Malignant mesothelioma is a rare, aggressive cancer arising from mesothelial cells lining the pleura, peritoneum, pericardium , or tunica vaginalis of the testis. It results from uncontrolled proliferation and invasion of these cells.
Anatomy of Mesothelium
- Mesothelium : A membrane lining body cavities and organs.
- Visceral mesothelium : Covers internal organs.
- Parietal mesothelium : Lines the body walls.
Epidemiology
- ~3,000 new cases/year in the USA.
- 80% are pleural mesotheliomas (most common form).
- Latency: 20–50 years post asbestos exposure.
- Median diagnosis age: ~60 years.
- Male predominance: 5:1 male to female ratio.
- Risk varies with occupation (shorter latency in dock workers and insulators; longer in maritime and ship workers).
- Lifetime risk ~0.5–1%.
Etiology and Risk Factors
- Primary cause : Asbestos exposure.
- Blue asbestos (crocidolite) > Brown asbestos (amosite) > White asbestos (chrysotile) in carcinogenic potential.
- ~50% of patients have no known asbestos exposure.
- Simian Virus 40 (SV40) DNA found in 60–83% of tumors, suggesting a cofactor role.
- SV40 inactivates tumor suppressors p53 and Rb .
- Reactive oxygen species from asbestos cause DNA damage.
- Familial and secondary household exposure possible.
- Children rarely show asbestos exposure.
- No specific chromosomal abnormalities are consistently associated.
Pathogenesis
- Asbestos fibers induce chronic inflammation and genetic damage.
- Carcinogenicity depends on fiber type and shape (needle-shaped fibers more carcinogenic).
- Disease progression involves local invasion and lymphatic spread.
Clinical Features
- Majority present with pleural effusion or ascites .
- Symptoms (90% intrathoracic):
- Persistent cough
- Chest wall pain (non-pleuritic)
- Dyspnea
- Unilateral chest wall dullness and decreased expansion
- Systemic symptoms:
- Fever of unknown origin
- Night sweats
- Weight loss, anorexia
- Rare:
- Cardiac arrhythmias, dysphagia (mediastinal involvement)
- Thrombocytosis, DIC, thrombophlebitis, hemolytic anemia
Physical Exam & Imaging
- Chest X-ray :
- Pleural-based nodular, irregular masses
- Pleural thickening (>1 cm)
- Pleural plaques (due to asbestos)
- Moderate-large pleural effusion, usually unilateral (right side more common)
- CT Scan :
- Defines extent of pleural/peritoneal tumor
- Detects pleural thickening, fissure involvement, calcifications
- Differentiates benign vs malignant pleural thickening but not primary vs metastatic
- MRI and PET : Used for staging and extent assessment.
- Pulmonary function tests: Restrictive pattern common.
Spread
- Local invasion to lung, chest wall, mediastinum, diaphragm.
- Thoracic lymph node involvement in ~70%.
- Hematogenous metastases: liver, lung, kidney, adrenal, bone (rare).
Diagnosis
- Cytology of pleural fluid has low sensitivity.
- Biopsy required for definitive diagnosis:
- Thoracoscopic biopsy preferred.
- Percutaneous needle biopsy diagnostic in ~60% cases.
- Open biopsy sometimes needed.
- Tumor seeding possible along biopsy tract; prophylactic radiotherapy may prevent nodule growth.
- Pathology can mimic lung adenocarcinoma.
- Serum markers (experimental):
- Osteopontin
- Soluble mesothelin-related proteins (SMRP)
Staging (Pleural Mesothelioma)
- Stage I : Tumor limited to pleura; may involve ipsilateral lung, pericardium, or diaphragm; no lymph nodes.
- Stage II : Tumor plus ipsilateral lymph node involvement.
- Stage III : Tumor invades chest wall, heart, esophagus, or other thoracic structures; ipsilateral lymph nodes may be involved.
- Stage IV : Advanced tumor involving contralateral pleura or distant metastases.
(No established staging for peritoneal mesothelioma)
