Summary: Mesothelioma is a rare tumour that is more common in countries that use asbestos, which is responsible for > 80% of cases. In Australia the incidence is 6/100,000 in men. There are three common types: epithelioid (resembles epithelial tumours), sarcomatoid and biphasic (30%) which contains a mixture of types. T stage indicates resectability - T1 is very local, T2 invades lung or diaphragm, T3 is advanced but possibly resectable whereas T4 is unresectable. N stage is similar to the lung.


Mesothelioma is a relatively rare tumour but its incidence is higher in countries that have used asbestos as a construction material (eg. Australia, UK, Canada). In Australian men, the incidence is 6 per 100,000 per year. It is more common in men than women.

Aetiology and Pathogenesis

Mesothelioma is almost always caused by exposure to asbestos, particularly crocodilite. The fibres are inhaled and remain inside the lung. They act as a carcinogenic stimulus to cause mesothelioma and other lung malignancies.
About 20% of cases have no past history of asbestos exposure. Other factors can include radiotherapy, other inhaled fibres, and exposure to SV40 (a virus).

Natural History

Mesothelioma typically spreads diffusely throughout the pleural cavity making cure almost impossible. It sequesters blood from the lung, causing ventilation/perfusion mismatch due to shunting of blood away from the alveoli. Metastases occur

Clinical Presentation

Patients typically present with dyspnoea and/or chest pain due to local invasion and pleural effusion.

Tumour Features


About 1% of malignant effusions are due to mesothelioma. Sarcomatoid mesothelioma cells are generally not found in fluid, whereas epithelioid variants may be. Cytology of these effusions is not often helpful, due to two main reasons:

  • Mesothelioma cells may appear cytologically bland
  • Reactive mesothelial cells may appear atypical or show mitoses

Therefore, a high index of suspicion for mesothelioma must be maintained. If the cytology can be arranged in a cell block, then immunostaining may be helpful.


Macroscopically, mesothelioma forms nodules on the pleural surface at early stages. Late stage can be diagnosed by caking of the entire pleural space. The tumour is typically tan.


There are four recognised mesothelioma variants by the WHO.

Epithelioid Mesothelioma

These tumours have a microscopic appearance that resembles epithelial neoplasms. There are several subtypes, the most common being tubulopapillary and adenomatoid. These appearances make diagnosis on microscopy alone difficult; immunohistochemistry and electron microscopy are both useful adjuncts.

Sarcomatoid Mesothelioma

Sarcomatoid mesothelioma is a less common pattern, with the tumour consisting of spindle cells that may resemble a sarcoma. Important differentials include sarcoma and sarcomatoid tumours of the lung.

Desmoplastic Mesothelioma

This rare variant usually occurs in the peritoneal mesothelium.

Biphasic Mesothelioma

This variant is about 30% of cases, and contains elements of epithelioid and sarcomatoid mesothelioma.


Grading is not performed. Tumours often exhibit minimal anaplastic features despite their poor prognosis.


Immunohistochemistry is essential to the diagnosis of mesothelioma. The tests can be divided into several groups:

  • Tests to demonstrate epithelioid mesothelioma: There are numerous tests, but cytokeratin 5/6, AE1/3 may be helpful. Mesothelin is essentially positive in almost all cases, making it particularly useful for the epithelioid variant.
  • Tests to demonstrate sarcomatoid mesothelioma: There are fewer tests available for this variant, but calretinin is positive in the majority.
  • Tests to rule out epithelial malignancy: The epithelioid type often produces gland-like structures, and adenocarcinoma is a distinct possibility. This can be excluded through negative reactions for CEA, villin, Napsin-A and TTF1.
  • Tests to rule out benign reactive mesothelial changes: This can sometimes appear similar to mesothelioma; it can be excluded by positive testing for AE1/AE3, TP53, and epithelial membrane antigen. Desmin is often positive in benign cells and rarely in mesothelioma.

Electron Microscopy

Electron microscopy is used less frequency with effective immunohistochemistry, but remains useful in some cases. Well differentiated mesothelioma cells contain long microvilli and characteristic desmosomes.


Mesothelioma is staged through the TNM system. Most cases are incurable.

T Stage

  • T1a: Limited to parietal pleural surface
  • T1b: Involving parietal and visceral pleural surface
  • T2: Involves underlying diaphragm or pulmonary parenchyma
  • T3: Invades locally into mediastinal fat, pericardium, chest wall or endothoracic fascia (potentially resectable)
  • T4: Invasion into mediastinal organs, spinal cord, peritoneum, contralateral pleura, diffusely into the chest wall (unresectable)

N Stage

N stage is similar to lung cancer.

  • N1: Ipsilateral hilar nodes
  • N2: Ipsilateral mediastinal or subcarinal nodes (note: this includes internal thoracic nodes)
  • N3: Contralteral mediastinal or any supraclavicular nodes

M Stage

  • M1: Distant metastases

Final Stage

Stage T N M
IA T1a N0 M0
IB T1b N0 M0
II T2 N0 M0
III T1-2