Skip to main content

Advertisement

Log in

Histologic analysis has a prognostical value in colorectal biopsies assessed for suspicion of graft-versus-host disease

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Gastrointestinal (GI) graft-versus-host-disease (GVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation, but clinical and histological features are unspecific. The aim of this study was to correlate the histological GI GVHD grade with the clinical outcomes. In a retrospective study of 112 patients with clinically suspected GI GVHD, colonic biopsies were reviewed by three pathologists without knowledge of the corresponding clinical data and classified in four scores, according to the NIH Consensus Project recommendations: no GVHD, possible, probable, and unequivocal GVHD. At the end of the study, the histological and clinical data were confronted with the following results: clinical diagnosis of GI GVHD was established for 70 patients (62.5%) and histological scores correlated well with the clinical diagnosis (p < 0.001) and particularly with the prognosis (p < 0.05).When severe lesions were observed, the 1 year overall survival declined to 9%. None of the features reported in the literature to support GVHD diagnosis, eosinophil count, endocrine cells aggregate, immunohistochemical analysis (cytomegalovirus, CD123, chromogranin), did not help us for diagnosis. So routine histopathology alone without immunohistochemistry is a strong and reproducible tool to diagnose GI GVHD with the help of clinical and biological information, and most importantly, histological grading proved to be a powerful prognostic value.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

AB:

Apoptotic body

CMV:

Cytomegalovirus

GI:

Gastrointestinal

GVHD:

Graft versus host disease

H&E:

Hematoxylin eosin

HES:

Hematoxylin eosin saffron

HPF:

High power field

HSCT:

Hematopoietic stem cell transplantation

MMF:

Mycophenolate mofetil

NC:

Non contributory

References

  1. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, Barrett J, Blaise D, Lowski R, Horowitz M (2009) Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 15(12):1628–1633. https://doi.org/10.1016/j.bbmt.2009.07.004

    Article  PubMed  PubMed Central  Google Scholar 

  2. Castilla-Llorente C, Martin PJ, McDonald GB, Storer BE, Appelbaum FR, Deeg HJ, Mielcarek M, Shulman H, Storb R, Nash RA (2014) Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 49(7):966–971. https://doi.org/10.1038/bmt.2014.69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Epstein RJ, McDonald GB, Sale GE, Shulman HM, Thomas ED (1980) The diagnostic accuracy of the rectal biopsy in acute graft-versus-host disease: a prospective study of thirteen patients. Gastroenterology 78(4):764–771

    CAS  PubMed  Google Scholar 

  4. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME (2005) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Bone Marrow Transplant 11(12):945–956. https://doi.org/10.1016/j.bbmt.2005.09.004

    Article  Google Scholar 

  5. Lee FD (1993) Importance of apoptosis in the histopathology of drug related lesions in the large intestine. J Clin Pathol 46(2):118–122. https://doi.org/10.1136/jcp.46.2.118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Leino DG, Greenson JK (2012) Can we distinguish mycophenolate-induced colitis from colonic graft-versus-host disease? Modern Pathol 25:167–168A

  7. Lin J, Chen S, Zhao Z, Cummings OW, Fan R (2013) CD123 is a useful immunohistochemical marker to facilitate diagnosis of acute graft-versus-host disease in colon. Hum Pathol 44(10):2075–2080. https://doi.org/10.1016/j.humpath.2013.02.023

    Article  CAS  PubMed  Google Scholar 

  8. Lin J, Fan R, Zhao Z, Cummings OW, Chen S (2013) Is the presence of 6 or fewer crypt apoptotic bodies sufficient for diagnosis of graft versus host disease? A decade of experience at a single institution. Am J Surg Pathol 37(4):539–547. https://doi.org/10.1097/PAS.0b013e318272c62a

    Article  PubMed  Google Scholar 

  9. Nguyen CV, Kastenberg DM, Choudhary C, Katz LC, DiMarino A, Palazzo JP (2008) Is single-cell apoptosis sufficient for the diagnosis of graft-versus-host disease in the colon? Dig Dis Sci 53(3):747–756. https://doi.org/10.1007/s10620-007-9904-3

    Article  PubMed  Google Scholar 

  10. Papadimitriou JC, Cangro CB, Lustberg A, Khaled A, Nogueira J, Wiland A, Ramos E, Klassen DK, Drachenberg CB (2003) Histologic features of mycophenolate mofetil-related colitis: a graft-versus-host disease-like pattern. Int J Surg Pathol 11(4):295–302. https://doi.org/10.1177/106689690301100406

    Article  PubMed  Google Scholar 

  11. Remberger M, Ackefors M, Berglund S, Blennow O, Dahllof G, Dlugosz A, Garming-Legert K, Gertow J, Gustafsson B, Hassan M, Hassan Z, Hauzenberger D, Hagglund H, Karlsson H, Klingspor L, Kumlien G, Le Blanc K, Ljungman P, Machaczka M, Malmberg KJ, Marschall HU, Mattsson J, Olsson R, Omazic B, Sairafi D, Schaffer M, Svahn BM, Svenberg P, Swartling L, Szakos A, Uhlin M, Uzunel M, Watz E, Wernerson A, Wikman A, Wikstrom AC, Winiarski J, Ringden O (2011) Improved survival after allogeneic hematopoietic stem cell transplantation in recent years. A single-center study. Biol Blood Marrow Transplant 17(11):1688–1697. https://doi.org/10.1016/j.bbmt.2011.05.001

    Article  PubMed  Google Scholar 

  12. Ross WA, Couriel D (2005) Colonic graft-versus-host disease. Curr Opin Gastroenterol 21(1):64–69

    PubMed  Google Scholar 

  13. Schulenburg A, Turetschek K, Wrba F, Vogelsang H, Greinix HT, Keil F, Mitterbauer M, Kalhs P (2004) Early and late gastrointestinal complications after myeloablative and nonmyeloablative allogeneic stem cell transplantation. Ann Hematol 83(2):101–106. https://doi.org/10.1007/s00277-003-0756-4

    Article  CAS  PubMed  Google Scholar 

  14. Shidham VB, Chang CC, Shidham G, Ghazala F, Lindholm PF, Kampalath B, George V, Komorowski R (2003) Colon biopsies for evaluation of acute graft-versus-host disease (A-GVHD) in allogeneic bone marrow transplant patients. BMC Gastroenterol 3(1):5. https://doi.org/10.1186/1471-230X-3-5

    Article  PubMed  PubMed Central  Google Scholar 

  15. Shulman HM, Cardona DM, Greenson JK, Hingorani S, Horn T, Huber E, Kreft A, Longerich T, Morton T, Myerson D, Prieto VG, Rosenberg A, Treister N, Washington K, Ziemer M, Pavletic SZ, Lee SJ, Flowers ME, Schultz KR, Jagasia M, Martin PJ, Vogelsang GB, Kleiner DE (2015) NIH Consensus development project on criteria for clinical trials in chronic graft-versus-host disease: II. The 2014 Pathology Working Group Report. Biol Blood Marrow Transplant 21(4):589–603. https://doi.org/10.1016/j.bbmt.2014.12.031

    Article  PubMed  PubMed Central  Google Scholar 

  16. Shulman HM, Kleiner D, Lee SJ, Morton T, Pavletic SZ, Farmer E, Moresi JM, Greenson J, Janin A, Martin PJ, McDonald G, Flowers ME, Turner M, Atkinson J, Lefkowitch J, Washington MK, Prieto VG, Kim SK, Argenyi Z, Diwan AH, Rashid A, Hiatt K, Couriel D, Schultz K, Hymes S, Vogelsang GB (2006) Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report. Biol Blood Marrow Transplant 12(1):31–47. https://doi.org/10.1016/j.bbmt.2005.10.023

    Article  PubMed  Google Scholar 

  17. Snover DC, Weisdorf SA, Vercellotti GM, Rank B, Hutton S, McGlave P (1985) A histopathologic study of gastric and small intestinal graft-versus-host disease following allogeneic bone marrow transplantation. Hum Pathol 16(4):387–392. https://doi.org/10.1016/S0046-8177(85)80232-X

    Article  CAS  PubMed  Google Scholar 

  18. Star KV, Ho VT, Wang HH, Odze RD (2013) Histologic features in colon biopsies can discriminate mycophenolate from GVHD-induced colitis. Am J Surg Pathol 37(9):1319–1328. https://doi.org/10.1097/PAS.0b013e31829ab1ef

    Article  PubMed  Google Scholar 

  19. Sviland L, Pearson AD, Eastham EJ, Hamilton PJ, Proctor SJ, Malcolm AJ (1988) Histological features of skin and rectal biopsy specimens after autologous and allogeneic bone marrow transplantation. J Clin Pathol 41(2):148–154. https://doi.org/10.1136/jcp.41.2.148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Thompson B, Salzman D, Steinhauer J, Lazenby AJ, Wilcox CM (2006) Prospective endoscopic evaluation for gastrointestinal graft-versus-host disease: determination of the best diagnostic approach. Bone Marrow Transplant 38(5):371–376. https://doi.org/10.1038/sj.bmt.1705453

    Article  CAS  PubMed  Google Scholar 

  21. Washington K, Bentley RC, Green A, Olson J, Treem WR, Krigman HR (1997) Gastric graft-versus-host disease: a blinded histologic study. Am J Surg Pathol 21(9):1037–1046. https://doi.org/10.1097/00000478-199709000-00008

    Article  CAS  PubMed  Google Scholar 

  22. Washington K, Jagasia M (2009) Pathology of graft-versus-host disease in the gastrointestinal tract. Hum Pathol 40(7):909–917. https://doi.org/10.1016/j.humpath.2009.04.001

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fanny Sauvestre.

Ethics declarations

Authors are compliant with these ethical standards (VirchowsArchiv conforms to the ICMJE recommendation for qualification of authorship):

• Authors had substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; and

• Authors drafted the work or revised it critically for important intellectual content; and

• Authors read final approval of the version to be published; and

• Authors gave their agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

All individuals listed as co-authors of the manuscript must qualify for every one of the four criteria listed above.

Conflict of interest

All authors declare no conflict of interest.

Electronic supplementary material

ESM 1

(DOCX 94 kb)

ESM 2

(DOCX 95 kb)

ESM 3

(DOCX 40 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sauvestre, F., Belleannée, G., Bréal, C. et al. Histologic analysis has a prognostical value in colorectal biopsies assessed for suspicion of graft-versus-host disease. Virchows Arch 472, 213–220 (2018). https://doi.org/10.1007/s00428-017-2272-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-017-2272-2

Keywords

Navigation