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Thoracentesis
Pleural effusions in patients with MPM are typically exudative and may be hemorrhagic (32). Levels of hyaluronic acid in pleural fluid that are greater than 0.8 mg/mL are said to establish the diagnosis of MPM; but the majority of patients with MPM have intermediate levels of hyaluronic acid, and these levels are also seen in association with other carcinomas metastatic to the pleura and in inflammatory processes (32). A protein concentration of more than 3.4 g/dL and an elevated lactase dehydrogenase level are found in the pleural effusion of MPM; and the concentrations of protein and lactase dehydrogenase are usually higher than those found in association with metastatic adenocarcinoma (21,33). The glucose concentration is variable and tends to decrease in inverse proportion to the number of malignant cells present in the pleural fluid (21). Pleural fluid analysis alone is usually not diagnostic of MPM.
Cytology
Pleural fluid cytologic analysis is generally not helpful, as sensitivity is 0%-64%. Results of cytologic analysis are often negative or indeterminate, despite the presence of active tumor, and differentiation between cells of MPM, metastatic adenocarcinoma, and severe atypia can be extremely difficult (33,59). In a study of 51 cases of MPM, cytologic analysis of pleural fluid was diagnostic of MPM in 27 cases (53%), was suggestive of MPM in three cases (6%), did not allow exclusion of MPM in nine cases (18%), and was nondiagnostic in eight cases (16%); it resulted in a misdiagnosis of adenocarcinoma in four cases (8%) (59).
Percutaneous Needle Biopsy
Cutting needle biopsy performed under CT guidance has a limited sensitivity (25%-60%) in the diagnosis of MPM (60,61) because the sample volume is too small for accurate histologic evaluation. Also, sampling error may yield a negative biopsy result, despite the presence of a malignant mesothelioma. Some investigators have reported a diagnostic rate of higher than 80%, but complications of pneumothorax (9.5%) and tumor seeding of the needle track (21%) are not inconsequential (61). Preventive local radiation therapy is now used to prevent tumor growth within needle tracks (60).
Thoracoscopic Surgery
Video-assisted thoracoscopic surgery (VATS) is rapidly becoming accepted as the best way to obtain a prompt diagnosis, determine the stage of the disease process, and initiate early treatment (Figure 37). Boutin and Rey (60) reported a diagnostic rate of 98% with thoracoscopy. Surgical biopsy may be required in a limited number of patients with thick adhesions that prevent the use of the thoracoscope. Thoracoscopy failed in only three of the 188 patients in their series; failure was due to adhesions, and thoracoscopy had to be converted to an open procedure (60). Advantages of VATS over open techniques include reduced patient pain and decreased postoperative morbidity and mortality. An additional advantage is that lung biopsy can be performed at VATS to determine whether asbestos fibers are present (33). To prevent seeding along trocar ports and thoracoscopic tracts, radiation therapy of all entry ports is performed 10-12 days after the procedure. In the study by Boutin and Rey (60), no patient who underwent preventive radiation therapy developed tumor nodules along entry ports, whereas nine of 20 untreated patients developed nodules. Thoracoscopic evaluation may allow more accurate staging of MPM compared with noninvasive methods such as CT and MR imaging.
Open Surgical Biopsy
Open surgical biopsy may be necessary if thoracoscopy is hindered by adhesions or if more tissue is needed for diagnosis; however, even after thoracotomy, the diagnosis can be in doubt. Adams et al (31) described 92 patients with MPM who underwent open pleural biopsy. A definitive diagnosis of MPM was made in only 77% of these patients. In another 15%, the initial diagnosis was malignancy suggestive of MPM. In 5.5% of the patients, MPM was initially misdiagnosed as benign pleural fibrosis (two patients), an atypical inflammatory process (one patient), malignant fibrous histiocytoma (one patient), and fibrosarcoma (one patient). In the remaining patients (2.5%), the pathologist could not distinguish between MPM and metastatic adenocarcinoma (31).
Sensitivity of Various Diagnostic Methods
Boutin and colleagues (60), in a study of 188 patients with MPM, compared the sensitivity of the diagnostic techniques currently used in the diagnosis of MPM. They found the following rates of sensitivity: pleural fluid cytology, 26%; Abrams percutaneous needle biopsy, 20.7%; pleural fluid cytology and Abrams needle biopsy, 38.7%; and thoracoscopic biopsy, 98.4%. For this reason, thoracoscopic biopsy is becoming the preferred method of diagnosis.
Diagnostic Methods