Mesothelioma

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • High suspicion for mesothelioma
    • Abnormal chest x-ray (eg, pleural effusion, pleural plaques)
  • History of asbestos exposure and chest symptoms (eg, cough, dyspnea)

Histology

  • Diagnosis is based on combination of appropriate histology and immunohistochemistry (IHC) using adequate biopsy in conjunction with clinical surgical and radiographic history (2013 Consensus International Mesothelioma Interest Group)
    • Consultation with a specialist is recommended
    • Guidance on evaluation of possible malignant mesothelioma varies across medical literature
  • Body cavity fluid studies
    • May be negative – not usually diagnostic and may be difficult to differentiate from benign hyperplasia
    • Cytology – elevated hyaluronic acid levels are suggestive
    • Not all patients with mesothelioma develop effusions
  • Tissue specimens required for diagnosis
    • Pleural biopsy – CT-guided or thorascopic video-assisted thoracic surgery biopsy, Abrams needle
    • Open thoracotomy – use only if less invasive testing not diagnostic
  • Immunohistochemistry
    • Usefulness depends on
      • Histologic subtype (epithelioid vs. sarcomatoid vs. desmoplastic variant of sarcomatoid)
      • Location (pleural vs. peritoneal)
      • Differential diagnosis
    • IHC staining may be chosen by subtype of pathology
      • Morphologic assessment performed first; IHC is adjunct testing
      • Acceptable method – use 2 markers for mesothelioma subtype and 2 for suspected carcinoma cell type
      • Add markers based on initial marker pattern in a stage-wise approach if testing combination yields no definitive answer
  • Molecular markers – homozygous deletion of qp21 locus; p16/CDKN2A deletions most often in pleural subtypes
    • IHC p16 positivity does not translate to molecular deletion

Imaging Studies

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

Differential Diagnosis

  • Pleural
    • Fibrous pleurisy secondary to a variety of inflammatory causes (eg, infections, collagen vascular diseases, pulmonary infarcts, trauma, surgery, drug reactions)
    • Malignancy
    • Other – solitary fibrous tumor, pleural epithelioid hemangioendothelioma
  • Peritoneal
  • Screening not recommended (even in high risk patients)
    • No recommendation for CT/MRI (NCCN, 2015)
  • Serum biomarkers – no proven efficacy in screening of asbestos-exposed workers
  • Soluble mesothelial-related peptides (Mesomark)
    • Useful for monitoring epithelial or biphasic mesothelioma
    • Requires serial measurement
    • Not useful as a diagnostic test
    • Values affected by renal function

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 million – ~2,500 new cases each year in U.S. (NCCN, 2015)
    • 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 (due to highest rate of asbestos exposure)
  • 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 histological types
      • Epithelioid – 50-60%
      • Biphasic (or mixed) – 25-35% 
      • Sarcomatoid – 10-20%
    • May be mistaken for adenocarcinoma of the lung; histologically heterogeneous tumors
      • Histology of mesothelioma affects survival
    • Long latency period (20-40 years) between asbestos exposure and disease development
      • Not all mesotheliomas are related to asbestos exposure, and the absence of an asbestos exposure history does not exclude the diagnosis
    • Asbestos fibers are mutagenic and carcinogenic to several cells – commonly found in excised tumors
  • Peritoneal malignant mesothelioma (PMM)
    • Less likely to be related to asbestos exposure
    • Malignant
  • Benign multicystic mesothelioma – well-differentiated
  • Papillary mesothelioma – well-differentiated

Clinical Presentation

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

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.

Cytology, Non-Gynecologic 2000623
Method: Microscopy

Limitations

Low diagnostic yield

Follow Up

Obtain tissue for histological evaluation

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

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

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

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

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

Calretinin by Immunohistochemistry 2003490
Method: Immunohistochemistry

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

D2-40 by Immunohistochemistry 2003857
Method: Immunohistochemistry

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

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

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

Breast Carcinoma b72.3 by Immunohistochemistry 2003445
Method: Immunohistochemistry

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

CD15, Leu M1 by Immunohistochemistry 2003529
Method: Immunohistochemistry

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

Limitations

Not a diagnostic test

Humanitarian-use device; requires IRB approval for use

Follow Up

Requires serial measurements

Related Tests

Guidelines

British Thoracic Society Standards of Care Committee. BTS statement on malignant mesothelioma in the UK, 2007. Thorax. 2007; 62 Suppl 2: ii1-ii19. PubMed

Deraco M, Bartlett D, Kusamura S, Baratti D. Consensus statement on peritoneal mesothelioma. J Surg Oncol. 2008; 98(4): 268-72. PubMed

Hassan R, Alexander R, Antman K, Boffetta P, Churg A, Coit D, Hausner P, Kennedy R, Kindler H, Metintas M, Mutti L, Onda M, Pass H, Premkumar A, Roggli V, Sterman D, Sugarbaker P, Taub R, Verschraegen C. Current treatment options and biology of peritoneal mesothelioma: meeting summary of the first NIH peritoneal mesothelioma conference. Ann Oncol. 2006; 17(11): 1615-9. PubMed

Husain AN, Colby T, Ordonez N, Krausz T, Attanoos R, Beasley MBeth, Borczuk AC, Butnor K, Cagle PT, Chirieac LR, Churg A, Dacic S, Fraire A, Galateau-Salle F, Gibbs A, Gown A, Hammar S, Litzky L, Marchevsky AM, Nicholson AG, Roggli V, Travis WD, Wick M, International Mesothelioma Interest Group. Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2013; 137(5): 647-67. PubMed

NCCN Clinical Practice Guidelines in Oncology, Malignant Pleural Mesothelioma. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Jan 2016]

Protocol for the Examination of Specimens from Patients with Malignant Pleural Mesothelioma. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: October 2009. College of American Pathologists (CAP). Northfield, IL [Accessed: Jan 2016]

General References

Arif Q, Husain AN. Malignant Mesothelioma Diagnosis Arch Pathol Lab Med. 2015; 139(8): 978-80. PubMed

Beasley MBeth. Immunohistochemistry of pulmonary and pleural neoplasia. Arch Pathol Lab Med. 2008; 132(7): 1062-72. PubMed

Cristaudo A, Bonotti A, Simonini S, Bruno R, Foddis R. Soluble markers for diagnosis of malignant pleural mesothelioma. Biomark Med. 2011; 5(2): 261-73. PubMed

Grigoriu BD, Grigoriu C, Chahine B, Gey T, Scherpereel A. Clinical utility of diagnostic markers for malignant pleural mesothelioma. Monaldi Arch Chest Dis. 2009; 71(1): 31-8. PubMed

Henderson DW, Reid G, Kao SC, van Zandwijk N, Klebe S. Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA. J Clin Pathol. 2013; 66(10): 854-61. PubMed

Kao SChuan-Hao, Reid G, van Zandwijk N, Henderson DW, Klebe S. Molecular biomarkers in malignant mesothelioma: state of the art. Pathology. 2011; 43(3): 201-12. PubMed

Klebe S, Henderson DW. Early stages of mesothelioma, screening and biomarkers. Recent Results Cancer Res. 2011; 189: 169-93. PubMed

Ordóñez NG. What are the current best immunohistochemical markers for the diagnosis of epithelioid mesothelioma? A review and update. Hum Pathol. 2007; 38(1): 1-16. PubMed

Rodríguez Panadero F. Diagnosis and treatment of malignant pleural mesothelioma. Arch Bronconeumol. 2015; 51(4): 177-84. PubMed

Tsao AS, Wistuba I, Roth JA, Kindler HLee. Malignant pleural mesothelioma. J Clin Oncol. 2009; 27(12): 2081-90. PubMed

van der Bij S, Schaake E, Koffijberg H, Burgers JA, de Mol BA J M, Moons KG M. Markers for the non-invasive diagnosis of mesothelioma: a systematic review. Br J Cancer. 2011; 104(8): 1325-33. PubMed

Medical Reviewers

Last Update: March 2016