Can We Distinguish Mycophenolate-Induced Colitis from Colonic Graft-Versus-Host Disease?
Daniel G Leino, Joel K Greenson. University of Michigan Medical School, Ann Arbor, MI
Background: Mycophenolate mofetil (MMF) is an immunosupressive agent commonly used in solid organ transplant recipients. More recently it has been used to treat Graft-versus-host disease (GVHD). Previous studies have documented that MMF can cause GI tract damage that is very similar to GVHD. Our anecdotal experience was that MMF colitis often had dilated crypts containing esoinophils and debris, while GVHD did not. We undertook the following morphologic study to see if we could identify any histologic features that would allow us to separate these two entities.
Design: All colonic biopsies signed-out as either GVHD or MMF colitis between 2004 and 2010 were reviewed. The MMF cases entered into the study were all solid-organ transplant patients that had no evidence of GVHD (no bone marrow transplant patients). The GVHD cases were all bone marrow transplant patients that had no prior treatment with MMF. Twenty-eight cases of MMF colitis and 34 cases of GVHD had enough intact tissue in their biopsies for further study. All cases were reviewed blindly for the following features: amount and character of lamina propria and epithelial inflammation, Grade of GVHD, number of apoptotic bodies / 10 crypts, amount of crypt distortion and dilatation and number of Ki-67 positive cells/crypt.
Results: The number of apoptotic cells per 10 crypts was statistically higher in cases of colonic GVHD vs MMF colitis (p<0.000002) with a range of 6 - 60 for GVHD (mean 30.94) and 0 - 28 for MMF (mean 12.26). There were no statistically significant differences with regards to Ki-67 labeling, crypt distortion or crypt dilation, nor any types or intensity of inflammatory cells. The only other significant finding was the presence of endocrine cell nests in the deep lamina propria of 8 severe cases of GVHD as compared to 0 cases of MMF colitis (despite having similar denuded areas)(p<0.006).
Conclusions: This study confirms that MMF colitis is a great mimicker of colonic GVHD. While the number of apoptotic cells per 10 crypts was much higher in GVHD cases as a whole, there was considerable overlap, particularly in Grade 1 GVHD as compared to MMF colitis. In severe cases of GVHD, denuded areas often had endocrine cell nests at the base of the lamina propria that were not seen in cases of severe MMF colitis with similarly denuded areas. Dilated crypts containing eosinophils and necrotic debris were seen in cases of GVHD and MMF and were not helpful in distinguishing one entity from another.
Monday, March 19, 2012 9:15 AM
Platform Session: Section D, Monday Morning