Diagnosis of malignant mesothelioma

A definitive pathological diagnosis of malignant pleural mesothelioma usually requires a tissue (biopsy) specimen to demonstrate that the lesion has a mesothelial phenotype and that it shows neoplastic invasion, as opposed to benign entrapment of mesothelium as part of a fibro-inflammatory process. 

• Evidence of malignant mesothelioma on cytological examination of pleural effusion fluid should be confirmed by tissue biopsy or, if a biopsy is considered inadvisable, impractical, or unnecessary, the cyst diagnosis should be supported by clinical and radiological data as a surrogate for the histological demonstration of invasion. 

• The anatomical location and extent of the pleural tumor should be ascertained by imaging studies. 

• The histological appearances of malignant pleural mesothelioma can vary widely, from epithelioid, to sarcomatoid and biphasic mesotheliomas – together with distinctive subtypes – and such variation occurs not only from one mesothelioma to another but sometimes within single mesothelioma. 

• Recognition of the histological subtype can facilitate diagnosis and provides important prognostic information. 

• Immunohistochemistry is essential for the diagnosis and differential diagnosis of malignant pleural mesothelioma and should include positive and negative (carcinoma-related) markers.

The diagnosis of malignant mesothelioma can be difficult, with symptoms and clinical findings that can mimic and be mimicked by other diseases. Pleural mesothelioma patients may present with dyspnoea, chest pain (pleuritic or non-pleuritic), cough, weight loss, or any combinations of these symptoms. Initial clinical and radiological examination usually reveals a pleural effusion, often massive. 

Rarely, patients are asymptomatic at the time when a radiological abnormality is demonstrated, and patients seldom present with metastatic disease. Some patients with malignant mesothelioma experience a long interval between the first onset of symptoms and subsequent diagnosis, but whether a long interval signifies enhanced or diminished survival following diagnosis is unclear. 

Most patients with malignant pleural mesothelioma have a background of asbestos exposure, and some may have had antecedent symptoms associated with the benign asbestos-related disease – for example, symptoms related to asbestosis or benign asbestos pleuritis with effusion. Others may have radiological evidence of past asbestos exposure, such as pleural plaques. 

In general, biopsy, immunohistochemical analysis, and correlation with radiological and clinical features are needed for the diagnosis of mesothelioma. When immunohistochemical findings are non-diagnostic or discordant, electron microscopy – including electron microscopic examination of tissue retrieved from blocks of paraffin embedded biopsy tissue or cytology cell blocks – can be used, but electron microscopy is not recommended for ‘routine’ diagnosis of mesothelioma. 

Although several cytological and histological findings may raise varying levels of suspicion of malignant pleural mesothelioma a current requirement for the definitive clinicopathological diagnosis of malignant pleural mesothelioma is the demonstration of neoplastic invasion – for example, infiltration into subpleural fat, chest wall skeletal muscle, rib or lung – by histological examination or by imaging studies, and by the clinical exclusion of alternative causes for an atypical mesothelial proliferation. 

A component of malignant mesothelioma in situ can be diagnosed when invasion has been demonstrated in the same or different biopsy or by imaging studies. This applies specifically to epithelioid malignant mesotheliomas. Sarcomatoid malignant mesotheliomas are rarely diagnosable from effusion fluid cytology and are usually identified histologically, by the demonstration of invasion or overtly sarcomatoid areas.