10th January 2024

Miscellaneous Pleural Disease

Background

In addition to the common forms of pleural disease discussed above, there are some less common forms of pleural disease to consider: pleural plaques and mesothelioma (cancer of the mesothelial cells within the pleura). Both conditions typically occur following exposure to asbestos, a naturally occurring fibre composed of hydrated magnesium silicates. Asbestos exposure also has the ability to cause interstitial lung changes, termed asbestosis.

Asbestos was a fibre used commonly in many industries up until around the 1970s. It was subsequently banned in the UK in 1999. It was mainly used in construction and insulation, and patients who have worked within the following vocations may be at risk of previous asbestos exposure:

• Plumbers
• Electricians
• Boilermakers
• Welders
• Insulation workers

The development of pleural changes is a hallmark of asbestos exposure.

Pleural Plaques

Pleural plaques refer to the benign development of clearly defined areas of pleural thickening following previous exposure to asbestos. The mean time to onset following exposure is quoted at 20-30 years and preferentially involves the parietal pleura in the majority of cases.

When visualised directly pleural plaques appear as grey-white thickened regions of pleura with a “holly-leaf appearance.” They are composed of collagen deposits thought to arrive at the pleural space via the lymphatic system. Subsequent inflammation of the pleura is then thought to create the characteristic pleural plaque seen. Patients may well be asymptomatic of these and only have them picked up on chest radiograph for another reason. On a chest x-ray, plaques that have become calcified are the easiest to see. They are typically found in the lower zones bilaterally with an associated “incomplete border sign.”

Image Source: Wikimedia Commons (2017). Pleurosis calcarea wohl nach, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/1/13/Pleurosis_calcarea_wohl_nach_Tbc_93W_-_CR_pa_-_001.jpg?20201125151008  (Accessed on: 21 June 2022).

Importantly, pleural plaques are benign entities, and no further follow-up is required. However, as they are a marker of asbestos exposure, if a patient develops any sign which may be suggestive of an underlying cancer (see below), urgent imaging under the 2-week-wait pathway should be arranged.

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).

References 

• British Thoracic Society. BTS Guideline for the investigation and management of malignant pleural mesothelioma Appendix 2: Evidence tables. Thorax. 2018;73(March).
• King T. Asbestos-related pleuropulmonary disease [Internet]. UpToDate. 2021 [cited 2022 Jun 21]. Available from: https://www.uptodate.com/contents/asbestos-related-pleuropulmonary-disease
• NICE. Suspected Cancer: Recognition and Referral – PubMed – NCBI. NICE Guidel [Internet]. 2015;(July 2017):1–378. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26180880%5Cnhttps://www.nice.org.uk/guidance/ng12/evidence/full-guidance-74333341
• Radiopedia. Pleural plaque [Internet]. 2021 [cited 2022 Jun 21]. Available from: https://radiopaedia.org/articles/pleural-plaque?lang=gb
• Sternam, D; Litzky, Leslie; Kaiser L. Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma [Internet]. UpToDate. 2020 [cited 2022 Jun 21]. Available from: https://www.uptodate.com/contents/presentation-initial-evaluation-and-prognosis-of-malignant-pleural-mesothelioma?search=malignant pleural mesothelioma&source=search_result&selectedTitle=1~23&usage_type=default&display_rank=1
• Sternam, D; Litzky, Leslie; Kaiser L. Epidemiology of malignant pleural mesothelioma [Internet]. UpToDate. 2022 [cited 2022 Jun 21]. Available from: https://www.uptodate.com/contents/epidemiology-of-malignant-pleural-mesothelioma?search=epidemiology of malignant pleural&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1