Pleural mesothelioma, a rare, primary cancer of mesothelial serosa, is caused by asbestos exposure in the great majority of cases. Symptoms include persistent cough, shortness of breath, chest pain, and unexplained weight loss. Diagnosis is based on history of exposure, chest imaging, and tissue biopsy. Diffuse malignant mesothelioma is almost always fatal.
(See also Overview of Asbestos-Related Disorders and Overview of Environmental and Occupational Pulmonary Disease.)
The term mesothelioma (or malignant mesothelioma) generally refers to a malignant primary cancer of mesothelial serosa that is almost always caused by asbestos exposure.
Asbestos is a family of naturally occurring silicates whose heat-resistant and structural properties are useful in construction and shipbuilding materials, automobile brakes, and some textiles. There are two main classes of asbestos: serpentine (which includes chrysotile) and amphibole (which includes amosite, crocidolite, anthophyllite, tremolite, and actinolite).
Asbestos causes the great majority of malignant mesotheliomas. All types of asbestos can cause malignant mesothelioma, but some fiber types are more likely to do so than others (amphibole fibers generally having higher potency than serpentine).
The risk of malignant mesothelioma due to asbestos is dose dependent. However, cases are known to occur at low levels of exposure.
There is a long latency of 30 to 50 years from time of asbestos exposure to development of mesothelioma.
In addition to occupational exposure, malignant mesothelioma can occur as a result of para-occupational (or take-home) exposure to asbestos as well as through environmental exposures. Notable sites where environmental exposure to naturally occurring asbestos has been associated with mesothelioma include erionite in Cappadocia, Turkey, tremolite in Mediterranean regions, crocidolite in rural Southwestern China, antigorite in New Caledonia, and Libby asbestos in Libby, Montana.
Asbestos-contaminated talcum powder is another nonoccupational source of asbestos exposure associated with mesothelioma (1). Other causes of mesothelioma include other mineral fibers, radiation therapy for lymphoma, and the DNA virus SV40. Risk is independent of smoking.
Historically, most cases of mesothelioma occurred in males, given work in industrial jobs with heavy asbestos exposure. As the incidence of mesothelioma in males has declined over time, the proportionate disease burden of malignant mesothelioma in females has increased (2, 3).
Up to 90% of malignant mesotheliomas arise in the pleura, with most of the remaining cases in the peritoneum (4). Uncommonly, mesothelioma can occur in the pericardium and the tunica vaginalis.
There are two major histological subtypes:
Epithelioid, which accounts for approximately ≥ 60% of mesotheliomas
Sarcomatoid
General references
1. Moline J, Bevilacqua K, Alexandri M, Gordon REJ Occup Environ Med 2020; 62(1), 11-17. doi:10.1097/JOM.0000000000001723
2. Mazurek JM, Blackley DJ, Weissman DN. Malignant Mesothelioma Mortality in Women - United States, 1999-2020. MMWR Morb Mortal Wkly Rep 2022; 71(19), 645-649. doi:10.15585/mmwr.mm7119a1
3. Alpert N, van Gerwen M, Taioli E. Epidemiology of mesothelioma in the 21(st) century in Europe and the United States, 40 years after restricted/banned asbestos use. Transl Lung Cancer Res 2020; 9(Suppl 1), S28-S38. doi:10.21037/tlcr.2019.11.11
4. Markowitz S. Asbestos-related lung cancer and malignant mesothelioma of the pleura: selected current issues. Semin Respir Crit Care Med 2015; 36(3), 334-346. doi:10.1055/s-0035-1549449
Symptoms and Signs of Mesothelioma
Patients most often present with dyspnea and nonpleuritic chest pain. Pleural effusions, usually unilateral and hemorrhagic, are present in up to 90% of patients. Constitutional symptoms are uncommon at presentation.
Tumor invasion of the chest wall and other adjacent structures may cause severe pain, hoarseness, dysphagia, brachial plexopathy, or ascites.
Diagnosis of Mesothelioma
Chest imaging (x-ray, CT)
Pleural fluid cytology or pleural biopsy
The diagnosis of malignant pleural mesothelioma can be challenging.
Chest imaging is key to diagnosis and staging. Typical findings on chest x-ray are nodular pleural thickening, pleural effusion, and loss of thoracic volume. Chest CT enables better visualization of the pleural changes and extent of the disease. PET-CT and MRI scanning may help identify more extensive disease.
A pleural biopsy is usually required as pleural fluid cytology is usually nondiagnostic. The diagnosis of malignant mesothelioma is based on histologic appearance and immunohistochemical staining. However, the histology can make it challenging to distinguish mesothelioma from other tumors.
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 and MRI. MRI is helpful in characterizing tumor extension.
There are no definitive screening recommendations for mesothelioma to detect early-stage disease in asbestos-exposed populations.
Treatment of Mesothelioma
Supportive care, including thoracentesis, pleurodesis, and pain control
Chemotherapy and immunotherapy
Malignant pleural mesothelioma is typically unresectable at the time of diagnosis. The major focus of treatment is supportive care and relief of pain and dyspnea.
Surgical resection can be considered in patients with early-stage disease. In more advanced disease, surgical approaches have been used for debulking or attempting to resect all macroscopic disease; the survival benefit of these approaches is unclear.
Radiation therapy can be used to reduce tumor bulk and as a palliative measure to relieve symptoms.
Chemotherapy (eg, platinum agents plus folate antimetabolites) has shown limited benefit, with little impact on long-term survival. Immunotherapy1, 2).
Supportive care includes thoracentesis, pleurodesis, and pain control. Treatment of malignant pleural effusions, which are common, can improve symptoms and quality of life. Palliative care to control pain and optimize quality of life is a key priority.
Treatment references
1. Banna GL, Signori A, Curioni-Fontecedro A, et al. Systemic therapy for pre-treated malignant mesothelioma: A systematic review, meta-analysis and network meta-analysis of randomised controlled trials. Eur J Cancer 2022; 166, 287-299. doi:10.1016/j.ejca.2022.02.030
2. Fennell DA, Dulloo S, Harber J. Immunotherapy approaches for malignant pleural mesothelioma. Nat Rev Clin Oncol 2022; 19(9), 573-584. doi:10.1038/s41571-022-00649-7
Prognosis for Mesothelioma
Prognosis remains poor despite novel therapeutic approaches such as immunotherapy. Median survival is approximately 6 to 18 months, depending on stage and histology (1). Epithelioid mesothelioma, which is the most common histological subtype, is associated with longer median survival than sarcomatoid mesothelioma.
Aside from histologic subtype, prognostic indicators and biomarkers have limited prognostic value.
Prognosis reference
1. Alpert N, van Gerwen M, Taioli E. Epidemiology of mesothelioma in the 21(st) century in Europe and the United States, 40 years after restricted/banned asbestos use. Transl Lung Cancer Res 2020; 9(Suppl 1), S28-S38. doi:10.21037/tlcr.2019.11.11
Key Points
Malignant mesothelioma is a rare, aggressive, and almost always fatal cancer, with a 5-year survival rate of about 10%.
The great majority of malignant mesotheliomas are related to asbestos exposure, which can be occupational, para-occupational, or from environmental sources.
Treatment is focused on supportive care. Although immunotherapy has shown promise, prognosis remains poor.
