Malignant mesotheliomas are neoplastic growth of the mesothelial cells in the body. Mesothelial cells are found in the lining of various body cavities. To name, the pleura, peritoneum, pericardium and the testes are lined by these cells. The majority of malignant mesothelioma occurs in the pleura, accounting for almost 90% of all cases.
In the United States, the incidence of malignant mesothelioma is pegged at 0.1-0.2 in 100,000 which is higher than the international incidence of 0.9 per 100,000 for both sexes. A two to 10-fold increase in risk is seen among populations that are exposed to asbestos. Around 2500 to 3000 cases are diagnosed each year in the country. Peak incidence of the disease occurs in the 3rd and 4th decade of life, with two thirds of cases occurring in the 5th and 6th decades.
Malignant mesothelioma is more commonly seen among men with a male to female ratio of 3:1. Among men, 53% reported an occupational exposure to asbestos. The most commonly cited job descriptions were explosives workers, naval mechanics, construction workers, miners, automotive mechanics and even bakers. Around 46% of the men reported a prior non-occupational exposure to asbestos. Among women, 75% were reported to have prior exposure to asbestos, half of which were secondary household contact. Epitheloid was the most common histologic subtype found among women, and the mesothelioma most commonly affected the pleura.
Epitheloid, sarcomatous and biphasic (mixed) are the three major histologic subtypes of malignant mesothelioma. Sixty to seventy (60-70%) of mesothelioma are epitheloid. These transformed cells start off as individual nodules and plaques which then later on come together to form sheets. The plaques start at the lower portions of the chest, and slowly progresses upwards to encroach on the upper parts of the chest and interlobar fissures. Tumor growth, in most cases also encases the diaphragm, chest tube and various drainage tracts. If left untreated, the disease can quickly invade the parenchyma of the lungs, the esophagus, and may even reach the great vessels of the heart, as well as the surrounding bony structures such as the chest wall, ribs and vertebrae.
Exposure to asbestos is the principal and commonly cited trigger in the pathogenesis of malignant mesothelioma. Different forms of asbestos, such as chrysotile, amphibole, erionite, crocidolite, and amosite are all cited to cause the formation of more than 80% of mesotheliomas. Crocidolite asbestos is commonly the cause for mesotheliomas found among miners, asbestos manufacturers, construction and heat workers. The amphiboles are found to be more carcinogenic than its chrysotile counterparts.
Exposure to radiation using silicates such as zeolite and thorium dioxide has also been linked to the pathogenesis of malignant mesothelioma. Although as of yet controversial, Simian virus 40 has also been touted to have an etiological role in mesothelioma formation. Chromosomal changes most frequently found in malignant mesothelioma include a loss of a single copy of chromosome 22, modifications to the p16 (CDKN2A) and p14 (ARF) of the tumor suppressor gene, as well as a functional loss of neurofibromin 2 (NF2). Interleukin 8 has also been shown to have a direct effect on the growth potential of mesothelial cells and thus also contributes to the sustained growth of malignant mesothelial cells.
In essence, exposure to asbestos still remains to be the most common instigator in the pathogenesis of malignant mesothelioma. Exposure to asbestos by itself has also been touted to cause the majority of mesotheliomas.
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