Colon
Noninfectious colitis
Graft versus host disease


Topic Completed: 14 January 2020

Minor changes: 29 September 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: Graft versus host disease[TI] colon[TIAB] pathology

Gustavo Moreno, M.D.
Catherine E. Hagen, M.D.
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Cite this page: Moreno G, Hagen CE. Graft versus host disease. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/colonGVHD.html. Accessed October 25th, 2020.
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
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)
  • 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
Prognostic factors
Case reports
Treatment
  • Increased immunosuppression
Clinical images

Contributed by Gustavo Moreno, M.D., 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
  • 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
  • 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., 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
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. The most likely diagnosis is



  1. Chemotherapy induced injury
  2. Crohn's disease
  3. Graft versus host disease
  4. Ischemic colitis
  5. NSAID related injury
Board review answer #1
C. Graft versus host disease

Comment Here

Reference: Graft versus host disease
Board review style question #2
The most characteristic histologic feature of colonic graft versus host disease is

  1. Architectural distortion
  2. Crypt apoptosis
  3. Eosinophilic inflammation
  4. Lamina propria hyalinization
  5. Neutrophilic inflammation
Board review answer #2
B. Crypt apoptosis

Comment Here

Reference: Graft versus host disease
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