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]], [[serous carcinoma]]
| 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, MTAP -ve (pleural mesothelioma), BAP1 -ve
| EM        =
| EM        =
| Molecular  = +/-p16 deletion
| Molecular  = +/-p16 deletion
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==General==
==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<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>
*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>


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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>
<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.
*[[Fibrosing pleuritis]] - should ''not'' have nodules, more cellular on the aspect adjacent to the effusion.
*Reactive mesothelial cells - may be atypical.
*Reactive mesothelial cells - may be atypical.
Line 82: Line 86:
*[[Adenocarcinoma]] - esp. [[lung adenocarcinoma]].
*[[Adenocarcinoma]] - esp. [[lung adenocarcinoma]].
*[[Serous carcinoma]].
*[[Serous carcinoma]].
*[[Synovial sarcoma]].


===Images===  
===Images===  
Line 93: 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===
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*EMA +ve ~100% (vs. ~10%).  
*EMA +ve ~100% (vs. ~10%).  
*Desmin -ve ~5% (vs. ~85%).
*Desmin -ve ~5% (vs. ~85%).
*GLUT1 +ve ~50% (vs. ~10%)
*GLUT1 +ve ~50% (vs. ~10%).
*p53 +ve ~50% (vs. ~2%).
*p53 +ve ~50% (vs. ~2%).
*BAP1 -ve<ref name=pmid29085180>{{cite journal |authors=Pulford E, Huilgol K, Moffat D, Henderson DW, Klebe S |title=Malignant Mesothelioma, BAP1 Immunohistochemistry, and VEGFA: Does BAP1 Have Potential for Early Diagnosis and Assessment of Prognosis? |journal=Dis Markers |volume=2017 |issue= |pages=1310478 |date=2017 |pmid=29085180 |pmc=5612603 |doi=10.1155/2017/1310478 |url=}}</ref> ~57%.<ref name=pmid26226841>{{cite journal |authors=Andrici J, Sheen A, Sioson L, Wardell K, Clarkson A, Watson N, Ahadi MS, Farzin M, Toon CW, Gill AJ |title=Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology |journal=Mod Pathol |volume=28 |issue=10 |pages=1360–8 |date=October 2015 |pmid=26226841 |pmc=4761613 |doi=10.1038/modpathol.2015.87 |url=}}</ref>


Note:
Note:
*The above are ''not'' very useful in individual cases.
*The above are ''not'' very useful in individual cases.
*A simple pankeratin is useful for seening where epithelial cells are.
*A simple pankeratin is useful for seening where epithelial cells are.
Others:
*MTAP -ve.<ref name=pmid34465883>{{cite journal |authors=Dacic S |title=Pleural mesothelioma classification-update and challenges |journal=Mod Pathol |volume=35 |issue=Suppl 1 |pages=51–56 |date=January 2022 |pmid=34465883 |doi=10.1038/s41379-021-00895-7 |url=}}</ref>
**May not be sensitive and specific for peritoneal mesothelioma.{{fact}}


===Mesothelioma versus adenocarcinoma===
===Mesothelioma versus adenocarcinoma===
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**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]].
***100% of lung adenocarcinoma versus ~25% of mesotheliomas.<ref>{{cite journal |authors=Ordóñez NG |title=Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma. The M.D. Anderson experience and a critical review of the literature |journal=Am J Clin Pathol |volume=109 |issue=1 |pages=85–9 |date=January 1998 |pmid= |doi=10.1093/ajcp/109.1.85 |url=}}</ref>
**MOC-31.
**MOC-31.
**CD15.
**CD15.
**[[B72.3]].


Other carcinoma markers:
===Other carcinoma markers===
*PAX-8.<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>
*[[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.
*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>
**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==
==Molecular==
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*p16 IHC does ''not'' give the same result.
*p16 IHC does ''not'' give the same result.
*Sensitivity of p16 deletion is low.
*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==

Latest revision as of 14:25, 9 October 2024

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, MTAP -ve (pleural mesothelioma), BAP1 -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

  • Ferruginous body. (WC)

  • MM - low mag.

  • MM - intermed. mag.

  • MM - high mag.

  • MM - very high mag.

  • MM - calretinin - intermed. mag.

  • MM - calretinin - high mag.

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%).
  • BAP1 -ve[14] ~57%.[15]

Note:

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

Others:

Mesothelioma versus adenocarcinoma

  • Several panel exists - no agreed upon best panel.[17]
    • Usually two carcinoma markers + two mesothelial markers.

Panel:[17]

  • Mesothelial markers:
    • Calretinin.
    • WT-1.
    • D2-40.
    • CK5/6.
  • Carcinoma markers:
    • CEA (monoclonal and polyclonal).
    • TTF-1.
    • Ber-EP4.
      • 100% of lung adenocarcinoma versus ~25% of mesotheliomas.[18]
    • MOC-31.
    • CD15.
    • B72.3.

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. ↑ Pulford E, Huilgol K, Moffat D, Henderson DW, Klebe S (2017). "Malignant Mesothelioma, BAP1 Immunohistochemistry, and VEGFA: Does BAP1 Have Potential for Early Diagnosis and Assessment of Prognosis?". Dis Markers 2017: 1310478. doi:10.1155/2017/1310478. PMC 5612603. PMID 29085180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612603/.
  15. ↑ Andrici J, Sheen A, Sioson L, Wardell K, Clarkson A, Watson N, Ahadi MS, Farzin M, Toon CW, Gill AJ (October 2015). "Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology". Mod Pathol 28 (10): 1360–8. doi:10.1038/modpathol.2015.87. PMC 4761613. PMID 26226841. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761613/.
  16. ↑ Dacic S (January 2022). "Pleural mesothelioma classification-update and challenges". Mod Pathol 35 (Suppl 1): 51–56. doi:10.1038/s41379-021-00895-7. PMID 34465883.
  17. ↑ 17.0 17.1 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.
  18. ↑ Ordóñez NG (January 1998). "Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma. The M.D. Anderson experience and a critical review of the literature". Am J Clin Pathol 109 (1): 85–9. doi:10.1093/ajcp/109.1.85.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
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