Difference between revisions of "Malignant mesothelioma"

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| Micro      = infiltrative atypical cells (epithelioid, spindled or both)
| Micro      = infiltrative atypical cells (epithelioid, spindled or both)
| Subtypes  = biphasic mesothelioma, epithelioid mesothelioma, desmoplastic mesothelioma, sarcomatoid mesothelioma.
| Subtypes  = biphasic mesothelioma, epithelioid mesothelioma, desmoplastic mesothelioma, sarcomatoid mesothelioma.
| LMDDx      = mesothelial hyperplasia, fibrosing pleuritis, [[adenocarcinoma]] - esp. [[lung adenocarcinoma|lung]]
| LMDDx      = mesothelial hyperplasia, [[fibrosing pleuritis]], [[adenocarcinoma]] - esp. [[lung adenocarcinoma|lung]], [[serous carcinoma]]
| Stains    =  
| Stains    =  
| IHC        = calretinin +ve, D2-40 +ve, CK5/6 +ve, WT-1 +ve, CK7 +ve, CEA -ve, TTF-1 -ve
| IHC        = calretinin +ve, D2-40 +ve, [[CK5/6]] +ve, WT-1 +ve, [[CK7]] +ve, CEA -ve, [[TTF-1]] -ve
| EM        =
| EM        =
| Molecular  =
| Molecular  = +/-p16 deletion
| IF        =
| IF        =
| Gross      =
| Gross      =
| Grossing  =
| Grossing  =
| Site      = [[lung]], peritoneum
| Site      = [[lung]], [[peritoneum]], [[omentum]], [[pericardium]]
| Assdx      =
| Assdx      = [[asbestosis]]
| Syndromes  =
| Syndromes  =
| Clinicalhx = asbestos exposure, smoking
| Clinicalhx = +/-asbestos exposure
| Signs      =
| Signs      =
| Symptoms  =
| Symptoms  =
Line 33: Line 33:


==General==
==General==
*Poor prognosis - median survival <12 months.<ref name=pmid23413596>{{Cite journal  | last1 = Mineo | first1 = TC. | last2 = Ambrogi | first2 = V. | title = Malignant pleural mesothelioma: factors influencing the prognosis. | journal = Oncology (Williston Park) | volume = 26 | issue = 12 | pages = 1164-75 | month = Dec | year = 2012 | doi =  | PMID = 23413596 }}</ref>
*Incidence
**Rare tumor accounting for 4-7 cases per million individuals.
**More common in men in 5th and 6th decades of life.
*Poor prognosis<ref>{{Cite journal  | last1 = Haber | first1 = SE. | last2 = Haber | first2 = JM. | title = Malignant mesothelioma: a clinical study of 238 cases. | journal = Ind Health | volume = 49 | issue = 2 | pages = 166-72 | month =  | year = 2011 | doi =  | PMID = 21173534 }}</ref> - median survival <12 months.<ref name=pmid23413596>{{Cite journal  | last1 = Mineo | first1 = TC. | last2 = Ambrogi | first2 = V. | title = Malignant pleural mesothelioma: factors influencing the prognosis. | journal = Oncology (Williston Park) | volume = 26 | issue = 12 | pages = 1164-75 | month = Dec | year = 2012 | doi =  | PMID = 23413596 }}</ref>


Locations:
Locations:
*Lung.
*Lung.
*Primary peritoneal.
*Primary [[peritoneum|peritoneal]].
*Primary [[pericardium|pericardial]].<ref name=pmid22740748>{{Cite journal  | last1 = Sardar | first1 = MR. | last2 = Kuntz | first2 = C. | last3 = Patel | first3 = T. | last4 = Saeed | first4 = W. | last5 = Gnall | first5 = E. | last6 = Imaizumi | first6 = S. | last7 = Lande | first7 = L. | title = Primary pericardial mesothelioma unique case and literature review. | journal = Tex Heart Inst J | volume = 39 | issue = 2 | pages = 261-4 | month =  | year = 2012 | doi =  | PMID = 22740748 }}</ref>


Epidemiology:
Epidemiology:
*Strong association with asbestos exposure.
*Strong association with asbestos exposure.


Treatment:
*+/-Surgical debulking (cytoreduction) with heated chemotherapy - for intraperitoneal mesothelioma.<ref name=pmid24158467>{{cite journal |author=Wong J, Koch AL, Deneve JL, Fulp W, Tanvetyanon T, Dessureault S |title=Repeat cytoreductive surgery and heated intraperitoneal chemotherapy may offer survival benefit for intraperitoneal mesothelioma: a single institution experience |journal=Ann. Surg. Oncol. |volume=21 |issue=5 |pages=1480–6 |year=2014 |month=May |pmid=24158467 |doi=10.1245/s10434-013-3341-7 |url=}}</ref>
Note:
*No association with [[smoking]].{{fact}}<ref name=pmid24351898>{{Cite journal  | last1 = Offermans | first1 = NS. | last2 = Vermeulen | first2 = R. | last3 = Burdorf | first3 = A. | last4 = Goldbohm | first4 = RA. | last5 = Kauppinen | first5 = T. | last6 = Kromhout | first6 = H. | last7 = van den Brandt | first7 = PA. | title = Occupational asbestos exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective Netherlands cohort study. | journal = J Occup Environ Med | volume = 56 | issue = 1 | pages = 6-19 | month = Jan | year = 2014 | doi = 10.1097/JOM.0000000000000060 | PMID = 24351898 }}</ref>
===Asbestos===
Conditions associated with asbestos exposure (mnemonic ''PALM''):<ref name=Ref_PCPBoD8_375>{{Ref PCPBoD8|375}}</ref>
Conditions associated with asbestos exposure (mnemonic ''PALM''):<ref name=Ref_PCPBoD8_375>{{Ref PCPBoD8|375}}</ref>
*Pleural plaques.
*[[Pleural plaques]].
*[[Asbestosis]].
*[[Asbestosis]].
*[[Lung carcinoma]].
*[[Lung carcinoma]].
Line 54: Line 65:
Features:<ref name=Ref_WMSP156>{{Ref WMSP|156}}</ref>
Features:<ref name=Ref_WMSP156>{{Ref WMSP|156}}</ref>
*Infiltrative atypical cells - '''key feature'''.
*Infiltrative atypical cells - '''key feature'''.
**Infiltration into fat - ''diagnostic''.
**+/-Epithelioid cells - may be cytologically bland, i.e. benign appearing.
**+/-Epithelioid cells - may be cytologically bland, i.e. benign appearing.
***Variable architecture: sheets, microglandular, tubulopapillary.
***Variable architecture: sheets, microglandular, tubulopapillary.
***+/-[[Psammoma bodies]].
***+/-[[Psammoma bodies]].
**+/-Spindle cells.
**+/-Spindle cells.
*+/-''Ferruginous body'' - '''strongly supportive'''.<ref>URL: [http://medical-dictionary.thefreedictionary.com/asbestos+body http://medical-dictionary.thefreedictionary.com/asbestos+body]. Accessed on: 4 November 2011.</ref>
*+/-''[[Ferruginous body]]'' - '''strongly supportive'''.<ref>URL: [http://medical-dictionary.thefreedictionary.com/asbestos+body http://medical-dictionary.thefreedictionary.com/asbestos+body]. Accessed on: 4 November 2011.</ref>
** Looks like a (twirling) baton - segemented appearance, brown colour.
** Looks like a (twirling) baton - segemented appearance, brown colour.
** Thin (asbestos) fiber in the core.  
** Thin (asbestos) fiber in the core.  


Note:
Notes:
*''Asbestos body'' is not strictly speaking a synonym for ''ferruginous body''.
*''Asbestos body'' is not strictly speaking a synonym for ''ferruginous body''.
*Don't diagnose ''mesothelioma in situ''.{{fact}}


DDx:<ref name=pmid15559051>{{Cite journal  | last1 = Corson | first1 = JM. | title = Pathology of mesothelioma. | journal = Thorac Surg Clin | volume = 14 | issue = 4 | pages = 447-60 | month = Nov | year = 2004 | doi = 10.1016/j.thorsurg.2004.06.007 | PMID = 15559051 }}
DDx:<ref name=pmid15559051>{{Cite journal  | last1 = Corson | first1 = JM. | title = Pathology of mesothelioma. | journal = Thorac Surg Clin | volume = 14 | issue = 4 | pages = 447-60 | month = Nov | year = 2004 | doi = 10.1016/j.thorsurg.2004.06.007 | PMID = 15559051 }}
</ref>
</ref>
*[[Fibrosing pleuritis]].
<ref name="pmid15725802">{{Cite journal  | last1 = Bégueret | first1 = H. | last2 = Galateau-Salle | first2 = F. | last3 = Guillou | first3 = L. | last4 = Chetaille | first4 = B. | last5 = Brambilla | first5 = E. | last6 = Vignaud | first6 = JM. | last7 = Terrier | first7 = P. | last8 = Groussard | first8 = O. | last9 = Coindre | first9 = JM. | title = Primary intrathoracic synovial sarcoma: a clinicopathologic study of 40 t(X;18)-positive cases from the French Sarcoma Group and the Mesopath Group. | journal = Am J Surg Pathol | volume = 29 | issue = 3 | pages = 339-46 | month = Mar | year = 2005 | doi =  | PMID = 15725802 }}</ref>
*[[Fibrosing pleuritis]] - should ''not'' have nodules, more cellular on the aspect adjacent to the effusion.
*Reactive mesothelial cells - may be atypical.
*Mesothelial hyperplasia.
*Mesothelial hyperplasia.
*[[Adenocarcinoma]] - esp. [[lung adenocarcinoma]].
*[[Adenocarcinoma]] - esp. [[lung adenocarcinoma]].
*[[Serous carcinoma]].
*[[Synovial sarcoma]].


===Images===  
===Images===  
Line 81: Line 98:
Image: Malignant epithelioid mesothelioma - calretinin - high mag.jpg | MM - calretinin - high mag.
Image: Malignant epithelioid mesothelioma - calretinin - high mag.jpg | MM - calretinin - high mag.
</gallery>
</gallery>
====www====
*[http://www.rosaicollection.org/searchresults.cfm/ Mesothelioma (rosaicollection.org/index.cfm)].


===Subtypes===
===Subtypes===
Line 90: Line 110:
**Should be 50%+ dense tissue with storiform pattern & atypical cells.
**Should be 50%+ dense tissue with storiform pattern & atypical cells.
*Sarcomatoid mesothelioma.
*Sarcomatoid mesothelioma.
Other:
*Small cell mesothelioma.<ref name=pmid1310669>{{Cite journal  | last1 = Mayall | first1 = FG. | last2 = Gibbs | first2 = AR. | title = The histology and immunohistochemistry of small cell mesothelioma. | journal = Histopathology | volume = 20 | issue = 1 | pages = 47-51 | month = Jan | year = 1992 | doi =  | PMID = 1310669 }}</ref>


==Stains==
==Stains==
Line 103: Line 125:
*GLUT1 +ve ~50% (vs. ~10%)
*GLUT1 +ve ~50% (vs. ~10%)
*p53 +ve ~50% (vs. ~2%).
*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===
===Mesothelioma versus adenocarcinoma===
Line 113: Line 139:
**WT-1.
**WT-1.
**D2-40.
**D2-40.
**CK5/6.
**[[CK5/6]].
*Carcinoma markers:
*Carcinoma markers:
**CEA (monoclonal and polyclonal).
**CEA (monoclonal and polyclonal).
**TTF-1.
**[[TTF-1]].
**Ber-EP4.
**[[Ber-EP4]].
**MOC-31.
**MOC-31.
**CD15.
**CD15.
**[[B72.3]].
===Other carcinoma markers===
*[[PAX8]] -ve.<ref name=pmid23846294>{{cite journal |author=Lee M, Alexander HR, Burke A |title=Diffuse mesothelioma of the peritoneum: a pathological study of 64 tumours treated with cytoreductive therapy |journal=Pathology |volume=45 |issue=5 |pages=464–73 |year=2013 |month=August |pmid=23846294 |doi=10.1097/PAT.0b013e3283631cce |url=}}</ref>
*Claudin-4.
**Mesothelioma may be focally positive.<ref name=pmid23775021>{{cite journal |author=Ohta Y, Sasaki Y, Saito M, ''et al.'' |title=Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma |journal=Int. J. Surg. Pathol. |volume=21 |issue=5 |pages=493–501 |year=2013 |month=October |pmid=23775021 |doi=10.1177/1066896913491320 |url=}}</ref>
*[[p63]] -ve.<ref name=pmid18064689>{{Cite journal  | last1 = Pu | first1 = RT. | last2 = Pang | first2 = Y. | last3 = Michael | first3 = CW. | title = 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. | journal = Diagn Cytopathol | volume = 36 | issue = 1 | pages = 20-5 | month = Jan | year = 2008 | doi = 10.1002/dc.20747 | PMID = 18064689 }}</ref>
*[[CD138]] +ve.
**Usually -ve in mesothelioma.<ref name=pmid12866374>{{Cite journal  | last1 = Chu | first1 = PG. | last2 = Arber | first2 = DA. | last3 = Weiss | first3 = LM. | title = Expression of T/NK-cell and plasma cell antigens in nonhematopoietic epithelioid neoplasms. An immunohistochemical study of 447 cases. | journal = Am J Clin Pathol | volume = 120 | issue = 1 | pages = 64-70 | month = Jul | year = 2003 | doi = 10.1309/48KC-17WA-U69B-TBXQ | PMID = 12866374 }}</ref>
==Molecular==
*p16 deletion by [[FISH]].<ref name=pmid24503757>{{cite journal |author=Hwang H, Tse C, Rodriguez S, Gown A, Churg A |title=p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma |journal=Am. J. Surg. Pathol. |volume=38 |issue=5 |pages=681–8 |year=2014 |month=May |pmid=24503757 |doi=10.1097/PAS.0000000000000176 |url=}}</ref>
Notes:
*p16 IHC does ''not'' give the same result.
*Sensitivity of p16 deletion is low.
==Sign out==
<pre>
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.
</pre>


==See also==
==See also==
*[[Lung tumours]].
*[[Lung tumours]].
*[[Omentum]].
*[[Empyema peel]].


==References==
==References==

Revision as of 22:22, 22 January 2019

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

  • Incidence
    • Rare tumor accounting for 4-7 cases per million individuals.
    • More common in men in 5th and 6th decades of life.
  • 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] [11]

Images

www

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.[12]

Stains

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

IHC

Mesothelioma versus mesothelial hyperplasia

Features:[13]

  • 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.[14]
    • Usually two carcinoma markers + two mesothelial markers.

Panel:[14]

  • Mesothelial markers:
    • Calretinin.
    • WT-1.
    • D2-40.
    • CK5/6.
  • Carcinoma markers:

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. Bégueret, H.; Galateau-Salle, F.; Guillou, L.; Chetaille, B.; Brambilla, E.; Vignaud, JM.; Terrier, P.; Groussard, O. et al. (Mar 2005). "Primary intrathoracic synovial sarcoma: a clinicopathologic study of 40 t(X;18)-positive cases from the French Sarcoma Group and the Mesopath Group.". Am J Surg Pathol 29 (3): 339-46. PMID 15725802.
  12. Mayall, FG.; Gibbs, AR. (Jan 1992). "The histology and immunohistochemistry of small cell mesothelioma.". Histopathology 20 (1): 47-51. PMID 1310669.
  13. 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.
  14. 14.0 14.1 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.