Pleural Mesothelioma: Causes, Symptoms & Treatment
Pleural mesothelioma is a rare but aggressive malignant tumor of the pleura (lining of the lungs). It is most commonly caused by long-term asbestos exposure and is often diagnosed at an advanced stage.
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Pleural mesothelioma is a rare but aggressive malignant tumor of the pleura (lining of the lungs). It is most commonly caused by long-term asbestos exposure and is often diagnosed at an advanced stage.
What is Pleural Mesothelioma?
Pleural mesothelioma is a rare and aggressive malignant tumor that arises from the mesothelial cells lining the pleura – the thin membrane surrounding the lungs and lining the chest cavity. It is the most common form of mesothelioma, accounting for approximately 80% of all cases. Due to its long latency period of 20 to 50 years between initial exposure and disease onset, it is frequently diagnosed only at an advanced stage.
Causes and Risk Factors
The primary cause of pleural mesothelioma is exposure to asbestos fibers. Asbestos was widely used in construction, shipbuilding, and various industries until its ban in many countries during the 1990s. Inhaled asbestos fibers become lodged in the pleural lining, causing chronic inflammation that can lead to malignant transformation over decades.
- Asbestos exposure: Occupational or domestic exposure accounts for more than 80% of cases.
- Erionite exposure: A naturally occurring fibrous mineral found in specific geographic regions, also linked to mesothelioma.
- Prior radiation therapy: Previous chest irradiation may rarely increase the risk.
- Genetic predisposition: Mutations in the BAP1 gene are associated with increased susceptibility.
Symptoms
The symptoms of pleural mesothelioma develop gradually and are often nonspecific in the early stages, which contributes to delayed diagnosis:
- Persistent, unilateral chest pain
- Dyspnea (shortness of breath), often caused by a pleural effusion (fluid accumulation in the pleural space)
- Chronic cough
- Unexplained weight loss and fatigue
- Fever and night sweats
- In advanced stages: difficulty swallowing and hoarseness due to compression of adjacent structures
Diagnosis
Diagnosing pleural mesothelioma requires a combination of imaging, tissue sampling, and laboratory tests.
Imaging
Computed tomography (CT) of the chest is the primary imaging modality and typically reveals pleural effusion, pleural thickening, or pleural plaques. MRI and PET-CT provide supplementary information regarding tumor extent and potential metastatic spread.
Biopsy and Histology
Definitive diagnosis requires tissue biopsy, most commonly obtained via video-assisted thoracoscopic surgery (VATS). Histological examination identifies three main subtypes:
- Epithelioid type (most common, approximately 60%, best prognosis)
- Sarcomatoid type (most aggressive, worst prognosis)
- Biphasic (mixed) type
Laboratory Markers
Serum biomarkers such as soluble mesothelin-related peptides (SMRP) and fibulin-3 can support the diagnosis but do not replace histological confirmation.
Staging
Pleural mesothelioma is staged according to the TNM classification (Tumor, Nodes, Metastasis) of the AJCC/UICC. Stages I through IV describe local tumor extent through to distant metastases. The stage at diagnosis is a key determinant of treatment options and prognosis.
Treatment
Treatment of pleural mesothelioma is multimodal and tailored to the stage, histological subtype, and overall health status of the patient.
Chemotherapy
The standard first-line regimen is the combination of cisplatin and pemetrexed, which has been shown to significantly improve median overall survival compared to single-agent therapy. Folic acid and vitamin B12 supplementation are administered concurrently to reduce toxicity.
Immunotherapy
The combination of nivolumab and ipilimumab (immune checkpoint inhibitors) demonstrated significantly improved overall survival compared to chemotherapy in the CheckMate-743 trial and is approved as a first-line treatment option, particularly for the non-epithelioid subtype.
Surgery
Surgical procedures such as pleurectomy/decortication (P/D) or the more radical extrapleural pneumonectomy (EPP) are performed in selected patients with early-stage disease at specialized centers. The goal is macroscopic complete resection of the tumor.
Radiation Therapy
Radiation therapy is primarily used adjuvantly following surgery and as palliative treatment for pain control. Intensity-modulated radiation therapy (IMRT) allows for more precise dose delivery while minimizing damage to surrounding structures.
Palliative Care
In advanced disease, maintaining quality of life is the primary goal. This includes repeated thoracentesis or placement of an indwelling pleural catheter to relieve recurrent pleural effusions, as well as adequate pain management and symptom control.
Prognosis
The overall prognosis for pleural mesothelioma remains poor. Median overall survival ranges from 9 to 18 months depending on subtype and stage. The epithelioid subtype and early-stage disease are associated with more favorable outcomes. Advances in immunotherapy are improving survival for a subset of patients.
References
- Ettinger DS et al. - NCCN Clinical Practice Guidelines in Oncology: Malignant Pleural Mesothelioma, Version 2023. National Comprehensive Cancer Network (NCCN), 2023.
- Baas P et al. - First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. The Lancet, 2021; 397(10272): 375-386.
- Robinson BWS, Musk AW, Lake RA - Malignant mesothelioma. The Lancet, 2005; 366(9483): 397-408.
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