10th January 2024

Malignant Mesothelioma

Malignant mesothelioma (MM) is a rare cancer of the pleura arising from mesothelial cells within the pleural cavity. It is highly associated with asbestos exposure, typically developing 30-40 years after exposure to the fibre, and unfortunately carries a poor prognosis. The median survival following diagnosis is quoted at 9.5 months by the British Thoracic Society.

Clinical Features and Diagnosis

MM can present insidiously with non-specific symptoms such as chest pain, prolonged cough, shortness of breath and weight loss with a significant male-predominance of disease. Clinical signs may be limited unless pleural effusion (see Pleural Effusion Clinical Features) or lymphadenopathy are present.

In NICE’s guideline NG12: Suspected cancer: recognition and referral, an urgent chest x-ray under the 2-week-wait pathway would be the first-line investigation to assess for MM. Their criteria recommend that in those aged over 40 with previous asbestos exposure, 1 of the following symptoms would trigger this referral:

• Cough
• Fatigue
• Shortness of breath
• Chest pain
• Weight loss
• Appetite loss

A chest x-ray in MM may show evidence of pleural effusion, unilateral focal pleural thickening, a pleural mass or pleural plaques. If suspicion is high, then proceeding to a CT Thorax with contrast can allow further evaluation of this pathology. Changes can be identified on CT imaging, but to establish a definitive diagnosis of MM, a tissue diagnosis is required. This can be achieved either via pleural biopsy with confirmation histologically or via the presence of abnormal mesothelial cells obtained from pleural fluid sampling (either via diagnostic aspiration or via medical thoracoscopy).

Once a tissue sample is obtained, immunohistochemistry can be utilised to differentiate MM from other forms of bronchial carcinoma. At least two positive mesothelial markers need to be present to make a diagnosis of MM: calretinin, cytokeratin 5/6, Wilms tumour 1, D-240. In addition to the positive markers, markers for lung adenocarcinoma should also be negative.

Management

As highlighted above, the prognosis of MM, once diagnosed, is poor. In those patients with a good performance status (WHO performance status 0-1), combination chemotherapy can be utilised as a first-line management option with cisplatin-based chemotherapy. In those with a lower performance status (WHO performance status >2), palliative management of symptoms should be considered first-line.

Management of pleural effusions in MM can be completed in the same way as all other malignant pleural effusions (see Pleural Effusion Management section for further details).