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Malignant Mesothelioma: Causes, Symptoms & Treatment

Malignant mesothelioma is a rare, aggressive cancer of mesothelial cells, most commonly caused by asbestos exposure. It primarily affects the pleura surrounding the lungs.

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Things worth knowing about "Malignant Mesothelioma"

Malignant mesothelioma is a rare, aggressive cancer of mesothelial cells, most commonly caused by asbestos exposure. It primarily affects the pleura surrounding the lungs.

What is Malignant Mesothelioma?

Malignant mesothelioma is a rare but highly aggressive cancer that originates from mesothelial cells -- the thin layer of tissue (mesothelium) lining the inner surfaces of body cavities. It most commonly affects the pleura (the membrane surrounding the lungs), and less frequently the peritoneum (abdominal lining), the pericardium (heart sac), or the tunica vaginalis of the testis. The disease is strongly associated with prior asbestos exposure and is recognized as one of the most serious occupational cancers.

Causes and Risk Factors

The primary and most well-established cause of malignant mesothelioma is exposure to asbestos fibers. Asbestos is a naturally occurring silicate mineral that was widely used in the construction, shipbuilding, and manufacturing industries until its ban in many countries in the 1980s and 1990s.

Asbestos exposure: Inhaled or ingested asbestos fibers become embedded in tissue, causing chronic inflammation and DNA damage over decades.
Long latency period: The disease typically develops 20 to 50 years after initial asbestos exposure.
Erionite: A naturally occurring fibrous mineral linked to elevated mesothelioma rates in certain regions of Turkey.
Prior radiation therapy: In rare cases, previous radiotherapy to the chest area may increase the risk.
Genetic predisposition: Mutations in the BAP1 gene have been associated with increased susceptibility to mesothelioma.

Symptoms

The symptoms of malignant mesothelioma often develop gradually and may be easily overlooked in the early stages. They vary depending on the region of the body affected.

Pleural Mesothelioma (Lining of the Lungs)

Persistent, dull chest pain
Shortness of breath due to pleural effusion (fluid buildup between the lung and chest wall)
Dry, persistent cough
Unexplained weight loss
Fatigue and general weakness

Peritoneal Mesothelioma (Abdominal Lining)

Abdominal pain and bloating
Ascites (fluid accumulation in the abdominal cavity)
Nausea and loss of appetite
Weight loss

Diagnosis

Diagnosing malignant mesothelioma is often challenging due to its nonspecific symptoms and requires a combination of diagnostic steps.

Imaging: Chest X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) are used to visualize tumor extent and fluid accumulations.
PET-CT: Used to assess metastatic spread and guide treatment planning.
Thoracentesis / Paracentesis: Sampling of effusion fluid for cytological analysis.
Biopsy: Thoracoscopy (minimally invasive camera examination of the chest cavity) with tissue sampling is the gold standard for histological confirmation.
Immunohistochemistry: Used to classify the tumor subtype (epithelioid, sarcomatoid, or biphasic).
Biomarkers: Mesothelin and Fibulin-3 in the blood may serve as supplementary diagnostic markers.

Treatment

Treatment of malignant mesothelioma depends on the disease stage, the overall condition of the patient, and the histological subtype. A cure is rarely achievable; the primary goals are to extend survival and improve quality of life.

Surgery

In early-stage, operable pleural mesothelioma, a pleuropneumonectomy (removal of the lung, pleura, and parts of the diaphragm) or the less radical pleurectomy/decortication may be considered.

Chemotherapy

The standard first-line treatment is a combination of pemetrexed and cisplatin (with folic acid and vitamin B12 supplementation to reduce side effects). This regimen has been shown to extend survival and improve symptoms compared to monotherapy.

Immunotherapy

The combination of nivolumab and ipilimumab (checkpoint inhibitors) has emerged as a new first-line therapy for unresectable malignant pleural mesothelioma, with clinical trials demonstrating improved overall survival compared to standard chemotherapy.

Radiation Therapy

Radiotherapy is primarily used for palliative pain relief or to prevent seeding of cancer cells along biopsy tracts.

Palliative Care

Palliative measures are an essential part of management and include drainage of pleural effusions, pain control, and psychosocial support for patients and their families.

Prognosis

Malignant mesothelioma carries an overall poor prognosis. The median survival after diagnosis ranges from 12 to 18 months depending on treatment and disease stage. The epithelioid subtype has a more favorable prognosis compared to the sarcomatoid subtype. Early diagnosis and treatment at specialized centers can improve outcomes.

References

Ettinger DS et al. - Malignant Pleural Mesothelioma: NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network (NCCN), 2023.
Baas P et al. - First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma. The Lancet, 2021; 397(10272): 375-386.
World Health Organization (WHO) - Asbestos: elimination of asbestos-related diseases. WHO Fact Sheet, 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/asbestos-elimination-of-asbestos-related-diseases

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