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acute cutaneous GVHD

Thursday 18 March 2004

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

Acute phase

- individual keratinocyte apoptosis

  • eosinophilic necrotic keratinocytes
  • satellite cell necrosis
  • satellitosis (lymphocytes in close proximity to apoptotic keratinocytes)
  • apoptotic keratinocytes in hair follicles in 50-100% of cases

- basal cell vacuolizationor vacuolar degeneration of basac cells (grade 1) (nonspecific)

  • may be caused by pre-transplant chemoradiation or drugs

- lymphocyte exocytosis in epidermis
- Lymphocytic infiltrate and vacuolar alteration at the dermo-epidermal junction
- sparse, diffuse lymphocytic infiltrate in the upper dermis
- Higher grades exhibit dermo-epidermal separation and epithelial separation.


- acute cutaneous GVHD grade 1

  • Vacuolar degeneration of basal and suprabasal epidermal cells
    (Not specific for GVHD)

- acute cutaneous GVHD grade 2

  • Vacuolar degeneration
  • Scattered apoptosis of individual keratinocytes
  • Epidermotropic lymphocytic infiltrate

- acute cutaneous GVHD grade 3

  • Focal dermo-epidermal separation and cleft formation

- acute cutaneous GVHD grade 4

  • Extensive necrosis of epidermis with denudation

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.

- Eruption of lymphocyte recovery

  • Histologically indistinguishable
  • Limited descriptions reported

Nota bene: Biopsies should be taken 24-48 hours after onset of rash to avoid false negative results seen in earlier biopsies.


- 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.