Diffuse Mesothelioma Research Articles

Clinical study on mesothelioma of the pleura.

【We reviewed 15 cases of mesothelioma of the pleura, of which three cases were localized benign form and 12 cases were malignant diffuse form. The tumors were distributed equally in both sexes, and occured most commonly in fifth to seventh decades. The history of exposure to asbestos was present in only one case. The chief complaints were mainly chest pain and dyspnea. Associated symptoms were cough, sputum, hemoptysis, weight loss, anorexia, chill. On physical examination, unilateral, decreased breathing sound was main feature. The simple chest radiograph showed masses in all localized mesotheliomas (100%) and in 2 diffuse mesotheliomas (17%). 8 cases of diffuse mesotheliomas (67%) showed unilateral pleural effusions. Pleural effusions were mainly bloody (67%), and almost all were exudates. In all localized mesotheliomas, final diagnosis was made by open thoracotomy. In diffuse mesotheliomas, final diagnosis was made by open thoracotomy in 7 cases, chest wall mass biopsy in 2 cases, thoracoscopic biopsy in 1 case, pleural biopsy in 1 case, and pleural biopsy combined with axillary lymph node biopsy in 1 case. Localized mesotheliomas were treated by simple excision with good prognosis. In diffuse mesotheliomas, surgical treatment (pleuropneumonectomy, pleurectomy), chemotherapy, or radiotherapy, alone or in combination, were used with dismal prognosis. The prognostic factors were not found due to the small number of cases, incomplete follow up, and early drop out.】

Induction of a diffuse mesothelioma in chickens by intraperitoneal inoculation of v- src DNA

The presence of peritoneum-based, cytokeratin-positive tumor cells, as detected under conditions of intravenous inoculation of chickens with a v- src-positive DNA fragment, raised the possibility that such DNA may be inductive for diffuse mesothelioma. To investigate this possibility, chickens were inoculated intraperitoneally with v- src DNA, and the resultant peritoneum-based tumor tissue was subjected to histopathological analysis. On the basis of (i) morphology, (ii) immunohistochemistry/histochemistry, and (iii) ultrastructure, we concluded that this tissue represents a diffuse mesothelioma.

Pleural mesothelioma

Pleural mesotheliomas are uncommon tumors that can be classified as localized or diffuse. Diffuse pleural mesotheliomas are invariably malignant. Although the frequency is low in the general population, it is more common in persons with a heavy occupational exposure to asbestos, and is considered as a signal tumor to asbestos exposure with medicolegal consequences. Mesothelioma incidence has been steadily rising during the past two decades, reflecting the increase in asbestos exposure during and following World War II. Clinical features include initial complaints of nonpleuritic chest pain and dyspnea. Distinguishing malignant mesothelioma from metastatic adenocarcinoma can be difficult, and can require large tissue biopsy with special stains and electron microscopy. The median survival of about 9 to 12 months confirms the poor outcome of pleural mesothelioma. The clinical deterioration is primarily attributable to locoregional spread of tumors, but metastasis is not rare. Several factors seem to have a prognostic value: performance status, stage, platelet count, age, histologic subtype, and asbestos exposure. In spite of the different therapeutic modalities such as surgery, radiotherapy, and chemotherapy used alone or in combination, the median survival is fairly different from survival among untreated patients. Because of the uncommon occurrence of this tumor and the existence of several different prognostic categories, a cooperative effort will be necessary for future therapeutic trials. If these active new therapies are identified, it would be useful to compare them to a best supportive care regimen in order to demonstrate an advantage of the treatment.

Well-differentiated papillary mesothelioma of the peritoneum: A borderline mesothelioma

Well-differentiated papillary mesothelioma (WDPM) is considered to be a distinct subtype of peritoneal mesothelioma. Although the WDPM is usually qualified as benign, the natural history of this lesion has not been clearly established. This report relates to two WDPMs which were found incidentally. In a 51-year-old man the WDPM developed over a period of 5 years into a typically malignant diffuse mesothelioma. Thus, although the WDPM morphologically lacks signs of malignancy, it should be regarded as a borderline mesothelioma.

Diagnosis and treatment of pleural mesothelioma

Pleural mesotheliomas are uncommon tumors. They can be broadly classified as localized and diffuse. The localized form is a non-epithelial neoplasm that occurs as commonly in women as in men and is not related to asbestos exposure. It is usually asymptomatic, and is occasionally associated with paraneoplastic syndromes. Localized mesotheliomas arise more frequently from the visceral than from the parietal or mediastinal pleura. The long-term outcome of these tumors is determined mainly by their clinical presentation, and by whether or not they can be completely resected. Diffuse pleural mesotheliomas are invariably malignant. They are clearly related to asbestos exposure, and are far more common in men than in women. Histologically, they are completely or partially epithelial tumors. Diffuse mesotheliomas present with dyspnea, chest pain, and weight loss and are not associated with paraneoplastic syndromes. Distinguishing malignant mesothelioma from metastatic adenocarcinoma can be difficult and usually requires a large tissue biopsy on which immunohistochemistry and electron microscopy can be performed. The management of diffuse malignant mesothelioma remains controversial. Treatment appears to prolong survival which ranges from 6 to 12 months with supportive care alone. Surgical resection, either with extrapleural pneumonectomy or by pleurectomy/decortications remains the mainstay of treatment because of the relative ineffectiveness of radiation and chemotherapy. Surgical resection alone, however, is inadequate, so most current treatment regimens combine operation with radiation and/or chemotherapy. Even with aggressive multimodality treatment, the median survival currently ranges from 18 to 24 months. A better understanding of prognostic factors, a better staging system, and innovative treatment strategies are desperately needed in this disease.

Monoclonal antibodies to human malignant mesothelioma.

Murine monoclonal antibodies were used to identify tumor-cell membrane antigens on a new human mesothelioma cell line. Hybridomas were constructed by fusing SP2/0 mouse myeloma cells with spleen cells from Balb/C mice immunized by the human mesothelioma cell line MT-1. Hybridoma antibody was detected in 55/672 microculture wells that reacted to these MT-1 tumor cells by an indirect 125I-protein A binding assay. Six cultures produced antibody binding selectively to the MT-1 tumor cells but not to a human lymphoblastoid cell line. These six hybridomas were cloned: three were IgG and three were IgM antibodies. One monoclonal, MAb 45, reacted with 4 of 7 human mesothelioma cell lines but with only 1 of 11 carcinomas, 1 of 3 sarcomas, 4 of 11 melanomas, and 0 of 5 lymphoid lines. The other five monoclonals had a much broader cross-reactivity. Using an immunoperoxidase technique, MAb 45 bound to mixed-type malignant mesotheliomas but not to normal lung and pleura. The specificity of MAb 45 for diffuse mesotheliomas and the low cross-reactivity with carcinomas and normal adjacent tissues suggest that this monoclonal may be clinically useful.

Localized fibrous tumour of serosal surfaces

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.

Ultrastructure of poorly differentiated diffuse epithelial mesothelioma

Ultrastructure of poorly differentiated diffuse epithelial mesothelioma

Glycosaminoglycans in malignant diffuse mesothelioma.

Because of frequently encountered diagnostic difficulty due to a morphologic similarity between diffuse pleural mesothelioma and peripheral pulmonary adenocarcinoma, glycosaminoglycans (GAG) of human malignant diffuse mesothelioma were histochemically stained and chemically quantitated, and were compared with GAG of papillary adenocarcinoma of the lung. In all seven patients, the diagnosis of diffuse mesothelioma was confirmed morphologically by such findings as abundant bushy microvilli on cell surface and intermediate filaments in cytoplasm. The total GAG in mesothelioma obtained from fresh materials (5 cases) was significantly increased over that in pleural connective tissue (P less than 0.01) and lung adenocarcinoma (P less than 0.02). Two dimensional electrophoretic separation of GAG of mesothelioma and lung cancer showed hyaluronic acid, heparan sulfate, heparin, dermatan sulfate and chondroitin sulfate; among them, the two predominant fractions were hyaluronic acid and chondroitin sulfate. In the quantitative analysis, the hyaluronic acid content of mesothelioma averaged 57% of the total GAG, but that of lung adenocarcinoma, 38%. The results suggest that chemical analysis of GAG may be useful as supplementary diagnostic procedure to morphologic examination in the differentiation of diffuse mesothelioma from papillary adenocarcinoma of the lung.

Immunohistological study of malignant diffuse mesotheliomas of the pleura.

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.

Ultrastructural aspects of the histogenesis of diffuse and localized mesothelioma.

During an ultrastructural review of 30 diffuse and 10 localized mesotheliomas, it was apparent that some micrographs showed various stages in the developmental processes involved in the formation of histological patterns in diffuse mesotheliomas and a histogenetic link between diffuse and localized mesotheliomas. Cells in the stromal or sarcomatous regions of diffuse mesothelioma often show varying degrees of mesothelial differentiation and a gradual transition to cells with typical mesothelial characteristics that organize into structures recapitulating the surface layer of serosal membranes. Tumor cells in localized mesotheliomas had many similarities to the "stromal" cells in the diffuse counterpart including intercellular junctions, rare microvilli and occasional foci of basal lamina. It is postulated that diffuse and localized mesotheliomas share a common histogenetic origin as a result of neoplastic induction of specialized submesothelial cells. In this concept, tumor cells in diffuse mesotheliomas reflect stages in the differentiation and organization of normal serosal membranes and localized mesotheliomas mirror the earliest phases of this process.

Diffuse Epithelial Pleural Mesothelioma Presenting as a Solitary Lung Mass

We report the occurrence of a malignant pleural epithelial mesothelioma which presented radiographically and at surgery as a localized solitary mass, but was found microscopically to involve grossly normal pleura. Clinically diffuse mesothelioma recurred 19 months later. Localized malignant mesothelioma has been associated with the same poor prognosis as the diffuse form and, as suggested by this case, may represent an early phase of diffuse disease.

Surgical treatment of pleural mesothelioma

From 1939 through 1981, 170 patients were seen and treated for pleural mesothelioma. Twenty-one tumors were benign, 47 were fibrosarcomatous, and 102 were epithelioma. Resection was the main mode of treatment in benign and fibrosarcomatous mesothelioma. Treatment of diffuse epithelial mesothelioma presented the greatest challenge. Surgical therapy, radiation therapy, and chemotherapy were used in combination in these patients. The review of our patients treated prior to 1972 had shown no benefit from including pulmonary resection in the surgical treatment of these tumors. Since then, all patients with diffuse mesothelioma were treated by pleurectomy without pulmonary resection. Both internal and external radiation therapy were also used to enhance local control. Forty-nine percent of patients with epithelial mesothelioma lived 1 year. The median survival in patients whose disease was controlled by these methods was 21 months. Despite the poor prognosis in malignant mesothelioma, better controlled by these methods was 21 months. Despite the poor prognosis in malignant mesothelioma, better survival was achieved when the treatment included operation combined with radiation and chemotherapy.

Desmoplastic diffuse mesothelioma.

Twenty-seven cases of desmoplastic diffuse malignant mesothelioma (26 pleural, one peritoneal) are described. In 19 cases the tumor cell type was sarcomatous and in six others it was biphasic (malignant elements of both epithelial and mesenchymal aspect). There were only two cases where the tumor cell type was purely epithelial. The clinical course was often rapid; the mean survival period in 11 cases of purely sarcomatous type was 6.18 months. Only one case of purely sarcomatous type lived for more than 1 year as opposed to four of eight cases with an epithelial component. Metastases occurred more frequently in desmoplastic (60.1%) than in nondesmoplastic diffuse mesothelioma (42.5%). The tumor cell type (epithelial, mesenchymal) accompanying desmoplastic mesotheliomas and not the extent of desmoplasia determines their behavior. Desmoplasia in diffuse mesotheliomas is often the result of tumor cells assuming the functional capacity of fibroblasts and has frequently been confused with reactive fibrosis. Cytologic abnormalities, tissue infiltration, and foci of necrosis indicate the neoplastic nature of the process in most instances.

Reactive mesothelial cell and mesothelioma of the pleura

The results of a light and electron microscopic study and enzyme histochemistry of reactive mesothelial cells and diffuse and localized (solitary) pleural mesotheliomas were compared, in order to establish a diagnosis and elucidate the cell of origin of the mesotheliomas. The reactive mesothelial cells were usually regular in appearance but could be cuboidal or columnar, or even peg-shaped with large nuclei and prominent nucleoli. Colloidal iron and alcian blue staining were positive in the plasma membrane, microvilli and in parts of the cytoplasm of mesothelial cells. These stains were mostly negative following testicular hyaluronidase treatment. The neoplastic cells of diffuse pleural mesothelioma had some epithelial characteristics such as microvilli, desmosomes, and a prominent basement membrane and were similar to reactive mesothelial cells with regard to cellular form and staining for acid mucopolysaccharides. In this study the colloidal iron and PAS stains appeared to be more intense in mesothelioma cells than in reactive mesothelial cells.

隣接組織へ結節状浸潤を著明に示したびまん性胸膜中皮腫の一剖検例

隣接組織へ結節状浸潤を著明に示したびまん性胸膜中皮腫の一剖検例

Absence of carcinoembryonic antigen-like material in mesotheliomaAn immunohistochemical differentiation from other lung cancers

This study is to examine the potential usefulness of immunohistochemical staining for carcinoembryonic antigen (CEA)-like material in the differential diagnosis of mesotheliomas (12 cases) from other lung cancers (14 cases) that had been previously diagnosed by transmission and scanning electron microscopy and conventional light microscopy. Indirect immunofluorescent staining for CEA was carried out on formalin-fixed paraffin-embedded sections, and the slides were examined under code. All 9 cases of diffuse mesothelioma were negative, and all 12 cases of adenocarcinoma and bronchioloalveolar carcinoma were positive for CEA-like material. Three localized mesotheliomas and a carcinoid tumor were also negative. A squamous cell carcinoma was positive. A positive immunohistochemical result for CEA-like material in lung cancers will raise the possibility of its being of bronchial epithelial origin.

HISTOPATHOLOGICAL STUDIES ON EXPERIMENTALLY INDUCED PULMONARY, PLEURAL AND PERITONEAL NEOPLASMS IN MICE BY INTRAPERITONEAL INJECTION OF CHRYSOTILE ASBESTOS AND N‐METHYL‐N‐NITROSOURETHANE

The cocarcinogenic effects of asbestos are presented. In lung carcinomas induced in mice, the number of carcinomas and the time of detection of the first carcinoma per tumor-bearing animals were greater and faster in the group with chrysotile plus MNU than either chrysotile or MNU alone. This suggested that chrysotile asbestos had a promoting or cocarcinogenic effect on some carcinogens in the respiratory tract. In the group treated with chryotile alone, a tumor was found in the right pleural cavity at 15 months. This tumor microscopically was similar to the biphasic form of the human diffuse mesothelioma. Microvilli, basement membrane, and junctional apparatus were seen by electron microscope, but other cytoplasmic organelles of the tumor cells were relatively scanty. Two peritoneal tumors developed in gastric and intestinal serosa at 11 and 12 months. Light and electron microscopic studies suggested that the tumors were probably myosarcomas or fibrosarcoms.

Diffuse pleural mesothelioma in Trieste. A survey based on autopsy cases.

Records of necropsies performed at the Institute of Pathological Anatomy and Histology of the University of Trieste during the period December 1 1971-December 31 1977 have been reviewed. Cases with a necropsy diagnosis of pleural tumor or lung sarcoma were reexamined. Twenty-six cases were accepted as definite diffuse pleural mesothelioma. Occupational history was indicative of asbestos exposure in 22 cases, with 12 patients having worked in shipyards. The high incidence of diffuse pleural mesothelioma in the Province of Trieste is emphasized.

A scanning electron microscopic study of diffuse mesothelioma and some lung carcinomas

Seventeen cancers from lung and pleura were studied with scanning, transmission electron, and light microscopy (SEM, TEM and LM). Diffuse mesothelioma mimics bronchioloalveolar carcinoma at LM but shaggy microvilli were found on the cellular surface of the former, and short sprouts densely packed or loosely scattered, on that of the latter. Neolumen formation was found in both. Oat cell carcinoma had a smooth surface with occasional tiny projections and minute surface depressions. The cellular projections of squamous cell carcinoma were quite irregular. Differentiation between diffuse mesothelioma and bronchioloalveolar carcinoma appears feasible with SEM in tissue appropriately fixed either with formaldehyde or glutaraldehyde. The role SEM can play in diagnostic pathology is yet to be explored.