Definition : An aggressive malignant tumour arising in pleural mesothelium.

Epidemiology : Most cases are seen in males aged over 60 years old. Nearly 7000 cases were diagnosed in the UK between 2016 and 2018. An expected downward trend in incidence is still yet to be seen.

Aetiology :

 -  >90% of cases are directly attributable to asbestos exposure.

- Amphibole asbestos is the most potent type, followed by chrysotile, and then amosite.

- Rarer causes include exposure to non-asbestos mineral fibres and therapeutic radiation.

Pathogenesis

• Inhaled asbestos fibres become permanently entrapped in the lung.

- Most do not cause a tissue reaction and these are probably the ones responsible for the carcinogenic effects.

- A minority become coated with iron, forming asbestos bodies.

Genetic mutations

- A relatively low tumour mutation burden is seen in comparison with lung carcinomas.

- Involved genes are mostly tumour suppressor genes, the most common being CDKN2A, BAP1, and NF2.

Presentation

- Breathlessness, often due to a large pleural effusion, and chest pain.

- Weight loss and malaise are often profound.

Macroscopy

- Initially, multiple small nodules stud the parietal pleura.

- As the tumour grows, the nodules become confluent and form a tumour mass that encases the entire lung and fuses to the chest wall (Fig. 5.4).

Cytopathology

- Cytological examination of pleural fluid from a pleural effusion may reveal the presence of malignant mesothelial cells forming sheets, clusters, and papillae.

Histopathology

-  Epithelioid mesothelioma (representing the majority of cases) is composed of round malignant cells forming tubules and papillae. Grading of epithelioid mesothelioma can predict behaviour with high grade tumours showing shorter survival than low grade tumours.

- Sarcomatoid mesothelioma is composed of elongated spindled malignant cells.

- Biphasic mesothelioma contains a mixture of epithelioid and sarcomatoid types.

Ancillary tests

- Immunohistochemistry shows positive staining for mesothelial markers such as cytokeratin 5/6, WT1, D2-40, and calretinin.

- Loss of BAP1 expression by immunohistochemistry and deletion of CDKN2A by fluorescence in situ hybridization (FISH) analysis supports a diagnosis of mesothelioma.

Prognosis

- Very poor, with half of patients dying within a year of diagnosis.

- Few survive >2 years from diagnosis.