Graft-versus-host disease

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Graft-versus-host disease, abbreviated as GVHD, is a rare thingy seen mostly in tertiary care centres. It is a complication of hematopoietic stem cell transplantation.


  • Complication of hematopoietic stem cell transplantation, i.e. bone marrow transplantation (BMT).
    • Affects skin, liver (bile ducts), gastrointestinal tract.[1][2]
  • The histology of GVHD in the intestine is the same as rejection in bowel transplantation.[3]


  • May present as diarrhea.
  • Main DDx (clinical): infection and certain drugs, especially mycophenolate


Microscopic (skin)


  1. Keratinocyte apoptosis.
    • Intensely eosinophilic on H&E.
  2. Epidermotropic lymphocytic infiltrate = lymphocytes in the epidermis.
  3. Vacuolar degeneration of basal and suprabasal cells in the epidermis.


  • Apoptotic cells should not be confused with dyskeratotic cells.[5]


  • Grade I: Only vacuolar changes, no apoptosis, no lymphocytes; not treated.
  • Grade II: Only scattered apoptotic cells.
  • Grade III: Focal separation/cleft formation at the dermal-epidermal junction.
  • Grade IV: Extensive necrosis with degeneration of epidermis.


  • Same scheme applies to esophagus... it has the same structure.
  • Originally described in NEJM.[6]

Microscopic (intestine)


  • Isolated epithelial cell apoptosis - key feature.
  • +/-Crypt destruction (focal or extensive).
  • +/-Loss of epithelium (denudation).


  • Neutrophils may be present.


  • Drug effect (mycophenolate mofetil) - cannot be distinguished from GVHD.


  • Grade 1 = isolated epithelial cell apoptosis.
    • No crypt loss/destruction.
  • Grade 2 = individual crypts are lost/scatter destruction of single crypts.
  • Grade 3 = foci several adjacent crypts lost.
  • Grade 4 = large number of adjacent crypts lost/loss of epithelium.


  • Low-grade rejection is a diagnosis that requires a careful examination, i.e. it is subtle.

Microscopic (liver)

See: Vanishing bile duct syndrome.


See also


  1. Niino D, Nakashima M, Kondo H, et al. (2005). "Correlation of donor-derived keratinocytes and severity of graft-versus-host disease (GVHD) in epidermis". Pathol. Res. Pract. 200 (11-12): 775–81. PMID 15792120.
  2. van Dijk AM, Kessler FL, Verdonck LF, et al. (December 2000). "Primary human keratinocytes as targets in predicting acute graft-versus-host disease following HLA-identical bone marrow transplantation". Br. J. Haematol. 111 (3): 791–6. PMID 11122139.
  3. GT. 14 January 2011.
  4. 4.0 4.1 "Acute Graft versus Host Disease of the Skin". Retrieved January 17, 2011.
  5. Judith S. Nimmo. "Dyskeratotic, apoptotic or acantholytic keratinocytes? How to differentiate these on histology and what meaning does this have to the disease in question".,%20apoptotic%20or%20acantholytic%20keratinocytes.pdf. Retrieved 17 January 2011.
  6. Thomas ED, Storb R, Clift RA, et al. (April 1975). "Bone-marrow transplantation (second of two parts)". N. Engl. J. Med. 292 (17): 895–902. doi:10.1056/NEJM197504242921706. PMID 235092.
  7. 7.0 7.1 7.2 Cogbill CH, Drobyski WR, Komorowski RA (January 2011). "Gastrointestinal pathology of autologous graft-versus-host disease following hematopoietic stem cell transplantation: a clinicopathological study of 17 cases". Mod. Pathol. 24 (1): 117–25. doi:10.1038/modpathol.2010.163. PMID 20953169.