Mesothelioma

Diagnosis

Indications for Testing

• High suspicion for mesothelioma – includes abnormal chest x-ray (pleural effusion, pleural plaques)
• History of asbestos exposure

Laboratory Testing

• Serum testing – not useful in diagnosis

Histology

• Tissue specimens required for diagnosis
  • Body cavity fluid cytology – may be negative; not usually diagnostic
    • Not all patients with mesothelioma develop effusions
  • Pleural biopsy – CT-guided or thorascopic video-assisted thoracic surgery biopsy, Abrams needle
  • Open thoracotomy – use only if less invasive testing not diagnostic
• Immunohistochemistry
  • Epithelioid markers
    • Typically positive for pan cytokeratin (AE1,3) and CK 7
    • May or may not be positive for CK 20
  • Mesothelial markers
    • CK 5,6, WT-1,  calretinin,  mesothelin,  HBME-1 (mesothelial cell),  thrombomodulin,  D2-40
    • Tendency to stain higher in epithelioid tumors
  • Sarcomatoid markers
    • Main differential is adenocarcinoma
      • TTF-1, CEA, b72.3, Ber-EP4, Leu M1 are typically positive in adenocarcinomas
    • >60% positive for calretinin; usually positive for keratin 903 (K903)
  • Typically negative stains in mesothelioma
    • Carcinoembryonic antigen (CEA), BG 8, epithelial-related antigen (MOC-31), E-cadherin, anti-human epithelial antigen (Ber-EP4), thyroid transcription factor (TTF-1), CD15 (Leu M1), breast carcinoma b72.3

Imaging Studies

• CT (with contrast)/MRI for initial evaluation of abnormal chest x-ray

Differential Diagnosis

• Pleural
  • Infection 
    • Mycobacterium tuberculosis
    • Pneumonia
  • Malignancy
    • Adenocarcinoma
    • Lung cancer
    • Metastatic malignancy
    • Other malignancy – B-cell and T/NK-cell lymphomas, sarcomas
  • Other – solitary fibrous tumor

• Peritoneal
  • Ovarian cancer with metastatic disease
  • M. tuberculosis
  • Lymphomatosis
  • Peritoneal carcinomatosis
  • Endometriosis

Screening

Monitoring

Clinical Background

Mesothelioma is a rare malignancy involving the serous lining of body cavities, including pleura (most common), peritoneum, pericardium, tunica vaginalis testis in men, or tunica serosa uteri in women.

Epidemiology

• Incidence
  • 1-2/100,000,000 – 2,500 new cases each year in U.S.
  • Increasing incidence in Russia, Western Europe, China, India
  • Increasing incidence in males ≥75 years
    • No increase in U.S. males or females <75 years (coincides with OSHA asbestos restrictions)
• Age
  • 72 – median
  • Maximum lifetime risk for developing mesothelioma – individuals born 1925-1929
• Sex – M>F; 5:1

Risk Factors

• Asbestos exposure – amphiboles more carcinogenic than chrysotile fibers
  • 70-80% of mesothelioma cases occur in patients with history of asbestos exposure
  • At-risk occupations include shipbuilding, construction (ceiling tiles and boilers, especially prior to 1970), fireproofing, automobile brakes and clutches
• Genetics
  • Chromosome deletions (1p, 3p, 9p, 6q)

Pathophysiology

• Malignant pleural mesothelioma (MPM)
  •  3 histologic types
    • Epithelial – 50%
    • Biphasic (or mixed) – 25% 
    • Sarcomatous – 15%
  • May be mistaken for adenocarcinoma of the lung; histologically heterogeneous tumors
    • Histology affects survival
  • Long latency period (30-50 years) between asbestos exposure and disease development
  • Asbestos fibers are mutagenic and carcinogenic to several cells – commonly found in excised tumors
• Peritoneal mesothelioma
  • Histology associated with asbestos
    • Well-differentiated papillary
  • Histology not associated with asbestos
    • Cystic
    • Malignant

Clinical Presentation

• Disease usually advanced at time of presentation
  • Pleural – dyspnea, nonpleuritic chest pain, pleural effusion, cough, fatigue
  • Peritoneal – abdominal pain, ascites, anorexia, bloating, blood clotting abnormalities, anemia
  • Pericardial – chest pain, constrictive pericarditis

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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Cytology, Pulmonary 8209702 Method: Microscopy	Aid in the diagnosis of mesothelioma
Epithelial-Related Antigen, MOC-31 by Immunohistochemistry 2003875 Method: Immunohistochemistry	Aid in histologic diagnosis of mesothelioma Stained and returned to client pathologist; consultation available if needed
E-Cadherin by Immunohistochemistry 2003869 Method: Immunohistochemistry	Aid in histologic diagnosis of mesothelioma Stained and returned to client pathologist; consultation available if needed