Description
Mesothelioma is a malignant neoplasm originating from mesothelial cells that line the pleura, peritoneum, pericardium, and tunica vaginalis. Pleural mesothelioma is the most common subtype, notorious for its strong association with asbestos exposure.
Pleural mesothelioma is a rare but highly aggressive form of cancer originating from the mesothelial cells of the pleura. It’s most commonly seen in adults, with a higher prevalence in males due to historical occupational exposure to asbestos.
Pathogenesis
Mesothelioma pathogenesis primarily involves the inhalation of asbestos fibres, which become lodged in the lungs, leading to long-term inflammation and eventually malignant transformation of the mesothelium.The latency period between asbestos exposure and the development of disease can be several decades.
Subtypes
- Epithelioid mesothelioma (60%): Most common and has a better prognosis compared to other subtypes.
- Sarcomatoid mesothelioma (25%): Less common and carries a worse prognosis.
- Biphasic/mixed mesothelioma (40%): Contains both epithelioid and sarcomatoid components.
Epidemiology, Risk Factors & Associations
- Primarily associated with occupational asbestos exposure (70-90% of cases).
- Amphibolic fibres (e.g. crocidolite) are more carcinogenic than chrysotile type of asbestos.
- Male predominance due to occupational exposure (strong association with shipbuilding, roofing, and plumbing industries)
- Median age at diagnosis is about 60 years.
Clinical Features
- Symptoms include chest pain, dyspnoea, weight loss, and fatigue.
- A clinical hallmark is a recurrent pleural effusion.
Complications
- Local invasion via direct invasion to adjacent structures, including lung, chest wall, and mediastinal and hilar lymph nodes.
- Distant metastasis via haematogenous and lymphatic spread, though less common, can occur late in the disease, often to liver and adrenal glands.
- Progressive respiratory failure
Pathological Features
Histopathology
- Macroscopic: Tumour often encases the lung and can present as a thick white rind.
- Microscopic: Epithelioid subtype demonstrates cuboidal cells and may resemble adenocarcinoma. Sarcomatoid subtype shows spindle-shaped cells with high mitotic activity and may resembler fibrosarcoma. Biphasic has a mixture of both.
Serology
- Elevated levels of soluble mesothelin-related peptides can be detected in some patients.
Biochemistry
- No specific biochemistry markers.
Radiological Features
General Features
- Characteristically demonstrates unilateral pleural thickening, which may be nodular or smooth.
- Pleural effusions are commonly seen.
- Calcification seen in advanced disease, particularly in patients with a history of asbestos exposure (pleural plaques).
CT
- Non-contrast: Shows pleural thickening and effusion.
- Contrast-enhanced: Enhanced nodular pleural thickening or mass can be appreciated.
MRI
- T1WI: Pleural thickening appears isointense or slightly hypointense compared to muscle.
- T2WI: Generally hyperintense.
- T1 C+: Heterogenous enhancement of the pleural thickening or mass.
- DWI/ADC: Restriction may be seen in malignant pleural thickening
PET FDG
- Demonstrates increased uptake in the pleural thickening or mass, aiding in disease staging and response evaluation.
Grading and Staging
T: Tumour
- TX: Primary tumour cannot be assessed.
- T0: No evidence of primary tumour.
- T1: Tumour limited to the ipsilateral parietal pleura, with or without involvement of the visceral pleura.
- T1a: Tumour involves the ipsilateral parietal pleura (including mediastinal and diaphragmatic pleura), without involvement of the visceral pleura.
- T1b: Tumour involves the ipsilateral parietal pleura (including mediastinal and diaphragmatic pleura) and also involves the visceral pleura.
- T2: Tumour involves any of the ipsilateral pleural surfaces with at least one of the following:
- Involvement of the diaphragmatic muscle.
- Extension of tumour from visceral pleura into the underlying pulmonary parenchyma.
- T3: Locally advanced but potentially resectable tumour; involves any of the following:
- Involvement of the endothoracic fascia.
- Extension into the mediastinal fat.
- Solitary, completely resectable focus of tumour extending into the soft tissues of the chest wall.
- Non-transmural involvement of the pericardium.
- T4: Locally advanced, technically unresectable tumour; involves any of the following:
- Diffuse extension or multifocal masses of tumour in the chest wall, with or without associated rib destruction.
- Direct transdiaphragmatic extension of tumour to the peritoneum.
- Direct extension of tumour to the contralateral pleura.
- Direct extension of tumour to mediastinal organs.
- Direct extension of tumour into the spine.
- Direct extension of tumour to the internal surface of the pericardium with or without a pericardial effusion, or tumour involving the myocardium.
N: Regional Lymph Nodes
- NX: Regional lymph nodes cannot be assessed.
- N0: No regional lymph node metastasis.
- N1: Metastasis in the ipsilateral bronchopulmonary or hilar lymph nodes.
- N2: Metastasis in the subcarinal or ipsilateral mediastinal lymph nodes, including ipsilateral internal mammary and peridiaphragmatic nodes.
- N3: Metastasis in the contralateral mediastinal, contralateral internal mammary, or ipsilateral or contralateral supraclavicular lymph nodes.
M: Distant Metastasis
- M0: No distant metastasis.
- M1: Distant metastasis is present.
Staging Groups
The TNM classifications are grouped into stages to aid in prognosis and treatment planning:
- Stage I:
- IA: T1a, N0, M0.
- IB: T1b, N0, M0.
- Stage II: T2, N0, M0.
- Stage III:
- IIIA: T3, N0, M0.
- IIIB: T1-T3, N1, M0 or T1-T3, N2, M0.
- Stage IV:
- IVA: T4, any N, M0 or any T, N3, M0.
- IVB: Any T, any N, M1.
Diagnosis
- Diagnosis requires a combination of clinical history, imaging, and pathological examination (tissue biopsy).
Differential Diagnosis
- Metastatic disease to the pleura.
- Benign asbestos-related disease.
- Other causes of pleural thickening, such as TB or haemothorax.
Differential Diagnosis
- Metastatic disease to the pleura: Typically demonstrates pleural-based masses rather than diffuse pleural thickening, often associated with a known primary malignancy.
- Pulmonary fibrosis: More likely to show interstitial changes and honeycombing on imaging. Pleural thickening can be seen but is generally not as pronounced as in pleural mesothelioma.
- Tuberculous pleuritis: Classically presents with pleural effusion in a younger population, often accompanied by symptoms of systemic illness such as fever and weight loss. The CT may show pleural thickening but is generally less nodular than in mesothelioma.
- Benign asbestos-related pleural disease: Often demonstrates pleural thickening and pleural plaques, similar to pleural mesothelioma. However, the thickening tends to be more smooth and circumferential, without the nodularity typically seen in mesothelioma.
- Empyema: Infected pleural effusion can cause pleural thickening and enhancement, but it typically demonstrates higher attenuation on CT and is accompanied by signs of infection such as fever and raised inflammatory markers.
- Pleural haematoma: Usually associated with recent trauma or anticoagulant use. Imaging typically shows a pleural fluid collection with high attenuation on CT, correlating with the high protein content of blood.
Management
Early-Stage Disease (Stages I-III)
- Surgical Treatment:
- Extrapleural Pneumonectomy (EPP): Removal of the affected lung, pleura, diaphragm, and pericardium. Indicated for selected patients with resectable disease and good performance status.
- Pleurectomy/Decortication (P/D): Removal of the pleura and as much tumour as possible while preserving the lung.
- Preferred for patients who cannot tolerate EPP but still have resectable disease.
- Adjuvant Therapy:
- Chemotherapy: Typically cisplatin or carboplatin combined with pemetrexed. Reduces the risk of recurrence and treats microscopic residual disease.
- Radiotherapy: Postoperative radiation to the chest. Helps control local disease and prevent recurrence.
- Neoadjuvant Therapy:
- Chemotherapy: Given before surgery to shrink the tumour and increase the likelihood of complete resection.
- Radiotherapy: Sometimes used preoperatively in select cases.
Advanced-Stage Disease (Stage IV)
- Chemotherapy:
- First-line: Combination of cisplatin or carboplatin with pemetrexed.
- Second-line: Options include gemcitabine or vinorelbine.
- Immunotherapy:
- Checkpoint Inhibitors: Nivolumab and ipilimumab have shown efficacy in some patients with advanced mesothelioma. Can be considered for patients who have progressed after first-line chemotherapy.
- Palliative Care:
- Radiotherapy: Palliative radiation to control symptoms such as pain and dyspnoea.
- Symptom Management: Includes pain relief, management of pleural effusions, and other supportive measures.
- Pleurodesis: A procedure to prevent recurrent pleural effusions by causing the pleural layers to stick together.
- Palliative Surgery: Partial debulking to relieve symptoms if complete resection is not possible.