Description

• Mesothelioma is a rare, insidious, and aggressive malignancy of the mesothelial or serous tissues primarily found in the pleura (80–95%), peritoneum (5–20%), and rarely, the tunica vaginalis and pericardium (1–2%).
• Inhalation of asbestos is the predominant cause of mesothelioma, most often from remote occupational exposure (≥20 years earlier).
• Histologically, there are three types of malignant mesothelioma: epithelioid type (most common and least aggressive), sarcomatoid type (most aggressive), and biphasic type.
• Mesothelioma has a rapidly fatal course (median survival 17 to 25 months for resectable pleural mesothelioma) (1).

Epidemiology

Incidence

• The incidence in the United States has recently begun to decline, a trend attributable to the delayed effects of the asbestos ban initiated in the 1970s.
• Globally, areas of endemic clustering persist, typically in regions with high levels of ongoing asbestos-related industry. Incidence rates are not available, however, due to lack of quality reporting data.
• Incidence increases with age, peaking in the 5th and 6th decade of life, with 70% of pleural disease occurring in males. Peritoneal involvement is slightly higher in women.
• There are 3,000 cases of mesothelioma diagnosed in the United States annually (1).

Prevalence
In the United States, 1 case per 100,000 persons without asbestos industry exposure and 2 to 3 per 100,000 persons with asbestos exposure (1).

Etiology and Pathophysiology

• The predominant cause of mesothelioma is exposure to asbestos (hydrated magnesium silicate fibrous minerals).
• The majority of asbestos fibers are either amphibole (needle-like) or serpentine (curved). All types are capable of causing mesothelioma, although amphiboles (particularly crocidolite and amosite) are more carcinogenic. Serpentine fibers, the predominant fiber type in the United States, are mostly found in ships, buildings, brake lining, and ceiling tiles (2).
• There is a long latent period, typically 20 to 50 years, between exposure and the development of mesothelioma (3).
• The pathogenesis of mesothelioma is multifactorial and not fully understood, but the predominant cause is via inhaled or ingested asbestos fibers becoming trapped in pleural or peritoneal membranes, causing irritation and inflammation. This continued tissue damage and inflammation leads to tumor formation (3).
• Tumors coalesce with a gradual progression from the parietal to visceral pleura and eventual invasion of surrounding structures (2).
• In addition to asbestos, tumors have arisen after prior radiation or exposure to talc, erionite, or mica or in patients with familial Mediterranean fever and diffuse lymphocytic leukemia.

Genetics

• A substantial percentage (>10%) of patients harbor germline mutations in cancer predisposition genes, notably BAP1. BAP1 mutations are linked to an inherited susceptibility to mesothelioma and a pattern of familial cancers. Patients may report an elevated personal or familial history of cancers, especially mesothelioma and uveal melanoma (1),(4).
• In addition to BAP1, other mutations have been associated with genetic predisposition, including MLH1, MLH3, TP53, BRAC2 (1),(4).

Risk Factors

• The predominant risk factor is exposure to asbestos with a dose-dependent risk.
• Occupational exposures involve mining or milling of fibers; work with textiles, cement, friction materials, or insulation; or shipbuilding.
• Nonoccupational exposures include renovation or destruction of asbestos-containing buildings, exposure to industrial sources in the community or natural geologic sources, or exposure to soiled clothing of asbestos workers.
• Radiation exposure, proximity to naturally occurring asbestos deposits, or inhalation of other fibrous silicates can contribute to malignant mesothelioma.
• In contrast to lung cancer and asbestosis, it appears to be no synergistic effect between smoking and the development of mesothelioma.

General Prevention

• Avoidance of asbestos exposure
• Strict adherence to protective protocols for workers in buildings where asbestos is found
• Continued aggressive remediation of asbestos-affected buildings and homes