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Introduction

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Malignant mesothelioma (MM) is an uncommon disease with approximately 3000 new cases diagnosed each year in the United States. Most occur in the pleura. However, each year about 300 new cases occur in the peritoneum and many fewer in the pericardium and paratesticular serous membranes. Although most persons with pleural malignant mesothelioma (PMM) are middle-aged males (median 62 years), the disease also occurs in lesser numbers of women and over a wide age range. The presentation is usually with dyspnea secondary to a pleural effusion and/or chest wall pain. Most give a history of occupational exposure to asbestos 20 to 40 years or more earlier. Pathologic diagnosis guides treatment and is generally based on a pleural biopsy obtained by VATS. Prognosis is poor in most cases with few surviving 2 years following diagnosis. However, some recent reports indicate palliation with therapy and present studies aim at cure. This article will focus on the critical role pathology plays1 as it interfaces with surgery, radiology, and oncology in the management of PMM. We will consider surgical pathology procedures and tissue collection, classification, differential diagnosis, prognostic factors, grading, and causation and pathogenesis of PMM.

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Surgical Pathology Procedures and Tissue Collection

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Important elements in the pathologic diagnosis of PMM are the clinical history, especially the presenting symptom, any history of past or present tumor and relevant radiologic features, especially those seen in the chest x-ray, CT, and/or PET scan. Diffuse nodular pleural thickening or a pleural-based mass are characteristic of PMM. However, in some cases, tumor nodularity is lacking and the pleura is thickened by diffusely fibrotic tumor.

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Cytologic examination with cell block examination of pleural fluid is usually one of the first steps after radiologic examination in the workup of patients suspected of PMM. Cytologic examination may establish a diagnosis of adenocarcinoma. In other cases atypical, or even frankly malignant mesothelial cells, may be present. Fluorescence in situ hybridization (FISH) and immunohistochemical studies of pleural fluid specimens may help to establish a malignant diagnosis in some cases. However, tissue invasion, required for the pathologic diagnosis of PMM, is not feasible in pleural fluid specimens. Pathologic diagnosis may be based on a fine needle aspirate or core biopsy, but usually requires examination of a VATS biopsy, or rarely, an open biopsy.

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Frozen Section Examination
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PMM usually begins in the parietal pleura, rather than in the visceral pleura. This is supported by several observations including those in a thoracoscopic and pathologic prospective study of biopsies of 188 early cases of PMM, which revealed that patients whose tumor was confined to the parietal pleura survived significantly longer (median survival time 32.7 months) than those with involvement of both parietal and visceral pleura (median survival time 7 months). No instances of tumors involving only visceral pleura were encountered.2 Tumor first appears on gross examination as tiny, 1 to 2 mm ...

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