Mesothelioma, in general, is an aggressive malignant tumour of the mesothelium. The overwhelming majority arise from the pleura, pleural mesothelioma, which this article will focus on.
Given the presence of the mesothelium in different parts of the body, mesothelioma can arise in various locations which as covered in separate articles:
- peritoneal mesothelioma
- pericardial mesothelioma 10
- cystic/multicystic mesothelioma
- tunica vaginalis testis mesothelioma
Mesothelioma is an uncommon entity and accounts for 5-28% of all malignancies that involve the pleura 1,7. There is a strong association with exposure to asbestos fibres (~10% risk during lifetime; 40-80% of patients have a history of asbestos exposure). Unlike other asbestos-related lung diseases, it does not appear to be dose-dependent 1.
Not all types of asbestos are strongly implicated, with crocidolite being the main causative fibre type. Not surprisingly, given the sources of asbestos exposure being predominantly mining, construction, lagging and machinery mechanics, 60-80% of cases are encountered in males, in general, 20 to 35 years after exposure 1,5,6. Some areas of the world have very regional hotspots, such as Belfast in Northern Ireland, due to the historic shipbuilding industry.
There is also increased risk for those with household exposure (e.g. family of exposed workers) 14.
There has been no convincing evidence for an association with smoking 6.
Typically patients present with dyspnoea and low back non-pleuritic chest pain. Pleural effusions are seen in the vast majority of patients at some stage during their disease. Up to 25% of patients have metastatic disease at the time of presentation if staged with FDG PET 5.
Typically mesothelioma is thought of as a locally-aggressive disease, however distant extranodal metastases are seen 15, albeit uncommonly. In a postmortem study of 318 patients, 55% patients were found to have extrathoracic metastases, the commonest sites being the liver (32%), spleen (11%), thyroid (7%) and brain (3%) 16. Of course prevalence of metastases on imaging is likely to be lower than on postmortem studies.
- asbestos-fibre exposure: causes majority of cases
- erionite-fibre exposure: naturally occurring mineral used in building, particularly in Turkey 12
- simian virus 40 (SV40) 13
- radiation exposure 13
There are three histological types of mesothelioma:
- epithelial: ~60% *
- mixed: 25%
- sarcomatoid: 15%
The cytological and histological diagnosis can be difficult, with mesothelial hyperplasia and metastatic adenocarcinoma appearing similar. Specific markers are helpful including:
- epithelial membrane antigen
- mesothelin (elevated in 84% of malignant mesothelioma versus <2% with other pleural diseases 6)
Subtypes such as multicystic/cystic mesothelioma are rarer and less aggressive.
Chest radiographs are of limited utility and are non-specific 6, demonstrating a pleural opacity which may extend around and encase the lung. Reduction in volume of the affected hemithorax is common resulting in a shift of the mediastinum towards the lesion 4.
Rib destruction or extension beyond the lateral and anterior margins of the chest wall may be evident. Mediastinal lymph node enlargement and pleural effusion may also be seen.
CT is the most commonly used modality for the assessment of mesothelioma and is able to stage the disease accurately in most patients.
The appearance is that of a soft tissue attenuation nodular mass which spreads along pleural surfaces including into pleural fissures and often creating a pleural rind.
Calcification is seen in 20% of cases which usually represents engulfed calcified pleural plaques rather than true tumour calcification 4. Sarcomatoid variants may demonstrate osteosarcoma or chondrosarcomatous components which may also be calcified.
Mesotheliomas have a predilection for a direct invasion of adjacent structures (chest wall, diaphragm and mediastinal content) but also frequently metastasise to the contralateral lung and local nodes 1-2,4.
To confidently predict chest wall invasion the extrapleural fat plane should be seen to be infiltrated and/or direct extension in bone or muscle identified 4.
Presence of a pericardial effusion suggests transpericardial extension 3-4.
MRI, although not routinely used, may have a role in refining the staging and better delineating the extent of the disease in surgical candidates especially concerning the chest wall and diaphragmatic invasion 4.
- T1: iso to slightly hyperintense c.f muscle 4,6
- T2: iso to hyperintense c.f muscle 4,6
- C+ (Gd): enhancement usually present
Positron emission tomography is becoming useful in two clinical settings 4:
- differentiating between benign and malignant asbestos-related pleural thickening
- assessing for nodal metastases
In addition, there appears to be a correlation between the degree of FDG uptake and the biological aggressiveness of the tumour, which may help to guide treatment 4.
Treatment and prognosis
Treatment continues to be challenging and the long-term survival is poor. Single modality treatment (surgery, radiotherapy, chemotherapy, immunotherapy and even photodynamic therapy) have not been shown to improve survival 3. More recently multi-modality treatment has had some impact on favourable subgroups (early disease, and epithelioid histology). Treatment includes:
- extrapleural pneumonectomy
- adjuvant chemotherapy
The prognosis is poor for all tumour types with a median overall survival without treatment of 4-12 months 3. In favourable patient subgroups up to 45% 5-year survival may be achievable 3, however even with aggressive multi-modality therapy overall 5-year survival remains poor (3-18%) 3 with a median survival time of approximately 18 months 4.
The differential is dependent on the exact nature of tumour involvement and the modality. General imaging differential considerations include
- pleural effusion (especially if loculated): on radiographs
- pleural metastases (especially with pleural carcinomatosis)
- peripheral bronchogenic carcinoma
- solitary fibrous tumour of pleura
- other pleural based tumours
- tumour like conditions of the pleura
- avoid the temptation of performing an image-guided biopsy, as mesothelioma is notorious for aggressively seeding along the biopsy track
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