Understanding malignant mesothelioma

What is mesothelioma?

Mesothelioma is a rare tumor most commonly originating in the pleura and less commonly in the peritoneum. In 2002, 65 cases were reported to the BC Cancer Agency. The annual incidence in the general population is estimated at 1 to 1 cases per million. The incidence of mesothelioma has increased substantially since the 1940s, especially among older men. The estimated incidence rate for men aged 40 to 50 is 5 per million, and 17 per million for men in their 70s and 80s.

Types

Three basic morphologic types of mesothelioma occur: epithelial, sarcomatous, and mixed. Epithelial is the most common and has the better prognosis, however the overall prognosis for this tumor is dismal. The median survival rate for pleural mesothelioma from the onset of symptoms is less than 11/2 years, and for peritoneal tumors it’s less than 1 year.

Causes

While several causes of mesothelioma have been identified (convincing evidence exists for genetic predisposition and a contributory role by Simian Virus 40 [SV 40] infection), the most likely causal factor of mesothelioma in industrialized nations is asbestos exposure. Fairly consistent and strong epidemiological evidence indicates that approximately 70% to 90% of mesothelioma cases can be related to asbestos exposure. This is a direct consequence of past industrial use of asbestos in our society. All asbestos fibre types can cause mesothelioma, though not to the same extent. Amphibole types of asbestos, including crocidolite and tremolite, pose the most significant risk, while the serpentine chrysotile asbestos poses a much lower but not insignificant risk. High-risk occupations related to asbestos exposure include insulators, ship builders, railway mechanics, miners and millers of asbestos, asbestos textile workers, boilermakers, welders, pipefitters, plumbers, construction workers, building maintenance and renovation workers, and asbestos abatement workers.

Unique characteristics

Unlike asbestos-related lung cancer, asbestos-related mesothelioma does not demonstrate a dose-response relationship or a relation to smoking. Asbestos exposure among mesothelioma victims is often not protracted or as heavy as in cases of asbestosis or asbestos-related lung cancer. The latency period for asbestos-related mesothelioma is extremely long—almost always greater than 15 years—and commonly as long as 30 to 40 years.

What is the presentation of mesothelioma?

Pleural tumors typically present with localized chest pain and dyspnea. Chest X-rays may demonstrate pleural effusion or a pleural mass. The disease tends to progress with local invasion and lymphatic spread, although hematogenous dissemination and distant metastasis do occur. As the disease progresses, the pleural space is obliterated, the lungs may become encased, and ipsilateral mediastinal retraction can occur. Local tumor extension into the larynx, esophagus, mediastinum, and neck results in dysphagia, hoarseness, Horner syndrome, and superior vena cava syndrome. Intractable chest pain, weight loss, fever, and cardiac dysrhythmias commonly occur.

Diagnosis

Diagnosis requires a tissue sample. This is best obtained by thoracoscopy-guided biopsy or thoracotomy. It is necessary to differentiate mesothelioma from metastatic adenocarcinoma of the lung or other tissue in order to determine treatment. This typically requires histochemical and immunohistochemical staining as well as electron microscopy evaluation.

Treatment

Treatment is primarily palliative. No single treatment option has proved very successful and a combination of modalities is commonly used including surgery, chemotherapy, and radiotherapy. Other treatments such as photodynamic therapy, the use of biological agents including interferon and interleukin 2, and gene therapy are being explored. As knowledge of the molecular biology of this malignancy increases, more novel and less toxic treatment options should become available. Some combination therapies using newer cytotoxic agents have demonstrated modest success in improving survival. The lack of major breakthroughs in treatment, however, has led many afflicted individuals to seek non-traditional, unproven treatments.

What is the physician’s role?

Given the specific causal association between asbestos exposure and mesothelioma, and the fact that most asbestos exposure in Canada is likely of occupational origin, it is not unreasonable to conclude that mesothelioma is an occupational disease unless proved otherwise. The WCB recognizes this presumptive association under Schedule B.

However, data available from the BC Cancer Agency and the WCB indicate that from 1970 to 2002, only about one-third of mesothelioma cases have been compensated in BC (349 compensated cases of 981 registered cases). Most physicians may never see a case of mesothelioma, but those who do should ensure it is reported to the WCB for consideration.

The usefulness and benefit of screening for mesothelioma is unknown given the rarity of the tumor, the long latency period, and lack of effective treatment. Physicians should provide compassionate support, adequate symptom control, and prompt referral for appropriate treatment. They should also advise their patients regarding non-conventional treatments, ensuring no harm is done and that their patients are not taken advantage of in their time of need.

—Sami Youakim, MD, FRCP
Medical Advisor
WCB Occupational Diseases Service

Selected reading

Cabone M, Kratzke A, Testa JR. The pathogenesis of mesothelioma. Seminars Oncol 2002;29:2-17. PubMed Abstract Full Text

Chanhinian AP, Pass HI. Malignant mesothelioma. In: Kufe DW (ed). Cancer Medicine. 6th ed. Hamilton: BC Decker Inc. 2003:1447-1466.

Mark EJ, Yokoi T. Absence of evidence for a significant background incidence of diffuse malignant mesothelioma apart from asbestos exposure. Ann NY Acad Sc 1991;643:196-204. PubMed Abstract

McDonald JC, McDonald AD. The epidemiology of mesothelioma in historical context. Eur Respir J 1996;9:1932-1942. PubMed Abstract Full Text

Nichloson WJ. The carcinogenicity of chrysotile asbestos: A review. Indust Health 2001;39:57-64. PubMed Abstract

Pistolesi M, Rusthoven J. Malignant pleural mesothelioma: update, current management, and newer therapeutic strategies. Chest 2004;126:1318-1329. PubMed Abstract Full Text