Diffuse malignant mesothelioma (MM) is the most common primary tumour of the pleura, and also occurs less frequently in the peritoneum (6–10%), pericardium, tunica vaginalis and ovary. There is a well‐established link between asbestos exposure and MM, as demonstrated by Wagner et al., who investigated asbestos miners dying with pleural tumours in the North West Cape province of South Africa in 1960. Although still a rare tumour, MM has become increasingly common over the last few decades (the number of deaths from MM in the UK increased from 153 in 1968 to 2249 in 2008; Health and Safety Executive statistics 2009/2010). The annual incidence in the UK is expected to peak around the year 2016, with just over 2000 deaths from MM expected in males alone. The rising incidence is a result of the long latency period between exposure to asbestos and the development of MM, which is greater than 20 years in 96% of cases. Despite causing a relatively small number of cancer‐related deaths, MM receives a considerable amount of attention because of the legal implications of asbestos‐related occupational exposure and the not infrequent difficulties in confirming the diagnosis. MM needs to be distinguished from reactive mesothelial proliferations and is a well‐known mimic of other tumours, necessitating the use of immunohistochemical staining of appropriate surgical biopsy material and careful correlation with the clinical and radiological findings. As the prognosis of patients diagnosed with diffuse pleural MM remains universally poor (median survival from diagnosis of 6–12 months) with no reliable definitive therapy, it is paramount that the diagnosis is made correctly.

Epidemiology and aetiology

Because of its fire‐resistant properties (the word ‘asbestos’ is derived from a Greek word meaning ‘unquenchable’), asbestos was widely used in the ship‐building and construction industries, and affected individuals include electricians, plumbers and carpenters. Of those diagnosed with MM, most are men (male to female ratio = 9 : 1) in the 50–70 year age group. It is estimated that about 5–10% of individuals with significant prolonged asbestos exposure will develop MM and, conversely, more than 90% of patients with MM have had some form of asbestos exposure. Other potential factors predisposing to MM include exposure to the non‐asbestos fibre erionite (found in the Cappadoccia region of Turkey) and possibly simian virus 40 (controversial), thorotrast and radiation.

Pathogenesis

Asbestos probably causes MM through a combination of mechanisms ranging from direct to indirect, and genetic to molecular. Direct mechanisms include the deposition of asbestos fibres in the pleura, which is more likely to occur with long, thin, straight fibres of the amphibole group (e.g. crocidolite and amosite) than with the curly fibres of the serpentine group (mainly chrysotile). Some investigators question the role of chrysotile in the development of MM.

Indirectly, asbestos causes MM through the release of reactive oxygen species from macrophages that have ingested fibres, which result in damage to DNA, possible suppression of the immune system and activation of cell signalling pathways. Chromosomal deletions accumulate in many MM, resulting in loss or inactivation of tumour suppressor genes (e.g. CDKN2A/ARF locus at 9p21). Possible contributing genetic factors are suggested by the occurrence of rare familial cases of MM.

Clinical presentation and investigation

Patients with MM often present with dyspnoea related to pleural effusion and/or chest wall pain, but may have associated constitutional symptoms (weight loss, sweats, malaise and anorexia) and, less commonly, symptoms related to invasion of thoracic viscera or vital structures (e.g. dysphagia, hoarseness or superior venal caval obstruction). Physical examination may show signs of a pleural effusion (reduced chest expansion, dull percussion note and decreased breath sounds), chest wall mass, finger clubbing (30%) or signs related to local infiltration (e.g. cardiac tamponade). Patients with MM may present with an incidental finding on chest X‐ray, with focal pleural disease in the absence of symptoms. Lymphadenopathy is less commonly present.

Although cytological examination of pleural fluid reveals malignant cells in only about one‐third of cases, a pleural biopsy to obtain tissue for diagnosis is recommended, by means of image guided (ultrasound or computed tomography) biopsy, medical thoracoscopy or video‐assisted thoracoscopic surgery (VATS).

Radiological investigation, which is mainly with CT, is vital for diagnosis and staging purposes. Various serum markers (e.g. serum osteopontin, soluble mesothelin‐related protein and megakaryocyte potentiating factor) are proposed as possible indicators of pleural MM in at‐risk patients, but these have not been accepted into routine clinical practice, and may have more of a role in monitoring response to therapy.