A Skin Rejection Grading System for Vascularized Composite Allotransplantation in a Preclinical Large Animal Model

BACKGROUND. The Banff Criteria have been accepted as a system for grading histological rejection in graft skin in human vascularized composite allotransplantation (VCA). Preclinical swine hindlimb transplantation models have an important role in translational studies in VCA. However, unified grading criteria for rejection in swine skin have not yet been established. METHODS. Two hundred fourteen swine skin biopsy specimens were reviewed, including 88 native skin biopsies and 126 specimens from the skin component of heterotopic swine hindlimb transplants. Thorough review was performed in a blinded fashion by an expert veterinary pathologist with attention paid to the applicability of the Banff criteria as well as specific histologic characteristics and trends. Clinical and histopathologic rejection scores were then directly compared. RESULTS. Two hundred fourteen specimens reviewed showed significant similarities between swine and human skin, as previously published. Notable swine-specific characteristics, including paucicellular infiltration with rare epidermal cell infiltration or necrosis, were accounted for in a proposed grading system that parallels the Banff Criteria. CONCLUSIONS. This comprehensive grading system, based on the Banff Classification for skin rejection in VCA, provides a standardized system for more accurate comparison of rejection in preclinical swine VCA models.