Skin-nontumor / Clinical dermatology
Other dermatoses
Skin graft rejection

Author: Mowafak Hamodat, M.D., MB.CH.B, MSc., FRCPC (see Authors page)

Revised: 21 July 2016, last major update August 2011

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Skin graft rejection [title]

Definition / General
  • Clinically, rejection appears as maculopapular rash at mean 8 weeks after transplant

  • Proposed grading system for rejection of full-thickness cadaver skin transplant for large abdominal defects:
    • Grade 0: no rejection; no perivascular infiltrates; normal skin
    • Grade 1: indeterminate for rejection; 1 - 10% of vessels have infiltrates of small lymphocytes; no eosinophils, large lymphocytes, spongiosis, epidermis or stromal inflammation; basal vacuolar change
    • Grade 2: mild rejection; 11 - 50% of vessels have infiltrates of small lymphocytes, variable eosinophils or mild spongiosis; no epidermal or stromal infiltrates or large lymphocytes; basal vacuolar change
    • Grade 3: moderate rejection: 51%+ of vessels have infiltrates of small lymphocytes, variable epidermal and stromal inflammation, at most mild spongiosis, possible endothelial plumping, eosinophils and large lymphocytes; fusion of basilar vacuoles to form clefts and microvesicles
    • Grade 4: severe rejection; 51% of vessels have infiltrates of small lymphocytes, but also dyskeratosis, epidermis has heavier lymphocytic infiltrates and moderate to severe spongiosis; stroma shows infiltrates extending into base of epidermis; also endothelial plumping, eosinophils and large lymphocytes; separation of epidermis from dermis
    • Am J Surg Pathol 2004;28:670

  • Another grading system:
    • Grade 0: normal skin
    • Grade 1: basal vacuolar change
    • Grade 2: dyskeratotic cells in the epidermis or follicle, dermal lymphocytic infiltrate
    • Grade 3: fusion of basilar vacuoles to form clefts and microvesicles
    • Grade 4: separation of epidermis from dermis

  • Acute GVHD develops in one-third of HLA-matched recipients of allogeneic bone marrow; also follows stem cell transplantation; is seen only rarely after solid organ transplantation
Clinical Features
  • Early acute GVHD has vomiting, diarrhea, hepatic manifestations and erythematous macular rash; rarely it is confined to the flexures, there are follicular papules or blisters, or toxic epidermal necrolysis ensues
  • In one case, just two erythematous nodules were the presenting features
  • A pustular acral erythema with associated eccrine squamous syringometaplasia has also been reported
  • Ichthyosiform features may occur in both the acute and chronic forms
  • Chronic GVHD has an early lichenoid phase which resembles lichen planus and includes oral lesions
  • Sclerodermatous GVHD has a 3% prevalence in patients receiving allogeneic bone marrow transplants
  • Other late manifestations include alopecia, a lupus erythematosus-like eruption, cicatrizing conjunctivitis, pyogenic granuloma and angiomatous lesions, wasting, diffuse melanoderma, leukoderma and leukotrichia, esophagitis, liver disease and the sicca syndrome
Treatment
  • Chronic cutaneous GVHD has been treated with corticosteroids and immunosuppressants such as cyclosporine and extracorporeal photopheresis (ECP)
Micro Description
  • Acute GVHD:
    • Focal or diffuse basal cell hydropic changes
    • Apoptotic and dyskeratotic keratinocytes at all levels of the epidermis and associated with adjacent lymphocytes (satellite cell necrosis) are characterstic
    • Isolated cytoid bodies are also evident
    • Lymphocytic exocytosis and spongiosis is sometimes a feature
    • Also microvesiculation at the epidermodermal junction, follicular involvement; endothelial cell swelling and intimal and perivascular lymphocytic infiltrate, perivascular edema and nuclear dust

  • Chronic GVHD:
    • Typically lichenoid, resembles lichen planus
    • Hyperkeratosis, hypergranulosis, irregular acanthosis, basal cell hydropic changes, cytoid body formation, pigment incontinence and band like lymphohistiocytic infiltrate
    • In contrast to idiopathic lichen planus, satellite cell necrosis is often present in the early phase of Chronic GVHD, and the infiltrate sometimes contain plasma cells and eosinophils
    • Squamous metaplasia of eccrine sweat ducts have been described
    • The late stage of chronic GVHD is charaterized by epidermal atrophy, with abolition of ridge pattern and scarring of superficial and deep dermis, with loss of adnexal structures
Micro Images

Images hosted on PathOut servers:

Moderate acute rejection (right: CD3 stain), courtesy of Anabel Bejarano, M.D., Ph.D.

Differential Diagnosis
  • Acute contact dermatitis: more severe spongiosis, often intraepidermal vesicles and inflammatory cells in epidermis; also affects areas other than transplanted skin
  • Drug, viral infection, chemotherapy effect: the use of skin biopsies to differentiate between drug reaction, chemotherapy effect, viral infection and GVHD has no real practical value; the presence of eosinophils is generally taken to favor a drug reaction, but this is not a correct assumption as eosinophils are occasionally seen in GVHD; the presence of more than five apoptotic keratinocytes, predominantly involving adnexal keratinocytes, is said to favor GVHD
Additional References