39-05: Mesothelioma

ESSENTIALS OF DIAGNOSIS

GENERAL CONSIDERATIONS

Mesotheliomas are primary tumors arising from the surface lining of the pleura (80% of cases) or peritoneum (20% of cases). About three-fourths of pleural mesotheliomas are diffuse (usually malignant) tumors, and the remaining one-fourth are localized (usually benign). Men outnumber women by a 3:1 ratio. Numerous studies have confirmed the association of malignant pleural mesothelioma with exposure to asbestos (particularly the amphibole form). The lifetime risk to asbestos workers of developing malignant pleural mesothelioma is as high as 10%. Sixty to 80 percent of patients with malignant mesothelioma report a history of asbestos exposure. The latent period between exposure and onset of symptoms ranges from 20 to 40 years. The clinician should inquire about asbestos exposure through mining, milling, manufacturing, shipyard work, insulation, brake linings, building construction and demolition, roofing materials, and other asbestos products (pipes, textiles, paints, tiles, gaskets, panels). Although cigarette smoking significantly increases the risk of bronchogenic carcinoma in asbestos workers and aggravates asbestosis, there is no association between smoking and mesothelioma.

CLINICAL FINDINGS

A. Symptoms and Signs

The average interval between onset of symptoms and diagnosis is 2–3 months; the median age at diagnosis is 72–74 years in Western countries. Symptoms include the insidious onset of shortness of breath, nonpleuritic chest pain, and weight loss. Physical findings include dullness to percussion, diminished breath sounds and, in some cases, digital clubbing.

B. Laboratory Findings

Pleural fluid is exudative and often hemorrhagic. Cytologic tests of pleural fluid are often negative. VATS biopsy is usually necessary to obtain an adequate specimen for histologic diagnosis. The histologic variants of malignant pleural mesothelioma are epithelial (50–60%), sarcomatoid (10%), and biphasic (30–40%). Since distinction from benign inflammatory conditions and metastatic adenocarcinoma may be difficult, immunohistochemical stains are important to confirm the diagnosis. Epithelial malignant mesothelioma stains positive for calretinin, cytokeratin 5/6, WT-1, and podoplanin (D2-40) and stains negative for MOC-31, BG8, and Ber-EP4. Epithelial mesothelioma also stains negative for TTF-1 and Napsin-A, which are specific for lung adenocarcinomas. Note that squamous cell lung carcinomas can be positive for D2-40, cytokeratin 5/6, and calretinin, but squamous cell lung cancers also stain positive for p40 and p63, in addition to other epithelial markers that are negative in epithelial mesotheliomas. Soluble mesothelin-related peptide and fibulin-3 may be found in serum or pleural fluid (or both) of patients with malignant mesothelioma.

C. Imaging

Radiographic abnormalities consist of nodular, irregular, unilateral pleural thickening and varying degrees of unilateral pleural effusion. Sixty percent of patients have right-sided disease, while only 5% have ...