bromochloroacetic-acid and Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose main etiology is exposure to asbestos fibers. The incidence of MPM is anticipated to increase worldwide during the first half of this century. For various reasons, MPM is difficult to diagnose and is notoriously refractory to most treatments. However, recently two active chemotherapy regimens have been demonstrated to significantly increase survival in patients with MPM, and several therapeutic agents and strategies are currently under evaluation.Researchers have actively sought MPM biomarkers for more than 20 years. Biomarkers would be helpful in managing three clinical aspects of MPM: early diagnosis, prognosis, and treatment outcome prediction. The aims of the present review are to summarize the published and recently presented data on MPM biomarkers and to identify the prospects for future translational research projects.Among the 'classical' diagnostic biomarkers measured in biological fluids, such as cytokeratins and cell surface antigens, none discriminate patients with MPM from those with other malignancies and nonmalignant diseases. Osteopontin, soluble mesothelin, and megakaryocyte potentiating factor (MPF) appear to be the most promising of the recent biomarkers, but are still subject to some limitations. Osteopontin lacks specificity for mesothelioma, while both soluble mesothelin and MPF lack sensitivity for detecting non-epithelial subtypes. Panels consisting of a small set of biomarkers do not improve the diagnostic yield, and results from molecular profiling are too preliminary to be brought into daily clinical practice. While a large number of biomarkers have been assessed in biological fluids and tumor tissue for their prognostic value, none have had a widespread impact on clinical practice. In contrast, data concerning predictive biomarkers are very limited, even though they are most interesting from the perspective of clinicians.Additional prospective studies, in large and independent samples of patients, with rigorous statistical methodology and standardized laboratory techniques are now warranted to validate and define the precise value of diagnostic and prognostic MPM biomarkers. Future research efforts should focus on biomarkers predictive of the efficacy and toxicity of standard chemotherapy. Translational research should be systematically incorporated into the design of clinical trials assessing new targeted agents in MPM.

Topics: Antigens, Neoplasm; Biomarkers; Clinical Trials as Topic; GPI-Linked Proteins; Humans; Keratins; Membrane Glycoproteins; Mesothelin; Mesothelioma; Prognosis

Topics: Adenocarcinoma; Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cytogenetic Analysis; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Lymphatic Metastasis; Magnetic Resonance Imaging; Mesothelioma; Neoplasm Metastasis; Neoplasms, Unknown Primary; Peritoneal Neoplasms; Positron-Emission Tomography; Prognosis; Rhabdomyosarcoma; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

Mesothelioma is a rare neoplasm of the serosal membranes. Signs and symptoms of a pleural effusion typically herald discovery of the tumor. We report a case of miliary metastatic mesothelioma involving both lungs in a 54-year-old man who presented with right-sided chest discomfort, numerous pulmonary nodules detected by computed tomography of the chest, and absent pleural effusion. Immunohistochemical and electron microscopy studies performed on wedge biopsies of parenchymal pulmonary nodules led to the diagnosis of metastatic mesothelioma. Subsequent pleural evaluation and biopsy of pleural thickening noted at a site of prior chest wall trauma identified the primary neoplasm and confirmed the diagnosis as malignant epithelioid mesothelioma. The histologic appearance of discohesive epithelioid cells in a distinctly myxoid background was the clue in this case leading to the consideration of metastatic mesothelioma and a thorough immunohistochemical evaluation of the tumor. This case shows that mesothelioma may metastasize throughout the lungs in a miliary pattern and the metastases may be clinically detected before the primary pleural tumor. Metastatic mesothelioma is a consideration for metastatic pulmonary tumors of unknown origin.

Topics: Biomarkers, Tumor; Biopsy; Calbindin 2; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Neoplasms, Unknown Primary; Pleural Neoplasms; Radiography, Thoracic; S100 Calcium Binding Protein G; Tomography, X-Ray Computed

Although it is generally accepted that immunohistochemistry can assist in distinguishing between epithelial mesotheliomas and metastatic adenocarcinomas to the serosal membranes, a great deal of controversy exists regarding not only the practical value of some of the markers currently used, but also which should be included as part of the routine diagnostic panel. Until recently, these panels consisted primarily of antibodies that stained adenocarcinomas but not mesotheliomas. Over the last few years, however, markers that are commonly expressed in mesotheliomas but not in adenocarcinomas have been recognized. The focus of this review is on those markers for which there is an indication that they have a practical use in the diagnosis of mesothelioma. Special emphasis is placed on those which have been most recently recognized.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Cadherins; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; DNA-Binding Proteins; Humans; Hyaluronan Receptors; Keratins; Lewis X Antigen; Mesothelioma; S100 Calcium Binding Protein G; Thrombomodulin; Transcription Factors; WT1 Proteins

Topics: Adenocarcinoma; Biomarkers, Tumor; Cadherins; Calbindin 2; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

Pleural cancers are tumours which are frequently refractory to all treatment. Faithful animal models (experimentally reproducing the human disease) are necessary to study the natural history of this disease and to test standard or experimental treatments. The athymic bald mouse is currently used for the construction of experimental models because it avoids immunological rejection. Initially murine models were constructed following subcutaneous injection of cloned cells then implantation of tumour fragments. The tumours obtained are not superimposable on the human disease in terms of local, regional or metastatic development and the results from these studies, using such models, are difficult to transpose to humans. It is possible to implant fragments of histologically intact human tumour into the pleura of bald mice. This orthoptic (site for site) transplantation enables one to obtain in the mouse a tumour which tends to conserve the biological characteristics of the original tumour and to develop locally, regionally and at distance in a fashion which is similar to the human disease. In spite of the inherent limits of immunotolerance of the host and thus difficulties of extrapolation to man, this review attempts to point out the place for these models and for an understanding of the therapy of pleural cancers.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Autopsy; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Interferon-gamma; Keratins; Mesothelioma; Mice; Mice, Nude; Mucin-1; Neoplasm Transplantation; Neoplasms, Experimental; Pleura; Pleural Neoplasms; Recombinant Proteins; Vimentin

Six examples of malignant mesothelioma appearing as a localized pleural mass are described. There were four women and two men, ranging in age from 42 to 76 years. A history of asbestos exposure was obtained from three patients. The tumors ranged in size from 2.8 to 10 cm. Two were pedunculated and four were sessile with broad-based pleural attachments. Histologically, three tumors were purely epithelioid and three were biphasic. Immunohistochemical stains in all six cases were positive for cytokeratin and negative for carcinoembryonic antigen. Five were also positive for epithelial membrane antigen. Five were negative for Leu-M1, while one showed focal staining in a peripheral membrane pattern. Electron microscopy in two purely epithelioid tumors showed long, thin microvilli, well-developed desmosomes, and numerous tonofilaments. Flow cytometry showed an aneuploid DNA content in four tumors and a diploid content in one. Flow cytometry in five cases identified a DNA aneuploid cell population in four tumors and a diploid population in one. Three patients showed signs of local recurrences 4, 7, and 18 months after excision and died of their disease 12, 10, and 24 months after diagnosis, respectively. Three patients are well with no evidence of disease 8, 24, and 96 months after diagnosis. These findings indicate that malignant mesotheliomas of the pleura may rarely appear as a localized mass. The biologic behavior of such tumors is difficult to predict, but some patients survive disease-free for a long time after surgical excision.

Topics: Adult; Aged; Aneuploidy; Asbestos; DNA, Neoplasm; Female; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Mesothelioma; Middle Aged; Mucin-1; Pleural Neoplasms

Diffuse malignant mesothelioma is a rare tumor in the general population, yet is unique in that it is caused almost exclusively by exposure to asbestos with long-term latency (15 years and over). Pathologists are required to provide a reliable diagnosis of the tumor for clinicians who are responsible for the treatment of affected patients. Pathological diagnosis of diffuse malignant mesothelioma is not always easy; however, it has improved over the last few decades. Currently, comprehensive analysis, including gross appearance, histology, histochemistry, immunocytochemistry and electron microscopy is recommended as the best approach to an accurate diagnosis of diffuse malignant mesothelioma.

Topics: Carcinoembryonic Antigen; Humans; Hyaluronic Acid; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mesothelioma; Microscopy, Electron; Mucin-1; Mucins; Peritoneal Neoplasms; Pleural Neoplasms

A diffuse, well-differentiated, malignant peritoneal mesothelioma (MPM) developed in a nine-year-old girl. She received limited chemotherapy and radiation therapy and is alive and well without clinical evidence of disease 109 months after diagnosis. The neoplastic cells stained immunohistochemically for cytokeratin and epithelial membrane antigen but were unreactive with B72.3, anti-carcinoembryonic antigen, and anti-Leu-M1. Ultrastructurally, the tumor cells had abundant desmosomes, numerous tonofilament bundles, and variable-length microvilli. These findings confirm the mesothelial nature of the cells. Features consistent with malignancy included DNA aneuploidy by flow cytometric analysis and diffuse peritoneal involvement. The three previously described survivors with MPM were also premenarchal girls. Some MPMs in premenarchal girls have an indolent biologic behavior similar to that of low-grade peritoneal serous neoplasia or well-differentiated papillary mesothelioma in adult women.

Topics: Adolescent; Child; Child, Preschool; DNA, Neoplasm; Female; Flow Cytometry; Humans; Immunohistochemistry; Infant; Keratins; Male; Membrane Glycoproteins; Mesothelioma; Microscopy, Electron; Mucin-1; Peritoneal Neoplasms

We report three cases of brain metastases from malignant pleural mesothelioma that were seen at autopsy. We present a summarized review of 15 similar reports that were previously published. Our study included three aged male patients with a long occupational history of heavy asbestos exposure. In two patients, the metastases were discovered incidentally at autopsy, and there were no neurologic symptoms referred to before death. In the other patient, who had clinically occult mesothelioma, the intracranial tumor was discovered ante mortem: in this patient, the clinical features, as well as a computed tomographic scan, suggested a primary tumor of the brain. Interestingly, the histologic features of the latter case that were seen at autopsy depicted a spindle cell tumor that focally exhibited pseudopalisading, necrosis, vascular buds, which deceptively recalled a glioblastoma. All the three cases shared a basic sarcomatous pattern of malignant pleural mesothelioma in both primary and metastatic tumors. The immunohistochemical profile was consistent with such interpretation. It was concluded that metastases to the brain from malignant pleural mesothelioma, although rare, are not exceptional even if their clinical relevance is not prominent. They are seen concomitantly with high-grade tumors, and by mimicking a primary tumor on a clinical, instrumental, and histologic ground, they may occasionally represent a potential source of diagnostic pitfall.

Topics: Adult; Aged; Asbestos; Brain Neoplasms; Female; Humans; Keratins; Male; Mesothelioma; Middle Aged; Neoplasm Metastasis; Pleural Neoplasms; Vimentin

We report a case of benign multicystic mesothelial proliferation (the so-called multicystic peritoneal mesothelioma) arising multifocally in the abdomen of a 46-year-old white man. His anamnesis showed an 8-year history of intermittent pain in the right lower abdominal quadrant. Mucin stains, immunohistochemistry, and electron microscopy confirmed the mesothelial origin of the lesion. Review of the available literature allowed us to find another 85 reported cases of benign multicystic mesothelial proliferations of the peritoneum. Out of these cases, eighteen only occurred in men, the majority being reported in middle-aged women mostly with complaints of abdominal pain. Electron microscopy or immunohistochemistry are needed to make a differential diagnosis towards other multicystic lesions, such as peritoneal cystic lymphangioma. Although multicystic mesothelial proliferations of the peritoneum have often been regarded as benign neoplasms, the true nature--neoplastic or hyperplastic--of these lesions still remains greatly elusive. Therefore, we believe that the unbinding term benign multicystic mesothelial proliferation (first used with regard to the unique hitherto reported case arisen in the pleural cavity) should be considered at present more appropriate to indicate even these peritoneal lesions.

Topics: Abdominal Pain; Actins; Cysts; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Peritoneal Neoplasms

A rare case of adenomatoid tumor arising in the ovary is presented. At autopsy on a 61-year-old woman, a soft, solid and cystic tumor, measuring 0.8 X 0.7 cm, was detected in the hilus of the left ovary. Light microscopic study showed characteristic features of adenomatoid tumor. Alcian blue stain, with and without hyaluronidase pretreatment, revealed the presence of hyaluronic acid on the luminal surface and in the vacuoles of the tumor cells. Immunohistochemical stains of tumor cells were positive for low-molecular-weight cytokeratin (PKKL), vimentin, and carbohydrate antigen (CA) 125, whereas they were focally positive for high-molecular-weight cytokeratin (34 beta E12). They were negative for factor VIII-related antigen (FVIII-RAG), Ulex europaeus I lectin (UEA I), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Ultrastructural studies disclosed surface microvilli and bundles of tonofilaments. These observations strongly support the idea of this tumor being of mesothelial origin.

Topics: Cytoplasm; Female; Humans; Immunohistochemistry; Keratins; Mesothelioma; Microvilli; Middle Aged; Ovarian Neoplasms; Staining and Labeling

Topics: Adenocarcinoma; Adenoma, Islet Cell; Animals; Antibodies, Monoclonal; Breast Neoplasms; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cytoskeletal Proteins; Desmoplakins; Desmosomes; Electrophoresis, Polyacrylamide Gel; Granulosa Cell Tumor; Humans; Immunosorbent Techniques; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Kidney Neoplasms; Lung Neoplasms; Melanoma; Membrane Proteins; Meningioma; Mesothelioma; Microscopy, Electron; Microscopy, Fluorescence; Neoplasms; Neurosecretory Systems; Skin Neoplasms

Most mammalian nucleated cells contain a cytoplasmic fibril system called intermediate filaments. Unlike other cytoskeletal proteins, the subunit proteins of intermediate filaments show a remarkable cell-type-specificity in their expression: mesenchymal, muscle, epithelial, glial and neuronal cells containing each their cell type specific filaments. In this review we discuss the possibilities to use antibodies to these filaments in the diagnosis and histogenetic analysis of human tumors. This approach is based on findings which indicate that these filaments retain their cell-type specific expression also in tumors.

Topics: Antibodies; Carcinoma; Cytoskeleton; Desmin; Glial Fibrillary Acidic Protein; Glioma; Humans; Intermediate Filaments; Keratins; Mesothelioma; Neoplasms; Rhabdomyosarcoma; Sarcoma; Vimentin

Immunohistochemistry of intermediate filaments (IF) is a new and important way to evaluate the epithelial, mesenchymal, muscular, glial, or neural differentiation in tumors. This is based on the stable cell-type-specific expression of IF proteins in normal and neoplastic tissues. Immunohistochemical studies with antibodies to intermediate filaments have also given new perspectives in the histogenesis and biologic nature of many tumors. This article reviews both the recent findings and the authors' experience in the use of intermediate filament antibodies in tumor diagnosis and classification.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Carcinoma, Squamous Cell; Desmin; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Immunochemistry; Keratins; Melanoma; Mesothelioma; Microfilament Proteins; Microscopy, Electron; Neoplasm Proteins; Neoplasms; Nervous System Neoplasms; Sarcoma; Soft Tissue Neoplasms; Thyroid Neoplasms; Urinary Bladder Neoplasms; Vimentin

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Humans; Keratin-19; Keratins; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Prognosis

A 67-year-old woman was referred to our hospital for cough and fever. Chest computed tomography (CT) showed some masses showing slightly enhanced effect in the pericardium. FDG-PET showed the accumulation of FDG in the masses. Thoracoscopic surgical biopsy was performed to establish the diagnosis. The histological study showed proliferation of short spindle-shaped cells surrounded by lymphocyte, and the spindle cells were immunohistochemically positive for cytokeratin AE1/AE3, WT-1, D2-40, CAM5.2, intelectin-1 and negative for CEA, TTF-1, napsin A, claudin-4, calretinin, MUC4, PAX8, CD30. These findings were compatible with epithelial pericardial malignant mesothelioma.

Topics: Aged; Calbindin 2; Claudin-4; Female; Fluorodeoxyglucose F18; Heart Neoplasms; Humans; Keratins; Lung Neoplasms; Mediastinal Neoplasms; Mesothelioma; Mesothelioma, Malignant; Thymus Neoplasms

Topics: Aged, 80 and over; Biomarkers, Tumor; Humans; Keratins; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms

Primary pericardial malignant mesothelioma (PPM) is a very rare malignancy, with an incidence of less than 0.002% and represents less than 5% of all mesotheliomas. The cause of pericardial mesothelioma is uncertain that differ from pleural mesothelioma which is associated with asbestos exposure. This malignancy is terribly aggressive and has very poor prognosis with less than six months of overall survival. We present a case of a 71-year-old woman who was diagnosed with cardiac tamponade caused by PPM and received chemotherapy with pemetrexed and cisplatin for six months. During two years she was alive without disease progression. To better understand the clinical, pathologic features and treatment outcome of this entity, we reviewed 23 cases described in the English literature from 2009, together with our case, provided a total of 24 cases. Based on this review, we suggest that PPM must be considered in patients who have unexplained massive pericardial effusion and recommend chemotherapy with pemetrexed and cisplatin for the better outcome of PPM.

Topics: Aged; Antineoplastic Agents; Calbindin 2; Cardiac Tamponade; Cisplatin; Drug Therapy, Combination; Female; Humans; Keratins; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pemetrexed; Pleural Neoplasms; Thorax; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography; Vimentin

Peritoneal mesothelioma is rare, and the sarcomatoid variant is more infrequent, with <30 cases reported to date in the literature. Several case series have described the morphologic features of sarcomatoid peritoneal mesothelioma (SPe); however, the clinicopathologic features are not well characterized. To our knowledge, this is the first large series reporting the clinicopathologic features of SPe. We reviewed our database of 3106 malignant mesothelioma cases. Of 248 peritoneal mesotheliomas, 15 (4%) were sarcomatoid variant (0.5% of all mesotheliomas). Only cases with 100% sarcomatoid morphology diagnosed by open surgical biopsy and/or autopsy were included. Thus, 4 cases were excluded leaving 11 cases of SPe. Two additional cases of SPe previously published by 1 of the authors (V.L.R.), not included in the database, are added yielding 13 cases total. The median age at diagnosis was 66 years (range=48 to 85 y), and there was a male predominance (M:F=3.25:1). Survival from date of diagnosis to date of death was 5 months (range=0 to 12 mo). The most common presenting symptom was abdominal pain, and 3 of 4 women were suspected to have cholecystitis/cholelithiasis. All cases stained positive for cytokeratins, and 2 contained heterologous elements. Seven cases had objective markers of asbestos exposure, and 2 additional cases had occupations strongly associated with mesothelioma. Two cases with alleged household contact exposures could not be confirmed to be asbestos related by lung fiber analysis. SPe is a rare variant of mesothelioma attributed to asbestos exposure in 69% of our cases.

Topics: Aged; Aged, 80 and over; Asbestos; Autopsy; Biomarkers, Tumor; Biopsy; Databases, Factual; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Incidence; Inhalation Exposure; Keratins; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Occupational Exposure; Peritoneal Neoplasms; Predictive Value of Tests; Prognosis; Risk Factors; Sarcoma; Survival Analysis

Four cases of tumors in which cell internalization was frequently visualized are reported: one feline mammary carcinoma, one feline cutaneous squamous cell carcinoma, one canine pulmonary squamous cell carcinoma and one canine pleural mesothelioma. Cell internalization was observed by cytology in two of these cases (the feline mammary tumour and the pleural effusion in the canine mesothelioma) and by histopathology in all but the canine mesothelioma. Immunohistochemical staining for pancytokeratin was positive for both internalized and host cells, while E-cadherin expression was frequently absent, although internalized cells occasionally stained positive. This cell-to-cell interaction seems to be associated with tumors displaying a strong epithelial-mesenchymal transitional phenotype, in which cancer cells become engulfed by other cancer cells. Such event could be regarded as an important hallmark of very high malignancy.

Topics: Animals; Biomarkers, Tumor; Biopsy; Cadherins; Carcinoma, Squamous Cell; Cat Diseases; Cats; Cytophagocytosis; Dog Diseases; Dogs; Female; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mammary Neoplasms, Animal; Mesothelioma; Pleural Neoplasms; Skin Neoplasms

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Calbindin 2; Cholecystitis; Cisplatin; Cystitis; Diagnosis, Differential; Female; Glutamates; Guanine; Humans; Inflammation; Keratins; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Pemetrexed; Peritoneal Neoplasms; Survival Rate; Vimentin

The workup of a malignant effusion usually requires immunostaining with a panel of markers. Although nuclear Wilms tumor 1 (WT1) expression is widely used to detect tumors of ovarian and mesothelial origin, it is less well known that WT1 is also expressed in the cytoplasm of melanomas and mesenchymal tumors. Because to the authors' knowledge the diagnostic utility of cytoplasmic WT1 expression has not been explored to date, the usefulness of a WT1/AE1/AE3 dual-color immunostain in the workup of malignant effusions was evaluated.. A total of 86 pleural effusions, including 17 metastatic melanomas, 31 metastatic adenocarcinomas, 10 malignant mesotheliomas, 10 lymphoproliferative disorders, 5 metastatic sarcomas, and 13 benign specimens, were immunostained using a peroxidase-based brown chromogen for WT1 and an alkaline phosphatase-based red chromogen for AE1/AE3 on cell block sections.. The majority of malignant effusions stained in 1 of 4 distinctive patterns: 1) all lung and breast adenocarcinomas demonstrated cytoplasmic AE1/AE3 expression without nuclear or cytoplasmic WT1 expression; 2) serous carcinomas of Müllerian origin, mesotheliomas, and benign mesothelial cells were positive for cytoplasmic AE1/AE3 as well as nuclear WT1; 3) melanomas, sarcomas, and a subset of plasma cell neoplasms were positive for cytoplasmic expression of WT1 but negative for AE1/AE3; and 4) large B-cell lymphomas and a subset of plasma cell neoplasms were negative for both markers.. A WT1/AE1/AE3 dual-color immunostain can reliably identify malignancy in pleural effusions and group malignant cells into discrete subsets, thereby narrowing the differential diagnosis. This simple double stain can be a cost-effective, first-line test in the workup of patients with malignant effusions.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma; Coloring Agents; Epithelium; Humans; Immunohistochemistry; Keratins; Lymphoproliferative Disorders; Melanoma; Mesothelioma; Neoplasm Metastasis; Pleural Effusion, Malignant; Sarcoma; WT1 Proteins

It is difficult to distinguish desmoplastic malignant mesothelioma (DMM) from fibrous pleuritis (FP). We investigated the utility of immunohistochemistry as a way of differentiating between DMM and FP. We examined 11 DMMs and 46 FPs with the aid of antibodies against 18 cytokeratin (CK) subtypes, calponin, caldesmon, desmin, and GLUT-1. The best sensitivity and specificity cut-off values in the receiver operating characteristic curves (ROC) for CKs 7, 8, 17, 18, and 19, and GLUT-1 were each above 60%. When cases with either DMM or FP were partitioned by the staining score associated with the best sensitivity and specificity cut-off values in ROC, the incidence of a positive expression for CKs 7, 8, 17, 18, and 19, and GLUT-1 was significantly higher in DMM than in FP. In conclusion, immunohistochemistry for CKs 7, 8, 17, 18, and 19, and GLUT-1 may be useful, alongside histological characteristics, for separating DMM from FP.

Topics: Aged; Aged, 80 and over; Biomarkers; Biomarkers, Tumor; Diagnosis, Differential; Female; Glucose Transporter Type 1; Humans; Immunohistochemistry; Keratin-17; Keratin-18; Keratin-19; Keratin-7; Keratin-8; Keratins; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Pleurisy; Retrospective Studies

A 53-year-old Taiwanese male had several episodes of left epididymitis with hydrocele refractory to antibiotic treatment. Partial epididymectomy plus preventive vasectomy were planned, and, incidentally, an ill-defined nodule was found lying on the tunica vaginalis near the epididymal head. The pathological diagnosis was malignant mesothelioma of the tunica vaginalis testis. Radical orchiectomy with wide excision of the hemi-scrotal wall was performed. So far, there is no evidence of recurrence after more than 3 years of follow-up. Malignant tumor should be considered in the case of recurrent epididymitis refractory to empirically effective antibiotic treatment. Although the nature of this tumor is highly fatal, the malignancy can possibly be cured by early and aggressive surgical treatment.

Topics: Epididymitis; Humans; Keratins; Male; Mesothelioma; Middle Aged; Orchiectomy; Recurrence; Testicular Neoplasms

Decidualized endometrioma is a pseudoneoplastic lesion that may appear as a solitary nodule in the hypodermis, simulate a malignant epithelioid tumor, and can represent a diagnostic challenge. A 36-year-old woman delivered a full-term baby by cesarean. At the immediate puerperium, she complained of a subcutaneous nodule measuring 2.5 cm, underneath a previous caesarean scar from the former full-term delivery 3 years earlier. Histologic features included a nodular growth pattern of large monomorphic epithelioid cells showing diffuse positivity for cytokeratin (AE1/AE3, 18), human placental lactogen, and CD10 and focal positivity for inhibin alpha. The main differential diagnoses include trophoblastic neoplasia and deciduoid mesothelioma. Good clinicopathological correlation is essential for the correct diagnosis. Immunohistochemical stains can be misleading. An important clue is the combination of large decidualized cells and lumens lined by flat or low cuboidal cells that are atrophic endometrial glands. This lesion has a benign behavior.

Topics: Adult; Diagnosis, Differential; Endometriosis; Female; Gestational Trophoblastic Disease; Humans; Immunohistochemistry; Keratins; Mesothelioma; Pregnancy; Skin

Malignant peritoneal mesothelioma (MPM) is a rare tumor that develops in the peritoneum. In this paper, we describe an extremely rare case of MPM metastasizing to the appendix in a 48-year-old female who initially presented with a persistent high fever. The woman reported a slight lower abdominal discomfort which had been relieved by urination for four months. She had lost 5 kg of weight. There was no nausea, vomiting, diarrhea, abdominal pain, or abdominal distension. Many broad spectrum antibiotics were given without relief of fever. Computed tomography (CT) scans revealed a thickened omentum majus and diffused multiple omental nodules. An omentectomy, appendectomy, and adnexectomy were carried out. A gross pathologic specimen of omentum tissue revealed a firm gray-white mass. Microscopic and immunohistochemical examinations confirmed the diagnosis of appendiceal and bilateral adnexal metastases of an MPM. These results suggest that MPM should be considered in the differential diagnosis of unexplained persistent high fever. Awareness of such atypical presentations of mesothelioma may help to make a correct diagnosis.

Topics: Appendiceal Neoplasms; Biomarkers, Tumor; Calbindin 2; Diagnosis, Differential; Female; Fever of Unknown Origin; Humans; Immunohistochemistry; Keratins; Mesothelioma; Middle Aged; Peritoneal Neoplasms; S100 Calcium Binding Protein G; Tomography, X-Ray Computed; WT1 Proteins

Primary peritoneal serous papillary carcinoma (PPSPC) is a rare primary tumor of the peritoneum that found predominantly in elderly and post-menopausal women. The aim of our study is to review the clinical and pathologic information of 22 patients, and then try to summarize clinical behavior and pathological characteristics of PPSPC, in order to be better recognized of this entity in future. We retrospectively reviewed the data from 22 patients with PPSPC treated at our hospital from 1992 to 2008. All paraffin blocks were recut for periodic acid-Schiff diastase and immunohistochemical staining for CD15, cytokeratin7(CK7), cytokeratin20(CK20), S-100 protein, carcinoembryonic antigen (CEA), CA125, estrogen receptor(ER) and progesterone receptor(PR). The median age of the patients at the time of surgical staging was 56 years (range, 32-77 years). The most common presenting symptoms were abdominal distension (59.1%) and ascites (63.6%). Pretreatment CA125 levels were significant elevated in 90.5% patients. Optimal debulking was performed in 18 patients. All patients were consequently treated with platinum-based chemotherapy. Response to treatment is promising, and the median overall survival of all patients was 21.0 months (95% CI 16.9, 25.1 months). The positive rate of immunohistochemical staining was CD15 95.5%, CK7 90.9%, S-100 protein 68.2%, CA125 59.1%, CK20 31.8%, ER 31.8%, CEA 27.3% and PR 9.1%, respectively. Gynecologist should be aware of PPSPC when abdominal distension, gross ascites and a raised level of CA125 in women without ovarian enlargement. Immunohistochemical staining might be helpful as accessory criteria for the differential diagnosis among the PPSPC, peritoneal malignant mesothelioma (PMM), primary epithelial ovarian carcinoma (PEOC) and peritoneal carcinomatosis from the gastrointestinal tumors (SPCGT). Cytoreductive surgery combined with pre/postoperative platinum-based chemotherapy may be effective for PPSPC patients.

Topics: Adult; Aged; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Carcinoma, Papillary; Cystadenocarcinoma, Serous; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Middle Aged; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; S100 Proteins; Survival Rate

Primary pleural angiosarcoma is a rare and clinically aggressive tumor. Patients usually present with chest pain, dyspnea, hemoptysis and/or cough. Radiologic studies reveal diffuse pleural thickening and pleural effusion with or without mass lesion. The clinical and radiological features both resemble those of mesothelioma, and its definite diagnosis requires careful histologic examination. However, frequent epithelioid feature and immunoreactivity to cytokeratin in primary pleural angiosarcoma further complicate the pathologic diagnosis. The use of proper immunohistochemical stains is often needed to support endothelial differentiation in the tumor cells and to exclude metastatic carcinoma and mesothelioma. We report the case of a 49-year-old male patient with primary pleural angiosarcoma, who presented with initial hemothorax, followed by a rapid progress to an inoperable status.

Topics: Antineoplastic Agents; Biomarkers, Tumor; Chemoradiotherapy; Diagnosis, Differential; Hemangiosarcoma; Hemothorax; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Pleura; Pleural Neoplasms

Topics: Adult; Calbindin 2; Endometrium; Female; Humans; Keratins; Mesothelioma; Mucin-1; Radiography; S100 Calcium Binding Protein G; Uterine Cervical Neoplasms; Vaginal Smears

The differential diagnosis of pleural sarcomatoid mesothelioma (SM) from lung sarcomatoid carcinoma (LSC) invading parietal pleura and chest wall is a challenging issue. The aim of this study was to identify useful antibodies that can be used for the differential diagnosis of pleural SM from LSC.. Forty-five cases of pleural SM and 27 cases of LSC were immunohistochemically analysed by using 15 commercially available antibodies, including D2-40 and antibodies to calretinin, thrombomodulin, Wilms' Tumour 1, carcinoembryonic antigen (CEA), Napsin A, thyroid transcription factor (TTF)-1, pan-cytokeratin, CAM5.2, epithelial membrane antigen, Ber-EP4, MOC-31, alpha-smooth muscle actin, h-caldesmon and desmin. The results revealed that D2-40 positivity was significantly higher in pleural SM (86.7%) than in LSC (25.9%). The positivity of the adenocarcinoma markers, including CEA, Napsin A, and TTF-1, was low even in LSC.. Evaluating the positivity and degree of staining of the well-known mesothelial marker D2-40 could be applied to differentiate pleural SM from the sarcomatoid component of LSC, in addition to assessing clinical and radiological information.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Biomarkers; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Mesothelioma; Middle Aged; Pleural Neoplasms

This report describes the macroscopic, histologic, immunohistologic and ultrastructural characteristics ofa biphasic malignant mesothelioma in the peritoneal and pleural cavity of a 13-year-old Icelandic pony mare, which exhibited recurrent ascites clinically. Immunohistology was performed employing multiple monoclonal antibodies against cytokeratins (CK) and vimentin. The ultrastructural examination included the quantitative evaluation of the length to diameter ratio of the microvilli. Post mortem examination revealed a severe ascites and hydrothorax. The serosal surfaces of the peritoneum and pleura displayed poorly-demarcated, multifocal to coalescing laminar masses and small nodules. Histology revealed a bimorphic mass consisting of spindle-shaped cells and microcystic epithelioid areas. A transcoelomic and local invasive growth pattern as well as lymph node metastases were noticed. Immunohistology revealed a strong expression of CK. Though a low and moderate expression of CK5/6 and CK20 was present, respectively, CK7 and CK10-antigens were lacking. Ultrastructurally, the epithelioid mesothelioma cells displayed long microvilli, cytoplasmic tonofilaments, and desmosomes. Quantitative evaluation of the length to diameter ratio of the 10 longest microvilli revealed a mean value of approximately 16.2. Summarized, this report described the case of a malignant biphasic mesothelioma with an atypical CK20 expression but a characteristic ultrastructural morphology including long microvilli.

Topics: Animals; Antibodies, Monoclonal; Fatal Outcome; Horse Diseases; Horses; Immunohistochemistry; Keratins; Male; Mesothelioma; Microvilli; Peritoneal Neoplasms; Pleural Neoplasms; Vimentin

Only a small number of malignant mesotheliomas with heterologous elements have been described. There are currently no criteria for diagnosis and little data regarding prognosis. We suggest that the term heterologous mesothelioma should be reserved for tumours that show malignant heterologous elements, notably osteosarcomatous, chondrosarcomatous, or rhabdomyoblastic elements but have immunohistochemical and clinical characteristics of mesothelioma. We identified 27 such cases and characterized the clinical and pathological characteristics of these tumours. In our series, 89% originated in the pleura, and 11% from the peritoneal cavity. The median age at diagnosis was 68 years, ranging from 27 to 85 years. Of these cases, 93% occurred in males and 7% in women. Of the 27 mesothelioma cases 16 (59%) were sarcomatoid, 10 (37%) were biphasic, and one was reported as epithelioid; 40% (11 cases) showed osteosarcomatous elements only, 19% showed areas of rhabdomyosarcoma only, 19% contained areas of chondrosarcoma only, and 22% exhibited osteochondromatous elements. Immunohistochemical labelling for cytokeratins was present in the majority of cases. Exposure to asbestos was identified in all the 17 cases for which an exposure history was available (63%). Median survival was 6 months after diagnosis, similar to the survival seen in sarcomatoid mesotheliomas. The differential diagnosis includes primary and secondary pleural sarcomas, including osteosarcomas and chondrosarcomas. Immunohistochemical labelling for cytokeratins is helpful in the distinction, but lack of labelling for cytokeratins in a spindle cell/sarcomatoid tumour does not exclude the diagnosis of mesothelioma, irrespective of the presence of heterologous elements. We suggest that if the anatomical distribution conforms to that of mesothelioma, a diagnosis of heterologous mesothelioma should be made in preference to a diagnosis of primary pleural osteosarcoma or chondrosarcoma, regardless of cytokeratin positivity, as for conventional non-heterologous sarcomatoid mesothelioma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chondrosarcoma; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Mesothelioma; Middle Aged; Osteosarcoma; Peritoneal Neoplasms; Pleural Neoplasms; Rhabdomyosarcoma; Sarcoma; Survival Rate

Soluble mesothelin-related protein (SMRP) in serum is potentially a sensitive marker of malignant mesothelioma (MM) diagnosis and progression, and may be useful as screening marker. Mesothelin expression in tumors is regarded as a sensitive marker for diagnosis and disease progression, and is a candidate prognostic marker. Levels of SMRP, CA125 and CYFRA 21-1 in pre-diagnostic (1-30 years) serum samples from 47 mesothelioma cases and 141 matched controls were analysed. Mesothelin expression in tumors was assessed. The association between biomarker level and mesothelioma risk and survival was analysed, adjusting for asbestos exposure. Survival related to tumor mesothelin expression, age, sex, histological type, location, asbestos exposure and pre-clinical SMRP was analysed. There was no significant association between biomarker levels and mesothelioma risk when analysed as continuous variables or as tertiles. Biomarker levels <10, 10-19 and >or=20 years before diagnosis were not significantly associated to mesothelioma risk. Mesothelin expressed in >50% of tumor cells was seen in 36 of 47 (77%) tumors. Mesothelin expression in <50% of tumor cells was a significant negative prognostic marker in all cases of malignant mesothelioma (median survival=6 months vs. 12 months, hazard ratio (HR)=2.49, 95%CI 1.17-5.27), and also when only epithelial mesothelioma was analysed (median=6 months vs. 14 months, HR=2.36, 95%CI 1.07-5.22). When adjusted for age and gender, the prognosis was still dismal, but non-significant (HR=1.85, 95%CI 0.85-4.05). High age (>65 years) was an independent negative prognostic factor that was related to both mesothelin expression and asbestos exposure. Mesothelioma of the epithelial type of the peritoneum had a significantly longer survival than epithelial type in pleura and was also related to mesothelin expression.

Topics: Adolescent; Adult; Age Factors; Antigens, Neoplasm; Asbestos; Biomarkers, Tumor; Case-Control Studies; Child; Child, Preschool; Female; GPI-Linked Proteins; Humans; Infant; Intracellular Signaling Peptides and Proteins; Keratin-19; Keratins; Male; Membrane Glycoproteins; Mesothelin; Mesothelioma; Occupational Exposure; Peritoneal Neoplasms; Pleural Neoplasms; Prognosis; Proteins; Survival Analysis

To present eight cases of primary diffuse peritoneal malignant mesothelioma in children <15 years old, with a discussion of the pitfalls of this diagnosis in the paediatric age group.. The cases were selected based on the following criteria: (i) primary peritoneal neoplasms confined grossly or radiographically to the abdominal cavity; (ii) negative history of previous or another associated malignancy; (iii) histopathological confirmation. All patients (five female, three male) presented clinically with symptoms of abdominal pain, distention and ascites. Grossly, the tumours showed multiple, diffuse peritoneal nodules. Histologically, seven cases corresponded to epithelioid mesotheliomas and one case displayed biphasic (epithelioid and spindle) cellular proliferation. Immunohistochemical studies for cytokeratin (CK) 5/6, calretinin and low-molecular-weight CK (CAM5.2) showed strong cytoplasmic positivity in the neoplastic cells. Three patients were treated by chemotherapy. On clinical follow-up, four patients with epithelioid mesotheliomas were alive and well from 12 to 18 months after initial diagnosis; one patient with a mixed (biphasic epithelioid/sarcomatoid) mesothelioma died of tumour 24 months after diagnosis.. Peritoneal malignant mesothelioma in children is a rare condition that can introduce difficulties in histopathological diagnosis.

Topics: Adolescent; Biomarkers; Biomarkers, Tumor; Calbindin 2; Child; Fatal Outcome; Female; Humans; Keratin-5; Keratin-6; Keratins; Male; Mesothelioma; Peritoneal Neoplasms; S100 Calcium Binding Protein G

A 68-year-old man complaining of hoarseness and back pain, with no history of exposure to asbestos, was referred to our hospital in June 2002. He was admitted because his chest X-ray and CT scan showed atelectasis and a tumor-like region in the right lower lobe of the lung. Serum-CYFRA was 2.8 ng/ml, elevated slightly; however, no other tumor markers for lung cancer were elevated. A diagnosis of squamous cell lung cancer was made based on bronchial washing cytology. Persistent high fever and WBC count elevation did not respond to antibiotics, and reduced only after chemotherapy. Both serum G-CSF (217.0 pg/ml) and CYFRA in the pleural effusion (107.1 ng/ml) were elevated. The biopsy of the growing tumor in the right lateral abdominal wall revealed carcinoma with sarcomatous component or biphasic-type malignant pleural mesothelioma (MPM). In spite of chemotherapy and radiation therapy for the abdominal wall tumor, the tumor rapidly progressed and the patient died three months after admission. The findings at autopsy suggested the tumor was a sarcomatous MPM. However, immunohistochemical staining and tissue HABP staining revealed biphasic type MPM. Although CYFRA elevation in the serum and/or the pleural effusion in MPM patients has been previously reported, it has not been reported in any of the 5 MPM patients reported to have G-CSF elevation. Therefore, this is the first reported case of G-CSF-producing MPM with CYFRA elevation in both serum and the pleural effusion.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Granulocyte Colony-Stimulating Factor; Humans; Hyaluronan Receptors; Keratin-19; Keratins; Male; Mesothelioma; Pleural Effusion; Pleural Neoplasms; Staining and Labeling

The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Calbindin 2; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Membrane Glycoproteins; Mesothelioma; Microscopy, Electron; Ovarian Neoplasms; Peritoneal Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

We examined 14 spindle cell tumours of the pleura that were sent to a Mesothelioma Panel for re-evaluation after a primary suspicion of mesothelioma. The clinical, histological, immunohistochemical and CGH findings were investigated. Final diagnoses were eight sarcomatoid mesotheliomas (SM) and six non-mesotheliomas: two pulmonary sarcomatoid carcinomas, an epithelioid hemangioendothelioma, a malignant solitary fibrous tumour, a malignant pleural smooth muscle tumour and an extraskeletal osteosarcoma. Seven of the eight SM and two of the other six tumours presented with unilateral pleural effusion, dyspnoea, and chest pain, which are characteristic clinical findings in malignant mesothelioma. No single antibody used in the immunohistochemistry separated SM from other tumour types. The most frequently observed chromosomal losses in SM were 4q, 4p11-p13/p15, 6q and 13. Losses of 4p11-p13/p15 and 4q occurred in combination in four out of five SM with detectable chromosomal changes, but neither was found in any of the other tumours. Gain or high-level amplification of 5p was also common in SM. According to our results and literature, losses at 4p, 4q and 9p and gain at 5p are the chromosomal changes that best differentiate SM from pleural sarcomas and lung carcinomas. CGH analysis may help distinguish a cytokeratin-positive SM from a sarcomatoid carcinoma. Similarly, in the case of a cytokeratin-negative tumour, CGH analysis may disclose chromosomal changes characteristic of sarcomas or mesotheliomas.

Topics: Aged; Aged, 80 and over; Calbindin 2; Chromosome Aberrations; Diagnosis, Differential; Female; Genome, Human; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Nucleic Acid Hybridization; Pleural Neoplasms; S100 Calcium Binding Protein G; Survival Analysis; Vimentin

Mesotheliomas with rhabdoid morphology are rare and only two individual case reports have been documented in the literature. This author reports a series of 10 cases of mesotheliomas with rhabdoid features, nine of which originated in the pleura and one in the peritoneum. Eight of the patients were men and two were women. Six patients had a history of asbestos exposure. Histologically, seven of the mesotheliomas were epithelioid, two sarcomatoid, and one biphasic. The proportion of the rhabdoid cells seen in these cases constituted 15-75% of the individual tumors. Cytoplasmic staining in the rhabdoid cells was seen for pan-keratin and vimentin in all 10 cases, for keratin 7 in eight of eight, for calretinin in nine of 10, and for keratin 5/6 in seven of nine. Nuclear positivity for WT1 was observed in the rhabdoid cells of four of seven cases and membranous reactivity for mesothelin in four of six, and for podoplanin in two of six. Only one case showed desmin positivity in sparse cells in the nonrhabdoid component of the tumor. All of the cases were negative for CEA, MOC-31, TAG-72, CD15, CD34, bcl2, muscle-specific actin, and TTF-1. Ultrastructural studies revealed paranuclear collections of intermediate filaments, but no evidence of rhabdomyoblastic differentiation was seen. The mean survival of five of the six patients for whom this information was available was 3.8 months. The remaining patient had a survival time of 1 year. It is important for pathologists to be aware that mesotheliomas can present rhabdoid features, not only because they can be confused with other malignancies that can exhibit a similar morphology, but also because of their apparently unusually aggressive behavior. The value of immunohistochemistry and electron microscopy in the differential diagnosis of these tumors is discussed.

Topics: Aged; Calbindin 2; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Mesothelioma; Microscopy, Electron; Middle Aged; Pleural Neoplasms; Rhabdoid Tumor; S100 Calcium Binding Protein G; Survival Analysis; Vimentin

As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis(y)), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1 and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.

Topics: Biomarkers, Tumor; Calbindin 2; Carcinoma, Squamous Cell; Diagnosis, Differential; Epithelioid Cells; GPI-Linked Proteins; Humans; Immunohistochemistry; Keratin-5; Keratin-6; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelin; Mesothelioma; S100 Calcium Binding Protein G; WT1 Proteins

Topics: Adult; Axilla; Calbindin 2; Desmin; Diagnosis, Differential; Epithelium; Female; Fibroma; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Mesothelioma; Mucin-1; S100 Calcium Binding Protein G; Thoracic Neoplasms; Tumor Suppressor Protein p53

This study was performed to characterize the gene expression profile and to identify the major carcinogenic pathways involved in rat peritoneal mesothelioma (RPM) formation following treatment of Fischer 344 rats with o-nitrotoluene (o-NT) or bromochloracetic acid (BCA). Oligo arrays, with over 20,000 target genes, were used to evaluate o-NT- and BCA-induced RPMs, when compared to a non-transformed mesothelial cell line (Fred-PE). Analysis using Ingenuity Pathway Analysis software revealed 169 cancer-related genes that were categorized into binding activity, growth and proliferation, cell cycle progression, apoptosis, and invasion and metastasis. The microarray data were validated by positive correlation with quantitative real-time RT-PCR on 16 selected genes including igf1, tgfb3 and nov. Important carcinogenic pathways involved in RPM formation included insulin-like growth factor 1 (IGF-1), p38 MAPkinase, Wnt/beta-catenin and integrin signaling pathways. This study demonstrated that mesotheliomas in rats exposed to o-NT- and BCA were similar to mesotheliomas in humans, at least at the cellular and molecular level.

Topics: Acetates; Animals; Cell Line; Gene Expression Regulation, Neoplastic; Insulin-Like Growth Factor I; Integrins; Male; Mesothelioma; Oligonucleotide Array Sequence Analysis; p38 Mitogen-Activated Protein Kinases; Peritoneal Neoplasms; Rats; Rats, Inbred F344; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Toluene; Wnt Proteins

The role of immunohistochemical markers in distinguishing peritoneal mesothelioma from primary or metastatic serous papillary carcinoma of the peritoneum was evaluated. We immunostained 20 peritoneal mesotheliomas (from 14 men and 6 women), 14 primary peritoneal carcinomas, and 14 metastatic serous ovarian carcinomas with a panel of 16 antibodies. Positive staining for calretinin was identified in 17 (85%) of 20 mesotheliomas, but all carcinomas were negative. Positive staining for Ber-EP4 was identified in 27 (96%) of 28 carcinomas and in 2 (10%) of 20 mesotheliomas. Estrogen receptors were positive in 26 (93%) of 28 carcinomas, and progesterone receptors were positive in 8 (29%) of 28 carcinomas. All mesotheliomas were negative for estrogen and progesterone receptors. The other antibodies evaluated were insufficiently sensitive and/or specific to be diagnostically useful. In conjunction with calretinin and Ber-EP4, estrogen and progesterone receptors are useful discriminatory markers for distinguishing peritoneal mesothelioma from primary or metastatic serous carcinoma.

Topics: Antibodies, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Cystadenocarcinoma, Serous; Female; Glycoproteins; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Mesothelioma; Peritoneal Neoplasms; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Breast Neoplasms; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Female; GPI-Linked Proteins; Humans; Immunohistochemistry; Keratin-5; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelin; Mesothelioma; Multivariate Analysis; Ovarian Neoplasms; S100 Calcium Binding Protein G; Sensitivity and Specificity; Stomach Neoplasms; Thrombomodulin; WT1 Proteins

A 61-year-old man with a sensation of chest compression was admitted to our hospital. He had hemothorax. After drainage with a chest tube, chest CT scan revealed multiple bilateral pulmonary nodules with slight pleural thickening. Open pleural biopsy was performed and the biopsy specimens showed tumor cells with sarcomatoid proliferation, but no definite epithelial pattern. Initial immunohistochemical staining was negative for keratin and carletinin, but positive for desmin, suggesting rhabdomyosarcoma. After supportive care, he died due to progression of the disease. Autopsy revealed extensive invasion suggesting mesothelioma, so the immunohistochemical staining was repeated. Because it revealed patchy staining for keratin and carletinin, this case was diagnosed as sarcomatoid mesothelioma. Differential diagnosis of sarcomatoid mesothelioma or rhabdomyosarcoma is made by immunohistochemical staining, but it is sometimes difficult. For the selection of the best treatment strategy for mesothelioma especially in the early stage, we should be aware of this difficulty.

Topics: Autopsy; Diagnosis, Differential; Fatal Outcome; Hemothorax; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Pleura; Pleural Neoplasms; Rhabdomyosarcoma; Sarcoma

Immunomodulation of malignant mesothelioma (MM) is variable considering host immune mechanisms. This study has investigated the immunophenotyping of peripheral-blood leukocytes of patients with mesothelioma in relation to different histopathologic types and proliferative potentiality. The study was achieved on 18 patients presented by massive effusion accompanying MM. Circulating CD4+ and CD8+ T cells were counted using two-colour flowcytometry. Pleural effusion cell block preparation and pleural biopsies were processed for immunohistochemical analysis of intratumoral CD8+ lymphocytes, cytokeratin and vimentin antigens expression, and modified one step silver stain to identify the Argyrophilic nucleolar organizer regions (AgNors) for evaluation of the proliferative potentiality of the tumor. Blood samples of five normal individuals were considered as controls. Histopathologic examination demonstrated epithelial variant in 12 cases, mixed (biphasic) variant in 4 cases and 2 cases were sarcomatoid. Flowcytometric analysis exhibited a significant increase in the mean percentage of circulating CD4+ T cell count in mesothelioma (56.7% +/- 6.99) versus control (43% +/- 1.58), p < 0.001. In contrast, cytotoxic CD8+ cells were significantly reduced (p < 0.001) in comparison to the control (25.2% +/- 2.96 versus 32% +/- 4.6 respectively). CD4/CD8 ratio was significantly increased versus control (2.06 +/- 0.57 versus 1.3 +/- 0.02 p < 0.05). Intratumoral CD8+ lymphocytes were depleted in mesothelioma cases. There was significant reduction of circulating cytotoxic T lymphocytes (CTL) in relation to mixed and sarcomatoid variants versus epithelial differentiation (mean = 25.25 +/- 4.86, 22 +/- 1.41 and 29.5 +/- 9.9 respectively with a p value < 0.05). Reduction of cytotoxic T cells was also associated with increased expression of vimentin and increased proliferative activity which has been identified by increased AgNors in mixed and sarcomatoid differentiation. In conclusion, mesothelioma might be associated with modulation of the tumoricidal effect of cytotoxic T lymphocytes in relation to tumor differentiation and its proliferative potentiality. Immunophenotyping analysis of leukocytes may reflect the competence of immune system against malignancy and act as an additive prognostic parameter for mesothelioma progression and probably expecting response to oncotherapy protocols.

Topics: Adult; Antigens, Nuclear; Biomarkers, Tumor; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Proliferation; Female; Flow Cytometry; Humans; Immunophenotyping; Keratins; Leukocytes; Male; Mesothelioma; Middle Aged; Nuclear Proteins; Pleural Neoplasms; Vimentin

A 10-year-old German shepherd dog was presented with a severe abdominal distension. At necropsy, whitish and firm mass was observed in the mesentery with metastases in the pericardium and pleura. The intestinal serosa was thickened and stiff. Histologically, the tumours were composed of a biphasic population of cells, which reacted with cytokeratin, vimentin and Wilms' tumour 1 protein antibody. Ultrastructural examination revealed numerous microvilli, abundant rough endoplasmic reticulum, numerous desmosomes and bundles of microfilament. The tumour was classified as biphasic mesothelioma of peritoneal origin.

Topics: Animals; Dog Diseases; Dogs; Fatal Outcome; Immunohistochemistry; Keratins; Male; Mesothelioma; Neoplasm Metastasis; Peritoneal Neoplasms; Vimentin

To see the distribution of Calretinin, thrombomodulin, CK5/6 and HBME-1 markers in various subtypes of mesotheliomas and extend the published data on this topic. The positivity of adenocarcinoma specific markers (CEA and BerEP4) in malignant mesotheliomas have also been evaluated.. Various markers in 173 cases of malignant mesotheliomas received over a period of 8 years were evaluated by immunohistochemistry.. In majority of malignant mesotheliomas i.e., epithelioid and biphasic types, the positive staining patterns complement the gold standard histologic diagnosis. However, in a small minority mainly sarcomatoid variant, heavy reliance cannot be placed on these markers. CEA and BerEP4 are useful negative markers of mesotheliomas, although occasionally these are positive in clear cut mesotheliomas.. Specificity of various markers in malignant mesotheliomas should be assessed according to histologic subtypes. The existing generation of markers is not reliable in diagnosis of sarcomatoid mesotheliomas. Fortunately this forms only a small group of mesothelial malignancy. In common epithelioid and biphasic variants calretinin, thrombomodulin, CK5/6, HBME-1 are sensitive positive markers whereas CEA and BerEP4 are negative markers of malignant mesotheliomas.

Topics: Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Calbindin 2; Coloring Agents; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Mesothelioma; S100 Calcium Binding Protein G; Sarcoma, Synovial; Soft Tissue Neoplasms; Thrombomodulin

Reported herein is a case of hepatocellular carcinoma (HCC) with unusual peritoneal dissemination masquerading as peritoneal mesothelioma. A 61-year-old man was clinically found to have multiple tumors in his abdominal cavity; peritonitis carcinomatosa was suspected. An autopsy revealed numerous tumors of various sizes in the abdominal serosa, omentum, and diaphragm. No signs of tumor, fibrosis, or cirrhosis were found in the liver, except for a small nodule in the hepatic triangular ligament. Histologically, the tumor cells proliferated in thick trabeculae or in sheets and formed a few canaliculi and tubules with homogenously brown contents in their lumina, which stained positively with Hall stain. Immunohistochemically, these tumors were positive for hepatocyte, alpha-fetoprotein (AFP) and low-molecular-weight cytokeratin; were focally positive for pan-cytokeratin and epithelial membrane antigen (EMA); and were negative for high-molecular-weight cytokeratin, vimentin, and calretinin. Carcinoembryonic antigen (CEA) produced a bile canalicular immunohistochemical staining pattern. Thus, the tumor was diagnosed as an HCC (Edmondson II type) of the triangular ligament with massive peritoneal dissemination. The origin of this tumor and its differential diagnosis (malignant mesothelioma, hepatoid adenocarcinoma, and hepatoid yolk sac tumor) are discussed.

Topics: Adenocarcinoma; alpha-Fetoproteins; Calbindin 2; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Mesothelioma; Middle Aged; Mucin-1; Peritoneal Neoplasms; S100 Calcium Binding Protein G; Vimentin

Recurrent solitary fibrous tumor of the pleura with malignant progression occurs rarely. We report a case of solitary fibrous tumor of the pleura in an 85-year-old white woman that recurred 4 times during a span of 10 years and subsequently underwent malignant transformation. The accurate diagnosis of solitary fibrous tumor is aided by ancillary techniques, such as immunohistochemical staining; however, with malignant transformation, such tools may be of limited value. Long-term clinical follow-up is recommended for all patients with solitary fibrous tumor because of the potential adverse biological behavior of this tumor, which may lead to repeated recurrences and/or malignant transformation.

Topics: Actins; Aged; Aged, 80 and over; Antigens, CD34; Biomarkers, Tumor; Diagnosis, Differential; Disease Progression; Female; Fibroma; Humans; Keratins; Mesothelioma; Mitotic Index; Neoplasm Recurrence, Local; Pleural Neoplasms; S100 Proteins; Sarcoma; Thoracic Wall

Topics: Adult; Biomarkers, Tumor; Cardiac Tamponade; Diagnosis, Differential; Down Syndrome; Dyspnea; Fatal Outcome; Heart Neoplasms; Humans; Keratins; Male; Mesothelioma; Microvilli; Neoplasm Proteins; Pericarditis; Pericardium; Ventricular Fibrillation; Vimentin

Topics: Aged; Aged, 80 and over; Asbestos; Biomarkers; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Carcinoma, Small Cell; CD56 Antigen; Fatal Outcome; Histocytochemistry; Humans; Keratin-5; Keratins; Lung Neoplasms; Male; Mesothelioma; Neoplasms, Multiple Primary; Nuclear Proteins; Occupational Exposure; Pleural Neoplasms; S100 Calcium Binding Protein G; Thyroid Nuclear Factor 1; Transcription Factors; Vimentin

Malignant mesothelioma is a rare tumor arising from the pleura or peritoneum. Distant hematogenous metastasis is seen in more than half of cases, preferentially to the brain, lung, bone and soft tissues [Br. J. Dis. Chest 70 (1976) 246]. There has been only one previous report of this tumor metastasizing to the jaw bone [Pathologica 92 (2000) 273].

Topics: Diagnosis, Differential; Humans; Keratins; Male; Mandibular Neoplasms; Mesothelioma; Middle Aged; Pleural Neoplasms; Radicular Cyst; Vimentin

Diagnostic utility of E-cadherin (E-CD) and cytokeratin (CK) subtype profiling in effusion cytology was investigated, employing immunocytochemistry on cellblock sections available from 211 metastatic carcinomas (MC), 6 mesotheliomas and 73 reactive mesothelial hyperplasias (MH). E-CD and monoclonal carcinoembryonic antigen (mCEA) stained 85% (120/141) and 65% (138/211) of MC, respectively. E-CD staining of MC was frequently heterogeneous (76/120) and absent in all anaplastic carcinomas (0/2). E-CD stained none (0/57) of MH while mCEA and epithelial membrane antigen (EMA) stained 12% (9/73) and 32% (16/32) of MH, respectively. Of 6 mesotheliomas, E-CD focally stained in 2 while mCEA stained none and EMA stained all. CK20 and CK17 stained none of MH or mesotheliomas. CK20 stained 15% of MC and CK 17 stained 22% of MC. CK5/6 and high molecular weight CK stained all mesotheliomas, 56% and 88% of MH, 26% and 39% of MC, respectively. MC showed predominant CK7+/20-expression, with the exceptions of MC from mucinous type of colon/rectum and ovary showing predominant CK20 positive. E-CD may be a useful positive marker for MC in effusion cytology, although it may focally stain in some mesotheliomas. Any positive staining for CK20 of MC suggests MC from the gastrointestinal tract or ovary among others.

Topics: Biomarkers, Tumor; Cadherins; Carcinoma; Diagnosis, Differential; Epithelium; Humans; Hyperplasia; Immunohistochemistry; Keratins; Mesothelioma

A spontaneous pleural mesothelioma was observed in a 4-year-old female woodchuck (Marmota monax). At necropsy, multifocal, tan to white, firm discrete nodules, 2 to 40 mm in diameter, were scattered over the ventral parts of the lungs and their corresponding parts of the diaphragm and the thoracic wall. Histopathologically, the tumor cells were large, cuboidal-shaped and variable size, and were weakly positive with PAS and Alcian blue. Immunohistochemically, neoplastic cells were positive for both vimentin and cytokeratin, indicating mesothelial origin. This report represents, as far as we know, the first reported case of a spontaneous mesothelioma in woodchucks.

Topics: Animals; Fatal Outcome; Female; Histological Techniques; Immunohistochemistry; Keratins; Korea; Lung; Marmota; Mesothelioma; Pleural Neoplasms; Vimentin

Several immunohistochemical markers, among them calretinin, thrombomodulin (CD141), keratin 5, and mesothelin, have been documented or suggested as useful markers for positive identification of mesothelioma and to differentiate it from pulmonary adenocarcinoma; numerous studies have documented their variable specificity. However, expression of these markers in other types of lung carcinomas has not been systematically explored, although these tumors can enter in the differential diagnosis of mesothelioma. In this study we immunohistochemically evaluated 596 lung carcinomas of different types for the four above-mentioned mesothelioma markers, all of which reacted with a great majority of epithelioid mesotheliomas studied for comparison. Calretinin expression was common in giant cell carcinomas (67%), small cell carcinomas (49%), and large cell carcinomas (38%), whereas it was rare in usual adenocarcinomas but slightly more common in those with neuroendocrine differentiation (11% and 17%, respectively). Thrombomodulin was present in all keratinizing squamous carcinomas and the great majority (87%) of nonkeratinizing tumors in a membrane-staining pattern. It was moderately common in small cell (27%) and large cell carcinomas (25%) but relatively rare in adenocarcinomas (13%). Keratin 5 was expressed in all keratinizing and the great majority (87%) of nonkeratinizing squamous carcinomas, and a majority of large cell carcinomas (56%) and some small cell carcinomas (27%). It was rare in acinar adenocarcinomas (12%) and absent in those with neuroendocrine differentiation. Mesothelin was present in more than half (53%) of adenocarcinomas and a minority (13%) of large cell carcinomas but was absent in small cell carcinomas. In squamous carcinomas it was more often seen in nonkeratinizing versus keratinizing tumors (31% vs 16%). These results show that each of these "mesothelioma" markers reacts with different subsets of pulmonary carcinomas with a variable frequency; this should be considered when using these markers in the differential diagnosis of thoracic tumors.

Topics: Biomarkers, Tumor; Calbindin 2; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-5; Keratins; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

Desmoplastic mesothelioma is a rare subtype of diffuse malignant mesothelioma, and is often difficult to distinguish from reactive pleural fibrosis because of associated extensive collagen fibrosis. An 82-year-old woman with a severe cough was revealed to have pleural effusion and diffuse pleural thickening on the right side. Antibiotics were ineffective, and a compression fracture of the ninth and tenth thoracic vertebral bodies was recognized on X-ray. Autopsy revealed a diffuse pleural thickening with hyalinized collagen tissue in the central part of the pleura. However, the peripheral part of the fibrous tissue was composed of spindle and polygonal cell proliferation that were immunohistochemically positive for antibodies against cytokeratin and vimentin. In addition, the ninth and tenth thoracic spines were infiltrated by similar cells. The condition was diagnosed as desmoplastic mesothelioma with bone metastases. Asbestos bodies were detected in the thickened pleura and fibrosed alveolar septa, and it was suggested retrospectively that the patient had been exposed to asbestos. Thus, autopsy analyses of fibrous pleurisy are necessary to detect a desmoplastic variant of mesothelioma of the pleura and its association with asbestos exposure.

Topics: Aged; Aged, 80 and over; Asbestos, Crocidolite; Bone Neoplasms; Fatal Outcome; Female; Humans; Keratins; Mesothelioma; Pleural Neoplasms; Radiography, Thoracic; Vimentin

A case of peritoneal sclerosing mesothelioma in a 3-year-old German shepherd dog is reported. The dog presented a severe abdominal distension. Cytological examination of the peritoneal fluid revealed anaplastic epithelioid cells. Necropsy findings revealed an irregular-shaped mass attached to the pancreas and stomach with numerous nodules covering the intestinal and urinary bladder serosa. The diagnosis was made by histology and immunohistochemistry, with cytokeratin, vimentin and calretinin antibodies. Differential diagnosis with chronic peritonitis and spreading of abdominal primary carcinoma is discussed.

Topics: Animals; Ascites; Diagnosis, Differential; Dog Diseases; Dogs; Immunohistochemistry; Keratins; Male; Mesothelioma; Peritoneal Neoplasms; Vimentin

A cell line designated "HMMME" was established from the pleural fluids of a malignant mesothelioma patient. This line grew well without interruption for 12 years and was subcultured over 200 times. The cells were spindle and roundish in shape and displayed a monolayer sheet in an epithelial pavement cell arrangement. They were neoplastic, had pleomorphic features, and easily formed multilayering without contact inhibition. The cell cytoplasm was strongly positive against anti-vimentin, anti-calretinin and anti-pan-keratin, but negative against anti-BerEP4. The cells proliferated rapidly, and the population doubling time was about 42 hours. Their chromosome number showed a wide distribution of aneuploidy with a mode in the diploid range; many marker chromosomes were observed. The cultured cells were easily transplanted into the subcutaneous of nude mice and produced a tumor classified as a malignant mesothelioma.

Topics: Animals; Calbindin 2; Cell Division; Cell Line, Tumor; Chromosome Aberrations; Humans; Immunohistochemistry; Keratins; Mesothelioma; Mice; Mice, Nude; Neoplasm Transplantation; S100 Calcium Binding Protein G; Vimentin

To illustrate the macroscopic, light microscopic and immunophenotypic similarities that exist between primary pleural thymic epithelial tumours and diffuse malignant mesothelioma. To investigate the expression of the mesothelial markers, cytokeratin (CK) 5/6, calretinin and thrombomodulin in a series of mediastinal thymic epithelial tumours.. Over a 10-year period, 64 diffuse pleural tumours of non-mesothelial histogenesis were identified in the files of referrals to the South Wales regional thoracic centre (Llandough Hospital, Cardiff). Of these, five pleural tumours were diagnosed as primary pleural thymic epithelial neoplasms. From the files of the Mesopath group, Caen, three additional cases of thymic epithelial tumours with pleural involvement were identified. The study group comprised eight cases (four males, four females) with median age at presentation of 56 years (range 19-75 years). In one case there was a history of asbestos exposure. Macroscopically, seven tumours formed diffuse pleural masses. No mediastinal abnormality or intraparenchymal lesions were seen in five cases. By light microscopy, seven thymic epithelial neoplasms showed a lobulated architecture, one appeared extensively cystic. The tumours were of varied morphological subtypes: one medullary (WHO Type A), two mixed (WHO Type AB), three predominantly cortical (WHO Type B1) and two cortical (WHO Type B1). The subtypes morphologically mimicked sarcomatoid, biphasic, lymphohistiocytoid variant and epithelioid mesothelioma. The pleural thymic epithelial tumours showed immunoreactivity with broad spectrum cytokeratin AE1/AE3 (8/8; 100%), CK5/6 (8/8; 100%), and 1/8 (13%) expressed thrombomodulin. Calretinin showed variable nuclear and cytoplasmic expression in all cases, but equivocally in the thymic epithelial cell component. In 7/8 (88%) the thymic epithelial cells exhibited focal aberrant expression of CD20. Epithelial membrane antigen (EMA) showed focal expression in the perivascular and organoid areas in 6/8 (75%) cases. Carcinoembryonic antigen (CEA) and CD34 were uniformly negative. In 4/8 (50%) cases the lymphoid cell component was of immature phenotype expressing CD99, terminal deoxynucleotidyl transferase (TdT) and lymphoid precursors had a high proliferation fraction with Ki67. In the series of 20 primary mediastinal thymic epithelial tumours tested, mesothelial marker expression revealed CK5/6 (20/20), thrombomodulin (3/20; 15%) and calretinin (0/20; 0%). Varying amounts of calretinin-positive stromal cells were present.. Primary pleural thymic epithelial tumours are rare but may mimic malignant mesothelioma by forming diffuse serosal-based masses. In addition, both tumours may show morphological diversity (with epithelial, spindled and mixed components present). An awareness that thymic epithelial tumours may variably express the mesothelial markers CK5/6, calretinin and thrombomodulin prevents misdiagnosis. In the distinction from malignant mesothelioma a lobulated architecture and organoid features favour a thymic epithelial neoplasm. The presence of aberrant CD20 expression in a cytokeratin-positive epithelial neoplasm and/or the presence of an immature lymphoid population (by demonstration of CD1a, CD2, CD99 and TdT) indicates a thymic epithelial neoplasm. In contrast, nuclear calretinin expression favours malignant mesothelioma.

Topics: Adult; Aged; Biomarkers, Tumor; Calbindin 2; Diagnosis, Differential; Female; Humans; Keratins; Male; Mediastinum; Mesothelioma; Middle Aged; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin; Thymus Neoplasms

We report a localized malignant mesothelioma of the epithelial type, occurring as a primary hepatic neoplasm in a 64-year-old male. He was found to have a mass located in the right lobe of the liver. Surgery was carried out with resection of the mass from the right hepatic lobe, with partial resection of the diaphragm. Grossly, an ill-defined tumor was present in the hepatic parenchyma. Histologically, the tumor displayed a predominant tubular pattern of growth with a desmoplastic stroma. The tubules were lined by a single layer of cuboidal or flattened cells with pleomorphic vesicular nuclei. A hyaluronidase-digestible, mucin-like substance was demonstrated in the lumen and tumor cytoplasm. The tumor cells were immunohistochemically positive for calretinin, HBME-1, cytokeratin, i.e. AE1/AE3 and CAM 5.2, but negative for carcinoembryonic antigen, CD 34 and Leu M1. Moreover, the tumor cells showed nuclear accumulation of the p53 oncopotein and reacted frequently with Ki-67 antibody. These findings support the concept that malignant mesothelioma of the epithelial type may occur at extrapleural sites. To the best of our knowledge, this is the first reported case of localized malignant primary mesothelioma arising in the liver.

Topics: Biomarkers; Biomarkers, Tumor; Calbindin 2; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Liver Neoplasms; Magnetic Resonance Imaging; Male; Mesothelioma; Middle Aged; S100 Calcium Binding Protein G; Tumor Suppressor Protein p53

Cytokeratin 5/6 (CK 5/6) immunoreactivity has been observed in the vast majority of cases of malignant mesothelioma but only rarely in pulmonary adenocarcinomas. Thus, CK 5/6 has been used to distinguish malignant mesothelioma from pulmonary adenocarcinoma. However, the utility of CK 5/6 in distinguishing pleural malignant mesothelioma from pleural metastases from nonpulmonary adenocarcinoma, as well as peritoneal malignant mesothelioma from peritoneal metastatic adenocarcinoma, has not yet been adequately addressed because the tissue expression of CK 5/6 in nonpulmonary neoplasms has not been well defined. We have studied the CK 5/6 expression in 509 cases of various epithelial tumors by immunohistochemistry. We found that the vast majority of cases of squamous cell carcinoma, basal cell carcinoma, thymoma, salivary gland tumor, and biphasic malignant mesothelioma were positive for CK 5/6. In addition, CK 5/6 immunoreactivity was detected in 15 of 24 cases (62%) of transitional cell carcinoma, in 5 of 10 cases (50%) of endometrial adenocarcinoma, in about one third of cases of pancreatic adenocarcinoma (38%) and breast adenocarcinoma (31%), and in one quarter of cases of ovarian adenocarcinomas (25%). Our study confirms the diagnostic utility of CK 5/6 immunohistochemistry in distinguishing biphasic mesothelioma from pulmonary adenocarcinoma but raises caution about its use for the differential diagnosis of pleural or peritoneal malignant mesothelioma versus pleural or peritoneal metastatic nonpulmonary adenocarcinoma, because many types of nonpulmonary adenocarcinomas may be positive for CK 5/6.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratin-14; Keratin-5; Keratin-7; Keratins; Male; Mesothelioma; Neoplasms

Benign mesothelioma is a rare tumor nearly always find in relation to the genital tract. We report the case of a 47-year, old woman admit in the gynecologic department for metrorragia. The tumor was composed of irregular tubules between smooth muscle cells, lined by flattened or cuboidal cells without nuclear atypia or mitoses. The tumor cells express cytokeratins and vimentin. Histologically, differential diagnosis can be made with adenocarcinoma or vascular proliferation like lymphangioma, hemangioma or angiomyoma. Clinical outcome is always favourable without recurrence or malignant transformation.

Topics: Diagnosis, Differential; Female; Humans; Hysterectomy; Immunohistochemistry; Keratins; Mesothelioma; Middle Aged; Uterine Neoplasms; Vimentin

To evaluate the role of mesothelial markers (calretinin, thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal carcinoembryonic antigen, Leu-M1, CA-125 and Ber-EP4) in distinguishing diffuse peritoneal malignant mesothelioma from primary serous papillary adenocarcinoma of the ovary and peritoneum.. Paraffin-embedded formalin-fixed blocks from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all females), 20 serous papillary ovarian carcinomas and three primary peritoneal serous papillary carcinomas were studied. Calretinin and Ber-EP4 appeared to be the best positive mesothelial and carcinoma marker, respectively. Nuclear calretinin expression was identified in 28 of 32 malignant mesotheliomas with no nuclear immunoreactivity in the cohorts of serous papillary ovarian and peritoneal carcinomas, thus yielding 88% sensitivity and 100% specificity. Ber-EP4 showed 95% sensitivity and 91% specificity for serous papillary ovarian carcinoma. Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas, respectively, and in six (30%), five (25%) and five (25%) of the ovarian tumours, respectively. None of the three primary peritoneal serous papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin 5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu-M1 were expressed by two (10%), one (5%) and seven (35%) serous papillary ovarian carcinomas, respectively. None of the serous papillary peritoneal carcinomas expressed polyclonal CEA, monoclonal CEA or Leu-M1. CA-125 was positive in 19 (95%) and two (67%) ovarian and peritoneal carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas.. Calretinin and Ber-EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu-M1) yielded a too low sensitivity for practical use.

Topics: Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; CA-125 Antigen; Calbindin 2; Carcinoembryonic Antigen; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Diagnosis, Differential; Epithelium; Female; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratin-5; Keratins; Lewis X Antigen; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms; Predictive Value of Tests; S100 Calcium Binding Protein G; Thrombomodulin

To present two rare cases of malignant mesotheliomas with deciduoid features arising in the pleura, both with long survival.. These two cases of deciduoid mesotheliomas were observed in adult patients (one 73-year-old male and one 23-year-old female). Only the male had a history of occupational asbestos exposure, whereas the woman had a history of familial mesothelioma. A deciduoid morphology was predominant and focal areas with tubular-papillary features were noted. The tumour cells were positive for cytokeratins, HMBE-1, calretinin, EMA and mitochondrion antibodies. The follow-up data did not suggest a particularly poor prognosis; the mean survival observed was 23 months (17 and 39 months, respectively).. This deciduoid mesothelioma histological subtype does not appear to represent an unfavourable prognostic category.

Topics: Adult; Aged; Antibodies; Calbindin 2; Fatal Outcome; Female; Humans; Keratins; Ki-67 Antigen; Male; Mesothelioma; Mitochondria; Pleural Neoplasms; S100 Calcium Binding Protein G; Survival Analysis; Time Factors

An 11-month-old male mixed breed dog was euthanized due to two months history of vomiting and anorexia. At necropsy, numerous, multifocal or coalescing, firm, protruding nodules, 5 to 40 mm in diameter were scattered throughout the mesentery and omentum. Histologically and immunohistochemically, the nodules were diagnosed as malignant mesothelioma. Metastasis to the regional mesenteric, mediastinal and tracheobronchial lymph nodes were observed.

Topics: Abdominal Neoplasms; Animals; Dog Diseases; Dogs; Fatal Outcome; Female; Immunohistochemistry; Keratins; Mesothelioma; Omentum; Vimentin

A 70-year-old woman was admitted to our hospital for medical evaluation of a right side pleural effusion, which was pointed out at another hospital. Chest CT revealed a right pleural effusion with diffuse and irregular pleural thickening. Percutaneous pleural biopsy showed hypocellular collagenous tissue without malignant cells. Though she received antituberculosis therapy, the pleural thickening progressed and the serum CYFRA 21-1 level was elevated. Chest pain and dyspnea appeared, and she was readmitted. However, pneumonia was present as a complication, and she died. At autopsy, the right pleura was thickened and invasion of the lung and the chest wall was observed. Microscopic findings showed increased amounts of hyalinized collagen fibers forming a storiform pattern. At the tumor foci, atypical cells with distinct nucleoli were observed. Desmoplastic malignant mesothelioma, which is rarely reported in Japan, was diagnosed.

Topics: Aged; Antigens, Neoplasm; Female; Humans; Keratin-19; Keratins; Mesothelioma; Pleural Effusion, Malignant; Pleural Neoplasms

Immunohistochemistry provides an important indicator for differential diagnosis between pleural malignant mesothelioma and lung adenocarcinoma, which have complex therapeutic and medicolegal implications. To pinpoint a reliable, restricted panel of markers, the authors evaluated the efficacy of select commercial antibodies in a series of patients with confirmed clinicopathologic diagnosis of mesothelioma or lung adenocarcinoma with the aid of multiple logistic classification tables. Specimens of 46 mesotheliomas and 20 lung adenocarcinomas were examined with calretinin, thrombomodulin, cytokeratins (CKs) 5/6, and high-molecular weight CKs (indicators of mesothelioma), alongside MOC 31, Ber-EP4, and carcinoembryonic antigen (CEA; indicators of lung adenocarcinoma). Of the mesotheliomas, 40 of 46 (87%) were positive with calretinin, 29 of 46 (63%) with thrombomodulin, 40 of 46 (87%) with CKs 5/6, and 41 of 46 (89%) with high-weight CKs; five of 46 mesotheliomas (11%) were focally reactive with MOC 31, four of 46 (9%) with Ber-EP4, and two of 46 (4%) with CEA. Of the lung adenocarcinomas, 18 of 20 (90%) were positive with MOC 31, 20 of 20 (100%) with Ber-EP4, and 17 of 20 (85%) with CEA; and two of 20 (10%) were focally reactive with calretinin, one of 20 (5%) with thrombomodulin, none of 20 (0%) with CKs 5/6, and five of 20 (25%) with high-weight CKs. Multiple logistic modeling indicated two batteries of three antibodies permitting more than 98% overall accuracy: Ber-EP4 plus CKs 5/6 plus calretinin, and Ber-EP4 plus CKs 5/6 plus CEA.

Topics: Adenocarcinoma; Antibodies; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mesothelioma; Regression Analysis; S100 Calcium Binding Protein G; Thrombomodulin

The aim of this study was to analyse the diagnostic value of selected glyco- and immunohistochemical probes for discrimination between mesotheliomas and metastatic carcinomas within the pleura, and to evaluate prognostic indicators in the tested panel. A panel of nine markers (five antibodies, two neoglycoproteins, and labelled hyaluronic acid) was applied to a total of 264 specimens with mesotheliomas (118 cases) and metastatic carcinomas in the pleura (146 cases); the material consisted exclusively of surgical specimens. The diagnosis obtained by standard procedures was further substantiated through a detailed follow-up and clear-cut descriptions of primary sites. The metastatic tumours originated from the lung (82 cases), breast (47 cases), colon (three cases), and kidney (two cases); in 12 cases, however, the tumour origin could not be ascertained. In detail, the probes tested included antibodies against carcinoembryonic antigen (CEA), vimentin, calretinin, mesothelial cells (HBME-1), calcyclin and keratin-5; and also biotinylated neoglycoproteins with ganglioside GM1 and N-acetyl-D-glucosamine (GlcNAc) as the ligand part, and hyaluronic acid. Carrier-immobilized ganglioside GM1 and hyaluronic acid displayed the highest specificity and sensitivity for mesotheliomas, followed by calretinin and HBME-1, whereas keratin-5 and vimentin were of low specificity (43% and 52%, respectively). Metastatic carcinomas could be discerned by CEA detection and application of GlcNAc-bearing neoglycoprotein with similar sensitivity (76% and 72%, respectively) and specificity (91% and 86%, respectively). In cases of breast carcinoma, the maximum specificity (59%) and sensitivity (67%) were low for all markers. Patients with mesothelioma survived longer than those with metastatic carcinoma, especially those with detectable binding sites for hyaluronic acid. No association of tumour type and binding properties of the other applied probes with survival of the patients could be found at a statistically significant level. It is concluded that in routine practice, the application of carrier-immobilized GM1, hyaluronic acid, and antibodies against calretinin and HBME-1 is useful for confirmation of mesothelioma, whereas the detection of CEA and GlcNAc-specific binding sites is useful for distinguishing metastatic carcinoma from mesothelioma. Despite the rather infrequent occurrence of mesotheliomas in women, particular attention should be given to exclude or confirm metastatic

Topics: Acetylglucosamine; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Evaluation Studies as Topic; Female; Gangliosides; Humans; Hyaluronic Acid; Keratins; Male; Mesothelioma; Pleural Neoplasms; Sensitivity and Specificity; Vimentin

The aim of our study was to assess the clinical value of CYFRA 21-1 tumor marker and carcinoembryonic antigen (CEA) as diagnostic tools that are complementary to cytology in the diagnosis of malignant mesotheliomas.. We measured CEA and CYFRA 21-1 in the pleural effusions (PEs) and serum of 106 patients (benign lung disease, 34 patients; bronchogenic and metastatic carcinoma, 40 patients; mesothelioma, 32 patients).. CEA and CYFRA 21--1 levels were determined by means of two commercial enzyme immunoassays.. The cutoff levels of CYFRA 21--1 and CEA in malignant PEs, selected on the basis of the best diagnostic efficacy, were 41.9 ng/mL and 5.0 ng/mL, respectively. In all neoplastic PEs, CYFRA 21--1 and CEA sensitivity was 78% and 30.6%, respectively, with a specificity of 80% and 91%, respectively. The sensitivity of CYFRA 21--1 and CEA in patients with mesothelioma was 87.5% and 3.1%, respectively. The results of the CYFRA 21--1 assay were positive in 17 of 19 cases of mesothelioma (89.5%) with a negative or uncertain cytology. The association of the tumor marker assay and the cytology allowed a correct diagnosis in 30 of 32 cases of mesothelioma (93.7%).. This study suggests that CYFRA 21--1 would provide a useful parameter for the differential diagnosis between benign and malignant PE from mesothelioma when the result of cytology is negative or uncertain and the clinical context does not allow a more aggressive approach. Moreover, the association of CYFRA 21--1 with CEA could provide details for a differential diagnosis between mesotheliomas and carcinomas. In fact, an elevated CYFRA 21--1 level with a low CEA level is highly suggestive of mesothelioma, whereas high levels of CEA alone or high levels of both the markers suggest a diagnosis of malignant PE, excluding mesothelioma.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Keratin-19; Keratins; Lung Diseases; Lung Neoplasms; Mesothelioma; Pleural Effusion, Malignant; Pleural Neoplasms; Sensitivity and Specificity

The distinction between pleural epithelial mesothelioma and peripheral lung adenocarcinoma involving the pleura is still an important diagnostic problem for surgical pathologists. The aim of our study was to identify the most specific and sensitive markers for the positive identification of mesothelioma to select a limited, appropriate panel of antibodies to differentiate between mesothelioma and adenocarcinoma. Forty-two cases of epithelial mesotheliomas and 23 cases of pulmonary adenocarcinomas were stained with the following antibodies: anticalretinin, antithrombomodulin, anti-CD44H, and monoclonal antibody HBME-1. We also studied the value of other markers in current use: cytokeratins AE1/AE3 and CAM5.2, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Ber-EP4, B72.3, and CD15. Of the mesotheliomas, 42 stained for calretinin, 39 (92.8%) for thrombomodulin, 42 stained for CD44H, and 41 (97.6%) stained for HBME-1. Among negative markers, 4 (9.5%) mesothelioma cases stained for CEA, 5 (11.9%) stained for Ber-EP4, 6 (14.2%) stained for B72.3, and 2 (4.7%) stained for CD15. Of the lung adenocarcinomas, 2 (8.7%) cases showed reactivity for calretinin, 5 (21.7%) for thrombomodulin, 13 (56.5%) for CD44H, all for HBME-1, 22 (95.6%) for CEA, 22 (95.6%) for Ber-EP4, 8 (34.7%) for B72.3, and all for CD15. In conclusion, calretinin and thrombomodulin were the most specific positive mesothelial markers, whereas CD44H and HBME-1 showed high sensitivity but very low specificity. Among negative markers, we advocate the use of CEA and CD15 which were the most specific in differentiating mesotheliomas from adenocarcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Mucin-1; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

An unusual case of deciduoid mesothelioma occurring in the anterior abdominal wall of a 30-year-old woman is reported. The patient had a palpable mass that was resected. The mass appeared largely cystic with solid areas. Histologically, the tumor cells appeared epitheloid with eosinophilic cytoplasm and prominent nucleoli. The tumor was positive for keratins and vimentin and negative for CEA and Ber-EP4. Electron microscopy showed features of mesothelial cells characterized by well-formed desmosomes and long, slender microvilli. In contrast to previously reported cases of deciduoid mesothelioma, this tumor developed in the abdominal wall and appears to have a benign course.

Topics: Abdominal Muscles; Abdominal Neoplasms; Adult; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Decidua; Female; Humans; Immunohistochemistry; Keratins; Mesothelioma; Microvilli; Radiography

Topics: Aged; Asbestos; Calbindin 2; Carcinogens; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Pleural Neoplasms; S100 Calcium Binding Protein G

A 10-year-old male aardwolf (Proteles cristatus) was presented abdominal distention and emaciation for 3 months. Physical examination revealed firm abdominal masses with effusions. Cytologic assessment of the effusion showed uniform round tumor cells with a surface brush border. Necropsy showed white velvety masses covering the peritoneal surface of the liver, gall bladder, stomach, omentum, mesentery, spleen, intestine, abdominal wall and diaphragm. Histologic examination demonstrated papillary projections, lined with cuboidal tumor cells supported by fibrous connective tissue cores, arising from the serosa of visceral organs. Cytoplasmic vacuolation and a surface brush border were evident on some cells under light microscopy. Tumor cells stained positive for both cytokeratin (AE1/AE3) and vimentin. Electron microscopy showed prominent surface microvilli, rough endoplasmic reticulum, mitochondria and desmosomes in tumor cells. This may be the first reported case of peritoneal mesothelioma in a captive wild aardwolf.

Topics: Animals; Animals, Zoo; Ascites; Biomarkers, Tumor; Carnivora; Keratins; Male; Mesothelioma; Neoplasm Proteins; Neoplastic Stem Cells; Peritoneal Neoplasms; Vimentin

To identify the most accurate and useful panel to diagnose mesothelioma, we immunostained sections from 112 mesotheliomas, 18 adenocarcinomas, and 11 reactive pleural specimens with 13 antibodies. Positive results for mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were CAM5.2, 111, 18, and 11; vimentin, 30, 3, and 3; HBME-1, 75, 10, and 8; thrombomodulin, 31, 2, and 2; calretinin, 43, 6, and 11; and CD44H, 68, 10, and 4. Positive results for adenocarcinoma markers in mesotheliomas and adenocarcinomas, respectively, were carcinoembryonic antigen, 1 and 15; LeuM1, 7 and 9; and Ber-EP4, 5 and 12. All reactive pleura were negative. Positive results for markers to help distinguish mesothelioma from reactive pleura in mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were epithelial membrane antigen, 76, 17, and 6; p53, 78, 16, and 9; P-170 glycoprotein, 37, 4, and 2; and platelet-derived growth factor receptor beta, 31, 1, and 2. The differential diagnosis of mesothelioma from adenocarcinoma is based on negative markers. Individual mesothelial markers are of low sensitivity and specificity for mesothelioma. However, diagnostic accuracy is improved by the use of antibody panels. To date there are no antibodies that help distinguish mesothelioma from reactive pleura.

Topics: Adenocarcinoma; Antigens, Surface; ATP Binding Cassette Transporter, Subfamily B; Biomarkers; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Glycoproteins; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Lewis X Antigen; Mesothelioma; Mucin-1; Neoplasm Metastasis; Peritoneal Neoplasms; Pleural Neoplasms; Receptor, Platelet-Derived Growth Factor beta; S100 Calcium Binding Protein G; Thrombomodulin; Tumor Suppressor Protein p53; Vimentin

Topics: Aged; Antigens, Neoplasm; Ascites; Biomarkers, Tumor; Humans; Keratin-19; Keratins; Male; Mesothelioma; Peritoneal Neoplasms

Immunohistochemistry is a useful method in the differential diagnosis between pleural mesotheliomas and metastatic adenocarcinomas to the pleura. Cytokeratin (CK) 5-6 is one of the most specific mesothelioma-associated antibodies. Cytokeratin 20 and CK7 have been used successfully in studies determining primary location of adenocarcinomas from metastases. In the current study, the value of these CKs in differential diagnosis of malignant pleural lesions was examined.. Ninety-three autopsy-verified cases (14 mesotheliomas and 79 adenocarcinomas including 42 primary lung tumors and 37 adenocarcinomas metastatic to the pleura) were stained on CK20, CK7, and CK5-6 with commercially available primary antibodies. The staining was conducted in an automated immunohistochemical system. The results were analyzed statistically at different positivity thresholds: 10% and 0%.. None of the mesotheliomas stained positively for CK20 at the 10% positivity level, but 3 cases showed focal positivity in < 10% of the tumor cells. Eighty-six percent (12 of 14) of these tumors were CK7+ and 64% (9 of 14) were CK5-6+. None of the mesotheliomas expressed the CK20+/7- pattern. Lung adenocarcinomas, both primary and metastatic, and breast carcinomas were very similar to mesotheliomas with regard to expression of CK20 and CK7 but differed significantly with regard to expression of CK5-6. Conversely, gastrointestinal adenocarcinomas and pancreaticobiliary tumors expressed CK20 positivity in a high proportion, 86% (13 of 15) and 77% (7 of 9), respectively. The gastrointestinal tumors stained positively for CK7 in only 20% (3 of 15) of cases and differed significantly from the other adenocarcinomas in this aspect. The CK20+/7- pattern was typical for gastrointestinal tumors.. Adding CK20 and CK7 to the panel of antibodies in the differential diagnosis of pleural mesothelioma versus metastatic adenocarcinomas is useful because diffuse CK20 positivity seems to be an indicator of metastasis. Furthermore, CK7 negativity most often is associated with metastases, and the CK20+/7- pattern, typical of colorectal adenocarcinomas, is absent in pleural mesotheliomas.

Topics: Adenocarcinoma; Autopsy; Biomarkers, Tumor; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Mesothelioma; Neoplasm Metastasis; Pleural Neoplasms; Sensitivity and Specificity

Pleural malignant mesothelioma (PMM) is a rare tumor and it is commonly seen in the form of multiple nodules or a diffuse tumor. A localized tumor mass in the pleura is extremely rare. Only seven cases have been reported. In this report, we present an additional case of localized PMM and describe the immunohistochemical and flow cytometric findings. A 61-year-old woman, without a history of smoking or asbestos exposure, presented with a severe pain in her right shoulder and arm. Chest radiography showed a solitary mass in the right upper lung field. Computed tomography showed a 5 cm right upper lung mass. Magnetic resonance imaging showed that the mass extended to the wall of the thorax. The patient underwent surgery for total removal of the tumor. Pathology revealed a localized malignant mesothelioma. Immunohistochemical analysis showed that the tumor was strongly and diffusely positive for cytokeratins with high and low molecular weight, and focally positive for vimentin and epithelial membrane antigen (EMA), but it was negative for carcinoembryonic antigen, Factor VIII, alpha-fetoprotein and Leu-M1. Flow cytometry showed an aneuploid DNA content in the tumor. The final diagnosis was localized malignant mesothelioma (epithelial type). The patient showed signs of local recurrence 5 months after surgery, and radiotherapy was given.

Topics: Aneuploidy; Biomarkers, Tumor; Female; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Mesothelioma; Middle Aged; Neoplasm Recurrence, Local; Pleural Neoplasms; Radiography, Thoracic

Malignant epithelioid mesothelioma shows marked cytoarchitectural diversity. The aim of the study was to evaluate how immunoreactivity with mesothelial markers related to histological pattern.. Ninety-two cases of malignant epithelioid mesothelioma (60 pleural, 32 peritoneal) were examined and classified as exhibiting tubulopapillary, adenomatoid, solid, small cell or pleomorphic patterns. All cases were immunohistochemically stained with thrombomodulin, calretinin, CD44H, and cytokeratin 5/6. Cases of malignant mesothelioma exhibited a number of different histological forms. Immunohistochemical expression of each mesothelial marker tested was not homogeneous across different histological patterns of malignant epithelioid mesothelioma, even within the same tumour section. Calretinin (with nuclear expression) was identified to show the highest overall sensitivity and lowest range variation in staining (67% sensitivity in small cell areas to 100% expression in pleomorphic areas). Cytokeratin 5/6 and thrombomodulin yielded similar overall sensitivity. Thrombomodulin appeared to demonstrate higher sensitivity for small cell variant tumour (83% sensitivity). A notable advantage with cytokeratin 5/6 was that expression was more diffuse in nature rather than the focal membranous elaboration seen in thrombomodulin. The widest range of staining was seen in small cell mesothelioma (83% sensitivity with thrombomodulin to 17% sensitivity with cytokeratin 5/6) and in tubulopapillary areas (90% sensitivity with calretinin to 38% sensitivity with CD44H).. Calretinin appears most useful and shows the highest overall sensitivity for malignant epithelioid mesothelioma, with good expression in areas displaying a tubulopapillary, adenomatoid, solid and pleomorphic pattern. For small cell mesothelioma, thrombomodulin appears to confer higher sensitivity and is advocated, in this setting, as the first line mesothelial marker. Cytokeratin 5/6 is a useful and easily interpretable mesothelial marker. CD44H is not of particular use in the diagnosis of malignant epithelioid mesothelioma. Accurate interpretation of immunohistochemistry in mesothelioma requires an awareness of the immunophenotypic heterogeneity identified in different histological forms of the tumour, and this is of particular importance in small biopsies.

Topics: Biomarkers; Calbindin 2; Epithelioid Cells; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratin-5; Keratins; Mesothelioma; S100 Calcium Binding Protein G; Thrombomodulin

To investigate the histogenesis of paratesticular adenomatoid tumour by use of immunohistochemical markers for a variety of carcinomas and mesothelioma.. Immunohistochemical staining of sections from 12 cases of paratesticular adenomatoid tumour was undertaken using primary antibodies to antigens expressed by benign epithelial cells and carcinoma (cytokeratin AE1/AE3, cytokeratin 34ssE12, epithelial membrane antigen, MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1), stromal and vascular markers (vimentin, CD34, factor VIII), and mesothelioma-associated antigens (thrombomodulin, HBME-1, OC 125) and p53 protein. There was absence of immunohistochemical expression of epithelial/carcinoma markers MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1 and to factor VIII and CD34. All tumours expressed cytokeratin AE1/AE3, epithelial membrane antigen and vimentin, with weak expression of cytokeratin 34ssE12 in 25% of tumours. Each tumour showed expression of thrombomodulin, HBME-1 and OC 125 in a membranous distribution. p53 protein expression was not detected.. The immunohistochemical profile of paratesticular adenomatoid tumour is strongly supportive of a mesothelial cell origin.

Topics: Adenomatoid Tumor; Biomarkers, Tumor; CA-125 Antigen; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Mucin-1; Testicular Neoplasms; Testis; Thrombomodulin; Vimentin

Until recently, the standard approach of most laboratories in distinguishing epithelioid pleural mesothelioma from metastatic adenocarcinoma has been a negative result from a panel of adenocarcinoma-associated antibodies. However, several "mesothelium-associated" antibodies have been proposed as useful in this situation, and we have applied four of these putative mesothelioma markers--thrombomodulin, cytokeratin 5/6, calretinin, and CD44H--to a series of 61 epithelioid pleural mesotheliomas and 63 metastatic adenocarcinomas with known primary sites (lung = 19; breast = 21; ovary = 6; colon = 10; kidney = 4; uterus, epididymis, pancreas = 1 case each). Of the mesotheliomas, 55 of 61 (90%) stained for thrombomodulin, 56 of 61 (92%) for cytokeratin 5/6, 47 of 51 cases (92%) were positive for calretinin, and 39 of 43 (91%) were positive for CD44H. Of the metastatic adenocarcinomas, 12 of 63 (19%) cases were positive for thrombomodulin, 9 of 63 (14%) were positive for CK5/6, and 27 of 60 (45%) were positive for CD44H. With calretinin, only 1 case of 59 (2%) showed positive nuclear staining. All four antibodies stained reactive mesothelium; thrombomodulin also stained endothelium; and CD44H variably stained lymphocytes, macrophages, and fibroblasts. We conclude that all four antibodies show high sensitivity for epithelioid mesothelioma, but only calretinin (98%), cytokeratin 5/6 (86%), and thrombomodulin (81%) show sufficient specificity for practical use in this situation.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Antigens, Neoplasm; Calbindin 2; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleural Neoplasms; S100 Calcium Binding Protein G; Sensitivity and Specificity; Thrombomodulin

Anti-CEA, anti-vimentin, CAM5.2, BerEp4, Leu-M1 and anti-EMA were applied to effusions from 36 mesotheliomas, 53 adenocarcinomas and 24 reactive mesothelial proliferations. Stepwise logistic regression analysis selected three criteria of major importance for distinguishing between adenocarcinoma and mesothelioma: BerEp4, CEA and EMA accentuated at the cell membrane (mEMA), these three being of similar diagnostic value. The pattern BerEp4-, CEA- and mEMA+ was fully predictive for mesothelioma (sensitivity 47%), whereas the opposite pattern was fully predictive for adenocarcinoma (sensitivity 80%). Only EMA seemed to distinguish between mesotheliosis and mesothelioma. Comparison of reactivity in cytological and histological material from the same mesotheliomas showed similar staining frequencies for CEA and CAM5.2, with some random variation for Leu-M1 and EMA, whereas vimentin and BerEp4 reactivity was more frequent in cytological specimens.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Neoplasm; Antibody Specificity; Antigens, Neoplasm; Antigens, Surface; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Epithelium; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Lewis X Antigen; Logistic Models; Lung Neoplasms; Mesothelioma; Mucin-1; Neoplasm Proteins; Pleural Effusion, Malignant; Sensitivity and Specificity; Vimentin

Three cases of lympho-histiocytoid mesothelioma, a rare variant of pleural sarcomatoid malignant mesothelioma, are described. Histologically, the neoplasms were characterized by a diffuse discohesive proliferation of atypical histiocytoid cells intermixed with a marked lymphocytic and lesser plasmacytic infiltrate. One case initially was misdiagnosed as a ganglioneuroma, a second case was misinterpreted as malignant lymphoma, and a third case was sent in consultation with the differential diagnosis of inflammatory pseudotumor vs mesothelioma. Immunohistochemical studies showed strong and generalized expression of cytokeratins and vimentin by the neoplastic histiocytoid cells in all 3 cases. Two cases were positive for calretinin, one of which also was positive for HBME-1, thrombomodulin, and LeuM1. None of the cases stained with the epithelial glycoprotein markers carcinoembryonic antigen, B72.3, and Ber-EP4, or the blood group antigen, BG-8. The immunophenotype of the lymphoplasmacytic infiltrate revealed predominantly reactive, mature T cells, with fewer polytypic plasma cells, histiocytes, and B cells. In lymphohistiocytoid mesothelioma, as in the usual examples of sarcomatoid mesothelioma, the demonstration of cytokeratin expression by the neoplastic cells is the most useful diagnostic finding that allows exclusion of other neoplasms with which this entity may be confused.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Calbindin 2; Diagnosis, Differential; Ganglioneuroma; Granuloma, Plasma Cell; Histiocytes; Humans; Immunohistochemistry; Keratins; Lymphocytes; Lymphoma; Mesothelioma; Middle Aged; Plasma Cells; S100 Calcium Binding Protein G; Thrombomodulin; Vimentin

We report a case of localized pericardial mesothelioma with unusual histological features in a 44-year-old woman. Her radiological imagings showed an 11-cm pericardial tumor, between the heart and aortic arch. Microscopically, the tumor was predominantly composed of vacuolated cells and vaguely reminiscent of well differentiated "lipoma-like" liposarcoma, but only small foci of the tumor showed the papillotubular configuration. Histochemically, the tumor cells contained hyaluronic acid in the vacuoles but no lipids. Immunohistochemically, they showed immunoreactivity for cytokeratin, calretinin, vimentin, and epithelial membrane antigen. Ultrastructural study showed that the vacuoles of the tumor cells were intracytoplasmic lumina. The intracytoplasmic lumina and the surface membranes of the tumor cells had many long and slender microvilli with focal bush-like appearance. Desmosomes between adjacent cells were occasionally observed. To our knowledge, this is the first case report of epithelial type mesothelioma predominantly composed of vacuolated tumor cells, microscopically mimicking liposarcoma.

Topics: Adult; Calbindin 2; Diagnosis, Differential; Female; Heart Neoplasms; Histocytochemistry; Humans; Hyaluronic Acid; Immunohistochemistry; Keratins; Liposarcoma; Mesothelioma; Microscopy, Electron; Mucin-1; Pericardium; S100 Calcium Binding Protein G; Vacuoles; Vimentin

The clinicopathological, immunohistochemical and aetiological aspects, with respect to asbestos, of seven primary gonadal mesotheliomas (three intratesticular, four ovarian) are described and compared. These tumours are extremely rare, poorly described and the knowledge of their natural history is very limited.. The cases were collated from the UK Health and Safety Executive Mesothelioma Register over a 24-year period (1968-91). Primary mesotheliomas of the tunica vaginalis and ovary comprised 0. 09% (10 cases) and 0.03% (three cases) of mesothelioma deaths, respectively. No primary intratesticular (non-tunica vaginalis) malignant mesotheliomas have been described. In this study, we present seven (three intratesticular, four ovarian) primary malignant gonadal mesotheliomas. In both genders the tumours show a similar age distribution (with median onset in the sixth decade), a similar association with asbestos (in approximately 50% cases), a diverse histological spectrum (with predominantly tubulopapillary epithelial subtype tumours) and an immunophenotype that is comparable with malignant pleural and peritoneal mesothelioma. The clinical course appears variable (mean, 26 months; range, 9-50 months). All tumours in the study presented as localized masses and their prognosis appeared more favourable than that of diffuse pleural and peritoneal cases.. An awareness of the existence of these rare forms of malignant mesothelioma is important to prevent misdiagnosis. Immunohistochemistry has an important role in confirmation of the diagnosis. The accurate diagnosis of primary gonadal mesothelioma has potentially important medicolegal compensation considerations as a significant proportion of these cases are associated with asbestos.

Topics: Adult; Aged; Asbestos; Calbindin 2; Carcinogens; Fatal Outcome; Female; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Ovarian Neoplasms; S100 Calcium Binding Protein G; Testicular Neoplasms; Thrombomodulin

To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms.. Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified.. Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.

Topics: Biomarkers, Tumor; Calbindin 2; Carcinoma; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lung Neoplasms; Mesothelioma; S100 Calcium Binding Protein G; Sarcoma; Thrombomodulin

The aim of the study was to assess diagnosis value of tumor markers for differential diagnosis between mesothelioma and other pleural tumors.. Prospective study of 85 patients attending our hospital with malignant pleural effusion. The diagnostic approach involved routine pleurocentesis followed by pleural needle. When precise diagnosis was not achieved, thoracoscopy with pleural biopsies was performed. Carcinoembryonic antigen (CEA), hyaluronic acid, tissue polypeptide antigen and cyfra 21 to 1 were measured in serum and pleural fluid.. By using receiver operating characteristics curves and area under curves, the best diagnostic characteristics were obtained with pleural and serum CEA concentrations. The area under the curve was larger for pleural ACE than for serum ACE. The sensitivity and specificity of a pleural CEA level exceeding 3 ng/mL for ruling out the diagnosis of mesothelioma were 100% and 77%, respectively.. A CEA level above 3 ng/mL in pleural fluid eliminated the diagnosis of mesothelioma, whereas the other markers were not sufficiently discriminant. However, despite a negative predictive value of 100% at a cutoff of 3 ng/mL, CEA assay in pleural fluid only avoids a small number of diagnostic thoracoscopies.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Area Under Curve; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Hyaluronic Acid; Keratin-19; Keratins; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Pleural Effusion; Pleural Neoplasms; Prospective Studies; ROC Curve; Sensitivity and Specificity; Tissue Polypeptide Antigen

Synovial sarcoma is a mesenchymal neoplasm of unknown histogenesis that shows various degrees of epithelial differentiation. It is known to contain simple epithelial keratins, and the possibility of complex epithelial keratin expression has been suggested. In this study, we immunohistochemically examined 110 well-documented synovial sarcomas including 44 biphasic, 48 monophasic, and 18 poorly differentiated (undifferentiated, highly mitotically active) tumors for 11 different keratin (K) polypeptides of the Moll catalogue. The epithelia of biphasic synovial sarcomas showed consistent, extensive reactivity for K7, K8, K14, K18, and K19. Other keratins seen in the epithelia of biphasic tumors included K17 (variable, in 77%), K13 (25%), K16 (23%), and K6 (24%) in the minority of biphasic tumors, predominantly in stratified-appearing epithelia. K10 was detected only focally in one case that showed keratinizing squamous differentiation. Focal expression of K20 was seen in 27% of cases. Monophasic synovial sarcomas had a more limited keratin repertory. Simple epithelial keratin positivity was detected, usually focally for K7 (79%), K19 (60%), K8 (45%), and K18 (46%). Two cases showed more extensive keratin positivity in the spindle cells. The monophasic tumors showed limited positivity for complex epithelial keratins: K14 (28%) and K17 (10%). K20 was detected focally in 6% of the monophasic tumors; other keratins were not detected. The poorly differentiated synovial sarcomas showed limited simple epithelial keratin reactivity, usually limited to scattered cells: K19 (61%), K7 (50%), K18 (47%), K8 (33%), but five cases showed more extensive positivity. Complex epithelial keratins were scant: K14 in one case and K17 in two cases. The immunoreactivity of capillary endothelia seen for K7 and K18 (but not for K8 and K19 with the antibodies used) is a potential diagnostic pitfall, and may cause overdiagnosis of synovial sarcoma if not properly recognized. In summary, we show complex patterns of keratins in synovial sarcoma, especially in the biphasic tumors. Such patterns establish a baseline in differential diagnostic considerations, and give an insight into the complex epithelial differentiation of this enigmatic mesenchymal tumor.

Topics: Adolescent; Adult; Aged; Child; Female; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Sarcoma; Synovial Membrane

Topics: Epithelial Cells; Facial Neoplasms; Follow-Up Studies; Humans; Keratins; Male; Mesothelioma; Middle Aged; Pleural Neoplasms; Skin Neoplasms; Tongue Neoplasms; Vimentin

In malignant mesothelioma, survival is claimed to be related to age, duration of symptoms, performance status, histological subtype, stage and platelet count. However the exact prognostic value of these factors is still a matter of debate. We studied the two cytokeratin markers, Cyfra 21-1 and Tissue polypeptide antigen (TPA) for their significance in predicting survival retrospectively in 52 patients. Cyfra 21-1 and TPA were elevated in 26 (50%) and 30 (58%) patients, respectively, and were highly correlated (r = 0.98). Univariate analysis of data from 51 patients, showed a relation with survival for performance status (P = 0.010), thoracic pain (P = 0.014), platelet count (P = 0.027), Cyfra 21-1 (P = 0.002) and TPA (P = 0.003). Multivariate analysis identified independent prognostic significance for performance status, platelet count and Cyfra 21-1. In addition to performance status ( < 80 vs. > 80) the cytokeratin markers identified patients with good prognosis in a log rank test. Values of Cyfra 21-1 and TPA are significantly correlated.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Keratin-19; Keratins; Male; Mesothelioma; Middle Aged; Multivariate Analysis; Pleural Neoplasms; Prognosis; Survival Analysis; Tissue Polypeptide Antigen

We report six cases of hyperplastic mesothelial cells located in the sinuses of lymph nodes. All patients but one had a concurrent serosal fluid collection (two pericardial, two pleural, one abdominal) at the time of the lymph node biopsy. All effusions cleared with treatment of the underlying disorder, which included lymphoproliferative processes, congestive heart failure, and inflammatory diseases (Dressler syndrome, vasculitis, and glomerulonephritis). Four cases were associated with vascular prominence of the involved nodal sinuses, a feature that may reflect the cause of the underlying effusion or support the transient persistence of benign mesothelial cells in lymph nodes. Two cases were characterized by distention of the nodal sinuses by sheets of mitotically active mesothelial cells. The differential diagnosis includes metastatic carcinoma, keratin-positive dendritic cells native to lymph nodes, and metastatic malignant mesothelioma. Because the latter shares both clinical and morphological features with cases of benign mesothelial cells in lymph nodes, we believe that this distinction may not always be possible in a given biopsy specimen and therefore that careful clinical follow-up is required in such cases.

Topics: Actins; Adolescent; Adult; Biomarkers, Tumor; Carcinoma; Dendritic Cells; Diagnosis, Differential; Epithelium; Female; Glomerulonephritis; Heart Failure; Humans; Hyperplasia; Immunohistochemistry; Keratins; Lymph Nodes; Lymphoproliferative Disorders; Male; Mesothelioma; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; Vasculitis

Five patients with malignant pleural mesothelioma (MPM) were studied to determine whether CYFRA 21-1 is useful for diagnosis of this disease. In pleural effusions, the median concentration of CYFRA 21-1 from 4 patients with MPM was significantly higher than for 34 patients with benign diseases. The sensitivity of serum CYFRA 21-1 for diagnosis of MPM was 40% and its concentration changed in proportion to disease activity in all cases. Immunohistochemically, anticytokeratin 19 antibody revealed strong staining in both epithelial and sarcomatous MPM tissues. Based on these results, we conclude that measurement of CYFRA 21-1 in pleural effusions and serum may be useful for diagnosing and monitoring MPM.

Topics: Aged; Antibodies; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratin-19; Keratins; Male; Mesothelioma; Pleural Neoplasms; Radiography, Thoracic

We report two cases of diffuse malignant pleural mesothelioma occurring almost simultaneously in one family. Patient 1 was a 42-year-old Japanese man who had worked as an electrical engineer for 25 years. Patient 2, his mother, was 69 years old. She lived for 10 years with patient 1 after he started his work, and also worked at a shipyard herself for 6 years. The concentrations of cytokeratin subunit 19 fragment (CYFRA 21-1) in pleural fluid of the two patients were 1,500 ng/ml, and 1,200 ng/ml, respectively. Measurement of CYFRA 21-1 concentration in the pleural fluid may be a useful tool for a diagnosis of malignant mesothelioma.

Topics: Adult; Aged; Antigens, Neoplasm; Asbestos; Biomarkers, Tumor; Biopsy; Carcinogens; Female; Humans; Keratin-19; Keratins; Male; Mesothelioma; Occupational Exposure; Pedigree; Pleural Effusion, Malignant; Thoracotomy; Tomography, X-Ray Computed

We present rare case of a uterine adenomatoid tumor. In order to characterize the diversity of immunoreactive antigens associated with mesothelial differentiation, we immunohistochemically examined the tumor's epithelioid and myofibromatoid components, as well as the biphasic pattern of its adenomatoid changes. Immunostaining of tumor cells was positive for high- and low-molecular-weight cytokeratins and vimentin. Specific immunoreactions with antibodies against desmin, alpha-actin, and the S-100 protein also were observed. The present adenomatoid tumor can be explained in terms of various transformations and typical alterations in mesothelioma cells: (1) the mesothelial cells had differentiated to epithelial and stromal components, concomitant with the presence of predominant reactive foci; (2) intermediate cells expressed different types of cytoskeletal intermediate filament proteins (IMPs); and (3) the patterns of fibromatoid and leiomyoid differentiation resembled those of a benign mesothelioma of the ovarian or oviductal peritoneum. Our immunohistochemical investigations indicated that the present tumor exhibited the histogenesis of a true mesothelioma, an adenomatoid mesothelioma.

Topics: Actins; Adenomatoid Tumor; Adult; Antibodies, Monoclonal; Desmin; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Mesothelioma; Microscopy, Electron; S100 Proteins; Uterine Neoplasms; Vimentin

To determine the value of immunocytochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy using commercially available monoclonal antibodies.. A panel of monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), Leu-M1, CD30 (Ber-H2), vimentin and desmin, was applied to 40 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura (16 pulmonary and seven extrapulmonary). Positivities for Ber-EP4, CEA, B72.3 and Leu-M1 were found to have the highest nosologic sensitivities (87.0%, 65.2%, 52.5% and 43.5%, respectively) and specificities (97.5%, 97.5%, 100% and 95%, respectively) for carcinoma. Positive staining for vimentin had the highest sensitivity (87.5%) with 95.7% specificity for mesothelioma. Positive staining for desmin was found in 45% of mesotheliomas and 0% of carcinomas. Diagnostic sensitivity and diagnostic specificity (P-values) were calculated for these markers. In respect to the diagnostic power defined by the clinically relevant predictive values of positive and negative tests, we found that a two-marker panel of antibodies including vimentin and Ber-EP4 is most useful for the histopathological distinction between carcinoma (pulmonary or extrapulmonary) and malignant pleural mesothelioma.. A combination of Ber-EP4 and vimentin provides the most sensitive and specific pair of markers for distinguishing between malignant pleural mesothelioma and carcinoma metastatic to the pleura. The prevalence of the tested tumours should be taken into account when evaluating the clinical value of ancillary techniques in pathology.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Mesothelioma; Pleural Neoplasms; Predictive Value of Tests; Sensitivity and Specificity; Vimentin

Previously available serum tumor markers had a low clinical value in malignant pleural mesothelioma (MPM). The recently developed tissue polypeptide-specific antigen (TPS) and CYFRA 21-1 assays identify the soluble cytokeratin 18 and 19 fragments, respectively. In MPM these cytokeratins are expressed and may therefore be used as serum tumor markers. In this preliminary study, TPS and CYFRA 21-1 assays were evaluated to determine their potential for management of patients with MPM. Carcinoembryonic antigen (CEA) was evaluated as an additional marker. The study group consisted of 95 patients with benign lung and pleural diseases (BLPD), 14 patients with MPM, 41 patients with adenocarcinoma of lung (AC), and 40 patients with squamous cell carcinoma of lung (SQC). The utilized cutoff points corresponded to a 95% specificity for patients with BLPD. In MPM, TPS showed greater sensitivity (64.3%) than CYFRA 21-1 (50.0%), while CEA showed no sensitivity. In SQC, the marker CYFRA 21-1 had the highest sensitivity (52.5%), whereas in AC the most sensitive marker was CEA (56.1%). Significantly lower levels of CEA were found in MPM compared with BLPD (p < 0.001) or AC and SQC (p < 0.0001). Conversely, TPS levels in MPM were significantly higher than in SQC (p < 0.05). Close correlation of various individual pretreatment marker levels was observed only between TPS and CYFRA 21-1, both in MPM (r = 0.84; p < 0.001) and in non-small cell lung cancer (NSCLC) (r = 0.71; p < 0.001). In serial determinations of the markers during chemotherapy of MPM (n = 10), TPS and CYFRA 21-1 were shown to demonstrate more or less the same pattern of reactivity, although the changes in the TPS levels better reflected the clinical response to therapy. In conclusion, TPS seems to be a more sensitive marker than CYFRA 21-1.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Humans; Keratin-19; Keratins; Lung Neoplasms; Mesothelioma; Peptides; Pleural Neoplasms

Localized malignant mesothelioma is an extremely rare form of presentation of malignant mesotheliomas. Only six cases have been reported. A 66-year-old male, former smoker, with occupational exposure to asbestos for 35 years, presented complaining of increasing fatigability, low-grade fever and anorexia for 4 weeks. The chest radiography showed a left lung mass. The computed tomography showed a 5-cm left posterior mass. The biopsy showed malignant cells. The patient underwent a surgical en bloc resection of the tumor. Pathology revealed a localized, poorly differentiated mesothelioma. Immunohistochemistry was positive for cytokeratin and vimentin while negative for carcinoembryonic antigen and Leu-M1. The final diagnosis was localized malignant mesothelioma. Aggressive resection of the tumor has shown to increase survival in previous reports, although the biological behavior of such tumors is still difficult to predict.

Topics: Aged; Anorexia; Asbestos; Biopsy; Carcinoembryonic Antigen; Fatigue; Fever; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Mesothelioma; Occupational Exposure; Pleural Neoplasms; Prognosis; Smoking; Survival Rate; Tomography, X-Ray Computed; Vimentin

The immunohistochemical diagnosis of mesothelioma is commonly made by using a battery of antibodies that reacts with lung adenocarcinomas but not with epithelial mesotheliomas. Only recently have markers that are often expressed in mesotheliomas but not in adenocarcinomas been recognized. Some of these markers, however, require frozen tissue sections, whereas others are not commercially available, or their value remains controversial. In a recent publication, it was suggested that immunostaining for cytokeratin 5/6 could assist in distinguishing epithelial mesothelioma from lung adenocarcinoma. To determine the practical value of cytokeratin 5/6 immunostaining in the diagnosis of mesothelioma, 40 formalin-fixed, paraffin-embedded epithelial pleural mesotheliomas, 30 pulmonary adenocarcinomas, 93 nonpulmonary adenocarcinomas, 15 squamous carcinomas of the lung, 5 large cell undifferentiated carcinomas of the lung, and 12 metastatic transitional cell carcinomas to the lung were stained with the same antibody, which was obtained from a commercial source. Cytokeratin 5/6 reactivity was observed in all 40 mesotheliomas, but there was none in any of the 30 pulmonary adenocarcinomas. Focal or weak reactivity was observed in 14 of 93 nonpulmonary adenocarcinomas (10 of 30 ovarian, 2 of 10 endometrial, 1 of 18 breast, I of 7 thyroid, 0 of 10 kidney, 0 of 10 colonic, and 0 of 8 prostatic). All 15 squamous carcinomas of the lung, 6 of 12 transitional cell carcinomas metastatic to the lung, and 3 of 5 large cell undifferentiated carcinomas of the lung expressed cytokeratin 5/6. It is concluded that cytokeratin 5/6 immunostaining is not only useful in separating epithelial pleural mesotheliomas from pulmonary adenocarcinomas but also can assist in distinguishing epithelial mesotheliomas from nonpulmonary adenocarcinomas metastatic to the pleura.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Diagnosis, Differential; Epithelial Cells; Evaluation Studies as Topic; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Mesothelioma; Pleural Neoplasms; Retrospective Studies

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Humans; Keratin-19; Keratins; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Neoplastic Cells, Circulating; Pleural Effusion; Pleural Neoplasms

In many but not all cases, malignant mesothelioma is associated with an elevated content of hyaluronan in pleural fluid. The hyaluronan-producing mesothelioma has not yet been immunohistochemically characterized; therefore, the purpose of this study was to compare the immunohistochemical reactivity patterns in relation to the ability of this tumour to produce hyaluronan. Pleural fluid samples from 33 patients with malignant mesothelioma were analysed for content hyaluronan using a quantitative high performance liquid chromatographic method. Biopsy specimens from the patients were studied immunohistochemically, using monoclonal antibodies against carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), a low molecular weight cytokeratin antigen (CAM 5.2) and vimentin. An elevated hyaluronan content, i.e. > 100 mg.L-1, was noted in 23 patients (70%). There was no reactivity to the monoclonal antibody raised against CEA in any case. There was a significantly higher reactivity to EMA (p = 0.026), a higher reactivity to CAM 5.2 (p = 0.053) and a lower reactivity to vimentin (p = 0.057) in the hyaluronan-producing mesotheliomas as compared to those with normal levels of hyaluronan. Mesotheliomas that produced hyaluronan differed immunohistochemically from those that did not. The connection between the ability to produce different antigens and hyaluronan may relate to the degree of differentiation of the tumour. Both of these characteristics (immunophenotype and ability to produce hyaluronan) may, therefore, be of importance in studies concerning the prognosis and treatment of the malignant mesothelioma.

Topics: Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Chromatography, High Pressure Liquid; Humans; Hyaluronic Acid; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Mucin-1; Pleural Effusion, Malignant; Pleural Neoplasms; Vimentin

We report a 50-year-old man with a history of malignant pleural mesothelioma diagnosed 1 year previously and treated with pneumonectomy and radiotherapy who presented with an erythematous eruption on the left chest wall. A skin biopsy showed a proliferation of malignant epithelioid cells lining irregular clefts in the dermis. Some groups of cells were observed filling vascular lumina. Immunohistochemically, the tumor cells expressed cytokeratins (with antibodies AE1/AE3, MNF 116, and CAM 5.2), and epithelial membrane antigen (EMA), and were negative with Ulex europaeus (UE) and for carcinoembryonic antigen (CEA), CD34, CD15 (with LeuM1 antibody), and factor VIII-related antigen (FVIIIra). The histologic features and immunohistochemical profile were comparable to those observed in the primary pleural mesothelioma. This is the first reported case in which malignant mesothelioma metastatic to the skin presented as "inflammatory carcinoma." Although a very uncommon presentation, mesothelioma should be considered in the differential diagnosis of erythematous eruptions on the chest.

Topics: Adenocarcinoma; Antigens, CD34; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Mesothelioma; Middle Aged; Mucin-1; Pleural Neoplasms; Skin Neoplasms; Thorax; von Willebrand Factor

Previous studies using frozen material have suggested that cytokeratin 5 is expressed by pleural mesothelioma but not by adenocarcinoma. In the present study, reactions for cytokeratins 5 and 6 were investigated in 33 pleural mesotheliomas and 27 secondary adenocarcinomas of the pleura using formalin-fixed, paraffin-embedded material and a commercially available antibody (anti-cytokeratin 5/6).. All of the adenocarcinomas originated in the peripheral lung. The epithelioid component of the mesotheliomas gave a strongly positive reaction: the reaction in sarcomatoid or desmoplastic areas was absent or weak. Twenty-two of the adenocarcinomas were negative, in four there was a weak, equivocal reaction, and in one there was patchy positivity.. We conclude that this antibody is potentially a useful positive marker for the identification of the epithelioid variant of mesothelioma in formalin-fixed and paraffin-embedded material.

Topics: Antibodies, Neoplasm; Biomarkers, Tumor; Humans; Keratins; Mesothelioma; Pleural Neoplasms

The immunohistochemical diagnosis between epithelial mesothelioma and adenocarcinoma is currently based on the use of a panel of antibodies to adenocarcinoma-associated antigens and a few antibodies to mesothelial-associated antigens. Since the introduction of epitope retrieval methods, the sensitivity of many antibodies has been enhanced. Thus, a reevaluation of the mesothelioma/adenocarcinoma diagnostic panel becomes necessary. We studied 268 paraffin-embedded formalin-fixed tumor samples that included 57 epithelial mesotheliomas and 211 adenocarcinomas of various origins, comparing an extensive antibody panel with and without heat-induced epitope retrieval (HIER). Marked increase in the sensitivity of several antibodies, with no loss of specificity, was found when HIER was used. After statistical analysis, the antibodies to the epithelial glycoproteins carcinoembryonic antigen, BerEp4, and Bg8 emerged as the best discriminators between adenocarcinoma and epithelial mesothelioma within the entire panel. The mesothelium-associated antibodies, HBME-1, calretinin, and thrombomodulin were less sensitive and less specific than the former, although they were found to be useful on certain cases. Antibodies to cytokeratins and vimentin, although of minor diagnostic value in this context, may be helpful to evaluate the quality of antigen preservation. This study confirms the value of immunohistochemistry to accurately distinguish mesothelioma from adenocarcinoma when an antibody panel approach is used. The addition of heat-induced epitope retrieval methods increases the effectiveness of the procedure and is recommended for most of the antibody panel members.

Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Calbindin 2; Carcinoembryonic Antigen; Colorectal Neoplasms; Decision Trees; Diagnosis, Differential; Epitopes; Female; Hot Temperature; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms; Pleural Neoplasms; Retrospective Studies; S100 Calcium Binding Protein G; Sensitivity and Specificity; Thrombomodulin; Vimentin

A primary malignant peripheral nerve sheath tumor (MPNST) of the pleura that clinically mimicked a malignant mesothelioma in a 57-year-old man is described. Histologically, the tumor had features similar to those described in cases of the so-called epithelioid MPNST. A unique finding in this case was the demonstration of keratin expression in the epithelioid component of the tumor, as well as the presence of rhabdomyoblasts. This is the first example of an MPNST with heterologous elements arising in the pleura. Immunohistochemical and ultrastructural studies were important in differentiating this tumor from other malignancies with sarcomatoid and epithelioid features involving the pleura.

Topics: Actin Cytoskeleton; Biomarkers, Tumor; Cell Differentiation; Diagnosis, Differential; Fatal Outcome; Glycogen; Humans; Keratins; Male; Mesothelioma; Middle Aged; Neoplasm Recurrence, Local; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Pleural Neoplasms; Rhabdomyosarcoma

The prognosis of patients with pleural mesothelioma is more dependent on "pretreatment factors" than on the effect of therapeutic interventions. Histopathologic subtype is one of several important prognostic factors in pleural mesothelioma, and several studies indicate that the epithelial subtype of pleural mesotheliomas has a more favorable prognosis than the sarcomatoid. In this study, we retrospectively evaluated qualitative and quantitative aspects of the tissue specimens used for histopathologic diagnosis in 85 patients with pleural mesothelioma.. The prognostic roles of two different histopathologic classification systems were evaluated in 85 consecutive cases of pleural mesotheliomas. Efficiency of different diagnostic procedures, influence of the size of the biopsy specimens on the histopathologic diagnosis, and immunohistochemical profiles for histopathologic subtypes of mesotheliomas were also evaluated.. Patients with pure epithelial mesotheliomas (n = 35), and especially those with the tubulopapillary subtype (n = 18) of epithelial mesotheliomas, survived significantly longer than those with a sarcomatoid component (n = 50). With larger biopsy specimens (surgical biopsy, autopsy), more tumors were classified as biphasic (36/78 vs 9/44, p < 0.005). The sarcomatoid mesotheliomas comprised about 20% of the tumors regardless of type of biopsy. Staining intensity for cytokeratin CAM 5.2 was equal in all types of mesotheliomas, while intensity with cytokeratin AE1/AE3 decreased from the epithelial to the sarcomatoid mesotheliomas. Staining with vimentin was most intense among the sarcomatoid mesotheliomas, while with epithelial membrane antigen it was most intense among the epithelial mesotheliomas.. The quality of the biopsy specimens has considerable impact on the possibility to arrive at a correct histopathologic diagnosis. Based on our results, we suggest tubulopapillary mesotheliomas be regarded as "low-grade mesotheliomas" and other types, including the epithelioid type of epithelial mesotheliomas, as "high-grade mesotheliomas." This should be taken into account when designing clinical trials.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Biopsy; Clinical Protocols; Coloring Agents; Epithelium; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Mucin-1; Pleural Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Vimentin

We describe the cytohistological, immunohistochemical and ultrastructural findings in a 55-yr-old-man with history of asbestos exposure and diffuse malignant mesothelioma (DMM) of the pleura, peritoneum, and tunica vaginalis presenting with chest pain and scrotal swelling. Pleural fine-needle aspiration (FNA) revealed mesenchymal elements and spindle-shaped epithelial-like cells, while biopsy showed pure sarcomatous tumor invading lung parenchymal. In both samples tumor cells coexpressed cytokeratin and vimentin. Peritoneal and hydrocele effusions contained aggregates of malignant mesothelial cells. Electron microscopy showed intermediate filaments, rare desmosomes and sparse microvilli. Morphological findings were consistent with a DMM, with a biphasic pattern in the pleura and an epithelial one in the peritoneum and tunica vaginalis. Although the possibility of a multicentric origin cannot be ruled out, clinical chronologic sequence suggests that the pleura was the primary involved site, followed by spread to peritoneum and tunica vaginalis.

Topics: Asbestos; Biopsy, Needle; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Microscopy, Electron; Middle Aged; Neoplasms, Multiple Primary; Occupational Diseases; Peritoneal Neoplasms; Pleural Neoplasms; Testicular Neoplasms; Tomography, X-Ray Computed; Vimentin

An extremely rare case of malignant mesothelioma of the pericardium is reported. The tumor appeared to be the biphasic type of diffuse malignant mesothelioma which present many small to fine lipid droplets in the cytoplasm, particularly that of the epithelial cell, and a positive immunohistochemical reaction with antibodies to low molecular weight cytokeratin (45-50 kDa) in all of the tumor cells. The literature is also reviewed and the presence of lipid droplets and the importance of the immunohistochemical positivity to low molecular weight cytokeratin for differential diagnosis from other malignant tumors, such as invasive adenocarcinoma or primary sarcoma of the pleura, or soft tissue sarcoma involving the pleura is discussed.

Topics: Aged; Diagnosis, Differential; Heart Neoplasms; Humans; Keratins; Lipids; Male; Mesothelioma; Pericardium

Topics: Antibodies, Monoclonal; Diagnosis, Differential; Female; Humans; Keratins; Mesothelioma; Papanicolaou Test; Vaginal Smears

Solitary fibrous tumors (SFTs) often involve the pleura and also may encompass the peritoneum and nonserosal sites. On occasion SFTs mimics other neoplasms, including desmoplastic mesothelioma. CD-34, initially characterized as a hematopoietic progenitor cell antigen, recently has been identified in a small number of SFTs. Based on this observation, we compared the keratin, vimentin, and CD-34 expression of 19 SFTs and eight desmoplastic mesotheliomas. Fifteen of 19 SFTs (78.9%) expressed CD-34, whereas keratin expression was absent in all SFTs. In contrast, none of the desmoplastic mesotheliomas expressed CD-34 and keratin expression was found in seven of eight (87.5%). Vimentin expression was noted in 18 of 19 SFTs and in seven of eight desmoplastic mesotheliomas. We conclude that CD-34 expression distinguishes SFT from desmoplastic mesothelioma. Additionally, the results of our study support the idea that SFT is not derived from or related to conventional mesothelium.

Topics: Antigens, CD; Antigens, CD34; Biomarkers, Tumor; Cell Nucleus; Humans; Keratins; Mesothelioma; Pleural Neoplasms; Vimentin

We have tried to find a reliable panel of markers that would allow distinction between mesotheliomas and carcinomas metastatic to the pleura. In a prospective study, we evaluated 54 pleural effusions: In 27 of the patients, a diagnosis of histologically proven metastatic carcinoma was subsequently established, 7 patients had biopsy-proven malignant mesotheliomas and 20 had benign, reactive effusions whose benign etiologies were established by more than 2 years clinical follow-up. The MAb (monoclonal antibody) IOB3 proved to be diagnostic for carcinomas in all 27 cases (100%), whereas CEA (carcinoembryonic antigen) expression was found in only 22 out of 27 (81%). None of the malignant mesotheliomas, nor benign reactive mesothelial cells reacted with these two markers. All carcinomas, as well as one malignant mesothelioma, reacted with the MAb HEA125. Antibodies against 12 single cytokeratins, vimentin, and EMA (epithelial membrane antigen) were not helpful in the differentiation between malignant mesotheliomas and malignant carcinomatous pleural effusions. We conclude that adding the antibody IOB3 to the CEA assay should allow a reliable differentiation between these two entities.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, CD; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; CD24 Antigen; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Mesothelioma; Middle Aged; Pleura; Pleural Effusion, Malignant; Pleural Neoplasms; Predictive Value of Tests; Vimentin

Ultrastructural examinations have shown myofibroblastoid differentiation in sarcomatoid/desmoplastic mesotheliomas, but immunohistochemical expression of muscle actins seldom has been documented. We examined 10 sarcomatoid, 12 epithelial, and five biphasic mesotheliomas immunohistochemically for the expression of muscle-specific actin (MSA) and smooth muscle actin (SMA) and compared it with that in 12 specimens of lung cancer. All of the sarcomatoid mesotheliomas were found to be positive for both MSA and SMA. The epithelial cells in nine epithelial and two biphasic mesotheliomas were positive for MSA, but SMA was only positive in one epithelial mesothelioma. Conversely, the lung cancers were negative for both MSA and SMA in the epithelial cells, except for one specimen that was weakly positive for MSA. The stromal cells in both the epithelial mesotheliomas and lung cancers were negative for cytokeratin but were positive for MSA and SMA, whereas the sarcomatoid and biphasic mesothelioma spindle cells were positive for all three antibodies. We concluded that sarcomatoid mesothelioma was positive for MSA and SMA, which is in support of its myofibroblastic differentiation, and that positivity for MSA in some epithelial mesotheliomas might be of diagnostic value in differentiation from lung cancers.

Topics: Actins; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Mesothelioma; Muscle, Smooth; Muscles; Staining and Labeling

The most common carcinomas metastatic to the ovary that mimic ovarian primaries are colonic adenocarcinomas and endometrial carcinomas. Conventional histochemical staining procedures, even in combination with additional immunohistochemical assays, are of limited value in distinguishing between these metastases and primary ovarian carcinomas. In this study we investigated whether the application of monoclonal antibodies against keratins 7, 8, and 20 could help in differentiating between these categories. The reactivity patterns of 40 carcinomas metastatic to the ovary were compared with those of their primary carcinomas on the one hand and with various primary ovarian carcinomas and mesotheliomas on the other. Colon cancer metastatic to the ovary was keratin 7 negative and keratin 20 positive in 94% of the cases; in contrast, all primary ovarian carcinomas were keratin 7 positive and keratin 20 negative, with the exception of two cases of mucinous cystadenocarcinoma. Ovarian metastases of gastric cancer usually contained keratins 7 and 20. Metastases of endometrial cancer to the ovary and primary ovarian carcinomas usually showed similar keratin expression. We propose that keratin 7 and 20 antibodies may be of help to distinguish between primary ovarian carcinomas and carcinoma metastases in the ovary.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratins; Mesothelioma; Ovarian Neoplasms

Peritoneal mesotheliomas are rare in women, compared to serous epithelial neoplasms with which they are often confused. We evaluated the clinicopathologic features of 19 true mesothelial neoplasms affecting the genital tract or peritoneum of women (other than adenomatoid tumors, benign multicystic mesotheliomas, and localized fibrous tumors) to characterize their clinicopathologic features and to determine their clinical behavior. Six tumors were localized to one anatomic site at presentation, and 13 involved more than one anatomic site. The six localized tumors were solitary, small (0.8-2.0 cm), polypoid or nodular lesions, five of which were incidental findings. All had a predominantly tubulopapillary pattern, either pure or mixed with adenomatoid-like or small solid foci. Nuclear grade ranged from 0 to 2. Mitotic figures (MF) were absent in two tumors. The mitosis count in the other four tumors was < 1 MF/10 high-power microscopic fields (HPF) (average method) and ranged from 1 to 3 MF/10 HPF (highest count method). Five patients were alive without recurrence after postoperative intervals ranging from 19 months to 9 years (median, 5 years); one patient died of metastatic gastric carcinoma at 14 months. Thirteen tumors involved more than one anatomic site and were classified as diffuse mesothelioma. Typically, these tumors were symptomatic and accompanied by ascites. The tumors had either a plaque-like or endophytic configuration. Eleven were purely epithelial mesotheliomas, and two had a minor sarcomatoid component. Tubulopapillary patterns were present in 10 tumors, usually admixed with focal adenomatoid-like or solid patterns, and three had a purely solid pattern. All 13 tumors had grade 3 nuclei. The mitosis count ranged from < 1 to 2 MF/10 HPF (average count method) with a range of 1-4 MF/10 HPF by the highest count method. Immunohistochemically, 13/13 tumors stained for cytokeratin (AE1/AE3). None were immunoreactive for polyclonal carcinoembryonic antigen (CEA), Leu-M1, or B72.3. One diffuse mesothelioma stained focally for Ber-EP4, and electron microscopy confirmed the mesothelial nature of this tumor. Nine patients died of tumor after postoperative intervals ranging from 1 month to 6 years. Eleven patients had received postoperative adjuvant intraperitoneal or systemic chemotherapy. One patient died with increased abdominal girth 8 years after operation and one course of intraperitoneal chemotherapy, though the role of mesothelioma in her death

Topics: Adenomatoid Tumor; Adult; Aged; Aged, 80 and over; Female; Fibroma; Follow-Up Studies; Genital Neoplasms, Female; Humans; Immunohistochemistry; Keratins; Mesothelioma; Mesothelioma, Cystic; Microscopy, Electron; Middle Aged; Mitosis; Peritoneal Neoplasms; Prognosis

Topics: Abdominal Neoplasms; Animals; Cattle; Cattle Diseases; Female; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Mesothelioma; Vimentin

High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful research tool for the analytical separation of cellular proteins. The qualitative and quantitative pattern of polypeptides synthesized by a cell represents its phenotype and thus defines characteristics such as the morphology and the biological behavior of the cell. By analyzing and comparing the protein patterns of different cells it is possible to recognize the cell type and also to identify the most typical features of these cells. In applied pathology it is often difficult to identify the tissue of origin and the stage or grade of a neoplasia by cellular morphology analyzed by classical or immunostaining procedures. The protein pattern itself is the most characteristic feature of a cell and should therefore contribute to the identification of the cell type. For this reason we separated protein fractions originating from different lung tumor cell lines using 2-D PAGE and we compared the resulting patterns on a multivariate statistical level using correspondence analysis (CA) and ascendant hierarchical clustering (AHC). The results indicate that (i) protein patterns are highly typical for cells and that (ii) the comparison of the protein patterns of a set of interesting cell types allows the identification of potentially new marker proteins. 2-D PAGE is thus a unique and powerful tool for molecular cytology or histopathology, unveiling the protein expression level of tissues or cells.

Topics: Adenocarcinoma; Cytoskeletal Proteins; Electrophoresis, Gel, Two-Dimensional; Humans; Immunoblotting; Keratins; Lung Neoplasms; Membrane Proteins; Mesothelioma; Multivariate Analysis; Neoplasm Proteins; Tumor Cells, Cultured; Vimentin

A panel of nine monoclonal antibodies was used to characterize human mesothelioma cell lines that we established from human malignant mesothelioma. The antigens detected were cytokeratin, vimentin, epithelial membrane antigen, carcinoembryonic antigen, Leu-M1 (CD15), desmin, factor VIII-related antigen (von Willebrand factor antigen), OV632, and ME1, a specific monoclonal antibody directed against human malignant mesothelioma. The technique used was the alkaline phosphatase anti-alkaline phosphatase method. All 30 cell lines, either epithelial, sarcomatous, or mixed, showed strong reactivity with cytokeratin and vimentin antibodies. None of the cell lines demonstrated any reactivity with carcinoembryonic antigen, Leu-M1, or factor VIII antibodies; moreover, all of 22 cell lines studied were positive for ME1 antibody and 10 of 12 cell lines studied were positive for OV632. Some interesting features were noted: only two of the 30 cell lines presented a weak positive staining with epithelial membrane antigen, and nine of 19 cell lines tested demonstrated a cytoplasmic staining pattern with desmin antibody. These results show that established human mesothelioma cell lines still possess the immunocytochemical characteristics that are basically consistent with the immunohistochemical features described in tumor tissues of malignant mesothelioma. These characteristics can be used to identify the mesothelioma cells grown from human malignant mesothelioma. Hence, the mesothelioma cell lines will provide a useful tool for the investigation of the cell biology of the tumor and the mechanisms of mesothelial cell transformation, as well as the in vitro evaluation of the effects of some drugs in order to develop new therapies for malignant mesothelioma.

Topics: Actins; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Differentiation, Myelomonocytic; Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Desmin; Factor VIII; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Mesothelioma; Middle Aged; Mucin-1; Tumor Cells, Cultured; Vimentin; von Willebrand Factor

Two cases of malignant peritoneal mesothelioma are reported. These tumors affected young women and displayed an unusual histopathologic pattern that closely simulated exuberant, ectopic decidual reaction or at least a malignant counterpart thereof. The importance of the differential diagnosis from decidual reaction is emphasized because decidua-like mesothelioma appears to be a highly malignant neoplasm. The cause of this lesion is unknown; and, considering the young age of the patients and the failure to demonstrate hormone receptors in the neoplastic cells, it is unlikely that asbestos exposure or hormonal imbalance played any role in the development of the disease.

Topics: Adult; Decidua; Diagnosis, Differential; Female; Humans; Keratins; Mesothelioma; Microscopy, Electron; Peritoneal Neoplasms; Phenotype

We have performed immunocytochemical, immunoelectron microscopy, Western blot, and culture techniques using monoclonal antibodies against cytokeratin, vimentin, and desmin on 17 benign and 20 malignant effusions of pleural and ascitic origin. Triple coexpression of these three antigens was observed in benign reactive mesothelial cells as well as in one case of mesothelioma. All metastatic adenocarcinoma cells were consistently negative to desmin and positive to cytokeratin and vimentin. Present results were helpful to distinguish reactive and malignant mesothelioma from metastatic carcinoma cells in effusions.

Topics: Adenocarcinoma; Ascitic Fluid; Blotting, Western; Cells, Cultured; Desmin; Diagnosis, Differential; Epithelium; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Models, Biological; Pleural Effusion; Vimentin

The distribution of keratin, vimentin, desmin, muscular actin, S100, specific neuron enolase, and chromogranin was studied by immunoperoxidase staining in mesothelium, malignant mesotheliomas, and pulmonary carcinomas. The mesothelial cells were positive for keratin and vimentin on all smears of pleural and ascitic effusions; most of them were also positive for desmin but rarely for enolase and S100. None was positive for muscular actin. Sixteen malignant mesotheliomas expressed vimentin and keratin; six were also positive for desmin, three for desmin and neural markers, and five for neural markers. In comparison, none of the pulmonary carcinomas was positive for these markers. Mesothelial cells are able to express markers of divergent differentiation. Mesotheliomas also have such markers that are present in other malignant tumors and, in particular, in intra-abdominal desmoplastic small cell tumors with divergent differentiation. This entity and mesotheliomas probably originate from the same cell. Moreover, desmin, found in 56% of malignant mesotheliomas but absent in pulmonary carcinomas, may be useful in the differential diagnosis of these tumors.

Topics: Actins; Adult; Aged; Chromogranins; Desmin; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Nerve Tissue Proteins; Phosphopyruvate Hydratase; Pleural Neoplasms; Vimentin

We used RNA-RNA in situ hybridization to study expression of the human CC10 gene in morphologically normal and atypical areas of 32 non-neoplastic lung specimens resected from 26 non-small cell lung cancer patients. We scored strong, moderate or weak levels of CC10 mRNA expression in 3 distinct lung compartments. In morphologically normal lungs, strong and moderate levels of CC10 mRNA were observed in bronchioli and bronchi, respectively, but the expression was rarely observed in the alveolar region. Distinct alterations in CC10 mRNA expression were noted in specific histologic abnormalities within bronchi and the alveolar region. CC10 hybridization signal decreased markedly in bronchi containing diffuse goblet cell hyperplasia or squamous metaplasia, while CC10 mRNA expression remained unchanged in bronchi with basal cell hyperplasia or focal goblet cell hyperplasia. Bronchiolar CC10 mRNA levels remained unchanged in sections containing abnormalities elsewhere. Interestingly, in alveoli with bronchiolization of the alveoli, high levels of CC10 mRNA were observed. These regions also contained strongly stained keratin 14-positive cells, which may indicate a concurrent metaplastic process. In lungs with morphologic atypias, no correlation was found between abnormalities detected in bronchi and alveoli from the same lung. A comparison of mRNA expression and clinicopathologic features demonstrated that the amount of histologic abnormalities increased with smoking history (pack years); however, no correlation between CC10 mRNA expression and sex, age or smoking history was found.

Topics: Age Factors; Carcinoma, Non-Small-Cell Lung; Female; Gene Expression; Humans; In Situ Hybridization; Keratins; Lung Neoplasms; Male; Mesothelioma; Proteins; RNA, Messenger; Sex Factors; Uteroglobin

Topics: Alcian Blue; Animals; Cricetinae; Hyaluronoglucosaminidase; Immunohistochemistry; Keratins; Male; Mesocricetus; Mesothelioma; Periodic Acid-Schiff Reaction; Peritoneal Neoplasms; Rodent Diseases; Staining and Labeling; Vimentin

The localized fibrous tumors of the pleura are rare neoplasms, also known as "benign pleural fibromas" or "localized mesotheliomas", but those names are inaccurate. The tumors are composed of undifferentiated mesenchymal cells, intermediate and differentiated fibroblasts and collagenous interstitial tissue. Their origin is normally the submesothelial layer of the visceral pleura. Mesothelial differentiation is not present. The grading of malignancy doesn't correlate with final outcome, adequacy of surgical excision being the most important factor. This neoplasm may recur but retain its basical histologic features. The positive results for vimentin and negative results for cytokeratin antibodies help to distinguish the localized fibrous tumors from the mesothelioma. We present too cases and their diagnostic possibilities.

Topics: Adult; Biomarkers, Tumor; Diagnosis, Differential; Female; Fibroma; Humans; Keratins; Mesothelioma; Middle Aged; Pleura; Pleural Neoplasms; Vimentin

Immunostaining for cytokeratin has a well-established diagnostic application in distinguishing sarcomatous mesotheliomas from sarcomas based on the premise that cytokeratin expression is common in mesotheliomas but very rare in sarcomas. However, the frequency of cytokeratin detection is highly dependent on the choice of antibody. The aim of this study was to examine the distribution of simple cytokeratins and stratified cytokeratins in 45 mesotheliomas of various types and to assess the diagnostic utility of a simple cytokeratin antibody, a stratified cytokeratin antibody, and a broad spectrum cytokeratin antibody with the aim of establishing the superiority of one for routine diagnostic use. Particular attention was paid to the potential utility of these antibodies in biopsy specimens. The broad spectrum cytokeratin antibody performed better than both the simple cytokeratin antibody (paired t-test: P < 0.01) and the stratified cytokeratin antibody (P < 0.01) as a diagnostic marker of mesothelioma and should be used in preference to the other two antibodies, particularly when considering small biopsy specimens.

Topics: Antibodies; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Mesothelioma; Sarcoma

Topics: Humans; Immunohistochemistry; Keratins; Mesothelioma

The karyotypic evolution was evaluated in cells from recurring pleural effusions in a patient previously exposed to asbestos. Pleural malignant mesothelioma (MM) was diagnosed 4 years after the first cytogenetic examination. The primary cytogenetic changes consisted of loss of chromosomes 1p,14,21, Y, both 22, and derivative chromosomes involving 1, 2, and 14. The modal chromosome number was 44. Sixty-seven percent of the cells had a normal karyotype. After 4 years of spontaneous remission, only 6% of the cells had a normal karyotype, 42% had the same karyotypic changes as found previously, whereas 52% had additional derivative chromosomes involving chromosomes 1, 3, 5, 7, 8, and 12, trisomy 7, 7p, and 11, and partial or whole monosomy 3, 8, and 9. The chromosomal changes are in agreement with the main findings in previous reports. The karyotype remained quite stable for 7 months in vitro. After 23 months in culture, all the cells were near-triploid. Cells established in culture were cytokeratin positive. All derivative and marker chromosomes identified in the cultured cells had previously been observed in direct preparations from the pleural effusions. We conclude that chromosomes 1, 14, 21, and 22 may be involved in the preclinical stage of development of asbestos-induced mesothelioma, whereas the later chromosomal changes may be related to progression of the tumor.

Topics: Aged; Animals; Chromosome Aberrations; Chromosome Banding; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Karyotyping; Keratins; Male; Mesothelioma; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Pleural Effusion, Malignant; Polyploidy; Tumor Cells, Cultured

In this study we examined intermediate filament expression in 45 formalin-fixed mesotheliomas. Immunostaining for cytokeratin was found in 86%, for vimentin in 71%, and for desmin in 4%; none stained for glial fibrillary acidic protein or neurofilament. The two biphasic mesotheliomas which expressed desmin also expressed smooth muscle actin but were negative for myoglobin. This, together with the ultrastructural findings, was taken as unequivocal evidence of a leiomyoid form of mesothelioma which might easily be confused with leiomyosarcoma. Both of these tumours co-expressed cytokeratin, exemplifying the value of cytokeratin immunostaining in the distinction between mesothelioma and sarcoma. Consistent non-expression of glial fibrillary acidic protein in mesotheliomas may help to distinguish them from nerve sheath tumours.

Topics: Desmin; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Mesothelioma; Neurofilament Proteins; Vimentin

Routine paraffin-embedded sections from synovial sarcomas in 70 patients were stained immunohistochemically with monoclonal anti-cytokeratin antibody and serum against mesothelial cells. Positive reactions occurred in the epithelioid cells of biphasic tumors only. On the ground of the reaction with anti-mesothelial serum a hypothetical scheme of cell differentiation in synovial sarcoma was set up.

Topics: Antibodies, Monoclonal; Cell Differentiation; Diagnosis, Differential; Epithelium; Humans; Immune Sera; Immunohistochemistry; Keratins; Mesothelioma; Paraffin Embedding; Sarcoma, Synovial; Soft Tissue Neoplasms; Staining and Labeling

Primary tumors of the peritoneum are rare. Histological differentiation between papillary mesotheliomas, primary ovarian tumors, borderline tumors of the ovary with peritoneal deposits and primary peritoneal carcinoma may be difficult. The expression of vimentin, keratin, pankeratin, CEA, CA125, CA19-9, S100, B72.3 and BerEP4 was therefore investigated in twelve women with primary malignant peritoneal tumors, twelve women with pleural mesothelioma, eight women with serous ovarian carcinoma and four men with peritoneal mesothelioma. The marker pattern we used was no help in differentiating between metastatic ovarian carcinoma and primary peritoneal carcinomatosis. A combination of the markers S100, B72.3 and BerEP4 helped the distinction between mesotheliomas and the other malignancies. If two or all three markers are detectable, primary peritoneal carcinomatosis or metastatic ovarian carcinoma is the possible diagnosis. If none of the three markers are found, a diagnosis of mesothelioma is highly probable.

Topics: Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms

Topics: Animals; Dog Diseases; Dogs; Heart Neoplasms; Immunohistochemistry; Keratins; Male; Mesothelioma; Microscopy, Electron; Pericardium; Vimentin

Two cases of malignant pleural tumor producing human chorionic gonadotropin, one confirmed at surgery and autopsy and the other by biopsy, are reported. Both of the patients had bilateral gynecomastia with high levels of serum human chorionic gonadotropin. The first patient underwent panpleuropneumonectomy because of diffuse malignant pleural tumor, but died five months later due to recurrent disease. The histological diagnosis was diffuse, malignant, monophasic mesothelioma of the epithelial type. Immunostaining for alpha-, beta-human chorionic gonadotropin and human placental lactogen was positive in syncytiotrophoblast-like cells. The second patient had diffuse pleural tumor with massive effusion. A pleural biopsy specimen showed diffuse proliferation of epithelioid large cells. Immunostaining for alpha, beta-human chorionic gonadotropin and human placental lactogen was positive in mono- and multinucleated bizarre giant cells mimicking trophoblasts. A diagnosis of malignant mesothelioma with trophoblastic differentiation seemed most likely in both cases in view of the clinical and pathological findings. In both cases, results of mucin histochemistry and various immunohistochemical stains for antigens or with antibodies were consistent with diagnosis of mesothelioma except in a few cells in the choriocarcinomatous portion. This may be the first report describing human chorionic gonadotropin-producing malignant mesotheliomas of the pleura.

Topics: Adult; Autopsy; Biopsy; Chorionic Gonadotropin; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Mesothelioma; Middle Aged; Mucin-1; Pleural Neoplasms; Tomography, X-Ray Computed; Vimentin

A panel of seven monoclonal antibodies including anti-vimentin, anti-keratin markers AE1/AE3 and EAB902, human milk fat globule (HMFG-2), B72.3, anti-carcinoembryonic antigen (CEA), and anti-Leu-M1 were used for an immunoperoxidase staining assay to determine their value in the differentiation of pleural mesothelioma from lung adenocarcinoma. Anti-vimentin positively identified 86% of the mesotheliomas and none of the adenocarcinomas. AE1/AE3, EAB902, and B72.3 reacted with a high percentage of both mesothelioma and adenocarcinoma specimens. With HMFG-2, both membrane and cytoplasmic staining was observed in 92% of the adenocarcinomas and in 14% of the mesotheliomas, whereas 26% of the mesotheliomas only exhibited membrane staining. Eighty percent of the adenocarcinomas and 8% of the mesothelioma tissues stained with anti-Leu-M1. Anti-CEA did not react with any of the 50 mesotheliomas tested but did react with 95% of the lung adenocarcinomas tested. From this study, it was concluded that anti-CEA and anti-Leu-M1 were the most effective of the seven tumor markers evaluated; and that 100% of the pleural mesothelioma tissues could be correctly differentiated from lung adenocarcinomas using a panel consisting of anti-vimentin, HMFG-2, anti-CEA and anti-Leu-M1 monoclonal antibodies.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Carcinoembryonic Antigen; Diagnosis, Differential; Glycoproteins; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelioma; Mucin-1; Pleural Neoplasms; Vimentin

Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with exposure to asbestos. Studies of this tumour have been limited by a paucity of well-characterized human MM cell lines. In this study, 5 human MM cell lines were established from pleural effusions of patients with this malignancy. All 5 patients were males with known crocidolite asbestos exposure, who had received no treatment for their disease and in whom the diagnosis was confirmed by cytology, histology and electron microscopy (EM). These lines have been in culture from 11 to 25 months, and all of them for more than 18 passages. The appearance of the cells in culture was extremely varied; in 3 of the lines they were spindle-shaped with few vacuoles (JU77, LO68 and ONE58); in 1 line they had a thick, stellate shape with vacuoles (NO36) and in 1 they were very pleomorphic in both shape and size with irregular membranes and numerous vacuoles [DeH128 (M)]. Upon reaching confluence, cells in 3 of the 5 lines assumed the cobblestone-like pattern characteristic of epithelial-type cells, whereas in the other 2 (LO68 and ONE58) they remained spindle-shaped. All 5 lines demonstrated a loss of contact inhibition (i.e., piling) at confluence. Minimum doubling times varied significantly from 18 hr (JU77) to more than 30 hr [DeH128 (M)]. Cytological examination showed characteristic mesothelial/mesothelioma morphology, and epithelial membrane antigen (EMA) and cytokeratin were demonstrated in cells from all 5 lines. These cells lacked CEA and epithelial mucin. The presence of cell junctions, glycogen and numerous long, thin, branching microvilli was readily demonstrable by EM. All lines had abnormal karyotypes, with the modal chromosome number varying from 40 to 80. Variable chromosome numbers, numerous structural rearrangements and unrecognizable marker chromosomes were readily observed; however, the only consistent change seen was del 6q21 in 4 of the 5 lines. The establishment of these 5 cultured human MM cell lines now provides an opportunity for comparative study of several aspects of the biology of MM in vitro as well as screening new treatment modalities.

Topics: Adult; Asbestos; Carcinoembryonic Antigen; Cell Division; Cytoplasm; Glycogen; Humans; Karyotyping; Keratins; Male; Membrane Glycoproteins; Mesothelioma; Microscopy, Electron; Middle Aged; Mucin-1; Pleural Effusion; Polymorphism, Restriction Fragment Length; Tumor Cells, Cultured; Vacuoles

Monoclonal anticarcinoembryonic antigen (antiCEA), human milk factor globulin (HMFG2), and antikeratin antibodies were assessed for their value in the differential diagnosis of pleural mesothelioma (53 cases) and carcinoma of the lung (60 cases) in material from necropsies. In 40 of the cases pleural biopsies were also studied in the same manner. AntiCEA was found to be the best discriminating antibody for most types of mesothelioma; HMFG2 was slightly less valuable but a useful additional tool. Antikeratin was the least useful. For both antiCEA and HMFG2 antibodies, however, the proportion of carcinomas staining was smaller than in previous studies and this, combined with the positive staining of some mesotheliomas, reduces the value of the reactions in the individual case. Medical panels adjudicating compensation claims should not use these reactions as the sole criteria in deciding the origin of the tumours in these cases.

Topics: Antigens, Neoplasm; Autoantibodies; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelioma; Mucin-1; Occupational Diseases; Pleural Neoplasms

An autopsy case of diffuse malignant peritoneal mesothelioma in a young woman who showed a high serum level of CA125 is reported. Autopsy revealed extensive tumor involvement of the visceral and parietal peritoneum. The liver, spleen and other abdominal viscera were encased by tumor nodules. Histologically, the polygonal tumor cells were arranged mostly in a sheet-like fashion with a few tubular or papillary forms. No PAS reaction-positive mucin was recognized, but there was a strongly positive colloidal iron reaction. The colloidal iron positivity was effaced after combined treatment with hyaluronidase and sialidase. Immunohistochemically the tumor cells showed strongly positive reactions for CA125, epithelial membrane antigen (EMA) and cytokeratin, weak positivity for carcinoembryonic antigen (CEA) and focal positivity for vimentin. Ultrastructurally, the most characteristic feature was the expression of numerous long microvilli projecting from the tumor cell surfaces and abundant long desmosomes between the tumor cells. We consider that pretreatment using a combination of hyaluronidase and sialidase might be useful for the diagnosis of malignant mesothelioma. CA125 staining should be performed routinely in cases where this tumor is suspected.

Topics: Adolescent; Antigens, Tumor-Associated, Carbohydrate; Desmosomes; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mesothelioma; Microvilli; Mucin-1; Peritoneal Neoplasms; Vimentin

Immunohistochemical study was carried out in a case of adenomatoid tumor of the uterine corpus. The patient was a 35-year-old female. The tumor showed classical histochemical and immunohistochemical findings of mesothelioma, i.e., presence of hyaluronic acid on the cellular surface and cytokeratin in the cytoplasm. In addition, the tumor showed positive reaction to anti-vimentin. Furthermore, absence of Ber-Ep4 supports mesothelial origin of this tumor. EMA reaction was reported only in one case in the literature. The result was negative as in our case. Therefore, it was suggested that at least some of the adenomatoid tumor were negative for EMA as in malignant mesothelioma, although this tumor was benign. Therefore, it was suggested that loss of EMA in mesothelial tumor was not always related to anaplastic change.

Topics: Adenoma; Adult; Female; Humans; Hyaluronic Acid; Immunohistochemistry; Keratins; Mesothelioma; Uterine Neoplasms; Vimentin

The visceral pleura of 8 lung tissue specimens with non-tumorous pleural lesions and of 10 specimens with secondary pleural infiltration of different primary tumours were tested by avidin-biotin-method with the following antibodies: anti-keratin KL1, anti-vimentin V9, anti-CEA (BMA 130c), HEA 125, Leu M1, HMFG 2 and anti-collagen type IV. In all cases anti-keratin positive subserosal cells could be proved. Activated mesothelial cells expressed vimentin additionally to keratin. The antibodies Leu M1, HEA 125 and BMA 130c (against CEA) showed no reaction in subserosal and mesothelial cells. With the antibody HMFG 2, however, a weak reaction could be observed. A distinction between reactive and neoplastic pleural lesions is not possible by using these antibodies. The antibodies LeuM1, HEA 125 and BMA 130c can be helpful for differential diagnosis in single cases with pleural carcinosis. The antibody against collagen type IV demonstrates newly developed basal membrane structures in areas with proliferating subserosal cells. Considering our results the entity of mesothelium and submesothelium is discussed with regard to the histogenetical aspect of mesothelioma.

Topics: Antibodies, Monoclonal; Carcinoembryonic Antigen; Collagen; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleural Neoplasms; Pleurisy; Vimentin

The histogenesis of localized fibrous tumor of the pleura (LFTP) is controversial. We studied 12 LFTP's by light microscopy; by immunohistochemical staining for cytokeratin (CK), vimentin, muscle-specific actin, desmin, S-100 protein, epithelial membrane antigen (EMA) and factor VIII; by electron microscopy in 6 tumors; and by lung digestion for asbestos bodies in 4 cases. Three histologic patterns occurred in combination: 1) collagenous, 2) cellular and 3) hypocellular/myxoid. Hemangiopericytoma-like foci were prominent in the cellular areas of 9 tumors. Unusual features included diffuse small cells in 3 tumors, microcystic foci in 2, macrocystic areas in 5 and tumor giant cells in 4 tumors. Neoplastic cells in all patterns stained positively for vimentin and actin in 9 and 4 tumors, respectively, and were negative for all other markers. CK and EMA were identified in mesothelial and epithelial invaginations only. Ultrastructurally, neoplastic cells demonstrated intercellular junctions, intermediate or thin filaments, dense bodies and rough endoplasmic reticulum. Basal lamina was focally present in 5 tumors, while tonofilaments, desmosomes and short microvilli were observed in one case. Our results support the conclusion that LFTP is a neoplasm of the multipotential subserosal cell, and usually expresses mesenchymal (fibroblastic/myofibroblastic) differentiation. Coexpression of mesothelial features is rare. Lung asbestos body quantitation in 4 patients suggests that there is no association between LFTP and asbestos exposure.

Topics: Actins; Adult; Aged; Asbestos; Cell Transformation, Neoplastic; Desmin; Factor VIII; Female; Humans; Immunohistochemistry; Keratins; Lung; Lung Diseases; Male; Membrane Glycoproteins; Mesoderm; Mesothelioma; Microscopy, Electron; Middle Aged; Mucin-1; Pleural Neoplasms; Vimentin

The distinction between serous neoplasms of the peritoneum in women and conventional mesothelioma can be difficult. In order to determine any significant immunohistochemical differences, formalin-fixed, paraffin-embedded sections of 10 peritoneal serous tumors (PST), 10 ovarian serous tumors (OST), and 10 epithelial mesotheliomas were evaluated with a panel of 10 antibodies directed against carcinoembryonic antigen (CEA: polyclonal, monoclonal), high molecular weight keratin (34 beta E12), low molecular weight keratin (35 beta H11), Leu-M1, TAG-72 (monoclonal antibody B72.3), human milk fat globulin (HMFG-2), vimentin, placental alkaline phosphatase (PLAP), and S-100 protein. The antibodies CEA, Leu-M1, and B72.3 had the most discriminatory value in differentiating serous tumors from mesothelioma. Eighty-five percent of PSTs and OSTs (17 of 20) were positive with CEA, Leu-M1, and/or B72.3. None of the mesotheliomas stained for CEA or Leu-M1; three mesotheliomas had very focal positivity with B72.3 (1% or less). Vimentin, PLAP, HMGF-2, keratin, and S-100 had no significant discriminatory value. Epithelial mucin was present in 80% of serous tumors, while the mesotheliomas lacked epithelial mucin. Leu-M1, CEA, and/or B72.3 positivity in a peritoneal tumor supports a diagnosis of serous tumor. However, since some PST do not stain for any of the three antibodies and the focal nature of positive reactions in some cases may be difficult to interpret, exclusion of mesotheliomas is enhanced by the use of mucin stains.

Topics: Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antibodies; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Diagnosis, Differential; Female; Gene Expression; Glycoproteins; GPI-Linked Proteins; Humans; Isoenzymes; Keratins; Membrane Glycoproteins; Mesothelioma; Middle Aged; Mucin-1; Mucins; Ovarian Neoplasms; Peritoneal Neoplasms; Pleural Neoplasms; S100 Proteins; Vimentin

Filed formalin-fixed paraffin blocks of 128 cases of epithelial neoplasms were selected for immunohistochemical study of keratin and vimentin expression. The results showed that 35.1% (45/128) of different carcinomas expressed vimentin. The immuno-positivity of vimentin in thyroid carcinomas, ovarian carcinomas, prostatic adenocarcinomas, pulmonary carcinomas and malignant mesotheliomas were 81.8%, 42.8%, 66.7%, 30.5% and 53.4%, respectively. Carcinomas of breast, kidneys, salivary glands, adrenal glands and nasopharyngeal carcinomas also showed various degrees of positive reaction. The results suggest that an immunohistochemical positive vimentin reaction does not exclude histopathological diagnosis of carcinomas. The significance and noticeable aspects of immunohistochemical methods in histopathological diagnosis are also discussed.

Topics: Carcinoma, Squamous Cell; Female; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Male; Mesothelioma; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prostatic Neoplasms; Thyroid Neoplasms; Vimentin

Three cases of peritoneal cystic mesothelioma are reported. All patients were women who had undergone previous abdominal surgery for unrelated conditions. Tumors consisted of solitary and multiple cystic masses involving the abdominal and pelvic peritoneum. The cysts focally infiltrated the muscularis externa of the small intestine in case 1, the outer muscular layer of the uterus in case 2, and the omental tissue in case 3. These findings give morphologic support to the borderline clinical behavior of this tumor that often recurs and support the hypothesis that previous surgery may play a role in its pathogenesis.

Topics: Abdomen; Adult; Carcinoembryonic Antigen; Factor VIII; Female; Humans; Immunohistochemistry; Keratins; Mesothelioma; Middle Aged; Peritoneal Neoplasms; Vimentin

Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Cells, Cultured; Diagnosis, Differential; Epithelial Cells; Epithelium; Histocytochemistry; Humans; Keratins; Mesothelioma; Microscopy, Electron, Scanning; Serous Membrane

An immunohistochemical study of reactive pleural lesions, adenocarcinomas and mesotheliomas using carcinoembryonic antigen (CEA), cytokeratin and vimentin was carried out. All the specimens were obtained at surgery except for 11 mesotheliomas found at necropsy. Vimentin was positive in 23 of 27 mesotheliomas and negative in all the adenocarcinomas and 4 of 17 reactive mesothelial lesions. Conversely, CEA was positive in all the adenocarcinomas but negative in all mesotheliomas. Immunoreactivity for vimentin was seen in only 3 of 11 post-mortem mesotheliomas. Vimentin is a useful adjunct to the tissue diagnosis of mesothelioma especially when CEA is negative and cytokeratin positive. Its use appears largely confirmed to well fixed surgically derived tissues.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleura; Pleural Neoplasms; Vimentin

A case of solitary fibrous tumor of the pleura (SFT) is presented. The histogenesis of this uncommon tumor is debated with most investigators favouring origin in submesothelial fibroblasts. Part of the evidence supporting this has been the persistent negativity of the tumor cells for cytokeratin--a feature militating against origin in mesothelial-lining cells. Our case shows unequivocal focal cytokeratin positivity in tumor cells; we feel that although this indicates mesothelial differentiation it does not militate against origin in submesothelial fibroblasts since, in reactive conditions, these are capable of mesothelial differentiation including expression of cytokeratin. Indeed, it reinforces the hypothesis that SFT is of submesothelial origin. Solitary fibrous tumors can be cellular and atypical. The reactivity of the tumor with cytokeratin, albeit rarely, should be considered in differentiating SFT from sarcomatoid mesothelioma.

Topics: Aged; Aged, 80 and over; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Mesothelioma; Pleural Neoplasms

Four cases of a biphasic mediastinal tumor histologically identical to synovial sarcoma of soft tissue were observed. The tumors presented as solitary mediastinal masses. Although the tumors were frequently adherent to adjacent pleura or pericardium, none appeared to be arising from a mesothelial surface. All cases were composed of an intimate admixture of keratin-positive epithelial cells and vimentin-positive spindle cells with areas of transition, hyalinization, and calcification. Follow-up was available on three patients, who died of their disease 10 months, 14 months, and 4 years after diagnosis, respectively. Although synovial sarcoma usually occurs in deep soft tissues near joints in the extremities, it has been reported in locations removed from synovial, tendon sheath, and bursal structures. This report adds a previously unrecognized location for synovial sarcoma, the mediastinum. Occurrence in this location further supports an origin from pluripotential mesenchyme as opposed to synovium. The differential diagnosis includes mesothelioma, thymoma, germ cell tumors, malignant peripheral nerve sheath tumor with glandular differentiation, and metastatic carcinoma.

Topics: Adult; Aged; Diagnosis, Differential; Humans; Keratins; Male; Mediastinal Neoplasms; Mesothelioma; Middle Aged; Sarcoma, Synovial; Thymoma; Vimentin

In order to evaluate adjunctive histologic methods for separating mesothelioma (MM) and serous adenocarcinoma (SC), we studied 28 and 46 respective cases histochemically and immunohistochemically. Ten serous adenocarcinomas arose primarily in extraovarian sites within the abdomen. Diagnoses in each case were established retrospectively by a combination of electron microscopy and clinicopathologic correlation. A panel of antibodies to cytokeratin (CK), epithelial membrane antigen (EMA), B72.3, placental alkaline phosphatase (PLAP), S-100 protein, carcinoembryonic antigen (CEA), Leu M1, CA-125, and amylase (AM) was applied to paraffin sections of each case. Serous carcinoma was reactive for neutral mucins whereas mesothelioma was not; however, only 50% of adenocarcinoma cases stained in this manner. Peritoneal mesothelioma showed reactivity for CK (28 of 28 cases), EMA (24 of 28 cases), AM (five of 28 cases), CA-125 (four of 28 cases), and S-100 protein (three of 28 cases), but lacked B72.3, PLAP, and CEA. Three mesotheliomas expressed Leu M1, but in an extremely focal distribution. Serous carcinoma reacted for CK (46 of 46 cases), EMA (46 of 46 cases), CA-125 (42 of 46 cases), S-100 protein (40 of 46 cases), Leu M1 (34 of 46 cases; with diffuse staining), B72.3 (33 of 46 cases), PLAP (29 of 46 cases), AM (15 of 46 cases), and CEA (six of 46 cases). Two profiles (S-100 + B72.3; S-100 + PLAP) were seen in 41 of 46 serous adenocarcinoma cases but were absent in all mesotheliomas. Hence, these combinations of determinants are effective in separating such neoplasms diagnostically. Moreover, diffuse reactivity for Leu M1, B72.3, PLAP, or CEA in papillary peritoneal neoplasms appears to exclude the possibility of mesothelioma; however, focal Leu M1 reactivity may indeed be seen in mesothelioma. Although CA-125 is a sensitive marker for serous carcinoma, it is not effective in distinguishing it from mesothelioma.

Topics: Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Basement Membrane; Cell Nucleus; Cystadenocarcinoma; Cytoplasm; Female; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Peritoneal Neoplasms; S100 Proteins

A case of localized fibrous tumor (LFT) (localized fibrous mesothelioma) of the liver in an 83-year-old woman is presented. The tumor was 15 x 9 x 8 cm and was confined to the left lateral segment of the liver. Occasional mitotic figures (MF) (2 to 3 per 50 high-power fields [HPF]) were present. Strong, diffuse vimentin positivity was demonstrated by immunohistochemistry. Immunoreactivity for cytokeratins (AE1-3), epithelial membrane antigen (EMA), desmin, and desmosomal proteins (desmoplakin I + II) was absent. Electron microscopic examination showed a mesenchymal appearance of the majority of neoplastic cells, with a few ultrastructural features suggestive of mesothelial differentiation. These findings supported a submesothelial origin of the tumor. After a partial hepatectomy with total gross and microscopic removal of the tumor, the patient was alive without recurrence at 2 years, 5 months later. A review of the English literature showed six additional cases that are probably similar. Currently, all tumors have been clinically benign, although follow-up information has been limited.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Cell Nucleus; Cytoplasm; Cytoskeletal Proteins; Desmin; Desmoplakins; Female; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Membrane Glycoproteins; Mesothelioma; Microscopy, Electron; Mucin-1; Tomography, X-Ray Computed; Vimentin

Seventeen human malignant mesothelioma cell lines were isolated from 61 samples (46 effusions, 9 biopsies and 6 tumors obtained at autopsy) collected from patients with a confirmed malignant mesothelioma. The method used is given in detail. Cytogenetic analysis of growing cultures is the best indicator to determine whether the observed proliferation concerns malignant or normal mesothelial cells. The addition of epidermal growth factor (EGF) and hydrocortisone (HC), or EGF alone, to the culture medium increases the chances of successful isolation of a malignant mesothelioma cell line.

Topics: Animals; Chromosome Aberrations; Epidermal Growth Factor; Female; Humans; Hydrocortisone; Keratins; Mesothelioma; Mice; Mice, Inbred BALB C; Proto-Oncogenes; Tumor Cells, Cultured

Three cases of epididymal adenomatoid tumor are presented. The adenoid compositions of the tumors lined by epithelial cells showed a canalicular pattern with large vascular spaces, tubular pattern with glandlike regions or plexiform pattern with connective tissue strands. Immunohistochemistry demonstrated positive cytoplasmic staining for keratin, but negative for carcinoembryonic antigen and factor VIII-related antigen in each neoplastic tissue. These findings support the mesothelial origin of the epididymal adenomatoid tumors.

Topics: Adult; Carcinoembryonic Antigen; Epididymis; Humans; Keratins; Male; Mesothelioma; Middle Aged; Teratoma; Testicular Neoplasms; von Willebrand Factor

Localized fibrous tumor of the serosal cavities (localized fibrous mesothelioma) is a generally benign spindle cell neoplasm of uncertain histogenesis. Fourteen histologically similar primary tumors from different mesothelium-lined sites (11 pleural and 1 each in the pericardium, peritoneal cavity, and pouch of Douglas) and 2 recurrences of those tumors (pericardium and pouch of Douglas) were examined histopathologically and by flow cytometry to relate histologic features and DNA ploidy to biologic behavior (follow-up, 48-255 months among 13 patients). All 16 tumors (14 primaries and 2 recurrences) displayed diploid DNA pattern, and none of 13 patients died of disease (1 patient was lost to follow-up). To elucidate the histogenesis, seven primary tumors were examined for vimentin and keratin immunostaining and six primary tumors were assessed by electron microscopy. All cases exhibited spindle-fibroblastic cell proliferation with a prominent hemangiopericytic pattern. All cases so examined had positive results for vimentin and negative results for keratin. Ultrastructurally, the tumor cells showed mesenchymal-fibroblastic features. These results support a mesenchymal origin, most likely from submesothelial fibroblasts. Further, this neoplasm may recur but retain its basic histologic features, diploidy, and benign outcome.

Topics: Adult; Aged; DNA; Female; Flow Cytometry; Heart Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Microscopy, Electron; Middle Aged; Pericardium; Peritoneal Neoplasms; Pleural Neoplasms; Ploidies; Vimentin

A sizable proportion of pleural malignant mesotheliomas are sarcomatoid (22%) or biphasic (24%) and may need to be distinguished from other spindle cell neoplasms that occur as primary or metastatic tumors of the chest wall or lungs. To determine the utility of immunohistochemistry in the differentiation of sarcomatoid malignant mesotheliomas from other spindle cell neoplasms, the authors studied the immunostaining patterns of nine antibodies in four sarcomatoid mesotheliomas, one desmoplastic mesothelioma, two epithelial mesotheliomas, four spindle cell squamous carcinomas, and eight sarcomas of various differentiation. Three of the four sarcomatoid mesotheliomas and the desmoplastic mesothelioma had positive results for cytokeratin, which distinguishes them from sarcomas but not from spindle cell squamous carcinomas. The immunostaining pattern of 14 examples of benign spindle cell mesothelial proliferation was similar to that of the sarcomatoid mesotheliomas, which supports the theory that these tumors are mesothelial in origin. Although other antibodies occasionally may be helpful, depending on the differentiation of the sarcoma, cytokeratin immunostaining appears to be the best method to discriminate sarcomatoid mesotheliomas from sarcomas.

Topics: Aged; Cytoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Pleural Neoplasms; Vimentin

Tuberous sclerosis (Bourneville-Pringle phacomatosis) has been known to be associated with cardiac rhabdomyoma, but apparently never previously with primary pericardial mesothelioma. We present an autopsy case of this condition in a 59-year-old man, who had been diagnosed as having tuberous sclerosis in view of the presence of facial sebaceous adenoma, mental retardation, intracranial calcification, cerebral ventricular dilatation and renal tumor. During the clinical course, characterized by heart failure due to cardiac tamponade, cardiac sarcoma was diagnosed by imaging techniques. Autopsy revealed biphasic-type primary pericardial mesothelioma. As to the tuberous sclerosis, atypical giant cells in the tubers of the cerebral cortex and the lateral ventricular wall were found, which were considered to be derived from neurons rather than glial cells on the basis of staining with Bodian, Holzer, and antibodies against NSE, GFA and S-100 protein. In old tubers protruding into the lateral ventricles, fibrous glias were present with dense calcospherite deposits, coinciding with the CT findings. The renal tumors were angiomyolipomas, which were present bilaterally and showed partially infiltrative growth, but seemed to have a benign nature because of the lack of metastasis and atypism of the leiomyocytes.

Topics: Autopsy; Cerebellum; Glial Fibrillary Acidic Protein; Heart Neoplasms; Hemangioma; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Kidney; Kidney Neoplasms; Lipoma; Male; Membrane Glycoproteins; Mesothelioma; Middle Aged; Mucin-1; Pericardium; Phosphopyruvate Hydratase; S100 Proteins; Tuberous Sclerosis

In previous biochemical analyses, keratin 5 (Mr 58,000) has been detected in most mesotheliomas with epithelial component but not in pulmonary adenocarcinomas (Blobel et al., Am J Pathol 121: 235-247, 1985). In the present study, we have characterized a monoclonal antibody, AE14, as being selectively specific for keratin 5 (apart from the reactivity with certain hair proteins) as shown by immunoblotting of gel-electrophoretically separated proteins from various tissues. Immunohistochemical screening of a variety of normal human tissues, using immunoperoxidase microscopy on cryostat sections, revealed the binding of this antibody to the basal, immature cells of stratified squamous epithelia, to basal cells of pseudostratified epithelia, to some myoepithelial cells, thymic reticulum cells, certain pancreatic duct cells, as well as a variable subpopulation of mesothelial cells of the pleura and the peritoneum. In 12/13 epithelial and biphasic mesotheliomas of the pleura, heterogeneous but extended staining with antibody AE14 was seen whereas 21 pulmonary adenocarcinomas were negative or, in six of these cases, showed staining of only a few cells. Among carcinomas from other sites, colonic adenocarcinomas and renal cell carcinomas were negative whereas limited staining was found in some pancreatic adenocarcinomas. It is suggested that antibody AE14 may be useful, as a defined polypeptide-specific reagent, in the histologic distinction between mesotheliomas and most adenocarcinomas. Furthermore, the expression patterns of keratin 5 as detected by antibody AE14 in various normal and malignant epithelial tissues are discussed, particularly their relation to processes of squamous metaplasia and their indication of phenotypic tumor heterogeneity.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Diagnosis, Differential; Epithelium; Female; Hair; Humans; Immunoblotting; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Mesothelioma

A fibrous pseudotumor of the testis from a 46-year-old man was examined histologically and immunohistochemically. The tumor, situated in the tunica vaginalis, appeared as multiple round nodules up to 2 cm in diameter, and was composed largely of fibrous tissue with scanty inflammatory cell infiltration. Besides mesothelial cells covering part of the tumor, foci of piled-up cells were found among the fibrous tumor tissue. The cells in the foci were spindle and polygonal in shape, and contained oval nuclei. Immunohistochemically, these cells were positive for vimentin and keratin, but negative for CEA. Similar features have been found in pleural mesothelioma, supporting the concept that testicular fibrous pseudotumor could represent neoplastic growth of the mesothelium of the tunica vaginalis.

Topics: Fibroma; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Testicular Neoplasms; Vimentin

In order to differentiate between malignant pleural mesothelioma and adenocarcinoma of the lung, the glycoconjugate profiles of 6 reactive mesothelial lesions, 23 mesotheliomas (17 epithelial, 1 desmoplastic, 2 biphasic, and 3 fibrous types), and 28 well-differentiated pulmonary adenocarcinomas were evaluated with the use of 8 lectins in addition to anti-carcinoembryonic, anti-keratin and anti-epithelial membrane antigen. Formalin-fixed, paraffin-embedded tissues were stained with the avidin-biotin peroxidase complex method. Reactions of wheat germ (WGA) and peanut (PNA) agglutinin with neuraminidase treatment lectins were positive in 5 of 6 (83%) and 3 of 6 (50%) cases, respectively, in reactive mesothelial lesions. Thirteen of 23 (57%) malignant mesotheliomas of the pleura showed a positive reaction for WGA and PNA with neuraminidase treatment; other lectins were low-positive, below 9%. In contrast, pulmonary adenocarcinomas showed positive reactions in 27 of 28 cases (96%) for PNA, 26 of 28 (93%) for Ricinus communis (RCA-I), 25 of 28 (89%) for WGA, and 22 of 28 (79%) for succinylated WGA (SucWGA). The findings suggest that malignant pleural mesothelioma and pulmonary adenocarcinoma have consistent and distinct glycoconjugate profiles, and that stains for RCA-I and SucWGA may be useful for differential diagnosis.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Diagnosis, Differential; Histocytochemistry; Humans; Keratins; Lectins; Lung Neoplasms; Membrane Glycoproteins; Mesothelioma; Mucin-1; Pleural Neoplasms

To define the role of keratin protein immunohistochemistry in the pathologic diagnosis of the sarcomatoid type of diffuse malignant mesothelioma (DMM), we examined 30 DMM (16 pure sarcomatoid type and 14 mixed sarcomatoid-epithelial type) by an indirect immunoperoxidase technique using three commercially available antibodies to keratin proteins. The sarcomatoid (spindle-cell) areas of all 30 cases of sarcomatoid DMM were immunoreactive for keratin proteins. In 14 of 16 cases of sarcomatoid DMM, 50% or more of the tumor cells were reactive with one or more antibodies; however, polyclonal bovine muzzle and monoclonal AE1/AE3 antibodies were distinctly superior to polyclonal human callus keratin antibody in the detection of spindle tumor cells. In contrast with the staining patterns observed for DMM, 39 spindle-cell malignancies and tumor-like processes of 10 histogenetic types were unreactive with the three antibodies. Those spindle-cell tumors and reactive mesothelial proliferations that may enter into the differential diagnosis of sarcomatoid DMM are discussed. We conclude that keratin protein immunohistochemistry is a sensitive and highly useful method for the pathologic diagnosis of the sarcomatoid type of DMM and its distinction from other spindle-cell neoplasms.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Mesothelioma; Middle Aged

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

N-Propyl-N-nitrosourea is a strong leukemogen that induces myelogenic leukemia in Donryu rats and thymic lymphoma in F344 rats when administered in drinking water. In the present study, a single or multiple doses of PNU (total 500 mg/kg body weight) was given to young male and female F344 rats via a stomach tube. The results demonstrated that the percentage of tumor-bearing rats was 100% in all PNU-treated male groups, while that of the control group was 46%. Predominant tumors induced by PNU in male rats were lung adenoma/adenocarcinoma followed by peritoneal mesothelioma, and forestomach papilloma. In females, the tumor incidence of PNU-treated groups varied between 58% and 92% while that of the control group was 42%. Although pituitary tumor was the most frequent tumor in PNU-treated female rats, it was thought to be spontaneous since its incidence in each experimental group was not statistically different from that of the control group. Lung tumors and forestomach papillomas were also induced by PNU in female rats. No thymic lymphoma, however, was found in any of the PNU-treated groups of either sex. Lung tumors developed in almost all PNU-treated male rats and in about one-third of PNU-treated female rats. Mesothelioma was induced only in male rats, and its incidence depended on the treatment schedule. Induced mesotheliomas were extensively examined histologically, histochemically, immunohistochemically, and electron microscopically.

Topics: Animals; Female; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mesothelioma; Nitrosourea Compounds; Peritoneal Neoplasms; Rats; Rats, Inbred F344; Vimentin

We have established and characterized two mesothelioma cell lines, MS-1 and MS-2, in four attempts at long-term culture of these cells. Both MS-1 and MS-2 cells consistently express cytokeratin and vimentin, and both have long, slender microvilli. The cells that grew indefinitely (MS-1, MS-2) had a higher DNA index and a higher nucleus:cytoplasm ratio than did those cells that failed to grow (MS-3, MS-4). All mesothelioma cells, both in short- and in long-term culture, responded to phorbol ester induction by displaying morphological differentiation, such as an increase in the number of microvilli. The distribution of vimentin and cytokeratin in the cells, however, remained the same regardless of the growth pattern or the phorbol-ester treatment of the cells. We have used MS-1 cells to produce a monoclonal antibody (anti-MS) that reacts with mesothelioma cells, but rarely with reactive or normal mesothelial cells or with cells of normal tissues. The antibody does not induce the modulation of antigen, and it causes no direct or complement-mediated cytotoxicity of MS-1 or MS-2 cells. If a toxin or an isotope conjugate of the antibody is used, it may be valuable in the near future to test it for use in immunoimaging or immunotherapy.

Topics: Antibodies, Monoclonal; Antigen-Antibody Complex; Cell Line; Chromosome Banding; Humans; Immunohistochemistry; Keratins; Mesothelioma; Microscopy, Electron; Microscopy, Electron, Scanning; Pleural Neoplasms; Vimentin

We present a case of diffuse malignant peritoneal mesothelioma, initially misdiagnosed as benign. Electron microscopy and immunocytochemistry proved helpful diagnostically. Using monoclonal antibodies against cytokeratin and vimentin, we compared neoplastic with normal and reactive mesothelia and we found coexpression of these two intermediate filaments in the reactive and neoplastic mesothelial but not in the normal mesothelia, supporting the suggestion that surface mesothelial cells are derived from multipotential submesothelial cells.

Topics: Adolescent; Female; Humans; Keratins; Mesothelioma; Peritoneal Neoplasms; Vimentin

Topics: Biopsy; Carcinoembryonic Antigen; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleura; Pleural Neoplasms

Topics: Carcinoembryonic Antigen; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Mesothelioma; Peritoneal Neoplasms; Pleural Neoplasms; Vimentin

The immunohistochemical profile (i.e., carcinoembryonic antigen, keratin proteins, epithelial membrane antigen, human milk fat globule-derived antigen, and mucin) of paraffin-embedded cell blocks of 20 malignant effusions from patients with malignant mesothelioma was compared with that of 39 malignant effusions from patients with metastatic adenocarcinoma to determine whether these markers distinguished between these tumor types. Twenty-three adenocarcinomas (59 per cent) stained for mucin. Immunoreactivity for carcinoembryonic antigen (CEA) was observed in 28 adenocarcinomas (72 per cent). All were immunoreactive for keratin proteins, and 29 adenocarcinomas (74 per cent), including seven that were mucin and CEA negative and exhibited a "peripheral predominant" staining pattern for keratin proteins. By contrast, none of the mesotheliomas stained for mucin or for CEA, and, although all were immunoreactive for keratin proteins, none demonstrated a peripheral predominant pattern of staining. Epithelial membrane antigen and milk fat globule-derived antigen were identified in the majority of both mesotheliomas and adenocarcinomas. Neither staining intensity nor pattern of reactivity of these markers clearly distinguished the tumors. This study of cell blocks of serous effusions suggests that staining for mucin, immunoreactivity for carcinoembryonic antigen, and a peripheral predominant pattern of reactivity for keratin proteins represent highly characteristic markers of adenocarcinomas, which identify the majority of these tumors (38 of 39) and allow their distinction from malignant mesotheliomas.

Topics: Adenocarcinoma; Antigens; Carcinoembryonic Antigen; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Mesothelioma; Middle Aged; Mucin-1; Mucins; Pleural Effusion; Pleural Neoplasms

A panel of seven monoclonal antiepithelial antibodies of different specificities, including anticytokeratin, human milk fat globule membrane, C, and carcinoembryonic antigen (CEA) were used with the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique to determine their value in the differentiation between benign and malignant mesothelial cells and lung carcinoma in histological preparations. The anticytokeratin antibody reacted strongly with all cases of reactive mesothelium, mesothelioma, and lung carcinoma. Antibodies to human milk fat globule membrane and the Ca antigen stained mesothelioma and carcinoma and 43% of cases of reactive mesothelium. Staining for carcinoembryonic antigen was not detected in reactive mesothelium or mesothelioma, but was present in most of the lung carcinomas. CEA seemed to be the single most useful marker in distinguishing carcinoma from mesothelioma in that a positive reaction for CEA would indicate carcinoma rather than mesothelioma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Membrane Proteins; Mesothelioma; Mucin-1

The usefulness of tumor marker assay in pleural effusions for differential diagnosis is still debated. From the observation of common antigens on tissue polypeptide antigen (TPA) and keratins 8, 18 and 19 and vimentin, all substances contained in normal and neoplastic mesothelium, we felt it opportune to evaluate the use of TPA assay in 105 pleural effusions (46 benign and 59 malignant). The values were much higher than those found in blood. In hydrothorax the median value was 454 U/l (range, 59-1923), in exudative effusions 846 U/l (range, 258-4485), in metastatic pleural effusions 1277 U/l (range, 58-32352) and in mesotheliomas 7705 (range, 759-16000). The maximum value found in nonmalignant effusions was 4485 U/l; this value was taken as a cutoff level, so only 29.9% of the tumors were positive to the test. Our results showed this assay to be not very important for a differential diagnosis of malignant and nonmalignant pleural effusions. Nevertheless, the different TPA patterns in mesotheliomas (66.6% positive) and metastatic pleural effusions (15.9%) suggest that further studies are warranted.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Diagnosis, Differential; Female; Humans; Keratins; Male; Mesothelioma; Middle Aged; Neoplasm Proteins; Peptides; Pleural Diseases; Pleural Effusion; Pleural Neoplasms; Tissue Polypeptide Antigen; Vimentin

Sections of primary lung carcinomas, lung metastases, mesotheliomas, and lung metastases of some rare mesenchymal tumors were incubated with different cytokeratin (CK), vimentin, desmin, and tissue polypeptide antigen (TPA) antibodies and with antibodies reactive with different hormones (ACTH, PTH, alpha-HCG, Calcitonin CT), CEA, carcinoma-associated antigen (CA1), secretory component (SC), neuron-specific enolase (NSE), alpha-1-antitrypsin (alpha-1-AT), lysozyme (lyso), and S-100 protein (S 100). CK antibodies derived from a 49 kD (reactive with simple epithelia [SE]) and a 67 kD CK polypeptide fraction (reaction with complex epithelia [CE] were useful differentiation markers for the four major groups of lung carcinomas. In one half of small cell carcinomas a positive reaction with NSE antibodies was found. S 100 and SC were good markers for papillary and bronchioloalveolar adenocarcinomas, whereas CEA was less important because of its reactivity with different types of lung carcinomas. To discern clear cell carcinomas of lung and renal origin a positive reaction with vimentin antibodies (some renal but not lung types) and with CA1 (no renal but all lung types) seemed to be useful. All hormone antibodies were of no importance as markers for difficult differential diagnosis, because positive reactivities were found in cases from every major carcinoma group. In addition, a Ca2+-activated adenosine triphosphatase (ATPase) was found in mesotheliomas but not in papillary adenocarcinomas.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Desmin; Diagnosis, Differential; Histocytochemistry; Hormones; Humans; Immunologic Techniques; Keratins; Kidney Neoplasms; Lung Neoplasms; Mesothelioma; Muramidase; Neoplasm Metastasis; Peptides; Phosphopyruvate Hydratase; Pleural Neoplasms; S100 Proteins; Secretory Component; Tissue Polypeptide Antigen; Vimentin

Serosal tissues consist of a surface mesothelial layer and subsurface spindled connective tissue cells. Surface cells are decorated with antibodies to both low and high molecular weight cytokeratin whereas subserosal cells only express the intermediate filament vimentin. Serosal injury results in the proliferation of multipotential subserosal cells (MSC) which have the ultrastructural morphology of myofibroblasts and yet co-express low molecular weight cytokeratin and vimentin. These cells appear responsible for the re-establishment of surface mesothelium during which they acquire high molecular weight cytokeratin and loose vimentin. There are many parallels between reactive and neoplastic serosal tissues. Desmoplastic/sarcomatoid mesotheliomas resemble the MSC and co-express low molecular weight cytokeratin and vimentin and epithelial mesotheliomas resemble surface mesothelium and express both low and high molecular weight cytokeratin. The ability of normal serosal tissue to modulate its cell shape and intermediate filament expression helps understand the diversity of serosal tumors.

Topics: Antibodies; Antibodies, Neoplasm; Antigens, Neoplasm; Humans; Intermediate Filaments; Keratins; Mesothelioma; Microscopy, Electron; Models, Biological; Neoplasm Proteins; Serous Membrane; Vimentin; Wounds and Injuries

Pleural mesotheliomas and peripheral pulmonary adenocarcinomas were evaluated by immunohistochemistry at two institutions (Yale University School of Medicine and the City of Hope National Medical Center). Twenty-three mesotheliomas, 11 with ultrastructural verification, and 24 pulmonary adenocarcinomas were studied. Antikeratin, anticarcinoembryonic antigen, anti-human milk fat globule related antigen, MC-1, B72.3, and Leu M-1 antibodies were employed. The immunohistochemistry of each case prepared at one institution was reviewed at the other. As groups, the two tumor types were distinguishable using this antibody panel. Essentially, mesotheliomas were keratin positive only. The adenocarcinomas were positive for CEA, MFG, B72.3, and Leu M-1. However, there were some ambiguities presented by the immunohistochemistry. The higher molecular weight keratins were found in most but not all mesotheliomas and in only a few adenocarcinomas. Lower molecular weight keratins were positive not only in all the mesotheliomas, but also in nearly all the adenocarcinomas, but also in a tumor determined by electron microscopy to be mesothelioma. Preabsorption of CEA decreased the sensitivity for adenocarcinoma, but did not change the positivity of the putative mesothelioma. B72.3 and Leu M-1 were specific for adenocarcinoma, but were found in only half of them. The MFG was apparently specific for adenocarcinoma, but the findings were difficult to interpret. At the level of individual cases, greater sensitivity of separation can be achieved by combining the results of two or more antibodies, but the lack of a detectable specific antigen in mesothelioma continues to make some cases difficult to evaluate by immunohistochemistry alone.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Microscopy, Electron; Pleural Neoplasms

A mesothelial, endothelial and epithelial differentiation of the adenomatoid tumors is discussed in the literature. Aimed at this problem the cellular nature of 12 adenomatoid tumors was investigated by means of histochemical and immunohistochemical methods at light and electron microscopic level. In all these neoplasias prekeratin was demonstrated while factor VIII-associated antigen and myoglobin were lacking within the tumor cells. The ultrastructural picture of the tumor cells was similar to that of mesothelial cells; abundant intermediate filaments of the keratin type could be decorated by means of the protein A-gold technique in them. Furthermore hyaluronidase sensitive glycosaminoglycans but no sulfated and neutral mucoproteins were found. The results suggest a mesothelial nature of the tumor cells of adenomatoid tumors.

Topics: Antigens; Factor VIII; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Microscopy, Electron; Myoglobin; Protein Precursors; Terminology as Topic; von Willebrand Factor

In serous effusions the distinction between reactive mesothelial cells and malignant cells (especially adenocarcinoma cells and malignant mesothelial cells) is frequently a cause of diagnostic difficulty. The present paper describes the immunocytochemical staining of cells in 76 effusions from 71 patients with different malignancies. In 91% of the effusions obtained from patients with adenocarcinomas, the cells stained positive for anti-EMA, 94% for anti-CEA, 64% for anti-LeuM1-antigen and 75% for anti-keratins. In more than 90% of the cases the reactive mesothelial cells stained positive for anti-keratins, but not for anti-EMA, anti-CEA or anti-LeuM1-antigen. It is concluded that a panel of the antibodies against EMA, CEA, LeuM1-antigen and keratins is valuable in the distinction between adenocarcinoma cells, malignant mesothelial cells and reactive mesothelial cells in serous effusions.

Topics: Adenocarcinoma; Antibodies; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Ascitic Fluid; Carcinoembryonic Antigen; Histocompatibility Antigens; Humans; Keratins; Leukocyte Common Antigens; Membrane Proteins; Mesothelioma; Mucin-1; Pleural Effusion

The histological diagnosis of malignant mesothelioma of the pleura, especially the distinction from peripheral adenocarcinoma of the lung, may be difficult. The immunohistochemical reports previously published on this subject show diverging results mainly because a variety of antibodies and staining techniques have been used by the different authors. To obtain comparable and reproducible results standard techniques and commercialized antibodies should be applied in routine pathology. In order to investigate the value of immunohistochemistry for the separation of the two entities formalin fixed and paraffin embedded blocks of 47 mesotheliomas and 22 adenocarcinomas were investigated with the PAP technique and commercially available antibodies to carcino-embryonic antigen (CEA), keratin, vimentin, epithelial membrane antigen (EMA), pregnancy specific antigen (SP1), S-100 protein and monoclonal antibody lu-5 (mAB lu-5). CEA positivity was found in all 22 adenocarcinomas examined, but only 2/47 (4%) of all mesotheliomas showed a positive result. SP1 was positive in 13/22 (59%) of the adenocarcinomas, whereas only 3/47 (6%) mesotheliomas were positive for this marker. No significant difference in the rate of positive cases in the adenocarcinoma and mesothelioma group could be found with the other above mentioned antigens. The results of our study indicate that especially CEA, but also SP1 are valuable markers in the diagnosis of malignant mesothelioma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoembryonic Antigen; Diagnosis, Differential; Histocytochemistry; Humans; Immunochemistry; Keratins; Lung Neoplasms; Membrane Proteins; Mesothelioma; Mucin-1; Pleural Diseases; Pregnancy-Specific beta 1-Glycoproteins; Vimentin

Abdominal diffuse malignant mesotheliomas develop in rats administered asbestos by the intraperitoneal route. A latency period of 6 to 24 months precedes tumor development; the biological and morphological features of these tumors resemble mesotheliomas in humans. Using one- and two-dimensional gel electrophoresis and immunoblotting, rat mesotheliomas (n = 24) were shown to express two classes of intermediate filament (IF) proteins. The tumors contained both vimentin and at least one of six keratins (p40, Mr 40,000; Dm, Mr 50,000; p53, Mr 53,000; Bm, Mr 53,000; Cm, Mr 54,000; Am, Mr 54,000). Vimentin predominated in 15 of 16 tumors exhibiting either sarcomatous or mixed (epithelial and mesenchymal) appearance. One of eight mixed lesions and six of eight epithelial tumors had a complement of IF proteins in which cytokeratins predominated. A similar pattern has been reported in mesotheliomas in humans (Blobel et al., Am. J. Pathol. 121: 235, 1985). Epithelial tumors often contain comparable amounts of vimentin and low molecular weight cytokeratins, while vimentin is the most actively expressed IF protein in sarcomatous tumors. Thus, tumors induced by asbestos in the rat peritoneum express IF proteins in a manner that resembles human mesotheliomas, supporting the notion that these lesions are appropriate models of human mesothelioma.

Topics: Animals; Asbestos; Asbestos, Serpentine; Electrophoresis, Polyacrylamide Gel; Female; Immunosorbent Techniques; Intermediate Filament Proteins; Keratins; Mesothelioma; Molecular Weight; Peritoneal Neoplasms; Rats; Rats, Inbred F344; Vimentin

A localized benign biphasic mesothelioma of the pleura is described. Immunohistochemically the epithelial-like cells contained vimentin intermediate filaments only, while electron microscopy revealed signs of true mesothelial differentiation demonstrating the hybrid nature of neoplastic mesothelial cells.

Topics: Female; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Microscopy, Electron; Middle Aged; Pleural Neoplasms; Vimentin

The immunoreactivity of five antibodies was evaluated on six routinely processed mesotheliomas to evaluate their ability to distinguish mesothelioma from metastatic adenocarcinoma. The diagnosis in all cases was confirmed by electron microscopic examination and histochemical stains for neutral mucin (periodic acid-Schiff-diastase) and acid mucin (alcian blue with and without hyaluronidase). AE1, a monoclonal antikeratin antibody that stains most carcinomas, reacted with all six cases of mesothelioma. HMFG-2 and anti-epithelial membrane antigen (antibodies reactive with human milk fat globule proteins), two other closely related antibodies reactive with most carcinomas, also reacted with all of the mesotheliomas in the authors' series. A polyclonal antibody to carcinoembryonic antigen (anti-CEA) did not stain any of the mesotheliomas in their series. Anti-Leu-M1 did not react with the mesotheliomas. The authors conclude that none of these antibodies, when used alone on routinely fixed paraffin-embedded material, is both sensitive and specific in the distinction of mesothelioma from adenocarcinoma. However, immunoperoxidase studies using anti-CEA and anti-Leu-M1 may occasionally be helpful when used in conjunction with other histochemical stains and electron microscopic examination in distinguishing mesothelioma from metastatic adenocarcinoma.

Topics: Antibodies, Monoclonal; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mesothelioma; Mucin-1; Staining and Labeling

The correct distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung has become increasingly complex, with a variety of histochemical, immunohistochemical, and ultrastructural studies to be performed on biopsy material. The reliability of immunohistochemical studies has been hampered by the use of polyclonal antisera to "carcinoembryonic antigen (CEA)" and keratin. Hybridoma technology now offers monoclonal antibodies (MAbs) in unlimited quantity and standardized quality to selective ranges of specific antigenic determinants. MAb B72.3, generated against a membrane-enriched fraction of human metastatic breast carcinoma, was used to distinguish malignant mesothelioma of the pleura from adenocarcinoma of the lung in tissue sections and was compared in terms of diagnostic utility with polyclonal anti-keratin and anti-CEA to make the same distinction. Reactivity with MAb B72.3 in at least 10% of tumor cells or more was noted in 19 of 22 adenocarcinomas of the lung (P greater than 0.0001), whereas none of the 20 cases of malignant mesothelioma demonstrated comparable reactivity. Furthermore, MAb B72.3 showed no reactivity with benign mesothelial proliferations. MAb B72.3 thus appears to be an appropriate diagnostic adjunct capable of discriminating between these malignancies.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoembryonic Antigen; Diagnosis, Differential; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Pleural Neoplasms

The histologic distinction between desmoplastic mesothelioma and reactive fibrosis and between biphasic desmoplastic mesothelioma and pleural metastases with desmoplasia can be difficult. The presence of such epithelial markers as keratin and epithelial membrane antigen (EMA) within the fibrous areas of a pleural lesion might be construed as evidence in support of the diagnosis of desmoplastic mesothelioma. To test this hypothesis ten desmoplastic mesotheliomas were studied with monoclonal antisera to keratin and EMA and compared with ten hyaline pleural plaques, 11 pleural scars, five benign localized fibrous mesotheliomas, and eight desmoplastic pleural metastases. Although the hyalinized fibrous areas within the desmoplastic mesotheliomas stained with keratin (ten of ten) and EMA (five of ten), the following reactive fibrous pleural lesions were also positive: plaques (four of ten keratin-positive, five of ten EMA-positive); scars (six of 11 keratin-positive, four of 11 EMA-positive); and fibrosis induced by metastases (six of eight keratin-positive, one of eight EMA-positive). Benign localized fibrous mesotheliomas were keratin- and EMA-negative. This study suggests that both benign and malignant fibrous pleural lesions may be of mesothelial origin and demonstrates the need to determine by histologic criteria whether the spindle cell component is benign or malignant before assessing the significance of its keratin or EMA immunoreactivity. The lack of keratin and EMA staining in benign localized fibrous mesotheliomas might be of use in distinguishing benign localized cellular fibrous mesotheliomas from sarcomatous mesotheliomas.

Topics: Humans; Immunoenzyme Techniques; Keratins; Membrane Proteins; Mesothelioma; Mucin-1; Pleural Neoplasms

The clinical, pathological, and ultrastructural features of two cases of peritoneal cystic mesothelioma occurring in men were studied. The results of immunohistochemical staining for CAM 5.2, epithelial membrane antigen, carcinoembryonic antigen, and Factor VIII related antigen are reported for the first time and compared with the staining results of two peritoneal cystic lymphangiomas. Although resembling cystic lymphangioma by light microscopy, cystic mesothelioma may have a greater tendency for local recurrence. Staining for CAM 5.2 or epithelial membrane antigen may facilitate the differentiation of these two entities.

Topics: Adult; Antigens; Carcinoembryonic Antigen; Factor VIII; Humans; Keratins; Lymphangioma; Male; Membrane Proteins; Mesothelioma; Microscopy, Electron; Middle Aged; Mucin-1; Peritoneal Neoplasms; von Willebrand Factor

To evaluate the usefulness of an immunohistologic approach to the differential diagnosis of mesothelioma and pulmonary adenocarcinoma, the authors studied paraffin-embedded, fixed tissue sections from 50 primary adenocarcinomas of the lung and 28 mesotheliomas of the pleura by using a panel of monoclonal antikeratin, antihuman milk fat globule (HMFG-2), anti-Leu M1, and monoclonal anticarcinoembryonic antigen (CEA) antibody; we also used a conventional heterologous anti-CEA antiserum with and without prior absorption with spleen powder to remove antibodies to nonspecific cross-reacting antigen (NCA). Keratin was present in both mesotheliomas and adenocarcinomas and did not help in distinguishing between these two neoplasms. HMFG-2 was detected in 48 (96%), and Leu M1 was positive in 47 (94%) of the adenocarcinomas, but not in any of the mesotheliomas. By using conventional rabbit antiserum, the authors detected CEA in the majority of adenocarcinomas (96%), but also in two cases of mesothelioma. When the anti-CEA antiserum was absorbed with NCA, the number of positively reacting adenocarcinomas decreased considerably to 76%; however, after this treatment, none of the mesotheliomas gave positive reactions. The monoclonal anti-CEA antibody was reactive in 36 of the adenocarcinomas (72%), but in none of the mesotheliomas. Our results indicate that, in addition to HMFG-2 and CEA, the expression of Leu M1 antigen by most primary pulmonary adenocarcinoma (94%) and its absence in mesothelioma could be used as a valuable marker for primary adenocarcinoma of the lung that involves the pleura and permits its differentiation from mesothelioma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Keratins; Lung Neoplasms; Membrane Proteins; Mesothelioma; Mucin-1; Phenotype; Pleural Neoplasms

Tumours of uncertain tissue of origin were investigated by immunohistochemistry on formalin fixed paraffin embedded sections. Two antibodies--PD7/26, an anti common leucocyte antigen, and CAM5.2, an anticytokeratin--recognised most lymphomas and carcinomas, respectively: 88% of these tumours were identified by the two antibodies alone. These antibodies permitted the separation of the cases into groups: positive with CAM5.2, positive with PD7/26, and a third comprising those negative with both. The negative group contained other tumours and a small number of carcinomas and lymphomas; many of the lymphomas were, apparently, of histiocytic origin. Comparison of CAM5.2 with other epithelial markers showed that it was the most effective. Some further classification of the tumours was carried out with a panel of organ and cell specific antibodies: mesotheliomas were recognised by their pattern of reactivity with epithelial markers. Overall, the tumour type was determined in 90% of cases. Immunohistochemistry performed as described can be a potent aid to the diagnostic histopathology of tumours.

Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Histocompatibility Antigens; Humans; Keratins; Leukocyte Common Antigens; Lymphoma; Mesothelioma; Neoplasms; Sarcoma; Skin Neoplasms; Thyroid Neoplasms

It is uncertain whether localized lesions of serosal membranes have a kinship to mesotheliomas or are truly fibromatous in nature. Ultrastructural and immunohistochemical investigations were carried out on 12 localized benign and malignant pleural and peritoneal tumours from 10 patients. Electron microscopic findings, including the consistent and non-fibroblastic cellular organization of localized neoplasms, the presence of some form of intercellular junctions in 7 of 10 cases, basal lamina deposition in 3 cases, and polarized microvilli in one case indicated a form of mesothelial differentiation. Using monoclonal and polyclonal antibodies, positive immunostaining of tumour cells for cytokeratin peptides was detected in one case, while antibody to vimentin stained four cases. Light microscopic, ultrastructural and immunohistochemical features of one benign localized serosal tumour, with a unique blend of epithelial and spindle cells, provided further evidence for a histogenic link between localized serosal tumours and diffuse epithelial mesotheliomas. On the basis of the current findings and reports in the literature, it would appear that the majority of localized tumours of serosal membranes are a subset of mesothelioma, while a minority are fibromas.

Topics: Adult; Aged; Antibodies, Monoclonal; Female; Fibroma; Histocytochemistry; Humans; Keratins; Male; Mesothelioma; Microscopy, Electron; Middle Aged; Peritoneal Neoplasms; Pleural Neoplasms; Serous Membrane

Five cases of solitary (localized) fibrous mesothelioma were studied immunohistochemically, utilizing monoclonal antibodies against high and low molecular weight cytokeratin, vimentin, carcinoembryonic antigen, epithelial membrane antigen and factor VIII related antigen. In contrast to normal mesothelium and contrary to previous reports from malignant mesotheliomas all the tumours were negative for keratin. They were strongly positive for vimentin. Two cases were studied electron microscopically; no ultrastructural evidence of mesothelial cell differentiation was identified. Our immunohistochemical and ultrastructural findings argue against a mesothelial cell origin, whereas the presence of vimentin suggests a mesenchymal histogenesis. It is postulated that these tumours arise from sub-mesothelial mesenchymal connective tissue.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoembryonic Antigen; Factor VIII; Female; Humans; Keratins; Male; Mesothelioma; Microscopy, Electron; Middle Aged; Vimentin

An enzyme-linked immunosorbent assay (ELISA) for anti-keratin antibodies was prepared by coating microplates with epidermal keratin purified from the stratum corneum from human foot. Naturally occurring auto-antibodies bind keratin via their f(ab')2 fragment. They were assayed in the serum from 65 healthy people. The serum titer increased significantly with aging. Auto-antibodies stained all the layers of a normal human epidermis whereas an immune serum, prepared by injecting a rabbit with pure human keratin proteins, stained more efficiently the outer layers of the human skin; pre-immune rabbit serum did not stain human skin at all. The lowest anti-keratin activities were observed in serum from patients with squamous cell lung carcinoma and with mesothelioma. The activity was lower in pleural fluid from patients with pleural mesothelioma than in pleural fluid from other types of cancer. This is possibly due to the fixation of autoantibodies onto the pleural tumor or on cell debris arising from the tumor.

Topics: Animals; Antibodies; Autoantibodies; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lung Diseases; Lung Neoplasms; Mesothelioma; Pleural Effusion; Rabbits

The authors assessed whether distinct patterns for keratin could be demonstrated in 10 adenocarcinomas, 10 carcinoids, and 4 mesotheliomas by an immunoperoxidase reaction using 3 polyclonal and 3 monoclonal antibodies to keratin. When color development in diaminobenzidine (DAB) was allowed to proceed for less than 2 minutes, distinct patterns for keratin could be demonstrated using two polyclonal and two monoclonal antibodies; these were plasma membrane and/or web-like in the adenocarcinomas, punctate or crescentic in the carcinoids, and perinuclear in the mesotheliomas consisting of tumor cells with abundant cytoplasm. Immunoelectron microscopy using protein A colloidal gold confirmed these results. When color development in DAB was allowed to proceed for more than 2 minutes, only diffuse staining was seen. The distinct patterns of immunostaining for keratin obtained with the shorter color development were helpful in differentiating adenocarcinomas, carcinoids, and mesotheliomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoid Tumor; Electrophoresis, Polyacrylamide Gel; Female; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma

A so-called diffuse biphasic pleural and a monophasic malignant "fibrous" peritoneal mesothelioma were examined using monoclonal anticytoskeleton-antibodies and polyclonal antibodies against macrophage markers. Cytokeratin, vimentin and desmin were each expressed in both of the tumors. GFAP could not be detected. In addition the tumor cells differed in the quantity of macrophage markers. The immunologic findings corresponded to the histologic features of particular areas of the carcinosarcoma. This supports the view that malignant mesotheliomas derive from pluripotential mesothelial cells capable of both epithelial and mesenchymal differentiation. Contrary to some opinions expressed in the literature this histogenesis applies equally to the so-called monophasic diffuse "fibrous" mesotheliomas.

Topics: Aged; Antibodies, Monoclonal; Antigens, Surface; Desmin; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Mesothelioma; Peritoneal Neoplasms; Pleural Neoplasms; Vimentin

The occurrence and coexpression of the cytoskeletal proteins vimentin and cytokeratins were studied in malignant mesotheliomas and pulmonary carcinomas. For this purpose a double immunoenzyme staining with monoclonal antibodies was developed which made it possible to visualize vimentin and cytokeratins simultaneously within the same cell. A clear distinction between stromal cells (vimentin only) and tumour cells was also obtained. A total of 12 mesotheliomas (six mixed type and six epithelioid type) and 13 carcinomas (eight adenocarcinomas and five large cell undifferentiated carcinomas) were studied. The results revealed a clear difference between mesotheliomas and adenocarcinomas: 11 of 12 mesotheliomas showed coexpression of vimentin and cytokeratins in at least 50% of the tumour cells, while in seven of the eight adenocarcinomas none or only a few cells could be seen with this coexpression. In the undifferentiated large cell carcinomas three of five expressed both components, but in less than 25% of the cells. It is concluded that a reliable double immunoenzyme staining of vimentin and cytokeratins can be used as an additional means to distinguish malignant mesothelioma from pulmonary adenocarcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Peritoneal Neoplasms; Pleural Neoplasms; Staining and Labeling; Vimentin

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleural Neoplasms

A multicystic peritoneal mesothelioma in a 55-year-old man is reported. The large multicystic tumor was only partially removed. 36 months after the first presentation he is still working and his only complaint is abdominal swelling. The light microscopical, immunocytochemical and ultrastructural features are described and differential diagnoses discussed.

Topics: Histocytochemistry; Humans; Keratins; Male; Mesothelioma; Microscopy, Electron; Middle Aged; Peritoneal Neoplasms; Protein Precursors; Vimentin

Topics: Adult; Aged; Antigens; Epididymis; Factor VIII; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Mesothelioma; Middle Aged; Testicular Neoplasms; von Willebrand Factor

Twelve adenomatoid tumors were examined immunohistochemically with antibody probes to keratin and factor VIII-related antigen (FVIII-RA). None of the tumors labeled with FVIII-RA antibodies, whereas all but one labeled for keratin. Electron microscopy was done on tissue from paraffin-embedded blocks from all but one of the adenomatoid tumors. Both the immunohistochemical and electron microscopic results favor a mesothelial origin of adenomatoid tumors.

Topics: Adult; Aged; Antigens; Factor VIII; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Mesothelioma; Microscopy, Electron; Middle Aged; von Willebrand Factor

A uterine tumor from a 34-year-old woman was investigated morphologically and immunohistochemically. The tumor tissue was composed of multiple cystic spaces of various sizes. The cyst wall was covered by a single layer or occasionally multiple layers of flattened cells. Electron micrographs of the tumor tissue revealed that the cells were delimited with conspicuous basal lamina from the stroma, possessed numerous microvilli at the apical surface, and connected with desmosomes. Furthermore, immunohistochemical staining with antikeratin antibody disclosed the strong positivity of the tumor cells, whereas anti-UEA-I antibody could not stain the tumor cells. The results did not favor the theory of endothelial origin of the tumor and confirmed the mesothelial origin, namely, adenomatoid tumor of the uterus.

Topics: Adult; Female; Histocytochemistry; Humans; Hyaluronic Acid; Immunologic Techniques; Keratins; Mesothelioma; Uterine Neoplasms

The intermediate filament cytoskeleton of epithelial, biphasic, and fibrous malignant pleural mesotheliomas was studied by immunohistochemistry and gel electrophoresis. The results were compared with data similarly obtained from lung adenocarcinomas. All mesotheliomas immunostained with various monoclonal and polyclonal antibodies against cytokeratins. By double immunofluorescence microscopy, coexpression of cytokeratins and vimentin was found in the fusiform cells of biphasic and fibrous mesotheliomas. As determined by two-dimensional gel electrophoresis, lung adenocarcinomas exclusively expressed Cytokeratins 7, 8, 18, and 19, and the same polypeptides were found in the fibrous mesotheliomas. These four cytokeratins were also found in the epithelial and biphasic mesotheliomas, most of which, however, also expressed, additional cytokeratins, such as the basic Polypeptide 5 and, in some cases, Cytokeratins 4, 6, 14, and 17. The results demonstrate the epithelial nature of all types of malignant mesotheliomas and thus justify their classification as carcinomas. When epithelial morphology is evident, the pattern of cytokeratin expression is usually more complex, as indicated by the synthesis, in addition to the "simple epithelial" pattern (7, 8, 18, and 19), of certain cytokeratin polypeptides which hitherto have been presumed to be typical of stratified epithelia. This cytokeratin complexity and the coexpression of vimentin and cytokeratins in certain forms of mesotheliomas indicate that these tumors are a clearly distinct and complex group of carcinomas. Their special cytoskeletal filament protein expression should prove useful in differentiating mesotheliomas from other carcinomas, particularly from adenocarcinomas growing in the lung.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Cytoskeleton; Electrophoresis; Humans; Immunochemistry; Intermediate Filaments; Keratins; Lung Neoplasms; Mesothelioma; Microscopy, Fluorescence; Pleural Neoplasms; Vimentin

A 67-year-old male case of pericardial mesothelioma is reported. The diagnosis was established by the gross appearance at autopsy and its histological findings. The tumor arising from the anterior epicardium of the right half of the heart was located within the pericardial sac, and displaced and compressed the heart to the posterior direction. Histologically, large areas of the tumor were composed of spindle-shaped malignant cells which were arranged in interlacing bundles. The other areas showed the presence of tubular structures and ill-defined solid nests. Distant metastasis was found only in a small focus of the 8th vertebral bone marrow composed of spindle-shaped cells. A meticulous search failed to find any tumor in other organs. Based on these findings, the tumor was diagnosed as diffuse malignant mesothelioma of biphasic type.

Topics: Actins; Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Heart Neoplasms; Humans; Keratins; Male; Mesothelioma; Pericardium

Because tissue culture studies have suggested that mesothelial cells might produce large amounts of vimentin, I stained eight mesotheliomas (two fixed in alcohol) for vimentin using the Gown and Vogel monoclonal antibody 43 beta E8. The two tumors that had alcohol fixed blocks were strongly positive for vimentin, whereas one of the tumors fixed only in formalin showed moderately strong staining and two others showed very weak focal positivity; the remaining tumors were negative. In the mesotheliomas that did stain, both epithelial and spindled elements gave a positive reaction. Three alcohol-fixed lung cancers and two blocks of alcohol-fixed pleura failed to stain for vimentin. By contrast, all mesotheliomas and carcinomas, whether alcohol or formalin fixed, as well as sections of pleura, were strongly positive when stained with anticytokeratin antibody 35 beta H11. I conclude that the combination of staining for vimentin and keratin might be a useful diagnostic finding in malignant mesothelioma, but that specially fixed material is required for reliable vimentin staining.

Topics: Antibodies, Monoclonal; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleural Neoplasms; Vimentin

The mesothelial origin of epididymal adenomatoid tumor is supported by the current study for the presence of mesothelial antigen in the tumor cells. By an indirect immunoperoxidase technique, anti-mesothelial cell serum showed positive cytoplasmic staining in five of the six adenomatoid tumors studied. Previous findings of the presence of strong cytoplasmic keratin and the absence of carcinoembryonic antigen and Factor VIII-related antigen in these tumor cells are also confirmed by this study.

Topics: Antigens; Antigens, Neoplasm; Carcinoembryonic Antigen; Cytoplasm; Epididymis; Factor VIII; Humans; Immunoenzyme Techniques; Keratins; Male; Mesothelioma; Staining and Labeling; Testicular Neoplasms; von Willebrand Factor

Human lung tumor cell lines established from the major histological types of lung cancer were examined by immunofluorescent staining techniques for their patterns of intermediate filament (keratin, vimentin, and neurofilament triplet protein) expression. All cell lines examined, both small cell lung carcinoma (SCLC) and non-SCLC (squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and mesothelioma) contained keratin, consistent with their epithelial derivation. These lung carcinoma cell lines also expressed vimentin, the characteristic intermediate filament of mesenchymal cells in vivo. In light of the proposed neuroectodermal origin of SCLC, cell lines were also studied for neurofilament expression. Two of four SCLC tumor cell lines, as well as non-SCLC cell lines, showed no reactivity with antibodies to neurofilament triplet protein. Two of the SCLC cell lines stained weakly with anti-neurofilament antibody. Examination of specific keratin patterns in human lung tumor cell lines by selective immunoprecipitation with keratin antiserum and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that small-sized keratin proteins (Mr 44,000 to 52,000) were present in cell lines derived from SCLC and non-SCLC types of lung cancer. Tumor cell lines exhibiting squamous differentiation by light microscopic criteria (i.e., intracellular keratin, intercellular bridging, "pearl" formation, and/or individual cell keratinization) also displayed a preponderance of intermediate-sized keratins (Mr 57,000 and 59,000) and exhibited another feature of terminal keratinocyte differentiation (cross-linked envelope formation). Mesothelioma cell lines had varying keratin profiles. The presence of keratin proteins in all SCLC cell lines examined argues against a neuroectodermal origin for these tumors and is consistent with the notion that these tumors arise from a common bronchial "stem cell," similar to that from which other types of bronchogenic carcinomas arise.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line; Cell Transformation, Neoplastic; Cytoskeleton; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Lung Neoplasms; Mesothelioma; Mice; Microfilament Proteins; Molecular Weight; Protein Precursors; Vimentin

Immunohistological methods were used to investigate the presence of carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin in formalin fixed tissue from 29 malignant mesotheliomas and 27 pulmonary adenocarcinomas. Malignant mesotheliomas were negative for tumour markers except for the beta subunit of human chorionic gonadotrophin and keratin, one and 13 cases respectively being positive for these. Pulmonary adenocarcinomas, however, were frequently positive for tumour markers--namely, carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin. The presence of carcinoembryonic antigen and beta 1 pregnancy specific glycoprotein within an intrathoracic tumour is strong evidence against its being of mesothelial origin.

Topics: Adenocarcinoma; Calcitonin; Carcinoembryonic Antigen; Chorionic Gonadotropin; Diagnosis, Differential; Humans; Keratins; Lung Neoplasms; Mesothelioma; Placental Lactogen; Pregnancy-Specific beta 1-Glycoproteins

The authors investigated the expression of keratin, carcinoembryonic antigen (CEA), and an epithelial marker derived from milk fat globule membranes in 12 mesotheliomas and 100 diverse adenocarcinomas with immunohistochemical methods. The authors employed a monoclonal antibody to keratin designated as AE1, as well as the following commercially available antisera: rabbit anti-whole human keratin, rabbit anti-CEA, and a monoclonal antibody to an epithelial factor designated as MFG-2. Expression of keratin was found in all the mesotheliomas and adenocarcinomas with antibody AE1 as well as with the rabbit antiserum; CEA was detectable in 65% of the adenocarcinomas but two mesotheliomas also reacted weakly. With antibody MFG-2, positive results were obtained in 85% of the adenocarcinomas and in none of the mesotheliomas. All of 64 (100%) breast-, lung- and ovary-derived adenocarcinomas immunostained positively with antibody MFG-2. This is of particular significance because pulmonary and ovarian adenocarcinoma frequently may be indistinguishable clinically and histologically from epithelial mesothelioma. The authors conclude that antikeratin antibodies are not useful in the distinction of adenocarcinoma from mesothelioma. Because of its greater sensitivity and specificity, MFG-2 is superior to CEA in this differential diagnosis.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Breast Neoplasms; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Mesothelioma; Ovarian Neoplasms; Staining and Labeling

The effect of preliminary trypsinization on the immunoreactivity of keratin proteins in formalin-fixed, paraffin-embedded tissues of a variety of tumors (squamous cell carcinomas, adenocarcinomas, mesotheliomas, and transitional cell carcinomas) was evaluated. Three types of trypsin (Type II and Type IX porcine trypsin and Type III bovine trypsin) and varying concentrations of trypsin were assessed. Immunoreactivity of keratin proteins was determined using rabbit anti-keratin antibodies and monoclonal antibodies (combination of AE1 and AE3) and immunoperoxidase techniques. Preliminary trypsinization was mandatory for optimal immunoreactivity of keratin proteins using either polyclonal or monoclonal antibodies. Excellent results were obtained using Type II porcine trypsin at concentrations of 25 mg/dl for 30-45 min or 50 mg/dl for 20 min, at 37 degrees C. Trypsin treatment with excessive concentrations of enzyme and/or extended incubation times promoted tissue digestion and in some cases, yielded decreased immunoreactivity and altered staining patterns.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cattle; Female; Fixatives; Formaldehyde; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Neoplasm Proteins; Paraffin; Staining and Labeling; Swine; Trypsin

A 34-year-old woman with an adenomatoid tumor of the uterus is reported. Light-microscopic examination showed the tumor to be cystic with a canalicular pattern. The ultrastructural findings were numerous microvilli, various intercellular spaces, desmosomes, and rich 10-nm microfilaments like tonofilament. Histochemically, the tumor cells secreted hyaluronic acids. Keratin was demonstrated diffusely in the cytoplasms of tumor cells by PAP staining. From these findings, we concluded that the histogenesis of the adenomatoid tumor was of mesothelial origin.

Topics: Adult; Female; Histocytochemistry; Humans; Hyaluronic Acid; Keratins; Mesothelioma; Microscopy, Electron; Uterine Neoplasms

Paraffin sections from fifteen cases of malignant diffuse mesothelioma of the pleura and five cases of bronchial adenocarcinoma infiltrating the pleura were examined with an antiserum specific for factor VIII related antigen and with antisera against various epithelial markers: keratin, carcinoembryonic antigen (CEA), fat globule membrane antigen and secretory component. In all adenocarcinomas all the epithelial markers were present whereas the factor VIII related antigen was absent. The distribution of the fat globule membrane antigens, keratin, secretory component and factor VIII related antigen varied from one mesothelioma to another. The mesotheliomas were generally negative for CEA. The three mesotheliomas which were positive for CEA were also positive for alcian blue after hyaluronidase treatment. Amongst the markers used, CEA seems the most useful for the differential diagnosis between carcinoma and mesothelioma. However, the simultaneous detection of several markers allows the characterization of various phenotypes. Some of them are close to the phenotypes of true adenocarcinoma. A relation between a given phenotype and the biological behaviour of the tumour has still to be demonstrated.

Topics: Adenocarcinoma; Antigens; Antigens, Neoplasm; Carcinoembryonic Antigen; Factor VIII; Humans; Immune Sera; Keratins; Lung Neoplasms; Membrane Proteins; Mesothelioma; Mucin-1; Pleural Neoplasms; Secretory Component; von Willebrand Factor

In differentiating diffuse epithelial mesothelioma from metastatic adenocarcinoma in pleural and peritoneal biopsies, the number and form of microvilli and the amount and distribution of tonofilaments are thought to be the most useful criteria. This report details 5 cases of diffuse epithelial mesothelioma in which the characteristic fine structural features of neoplastic mesothelial cells were markedly modified. The majority or all tumor cells were poorly differentiated in electron micrographs, particularly with reduced prominence or absence of intermediate filaments, desmosomes, intracytoplasmic lumina, and microvilli. Immunohistochemistry revealed the absence of carcinoembryonic antigen and the presence of cytokeratin in all cases. Comparison with a better differentiated case suggests cytologic details that are useful in distinguishing the poorly differentiated type of epithelial mesotheliomas from adenocarcinoma. These include a mosaic pattern of closely associated tumor cells with a few long, narrow cytoplasmic processes lying parallel to adjacent plasma membranes, abundant cytoplasm with limited organelles usually having a polar arrangement, and nuclei with markedly disaggregated chromatin and prominent nucleolonemal-type nuclei.

Topics: Biopsy; Cell Differentiation; Cytoskeleton; Desmosomes; Female; Humans; Keratins; Male; Mesothelioma; Microscopy, Electron; Microvilli; Middle Aged; Peritoneal Neoplasms; Pleural Neoplasms

We report two cases of a malignant fibrous pleural tumor, one of the localized type and one of the diffuse type. In both cases, typing of intermediate filaments by immunofluorescence microscopy showed that the tumor cells were positive for vimentin and negative for (cyto)keratin and desmin. This result supports the concept that malignant fibrous pleural tumors do not arise from the (cyto)keratin-positive pleural mesothelium but from the submesothelial fibrous tissue. Thus, instead of the usual term "malignant fibrous mesothelioma", the term "malignant submesothelial fibrosarcoma" should be preferred.

Topics: Adolescent; Aged; Cytoskeleton; Female; Fibrosarcoma; Fluorescent Antibody Technique; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Mesothelioma; Microscopy, Fluorescence; Pleural Neoplasms; Vimentin

Keratin profiles of exfoliated mesothelial and adenocarcinoma cells were determined using antisera to different molecular weight keratins (45, 46, 55, 63 kdaltons) and the immunoperoxidase technic. Most metastatic adenocarcinomas in effusions stained for low (45, 46 kdaltons) and intermediate (55 kdaltons) molecular weight keratins but were negative for 63 kdalton keratin. In contrast, most reactive and malignant mesothelial cells in effusions stained strongly for 63 kdalton keratin and keratins of lower molecular weight. This is the first report of high molecular weight (greater than 60 kdaltons) keratin in exfoliated cells of nonepidermal origin. Differences in staining for 63 kdalton keratin between mesothelial and adenocarcinoma cells may help to distinguish these cells in effusions.

Topics: Adenocarcinoma; Breast Neoplasms; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Molecular Weight

Using formalin-fixed, paraffin-embedded tissue and commercial antisera, we evaluated the usefulness of immunohistochemical staining for carcinoembryonic antigen (CEA) and keratin in the diagnosis of malignant mesothelioma. All 18 adenocarcinomas of lung examined stained for CEA, usually strongly, while only eight of 22 mesotheliomas stained for CEA and the staining was generally weak. Staining for keratin was observed in 10 of 22 mesotheliomas and 12 of 18 adenocarcinomas; there were no differences in intensity of staining between the groups. We conclude that strong diffuse staining for CEA favors a diagnosis of carcinoma, and negative staining for CEA is against a diagnosis of carcinoma, but these are relative and not absolute criteria. We find that staining for keratin is of no use in distinguishing these types of tumors.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma

We have determined the intermediate filament proteins present in normal and malignant mesothelium in vivo. Pure sheets of normal lung mesothelium were obtained by transfer to agarcoated slides or by gentle scraping and cytocentrifugation. Cytoplasmic filament networks in the mesothelium were labeled via indirect immunofluorescence both by anti-Mr 40,000 keratin and anti-vimentin antisera. Two-dimensional gel electrophoresis of the Triton:high-salt-insoluble proteins of normal lung mesothelium disclosed the presence of vimentin and all but the largest (Mr 55,000) of the four simple epithelial keratins synthesized by mesothelial cells in culture. Samples of three peritoneal and three pleural mesotheliomas were found to contain either all four simple epithelial keratins or all but the Mr 55,000 keratin. Notably, none of the keratins characteristic of stratified and many glandular epithelia and their malignant forms was present in these mesotheliomas. Two mesothelioma samples from which the tumor cells could be obtained free of other cell types were found to contain vimentin as well as simple epithelial keratins and to synthesize these same proteins during short-term culture. None of the mesotheliomas placed in culture grew progressively in medium optimal for the growth of normal mesothelial cells. These data demonstrate that malignant mesothelial cells preserve the normal pattern of intermediate filament protein synthesis, including coexpression of simple epithelial keratins and vimentin, and suggest the use of this characteristic as an aid in the identification of cells of mesothelial origin.

Topics: Cells, Cultured; Epithelium; Female; Fetus; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Lung; Mesothelioma; Molecular Weight; Peritoneal Neoplasms; Pleural Neoplasms; Pregnancy; Vimentin

The absence of keratin staining in tumor cells from localized fibrous mesotheliomas in both paraffin-embedded and frozen sections with sensitive peroxidase-antiperoxidase and avidin-biotin techniques is described. In addition ot the absence of staining for whole-stratum corneum keratin proteins, sections were negative for keratins of different molecular weights (45, 55, and 63 kilodaltons) that are characteristically present in mesothelial cells. Ultrastructurally, the cells most closely resembled mesenchymal cells of the fibroblastic type. These findings are in accordance with recent theories that relate the derivation of localized fibrous mesotheliomas to nonmesothelial cells, including subpleural connective tissue. Based on differences in immunohistochemical staining, the tumors appear to be unrelated to diffuse malignant mesotheliomas.

Topics: Factor VIII; Frozen Sections; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Pleura; Pleural Neoplasms; Staining and Labeling

Mesotheliomata can be induced more rapidly and more frequently by inhalation of erionite than by asbestos inhalation. Erionite-induced tumours have in general a similar ultrastructural appearance to inoculum-induced pleural and peritoneal mesotheliomata. Unusual features of these tumours were the presence of dense-cored vesicles and cells staining positively for neuron-specific enolase which indicated the presence of endocrine cells. In addition, one tumour showed differentiation towards bone-forming cells. The expression of both epithelial and mesodermal characteristics demonstrates the pluripotential nature of mesothelial cells under certain circumstances.

Topics: Aluminum Silicates; Animals; Keratins; Mesothelioma; Microscopy, Electron; Phosphopyruvate Hydratase; Pleural Neoplasms; Rats; Zeolites

The immunoultrastructural localization of keratin proteins and carcinoembryonic antigen (CEA) in mesothelioma cells was accomplished with a low-temperature embedding colloidal gold technique. The keratin antiserum labeled only intermediate filaments. These filaments surrounded the cytoplasmic organelles and were inserted into desmosomes. The CEA antiserum labeled cytoplasmic vesicles and droplets. No definite labeling of microvilli was observed.

Topics: Carcinoembryonic Antigen; Humans; Immunologic Techniques; Intermediate Filament Proteins; Keratins; Mesothelioma; Microscopy, Electron; Neoplasm Proteins; Pleural Neoplasms

The distribution of intra-cellular keratins was studied in normal pleural mesothelium, malignant mesotheliomas and adenocarcinomas. This study was performed on deparaffinized sections of tissue fixed in Bouin's solution by indirect immunofluorescence with a monoclonal antibody (KL1) and a conventional keratin antiserum (AKS). Discrepancies were detected using one antibody or the other. Cells from normal mesothelium and 18 cases of malignant mesotheliomas (papillary, tubulary, solid epithelial type) were strongly labelled only by KL1. The 2 cases of sarcomatoid type were negative with both antibodies. In contrast 5 metastatic adenocarcinomas and 5 lung adenocarcinomas were weakly positive or negative with both antibodies. These data confirm the presence of cytokeratins in epithelial differentiation process. Although a clear-cut distinction between mesotheliomas and adenocarcinomas was not possible using these keratin antibodies. Our data point out the importance of reactivity pattern of the antibody used in such investigations.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Cell Differentiation; Epithelium; Humans; Immunochemistry; Keratins; Mesothelioma; Pleura; Pleural Neoplasms

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Diagnosis, Differential; Histocytochemistry; Humans; Immunochemistry; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma

A benign localized mesothelioma weighing 3800 g was removed from the liver of a 27-year-old woman. The tumor was studied by light and electron microscopy, and immunohistochemically, and was found to be composed of fibroblastic and epithelial cells.

Topics: Adult; Cytoskeleton; Female; Fluorescent Antibody Technique; Humans; Intercellular Junctions; Keratins; Liver Neoplasms; Mesothelioma

In this immunohistochemical study, antiserums to different molecular weight keratin proteins (45kd, 46kd, 55kd, and 63kd) were utilized to determine the profiles of keratin proteins present in a variety of pulmonary neoplasms. Different histologic types of lung carcinoma exhibited different patterns of keratin staining. Squamous cell carcinomas stained strongly for 45K, 46K, and 55K keratin, with staining for 63K restricted to areas or individual cells with cytoplasmic keratinization. Adenocarcinomas showed variable, generally weak staining for 45K, 46K, and 55K keratin and were uniformly negative for 63K keratin both in frozen and paraffin sections. Mesotheliomas and reactive mesothelial cells, by contrast, stained positively for 63K keratin in addition to keratins of lower molecular weights. Differences in staining for 63K keratin between mesothelioma and adenocarcinoma may have diagnostic application. Moreover, individual cytokeratins may serve as markers of tumor differentiation and provide information as to the origin of neoplastic cells.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Molecular Weight

Immunoperoxidase technics were used to identify keratin and carcinoembryonic antigen (CEA) in exfoliated cells of fine-needle aspirates and body cavity fluids. Staining was evaluated in cytocentrifuge preparations from 27 malignant and 30 benign cytologic specimens. Most reactive mesothelial cell preparations were strongly positive for keratin and negative or only weakly positive for CEA. Diffuse, peripheral, and perinuclear concentration of staining for keratin was noted in exfoliated reactive mesothelial cells. Positive staining for keratin, predominantly diffuse, was noted in exfoliated cells from 56% of the adenocarcinomas. Sixty-nine per cent of adenocarcinoma preparations were strongly positive for CEA. These findings suggest that keratin proteins are not restricted to squamous cells and that keratin staining does not permit distinction between adenocarcinoma and mesothelial cells in cytologic specimens. Staining for CEA and keratin was compared in cytocentrifuge preparations and histologic sections of 12 adenocarcinomas and 7 lymphomas. In some adenocarcinomas, staining was detected only in cytologic preparations. Possible explanations for these differences are discussed. Variable staining for keratin was observed among exfoliated reactive mesothelial cells, possibly identifying different mesothelial cell populations. All reactive and neoplastic lymphoid cells were negative for keratin and CEA in cytologic and histologic preparations. Immunoperoxidase technics can be applied to rehydrated Papanicolaou-fixed and Papanicolaou-stained cytologic preparations with excellent preservation of cytologic detail.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Epithelium; Female; Formaldehyde; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Mesothelioma; Paraffin

The distribution of keratin proteins and carcinoembryonic antigen (CEA) in 20 diffuse pleural malignant mesotheliomas and 20 adenocarcinomas of the lung was determined with the use of an indirect immunoperoxidase method. Keratin proteins were identified in all of the mesotheliomas, with strong staining observed in 17 of the cases. Tumor cells of various histologic types (tubular, papillary, solid, and spindle) revealed staining for keratin proteins. A variety of staining patterns were observed, but the homogeneous pattern predominated, in either a diffuse (16 cases) or focal form (4 cases). CEA was usually absent (11 cases), but weak or equivocal staining was also observed (8 cases), and 1 case uniquely exhibited moderate staining for CEA. In contrast, adenocarcinomas of the lung usually stained weakly or negatively (18 cases) for keratin proteins and exhibited a predominantly peripheral staining pattern. All cases, however, stained strongly or moderately for CEA. The profile of strong keratin staining and weak or absent CEA staining appears characteristic of mesotheliomas and may be diagnostically useful in defining the epithelial element of these neoplasms and in distinguishing them from adenocarcinomas.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Cytoplasm; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; Pneumothorax

An immunoperoxidase technique employing antibody to prekeratin was used to study distribution and pattern of staining of prekeratin filaments in cytological smears obtained from 42 specimens of pleural and peritoneal effusions (27 benign, 15 malignant). The smears were either air-dried or ethanol-fixed. Both benign and malignant mesothelial cells showed distinctive peripheral or perinuclear staining patterns which differed from the characteristic arborizing pattern in adenocarcinoma cells. The ultrastructure of these 2 cell types studied in 27 body fluids (12 benign, 15 malignant) and in 13 malignant tumors (3 mesotheliomas, 10 adenocarcinomas) showed a distinctive localizaton of intermediate filaments which corresponded to and could explain the pattern of staining obtained using the immunoperoxidase technique. The immunohistochemical and ultrastructural findings appeared characteristic for benign and malignant mesothelial cells as well as for adenocarcinoma cells, and could be used as markers to differentiate mesothelial tumors and reactive mesothelial cells from adenocarcinomas.

Topics: Adenocarcinoma; Ascitic Fluid; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mesothelioma; Pleural Effusion; Protein Precursors

The histogenesis of adenomatoid tumors has been a source of controversy. Although most investigators favor a mesothelial derivation, recent ultrastructural evidence suggests that some adenomatoid tumors may be vascular neoplasms. This study reports the pattern of staining of seven adenomatoid tumors with antisera to keratin, factor VIII, and carcinoembryonic antigen (CEA), using an immunoperoxidase technique. All the tumors revealed strong cytoplasmic staining for keratin with no staining for factor VIII (an endothelial cell marker) or CEA. An identical staining pattern was evident in normal and reactive mesothelial cells. These findings support a mesothelial rather than an endothelial derivation for the tumors studied.

Topics: Antigens; Carcinoembryonic Antigen; Cytoplasm; Factor VIII; Female; Genital Neoplasms, Female; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Staining and Labeling

Fifty primary gastrointestinal and breast carcinomas, four embryonal rhabdomyosarcomas, six nonmuscular mesenchymal malignant tumors and one mesothelioma have been studied to determine what type of intermediate filaments they express, using affinity purified antibodies to prekeratin, vimentin and desmin and FITC or peroxidase labeled second antibodies. The tissues were alcohol fixed and paraffin embedded before use. In all carcinoma cases the tumor cells are stained by antibodies to prekeratin, while the vimentin antibody only decorates the stroma. Prekeratin positive tumor cells are not only seen in well differentiated tumors, but also in signet ring cell carcinomas. In the case of rhabdomyosarcoma the tumor cells clearly were decorated by antibodies to desmin, while the vimentin antibody only stained very few tumor cells. In cases of nonmuscular mesenchymal tumors, the tumor cells could only be labeled by antibodies to vimentin and not by antibodies to prekeratin or desmin. In biphasic tumors like mesothelioma, different parts of the tumor were separated by antibodies to prekeratin and vimentin.

Topics: Adenocarcinoma, Mucinous; Breast Neoplasms; Carcinoma; Child; Cytoskeleton; Desmin; Female; Gastrointestinal Neoplasms; Humans; Intermediate Filament Proteins; Keratins; Mesothelioma; Neoplasms; Neoplasms, Germ Cell and Embryonal; Protein Precursors; Rhabdomyosarcoma; Sarcoma; Vimentin

The distribution of intracellular keratin was studied in a variety of human tumors using a previously described immunoperoxidase technique employing antikeratin antibodies. Squamous cell carcinomas, transitional cell tumors, and mesotheliomas exhibited strong reactivity with antikeratin antibodies. Mammary adenocarcinomas were either negative or weakly positive. In the lung, an organ which can give rise to several morphologically distinct forms of carcinoma, only the squamous cell type stained strongly for keratin; undifferentiated lung carcinomas were negative, and adenocarcinomas were either negative or weakly positive. Colonic, renal, and prostatic adenocarcinomas were negative. Sarcomas, lymphomas, and neural tumors were uniformly negative. The analysis of intracellular keratin by the immunoperoxidase technique appears helpful in establishing the epithelial nature of primary or metastatic poorly differentiated neoplasms.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Neoplasm Metastasis; Neoplasms

Topics: Amino Acids; Animals; Biopsy; Cattle; Chondroitin; Chromatography; Chromatography, Gel; Chromatography, Ion Exchange; Electrophoresis; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Hydrolysis; Keratins; Male; Mesothelioma; Neoplasm Metastasis; Neoplasm Proteins; Oxidation-Reduction; Periodic Acid; Pleural Effusion; Pleural Neoplasms; Proteins; Staining and Labeling; Sulfuric Acids; Testis; Vitreous Body