Malignant mesothelioma

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Malignant mesothelioma
Diagnosis in short

Malignant mesothelioma. H&E stain.

LM infiltrative atypical cells (epithelioid, spindled or both)
Subtypes biphasic mesothelioma, epithelioid mesothelioma, desmoplastic mesothelioma, sarcomatoid mesothelioma.
LM DDx mesothelial hyperplasia, fibrosing pleuritis, adenocarcinoma - esp. lung, serous carcinoma
IHC calretinin +ve, D2-40 +ve, CK5/6 +ve, WT-1 +ve, CK7 +ve, CEA -ve, TTF-1 -ve
Molecular +/-p16 deletion
Site lung, peritoneum, omentum, pericardium

Associated Dx asbestosis
Clinical history +/-asbestos exposure
Prevalence rare
Prognosis very poor

Malignant mesothelioma, also mesothelioma, is a form of cancer. It arises from the mesothelium.

It should not be confused with benign multicystic mesothelioma and benign papillary mesothelioma.

General

  • Poor prognosis[1] - median survival <12 months.[2]

Locations:

Epidemiology:

  • Strong association with asbestos exposure.

Treatment:

  • +/-Surgical debulking (cytoreduction) with heated chemotherapy - for intraperitoneal mesothelioma.[4]

Note:

Asbestos

Conditions associated with asbestos exposure (mnemonic PALM):[6]

Possible association with asbestos exposure:

Microscopic

Features:[8]

  • Infiltrative atypical cells - key feature.
    • Infiltration into fat - diagnostic.
    • +/-Epithelioid cells - may be cytologically bland, i.e. benign appearing.
      • Variable architecture: sheets, microglandular, tubulopapillary.
      • +/-Psammoma bodies.
    • +/-Spindle cells.
  • +/-Ferruginous body - strongly supportive.[9]
    • Looks like a (twirling) baton - segemented appearance, brown colour.
    • Thin (asbestos) fiber in the core.

Notes:

  • Asbestos body is not strictly speaking a synonym for ferruginous body.
  • Don't diagnose mesothelioma in situ.[citation needed]

DDx:[10]

Images

Subtypes

List of subtypes - mnemonic BEDS:[10][8]

  • Biphasic mesothelioma.
    • 10%+ of epithelioid & 10%+ sarcomatoid.
  • Epithelioid mesothelioma.
  • Desmoplastic mesothelioma.
    • Should be 50%+ dense tissue with storiform pattern & atypical cells.
  • Sarcomatoid mesothelioma.

Other:

  • Small cell mesothelioma.[11]

Stains

  • PASD -ve.
  • Mucicarmine -ve.
    • Typically +ve in adenocarcinoma.

IHC

Mesothelioma versus mesothelial hyperplasia

Features:[12]

  • EMA +ve ~100% (vs. ~10%).
  • Desmin -ve ~5% (vs. ~85%).
  • GLUT1 +ve ~50% (vs. ~10%)
  • p53 +ve ~50% (vs. ~2%).

Note:

  • The above are not very useful in individual cases.
  • A simple pankeratin is useful for seening where epithelial cells are.

Mesothelioma versus adenocarcinoma

  • Several panel exists - no agreed upon best panel.[13]
    • Usually two carcinoma markers + two mesothelial markers.

Panel:[13]

  • Mesothelial markers:
    • Calretinin.
    • WT-1.
    • D2-40.
    • CK5/6.
  • Carcinoma markers:
    • CEA (monoclonal and polyclonal).
    • TTF-1.
    • Ber-EP4.
    • MOC-31.
    • CD15.

Other carcinoma markers

Molecular

Notes:

  • p16 IHC does not give the same result.
  • Sensitivity of p16 deletion is low.

Sign out

Pleural Tissue of Right Lung, Removal:
- MALIGNANT MESOTHELIOMA, epithelioid type.

Comment:
IHC confirms the morphologic impression. 

The tumour stains as follows:
POSITIVE: calretinin (very strong), CK5/6.
NEGATIVE: TTF-1.

See also

References

  1. Haber, SE.; Haber, JM. (2011). "Malignant mesothelioma: a clinical study of 238 cases.". Ind Health 49 (2): 166-72. PMID 21173534.
  2. Mineo, TC.; Ambrogi, V. (Dec 2012). "Malignant pleural mesothelioma: factors influencing the prognosis.". Oncology (Williston Park) 26 (12): 1164-75. PMID 23413596.
  3. Sardar, MR.; Kuntz, C.; Patel, T.; Saeed, W.; Gnall, E.; Imaizumi, S.; Lande, L. (2012). "Primary pericardial mesothelioma unique case and literature review.". Tex Heart Inst J 39 (2): 261-4. PMID 22740748.
  4. Wong J, Koch AL, Deneve JL, Fulp W, Tanvetyanon T, Dessureault S (May 2014). "Repeat cytoreductive surgery and heated intraperitoneal chemotherapy may offer survival benefit for intraperitoneal mesothelioma: a single institution experience". Ann. Surg. Oncol. 21 (5): 1480–6. doi:10.1245/s10434-013-3341-7. PMID 24158467.
  5. Offermans, NS.; Vermeulen, R.; Burdorf, A.; Goldbohm, RA.; Kauppinen, T.; Kromhout, H.; van den Brandt, PA. (Jan 2014). "Occupational asbestos exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective Netherlands cohort study.". J Occup Environ Med 56 (1): 6-19. doi:10.1097/JOM.0000000000000060. PMID 24351898.
  6. Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 375. ISBN 978-1416054542.
  7. Reid, A.; Heyworth, J.; de Klerk, N.; Musk, AW. (Nov 2009). "Asbestos exposure and gestational trophoblastic disease: a hypothesis.". Cancer Epidemiol Biomarkers Prev 18 (11): 2895-8. doi:10.1158/1055-9965.EPI-09-0731. PMID 19900938.
  8. 8.0 8.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 156. ISBN 978-0781765275.
  9. URL: http://medical-dictionary.thefreedictionary.com/asbestos+body. Accessed on: 4 November 2011.
  10. 10.0 10.1 Corson, JM. (Nov 2004). "Pathology of mesothelioma.". Thorac Surg Clin 14 (4): 447-60. doi:10.1016/j.thorsurg.2004.06.007. PMID 15559051.
  11. Mayall, FG.; Gibbs, AR. (Jan 1992). "The histology and immunohistochemistry of small cell mesothelioma.". Histopathology 20 (1): 47-51. PMID 1310669.
  12. Hasteh, F.; Lin, GY.; Weidner, N.; Michael, CW. (Apr 2010). "The use of immunohistochemistry to distinguish reactive mesothelial cells from malignant mesothelioma in cytologic effusions.". Cancer Cytopathol 118 (2): 90-6. doi:10.1002/cncy.20071. PMID 20209622.
  13. 13.0 13.1 Marchevsky AM (March 2008). "Application of immunohistochemistry to the diagnosis of malignant mesothelioma". Arch. Pathol. Lab. Med. 132 (3): 397-401. PMID 18318582. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=397.
  14. Lee M, Alexander HR, Burke A (August 2013). "Diffuse mesothelioma of the peritoneum: a pathological study of 64 tumours treated with cytoreductive therapy". Pathology 45 (5): 464–73. doi:10.1097/PAT.0b013e3283631cce. PMID 23846294.
  15. Ohta Y, Sasaki Y, Saito M, et al. (October 2013). "Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma". Int. J. Surg. Pathol. 21 (5): 493–501. doi:10.1177/1066896913491320. PMID 23775021.
  16. Pu, RT.; Pang, Y.; Michael, CW. (Jan 2008). "Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions.". Diagn Cytopathol 36 (1): 20-5. doi:10.1002/dc.20747. PMID 18064689.
  17. Chu, PG.; Arber, DA.; Weiss, LM. (Jul 2003). "Expression of T/NK-cell and plasma cell antigens in nonhematopoietic epithelioid neoplasms. An immunohistochemical study of 447 cases.". Am J Clin Pathol 120 (1): 64-70. doi:10.1309/48KC-17WA-U69B-TBXQ. PMID 12866374.
  18. Hwang H, Tse C, Rodriguez S, Gown A, Churg A (May 2014). "p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma". Am. J. Surg. Pathol. 38 (5): 681–8. doi:10.1097/PAS.0000000000000176. PMID 24503757.