Histologic Features, Particularly Eosinophilic Inflammation, Can Discriminate Mycophenolate-Induced from GVHD-Induced Colitis
Kremena Star, Robert D Odze. Brigham and Women's Hospital, Boston
Background: Mycophenolate Motif (MMF) is a T cell inhibitor frequently used for the treatment of acute allograft rejection. MMF may cause colitis that clinically and histologically resembles Graft Versus Host Disease (GVHD). Some bone marrow (BM) transplant patients also receive MMF, and, are at risk for both forms of colitis. The aim of this study was to evaluate a wide range of histologic features that may help differentiate MMF from GVHD-induced colitis, and to validate any significant features on a test set of BM transplant patients who also received MMF.
Design: Routinely processed colonic biopsies from 17 patients (mean age: 48 years, M/F ratio: 6/11) and 40 cases of GVHD (mean age: 57 years, M/F ratio: 26/14) (grade 1:10 cases, 2:10 cases, 3:10 cases, 4:10 cases) were evaluated histologically for a wide range of inflammatory, epithelial, and architectural changes in a blinded manner, in both an absolute and semiquantitative manner, by evaluation of 10 high power fields (HPF). Statistically significant features were then tested on a group of 20 BM transplant patients who also received MMF (N=20) and developed a diarrheal illness.
Results: Patients with MMF-induced colitis showed significantly fewer lymphocytes/HPF (24.0 vs 40.0, p=0.03), crypt atrophy (p<0.0001), and significantly fewer apoptotic cells per crypt (1.1 versus 10.6, p=0.005), compared to GVHD. In contrast, both the presence and quantity of neutrophils (p=0.01 for both) and, in particular, eosinophils (EOS) (17/17 vs 28/40, median=40.0 vs 2.0, p=0.0002) were far more common in MMF colitis. Regarding EOS, ≥15 EOS/10 HPF showed 75% specificity and 100% sensitivity for MMF. Many of these features, were also significant when MMF colitis was compared to each individual grade of GVHD separately. Evaluation of the test (validation) set of cases in a blinded manner, showed that the quantity of lymphocytes, and the presence or absence, and quantity, of neutrophils and EOS, and the degree of crypt distortion, showed high sensitivity and specificity for distinguishing MMF from GVHD. In particular, EOS ≥ 15 showed 100% sensitivity and 67% specificity.
Conclusions: Evaluation of histologic features, such as the presence and quantity of lymphocytes, neutrophils, and, in particular, EOS, atrophy and apoptosis, can help distinguish MMF from GVHD-induced colitis in a reliable manner. The presence of EOS >15/10 HPF is a highly sensitive and reasonably specific indicator of MMF induced colitis in BM transplant patients who have received this drug in addition to usual immunosuppressive therapy.
Monday, March 19, 2012 1:00 PM
Poster Session II # 130, Monday Afternoon