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Surgical Pathology Criteria

Acute Graft versus Host Disease of the Skin


  • Attack by engrafted hematopoietic cells and their progeny on host cutaneous tissues resulting in changes ranging from apoptosis to epithelial denudation

Alternate/Historical Names

  • Cutaneous GVHD

Diagnostic Criteria

  • Lymphocytic infiltrate and vacuolar alteration at the dermo-epidermal junction
  • Individual keratinocyte apoptosis
    • Satellitosis (lymphocytes in close proximity to apoptotic keratinocytes)
    • Apoptotic keratinocytes in hair follicles in 50-100% of cases
  • Basal cell vacuolization (grade I) is nonspecific
    • May be caused by pre-transplant chemoradiation or drugs
  • Higher grades exhibit dermo-epidermal separation and epithelial separation, see Grading
  • Biopsies should be taken 24-48 hours after onset of rash to avoid false negative results seen in earlier biopsies

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

Original posting : June 30, 2007

Supplemental studies


  • Stainsi for viral infections may be used but are rarely helpful
    • CMV
    • Herpes simplex

Differential Diagnosis

Effect of preparatory regimens

  • Histologically indistinguishable
  • Often resolves in 3 weeks
  • Usually not inflammatory
Drug eruptions
  • Histologically indistinguishable
  • Apoptotic keratinocytes in hair follicles favor GVHD
Viral infections
  • Most common viruses
    • Herpes simplex
    • Cytomegalovirus
    • Varicella zoster
  • Specific viropathic changes
  • Viral exanthem may be histologically indistinguishable
  • Immunoperoxidase staining for viral antigens is seldom helpful in our experience
Eruption of lymphocyte recovery
  • Histologically indistinguishable
  • Limited descriptions reported


  • Acute vs. chronic GVHD
    • Poor correlation between pathologic features and clinical definition of acute vs. chronic
  • Acute GVHD
    • Rash develops 2-3 weeks after allogeneic transplant
    • Characteristic histologic changes develop 3-6 weeks after 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%


  • Grading is mainly of historical interest as GVHD > Grade I has become rare because of better clinical regimens
  • Grade I
    • Vacuoular degeneration of basal and suprabasal epidermal cells
    • (Not specific for GVHD)
  • Grade II (considered minimal criteria for diagnosis of GVHD)
    • Vacuolar degeneration
    • Scattered apoptosis of individual keratinocytes
    • Epidermotropic lymphocytic infiltrate
  • Grade III
    • Focal dermo-epidermal separation and cleft formation
  • Grade IV
    • Extensive necrosis of epidermis with denudation
  • Interobserver agreement excellent with grade III and IV lesions


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.
  • Massi D, Franchi A, Pimpinelli N, Laszlo D, Bosi A, Santucci M. A reappraisal of the histopathologic criteria for the diagnosis of cutaneous allogeneic acute graft-vs-host disease. Am J Clin Pathol. 1999 Dec;112(6):791-800.
  • Kohler S, Hendrickson MR, Chao NJ, Smoller BR. Value of skin biopsies in assessing prognosis and progression of acute graft-versus-host disease. Am J Surg Pathol. 1997 Sep;21(9):988-96.
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