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

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

Screening

  • Imaging (CT/x-ray/MRI) – not recommended on a regular basis for screening or monitoring of asbestos-exposed workers
  • Serum biomarkers – no proven efficacy in screening of asbestos-exposed workers
  • Screening studied in high-risk patients (those with asbestos exposure) – no guidelines currently recommend screening for malignant pleural mesothelioma

Monitoring

  • Soluble mesothelial-related peptides (Mesomark)
    • Useful for monitoring epithelial or biphasic mesothelioma
    • Requires serial measurement
    • Not useful as a diagnostic test

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
Test Name and Number Recommended Use Limitations Follow Up
Cytology, Body Cavity Fluid 8209701
Method: Microscopy

May aid in the diagnosis of mesothelioma

   
Pan Cytokeratin (AE1,3) by Immunohistochemistry 2003433
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Cytokeratin 7 (CK 7) by Immunohistochemistry 2003854
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Cytokeratin 20 (CK 20) by Immunohistochemistry 2003848
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Cytokeratin 5,6  (CK 5,6) by Immunohistochemistry 2003851
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Wilms Tumor (WT-1), N-terminus by Immunohistochemistry 2004184
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Calretinin by Immunohistochemistry 2003490
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
HBME-1 (Mesothelial Cell) by Immunohistochemistry 2003914
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
D2-40 by Immunohistochemistry 2003857
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Keratin 903 (K903) High Molecular Weight by Immunohistochemistry 2003978
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Thyroid Transcription Factor (TTF-1) by Immunohistochemistry 2004166
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Carcinoembryonic Antigen, Monoclonal (CEA M) by Immunohistochemistry 2003824
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Carcinoembryonic Antigen, Polyclonal (CEA P) by Immunohistochemistry 2003827
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Breast Carcinoma b72.3 by Immunohistochemistry 2003445
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Anti-Human Epithelial Antigen, Ber-EP4 by Immunohistochemistry 2003463
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
CD15, Leu M1 by Immunohistochemistry 2003529
Method: Immunohistochemistry

Aid in histologic diagnosis of mesothelioma

Stained and returned to client pathologist; consultation available if needed

   
Soluble Mesothelin Related Peptides (MESOMARK®0081284
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Monitor mesothelioma

Not a diagnostic test

Humanitarian-use device; requires IRB approval for use

Requires serial measurements

Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
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