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BASICS

DESCRIPTION
- Mesothelioma is a rare, insidious, aggressive malignancy of mesothelial/serous tissues primarily in:
- Pleura (80-95%)
- Peritoneum (5-20%)
- Rarely: tunica vaginalis, pericardium (1-2%)
- Predominant cause: inhalation of asbestos, typically from remote occupational exposure (≥20 years latency).
- Histologic types:
- Epithelioid (most common, least aggressive)
- Sarcomatoid (most aggressive)
- Biphasic
- Rapidly fatal course; median survival 17-25 months in resectable pleural disease.

EPIDEMIOLOGY

  • US incidence declining due to asbestos ban (1970s).
  • Global endemic clusters remain where asbestos industry persists.
  • Incidence peaks in 5th-6th decades; 70% pleural cases in males; peritoneal cases slightly more in females.
  • ~3,000 US cases diagnosed annually.
  • Prevalence: 1 per 100,000 persons without asbestos exposure; 2-3 per 100,000 with exposure.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Predominant cause: asbestos exposure (hydrated magnesium silicate fibers).
  • Types of asbestos fibers: amphibole (needle-like, more carcinogenic) and serpentine (curved, common in US).
  • Long latency (20-50 years) from exposure to disease development.
  • Inhaled/ingested fibers lodge in pleural/peritoneal membranes causing chronic irritation, inflammation, and tumor formation.
  • Tumors progress from parietal to visceral pleura and invade adjacent structures.
  • Other causes: prior radiation, talc, erionite, mica exposure; familial Mediterranean fever; lymphocytic leukemia.

Genetics:
- >10% have germline mutations in cancer predisposition genes, notably BAP1, associated with familial mesothelioma and other cancers (uveal melanoma).
- Other implicated genes: MLH1, MLH3, TP53, BRAC2.

RISK FACTORS

  • Dose-dependent asbestos exposure: mining, milling, textiles, cement, insulation, shipbuilding.
  • Nonoccupational: renovation, industrial contamination, paraoccupational exposure via clothing.
  • Radiation exposure, natural asbestos deposits, fibrous silicates also implicated.
  • No synergistic effect with smoking, unlike lung cancer.

GENERAL PREVENTION

  • Avoid asbestos exposure.
  • Strict protective protocols for workers in asbestos-containing environments.
  • Aggressive remediation of asbestos-affected buildings/homes.

DIAGNOSIS

  • Nonspecific symptoms; thorough exposure history critical.
  • Symptoms:
  • Pleural: chest pain (wall invasion), breathlessness (effusion), cough, fatigue, night sweats, anorexia, weight loss.
  • Peritoneal: vague abdominal pain, ascites, nausea, anorexia, weight loss.
  • Exposure history often remote; use asbestos-specific questionnaires.
  • Include household, community, and occupational exposures.

PHYSICAL EXAM
- Pulmonary signs of effusion: decreased breath sounds, dullness, asymmetric expansion.
- Abdominal signs of ascites: distension, fluid wave, tenderness.
- Clubbing, neurological signs (spinal cord compression) possible.

DIFFERENTIAL DIAGNOSIS
- Pleural: empyema, metastatic tumor, sarcomas, fibrosarcoma.
- Peritoneal: carcinomatosis, ovarian carcinoma, lymphomatosis, tuberculosis.

DIAGNOSTIC TESTS & INTERPRETATION

  • Biomarkers (mesothelin) under study; not routine.
  • Chest x-ray: insensitive/nonspecific; often requires CT, MRI, PET.
  • Tissue diagnosis needed: thoracentesis cytology, pleural biopsy, often VATS biopsy.
  • Imaging for staging: CT chest/abdomen, MRI, PET-CT.
  • Immunohistochemistry supports diagnosis.

Staging
- TNM system widely used; Butchart system used in some regions for resectability.
- Clinical staging often underestimates disease extent.

TREATMENT

  • Median survival 9-12 months; treatment mainly palliative and life-prolonging.
  • Multidisciplinary care (thoracic surgery, oncology, pulmonary, radiology, pathology).
  • Pain control per cancer pain management guidelines.

MEDICATION
- First line: chemotherapy (pleural disease):
- Cisplatin + gemcitabine, pemetrexed, or raltitrexed combinations superior to cisplatin alone.
- Bevacizumab addition: small survival benefit but unlicensed.
- Hyperthermic intraoperative/postop intraperitoneal chemo for peritoneal disease (cisplatin, mitomycin C, fluorouracil, doxorubicin, paclitaxel).

Second line:
- Palliative chemo: mitomycin C, vinblastine, cisplatin, pemetrexed ± carboplatin.
- Radiation therapy for palliation or adjunct; no proven survival benefit.

ISSUES FOR REFERRAL

  • Pulmonary, oncology, surgical follow-up.
  • Psychological support recommended.

ADDITIONAL THERAPIES

  • Nivolumab + ipilimumab immunotherapy: first systemic therapy approved since 2004, superior frontline treatment.
  • Experimental: gene therapy, photodynamic therapy, alternating electric fields.

SURGERY/OTHER PROCEDURES

  • Surgical role controversial; most patients unsuitable due to disease progression/functional status.
  • Pleurectomy/decortication (P/D) and extrapleural pneumonectomy (EPP) reduce tumor load, no clear mortality benefit.
  • Multimodality approach (surgery + radiation + intraoperative chemo lavage) used in stages I-III.
  • MARS trial showed no survival benefit with surgery added to chemo; MARS 2 ongoing.

ONGOING CARE

  • Smoking cessation.
  • Pneumococcal and influenza vaccination.
  • Monitor for paraneoplastic syndromes: fever, thrombocytosis, malignancy-related thrombosis, hypoglycemia, Coombs-positive hemolytic anemia.

PROGNOSIS

  • Individualized based on gender, stage, histology, cytoreduction completeness.
  • Poor prognosis factors: poorly differentiated tumors, advanced age, male sex.

COMPLICATIONS

  • Disease relapse and progression.
  • Infection, dysphagia.
  • Worse outcomes in patients >65 years.

REFERENCES

  1. Carbone M, Adusumilli PS, Alexander HR Jr, et al. Mesothelioma: scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin. 2019;69(5):402-429.
  2. Brims F. Epidemiology and clinical aspects of malignant pleural mesothelioma. Cancers (Basel). 2021;13(16):4194.
  3. Janes SM, Alrifai D, Fennell DA. Perspectives on the treatment of malignant pleural mesothelioma. N Engl J Med. 2021;385(13):1207-1218.
  4. Panou V, Gadiraju M, Wolin A, et al. Frequency of germline mutations in cancer susceptibility genes in malignant mesothelioma. J Clin Oncol. 2018;36(28):2863-2871.
  5. Scagliotti GV, Gaafar R, Nowak AK, et al. Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomized, placebo-controlled phase 3 trial. Lancet Respir Med. 2019;7(7):569-580.
  6. Gomez DR, Rimner A, Simone CB, et al. The use of radiation therapy for the treatment of malignant pleural mesothelioma: expert opinion from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation. J Thorac Oncol. 2019;14(7):1172-1183.

ICD10 Codes

  • C45.1 Mesothelioma of peritoneum
  • C45.2 Mesothelioma of pericardium
  • C45.0 Mesothelioma of pleura

Clinical Pearls

  • Mesothelioma is a rare but universally fatal disease with long latency.
  • Multimodal treatment decreases recurrence and extends survival.
  • Asbestos exposure is the main risk factor.