Sequential histologic changes in the healing process in small bowel allografts treated for acute cellular rejection

Introduction: Acute cellular rejection (ACR) is a common complication seen in small intestinal transplant patients. Once diagnosed, follow-up endoscopy/biopsies may be performed to assess for response to therapy and the pathologist is often asked to determine whether the findings are compatible with treated/resolving or ongoing ACR. To this end, the sequence of resolution of ACR's changes in biopsies is important. Methods: We retrospectively reviewed the clinical histories and hematoxylin and eosin-stained slides from 16 cases of ACR patients who underwent isolated small bowel or combined liver/small bowel/pancreas transplants. Selected cases were new diagnoses of mild ACR with prior negative biopsies in the preceding 2 months, treatment for rejection based on the ACR diagnosis, and biopsies in the following 4 weeks diagnosed as "treated ACR" or "normal." The presence of ACR diagnostic features (epithelial injury, lamina propria [LP] inflammation with resident cell population, and crypt apoptotic body [AB] quantification) were evaluated. A series of 15 age-matched screening intestinal allograft biopsies were used as controls. Results: After treatment, epithelial injury as manifested by mucin depletion resolved by 2 week. LP inflammation was significantly reduced by 1 week after therapy, with a marked decrease in activated lymphocytes and eosinophils, and completely returned to control levels by week 3. Apoptosis fell below the diagnostic threshold for rejection (<6 AB/10 crypts) by week 2 and was equivalent to control biopsies at week 3. Conclusion: Knowledge of the sequence of the resolution of the histologic features of ACR after treatment may provide useful information to pathologists evaluating follow-up biopsies. These data show that both LP inflammation and crypt epithelial injury are reduced by 1 week after anti-rejection therapy and their persistence may signify ongoing rejection.