Pleural mesothelioma is the only known pleural cancer and is caused by asbestos exposure in nearly all cases. Diagnosis is based on history and chest x-ray or CT findings and tissue biopsy. Treatment is supportive, which may require surgery, chemotherapy, or both.
(See also Overview of Asbestos-Related Disorders and Overview of Environmental Pulmonary Disease.)
Asbestos is a family of naturally occurring silicates whose heat-resistant and structural properties made it useful for inclusion in construction and shipbuilding materials, automobile brakes, and some textiles. Chrysotile (a serpentine fiber), crocidolite, and amosite (amphibole, or straight fibers) are the 3 main types of asbestos that cause disease.
Asbestos workers have up to a 10% lifetime risk of developing mesothelioma, with an average latency of 25 to 30 years. Risk is independent of smoking. Mesothelioma arises from the mesothelial surface of the pleural cavity and can spread locally, or it can metastasize to the hilar and mediastinal lymph nodes, pericardium, diaphragm, peritoneum, liver, adrenals, or kidneys and, rarely, the tunica vaginalis of the testis.
Patients most often present with dyspnea and nonpleuritic chest pain. Constitutional symptoms are uncommon at presentation. Invasion of the chest wall and other adjacent structures may cause severe pain, hoarseness, dysphagia, Horner syndrome, brachial plexopathy, or ascites.
The pleural form of mesothelioma, which represents > 90% of all cases (the other 10% include pericardial and peritoneal mesotheliomas), appears on x-ray as diffuse unilateral or bilateral pleural thickening that appears to encase the lungs, usually producing blunting of the costophrenic angles. Pleural effusions are present in 95% of cases and are typically unilateral, large, and hemorrhagic. Diagnosis is based on pleural fluid cytology or pleural biopsy. Increased levels of hyaluronidase in pleural fluid are suggestive but not diagnostic of mesothelioma.
If diagnosis is uncertain after these procedures, biopsy by VATS or thoracotomy is done. Soluble mesothelin-related proteins released into the serum by mesothelial cells are being studied as possible tumor markers for disease detection and monitoring, but the false-positive rate may limit their effectiveness.Pleural Mesothelioma
BY PERMISSION OF THE PUBLISHER. FROM HUGGINS J, SAHN S. IN BONE’S ATLAS OF PULMONARY AND CRITICAL CARE MEDICINE. EDITED BY J CRAPO. PHILADELPHIA, CURRENT MEDICINE, 2005.
Staging is done with chest CT, mediastinoscopy, and MRI. Sensitivity and specificity of MRI and CT are comparable, although MRI is helpful in determining tumor extension into the chest wall, diaphragm, mediastinal structures, spine, or spinal cord. PET may have better sensitivity and specificity for distinguishing benign from malignant pleural thickening. Bronchoscopy should be done to exclude coexisting endobronchial lung cancers.
Screening guidelines for mesothelioma for people who are exposed to asbestos are not currently available. Serum biomarkers are emerging as a potential modality to diagnose and monitor patients, but further work is required to validate their use in clinical practice (1).
Mesothelioma remains an incurable cancer, and long-term survival is uncommon. Surgery to remove the pleura, ipsilateral lung, phrenic nerve, hemidiaphragm, and pericardium combined with chemotherapy or radiation therapy may be considered, although it does not substantially change prognosis or survival time. No treatment substantially prolongs survival. Median survival from time of diagnosis is 9 to 12 months, depending on the location and cell type. Imaging and histopathologic stage provide the strongest prognostic information (1). Patients with the poorest prognosis are characterized by
The major focus of treatment is supportive care and relief of pain and dyspnea.
Given the diffuse nature of the disorder, radiation therapy is usually unsuitable except to treat localized pain or needle-tract metastases. It is not generally used for treatment of nerve root pain.
Pleurodesis or pleurectomy can be used to help reduce dyspnea caused by pleural effusions.
Adequate analgesia is important but difficult to achieve. Usually, opioids, both transdermal and delivered via indwelling epidural catheters, are used.
Because morbidity and mortality are high with extrapleural pneumonectomy, pleurectomy and decortication are used increasingly if all grossly visible tumor is limited to one hemithorax and can be removed. However, complete resection is usually not feasible, in which case adding chemotherapy and radiation therapy prolongs survival (1).
Nonsurgical therapies include combination chemotherapy regimens (eg, with pemetrexed and a platinum-based drug) plus radiation therapy. Chemotherapy can relieve symptoms in most cases and sometimes decreases tumor size. Combination chemotherapy of pemetrexed and cisplatin prolonged survival by 3 months compared to cisplatin alone (2). In this study, addition of folic acid and vitamin B12 supplementation reduced toxicity. Clinical trials have shown that adding bevacizumab to pemetrexed and cisplatin prolongs survival (3), as did the addition of nintedanib to cisplatin-pemetrexed (4). The tyrosine kinase inhibitor cediranib has demonstrated promise in clinical trials as a second-line drug (5, 6). Antimethothelin immunotherapy has demonstrated promise as well and is currently being investigated in combination with the standard cisplatin-pemetrexed treatment (7).
Therapies under investigation include immunotherapeutic vaccination, oncolytic virotherapy, gene therapy, photodynamic therapy, and hyperthermic intrapleural chemotherapy.
