Malignant mesothelioma

Malignant mesothelioma (MM) is a tumor derived from mesothelial cells, native cells of the body cavities. The pleural cavity is the most common site, with a present ratio of 9:1 with peritoneal tumors. Exposure to asbestos can be documented in about 80% of the cases. The disease develops decades after exposure, during which period the neoplastic cells accumulate a variety of chromosomal aberrations. The incidence of MM is on the rise in western countries. Patients are typically older than 50 years of age, with males being affected slightly more. The prognosis is extremely poor, with survival of 4 to 12 months from diagnosis, which has remained largely unaltered by medical intervention.

New agents, such as the antifolate drug pemetrexed, and currently evaluated as treatment for MMin combination with other drugs. The main differential diagnoses of the epithelioid type of MM is metastatic adenocarcinoma (AC) and reactive mesothelial proliferations. Benign mesothelial cells react to a wide variety of stimuli and injuries that break their continuity by proliferation and reactive cellular changes. Consequently, hyperplastic mesothelial cells in various benign clinical settings undergo marked nuclear and cytoplasmic alterations, some of them mimicking the morphology of malignant cells.

Adenocarcinomas metastatic to serosal surfaces are most commonly of breast, ovary and lung origin. Morphological guidelines for the separation of benign from malignant mesothelium have been described, but are often difficult to implement .

Pathology

On gross appearance, malignant mesothelioma is a firm, grayish tumour that coalesces on the visceral and parietal pleural surfaces into discrete plaques and nodules. The lung can be completely covered with a thick rind of tumour that can reach diameters of 5 cm or more, despite only minimal penetration of the underlying lung parenchyma. Adjacent structures are involved at an early stage, with invasion of the chest wall, pericardium, diaphragm and interlobar fissures. A total of 70% of patients will have mediastinal lymph node involvement at autopsy. Haematogenous metastases are more common than previously thought, particularly to liver, lung, bone and adrenal glands.

Histology

Malignant mesothelioma is typically classified into three histological subtypes: epithelial, sarcomatoid and biphasic. This categorization is somewhat of an oversimplification, in that the larger the tissue sample, the more frequent the histological variation. Nonetheless, the classification scheme has general diagnostic and prognostic utility. Epithelial mesotheliomas have been reported to have a better prognosis than sarcomatoid and biphasic forms. The epithelial variant is the most common, comprising 50–60% of all mesotheliomas. Typical histological appearances of this subtype include tubulopapillary, glandular and solid epithelial patterns. Sarcomatoid mesotheliomas are composed of malignant spindle cells which may mimic malignant mesenchymal tumours, such as fibrosarcoma or leiomyosarcoma. Biphasic or mixed mesotheliomas have epithelial and sarcomatoid features, but large tissue samples and multiple sections may be needed to demonstrate both components.

Mortality Rate

The median survival of patients with mesothelioma is between 6 and 18 months, and has not been significantly affected by most currently available therapeutic interventions. Some patients who undergo aggressive multimodality therapy for localized disease may demonstrate prolonged survival times compared with ‘matched’ historical controls. In addition, combination chemotherapy with novel antifolates has been shown to prolong median survival by approximately 3–4 months. The majority of affected patients die from local extension and respiratory failure; tumour extension below the diaphragm may result in death from small bowel obstruction. Patients may also die from arrhythmias, heart failure, or stroke caused by tumour invasion of the heart or pericardium.

Paraneoplastic Syndromes

A number of paraneoplastic syndromes have been described in the setting of mesothelioma, including: disseminated intravascular coagulation; migratory thrombophlebitis thrombocytosis; Coombs-positive haemolytic anaemia; hypoglycaemia; and hypercalcaemia associated with secretion of a parathyroid hormone-like peptide. While unusual in mesothelioma, metastases may occur to the contralateral lung, brain and other extrathoracic sites. Direct extension of the tumour into the abdominal cavity is more common, particularly in patients who have prolonged survival after primary aggressive therapy of their intrathoracic disease.

In these patients, a disseminated spread of tumour nodules throughout the abdominal cavity in a manner similar to primary peritoneal mesothelioma can be seen. In such patients, invasion of liver and other organs is rare, but bowel obstruction can be a major problem.

Last updated Dec 12/06