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Mesothelioma Update

By Mark Block, MD; and Alice M. Boylan, MD

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Diagnosis

Surgical biopsy is frequently required to establish a definitive diagnosis of malignant pleural mesothelioma. Clinical features may suggest mesothelioma, but adequate tumor sampling is necessary because the cytologic features alone may suggest other cancers or benign pleural inflammation. For example, epithelial mesotheliomas can be difficult to distinguish from metastatic adenocarcinoma, and sarcomatoid mesotheliomas can look like metastatic or primary sarcoma. To resolve these differences, pathologists employ both immunohistochemistry and electron microscopy. These additional special studies usually require more tissue than can be obtained by less invasive means.

Thoracentesis with pleural fluid cytology is often the first diagnostic test performed, but as noted above, is usually not diagnostic. Image-guided needle biopsy retrieves more tissue, and its tissue is diagnostic in up to 85% of cases.10 If these approaches fail to provide a definitive diagnosis, then surgical biopsy is indicated. If the disease process has obliterated the pleural space, an incisional biopsy is the only option. However, if there is at least a small pleural effusion, thoracoscopic biopsy is the preferred approach. This can be accomplished either by insertion of a mediastinoscope directly into the pleural space, or with video-assisted thoracoscopy. Surgical biopsies provide adequate tissue for diagnosis, but mesothelioma is notorious for seeding biopsy and chest tube sites.7 Therefore, thoracoscopy and chest tube incisions should be placed so that if a subsequent therapeutic resection is performed, the biopsy sites can be easily excised.

The critical advantage of surgical biopsy is that it provides the larger amounts of tissue required for analysis by routine histology as well as electron microscopy and immunohistochemistry. In addition, critical information about the biologic behavior and appearance of the tumor can be obtained. Malignant mesotheliomas typically originate in the parietal pleura, especially on the diaphragmatic surface, whereas primary lung cancers metastatic to the pleura show greater visceral tumor involvement.

Ultrastructural features diagnostic of mesothelioma include cytoplasmic tonofilaments and long, sinuous microvilli. In contrast, the microvilli of adenocarcinomas are relatively short, wide, and straight. Performance of electron microscopy requires that some biopsy material be preserved in glutaraldehyde, while formalin-fixed specimens can be analyzed by immunohistochemistry. Although a variety of immunohistochemical stains have been used to differentiate adenocarcinoma of the lung and mesothelioma, none is specific, especially with less well-differentiated tumors. Because of the difficulties in establishing the diagnosis in some cases, an expert panel of pathologists from the United States and Canada was formed. In their statement, they stressed the need for the pathologist to have information about the behavior of the tumor from the radiographic and intraoperative observations as well as the need for larger specimens to permit multiple immunohistochemical stains.11


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