This series of 113 sequential biopsies of full facial transplants provides findings of potential translational significance as well as biological insights that could prompt reexamination of conventional paradigms of effector pathways in skin allograft rejection. Serial biopsies before, during, and after rejection episodes were evaluated for clinicopathological assessment that in selected cases included specific biomarkers for donorversus-recipient T cells. Histologic evidence of rejection included lymphocyte-associated injury to epidermal rete ridges, follicular infundibula, and dermal microvessels. Surprisingly, during active rejection, immune cells spatially associated with target cell injury consisted abundantly or predominantly of lymphocytes of donor origin with an immunophenotype typical of the resident memory T-cell subset. Current dogma assumes that skin allograft rejection is mediated by recipient T cells that attack epidermal targets, and the association of donor T cells with sites of target cell injury raises questions regarding the potential complexity of immune cell interactions in the rejection process. A more histopathologically refined and immune-based biomarker approach to assessment of rejection of facial transplants is now indicated. Modern Pathology (2014) 27, 788-799; doi:10.1038/modpathol.2013.249; published online 17 January 2014Keywords: donor T cell; facial transplant; graft-versus-host disease; skin allograft; T resident memory cells; vascularized composite allotransplantation Recent reports emphasizing the critical therapeutic importance of accurate diagnosis of transplant rejection 1 have stressed the imminent need for more precise clinicopathologic criteria and complementary application of relevant biomarkers. 2 The first systematic studies of any form of human allograft rejection were reported by Gibson and Medawar 3 in their classic description of skin rejection involving wartime aviators. 4 Early clues regarding the immunologic basis of skin graft rejection came from studies by Dvorak et al 5 and Bhan et al 6 that implicated both CD4 þ and CD8 þ T cells. These T-cell populations were presumed to be of recipient origin and considered to be primary effectors of epidermal and dermal microvascular target cell injury. With the recent advent of fullfacial transplantation, 7 detailed and sequential histopathologic surveillance for rejection in a manner seldom feasible for conventional skin allografts has become a necessity. However, existing schemas 8 for histologic recognition and grading of rejection in vascular composite allotransplantation are based primarily on allografts that may express relevant structural and immunological differences from facial tissues, eg, extremities (hand) and
High-grade anal intraepithelial neoplasia is relatively common in HIV-infected patients regardless of sexual practice. Although risk increases with receptive anal intercourse, patient-provided information on this sexual practice should not be used as a determining factor for screening. Strategies to prevent anal cancer are necessary for all HIV-infected patients.
Background
Histopathological features in morphea (localized scleroderma) and their clinical correlates are poorly described.
Objective
Systematically describe histologic changes of morphea in a large, well annotated cohort and determine the association between histopathology and clinical features.
Methods
Cross-sectional study of 83 patients enrolled in the Morphea in Adults and Children (MAC) cohort. The main outcome measure was the association of microanatomical location and degree of sclerosis and inflammation seen on histologic samples with patient reported symptoms and physician-based measures of severity.
Results
Pattern of sclerosis was associated with morphea subtype, the presence of patient reported symptoms, and functional limitation. A bottom heavy pattern of sclerosis was associated with pain and tightness (P = 0.0039, 0.001 respectively). These symptoms were not associated with a top heavy pattern. Severe inflammation may be associated with pain and functional limitation (p = 0.073 for both).
Limitations
Small sample size limits ability to detect associations, particularly in subgroups.
Conclusions
Histopathological examination of morphea may assist in identifying patients who may require additional monitoring and treatment. Features such as patterns of sclerosis and severity of inflammation should be included in pathology reports to help aid in clinical management.
The diagnostic algorithm proposed by the ISCL is a statistically valid method for defining cases of early MF and distinguishing these cases from other benign dermatoses. However, the clinical utility of the algorithm may be limited by its low specificity. Further refinement of the algorithm may improve its accuracy.
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