Description

• Mesothelioma is a rare, aggressive malignancy of the mesothelial or serous tissues primarily found in the pleura (65–70%) or peritoneum (20–30%), tunica vaginalis (1–2%) or pericardium (1–2%) (1).
• Inhalation of asbestos is the predominant cause of mesothelioma, most often from occupational exposure.
• There are four different types of malignant mesothelioma: epithelioid type (most common), sarcomatoid type, biphasic or mixed type, and desmoplastic type
• Mesothelioma has a rapidly fatal course (median survival 6 to 12 months, mean symptoms-to-survival time 345 days) (1).

Epidemiology

Incidence

• The incidence in the United States is decreasing, but it is increasing in other countries, particularly in Great Britain and Australia. Great Britain and Australia currently have the highest incidence rates worldwide for malignant mesothelioma.
• Rates of mesothelioma have started to decline worldwide due to reduced exposure and better understanding of the pathophysiology. However, there are still areas of endemic clustering (usually areas with high levels of asbestos-related industry) (2).
• The 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 3,300 cases of mesothelioma diagnosed in the United States annually (2).

Prevalence
In the United States, the prevalence is 1 to 2 cases per million individuals (1).

Etiology and Pathophysiology

• The predominant cause of mesothelioma is exposure to asbestos (hydrated magnesium silicate fibrous minerals).
• There is a long latent period of up to 40 years between exposure and development of mesothelioma (2).
• Inhaled or ingested asbestos fibers become trapped in pleural or peritoneal membranes, causing irritation and inflammation. This continued tissue damage and inflammation leads to the release of oxygen free radicals which damages the DNA and leads to abnormal repair.
• The majority of asbestos fibers are either amphibole (sharp, rod like) or serpentine (curved). Serpentine fibers make up the majority of fibers in the United States and are less carcinogenic than the amphibole type. Serpentine fibers are mostly found in ship buildings, cement, brake lining, and ceiling and pool tiles (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

• Genetic profiling has unveiled common mutations, including decreased expression of key molecules in the p53 pathway, such as p14, p16, and NF2-MERLIN (3).
• Deletions and loss of other genes, including BAP1,SETD2, DDX3X, ULK2, RR2, CFAP45, SETDB1, and DDX51 have been demonstrated in mesothelioma as well (3).

Risk Factors

• The predominant risk factor is exposure to asbestos.
• Occupational exposures involve mining or milling of fibers, work with textiles, cement, friction materials, 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 (1),(2).
• Radiation exposure, smoking, proximity to naturally occurring asbestos deposits, or inhalation of other fibrous silicates can contribute to malignant 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