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

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.

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.

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.

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.