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Mesothelioma: Asbestos-Caused Cancer of the Pleura and Peritoneum

What Is Mesothelioma?

A rare, aggressive malignancy arising from mesothelial cells lining the pleural (lung), peritoneal (abdominal), pericardial, or tunica vaginalis cavities. Pleural mesothelioma accounts for 80–90%.

Cause: Asbestos Exposure

  • Amphibole asbestos (crocidolite, amosite) > serpentine (chrysotile) in potency.
  • Inhalation → fibers reach pleura → chronic inflammation, ROS, DNA damage, malignant transformation.
  • Latency: 20–50 years (mean 30–40).
  • Dose-response: risk ↑ with cumulative exposure, but no safe threshold.
  • Paraoccupational (take-home) and environmental exposure also cause disease.

Other Risk Factors

  • Erionite (zeolite mineral, Turkey/US) — more potent than asbestos.
  • Radiation therapy to chest/abdomen.
  • SV40 virus (controversial, not proven).
  • Genetic susceptibility (BAP1 mutation — predisposes to mesothelioma, uveal melanoma, RCC).

Clinical Presentation

  • Pleural: dyspnea, chest pain, pleural effusion, weight loss.
  • Peritoneal: abdominal distension, pain, ascites, bowel obstruction.
  • Often advanced at diagnosis (median survival 12–18 months).

Diagnosis

  • Imaging: CT chest/abdomen, PET-CT, MRI.
  • Thoracoscopy/laparoscopy with biopsy — gold standard.
  • Immunohistochemistry: calretinin, WT1, D2-40, cytokeratin 5/6 (+); CEA, MOC-31, Ber-EP4 (-) — distinguishes from adenocarcinoma.
  • BAP1 loss by IHC supports diagnosis.

Treatment by Stage

  • Early (I–II): Multimodal — EPP (extrapleural pneumonectomy) or P/D (pleurectomy/decortication) + chemo (cisplatin/pemetrexed) ± radiation.
  • Advanced (III–IV): Palliative chemo (cisplatin/pemetrexed + bevacizumab), immunotherapy (nivolumab/ipilimumab approved for unresectable), tumor treating fields (TTFields), clinical trials.
  • Peritoneal: CRS + HIPEC (cytoreductive surgery + hyperthermic intraperitoneal chemo) — best outcomes in selected patients.

Prognosis

5-year survival: ~10% overall. Better with epithelioid histology, female sex, early stage, multimodal therapy. BAP1 mutation paradoxically associated with longer survival.

Prevention and Screening

  • Asbestos bans (60+ countries; US partial).
  • Occupational surveillance for exposed workers (CXR, PFT, symptom questionnaire).
  • No proven screening for general population.

Mesothelioma is a sentinel disease of industrial asbestos use. Early specialist referral improves access to clinical trials and multimodal care.

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