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Surgical Pathology Criteria

Acute Graft versus Host Disease (GVHD) of Gastrointestinal Tract


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

Diagnostic Criteria

  • Increased crypt apoptosis
  • In higher grades, crypt destruction and mucosal necrosis
  • Grade I
    • Single cell apoptosis of crypt epithelium
      • At least one per tissue fragment
  • Grade II
    • Destruction of single crypts or glands
      • With apoptotic crypt abscesses
  • Grade III
    • Focal mucosal necrosis with ulceration
  • Grade IV
    • Diffuse mucosal necrosis with denudation
  • In grades III and IV, adjacent areas should show apoptosis or apoptotic crypt abscesses

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

Acute GVHD of GI Tract Chemoradiation Toxicity
May occur up to 100 days post-transplant May last 3-4 weeks
Impossible to distinguish histologically, especially for low grade GVHD

Acute GI GVHD vs. Opportunistic Infection

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


  • 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%
  • Specific features of GI GVHD
    • Nausea, vomiting
    • Abdominal pain
    • Diarrhea
  • GI involvement in acute GVHD of utmost prognostic significance
    • Usual causes of mortality
  • Manifests at same time or shortly after cutaneous GVHD
    • Isolated GI GVHD is rare


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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