Colon
Noninfectious colitis
Graft versus host disease
Authors: Gustavo Moreno, M.D., Catherine E. Hagen, M.D.
Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Last author update: 14 January 2020
Last staff update: 27 April 2022
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: Graft versus host disease colon pathology
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Negative stains | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Moreno G, Hagen CE. Graft versus host disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonGVHD.html. Accessed April 20th, 2024.
Definition / general
- Complication of allogeneic stem cell transplantation in which T cells from the donor recognize the recipient tissue as foreign, leading to organ damage
- May also occur in some autologous stem cell transplant patients (Mod Pathol 2011;24:117)
Essential features
- Complication of stem cell transplantation in which T cells from the donor recognize the recipient tissue as foreign, leading to organ damage
- Histologically characterized by crypt apoptosis, crypt dropout and ulceration
- Infection (especially cytomegalovirus) and drug induced injury are the most common differential considerations
ICD coding
- ICD-10: D89.813 - graft versus host disease, unspecified
Epidemiology
- Occurs in 30 - 70% of allogeneic stem cell transplant patients (Biol Blood Marrow Transplant 2015;21:389)
- M:F = 1.2:1 (Blood 2012;119:296, Bone Marrow Transplant 2013;48:587)
- Median age: 36 - 43 years (Blood 2012;119:296, Bone Marrow Transplant 2013;48:587)
Sites
- Skin > gastrointestinal tract > liver
- Other sites: mouth, eyes, lungs
Pathophysiology
- Tissue injury occurs following myeloablative or conditioning chemotherapy regimens in preparation for stem cell transplantation and leads to antigen upregulation on host tissues
- Donor T cells recognize host tissue antigens as foreign
- T cell activation and cytokine storm lead to end organ damage (Am J Clin Pathol 2016;145:591)
- Alteration of the microbiome is likely a contributing factor (Biol Blood Marrow Transplant 2018;24:1322)
- In autologous stem cell transplant patients, it is hypothesized to result from failure of self tolerance (Mod Pathol 2011;24:117)
Etiology
- Risk factors: human leukocyte antigen mismatch, age, sex disparity, stem cell source and intensity of the conditioning regimen (N Engl J Med 2017;377:2167)
Clinical features
- Clinically divided into classic acute graft versus host disease (occurring within 100 days of transplant), persistent / recurrent / late onset acute graft versus host disease (occurring > 100 days posttransplant) and chronic graft versus host disease (defined by presence of diagnostic clinical signs and symptoms; no specific features are diagnostic of chronic colonic GVHD)
- Histologic distinction of these groups not possible (Biol Blood Marrow Transplant 2015;21:589)
- Gastrointestinal symptoms: dysphagia, anorexia, nausea, vomiting, diarrhea (watery to mucoid / bloody), weight loss and failure to thrive (Nat Rev Gastroenterol Hepatol 2017;14:711)
- Coexisting skin graft versus host disease is often present, causing diffuse maculopapular rash
- Endoscopic findings range from edema and mild erythema to mucosal erosions, ulceration and denudation (Nat Rev Gastroenterol Hepatol 2017;14:711)
Diagnosis
- Combination of clinical, endoscopic and histologic features
- Biopsy is essential when the clinical presentation is atypical and helps exclude alternative diagnoses
Radiology description
- Bowel wall thickening with mucosal enhancement, mesenteric edema and vascular engorgement (AJR Am J Roentgenol 2017;209:33)
Prognostic factors
- Severity predicts treatment response and mortality (Biol Blood Marrow Transplant 2015;21:389)
- Gastrointestinal tract staging is based on severity of diarrhea and extent of weight loss
Case reports
- 23 year old man with defecation of a colon cast (Ann Saudi Med 2009;29:231)
- 44 year old woman with cytomegalovirus infection (World J Gastroenterol 2013;19:597)
- 56 year old man with idelalisib induced colitis and skin eruption (Clin J Gastroenterol 2017;10:14)
- 63 and 74 year old men with multiple myeloma and hematopoietic stem cell transplantation (Gastroenterology Res 2018;11:52)
- 3 patients with Epstein-Barr virus associated posttransplant lymphoproliferative disorder (Eur J Haematol 2019;103:519)
Treatment
- Increased immunosuppression
Clinical images
Contributed by Gustavo Moreno, M.D. and Catherine E. Hagen, M.D.
Endoscopic
Microscopic (histologic) description
- Characteristic histologic features include crypt apoptosis, crypt dropout and ulceration (Biol Blood Marrow Transplant 2015;21:589)
- Inflammation is generally sparse
- Endocrine cell nests may be seen (Am J Surg Pathol 2013;37:1319)
- Fibrosis and crypt architectural changes are markers of longstanding disease but not specific features of chronic graft versus host disease (Am J Clin Pathol 2016;145:591)
- Apoptosis in the colon is not specific to graft versus host disease and the lower diagnostic threshold is debated
- National Institute of Health proposes ≥ 1 apoptotic body per biopsy fragment (Biol Blood Marrow Transplant 2015;21:589)
- Others propose > 6 apoptotic bodies per 10 contiguous crypts for definitive diagnosis of graft versus host disease (Am J Surg Pathol 2013;37:539)
- Cases with ≤ 6 apoptotic bodies per 10 contiguous crypts are considered indeterminate for graft versus host disease (Histopathology 2016;69:802)
- Utility of histologic grading is questionable because of poor correlation with patient outcome
- When grading is performed, the Lerner system is most commonly utilized
- Grade I: crypt apoptosis without crypt dropout
- Grade II: single crypt dropout
- Grade III: contiguous crypt dropout
- Grade IV: diffuse crypt dropout with ulceration
- When grading is performed, the Lerner system is most commonly utilized
- Graft versus host disease in autologous stem cell transplant patients shows more prominent crypt apoptosis but is otherwise histologically identical to allogeneic graft versus host disease (Mod Pathol 2018;31:1619)
- Histologic examination of at least 8 serial sections is recommended to avoid missing rare apoptotic bodies (Biol Blood Marrow Transplant 2015;21:589)
Microscopic (histologic) images
Contributed by Gustavo Moreno, M.D. and Catherine E. Hagen, M.D.
Apoptosis
Apoptosis, no crypt loss
Ulceration
Crypt dropout
Architectural distortion
Crypt abscess
Indeterminate
Endocrine cell aggregates
Virtual slides
Images hosted on other servers:
GVHD, bone marrow
transplant for acute
myeloid leukemia
GVHD, colon
GVHD, bone marrow transplant with diarrhea
Negative stains
- Cytomegalovirus IHC, PAS and Giemsa negative for microorganisms (though their presence does not rule out coincident graft versus host disease)
Sample pathology report
- Colon, biopsy:
- Colonic mucosa with increased crypt apoptosis and crypt dropout (see comment)
- Comment: Given the patient's history of allogeneic stem cell transplant, the findings likely represent graft versus host disease.
Differential diagnosis
- Cytomegalovirus colitis:
- Presence of characteristic viral inclusions via immunohistochemistry or on H&E; always helpful to rule out in cases of suspected graft versus host disease
- Chemotherapy or radiation related changes:
- Usually resolve within 20 days
- Epithelial flattening with regenerative atypia, mucin depletion and crypt apoptosis
- Mycophenolate mofetil:
- Increased eosinophils in the lamina propria and fewer neuroendocrine cell nests (Am J Surg Pathol 2013;37:1319)
- Cryptosporidiosis:
- Identification of organisms attached to mucosal surface, Giemsa or PAS stains can highlight organisms; prominent neutrophilic inflammation (Hum Pathol 2010;41:918)
Board review style question #1
A 55 year old man undergoes peripheral blood stem cell transplant for multiple myeloma. 70 days after the transplant, he complains of mucoid to bloody diarrhea 3 - 5 times per day. Colonoscopy shows multiple ulcerations and biopsies are obtained. What is the most likely diagnosis?
- Chemotherapy induced injury
- Crohn's disease
- Graft versus host disease
- Ischemic colitis
- NSAID related injury
Board review style answer #1
Board review style question #2
What is the most characteristic histologic feature of colonic graft versus host disease?
- Architectural distortion
- Crypt apoptosis
- Eosinophilic inflammation
- Lamina propria hyalinization
- Neutrophilic inflammation
Board review style answer #2
