Malignant mesothelioma

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

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

Clinical history asbestos exposure
Prevalence rare
Prognosis very poor

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.

Note:

Asbestos

Conditions associated with asbestos exposure (mnemonic PALM):[5]

Possible association with asbestos exposure:

Microscopic

Features:[7]

  • 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.[8]
    • 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:[9]

Images

Subtypes

List of subtypes - mnemonic BEDS:[9][7]

  • 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.[10]

Stains

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

IHC

Mesothelioma versus mesothelial hyperplasia

Features:[11]

  • 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.[12]
    • Usually two carcinoma markers + two mesothelial markers.

Panel:[12]

  • 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:

  • PAX-8.[13]
  • Claudin-4.
    • Mesothelioma may be focally positive.[14]

Molecular

Notes:

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

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. 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.
  5. 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.
  6. 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.
  7. 7.0 7.1 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.
  8. URL: http://medical-dictionary.thefreedictionary.com/asbestos+body. Accessed on: 4 November 2011.
  9. 9.0 9.1 Corson, JM. (Nov 2004). "Pathology of mesothelioma.". Thorac Surg Clin 14 (4): 447-60. doi:10.1016/j.thorsurg.2004.06.007. PMID 15559051.
  10. Mayall, FG.; Gibbs, AR. (Jan 1992). "The histology and immunohistochemistry of small cell mesothelioma.". Histopathology 20 (1): 47-51. PMID 1310669.
  11. 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.
  12. 12.0 12.1 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.
  13. 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.
  14. 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.
  15. 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.