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Surgical Pathology Criteria

Chronic Graft versus Host Disease (GVHD) of Gastrointestinal Tract


  • Attack by engrafted hematopoietic cells and their progeny on host gastrointestinal tissues in at least 100 days post-transplant

Diagnostic Criteria

  • Changes are nonspecific
    • Submucosal fibrosis
    • Architectural distortion
    • Epithelial regeneration
    • Apoptosis
  • No grading scheme exists for chronic GI graft versus host disease

Neeraja Kambham MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting : May 9, 2007

Supplemental studies


  • Useful for detection of viral infections
    • CMV
    • Herpes simplex

Differential Diagnosis

Chronic GI GVHD vs. Infection

  • Consider infection in the setting of acute or chronic inflammation, crypt abscesses or ulceration
  • Use immunohistology to identify CMV or Herpes
  • Enteritis may also be nonspecific
  • Infection may coexist with GVHD

Chronic GI GVHD vs. Chemoradiation Effect

  • Histologically, the two can be indistinguishable
    • Submucosal fibrosis is uncommon in chemoradiation effect
  • Chemoradiation effect can last 3-4 weeks while GVHD may occur later


  • Acute vs. chronic GVHD: clinically 100 day cutoff
    • Poor correlation between pathologic features and clinical definition of acute vs. chronic
  • Acute GVHD
    • Develops 2-6 weeks after allogeneic transplant
    • Primary targets
      • Skin 90%
      • Liver 40-60%
      • GI tract 30-50%
    • Early recognition of GVHD and prompt intervention improves outcome
    • Advanced GVHD easy to diagnose but mortality can be 50%
  • Chronic GVHD
    • Resembles autoimmune connective tissue disorders
    • Mortality is high due to infections promoted by GVHD associated immunodeficiency
    • Target organs more widespread but skin, liver and GI tract play a major role
  • Specific features of chronic GI GVHD
    • Diarrhea
    • Malabsorption
    • Weight loss
  • Chronic GI GVHD usually occurs 3-16 months post-transplant
  • Chronic GI GVHD usually plays only a minor clinical role
    • Not usually a cause of mortality
    • May be a significant cause of morbidity


Principal sites of graft versus host disease


  • 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. 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. 2006 Jan;12(1):31-47.
  • Heymer B. Clinical and diagnostic pathology of graft versus host disease. Springer Verlag, 2002.
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