Complete definitions of Mesothelioma

Mesothelioma

Dr Henry Knipe◉ andA.Prof Frank Gaillard◉ et al.

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Mesothelioma, in general, is an aggressive malignant tumour of the Epidemiologyum. 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 mesotheliomapericardial mesothelioma 10cystic/multicystic mesotheliomatunica vaginalis testis mesothelioma Epidemiology

Mesothelioma is an uncommon entity and accounts for 5-28% of allmalignancies 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 otherasbestos-related lung diseases, it doesn't 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.

Clinical presentation

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.

Pathology

Aetiology

asbestos-fibre exposure: causes majority of caseserionite-fibre exposure: naturally occurring mineral used in building, particularly in Turkey 12simian virus 40 (SV40) 13radiation exposure 13

Histology

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:

calretininepithelial membrane antigencytokeratinmesothelin (elevated in 84% of malignant mesothelioma versus <2% with other pleural diseases 6)

Subtypes such as multicystic/cystic mesothelioma are rarer and less aggressive.

Radiographic features

See staging of malignant pleural mesothelioma.

Radiograph

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

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.

An uncommon variant is thesolitary mediastinal malignant mesotheliomawhich has appearances reminiscent of a solitary fibrous tumour of the pleura1.

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

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 invasion4.

T1: iso to slightly hyperintense c.f muscle4,6T2: iso to hyperintense c.f muscle 4,6C+ (Gd): enhancement usually present

PET

Positron emission tomography is becoming useful in two clinical settings 4:

differentiating between benign and malignant asbestos-related pleural thickeningassessing 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 pneumonectomyadjuvant chemotherapyradiotherapy

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 achievable3, 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.

See also:
MESOTHELIOMA

Differential diagnosis

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 radiographsbenign asbestos-related pleural diseasepleural metastases(especially with pleural carcinomatosis)peripheral bronchogenic carcinomasolitary fibrous tumour of pleurapleural fibrosis from infective/inflammatory source (e.g. actinomycetes, tuberculosis)

Also, consider other pleural based tumours.

Practical points

avoid the temptation of performing an image-guided biopsy, as mesothelioma is notorious for aggressively seeding along the biopsy track

References

1. Naidich DP, Srichai MB, Krinsky GA. Computed tomography and magnetic resonance of the thorax. Lippincott Williams & Wilkins. (2007) ISBN:0781757657.Read it at Google Books - Find it at Amazon2. Pineda V, Andreu J, Cáceres J et-al. Lesions of the cardiophrenic space: findings at cross-sectional imaging. Radiographics. 27 (1): 19-32.doi:10.1148/rg.271065089 -Pubmed citation3. Zielinski M, Hauer J, Hauer L et-al. Staging algorithm for diffuse malignant pleural mesothelioma. Interact Cardiovasc Thorac Surg. 2010;10 (2): 185-9.doi:10.1510/icvts.2009.213611 -Pubmed citation4. Wang ZJ, Reddy GP, Gotway MB et-al. Malignant pleural mesothelioma: evaluation with CT, MR imaging, and PET. Radiographics. 24 (1): 105-19.doi:10.1148/rg.241035058 -Pubmed citation5. DeVita VT, Lawrence TS, Rosenberg SA et-al. DeVita, Hellman, and Rosenberg's cancer, principles & practice of oncology. Lippincott Williams & Wilkins. (2008) ISBN:0781772079.Read it at Google Books - Find it at Amazon6. Tyszko SM, Marano GD, Tallaksen RJ et-al. Best cases from the AFIP: Malignant mesothelioma. Radiographics. 27 (1): 259-64.doi:10.1148/rg.271065105 -Pubmed citation7. Leung AN, Müller NL, Miller RR. CT in differential diagnosis of diffuse pleural disease. AJR Am J Roentgenol. 1990;154 (3): 487-92.AJR Am J Roentgenol (abstract) - Pubmed citation8. Wong WL, Johns TA, Herlihy WG et-al. Best cases from the AFIP: multicystic mesothelioma. Radiographics. 24 (1): 247-50.doi:10.1148/rg.241035068 -Pubmed citation9. Koo PJ, Wills JS. Case 146: Benign multicystic mesothelioma. Radiology. 2009;251 (3): 944-6.doi:10.1148/radiol.2513071235 -Pubmed citation10. Wang ZJ, Reddy GP, Gotway MB et-al. CT and MR imaging of pericardial disease. Radiographics. 2003;23 Spec No (suppl 1): S167-80.doi:10.1148/rg.23si035504 -Pubmed citation11. Bridda A, Padoan I, Mencarelli R et-al. Peritoneal mesothelioma: a review. MedGenMed. 2007;9 (2): 32. Free text at pubmed -Pubmed citation12. Demirer E, Ghattas CF, Radwan MO et-al. Clinical and prognostic features of erionite-induced malignant mesothelioma. Yonsei Med. J. 2015;56 (2): 311-23.doi:10.3349/ymj.2015.56.2.311 -Free text at pubmed -Pubmed citation13. Qi F, Carbone M, Yang H et-al. Simian virus 40 transformation, malignant mesothelioma and brain tumors. Expert Rev Respir Med. 2011;5 (5): 683-97.doi:10.1586/ers.11.51 - Free text at pubmed - Pubmed citation14. Ferrante D, Bertolotti M, Todesco A et-al. Cancer mortality and incidence of mesothelioma in a cohort of wives of asbestos workers in Casale Monferrato, Italy. Environ. Health Perspect.

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