Mesothelioma

Synonyms and related keywords: mesothelioma, asbestos-related cancer, cancer of the pleura, asbestos exposure, plural cancer, malignant mesothelioma, mesothelioma malignancy, pleural malignant mesothelioma, lung cancer, lung tumor, pulmonary cancer, pulmonary tumor, pulmonary malignancy, sarcomatous mesothelioma, epithelial mesothelioma, mixed mesothelioma, pleural mesothelioma

Background: Mesothelial cells normally line the body cavities, including the pleura, peritoneum, pericardium, and testis. Malignancies involving mesothelial cells in these body cavities are known as malignant mesothelioma, which may be localized or diffuse. Diagnosis is difficult because the results from fluid analysis of the effusion from the tumor are not usually diagnostic. Most, but not all, pleural malignant mesothelioma is associated with asbestos exposure. Of patients with pleural malignant mesothelioma, 77% have been exposed to asbestos in the past. Mesothelioma is more common in males than in females and it occurs in the fifth and seventh decade of life. Most of malignant mesothelioma occur in the pleura (90% of the time).

Pathophysiology: The 3 major histological types of mesothelioma are sarcomatous, epithelial, and mixed. Pleural mesothelioma usually begins as discrete plaques and nodules that coalesce to produce a sheetlike neoplasm. Tumor growth usually begins at the lower part of the chest. The tumor may invade the diaphragm and encase the surface of the lung and interlobar fissures.

The tumor may also grow along drainage and thoracotomy tracts. As the disease progresses, it often extends into the pulmonary parenchyma, chest wall, and mediastinum. Pleural mesothelioma may extend into the esophagus, ribs, vertebra, brachial plexus, and superior vena cava.

Asbestos is the principal carcinogen implicated in the pathogenesis. The industries associated with asbestos exposure include ship building, construction, ceramics, paper mill, auto parts, railroad and insulation.

Most malignant mesotheliomas have complex karyotypes, with extensive aneuploidy and rearrangement of many chromosomes. A loss of a single copy on chromosome 22 is the most common abnormality.

Frequency:

• In the US: Approximately 2500-3000 cases are diagnosed per year.

• Internationally: Frequency is 0.9 cases per 100,000 persons.

Mortality/Morbidity:

• Median survival for patients with malignant mesothelioma is 11 months. It is almost always fatal. Median survival based on histologic type is 9.4 months for sarcomatous, 12.5 months for epithelial, and 11 months for mixed. Approximately 15% of patients have an indolent course.

• Asbestos exposure is linked to at least 50% of patients developing malignant mesothelioma. Approximately 8 million people in the United States have been exposed to asbestos in the workplace. Family members are also exposed to asbestos embedded in the worker's clothing. The combination of tobacco and asbestos exposure greatly increases the risk of developing pleural mesothelioma.

Race:

• Mesothelioma has no racial predilection. Asbestos exposure is the most important factor. Race is not a factor.

Sex:

• Malignant mesothelioma is more common in men, with a male-to-female ratio of 3:1. It can also occur in children; however, these cases are not thought to be associated with asbestos exposure.

• With regard to women with mesothelioma, a 1996 case series by Ascoli et al showed 86% of tumors arising from the pleura, of which most were the epithelial type. Of the patients in this series, 75% had a history of exposure to asbestos and more than half developed the malignancy secondary to household contact with a worker exposed to asbestos.

• With regard to men with mesothelioma, the same case series demonstrated 45.5% with a history of exposure to asbestos and 53% with occupational exposure to asbestos. Most who were involved were construction workers, railroad workers, naval mechanics, bakers, explosive workers, and automobile mechanics.

Age:

• Malignant mesothelioma has a peak incidence 35-45 years after asbestos exposure. It commonly develops in the fifth to seventh decade of life.

History:

• Dyspnea and nonpleuritic chest wall pains are the most common presenting symptom.

• Chest radiographs show obliteration of the diaphragm, nodular thickening of the pleura, decreased size of the involved chest, radiolucent sheetlike encasement of the pleura, or a combination of these.

• A loculated effusion is present in more than 50% of patients, and a major portion of the pleura is opacified by the effusion.

• Chest discomfort, pleuritic pain, easy fatigability, fever, sweats, and weight loss are the other common accompanying symptoms. Patients may also be asymptomatic, with evidence of a pleural effusion noted incidentally on physical examination or by chest radiograph. Metastatic disease is uncommon at presentation and contralateral pleural abnormalities are usually secondary to asbestos-related pleural disease rather than metastatic disease.

• Approximately 60-90% of patients may have symptoms of chest pain or dyspnea.

Physical:

• Physical findings of pleural effusion are usually noted upon percussion and auscultation.

• In rare cases, malignant mesothelioma manifests as cord compression, brachial plexopathy, Horner syndrome, or superior vena cava syndrome. Death is usually due to infection or respiratory failure from the progression of mesothelioma.

• Primary sites include the pleura (87%), the peritoneum (5.1%), the pericardium (0.4%), and the right side of the thorax (more so than the left side, by a right-to-left ratio of 1.6:1).

Causes:

• A substantial proportion of patients were exposed to asbestos in asbestos mills, shipping yards, mines, or their homes.

• The crocidolite in asbestos is associated with mesothelioma in miners, manufacturers (using asbestos), and heating and construction workers. The rod-shaped amphiboles are more carcinogenic than the chrysotile.

• Malignant mesothelioma has also been linked to therapeutic radiation using thorium dioxide and zeolite, a silicate in the soil.

• An etiological role for simian virus 40 in malignant mesothelioma has also been suggested. Asbestos exposure alone was associated with malignant mesothelioma, but SV 40 alone was not. Thus giving some epidemiological evidence that SV 40 is a possible cocarcinogen. Its direct role at this point is still controversial.

• Interleukin 8 has direct growth-potentiating activity in mesothelial cell lines.

• Loss of one copy of chromosome 22 is the single most common karyotypic change in malignant mesothelioma. Other chromosomal changes commonly observed include 1p, 3p, 9p, and 6q. Several changes in the tumor suppressor gene p16 (CDKN2A) and p14 (ARF) and loss of function of neurofibromin 2 (NF2) or merlin are altered.