Abstract
The site of the gastrointestinal (GI) tract where biopsies are most likely to be diagnostic of graft-versus-host disease (GvHD) remains controversial. Recent reports have indicated that biopsies from the rectosigmoid have sufficient sensitivity and specificity for diagnosing GI GvHD and can be obtained via a less invasive flexible sigmoidoscopy procedure. While GvHD histologic grades 1–3 have little correlation with patients’ symptoms and overall clinical grade, histologic grade 4 GvHD does correlate with severe clinical presentation and a poor prognosis. We examined cases of lower GI biopsies obtained via a complete colonoscopy with ileal intubation for the evaluation of GvHD within a 2-year period from patients who underwent stem cell transplantation. In our study cohort, grade 4 GvHD was significantly more likely to be identified in a terminal ileum biopsy than in a biopsy from another site in the lower GI tract. Significantly, 5 of 6 patients with histologic grade 4 GvHD diagnosed on ileal biopsies died from complication of severe GI GvHD. Given the poor prognosis of histologic grade 4 GvHD in the terminal ileum, the detection of this finding may serve to inform clinicians that escalation or modification of treatment may need to be considered. Furthermore, our findings suggest that terminal ileal biopsies may help to increase sensitivity for identifying patients at high risk for poor outcome of GvHD.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Salomao M, Dorritie K, Mapara MY et al (2016) Histopathology of graft-vs-host disease of gastrointestinal tract and liver: an update. Am J Clin Pathol 145(5):591–603
Washington K, Jagasia M (2009) Pathology of graft-versus-host disease in the gastrointestinal tract. Hum Pathol 40(7):909–917
Shulman HM, Cardona DM, Greenson JK et al (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
Melson J, Jakate S, Fung H et al (2007) Crypt loss is a marker of clinical severity of acute gastrointestinal graft-versus-host disease. Am J Hematol 82(10):881–886
Ponec RJ, Hackman RC, McDonald GB (1999) Endoscopic and histologic diagnosis of intestinal graft-versus-host disease after marrow transplantation. Gastrointest Endosc 49(5):612–621
Roy J, Snover DC, Weisdorf S et al (1991) Simultaneous upper and lower endoscopic biopsy in the diagnosis of intestinal graft-versus-host disease. Transplantation 51:642–646
Ross WA, Ghosh S, Dekovich AA et al (2008) Endoscopic biopsy diagnosis of acute gastrointestinal graft-versus-host disease: rectosigmoid biopsies are more sensitive than upper gastrointestinal biopsies. Am J Gastroenterol 103(4):982–989
Aslanian H, Chander B, Robert M et al (2012) Prospective evaluation of acute graft-versus-host disease. Dig Dis Sci 57:720–725
Lerner KG, Kao GF, Storb R et al (1974) Histopathology of graft-vs.-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors. Transplant Proc 6(4):367–371
Therneau T. A package for survival analysis in R. https://CRANR-Project.org/Package=survival. Published online 2015
Kassambara A. Drawing survival curves using “ggplot2.” https://cran.r-Project.org/web/Packages/survminer/index.html. Published online 2018
Kreisel W, Dahlberg M, Bertz H et al (2012) Endoscopic diagnosis of acute intestinal GVHD following allogeneic hematopoietic SCT: a retrospective analysis in 175 patients. Bone Marrow Transplant 47(3):430–438
Shulman HM, Kleiner D, Lee SJ et al (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
Myerson D, Steinbach G, Gooley TA et al (2017) Graft-versus-host disease of the gut: a histologic activity grading system and validation. Biol Blood Marrow Transplant 23(9):1573–1579
Lin J, Fan R, Zhao Z et al (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 37:539–547
Gomez AJ, Arai S, Higgins JP et al (2016) Clinicopathologic threshold of acute colorectal graft-versus-host disease. Arch Pathol Lab Med 140:570–577
Castilla-Llorente C, Martin PJ, McDonald GB et al (2014) Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 49(7):966–971
Acknowledgements
We thank Dr. Basil A. Horst for his helpful critical review of the manuscript.
Funding
This study was funded by the Department of Pathology & Laboratory Medicine of the University of British Columbia.
Author information
Authors and Affiliations
Contributions
Raymond Yip and Hui-Min Yang conceived and designed the study and performed histologic assessment and confirmation of diagnoses. Julia Naso reviewed and analyzed the data and generated the boxplots and Kaplan–Meier curves. Raymond Yip and Hui-Min Yang wrote the manuscript. All authors edited and reviewed the manuscript and gave final approval for publication.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Communicated by H. Babaie
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yip, R.H.L., Naso, J.R. & Yang, HM. Terminal ileum is the most sensitive site for the histologic diagnosis of grade 4 graft-versus-host disease (GvHD) in the lower GI tract and is a harbinger of poor outcome. Virchows Arch 479, 919–925 (2021). https://doi.org/10.1007/s00428-021-03136-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-021-03136-z