Malignant Pleural Mesothelioma
Asbestos, diagnosis, staging, and the shift from EPP to pleurectomy/decortication.
Overview
Malignant pleural mesothelioma (MPM) is the most common primary malignant tumour of the pleura. It arises from mesothelial cells lining the pleural surfaces. 80% of mesotheliomas are pleural in origin; the remainder arise from the peritoneum. Despite being rare, it carries a poor prognosis — median survival without treatment is 6–18 months.
Risk factors
Asbestos exposure is the dominant risk factor — present in up to 70% of cases. The latency period is characteristically long, at 30–40 years from first exposure. The amphibole type of asbestos (particularly crocidolite — blue asbestos) carries the highest malignant potential, compared to chrysotile (white asbestos). Other documented risk factors include ionising radiation and SV40 (simian virus 40) exposure.
Always take a detailed occupational history in any patient with unexplained pleural disease: shipbuilding, construction, insulation fitting, pipe lagging, boiler making, asbestos mining, and demolition workers are at highest risk. Household contacts of asbestos workers also carry elevated risk through secondary exposure.
Histology and diagnosis
Four major histological subtypes of MPM:
- Epithelioid (50%): most common; best prognosis; resembles adenocarcinoma — requires IHC to distinguish
- Biphasic (30%): mixed epithelioid and sarcomatoid elements; intermediate prognosis
- Sarcomatoid (15–20%): worst prognosis; highly aggressive; chemotherapy-resistant
- Desmoplastic (<5%): variant of sarcomatoid; difficult to distinguish from fibrous pleuritis
Diagnosis requires histopathological confirmation — cytology alone is insufficient due to the difficulty in distinguishing reactive mesothelial cells from malignant ones. Thoracoscopy-guided pleural biopsy with targeted sampling from macroscopically abnormal pleura gives the highest yield.
Clinical features
Peak incidence 50–70 years with strong male preponderance. Common presenting symptoms: chest pain (dull, progressive, non-pleuritic in late disease), dyspnoea, and cough. As disease progresses the lung becomes entrapped, restricting chest wall movement. Local invasion causes dysphagia, hoarseness, and nerve palsies. Transdiaphragmatic spread causes GI symptoms. Distant metastases occur in liver, bone, brain, adrenals, and kidney.
Staging — IMIG/AJCC
| Stage | Description |
|---|---|
| I | Tumour confined to ipsilateral parietal pleura ± visceral pleura involvement |
| II | Tumour invades diaphragmatic muscle or lung parenchyma |
| III | Locally advanced — chest wall, mediastinum, pericardium, single N2 node |
| IV | Diffuse chest wall invasion, contralateral pleura, distant organs, N3 nodes |
Treatment
The MARS trial (2011) and MARS-2 trial (2021) changed practice significantly. Extrapleural pneumonectomy (EPP) — removal of the lung, pleura, pericardium, and hemidiaphragm — carries a perioperative mortality of 5–10% and did not show survival benefit over chemotherapy alone in the MARS trial. EPP is largely abandoned in most high-volume centres.
Pleurectomy/decortication (P/D) — removal of all visible tumour from the pleural surfaces while preserving the lung — is now preferred for surgical candidates. P/D has lower perioperative mortality (~2–4%) and comparable survival to EPP. Extended P/D (ePD) includes resection of pericardium and diaphragm when involved. Surgery is reserved for early-stage (I–II) epithelioid histology with good performance status, after multimodal staging.
Preferred surgical option. Lung-sparing. Lower mortality than EPP. Best results in early-stage epithelioid MPM.
Pemetrexed + cisplatin is standard first-line. Immunotherapy (nivolumab + ipilimumab) now approved for first-line unresectable MPM — significantly improved outcomes.
IPC or talc pleurodesis for effusion control. Palliative RT for chest wall pain. Best supportive care for PS >2 or sarcomatoid histology.
MPM treatment is evolving rapidly with immunotherapy combinations showing improved survival. For current systemic therapy and multimodal treatment protocols, refer to ESMO Mesothelioma Guidelines and the IMIG guidelines.
All clinical content should be verified against current guidelines before clinical application. This resource is intended for revision and educational purposes only.
Standard textbooks
- Shields TW, LoCicero J, Reed CE, Feins RH. General Thoracic Surgery. 7th ed. Lippincott Williams & Wilkins.
- Sellke FW, del Nido PJ, Swanson SJ. Sabiston & Spencer Surgery of the Chest. 9th ed. Elsevier.
- Pearson FG, et al. Thoracic Surgery. 3rd ed. Churchill Livingstone.