Skip to main content

Advertisement

Springer Nature Link
Log in

Consensus diagnostic histopathological criteria for acute gastrointestinal graft versus host disease improve interobserver reproducibility

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

Abstract

Graft versus host disease (GvHD) is a clinically important complication after allogeneic hematopoietic stem cell transplantation (HSCT). Its diagnosis relies on clinical and histopathological findings. In order to evaluate and improve inter-institutional diagnostic agreement on histological diagnosis and grading of acute gastrointestinal GvHD, we conducted a round robin test, which included 33 biopsies from 23 patients after HSCT. Five pathologists from different institutions independently evaluated the original sections from the biopsies submitted for diagnosis. Based on their results, consensus qualitative criteria for the assessment of typical histological features of GvHD (e.g., apoptosis, crypt destruction, mucosa denudation) were proposed, including detailed descriptions as well as histological images. In a second round robin test with involvement of the same pathologists, the reproducibility of both diagnosis and grading had improved. Remaining differences were mostly related to differential diagnostic considerations, including viral infection or toxic side effects of medication, which should be resolved by integrating histopathological findings with proper clinical information.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Abraham J, Janin A, Gornet JM, de Latour RP, Robin M, Xhaard A, de Fontebrune FS, Mary JY, Allez M, Porcher R, Socié G (2014) Clinical severity scores in gastrointestinal graft-versus-host disease. Transplantation 97:965–971

    CAS  PubMed  Google Scholar 

  2. Castagnola E, Cappelli B, Erba D, Rabagliati A, Lanino E, Dini G (2004) Cytomegalovirus infection after bone marrow transplantation in children. Hum Immunol 65:416–422

    Article  PubMed  Google Scholar 

  3. Cho BS, Yahng SA, Kim JH, Yoon JH, Shin SH, Lee SE, Choi SM, Lee DG, Eom KS, Park G, Kim YJ, Kim HJ, Lee S, Min CK, Cho SG, Kim DW, Lee JW, Min WS, Park CW (2013) Impact of cytomegalovirus gastrointestinal disease on the clinical outcomes in patients with gastrointestinal graft-versus-host disease in the era of preemptive therapy. Ann Hematol 92:497–504

    Article  CAS  PubMed  Google Scholar 

  4. Dahl J, Greenson JK (2012) Colon. In: Mills SE (ed) Histology for pathologists, 4 edn. Wolter Kluver, Lippincott Williams & Wilkins, Philadelphia, pp. 673–695

    Google Scholar 

  5. 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 78:764–771

    CAS  PubMed  Google Scholar 

  6. Feinstein AR, Cicchetti DV (1990). High agreement but low Kappa: I. the problems of two paradoxes. J Clin Epidemiol 43:543–549. doi: 10.1016/0895-4356(90)90158-L

    Article  CAS  PubMed  Google Scholar 

  7. Gwet KL (2012) Handbook of inter-rater reliability. Advanced analytics. LLC, Gaitersburg

    Google Scholar 

  8. Hymes SR, Alousi AM, Cowen EW (2012) Graft-versus-host disease: part I. Pathogenesis and clinical manifestations of graft-versus-host-ádisease. J Am Acad Dermatol 66:515

    Article  PubMed  Google Scholar 

  9. Kreisel W, Dahlberg M, Bertz H, Harder J, Potthoff K, Deibert P, Schmitt-Graeff A, Finke J (2011) Endoscopic diagnosis of acute intestinal GVHD following allogeneic hematopoietic SCT: a retrospective analysis in 175 patients. Bone Marrow Transplant 47:430–438

    Article  PubMed Central  PubMed  Google Scholar 

  10. Lerner KG, Kao GF, Storb R, Buckner CD, Clift RA, Thomas ED (1974) Histopathology of graft-vs-host reaction in human recipients of marrow from HL-A-matched sibling donors. Transplant Proc 4:367–371

    Google Scholar 

  11. Liapis G, Boletis J, Skalioti C, Bamias G, Tsimaratou K, Patsouris E, Delladetsima I (2013) Histological spectrum of mycophenolate mofetil-related colitis: association with apoptosis. Histopathology 63:649–658

    PubMed  Google Scholar 

  12. Melson J, Jakate S, Fung H, Arai S, Keshavarzian A (2007) Crypt loss is a marker of clinical severity of acute gastrointestinal graft-versus-host disease. Am J Hematol 82:881–886

    Article  PubMed  Google Scholar 

  13. Nguyen C, Kastenberg D, Choudhary C, Katz L, DiMarino A, Palazzo J (2008) Is single-cell apoptosis sufficient for the diagnosis of graft-versus-host disease in the colon? Dig Dis Sci 53:747–756

    Article  PubMed  Google Scholar 

  14. Sale GE, McDonald GB, Shulman HM, Thomas ED (1979) Gastrointestinal graft-versus-host disease in man: a clinicopathological study of the rectal biopsy am. J Surg Pathol 4:291–299

    Article  Google Scholar 

  15. Shulman HM, Kleiner D, Lee SJ, Morton T, Pavletic SZ, Farmer E, Moresi M, Greenson J, Janin A, Martin PJ, McDonald G, Flowers MED, Turner M, Atkinson J, Lefkowich J, Washington MK, Prieto VG, Kim SK, Argenyi Z, Diwan H, Rashid A, Hiatt K, Couriel D, Schultz K, Hymes S, Vogelsang GB (2006) Histopathologic diagnosis of chronic graft-versus-host disease: National Institut of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: II. Pathology working group report. Biology of Blood and Marrow Transplantation 12:31–47

    Article  PubMed  Google Scholar 

  16. 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 MED, 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 21:589–603. doi:10.1016/j.bbmt.2014.12.031

  17. Socié G, Blazar BR (2009) Acute graft-versus-host disease: from the bench to the bedside. Blood 114:4327–4336. doi:10.1182/blood-2009-06-204669

    Article  PubMed Central  PubMed  Google Scholar 

  18. Soldini D, Gaspert A, Montani M, Reineke T, Rogler G, Odze R, Weber A (2014) Apoptotic enteropathy caused by antimetabolites and TNF-a antagonists. J Clin Pathol 67:582–586

    Article  CAS  PubMed  Google Scholar 

  19. Stift J, Baba H, Huber E, Federmann B, Fischer HP, Schmitt-Graeff A, Baurmann H, Bethge W, Schirmacher P, Wrba F, Greinix H, Fend F, Schwerdtfeger R, Shulman H, Wolff D, Longerich T (2014) Consensus on the histopathological evaluation of liver biopsies from patients following allogeneic hematopoietic cell transplantation. Virchows Arch 464:175–190

    Article  PubMed  Google Scholar 

  20. 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 21:1037–1046

    Article  CAS  Google Scholar 

  21. Weisdorf DJ, Hurd D, Carter S, Howe C, Jensen LA, Wagner J, Stablein D, Thompson J, Kernan NA (2003) Prospective grading of graft-versus-host disease after unrelated donor marrow transplantation: a grading algorithm versus blinded expert panel review. Biol Blood Marrow Transplant 9:512–518

    Article  PubMed  Google Scholar 

  22. Wongpakaran N, Wongpakaran T, Wedding D, Gwet K (2013) A comparison of Cohen’s Kappa and Gwet’s AC1 when calculating inter-rater reliability coefficients: a study conducted with personality disorder samples. BMC Med Res Methodol 13:61

    Article  PubMed Central  PubMed  Google Scholar 

  23. Zhou Y, Barnett MJ, Rivers JK (2000) Clinical significance of skin biopsies in the diagnosis and management of graft-vs-host disease in early postallogeneic bone marrow transplantation. Arch Dermatol 136:717–721

    CAS  PubMed  Google Scholar 

  24. Ziemer M, Haeusermann P, Janin A, Massi D, Ziepert M, Wolff D, Greinix H, Hillen U (2013) Histopathological diagnosis of graft-versus-host disease of the skin—an interobserver comparison. J Eur Acad Dermatol and Venereol 28:1–10

Download references

Acknowledgments

The presented study was approved by the ethical committee of the medical board of Rhineland Palatinate (Nr. 0837.271.12 (8372)).

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Institute of Pathology, University Medical Center Mainz, Langenbeckstr. 1, 55101, Mainz, Germany

    Andreas Kreft

  2. Institute of Pathology, University of Würzburg and Comprehensive Cancer Centre Mainfranken, Josef-Schneider-Str. 2, 97080, Würzburg, Germany

    Anja Mottok

  3. Institute of Pathology, Medical University of Vienna, AKH, Währinger Gürtel 18 –20, A-1090, Vienna, Austria

    Ildiko Mesteri

  4. Department of Pathology, Duke University Medical Center, BOX 3712, Durham, NC, 27713, USA

    Diana M. Cardona

  5. Université Paris Diderot, Laboratoire de Pathologie, UMR_S1165, F-75010, Paris, France

    Anne Janin

  6. Department of Pathology, AP-HP, Hôpital Saint-Louis, F-75010, Paris, France

    Anne Janin

  7. Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany

    Anja A. Kühl

  8. Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany

    Mindaugas Andrulis

  9. Department of Pathology, Division of General Pathology, Medical University of Innsbruck, Muellerstrasse 44, A-6020, Innsbruck, Austria

    Andrea Brunner

  10. Seattle Cancer Center Alliance, Room G7-910, 825 Eastlake ave E, Seattle, WA, 98109, USA

    Howard M. Shulman

  11. Department of Pathology, Central Hospital Bolzano, Via Boehler 5, I-39100, Bolzano, Italy

    Giovanni Negri

  12. Institute of Pathology, University Hospital Basel, Schoenbeinstr. 40, CH-4031, Basel, Switzerland

    Alexandar Tzankov

  13. Institute of Pathology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany

    Elisabeth Huber

Authors
  1. Andreas Kreft
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Anja Mottok
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Ildiko Mesteri
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Diana M. Cardona
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Anne Janin
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Anja A. Kühl
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Mindaugas Andrulis
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Andrea Brunner
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Howard M. Shulman
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Giovanni Negri
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Alexandar Tzankov
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Elisabeth Huber
    View author publications

    You can also search for this author inPubMed Google Scholar

Consortia

on behalf of the Gastrointestinal Pathology Group of the German-Austrian-Swiss GvHD Consortium

Corresponding author

Correspondence to Andreas Kreft.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kreft, A., Mottok, A., Mesteri, I. et al. Consensus diagnostic histopathological criteria for acute gastrointestinal graft versus host disease improve interobserver reproducibility. Virchows Arch 467, 255–263 (2015). https://doi.org/10.1007/s00428-015-1803-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-015-1803-y

Keywords