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MALIGNANT PLEURAL MESOTHELIOMA


MALIGNANT PLEURAL MESOTHELIOMA
Malignant pleural mesothelioma (MPM) is a tumor arising in the pleura from mesothelial cells. It may also arise in the peritoneal cavity, pericardium, and tunica vaginalis (rarely). Pleural mesothelioma may be restricted to a small area or grow diffusely in a multifocal or continuous manner. The histologic types of MPM are epithelioid, which is the most common; sarcomatoid; and biphasic or mixed. Desmoplastic mesothelioma is considered a subtype of sarcomatoid mesothelioma. Localized malignant mesothelioma presents as a nodular lesion without diffuse pleural spread but is histologically identical to diffuse MPM. Results of immunohistochemical staining with cytokeratin 5/6, calretinin, and Wilms tumor-1 are positive in the vast majority of epithelioid mesothelioma but are less often positive in sarcomatoid mesothelioma. These markers are typically, but not always, negative in adenocarcinoma.

The etiologic agent of MPM is asbestos in a large majority of the cases, but documentation requires a careful exposure history, and the delay between exposure and disease is generally 30 to 50 years. The frequency of MPM increases with increasing asbestos exposure, but there is no documented lower limit or safe threshold level of asbestos exposure. Certain individuals are believed to be genetically more susceptible, but the exact genetics have not been delineated.
MALIGNANT PLEURAL MESOTHELIOMA

The most common presentations are pleural effusion or pain. Dyspnea may be present if the pleural effusion is of significant size. Pain is generally described as a dull ache or pulling sensation in the chest wall. The chest radiograph may show pleural effusion or pleural thickening with or without irregular thickening of the interlobar fissure. Calcified pleural plaques may be present and are a sign of prior asbestos exposure. Computed tomography (CT) of the chest usually demonstrates pleural thickening and nodularity if it is not hidden by the pleural effusion that is present in most cases. Thickening of the intralobar fissure is frequently present. With more extensive involvement, contraction of the involved hemithorax may occur.
The diagnosis can be difficult. Pleural fluid cytology results are positive for malignant cells in one-third of cases, but pathologists have difficulty determining adenocarcinoma involving the pleura versus MPM. Percutaneous or closed pleural biopsy often yields adequate tissue for diagnosis. When these test results are nondiagnostic, then thoracoscopy with biopsy under direct visualization is diagnostic in 90% of cases. The typical description at visualization is that of multiple nodular densities of the pleura. Because of the paucity of cases (~2000-3000 per year in the United States), many pathologists see few cases of MPM. It is therefore very important that biopsy samples be reviewed by a pathologist with particular expertise in mesothelioma.


The treatment of patients with MPM is difficult and somewhat controversial. For those with earlier stage tissue, aggressive trimodality treatment has been advocated by some. This approach includes induction chemotherapy followed by extrapleural pneumonectomy and postoperative hemithoracic radiotherapy. Most patients with MPM are clinically or medically inoperable, and these individuals should be considered for systemic chemotherapy or supportive care only.
The natural history of this disease is that of initial local progression in the pleura (with encasement of the lung), mediastinum, pericardium, and diaphragm.
Intraabdominal spread, contralateral pleura, and distant organs occur later in the disease process. The median survival in 9 to 12 months in most nonsurgical series and 16 to 18 months in surgical series with earlier stage patients. Twenty percent or fewer patients survive beyond 2 years, but there are reports of 4- to 5-year survival in selected patients with minimal treatment. Patients generally die of cardiorespiratory failure caused by encasement of the heart and lungs by tumor.