Malignant Mesothelioma

Cellular Classification

Histologically, mesotheliomas are composed of fibrous or epithelial elements or both. The epithelial form occasionally causes confusion with peripheral anaplastic lung carcinomas or metastatic carcinomas. Attempts at diagnosis by cytology or needle biopsy of the pleura are often unsuccessful. It can be especially difficult to differentiate mesothelioma from adenocarcinoma on small tissue specimens. Thoracoscopy can be valuable in obtaining adequate tissue specimens for diagnostic purposes. Examination of the gross tumor at surgery and use of special stains or electron microscopy can often help. The special stains reported to be most useful include periodic acid-Schiff diastase, hyaluronic acid, mucicarmine, CEA, and Leu M1. Histologic appearance appears to be of prognostic value, with most clinical studies showing that epithelial mesotheliomas have a better prognosis than sarcomatous or mixed histology mesotheliomas.

Stage Information

Patients with stage I disease have a significantly better prognosis than those with more advanced stages. However, because of the relative rarity of this disease, exact survival information based upon stage is limited. A proposed staging system based upon thoracic surgery principles and clinical data is shown below. It is a modification of the older system proposed by Butchart et al. Other staging systems that have been employed, including a proposed new international TNM staging system, are summarized by the International Mesothelioma Interest Group.

Stage I: Disease confined within the capsule of the parietal pleura: ipsilateral pleura, lung, pericardium, and diaphragm

Stage II: All of stage I with positive intrathoracic (N1 or N2) lymph nodes

Stage III: Local extension of disease into the following: chest wall or mediastinum; heart or through the diaphragm, peritoneum; with or without extrathoracic or contralateral (N3) lymph node involvement

Stage IV: Distant metastatic disease

Treatment Option Overview

Standard treatment for all but localized mesothelioma is generally not curative. Although some patients will experience long-term survival with aggressive treatment approaches, it remains unclear if overall survival has been significantly altered by the different treatment modalities or by combinations of modalities. Extrapleural pneumonectomy in selected patients with early stage disease may improve recurrence-free survival, but its impact on overall survival is unknown. Pleurectomy and decortication can provide palliative relief from symptomatic effusions, discomfort caused by tumor burden, and pain caused by invasive tumor. Operative mortality from pleurectomy/decortication is less than 2%, while mortality from extrapleural pneumonectomy has ranged from 6% to 30%. The addition of radiation therapy and/or chemotherapy following surgical intervention has not demonstrated improved survival. The use of radiation therapy in pleural mesothelioma has been shown to alleviate pain in the majority of patients treated. However, the duration of symptom control is short-lived. Single agent and combination chemotherapy have been evaluated in single and combined modality studies. The most studied agent is doxorubicin, which has produced partial responses in approximately 15% to 20% of patients studied. Some combination chemotherapy regimens have been reported to have higher response rates in small phase II trials. However the toxicity reported is also higher and there is no evidence that combination regimens result in longer survival or longer control of symptoms. Recurrent pleural effusions may be treated with pleural sclerosing procedures; however, failure rates are usually secondary to the bulk of the tumor, which precludes pleural adhesion due to the inability of the lung to fully expand.