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
Immunohistology
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
Clinical
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
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
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.
