topics: Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Cell Differentiation; Cell Hypoxia; Down-Regulation; Estrogen Receptor alpha; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Keratins; Necrosis; Receptors, Estrogen; Transcription Factors; Tumor Cells, Cultured; Up-Regulation

Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor of uncertain histogenesis that arises predominantly in the extremities of young adults. Immunohistochemically, the neoplastic cells are typically positive for vimentin, low molecular weight cytokeratin (CAM5.2) and epithelial membrane antigen (EMA).. We examined eight cases of ES from seven different patients. All cases were studied with immunohistochemistry for EMA, CAM5.2 (keratin 8 and 18), 34BE12 (keratins 1, 5, 10 and 14/15), cytokeratins 7 and 20 (CK7, CK20), and CD34.. The average patient age was 53 (range 43-76) and the male:female ratio was 5:2. The location was the upper extremity in five tumors, the lower extremity, the perineum, and the paraspinal soft tissue in one tumor each. All cases contained predominantly epithelioid cells, but spindle cells were also present in three cases. All cases contained areas of geographic necrosis. CAM5.2 was strongly positive in seven tumors and focally positive in one (8/8). EMA was diffusely positive in two cases and focally positive in five cases (7/8). CD34 was diffusely positive in 3/8 cases. 34BE12 was diffusely positive in one case and focally positive in two others (3/8). CK7 was diffusely positive in one case and focally positive in another (2/8). CK20 was negative in all cases (0/8). All cases tested were positive for vimentin (6/6), 2 cases were focally positive for HHF35 (2/5), and all cases tested were negative for S-100 protein (0/7).. In addition to the known immunoreactivity for CAM5.2 and EMA, there is positivity for CK7 and 34BE12 in a small proportion of cases. None of the cases expressed CK20. This immunophenotypic profile suggests that ES is more similar to carcinoma and synovial sarcoma than to other soft tissue tumors, and may be of diagnostic utility.

Topics: Adult; Aged; Biomarkers, Tumor; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Necrosis; Sarcoma; Soft Tissue Neoplasms

From 40 pigs rejected for human consumption at slaughter due to an apparent presence of pyemic lung lesions (defined as disseminated processes containing pus and/or necrotic material), the lungs, spleen, liver, and kidneys were subjected to an extended macroscopic examination. Several lung lesions were sampled from each animal for histological and bacteriological examination. Samples from the kidneys and spleens were also subjected to bacteriological examination. At gross level, four groups of lung lesions were identified: 1) disseminated foci with contents of pus and/or necrotic material (n=26); 2) disseminated or multifocally located ecchymoses with a central area of fibroplasia (n=9); 3) non-pneumonic lesions, i.e., disseminated areas of atelectasis (n=1) or haemorrhagic areas developing due to the process of slaughter (n=1); and 4) suppurative lesions without a disseminated distribution pattern (n=3). Histologically, the disseminated suppurative/necrotic foci were identified as: A) abscesses (n=10); B) necrotic lesions (n=6); and C) ectatic or ectatic-like bronchioles with contents of pus and necrotic material (n=10). The macroscopic observation of disseminated centres of fibroplasia with peripheral ecchymoses (n=9) was confirmed histopathologically. The livers of five pigs contained multiple areas of chronic interstitial fibrosis related to migration of Ascaris suum larvae ("milk spotted liver"). Such hepatic lesions were significantly (p<0.01) related to the simultaneous occurrence of disseminated pulmonary ecchymoses with a central area of fibroplasia. Generally, all lung lesions of each individual animal contained identical monocultures of bacteria following this pattern: Staphylococcus aureus (abscesses); Actinomyces hyovaginalis (necroses); S. aureus, A. hyovaginalis, and Arcanobacterium pyogenes (ectatic and ectatic-like bronchioles). Areas with fibrosis were sterile or contained bacteria considered to be a result of contamination. Apart from one kidney, from which S. aureus was cultured, all other organs were sterile. It is concluded that difficulties exist in differentiating pulmonary pyemic lesions from non-pyemic lesions at the gross level. Thus, it was not possible to distinguish between abscesses/necroses and ectatic bronchioles, the pathogenesis of the latter being uncertain. However, the chronic non-pyemic lesions related to the migration of A. suum larvae should be identified by the absence of pus/necrosis. S. aureus was predominantly

Topics: Abscess; Actinomyces; Actinomycosis; Animals; Keratins; Lung; Lung Diseases; Necrosis; Pneumonia, Bacterial; Suppuration; Sus scrofa; Swine Diseases

To determine the role of Bone morphogenetic protein (BMP) signaling in murine limb development in vivo, the keratin 14 promoter was used to drive expression of the BMP antagonist Noggin in transgenic mice. Phosphorylation and nuclear translocation of Smad1/5 were dramatically reduced in limbs of the transgenic animals, confirming the inhibition of BMP signaling. These mice developed extensive limb soft tissue syndactyly and postaxial polydactyly. Apoptosis in the developing limb necrotic zones was reduced with incomplete regression of the interdigital tissue. The postaxial extra digit is also consistent with a role for BMPs in regulating apoptosis. Furthermore, there was persistent expression of Fgf8, suggesting a delay in the regression of the AER. However, Msx1 and Msx2 expression was unchanged in these transgenic mice, implying that induction of these genes is not essential for mediating BMP-induced interdigital apoptosis in mice. These abnormalities were rescued by coexpressing BMP4 under the same promoter in double transgenic mice, suggesting that the limb abnormalities are a direct effect of inhibiting BMP signaling.

Topics: Animals; Apoptosis; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins; Carrier Proteins; Cyclin D1; DNA-Binding Proteins; Extremities; Female; Fibroblast Growth Factor 8; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Hedgehog Proteins; Homeodomain Proteins; Keratin-14; Keratins; Male; Mice; Mice, Transgenic; MSX1 Transcription Factor; Necrosis; Phosphorylation; Proteins; Signal Transduction; Syndactyly; Trans-Activators; Transcription Factors; Zebrafish Proteins

Epidermal lamellae (scutes) of the Texas tortoise, Gopherus berlandieri, from southern Texas (USA) were observed to be in various stages of necrosis, ranging from localized whitish blemishes to complete degradation of the external portion of the scute. Fusarium semitectum was consistently isolated from slivers of infected scute from tortoises. The fungus was not isolated from tortoises exhibiting no lesions. Confocal microscopy confirmed the presence of septate mycelia inside the scutes, and isolates of F. semitectum grown in the laboratory were successfully transferred to non-infected tortoises. Twenty-four tortoises maintained by two rehabilitators in southern Texas exhibited lesions; however, only one of 27 tortoises from Dimmit and Zavala counties was infected.

Topics: Animal Diseases; Animals; Epidermis; Fusarium; Keratins; Male; Mycoses; Necrosis; Skin Diseases; Texas; Turtles

Topics: Actins; Animals; Annexin A5; Apoptosis; Caspases; Epitopes; Histological Techniques; Humans; In Situ Nick-End Labeling; Keratins; Membrane Proteins; Necrosis; Neoplasms; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Polymerase Chain Reaction; Proteins; Rats

To clarify whether intraglandular necrotic debris (IND) is a diagnostic clue to noninvasive high-grade neoplasia or invasive neoplasia of the stomach, we reviewed 135 gastric biopsy specimens and 55 surgical materials. Intraglandular necrotic debris is defined as an eosinophilic material with necrotic epithelial fragments within the lumen of a dilated atypical gland. Using the Vienna classification, the incidence of IND in category 4 (noninvasive high-grade neoplasia) and category 5 (invasive neoplasia) was significantly higher than that of category 1 (negative for neoplasia/dysplasia), category 2 (indefinite for neoplasia/dysplasia), and category 3 (noninvasive low-grade neoplasia). The incidence of IND was much higher in category 5 than in category 4 in biopsy specimens. In addition, cases with IND in category 4 in biopsy specimens turned out to be either carcinoma in situ or invasive carcinoma in the surgical specimens. According to the histologic classification of surgically removed invasive carcinoma, moderately differentiated adenocarcinoma showed the highest incidence of IND. Intraglandular necrotic debris was not found in either signet-ring cell carcinoma or mucinous adenocarcinoma. Our results indicate that IND in biopsy specimens is a diagnostic clue to noninvasive high-grade neoplasia or invasive carcinoma, and the origin of IND may be associated with necrotic atypical epithelium.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Biopsy; Female; Gastric Mucosa; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Necrosis; Neoplasm Invasiveness; Stomach Neoplasms

Twenty-five cases of thymoma with prominent cystic and hemorrhagic changes and areas of necrosis and infarction are presented. The patients were 11 women and 14 men between the ages of 18 and 73 years (median 45.5 years). Clinically, nine patients were asymptomatic and their mediastinal tumor was discovered on routine chest radiograph. Sixteen patients presented with symptoms of chest pain and cough. All patients underwent surgical resection of their tumor. Grossly, the tumors were described as well circumscribed and encapsulated, with the exception of two that showed infiltration of pleura and pericardium. The tumors measured from 4 to 13 cm in greatest dimension. On cut surface they showed prominent cystic areas and foci of hemorrhage and necrosis. Histologically, the tumors contained solid areas showing an admixture of round to oval epithelial cells devoid of atypia admixed with small lymphocytes in varying proportions. Cystic changes with areas of necrosis, infarction, and hemorrhage were present in all cases and comprised extensive areas of the tumors. The areas of infarction showed features of ischemic necrosis and were always intimately associated with vaso-occlusive and thrombotic phenomena and with cystic and hyperplastic changes of adjacent thymic epithelium. Clinical follow-up in 14 patients showed that 11 were alive and well from 1 to 18 years after surgery (median follow-up 9 years). Three patients died: one of complications during the immediate postoperative period, one because of colonic adenocarcinoma 9 years after diagnosis of the mediastinal tumor, and one because of pneumonia 6 years later. The two patients with invasive tumors were lost to follow-up. The present study appears to indicate that areas of hemorrhage and necrosis in well encapsulated, noninvasive thymomas do not portend an adverse prognosis.

Topics: Adolescent; Adult; Aged; Cysts; Female; Follow-Up Studies; Hemorrhage; Humans; Immunoenzyme Techniques; Infarction; Keratins; Male; Middle Aged; Necrosis; Retrospective Studies; Thymoma; Thymus Neoplasms

Topics: Adult; Fingers; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Necrosis; Sarcoma; Soft Tissue Neoplasms

A 32-year-old woman underwent a suction curettage for missed abortion. The initial serum human chorionic gonadotropin (beta-hCG) level was 40 IU/ml. The histologic examination of the uterine curettage specimen showed scant strips of a poorly differentiated malignant neoplasm and no chorionic villi. The tumor showed strong immunoreactivity for cytokeratin (AE1/AE3) and beta-hCG but no reactivity for human placental lactogen. The combination of histologic appearance, beta-hCG immunoreactivity, and elevation of serum beta-hCG raised a strong suspicion for epithelioid trophoblastic tumor (ETT). Postcurettage serial serum beta-hCG levels remained in the range of 20 to 45 micrograms/ml. Computerized tomographic scan showed a 1.0-cm circumscribed mass in the upper endocervix. A radical hysterectomy and pelvic lymphadenectomy were performed. Gross examination of the hysterectomy specimen likewise showed a well-circumscribed mass in the upper endocervix. Histologic examination revealed an undifferentiated carcinoma accompanied by intense lymphoplasmacytic infiltrate. A final diagnosis of lymphoepithelioma-like carcinoma (LELC) was rendered. LELC with elevated serum beta-hCG level and immunoreactivity to beta-hCG should be distinguished from ETT in a small endocervical curettage sample.

Topics: Abortion, Missed; Adult; Carcinoma, Squamous Cell; Chorionic Gonadotropin, beta Subunit, Human; Diagnosis, Differential; Female; Humans; Hysterectomy; Keratins; Lymphocytes; Necrosis; Placental Lactogen; Plasma Cells; Pregnancy; Trophoblastic Neoplasms; Uterine Cervical Neoplasms

The roles of the different retinoid receptors on the differentiation of rabbit tracheal epithelial (RbTE) cells in primary culture were analysed using selective agonists for the retinoid acid receptor subtypes RARalpha (CD336), RARbeta (CD2019), RARgamma (CD437), an RAR panagonist (CD367), a retinoid X receptor RXR panagonist (CD2624) and an antagonist for RARbeta/gamma (CD2665). Squamous differentiation was assessed via expression of cytokeratins CK13/CK4 and transglutaminase I (TGI), specific markers of metaplasia. Treatment with RARalpha and beta agonists or RAR panagonist, but not the RARgamma agonist or RXR agonist, is required for the inhibition of squamous metaplasia, evidenced by inhibition of CK13/CK4 and TGI expression. The expression of CK10 cytokeratin of keratinizing epithelia, CK14/CK5 basal cell cytokeratins, and CK6 marker of cell proliferation decreases upon exposure of the RARaalpha/beta and RXR agonists. The RARgamma agonist CD437, inactive in the decrease in CK13/CK4, CK10 and CK14, reduces CK5/CK6 amounts. CD437 is responsible for a dose-dependent apoptotic response. Nuclear labelling with propidium iodide (PI) and electron microscopy revealed chromatin condensation and nuclear fragmentation. DNA cleavage and cell fragmentation were confirmed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The RARbetagamma antagonist was also slightly active. The results indicate that CD437 causes growth arrest in the early S-phase of the cell cycle and prevents the transition G1-S-phase. CD437 was demonstrated to induce apoptosis in the S-phase cells identified by bromodeoxyuridine (BrdU) incorporation. In conclusion, RARalpha/beta ligands are effective inhibitors of squamous differentiation. On the contrary, RARgamma ligand appears to be inefficient in metaplasia inhibition, but the selective RARgamma agonist CD437 induces growth arrest and apoptosis of basal proliferative cells.

Topics: Animals; Antineoplastic Agents; Apoptosis; Benzoates; Cell Differentiation; Cells, Cultured; DNA Fragmentation; Epithelial Cells; Keratins; Ligands; Metaplasia; Microscopy, Electron; Naphthalenes; Necrosis; Rabbits; Receptors, Retinoic Acid; Retinoids; S Phase; Teratogens; Tetrahydronaphthalenes; Trachea

We present a case of an unusual tumour arising in the forehead of a 52-year-old female. The tumour, diagnosed as sebaceoma (or sebomatricoma), showed predominantly differentiation towards ductal protion of the sebaceous gland. It was marked in tissue sections as areas of "poroid" cells and the tumour required differentiation from poroma. Focal areas of necrosis en masse in the present tumour contributed further difficulties in to the differential diagnosis. As single multivacuolar sebocytes were found and no cuticular cells could be identified, the tumour was diagnosed as ductal sebaceoma (sebomatricoma). The aspects of morphological distinction between sebomatricomas and poromas are presented with its clinical implications.

Topics: Diagnosis, Differential; E2F6 Transcription Factor; Female; Forehead; Humans; Keratins; Middle Aged; Necrosis; Repressor Proteins; Sebaceous Gland Neoplasms; Transcription Factors

Investigation of the histopathological changes in prostatectomy specimens of patients with prostate cancer after high intensity focused ultrasound (HIFU) and identification of immunohistochemical markers for tissue damage after HIFU treatment.. Nine patients diagnosed with adenocarcinoma of the prostate underwent unilateral HIFU treatment seven to 12 days before radical prostatectomy. The prostatectomy specimens were analysed histologically. Immunohistochemical staining and electron microscopy were performed to characterise more subtle phenotypic changes.. All prostatectomy specimens revealed well circumscribed HIFU lesions at the dorsal side of the prostate lobe treated. Most epithelial glands in the centre of the HIFU lesions revealed signs of necrosis. Glands without apparently necrotic features were also situated in the HIFU lesions, raising the question of whether lethal destruction had occurred. This epithelium reacted with antibodies to pancytokeratin, prostate specific antigen (PSA), and Ki67, but did not express cytokeratin 8, which is indicative of severe cellular damage. Ultrastructural examination revealed disintegration of cellular membranes and cytoplasmic organelles consistent with cell necrosis. HIFU treatment was incomplete at the ventral, lateral, and dorsal sides of the prostate lobe treated.. HIFU treatment induces a spectrum of morphological changes ranging from apparent light microscopic necrosis to more subtle ultrastructural cell damage. All HIFU lesions are marked by loss of cytokeratin 8. HIFU does not affect the whole area treated, leaving vital tissue at the ventral, lateral, and dorsal sides of the prostate.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Humans; Keratins; Male; Middle Aged; Necrosis; Neoplasm Proteins; Prostate; Prostatectomy; Prostatic Neoplasms; Ultrasonic Therapy

It has been reported previously that keratin 8 (K8)-deficient mice of one strain die from a liver defect at around E12.5, while those of another strain suffer from colorectal hyperplasia. These findings have generated considerable confusion about the function of K8, K18 and K19 that are co-expressed in the mouse blastocyst and internal epithelia. To resolve this issue, we produced mice doubly deficient for K18 and K19 leading to complete loss of keratin filaments in early mouse development. These embryos died at around day E9.5 with 100% penetrance. The absence of keratins caused cytolysis restricted to trophoblast giant cells, followed by haematomas in the trophoblast layer. Up to that stage, embryonic development proceeded unaffected in the absence of keratin filaments. K18/19-deficient mouse embryos die earlier than any other intermediate filament knockouts reported so far, suggesting that keratins, in analogy to their well established role in epidermis, are essential for the integrity of a specialized embryonic epithelium. Our data also offer a rationale to explore the involvement of keratin mutations in early abortions during human pregnancies.

Topics: Animals; Blotting, Western; Cytoskeleton; Embryo, Mammalian; Epithelial Cells; Female; Fetal Death; Fluorescent Antibody Technique; Gene Deletion; Genotype; Giant Cells; Intestinal Mucosa; Intestines; Keratins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutagenesis, Site-Directed; Necrosis; Phenotype; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications; Trophoblasts; Uterine Hemorrhage

Axillary granular parakeratosis is a recently described condition presenting with erythematous hyperkeratotic papules and plaques. We report on nine women and one man with eruptions not only localized to the axillae. Biopsy specimens were investigated by histology, immunohistochemistry, electron microscopy, immuno-electron microscopy, and in situ hybridization. In general, the epidermis was hyperplastic and showed a well preserved stratum granulosum. In the upper dermis a discrete perivascular CD4+ T-cell infiltrate was found, CD1+ dendritic cells were absent from the epidermis. The distribution pattern of the epidermal keratins (keratin 5/14, 1/10) and the expression of involucrin was regular. The horny layer was excessively thickened and parakeratotic. The nuclear remnants showed marginal chromatin condensation and were reactive for the nick-end labeling technique using TdT-mediated dUTP-biotin. The corneocytes were characteristically replete with basophilic granules which showed both ultrastructural features of keratohyalin granules and immunoreactivity for filaggrin. Loricrin was expressed irregularly in small L-granules. Granular parakeratotic cells revealed regular development of a cornified envelope while cell membranes and desmosomes remained undegraded. In conclusion, our studies on granular parakeratosis suggest a basic defect in processing of profilaggrin to filaggrin that results in a failure to degrade keratohyalin granules and to aggregate keratin filaments during cornification. Associated abnormalities of the cell surface structures and dysregulation of cornified envelope components may account for the retention hyperkeratosis. Further studies are necessary to clarify the etiology of this unique, acquired disorder of keratinization that localizes to intertriginous areas and body folds.

Topics: Adult; Aged; Antibodies, Monoclonal; Biopsy; Dermatitis; Epidermis; Female; Filaggrin Proteins; Humans; In Situ Nick-End Labeling; Keratinocytes; Keratins; Male; Microscopy, Immunoelectron; Middle Aged; Necrosis; Parakeratosis; Recurrence

We have previously shown that necrotic tumors retain their immunoreactivity for a range of cytokeratin antibodies. Some thyroid tumors undergo extensive necrosis after fine-needle aspiration (FNA) procedures. We evaluated the sensitivity of antibodies on necrotic thyroid tumors by examining a series of thyroid tumors consisting of 10 Hurthle cell neoplasms, 8 carcinomas, and 2 follicular adenomas (12 with post-FNA necrosis). These were stained with antibodies to AE1/3, PANCK, thyroglobulin and S100. Four of the cases of papillary carcinoma were also stained with antibodies to CK19. As a control for the specificity of thyroglobulin immunoreactivity in necrotic tissue, we also stained 11 nonthyroid tumors with extensive necrosis (7 carcinomas, 1 lymphoma, 2 melanomas, 1 sarcoma) for thyroglobulin. Six of 8 thyroid carcinomas were positive for AE1/3 and PANCK; AE1/3 reactivity was retained in necrotic areas of 4 of 6. AE 1/3 was positive in necrotic portions of 5 of 10 Hurthle cell lesions, whereas PANCKwas negative in all but 1. Thyroglobulin reactivity was present in 18 of 20 cases, and was preserved in necrotic portions of 5 of 6 carcinomas, as well as 8 of 10 Hurthle cell neoplasms. S100 cytoplasmic reactivity was present in 4 Hurthle cell neoplasms and 1 papillary carcinoma; this staining was lost in necrotic areas. No staining by thyroglobulin was observed in the viable or necrotic areas of nonthyroid neoplasms. The preservation of cytokeratin reactivity, measured by AE1/3, in thyroid neoplasms is a diagnostically useful feature in spontaneous and post-FNA infarction. PANCK is not a well-preserved marker in necrotic thyroid tissue. This difference may be due to detection of keratin 19 by AE1/3. Thyroglobulin is preserved in some necrotic thyroid carcinomas and in Hurthle cell lesions. Preservation of thyroglobulin reactivity in necrotic tissue is specific in that no staining was observed in nonthyroid neoplasms. These results suggest that thyroglobulin is useful in demonstrating thyroid lineage of both primary and metastatic necrotic tumor masses.

Topics: Adenoma; Adenoma, Oxyphilic; Carcinoma; Humans; Immunohistochemistry; Keratins; Necrosis; S100 Proteins; Thyroglobulin; Thyroid Neoplasms

Small, extraportal, hepatic parenchymal cells, positive for biliary-type cytokeratins, may represent hepatic stem cells, canals of Hering (CoH), and/or ductal plate remnants. We evaluated these cells 3 dimensionally in normal human liver and massive necrosis. Tissues from normal human livers and from 1 liver with acetaminophen-induced massive necrosis were serially sectioned, immunostained for cytokeratin 19 (CK19), and sequentially photographed. Images were examined to determine 3-dimensional relationships among CK19-positive cells. Immunostains for other hepatocyte and progenitor cell markers were examined. In normal livers, intraparenchymal CK19-positive cells lined up as linear arrays in sequential levels. One hundred of 106 (94.3%) defined, complete arrays within levels examined, most having 1 terminus at a bile duct, the other in the lobule, beyond the limiting plate. In massive necrosis, there were 767 individual CK19-positive cells or clusters around a single portal tract, 747 (97.4%) of which were spatially related forming arborizing networks connected to the interlobular bile duct by single tributaries. C-kit was positive in normal CoH. CK19 co-expressed with HepPar1, c-kit, and alpha-fetoprotein (AFP) in parenchymal cells in massive necrosis. Small, extraportal, biliary-type parenchymal cells represent cross-sections of the CoH that radiate from the portal tract, usually extending past the limiting plate into the proximate third of the hepatic lobule. The 3-dimensional structure of ductular reactions in massive necrosis suggests that these reactions are proliferations of the cells lining the CoH. Therefore, the CoH consist of, or harbor, facultative hepatic stem cells in humans.

Topics: Acetaminophen; Adult; Aged; alpha-Fetoproteins; Bile Ducts, Intrahepatic; Biomarkers; Female; Humans; Immunohistochemistry; Keratins; Liver; Male; Middle Aged; Necrosis; Portal System; Proto-Oncogene Proteins c-kit; Stem Cells

A rare case of primary squamous cell carcinoma surrounding Stensen's duct in a 75-year-old man is presented. The tumor was a relatively well-defined, hard, subcutaneous mass, measuring 18 x 14 x 9 mm and situated in the right cheek. Microscopic examination of an excisional biopsy specimen revealed tumor cells showing squamous differentiation, a papillary growth pattern, and ductal structures with comedo necrosis. Immunohistochemical studies showed positive reactivity for KL-1 (cytokeratin, monoclonal), epithelial membrane antigen, and carcinoembryonic antigen in some tumor cells. The origin of the tumor was thought to be the accessory parotid gland duct epithelium.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Differentiation; Cell Nucleolus; Cell Nucleus; Cell Transformation, Neoplastic; Cytoplasm; Epithelium; Humans; Keratins; Male; Mucin-1; Necrosis; Parotid Gland; Parotid Neoplasms; Salivary Ducts

Extensive epidermal necrosis in newborn infants is an unusual event of heterogeneous cause.. The objective of this article is to describe what seems to be a previously unrecognized lethal disease.. The clinical and histopathologic features of three premature infants, two of them nonidentical twins, and the autopsy findings of one of them were analyzed.. Intrauterine lethal epidermal necrosis with hair follicle calcification, except for the face, hands, feet, elbows, and knees, was present in all three patients. Some histopathologic features were suggestive of epidermal apoptosis.. We propose that the clinicopathologic alterations in our patients represent a new condition that may be caused by massive epidermal apoptosis.

Topics: Apoptosis; Calcinosis; Collagen; Diseases in Twins; Elbow; Epidermis; Face; Fatal Outcome; Female; Fetal Diseases; Foot; Hair Diseases; Hair Follicle; Hand; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Keratinocytes; Keratins; Knee; Necrosis; Skin; Skin Abnormalities; Twins, Dizygotic

Immunohistochemistry occasionally is used to determine the lineage of entirely necrotic tumors. However, the sensitivity and specificity of antibodies on necrotic tissue are unknown. To determine the usefulness of immunohistochemistry with necrotic lesions, a series of 24 known tumors consisting of 14 carcinomas, 2 lymphomas, 2 melanomas, and 6 sarcomas (all with extensive necrosis) was examined for reactivity with 6 cytokeratin antibodies, S100, and LCA. Carcinomas stained positively with at least 1 cytokeratin antibody in 78% of the cases. The cytokeratin antibodies with the highest sensitivity were AE1, AE1/3, S903, and PANCK. These antibodies also retained specificity for epithelial differentiation; no reactivity was observed in the 10 necrotic nonepithelial tumors. LCA retained its reactivity with necrotic lymphoma, but S100 reacted with only one third of the necrotic lesions. Unexpectedly, reactivity for LCA and S100 occurred in some necrotic carcinomas. Keratin markers can be used on necrotic tissue to determine epithelial differentiation, but the results obtained with S100 and LCA on necrotic tissue should be interpreted with caution.

Topics: Antibodies; Antibody Specificity; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Melanoma; Necrosis; Neoplasm Metastasis; Neoplasms; S100 Proteins; Sarcoma

From a series of 100 consecutive breast carcinomas with axillary lymph node metastases, two cases of necrotic granulomas in the nodes are presented. Lymph nodes in each case were characterized by areas of necrosis surrounded by a palisade of cells resembling histiocytes as seen in a rheumatoid nodule. Although the initial impression was that of a reactive granuloma, when immunostained for keratin and EMA, the areas of necrosis showed positive staining for keratin and EMA in a cytoplasmic pattern. The surrounding palisade of cells stained with histiocyte markers, while the necrotic area itself was negative. Staining for both estrogen and progesterone markers was also negative. Staining of nine lymph nodes with caseating granulomas not associated with carcinoma with the same panel of antibodies revealed no staining except for irregular, noncellular staining with EMA. This pattern of necrosis in axillary lymph nodes from two cases of breast carcinoma was interpreted as evidence of necrotic metastatic tumor cells. Necrosis in axillary lymph nodes associated with invasive breast cancer should arouse suspicion for metastasis.

Topics: Axilla; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Diagnosis, Differential; Female; Granuloma; Histiocytes; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Mucin-1; Necrosis

Liver regeneration after massive hepatic necrosis is characterized by the presence and formation of ductular hepatocytes (DHs). Several studies suggested that these structures might serve as bipotential progenitor cells, as demonstrated by phenotypic features characteristic of both hepatocytes and biliary epithelial cells. In this investigation, 33 liver allograft explants after primary graft failure 1 to 14 days after orthotopic liver transplantation were examined to study the formation and differentiation of DHs. As demonstrated by earlier studies, antibody to CK-19 defines the biliary epithelial cell lineage, whereas HepPar 1 is hepatocyte specific. Antibodies to CK-19, vimentin and alpha-fetoprotein, HepPar 1, and AE-1 were used for immunoperoxidase staining of 33 failed liver allograft specimens with regeneration. DHs were seen along the limiting plates at Day 1, but reactivity to HepPar 1 started only at Day 4 post injury. Vimentin and alpha-fetoprotein were not detectable in the DHs. The DHs reacted with AE-1 and anti-CK-19 starting at Day 1, but reactivity to HepPar 1 started only at Day 4 post injury. DHs are formed along the limiting plates and acquire phenotypic characteristics of bile duct epithelium as early as Day 1 after liver injury and of hepatocytes only at Day 4 after liver injury. We conclude that DHs might represent bipotential progenitor cells in regenerating liver.

Topics: Biomarkers; Graft Survival; Hepatic Duct, Common; Humans; Immunoenzyme Techniques; Immunophenotyping; Keratins; Liver Regeneration; Liver Transplantation; Necrosis

Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract.. In this study, clinical and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that underwent potentially curative resection (no distant metastases, no residual tumor) were compared. In addition, light microscopic, electron microscopic, and immunohistochemical features of BSCC were investigated, to determine whether this type of carcinoma could be differentiated from other poorly differentiated carcinomas of the esophagus.. Light microscopic study showed that BSCC was composed of relatively small tumor cells, arranged in solid lobules with abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of concomitant typical SCC, foci of squamous cell differentiation, and/or severe squamous cell dysplasia or carcinoma in situ of the adjacent mucosa. Ultrastructurally, BSCC inconsistently showed features of squamous cell differentiation. Immunohistochemically, BSCC displayed poor reactivity for antibodies against wide-range cytokeratins and cytokeratin subtypes that are typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14). Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was found. In comparison with typical SCC, the characteristic features of BSCC were older patient age, higher proliferative activity (MIB-1 labelling index), and higher apoptotic indices. No differences were found with regard to pT classification, pN classification, tumor size, blood vessel invasion, lymphatic vessel invasion, neural invasion, or patient gender. Moreover, no differences in overall survival rates were found.. BSCC is a distinct histopathologic variant of SCC, characterized by a poor degree of differentiation and high proliferative activity. However, after potentially curative resection, the prognosis of patients with BSCC of the esophagus does not differ from that of patients with typical SCC.

Topics: Actins; Adult; Age Factors; Aged; Aged, 80 and over; Antigens, Differentiation; Apoptosis; Carcinoma in Situ; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Diagnosis, Differential; Epithelium; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Mucous Membrane; Necrosis; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; S100 Proteins; Sex Factors; Survival Rate

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

The purpose of this study was to observe the epithelialization process of the muscle-only flap used for reconstruction of the oral mucosal defects.. Forty-three male adult Japanese rabbits were used. A superiorly based cleidomastoid muscle flap was designed after vascular assessment. The flap was transferred into the oral cavity to cover a mucoperiosteal defect made in the mandibular alveolus. Epithelialization of the flap was histologically evaluated at designated intervals.. The flaps survived without ischemic necrosis. By 8 days postoperation, the flap was infiltrated by acute inflammatory cells and being replaced by granulation tissue originating from the adjacent tissues. The oral epithelial cells advanced onto this granulating muscle flap, with eventual coverage by 21 days. The granulation tissue matured to fibrous tissue with significant contraction by 2 months. At 6 months postoperation, abnormally hyperkeratinized epithelium was seen on the flap. This differed from the surrounding parakeratinized oral epithelium.. The muscle-only flap in the oral cavity epithelializes after the granulation process.

Topics: Actins; Animals; Cell Movement; Connective Tissue; Epithelial Cells; Epithelium; Follow-Up Studies; Graft Survival; Granulation Tissue; Inflammation; Ischemia; Keratins; Male; Mandible; Mandibular Diseases; Mouth; Mouth Mucosa; Muscle, Skeletal; Necrosis; Periosteum; Rabbits; Surgical Flaps; Wound Healing

Lichen amyloidosus (LA) is generally said to be a pruritic type of amyloidosis of unknown cause. Histopathologically, it is characterized by epidermal changes of lichen simplex chronicus and by deposits of amyloid in the papillary dermis that are derived from keratin peptides of necrotic keratinocytes. Chronic scratching is responsible for the development of lichen simplex chronicus and may lead to necrosis of individual keratinocytes.. Our purpose was to evaluate whether chronic scratching may also be responsible for the formation of amyloid in LA.. We studied patients with LA in regard to histopathologic findings, onset of pruritus, associated diseases, and response to treatment.. In most cases, pruritus had preceded the skin lesions. Eight of nine patients suffered from diseases other than LA that may be associated with pruritus. Histopathologically, amyloid was confined to areas that also showed signs of lichen simplex chronicus. Systemic treatment with sedating antihistamines and intense local treatment with corticosteroids were found to be effective.. LA is considered to be a variant of lichen simplex chronicus in which scratching leads to necrosis of keratinocytes and eventually to the formation of amyloid in the papillary dermis. Because chronic scratching seems to be the cause and not the result of the deposits of amyloid, treatment should be directed at the amelioration of pruritus.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Aged; Amyloid; Amyloidosis; Antipruritics; Chronic Disease; Collagen; Disease; Female; Histamine H1 Antagonists; Humans; Keratinocytes; Keratins; Keratosis; Leg Dermatoses; Male; Middle Aged; Necrosis; Neurodermatitis; Pruritus; Remission Induction; Skin; Skin Diseases

Carcinomas metastatic to the ovary are often difficult to distinguish from primary ovarian carcinomas. Adenocarcinoma of the colon may simulate both primary endometrioid and mucinous ovarian tumors. The histologic finding of "dirty" necrosis in association with a "garland" or cribriform pattern has been suggested as a useful feature in distinguishing metastatic colonic carcinomas from primary endometrioid ovarian carcinomas. This study was performed to determine the use of "dirty" necrosis in distinguishing primary ovarian carcinoma from metastatic colonic carcinoma by studying 71 of the former and 10 of the latter. At least focal dirty necrosis was found in 68% of primary ovarian epithelial cancers, including 92% of the endometrioid subtype, and in 100% of the metastatic colonic carcinomas. A subgroup of cases was evaluated immunohistochemically using cytokeratin (CK) 7, CK 20 and carcinoembryonic antigen (CEA). The phenotype of CK 7 +/CK 20-/CEA-was present in 92% of primary ovarian carcinomas studied, whereas, 90% of metastatic colonic carcinomas were CK 7-/CK 20 +/CEA+. The finding of dirty necrosis is not specific for metastatic colonic cancer, and differential cytokeratin immunostaining is a useful adjunct in this differential diagnosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Middle Aged; Necrosis; Ovarian Neoplasms

Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (GY) in 2 fractions of 10 Gy each week were reviewed for radiation changes.. In all patients, preoperative biopsy specimens showed moderate to poorly differentiated squamous cell carcinoma with minimal to negligible keratin production. The esophagectomy specimens were sampled at the resection margins, the edge of irradiated length, 1 cm from the proximal and distal edge of visible tumor, the center of the tumor, and the lymph nodes.. Radiation change in the form of fibrosis was limited to the submucosa at the resection margins, the circular muscle layer at the edge of irradiated length, and full thickness at 1 cm from the edge of the visible tumor and the center of the tumor. Surface epithelium did not show any changes at the resection margins but did show basal cell hyperplasia at the edge of the irradiated length and ulceration at 1 cm from the edge of the visible tumor and the center of the tumor. Endarteritis obliterans was seen only 1 cm from the edge of the visible tumor and the center of the tumor. Necrosis, intense keratin formation, and giant cell reaction were observed at the center of the tumor. When compared with the preradiotherapy biopsies, the amount of keratin in the postradiotherapy specimens was extensive. HDRILBT may cause induction of the keratin gene in the irradiated cells to stimulate differentiation toward better differentiated cells.. HDRILBT may cause the keratin gene in the irradiated cells to induce differentiation toward better differentiated cells. Preoperative high dose rate intraluminal brachytherapy may have a role in improving the prognosis of patients with early esophageal cancer treated with a combination of radiotherapy and surgery.

Topics: Adult; Brachytherapy; Carcinoma, Squamous Cell; Cell Differentiation; Combined Modality Therapy; Endarteritis; Esophageal Neoplasms; Esophagectomy; Esophagus; Female; Giant Cells; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Necrosis; Neoplasm Proteins; Preoperative Care; Radiation Injuries; Radiotherapy, Adjuvant

The authors performed a retrospective study in ultrasound to investigate new aspects in the sonomorphology of lymph node metastases of the neck. In this study, it could be demonstrated the first time that the histologic characteristics of the metastases determine the sonographic appearance. In addition to criteria such as the longitudinal/ transversal quotient, sonomorphology could support a more precise differential diagnosis of neck lymph nodes.. In 105 of 145 patients with histologically proved head and neck carcinomas, 187 lymph node metastases were detected by ultrasound. Sonomorphology was compared with the corresponding histology.. Five sonomorphologic groups could be differentiated. (1) Thirty-one percent of the metastases were homogenous. (2) Concerning the more complex morphology of lymph node metastases in ultrasound, echolucent forms could be differentiated from echogenic textures: low- or nondifferentiated and nonkeratinizing metastases appeared echolucent and cyst-like, with dorsal signal amplification. (3) Nonkeratinizing lymphomas with necrosis showed single or multiple echolucent intranodal lesions. (4) In correlation with an increasing keratinization, the echogenecity of the lymph nodes increased and intranodal echogenic inclusions appeared. (5) An extended keratinization correlated with a central echogenecity.. The morphologic assessment of lymph nodes in ultrasound allows for primary histologic and prognostic evaluation of lymph node metastases.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Necrosis; Ultrasonography

Recent studies, including our own, suggest that intermediate filament proteins, particularly bile duct-specific cytokeratin 19 (CK19) and the hepatocyte-specific HepPar1 antigen define the developmental stages of hepatic progenitor cells during liver morphogenesis. We hypothesized that the HepPar1+ CK19+ progenitor cells are activated during human liver regeneration after massive hepatic necrosis and proliferate with the formation of so-called ductular hepatocytes or neocholangioles. We demonstrated previously that the ductular hepatocytes proliferate and share phenotypic characteristics with hepatocytes and biliary epithelial cells. In this investigation, we compared the expression pattern of intermediate filament proteins and HepPar1 antigen in ductular hepatocytes with that of bipotential hepatic progenitor cells. CK14, CK19, vimentin, and HepPar1 antigen were localized by immunoperoxidase staining in 13 human livers with regeneration after massive hepatic necrosis. Double immunostaining of three cases for CK14/CK19 and HepPar1/CK19 was also performed. CK19 reaction exhibited diffuse staining of the cytoplasm of many ductular hepatocytes and bile ducts in all cases. CK14 was expressed in the cytoplasm of ductular hepatocytes and few bile ducts in 5 of 12 specimens. HepPar1 staining was positive in many ductular hepatocytes in 11 of 13 cases. Vimentin was detected in the perinuclear cytoplasm of ductular hepatocytes and some bile duct epithelial cells in all regenerating livers. Double immunostaining for HepPar1/CK19 demonstrated that the ductular hepatocytes contained either HepPar1 or CK19 and that some ductular hepatocytes coexpressed both antigens. CK14, CK19, vimentin, and HepPar1 expression in ductular hepatocytes in human liver regeneration resembles the pattern seen in the developing human liver from 4 to 16 weeks' gestation. This suggests that the ductular hepatocytes recapitulate the developmental stages of bipotential liver progenitor cells and differentiate in steps marked by the acquisition or loss of specific phenotypic characteristics.

Topics: Adolescent; Adult; Aged; Female; Humans; Keratins; Liver Diseases; Liver Regeneration; Male; Middle Aged; Necrosis; Stem Cells; Vimentin

Epidermal growth factor receptor (EGFR) is a key regulator of keratinocyte biology. However, the physiological role of EGFR in vivo has not been well established. To analyze the role of EGFR in skin, we have generated transgenic mice expressing an EGFR dominant negative mutant in the basal layer of epidermis and outer root sheath of hair follicles. Mice expressing the mutant receptor display short and waved pelage hair and curly whiskers during the first weeks of age, but subsequently pelage and vibrissa hairs become progressively sparser and atrophic. Eventually, most mice present severe alopecia. Histological examination of the skin of transgenic mice shows striking alterations in the development of hair follicles, which fail to enter into catagen stage. These alterations eventually lead to necrosis and disappearance of the follicles, accompanied by strong infiltration of the skin with inflammatory elements. The interfollicular epidermis of these mice shows marked hyperplasia, expression of hyperproliferation-associated keratin K6 and increased 5-bromo-2-deoxyuridine incorporation. EGFR function was inhibited in transgenic skin keratinocytes, since in vivo and in vitro autophosphorylation of EGFR was almost completely abolished on EGF stimulation. These results implicate EGFR in the control of hair cycle progression, and provide new information about its role in epidermal growth and differentiation.

Topics: Animals; Cell Division; Epidermis; ErbB Receptors; Genes, Dominant; Hair Follicle; Keratins; Mice; Mice, Transgenic; Mutation; Necrosis; Skin

The development of ductular structures in acute hepatitis with panacinar necrosis was studied in 15 cases of fulminant hepatitis with variable clinical duration, using immunohistochemical markers. The immunophenotype of ductular structures was assessed by the expression of two bile duct epithelium determinants, wide spectrum cytokeratin and epithelial membrane antigen (EMA), and by their glycoconjugate expression using the specific binding lectins Dolichos biflorus agglutinin (DBA) and soybean agglutinin (SBA). Ductular structures showed a predilective, but not a strictly selective location in acinar zone 1 and at the periphery of newly formed parenchymal nodules. All were positive for keratin, while EMA and the lectins were identified less frequently. Cytokeratin expression was additionally observed in hepatic cells with no other phenotypic alteration: this occurred along isolated hepatic cords, within parenchymal remnants, in the spared parenchyma in acinar zone 1 and occasionally at the periphery of parenchymal nodules. The presence of cytokeratin expression in liver cell plates in association with intermediate morphological stages of tubular remodelling speaks in favour of biliary metaplasia of hepatocytes. This process may represent a phenotypic-functional accommodation of hepatocytes to an altered microenvironment, due to loss of parenchymal integrity. During the phenotypic shift, altered cytokeratin expression appears as one of the earliest biliary features, while EMA and the expression of glycoconjugates represent maturation markers.

Topics: Acute Disease; Antigens; Cytoplasm; Glycine max; Hepatitis; Humans; Immunohistochemistry; Keratins; Lectins; Liver; Membrane Glycoproteins; Mucin-1; Mucins; Necrosis; Plant Lectins; Soybean Proteins; Time Factors

All neoplasms require angiogenesis and resulting neovascularity for growth. The authors and others have confirmed the staging and prognostic significance of quantitative microvascularity density (MVD) in human prostate carcinoma (CAP). In the present investigation, the authors sought to identify the specific site of neovascularity within the neoplasm and adjacent benign tissue.. Histologically benign and malignant tissues from 14 random radical prostatectomy specimens were studied. The tumor edge was defined precisely by immunohistochemistry, suggesting a high molecular weight cytokeratin that stains only the basal cells of benign histology. Microvascularity density quantification was performed using von Willebrand factor antigen immunohistochemistry as previously defined. Five parallel arcs were defined along which vessel density was calculated including arcs within, on the edge, and removed from the neoplasm.. In 13 of 14 cases, the highest vessel density was found within the tumor. Significant differences were observed between the edge of the tumor and 2.5 mm within the benign periphery, between the benign and malignant tissue at the border, and between CAP at the edge and CAP 2.0 mm within the neoplasm. These findings suggest a stepwise increase in MVD toward the center of the neoplasm.. These data confirm the authors' previous observation that prostate cancer has approximately a two-fold increase in MVD compared with the benign tissue. Moreover, high vascularization of the center explains the rare finding of necrosis in CAP. These data suggest that angiogenic promoters may have their highest activity in the center of the neoplasm.

Topics: Carcinoma; Humans; Keratins; Male; Microcirculation; Necrosis; Neoplasm Staging; Neovascularization, Pathologic; Prognosis; Prostate; Prostatic Neoplasms; von Willebrand Factor

The authors compared 69 cases of surgically proven invasive squamous cell carcinoma (ISCC) of uterine cervix with 48 cone biopsy specimens that showed cervical intraepithelial neoplasia (CIN) grade III. Histologic features that were preferentially associated with ISCC included the following: giant bizarre cells (66.7% in ISCC, 6.26% in CIN III, P < .01); large keratinized cells (87% in ISCC, 0% in CIN III, P < .01); keratin pearls (40.6% in ISCC, 0% in CIN III, P < .01); necrosis (79.7% in ISCC, 8.3% in CIN III, P < .01); and neovascularization (56.5% in ISCC, 0% in CIN III). In 51 (74%) cases of ISCC, a CIN III component was present, of which 18 (35.3%) showed large keratinized cells or keratin pearls in the in situ components. None of the CIN III cases showed more than one of the above features. In the ISCC group, the above features occurred with similar frequency in microinvasive and frankly invasive tumors. The authors' results agree with previous Papanicolaou-smear cytologic studies, which found that ISCC can be distinguished accurately from CIN III by the morphology of the neoplasm. The authors concluded that cervical biopsy specimens that show two or more of the above features are highly suggestive of ISCC, even when stromal tissue is absent or insufficient for the assessment of invasion. Furthermore, in cervical biopsy specimens showing CIN III, the presence of large keratinized cells or keratin pearls may signify the presence of invasive lesions elsewhere in the cervical mucosa.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Giant Cells; Humans; Keratins; Middle Aged; Necrosis; Neoplasm Invasiveness; Neoplasm Staging; Neovascularization, Pathologic; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Changes in the expression of cytokeratin subunits during regeneration of the intralobular duct in partially injured rat submandibular glands were investigated. Limited parts of rat submandibular glands were injured by irradiation with YAG laser. Irradiated glands were investigated histologically and immunohistochemically using anti-cytokeratin monoclonal antibodies, RCK105 and CK19. Irradiated areas became necrotic one day after YAG laser irradiation. At three and five days, duct-like structures and epithelial clusters began to regenerate at the periphery of the remaining lobule. Epithelial clusters without ductal spaces were situated at the terminal portion of the duct-like structures. At seven and ten days, duct-like structures were composed of cuboidal or low columnar cells, and the number of epithelial clusters decreased. Immunohistochemically, cells of intralobular ducts in normal rat submandibular glands reacted to RCK105 and CK19. At three and five days, the epithelial cells of duct-like structures were positive for both antibodies. Many cells in the epithelial clusters showed negative reaction. However, in some epithelial clusters, inner cells and cells facing narrow luminal spaces were positive for both antibodies. At seven and ten days, positive reaction for both antibodies was identified in duct-like structures. This study showed that cells of the epithelial cluster were less mature than those of the duct-like structure, and that in the epithelial cluster, the inner cells were the first to differentiate into intralobular ductal cells.

Topics: Animals; Antibodies, Monoclonal; Cell Differentiation; Epithelium; Immunoenzyme Techniques; Keratins; Lasers; Male; Necrosis; Rats; Rats, Wistar; Regeneration; Submandibular Gland

An unusual case of ameloblastoma which depicts cystic follicles containing orthokeratin, parakeratin, desquamated epithelium and necrotic material with dystrophic calcification is presented. The presence of ameloblast-like cells confirms the diagnosis of an ameloblastoma. However, certain features resembled those of the keratoameloblastoma and others, less convincively, the papilliferous keratoameloblastoma. The extensive keratinisation in this tumour and in the aforementioned neoplasms raises the question whether they represent variants of the acanthomatous ameloblastoma.

Topics: Adult; Ameloblastoma; Ameloblasts; Calcinosis; Cysts; Epithelium; Female; Humans; Keratins; Mandibular Neoplasms; Necrosis

We examined the expression of carcinoembryonic antigen (CEA) and cytokeratin (CK) as well as the sialo- and sulphomucin content of 40 hyperplastic polyps (HPs), 6 mixed hyperplastic-adenomatous polyps, 30 adenomas and 40 adenocarcinomas of the colorectum. HPs showed a positive CEA expression in 95% of cases and a decreased sialo- and sulphomucin content compared with normal mucosa. Similar changes were observed in adenomas with low-grade dysplasia. The increase in CEA expression from HPs and adenomas to carcinomas was accompanied by a reduction of sialo- and sulphomucins with about three fourths of carcinomas being sialo- and sulphomucin negative. Oncofetal antigen expression concomitant with mucin changes observed in HPs may indicate impaired cellular maturation at a functional level before dysplastic changes become visible. CEA and CK positive macrophages were found in carcinomas predominantly at sites of tumor disruption and necrosis as well as within veins and lymphatic vessels. Our findings suggest that macrophages may play a role in CEA and CK release into the circulation and thus may be determinants of tumor marker serum levels.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenomatous Polyps; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Colon; Colonic Polyps; Colorectal Neoplasms; Humans; Hyperplasia; Keratins; Macrophages; Mucins; Necrosis; Neoplastic Cells, Circulating; Precancerous Conditions; Rectum

We investigated transglutaminase-induced cross-linking of cytokeratin polypeptides in liver and hepatoma cells. To overcome the difficulties in the biochemical analysis of highly cross-linked polymers and aggregates of cytokeratins, cross-linked cytokeratin dimers were analyzed by immunoblotting to evaluate the degree of cross-linking of cytokeratins. Covalently cross-linked cytokeratin dimers were not detectable in normal rat liver cells. However, cytokeratin dimers and high-molecular-weight cytokeratin polymers were detected in liver tissue with histological evidence of coagulative necrosis induced by ischemia or carbon tetrachloride. Treatment of cultured hepatoma cells with the Ca2+ ionophore A23187 showed a dose-dependent, time-dependent decrease of cell viability. The appearance of cytokeratin dimers was shown to be correlated with cell death. These results suggest that the transglutaminase-induced cross-linking of cytokeratin polypeptides in liver and hepatoma cells is closely associated with the process of cell degeneration and death.

Topics: Animals; Carbon Tetrachloride; Cell Survival; Ischemia; Keratins; Liver; Liver Circulation; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Necrosis; Peptides; Rats; Rats, Wistar; Tumor Cells, Cultured

Nine marrow allograft recipients who developed GVHD of the gastrointestinal tract accompanied by the passage of ropey necrotic material per rectum were studied. The material, resembling necrotic intestinal mucosa, was evaluated for the presence of epithelial cells using monoclonal antibodies for keratin and macrophages. Two keratins (AE1/AE3 and 34 beta E12) were detected within cells in all cases while macrophages were found in all but one case. In three cases, some cells were positive for both antibodies suggesting the presence of phagocytosed keratin in macrophage cytoplasm. Search for organisms with Gram and methenamine silver stains showed bacteria in six cases and fungus in one. Some cases of severe GVHD will be associated with the passage of ropey tan material grossly resembling sloughed mucosal tissue, but microscopically consisting largely of fibrin clots. The presence of free intestinal epithelial cells in this material is confirmed by the present study.

Topics: Bone Marrow Transplantation; Epithelium; Graft vs Host Disease; Humans; Immunohistochemistry; Intestinal Mucosa; Intestines; Keratins; Necrosis

The purpose of this study was to test the hypothesis that odontogenic cysts can be induced by periapical infection. Pulp extirpation and reaming beyond the root apices were performed in 53 lower first molars in 27 Sprague-Dawley rats. The cavities were left open to allow continuous contamination by oral bacteria. Animals were killed at 6 and more than 8 months after operation. Odontogenic cysts were found in association with 8/53 teeth in 6 animals. Histologically, cysts were observed around the lower incisors below the first molars. The cyst wall consisted of fibrous connective tissue with inflammation and was lined with keratinized squamous epithelium. The cyst cavity contained a mass of keratin and necrotic debris. These results support the hypothesis that inflammatory stimulation from the apices can cause cystic changes in the enamel epithelium of underlying teeth.

Topics: Animals; Bacterial Infections; Connective Tissue; Dental Pulp Cavity; Dental Pulp Exposure; Disease Models, Animal; Epithelium; Female; Inflammation; Keratins; Male; Mandibular Diseases; Necrosis; Odontogenic Cysts; Periapical Diseases; Periapical Periodontitis; Pulpectomy; Rats; Rats, Sprague-Dawley; Root Canal Therapy; Time Factors

We studied seven examples of the solid variant of adenoid cystic carcinoma of the uterine cervix in postmenopausal women who presented with vaginal bleeding and a large ulcerated or polypoid cervical mass. The tumors lacked the characteristic cribriform pattern of conventional adenoid cystic carcinoma. The neoplastic cells were small, undifferentiated, or basaloid and grew in cords, nests, trabeculae, and nodules. Foci of squamous cell carcinoma were seen in three tumors and areas of necrosis in four. A characteristic feature was the production of abundant periodic acid-Schiff's procedure (PAS)-positive basement membrane material that was immunoreactive for collagen IV and that in some areas compressed tumor cells. Electron microscopy on three cases showed globules and cylinders of redundant basal lamina. The tumor cells were joined by desmosomes and contained bundles of tonofilaments. Material similar to basement membrane material appeared to be intracytoplasmic in two tumors. No neurosecretory granules or myoepithelial cells were found. Four deaths were tumor related. Two patients are currently alive, but with local recurrence or metastases; another is alive and well 19 months after surgery. We believe that the solid variant of adenoid cystic carcinoma of the cervix is a distinctive neoplasm that should be separated from small cell carcinomas with or without endocrine features, adenoid basal cell carcinoma, and squamous cell carcinoma.

Topics: Aged; Basement Membrane; Carcinoma, Adenoid Cystic; Cell Nucleus; Collagen; Cytoplasm; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Necrosis; Staining and Labeling; Uterine Cervical Neoplasms

Studies were performed in vivo using 35S-(1,2-dichlorovinyl)-L-cysteine, a nephrotoxin that damages the S3 segment of the proximal tubule after metabolism to a reactive intermediate. Initiation of damage (35S covalent binding) was complete by 6 hour, and an early proliferative response was observed by 24 hour in the S2 or S3C segments. Necrosis in the S3M and increased blood urea nitrogen were maximal at 48 hours and were accompanied by an increase in proliferation of cells at the wound site. Regeneration was marked by the appearance of vimentin expressing cells that lacked brush border enzymes. The loss of differentiated character in the regenerative epithelium persisted after the proliferation (bromodeoxyuridine incorporation) had stopped; redifferentiation occurred between days 5 and 13. Much of the process was reproduced by culturing rat kidney proximal tubule epithelial cells in defined medium. As growth increased, the cells expressed vimentin and lost brush border marker enzymes. However, as the cells reached high density and stopped dividing there was an increase in brush border markers, as was seen in vivo. Vimentin expression did not decrease, however. The data support a mechanism for damage and nephrogenic repair composed of 1) interaction of the toxin with the target cells, 2) necrosis and exfoliation, 3) loss of differentiation and cell growth, 4) recovery of the damaged area and cessation of cell growth, and 5) differentiation of the quiescent cells. Nephrogenic repair may have similarities with the differentiation of the tubular epithelium during development.

Topics: Alkaline Phosphatase; Animals; Cell Division; Cells, Cultured; Cysteine; gamma-Glutamyltransferase; Keratins; Kidney; Kidney Tubules, Proximal; Male; Microvilli; Models, Biological; Necrosis; Rats; Rats, Inbred Strains; Urea; Vimentin

A case of papilliferous keratoameloblastoma is reported which is only the second ever documented. The patient was a 76-yr-old black woman with a large expansile multilocular radiolucency of the body, angle and ramus of the mandible. Histologically the lesion consisted of sheets of cystic follicles filled with necrotic debris and sometimes parakeratin. The vast majority of the follicles were lined by a papilliferous epithelium consisting of large rounded cells with centrally placed nuclei. True papillary projections with cores of connective tissue were also present. The remainder of the follicles were lined by a thin parakeratinising stratified squamous epithelium. Histological features characteristic of ameloblastoma were absent. Final classification of these lesions will have to await the reporting of further cases.

Topics: Aged; Ameloblastoma; Connective Tissue; Epithelium; Female; Humans; Keratins; Mandibular Neoplasms; Necrosis

Immediate fixation or snap freezing of tissue is ordinarily done to maximize antigen preservation for immunocytochemistry; however, delay in tissue allocation or spontaneous lymph node infarction can render tissue suboptimal for immunostaining. To test the effects of tissue autolysis/necrosis on the preservation of various lymphoid, epithelial, and mesenchymal markers, two lymph nodes (one with reactive lymphoid hyperplasia and one with metastatic ductal breast carcinoma) were evaluated for immunocytochemically demonstrated antigen preservation at 0-, 4-, 8-, 12-, 24-, 48-, and 72-hour intervals of autolysis at 37 degrees C. All specimens were stained by frozen section and formalin-fixed paraffin section immunocytochemical reactions with antibodies against CLA (CD45), UCHL-1 (CD45RO), L-26, kappa, lambda, anti-epithelial keratins (AE-1 and AE-3), epithelial membrane antigen, and vimentin. Frozen sections were additionally stained for Leu-1 (CD5), Leu-2a (CD8), Leu-3a+b (CD4), Leu-4 (CD3), and Leu-14 (CD22). The most resilient lymphoid antigen preservation was observed with CLA and UCHL-1, both exhibiting immunoreactivity at 72 hours in both frozen and fixed preparations. L-26 showed similar reactivity in frozen sections, but detectable antigen was observed only up to 24 hours in formalin-fixed tissue. Leu-2a proved to be the most labile antigen, persisting for only 12 hours in frozen sections. The epithelial markers epithelial membrane antigen and AE-1 exhibited excellent antigenic preservation in both frozen and fixed preparations; AE-3 persisted well in frozen section but was not demonstrated in fixed tissue. Vimentin immunoreactivity was vastly superior in frozen, as compared with fixed, tissue sections. Most antigens showed remarkable preservation despite morphologic degradation; however, differential antigenic resilience was demonstrated. Knowledge of this variation in antigen decay is critical for evaluation of immunoperoxidase phenotypic studies of autolyzed or necrotic tissue.

Topics: Antigens; Antigens, CD; Autolysis; Biopsy; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Membrane Glycoproteins; Mucin-1; Necrosis; Tissue Preservation; Vimentin

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

From a total material of 184 Swedish users of loose packed moist snuff and 68 users of portion-bag packed moist snuff, cases were selected from subgroups based on a four-point clinical grading scale. The selected material for the study comprised 70 cases (ten from each clinical grade group, no Degree 4 lesion was found among portion-bag users). Features recognized in biopsies from these cases together with findings in previous studies correlated well with the use of a four-point scale for the grading of clinical changes, especially in the context of discriminating lesions for which special efforts should be undertaken to make the patient stop or change the snuff dipping habit and for selecting patients in whom regular clinical follow-up including a biopsy should be carried out. In this article is also discussed the labeling of the clinical oral mucosal changes seen at the site where a quid of snuff is regularly placed. The conceptual use of "snuff dippers' lesions" is recommended instead of e.g. snuff-induced leukoplakia.

Topics: Adult; Atrophy; Epithelium; Humans; Hyperplasia; Keratins; Male; Mitosis; Mouth Diseases; Mouth Mucosa; Necrosis; Plants, Toxic; Sweden; Time Factors; Tobacco, Smokeless

Proliferation of bile ductules or ductular hepatocytes occurs in a variety of liver diseases. The origin of these ductular structures and the mechanism of their proliferation are controversial. Using cytokeratin as marker for ductular structures, liver diseases in which ductular proliferation was a consistent and prominent feature were studied. Paraffin-embedded sections of livers (five cases each) with acute or chronic obstruction of extrahepatic bile ducts, primary biliary cirrhosis (stage II), drug-induced cholestatic liver disease, liver allograft rejection, vicinity of metastatic carcinoma, and massive hepatic necrosis were studied by immunohistochemical methods using three kinds of antiserum against cytokeratin polypeptides of different molecular weights. Bile ductules in diseases involving bile ducts and ductular hepatocytes in massive hepatic necrosis were closely associated with hepatocytes at the limiting plate or with injured hepatocytes. These findings suggest that hepatocytes play an important role in the proliferation of ductular structures or may represent their origin.

Topics: Biliary Atresia; Cell Division; Epithelium; Hepatic Duct, Common; Humans; Immunoenzyme Techniques; Keratins; Liver; Liver Diseases; Liver Neoplasms; Necrosis

Thirty-six cases of synovial sarcoma (13 biphasic and 23 monophasic) were subjected to a clinicopathologic study that included electron microscopy and immunohistochemistry. The group consisted of 21 males and 15 females ranging in age from 2 to 63 years. The majority of tumors (27 cases) were found in the hip and lower extremity. Immunohistochemical study revealed that keratin, which was detected in 92% of the biphasic and 57% of the monophasic tumors, was a more sensitive marker of epithelial differentiation than EMA or CEA. The overall 5-year survival of the patients was 64%. Male sex, older age, presence of tumor necrosis, monophasic pattern, and absence of keratin positivity had an unfavourable effect on survival but lacked statistical significance. Survival was significantly lower in patients with tumors exhibiting more than 15 mitoses per 10 HPF (P less than .02) and in those with tumors showing necrosis and a mitotic rate greater than 5 mitoses per 10 HPF (P less than .005).

Topics: Adolescent; Adult; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Keratins; Leg; Male; Middle Aged; Mitotic Index; Necrosis; Prognosis; Sarcoma, Synovial; Survival Rate

Minoxidil, a potent vasodilator, stimulates the growth of terminal hair from vellus or miniaturized follicles in balding scalp. To study minoxidil's action on isolated follicles we developed and validated an organ culture system using mouse whisker follicles. Control follicles cultured without minoxidil showed macroscopic changes including kinking of the hair shafts and bending of the follicles. Necrosis was evident in the differentiating epithelial elements forming the cuticle, cortex, and inner root sheath. These abnormalities were eliminated or greatly reduced in minoxidil-treated follicles. The morphology of these follicles was consistent with the production of new hair during culture. Direct measurement demonstrated that minoxidil-treated follicles grew significantly longer than control follicles during the 3-d culture. Minoxidil increased the incorporation of radiolabeled cysteine and glycine in follicles compared with control treatment. Doses of minoxidil up to 1 mM caused increased cysteine incorporation, while higher doses were inhibitory. Experiments with labeled thymidine indicated that minoxidil induced proliferation of hair epithelial cells near the base of the follicle. Autoradiography also showed that cysteine accumulated in the keratogenous zone above the dermal papilla. These studies demonstrate that organ cultured follicles are suitable for determining minoxidil's mechanism of action and may be useful for studying other aspects of hair biology. The results also show that minoxidil's effect on hair follicles is direct. This suggests that minoxidil's action in vivo includes more than just increasing blood flow to hair follicles.

Topics: Animals; Cell Differentiation; Cysteine; Epidermis; Glycine; Keratins; Mice; Minoxidil; Necrosis; Organ Culture Techniques; Thymidine; Vibrissae

The clinical and pathological features of 33 previously untreated patients with primary breast sarcoma were retrospectively analysed to evaluate the prognostic significance of histologic variables on survival. The series comprised 17 cystosarcomas phyllodes and 16 stromal sarcomas (excluding angiosarcomas). All tumors were reviewed and classified in similar fashion to extramammary soft tissue sarcomas. In addition, immunohistochemical studies were performed on paraffin sections with a panel of several antibodies directed against cytoskeletal filaments and cellular enzymes; five cases were also examined by electron microscopy. Most tumors were malignant fibrous histiocytoma (21 cases) and fibrosarcoma (6 cases) types. Surgery was the main therapy. Metastasis-free survival rate was significantly correlated only with histological grade, consisting of tumor differentiation, tumor necrosis, and mitotic activity. Courses and survivals of the cystosarcoma and stromal groups were identical, questioning the clinical value of this pathologic distinction. All local recurrence, metastasis, or death occurred within 30 months, though follow-up was much longer. Immunohistochemistry was disappointing for identification of specific histologic sub-types.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Biomarkers, Tumor; Breast Neoplasms; Desmin; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mitosis; Necrosis; Neoplasm Metastasis; Phyllodes Tumor; Prognosis; Retrospective Studies; Sarcoma

According to the World Health Organization histological classification of bronchial tumors, clear and giant cell carcinomas are two subtypes of large cell carcinoma. As clear and giant cells can also be observed in other types of bronchial carcinoma, we investigated the frequency of the finding of these cells in different histological types. The tumor size and degree of differentiation, the amount of necrosis and keratinization, and the presence of giant and clear cells were analyzed. Statistical analysis by X2 test showed (for all classified histological types of bronchial carcinomas, except small cell carcinoma) that: 1) larger tumors had a great quantity of giant cells (P less than 0.05; P less than 0.01), 2) large tumors had more clear cells (P less than 0.05; P less than 0.01) and 3) tumors with a greater amount of necrosis had a larger number of giant and clear cells (P less than 0.05; P less than 0.01). Findings of an identical cytological characteristic can cause some difficulty in determination of bronchial cancer.

Topics: Adenocarcinoma; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Necrosis; World Health Organization

This report describes three cases of intrapulmonary fibromas which are histologically identical to localized fibrous tumors of pleura (localized fibrous mesothelioma). Morphologically these tumors are characterized by a haphazard proliferation of cytologically bland spindle cells separated by variable amounts of wavy hyalinized collagen. Entrapped bronchiolar and alveolar epithelium is common. These spindle cells lack expression of cytoplasmic keratin, S-100 protein, desmin, and epithelial membrane antigen, but are strongly decorated for intracellular vimentin. The clinical behavior, differential diagnosis, and histogenesis of these lesions are discussed.

Topics: Aged; Aged, 80 and over; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Necrosis; Periodic Acid-Schiff Reaction; Vimentin

A case of lichen striatus with transepidermal elimination of clusters of necrotic keratinocytes is reported. On the basis of the morphologic findings, we suggest that transepidermal elimination may be a mechanism of healing in some cutaneous lichenoid eruptions.

Topics: Biopsy; Child; Epidermal Cells; Female; Humans; Keratins; Necrosis; Skin; Skin Diseases

A middle-aged woman presented with a pelvic mass. Pathologic examination of the resected specimen revealed a primary adenosquamous carcinoma of the left fallopian tube. Special studies supported the concept of the neoplastic cells differentiating along two major pathways, squamous cell carcinoma and mucin-producing adenocarcinoma.

Topics: Adenocarcinoma; Adult; Carcinoma, Squamous Cell; Fallopian Tube Neoplasms; Fallopian Tubes; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Mucins; Necrosis

Primary neoplasms of the renal pelvis are rare. Most are malignant, and most of these are transitional cell carcinomas. We report the unusual occurrence of a squamous cell carcinoma with sarcomatoid stroma arising from the renal pelvic mucosa in a patient with renal lithiasis. Immunohistochemical stains for keratin intermediate filaments failed to demonstrate their presence in the spindle cell portion of the tumor. Transmission electron microscopic study did not reveal structures of an epithelial nature in these same cells. Our findings support the contention that the spindle cells of the stroma are not squamous in nature, but represent either a reactive or a neoplastic transformation of these underlying stromal elements.

Topics: Carcinoma, Squamous Cell; Epithelium; Humans; Immunohistochemistry; Keratins; Kidney Calculi; Kidney Neoplasms; Kidney Pelvis; Male; Microscopy, Electron; Middle Aged; Necrosis; Sarcoma

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

Infantile acropustulosis is a syndrome characterized by recurrent crops of 1- to 2-mm pruritic vesiculopustules, which appear predominantly on distal extremities of infants. Nine biopsy specimens from six cases of infantile acropustulosis have been studied. We found that necrolysis of keratinocytes is the initial event leading to an inflammatory reaction and to an intraepidermal pustule, which progresses to a subcorneal pustule. These different histologic stages are correlated with clinical features. We found that the pustules may be filled with neutrophils or eosinophils, without particular significance. We have not found a correlation among blood eosinophilia, composition of cutaneous infiltrate, age of infant, and course of eruption.

Topics: Diagnosis, Differential; Eosinophils; Epidermis; Erythema; Humans; Infant; Keratins; Male; Necrosis; Neutrophils; Recurrence; Skin Diseases, Vesiculobullous

Histological grading of squamous cell carcinoma is subjective and suffers from poor observer reproducibility. We investigated the feasibility of quantifying histological differentiation via point counting, using both the degree of keratinization and a novel definition of differentiation that was based on architectural features of the tumour. Multiple recounts of 20 cases of human oral squamous cell carcinoma were performed at several magnifications (X100, X160 and X250). Six lines of human squamous cell carcinoma tumour lines were examined for changes in differentiation following transplantation to athymic nude mice. Observer reproducibility was extremely high for all recounts except at the highest magnification, where the tumour architecture may have been obscured. Of the human squamous cell carcinomas transplanted to nude mice, five of six tumour lines showed significant histological changes, most commonly toward decreased differentiation. The changes were usually present in the initial transplant and were similar to those we have reported for transplants of adenocarcinomas. We conclude that histological differentiation can be quantified in squamous cell carcinomas with a high degree of observer reproducibility, even in the absence of keratinization; the method employed is sufficiently sensitive to be applied to practical problems of biological significance.

Topics: Animals; Carcinoma, Squamous Cell; Humans; Keratins; Mice; Mice, Nude; Mouth Neoplasms; Necrosis; Neoplasm Transplantation

The clinical and morphologic features of four cases of spindle cell carcinoma of the breast are presented, and the comparable features of 35 previously reported cases are reviewed. All tumors contained histologically malignant squamous carcinoma that tended to blend with a spindle cell "pseudosarcomatous" stroma. Patients with this rare tumor tend to present at the same age as patients with other histologic types of breast carcinoma, but the spindle cell tumors are somewhat larger. Although the number of reported patients is too small to serve as a basis for firm conclusions, the prognosis appears similar to that for patients with conventional infiltrating duct carcinoma of the breast.

Topics: Aged; Breast Neoplasms; Carcinoma; Cell Nucleus; Epithelium; Female; Humans; Keratins; Middle Aged; Necrosis; Prognosis

Pigs were exposed to heat of low and high temperature and electricity of various frequences. Comparable amounts of energy were transferred in all experiments. In lesions induced by heat of low temperature granularity and/or fibrillarity of the cytoplasm were present in the epidermal cells. Lesions induced by heat of high temperature had a similar appearance, but occasionally "white necrosis", defects in the epithelium and light yellow material in stratum corneum were present. Lesions induced by 100.000 hz alternating current were segmental but otherwise microscopically often indistinguishable from lesions produced via transfer of heat of low temperature. Lesions induced by 8000 hz and 59 hz alternating current were segmental. Vesicular nuclei, "white necrosis" and yellow, clumped keratin were present in most lesions. Anode areas in direct current induced lesions showed a shrunken epidermis. The cytoplasm of the epidermal cells were often eosinophilic and homogeneous, and the nuclei were small with condensed chromatin. Occasionally, "empty" nuclei were noted. Yellow, clumped keratin was presented in all lesions. In cathode areas epidermis was of varying thickness and "white necrosis" and vesicular nuclei were present. The pathogenesis of the individual morphological features is discussed based upon theoretical concepts and the difference in morphology of the various lesions encountered in the present study as well as in other studies in this series of experiments. It is concluded that except for lesions produced via transfer of high frequency alternating current the morphology of electrical lesions is specific. Further, an alleged torture instrument was able to produce lesions similar to those observed in the experimental studies.

Topics: Animals; Cytoplasm; Cytoplasmic Granules; Electric Injuries; Eosine Yellowish-(YS); Epidermis; Hot Temperature; Humans; Keratins; Necrosis; Skin; Swine; Torture

Fibrinoid necrosis which in previous investigations was demonstrated in the epithelial cells of the skin and of the liver in certain disorders, may also appear in the colloid bodies in lichen planus. Trichrome stainings were positive for fibrinoid, staining reactions with haematoxylin variants indicated the presence of keratin and precursors, and investigations in Wood's light permitted conclusions concerning the appearance of mixed proteins, of which keratofibrinoid seems to be the most important. Circulatory disturbances are emphasized as having an important role. The colloid bodies are extruded from the epidermis, according to the observations of Kerr et al., following the rules of apoptosis.

Topics: Epidermis; Epithelium; Fibrin; Histocytochemistry; Humans; Keratins; Lichen Planus; Microscopy, Fluorescence; Necrosis; Paraproteins; Staining and Labeling

A histometric method is used for the study of human skin kept in organ culture in a defined medium for up to 10 days. The method provides quantitative, reproducible data on tissue survival, cell migration, and cellular differentiation (keratinization). With this method, the behavior of epidermal skin tissue can be effectively monitored during organ culture. As quantitative data are obtained, even subtle changes can be accurately demonstrated, and accumulated data may be subjected to statistical analysis. The various applications of this method are pointed out.

Topics: Adult; Aged; Cell Count; Epidermis; Female; Humans; Keratins; Methods; Necrosis; Organ Culture Techniques; Skin; Time Factors

Topics: Adult; Collagen Diseases; Humans; Keratins; Male; Necrosis; Skin Diseases