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Diagnosing malignant mesothelioma, as with any other disease, starts with a meticulous and thorough gathering of information from the patient's history coupled with a directed physical examination. Particular effort and attention should be paid to the patient's occupation as well as the environment that he or she moves in everyday. Epidemiological studies have shown that more than 80% of mesotheliomas may be associated with asbestos exposure, thus a documented exposure to asbestos in a particular patient should be sought after. Asbestos is commonly encountered in certain occupations, to name, mining, milling, manufacturing, shipbuilding, construction trades, pipe fitters and boilermakers. A high index of suspicion for the diagnosis of malignant mesothelioma should be at hand, when a patient's occupation is one of those listed above.

Family members of persons with those at risk occupations are themselves at higher risk for developing malignant mesothelioma, and other asbestos related diseases compared to the general population. Among people living near natural sources of asbestos there is also seen a higher incidence of malignant mesothelioma. In three small villages in central Cappadocia, Turkey, malignant mesothelioma was found to be the cause for as high as 50% of all deaths.

Patients with malignant mesothelioma commonly present with chest pain and shortness of breath. These are brought about by the local extension of the tumor that impinges on nerves and blood vessels as well as the pleural effusion that it causes.

Laboratory examinations that are helpful in the diagnosis include a chest radiograph, lung function tests, a chest CT-scan or MRI, and pleural fluid cytopathology to detect abnormal cells. However, the gold standard for diagnosis still remains to be biopsy of the pleural tissue.

Bilateral pleural thickening or calcified plaques usually seen first on the lower lobes, and then progresses upwards towards the middle and upper lobes are usually seen in the chest radiographs of patients with mesothelioma. An indistinct heart border is also seen frequently. These thickenings are attributed to the chronic exposure to asbestos. In cases wherein chest radiographs are equivocal, helpful tools that can be used are chest CT-scans or MRI. With a chest CT-scan or MRI, subpleural reticulations, and lines that are 5 to 10 mm in length parallel to the pleural surface, as well as calcified plaques are usually seen. These, although not specific, are highly characteristic for asbestosis.

Cytopathologic examination of the pleural fluid must be done. Aspiration of the accumulated fluid can be done through thoracentesis or chest tube thoracotomy.

The gold standard for the diagnosis of malignant mesothelioma still remains to be biopsy. This could be achieved laparoscopically or through an open chest surgery.

Immunohistochemical studies are very helpful in differentiating malignant mesothelioma from other neoplastic entities. The presence of both proteins mesothelin-1 and HBME- 1 (human mesothelial cell 1) points towards the diagnosis of malignant mesothelioma.
Malignant mesothelioma can be one of three histologic subtypes. To name, epitheloid, sarcomatoid, or biphasic (mixed). Fifty to sixty percent of malignant mesotheliomas are epitheloid in histology. The epitheloid subtype also holds a more favorable prognosis compared to the other two subtypes.

A thorough history taking coupled with a targeted physical examination as well as the judicious use of laboratory examinations will go a long way in the diagnosis of any disease, particularly in the diagnosis of malignant mesothelioma.