Mycophenolate Mofetil (Cellcept) Induced Injury of the Upper GI-Tract
T Nguyen, JY Park, JR Scudiere, E Montgomery. Johns Hopkins Hospital, Baltimore
Background: Mycophenolate Mofetil (MM) is an immunosuppressant drug commonly used in patients undergoing solid organ transplant. While its pattern of inducing injury in the colon is well- known and features prominent crypt apoptosis that mimics graft versus-host-disease (GVHD), the injury pattern in the upper gastrointestinal (GI)-tract is less extensively documented. We studied the pattern of upper GI-tract injury patterns in patients taking MM.
Design: Seventeen solid organ transplant patients who were taking MM and had concurrent upper GI-tract biopsies were identified on a laboratory information system search. From these 17 patients, 15 duodenal, 15 gastric, and 6 esophageal biopsies were examined. Apoptosis and patterns of chronic injuries were assessed on standard H&E stained slides. In order to measure the significance of apoptosis, we standardized the apoptotic counts in normal biopsies using 26 normal control cases and performed statistical analysis. For the purposes of this study, we regarded apoptotic counts higher than the mean plus two standard deviations as significant. Thus the cut off values for apoptosis were >9 apoptotic bodies /100 crypts for duodenum, and >3/10HPF for both stomach and esophagus.
Results: Upper GI-symptoms manifested between 1 months to 10 years post-transplant and included nausea, vomiting, abdominal pain, odynophagia, dyspepsia, dysphagia, and GI-bleeding. Most (11/15, 73%) duodenal biopsies showed apoptotic counts of > 9/100 crypts; 67% (10/15) of gastric biopsies showed apoptotic counts of >3/10HPF, and all esophageal biopsies (6/6) showed apoptotic counts of >3/10 HPF. Two gastric biopsies with the highest apoptotic counts also showed a previously undescribed injury pattern of parietal cells resembling ballooning degeneration. Additional pathological findings included: intraepithelial lymphocytosis, chronic peptic duodenitis, and Brunner gland hyperplasia in duodenal biopsies; active and inactive chronic gastritis, and chemical gastropathy. H. pylori organisms were absent in gastric biopsies; ulcers seen in half (3/6) of esophageal biopsies. In most of the patients, symptoms were improved upon withdrawing MM or decreasing dosage (8/9).
Conclusions: As noted by others (Parfitt JR, Jayakumar S, Driman DK. Am J Surg Pathol 2008 32(9):1367-72.), MM-associated injury at the upper GI tract, like that in the colon, is characterized by prominent apoptosis similar to that of mild or grade I GVHD injury pattern. We have established apoptotic count guidelines that we hope will facilitate recognition of MM-associated injury in the upper GI-tract.
Monday, March 9, 2009 8:15 AM
Platform Session: Section C, Monday Morning