Mesothelioma is an aggressive malignant tumor of mesothelium and 90% of tumors arise from the pleura.

This article is about the pleural form of the disease, other locations include ¹⁷:

• peritoneal mesothelioma (~10%)

• pericardial mesothelioma (<1%)

• cystic/multicystic mesothelioma

• tunica vaginalis testis mesothelioma (<1%)

Epidemiology

Mesothelioma is an uncommon entity and accounts for ~15% (range 5-28%) of all malignancies that involve the pleura ^1,7. There is a strong association with exposure to asbestos fibers with a 10% lifetime risk; 40-80% of affected patients have a known history of asbestos exposure ¹ and risk is proportionate to duration and quantity ²⁰. Para-occupational exposure of household members of asbestos-exposed workers is documented ^14,20.

Crocidolite is the main causative fiber type. Sources of asbestos exposure are predominantly mining, construction, lagging and machinery mechanics and 60-80% of cases occur in males, typically with a latent period of 20 to 35 years following exposure ^1,5,6. Regional hotspots are related to local industries e.g. the historic shipbuilding industry in Belfast, Northern Ireland.

There is no convincing evidence for an association with smoking ⁶.

Clinical presentation

Typically patients present with dyspnea and low back non-pleuritic chest pain. Pleural effusions are seen in the vast majority of patients at some stage during their disease ²⁰. Up to 25% of patients have metastatic disease at the time of presentation if staged with FDG PET ⁵.

Typically mesothelioma is a locally-aggressive disease and distant extranodal metastases are uncommon in life¹⁵. 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.

Pathology

Etiology

• asbestos fiber exposure: causes the majority of cases

• erionite - a fibrous zeolite used in the building sector (particularly in Turkey) ¹² and for road-surfacing. Inhalational exposure occurs during mining, production and use and the mineral is highly toxic ²⁴. Exposure correlates with increased risk of lung cancer and mesothelioma ^25-28. Erionite has been included by the International Agency for Research on Cancer (IARC), as a human carcinogens (group 1 - volume publication year 2012) ²⁹.

• oncogenic simian virus 40 (SV40), belonging to the Polyoma viruses ^13,22. The transforming and oncogenic potential of the SV40 virus resides mainly in the viral oncoprotein large T antigen ²³.

• radiation exposure ¹³

Histology

There are three histological types of mesothelioma:

1. epithelial: ~60%

2. mixed: 25%

3. sarcomatoid: 15%

The cytological and histological diagnosis can be difficult, with mesothelial hyperplasia and metastatic adenocarcinoma appearing similar. Specific markers are helpful including:

• calretinin

• epithelial membrane antigen

• cytokeratin

• 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.

Radiographic features

See: staging of malignant pleural mesothelioma.

Plain radiograph

Chest radiographs are non-specific and of limited utility ⁶. The following features may be evident:

• pleural opacity which may extend around and encase the lung

• reduced volume of the affected hemithorax, resulting in ipsilateral shift of the mediastinum (common) ⁴

• rib destruction or extension beyond the lateral and anterior margins of the chest wall

• +/- mediastinal lymphadenopathy

• +/- pleural effusion; most commonly is unilateral and exudative or hemorrhagic in nature, with frozen hemithorax (not causing mediastinal shift)

CT

CT is most commonly used for imaging assessment of mesothelioma, and sufficient for accurate staging of disease in most patients.

• pleural mass or nodular thickening of soft tissue attenuation

  • tends to cause "inward" contraction of the hemithorax, e.g. ipsilateral mediastinal shift

• pattern of spread

  • pattern of spread initially to adjacent pleura

    • involvement pleural fissures

    • eventually grows toward lung encasement ("pleural rind')

  • predilection for local invasion

    • involvement of chest wall, diaphragm, and mediastinal content typical ^1,2,4

    • chest wall involvement

      • infiltration of the extrapleural fat plane ⁴

      • obvious direct extension in bone or muscle ⁴

      • known to invade along prior catheter and biopsy tracks ¹⁸

    • pericardial effusion may represent transpericardial extension ^3,4

  • frequent metastasis to local lymph nodes and contralateral lung

• calcification

  • seen in 20% - usually represents engulfment of calcified pleural plaques rather than true tumor calcification ⁴

  • sarcomatoid variants may contain calcific osteosarcoma or chondrosarcomatous components

An uncommon variant is the solitary mediastinal malignant mesothelioma which has appearances reminiscent of a solitary fibrous tumor of the pleura ¹.

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 invasion ⁴.

• T1: iso to slightly hyperintense cf. muscle ^4,6

• T2: iso to hyperintense cf. muscle ^4,6

• T1 C+ (Gd): enhancement usually present

PET

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

1. differentiating between benign and malignant asbestos-related pleural thickening

2. assessing for nodal metastases

In addition, there appears to be a correlation between the degree of FDG uptake and the biological aggressiveness of the tumor, 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. Multi-modality treatment has had some impact on favorable subgroups (early disease, and epithelioid histology). Treatment includes:

1. extrapleural pneumonectomy

2. adjuvant chemotherapy

3. radiotherapy

The prognosis is poor for all tumor types with a median overall survival without treatment of 4-12 months ³. In favorable 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.

Differential diagnosis

The differential is dependent on the exact nature of tumor involvement and the modality. General imaging differential considerations include

• pleural effusion (especially if loculated): on radiographs

• pleural metastases (especially with pleural carcinomatosis)

• peripheral lung cancer

• solitary fibrous tumor of pleura

• other pleural-based tumors

• tumor-like conditions of the pleura

  • benign asbestos-related pleural disease

  • pleural fibrosis from infective/inflammatory source (e.g. actinomycetes, tuberculosis)

Practical points

• some caution is raised with performing an image-guided biopsy, as mesothelioma can potentially cause tumor seeding along the biopsy track (with a reported incidence of around 4%) ²¹