Mesothelioma

Diagnostic Algorithm

Clinical Background

Mesothelioma is a rare malignancy involving the serous lining of body cavities (pleura, peritoneum, pericardium or tunica vaginalis testis).

Epidemiology

• Incidence – 1/100,000
• Age – peaks in 40s-50s
• Sex – M>F
• Occurrence – rising in males ≥75 years; however, it is not increasing in males and females <75 years (coincides with OSHA restrictions of permissible limits of asbestos exposure)
  • Maximum lifetime risk for the development of mesothelioma falls in the 1925-1929 birth cohort

Risk factors

• Asbestos exposure (amphiboles more carcinogenic than chrysotile fibers)
  • 80% of mesothelioma cases occur in patients with history of asbestos exposure
  • At-risk occupations include shipbuilding, construction, fireproofing, automobile brakes and clutches, ceiling tiles and boilers (especially in construction prior to 1970)
• Genetics
  • Chromosome deletions (1p, 3p, 9p, 6q)

Pathophysiology

• 3 types of malignant pleural mesothelioma
  • Epithelial – 50%
  • Sarcomatous – 15%
  • Biphasic (or mixed) – 25%
• May be mistaken for adenocarcinoma; histologically heterogeneous tumors
  • Histology affects survival
• Long latency period (>20 years) between asbestos exposure and development of mesothelioma
• Asbestos fibers are mutagenic and carcinogenic to several cells
  • Commonly found in excised tumors
• Peritoneal mesothelioma
  • Cystic – no association with asbestos
  • Well-differentiated papillary
  • Malignant – no association with asbestos

Clinical Presentation

• Pleural
  • Dyspnea, nonpleuritic chest pain, pleural effusion, cough, fatigue
• Peritoneal
  • Abdominal pain, ascites, anorexia, bloating
• Pericardial
  • Chest pain, constrictive pericarditis
• Disease process is usually advanced at time of presentation

Diagnosis

• Indications for testing – high suspicion including abnormal chest x-ray (pleural effusion, pleural plaques) and history of asbestos exposure
• Laboratory testing
  • Histology – special stains for tissue specimens
    • Body cavity fluid cytology – may be negative
      • Not all patients with mesothelioma develop effusions
    • Pleural biopsy – CT guided or thorascopic biopsy
    • Open thoracotomy – last resort
  • Serum testing is not useful in diagnosis
  • Immunohistochemistry
    • Pancytokeratin (AE1/AE3), CK-7, CK-20
      • Typically positive for pancytokeratin and CK-7; may or may not be positive for CK-20 in epithelioid mesothelioma
    • Mesothelial markers – CK5/6, WT-1, calretinin, mesothelin, HBME-1, thrombomodulin, D2-40
      • Tendency to stain higher in epithelioid tumors
    • Sarcomatoid mesothelioma
      • Main differential is adenocarcinoma
      • 2/3 positive for calretinin; usually positive for keratin
    • Typically negative stains include CEA, BG8, moc-31 (ERA), E-Cadherin, Ber-Ep4, TTF-1, CD15
• Imaging studies
  • CT/MRI for initial evaluation of abnormal chest x-ray

Differential Diagnosis

• Pleural
  • Tuberculosis
  • Adenocarcinoma
  • Metastatic malignancy
  • Other malignancy – lymphoma, sarcoma
  • Pneumonia
  • Solitary fibrous tumor
• Peritoneal
  • Ovarian cancer with metastatic disease
  • Tuberculosis
  • Lymphomatosis
  • Peritoneal carcinomatosis
  • Endometriosis

Pharmacogenetics and Therapeutic Drug Monitoring

Screening

Monitoring

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Interpretation of most stains is only available in conjunction with a consultation.  Stains can be performed and returned for client pathologists to interpret unless otherwise noted.

Guidelines

General References