A Four-Year Pathology Review of the Near Total Face Transplant

Abstract

In December of 2008, our institution performed a near total face transplant. The patient was monitored for signs of rejection assessed by paired skin and mucosa biopsies. The results of histological review of 120 biopsies collected during the first 4 years posttransplant are discussed. All biopsies were stained with hematoxylin and eosin, periodic acid-Schiff, immunohistochemical and TUNEL assays and graded using the Banff 2007 classification. Grade III rejection was diagnosed clinically at weeks 45 and 66, posttransplant; week 45 was determined as folliculitis while the erythema episode at week 66 confirmed an acute rejection (AR) that required hospitalization. The mucosa frequently showed interface inflammation without clinical signs of rejection and was not present in skin biopsies. In all, 34 of the 45 mucosal biopsies (75%) showed these interface changes. Clinical symptoms concurred with skin pathology in two grade III rejections. The mucosa showed histologic signs of rejection more frequently, which may indicate: increased mucosal sensitivity to rejection, a different type or subtype of AR that is specific to the mucosa, or a nonspecific process such as a drug effect. With more data and world experience, the diagnosis of face transplant rejection will be better defined and the Banff classification enhanced.

Biomarker evaluation of face transplant rejection: association of donor T cells with target cell injury

“…45 Site variation in determining in diagnosing and grading rejection must also be further explored, particularly in light of the robust study by Bergfeld et al, where examination of a large number of cutaneous and mucosal biopsies from a single face transplant patient indicated greater diagnostic sensitivity at the latter site. 29 Moreover, functional validation of the phenotypic findings presented herein will be required to more definitively understand the role of donor T cells in the rejection process. Finally, more comprehensive studies correlating detailed biomarker analysis of skin samples with systemic parameters of rejection are now indicated.…”

“…21 However, clinical assessment, histopathological diagnosis, and immunological mechanisms of facial composite allograft rejection remain incompletely studied, albeit being critical to further refinement of this new treatment option. Although a number of important studies have begun to address the issue of biomarkers and related immunopathology in vascular composite allotransplantation [22][23][24][25][26][27][28][29] (particularly in hand transplantation), our study represents a detailed and sequential histopathologic and immunophenotypic assessment of full facial transplant rejection. Facial allografts represent a unique setting where rejection can be evaluated for cutaneous biomarker expression in multiple and sequential biopsies not required in routine skin allograft transplantation.…”

“…Resident T cells within tracheal allografts have been shown to be radiation sensitive, 46 raising the possibility that pretransplant irradiation or other means of purging donor T cells from grafts might influence the clinical course of rejection post-transplant. Major strides have already been accomplished in understanding vascular composite allotransplantation rejection and biology, [22][23][24][25][26][27][28][29] and the Banff system is clearly useful in assessing allograft rejection. However, our findings underscore the critical role for further refinements in histopathology and biomarker application to the accurate diagnosis, therapeutic monitoring, and mechanistic understanding of vascular composite tissue transplantation.…”

Immunological and inflammatory mapping of vascularized composite allograft rejection processes in a rat model

“…Naturally, both face and hand transplantations inflict far more surgical damage to both the recipient and donor tissue as compared to transplantation of internal organs resulting in larger surface area of disrupted and damaged tissue. This may partly explain the rate of acute graft rejections within the first year of such transplantations, which is 85% in hand transplantations and 84% in face transplantations, higher than any other field of transplantation [12–15]. …”

Intraoral features and considerations in face transplantation

“…Similarly, a review of rejection episodes occurring during the first 8 months also found clinical oral mucosal rejection was less common than skin (Kanitakis et al , ). Despite this, however, surveillance biopsies of otherwise normal appearing oral mucosa are more likely to demonstrate evidence of rejection histopathologically than skin (Kanitakis et al , ; Hui‐Chou et al , ; Bergfeld et al , ). Whether this is the result of the chronic low‐grade trauma of the oral mucosa or in fact a predictor of rejection (a possible subtype of acute rejection specific to the mucosa), or a more non‐specific process is unclear (Kanitakis et al , ; Hui‐Chou et al , ; Bergfeld et al , ).…”