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Atlas of Graft-versus-Host Disease pp 43–56Cite as

Histopathology of Cutaneous Graft-Versus-Host Disease

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Abstract

Precise diagnosis of graft-versus-host disease (GVHD) remains elusive. The skin is one of the major organ systems affected by GVHD, but diagnosis of this entity in a timely manner is often hindered by clinical and histopathologic mimickers, such as drug hypersensitivity reactions, viral exanthema, and toxic erythema of chemotherapy. Microscopic findings in acute and chronic cutaneous GVHD are reviewed here, as are features of other entities in the clinical and histopathologic differential diagnosis.

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References

  1. Shulman HM, Kleiner D, Lee SJ, Morton T, Pavletic SZ, Farmer E, et al. 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;12:31–47.

    Article  PubMed  Google Scholar 

  2. Bridge AT, Nelson RP, Schwartz JE, Mirowski GW, Billings SD. Histological evaluation of acute mucocutaneous graft-versus-host disease in nonmyeloablative hematologic stem cell transplants with an observation predicting an increased risk of progression to chronic graft-versus-host disease. Am J Dermatopathol. 2007;29:1–6.

    Article  PubMed  Google Scholar 

  3. Hillen U, Häusermann P, Massi D, Janin A, Wolff D, Lawitschka A, et al. Consensus on performing skin biopsies, laboratory workup, evaluation of tissue samples and reporting of the results in patients with suspected cutaneous graft-versus-host disease. J Eur Acad Dermatol Venereol. 2015;29:948–54.

    Article  CAS  PubMed  Google Scholar 

  4. Zhou Y, Barnett MJ, Rivers JK. Clinical significance of skin biopsies in the diagnosis and management of graft-vs-host disease in early postallogeneic bone marrow transplantation. Arch Dermatol. 2000;136:717–21.

    Article  CAS  PubMed  Google Scholar 

  5. Ziemer M, Haeusermann P, Janin A, Massi D, Ziepert M, Wolff D, et al. Histopathological diagnosis of graft-versus-host disease of the skin – an interobserver comparison. J Eur Acad Dermatol Venereol. 2014;28:915–24.

    Article  CAS  PubMed  Google Scholar 

  6. Firoz BF, Lee SJ, Nghiem P, Qureshi AA. Role of skin biopsy to confirm suspected acute graft-vs-host disease: results of decision analysis. Arch Dermatol. 2006;142:175–82.

    PubMed  Google Scholar 

  7. Horn TD, Haskell J. The lymphocytic infiltrate in acute cutaneous allogeneic graft-versus-host reactions lacks evidence for phenotypic restriction in donor-derived cells. J Cutan Pathol. 1998;25:210–4.

    Article  CAS  PubMed  Google Scholar 

  8. Kuykendall TD, Smoller BR. Lack of specificity in skin biopsy specimens to assess for acute graft-versus-host disease in initial 3 weeks after bone-marrow transplantation. J Am Acad Dermatol. 2003;49:1081–5.

    Article  PubMed  Google Scholar 

  9. Ackerman AB, Penneys NS, Clark WH. Erythema multiforme exudativum: distinctive pathological process. Br J Dermatol. 1971;84:554–66.

    Article  CAS  PubMed  Google Scholar 

  10. Alsaad KO, Ghazarian D. My approach to superficial inflammatory dermatoses. J Clin Pathol. 2005;58:1233–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lerner KG, Kao GF, Storb R, Buckner CD, Clift RA, Thomas ED. Histopathology of graft-vs.-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors. Transplant Proc. 1974;6:367–71.

    CAS  PubMed  Google Scholar 

  12. Dickinson AM, Sviland L, Dunn J, Carey P, Proctor SJ. Demonstration of direct involvement of cytokines in graft-versus-host reactions using an in vitro human skin explant model. Bone Marrow Transplant. 1991;7:209–16.

    CAS  PubMed  Google Scholar 

  13. Dreno B, Milpied N, Harousseau JL, Stalder JF, Bureau B, Milpied B, Barriere H. Cutaneous immunological studies in diagnosis of acute graft-versus-host disease. Br J Dermatol. 1986;114:7–15.

    Article  CAS  PubMed  Google Scholar 

  14. Canninga-van Dijk MR, Sanders CJ, Verdonck LF, Fijnheer R, van den Tweel JG. Differential diagnosis of skin lesions after allogeneic haematopoietic stem cell transplantation. Histopathology. 2003;42:313–30.

    Article  CAS  PubMed  Google Scholar 

  15. Ruffin N, Ahmed SS, Osorio LM, Wang XN, Jackson GH, Collin MP, et al. The involvement of epithelial Fas in a human model of graft versus host disease. Transplantation. 2011;91:946–51.

    Article  CAS  PubMed  Google Scholar 

  16. Langley RG, Walsh N, Nevill T, Thomas L, Rowden G. Apoptosis is the mode of keratinocyte death in cutaneous graft-versus-host disease. J Am Acad Dermatol. 1996;35:187–90.

    Article  CAS  PubMed  Google Scholar 

  17. Goiriz R, Peñas P, Pérez-Gala S, Delgado-Jiménez Y, Aragüés M, García-Diez A, et al. Stage IV cutaneous acute graft-versus-host disease. Clinical and histological study of 15 cases. J Eur Acad Dermatol Venereol. 2009;23:1398–404.

    Article  CAS  PubMed  Google Scholar 

  18. Sviland L, Pearson AD, Eastham EJ, Hamilton PJ, Proctor SJ, Malcolm AJ. Histological features of skin and rectal biopsy specimens after autologous and allogeneic bone marrow transplantation. J Clin Pathol. 1988;41:148–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sale GE, Lerner KG, Barker EA, Shulman HM, Thomas ED. The skin biopsy in the diagnosis of acute graft-versus-host disease in man. Am J Pathol. 1977;89:621–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Dumler JS, Beschorner WE, Farmer ER, Di Gennaro KA, Saral R, Santos GW. Endothelial-cell injury in cutaneous acute graft-versus-host disease. Am J Pathol. 1989;135:1097–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Tsoi MS, Storb R, Jones E, Weiden PL, Shulman H, Witherspoon R, et al. Deposition of IgM and complement at the dermoepidermal junction in acute and chronic cutaneous graft-vs-host disease in man. J Immunol. 1978;120:1485–92.

    CAS  PubMed  Google Scholar 

  22. McCalmont TH. TEC. J Cutan Pathol. 2013;40:785–787.

    Google Scholar 

  23. Goddard DS, Horn BN, McCalmont TH, Cordoro KM. Clinical update on graft-versus-host disease in children. Semin Cutan Med Surg. 2010;29:92–105.

    Article  CAS  PubMed  Google Scholar 

  24. Weaver J, Bergfeld WF. Quantitative analysis of eosinophils in acute graft-versus-host disease compared with drug hypersensitivity reactions. Am J Dermatopathol. 2010;32:31–4.

    Article  PubMed  Google Scholar 

  25. Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;27:893–8.

    Article  CAS  PubMed  Google Scholar 

  26. Parker TL, Cooper DL, Seropian SE, Bolognia JL. Toxic erythema of chemotherapy following i.v. BU plus fludarabine for allogeneic PBSC transplant. Bone Marrow Transplant. 2012;48:646–50.

    Article  PubMed  Google Scholar 

  27. LeBoit PE. Interface dermatitis. How specific are its histopathologic features? Arch Dermatol. 1993;129:1324–8.

    Article  CAS  PubMed  Google Scholar 

  28. Dilday BR, Smoller BR. Intraepidermal bile pigment in skin biopsy specimens for graft-versus-host disease versus erythema multiforme. Mod Pathol. 1998;11:1005–9.

    CAS  PubMed  Google Scholar 

  29. Wang ECE, Lee JSS, Tan AWH, Tang MBY. Fas-ligand staining in non-drug- and drug-induced maculopapular rashes. J Cutan Pathol. 2011;38:196–201.

    Article  PubMed  Google Scholar 

  30. Roux J, Battistella M, Fornecker L, Legoff J, Deau B, Houhou N, et al. Human Herpesvirus-6 cytopathic inclusions: an exceptional and recognizable finding on skin biopsy during HHV6 reactivation after autologous stem-cell transplantation. Am J Dermatopathol. 2012;34:e73–6.

    Article  PubMed  Google Scholar 

  31. Choi YL, Kim JA, Jang KT, Kim DS, Kim WS, Lee JH, et al. Characteristics of cutaneous cytomegalovirus infection in non-acquired immune deficiency syndrome, immunocompromised patients. Br J Dermatol. 2006;155:977–82.

    Article  PubMed  Google Scholar 

  32. Clark WH, Reed RJ, Mihm MC. Lupus erythematosus. Histopathology of cutaneous lesions. Hum Pathol. 1973;4:157–63.

    Article  CAS  PubMed  Google Scholar 

  33. Crowson AN, Magro CM. The role of microvascular injury in the pathogenesis of cutaneous lesions of dermatomyositis. Hum Pathol. 1996;27:15–9.

    Article  CAS  PubMed  Google Scholar 

  34. Longley J, Demar L, Feinstein RP, Miller RL, Silvers DN. Clinical and histologic features of pityriasis lichenoides et varioliformis acuta in children. Arch Dermatol. 1987;123:1335–9.

    Article  CAS  PubMed  Google Scholar 

  35. Brüggen MC, Klein I, Greinix H, Bauer W, Kuzmina Z, Rabitsch W, et al. Diverse T-cell responses characterize the different manifestations of cutaneous graft-versus-host disease. Blood. 2014;123:290–9.

    Article  PubMed  Google Scholar 

  36. Paczesny S, Braun TM, Levine JE, Hogan J, Crawford J, Coffing B, et al. Elafin is a biomarker of graft-versus-host disease of the skin. Sci Transl Med. 2010;2:13ra2.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Brüggen MC, Petzelbauer P, Greinix H, Contassot E, Jankovic D, French L, et al. Epidermal elafin expression is an indicator of poor prognosis in cutaneous graft-versus-host disease. J Invest Dermatol. 2015;135:999–1006.

    Article  PubMed  Google Scholar 

  38. Levine JE, Logan BR, Wu J, Alousi AM, Bolaños-Meade J, Ferrara JL, et al. Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study. Blood. 2012;119:3854–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Goldberg JD, Linker A, Kuk D, Ratan R, Jurcic J, Barker JN, et al. T cell-depleted stem cell transplantation for adults with high-risk acute lymphoblastic leukemia: long-term survival for patients in first complete remission with a decreased risk of graft-versus-host disease. Biol Blood Marrow Transplant. 2013;19:208–13.

    Article  PubMed  Google Scholar 

  40. Fischer A, Jakubowski AA, Lacouture ME, Hollmann TJ, Drucker AM, Maloy M, et al. Histopathologic features of cutaneous acute graft-versus-host disease in T-cell-depleted peripheral blood stem cell transplant recipients. Am J Dermatopathol. 2015;37:523–9.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wagner JE, Ishida-Yamamoto A, McGrath JA, Hordinsky M, Keene DR, Woodley DT, et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010;363:629–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tolar J, Wagner JE. Allogeneic blood and bone marrow cells for the treatment of severe epidermolysis bullosa: repair of the extracellular matrix. Lancet. 2013;382:1214–23.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Linhares YPL, Pavletic S, Gale RP, Chronic GVHD. Where are we? Where do we want to be? Will immunomodulatory drugs help? Bone Marrow Transplant. 2013;48:203–9.

    Article  CAS  PubMed  Google Scholar 

  44. Hymes SR, Alousi AM, Cowen EW. Graft-versus-host disease. J Am Acad Dermatol. 2012;66:515.e1–18.

    Article  Google Scholar 

  45. Aractingi S, Chosidow O. Cutaneous graft-versus-host disease. Arch Dermatol. 1998;134:602–12.

    Article  CAS  PubMed  Google Scholar 

  46. Shulman HM, Sale GE, Lerner KG, Barker EA, Weiden PL, Sullivan K, et al. Chronic cutaneous graft-versus-host disease in man. Am J Pathol. 1978;91:545–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Inamoto Y, Storer BE, Petersdorf EW, Nelson JL, Lee SJ, Carpenter PA, et al. Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host disease. Blood. 2013;121:5098–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Uhm J, Hamad N, Shin EM, Michelis FV, Shanavas M, Gupta V, et al. Incidence, risk factors, and long-term outcomes of sclerotic graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014;20:1751–7.

    Article  PubMed  Google Scholar 

  49. Peñas PF, Jones-Caballero M, Aragüés M, Fernández-Herrera J, Fraga J, García-Díez A. Sclerodermatous graft-vs-host disease: clinical and pathological study of 17 patients. Arch Dermatol. 2002;138:924–34.

    Article  PubMed  Google Scholar 

  50. Chosidow O, Bagot M, Vernant JP, Roujeau JC, Cordonnier C, Kuentz M, et al. Sclerodermatous chronic graft-versus-host disease. Analysis of seven cases. J Am Acad Dermatol. 1992;26:49–55.

    Article  CAS  PubMed  Google Scholar 

  51. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.

    Article  CAS  PubMed  Google Scholar 

  52. Schaffer JV, McNiff JM, Seropian S, Cooper DL, Bolognia JL. Lichen sclerosus and eosinophilic fasciitis as manifestations of chronic graft-versus-host disease: expanding the sclerodermoid spectrum. J Am Acad Dermatol. 2005;53:591–601.

    Article  PubMed  Google Scholar 

  53. Janin A, Socie G, Devergie A, Aractingi S, Esperou H, Vérola O, Gluckman E. Fasciitis in chronic graft-versus-host disease. A clinicopathologic study of 14 cases. Ann Intern Med. 1994;120:993–8.

    Article  CAS  PubMed  Google Scholar 

  54. Jang S, Kim IS, Youn SW. Chronic graft-versus-host disease mimicking psoriasis in a patient with hemophagocytic lymphohistiocytosis. Ann Dermatol. 2016;28:90–3.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Matsushita T, Hasegawa M, Shirasaki F, Fujimoto M, Yamazaki H, Sato S, Takehara KA. A case of acute cutaneous graft-versus-host disease mimicking psoriasis vulgaris. Dermatology. 2008;216:64–7.

    Article  PubMed  Google Scholar 

  56. Taguchi S, Kawachi Y, Fujisawa Y, Nakamura Y, Furuta J, Otsuka F. Psoriasiform eruption associated with graft-versus-host disease. Cutis. 2013;92:151–3.

    PubMed  Google Scholar 

  57. Creamer D, Martyn-Simmons CL, Osborne G, Kenyon M, Salisbury JR, Devereux S, et al. Eczematoid graft-vs-host disease: a novel form of chronic cutaneous graft-vs-host disease and its response to psoralen UV-A therapy. Arch Dermatol. 2007;143:1157–62.

    Article  PubMed  Google Scholar 

  58. Goiriz R, Peñas PF, Delgado-Jiménez Y, Fernández-Herrera J, Aragüés-Montañés M, Fraga J, García-Díez A. Cutaneous lichenoid graft-versus-host disease mimicking lupus erythematosus. Lupus. 2008;17:591–5.

    Article  CAS  PubMed  Google Scholar 

  59. SW H, Myskowski PL, Papadopoulos EB, Busam KJ. Chronic cutaneous graft-versus-host disease simulating hypertrophic lupus erythematosus–a case report of a new morphologic variant of graft-versus-host disease. Am J Dermatopathol. 2012;34:e81–3.

    Article  Google Scholar 

  60. Spelman LJ, Robertson IM, Strutton GM, Weedon D. Pityriasis rosea-like eruption after bone marrow transplantation. J Am Acad Dermatol. 1994;31:348–51.

    Article  CAS  PubMed  Google Scholar 

  61. Cornejo CM, Kim EJ, Rosenbach M, Micheletti RG. Atypical manifestations of graft-versus-host disease. J Am Acad Dermatol. 2015;72:690–5.

    Article  PubMed  Google Scholar 

  62. Llamas-Velasco M, Solano-López Morel GE, Gruber-Wackernagel A, Concha-Garzón MJ, Requena L, Cerroni L. Comedonal graft-vs-host disease: a distinct clinical expression of a lichenoid follicular GVHD. J Cutan Pathol. 2014;41:853–8.

    Article  PubMed  Google Scholar 

  63. Kaffenberger BH, Zuo RC, Gru A, Plotner AN, Sweeney SA, Devine SM, et al. Graft-versus-host disease-associated angiomatosis: a clinicopathologically distinct entity. J Am Acad Dermatol. 2014;71:745–53.

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Dermatology, University of Minnesota, 516 Delaware Street SE, Minneapolis, MN, USA

    Cuong V. Nguyen

  2. Division of Dermatology, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA, USA

    Christiane Querfeld

  3. Department of Dermatology, University of Minnesota Medical Center, 4-240 Phillips Wangensteen Building, 516 Delaware Street SE, Minneapolis, MN, USA

    Daniel D. Miller

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  1. Cuong V. Nguyen
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  2. Christiane Querfeld
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  3. Daniel D. Miller
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Correspondence to Daniel D. Miller .

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Editors and Affiliations

  1. Division of Dermatology, City of Hope National Medical Center Division of Dermatology, Durante, California, USA

    Jonathan A. Cotliar

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Nguyen, C.V., Querfeld, C., Miller, D.D. (2017). Histopathology of Cutaneous Graft-Versus-Host Disease. In: Cotliar, J. (eds) Atlas of Graft-versus-Host Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-46952-2_5

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  • DOI: https://doi.org/10.1007/978-3-319-46952-2_5

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