acute cutaneous GVHD

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.

Grade

 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.

References

 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.