Mycophenolate mofetil-induced colitis versus colonic graft-versus-host disease: a comparative histologic study with artificial intelligence model development.

Abstract

Aim: The aim of this study was to compare the histopathologic features of MMF-induced colitis and colonic GVHD and develop a digital tool using deep learning convolutional neural networks (CNNs) to semi-automate the quantification of eosinophils.

Methods: MMF and GVHD colitis cases were retrieved. A cohort of transplant patients who were at risk for developing GVHD and were on MMF at the time of biopsy was also identified. Cases were reviewed for histologic features and a deep learning CNN was trained to quantify lamina propria eosinophils. Clinical history was collected.

Results: Ninety-five patients were included in the study group: GVHD (n = 37), MMF (n = 25) and GVHD vs. MMF (n = 33). Within the GVHD vs. MMF group, one patient was thought to have definitive MMF colitis and one possible MMF colitis. The GVHD group had a significantly higher apoptotic count compared to the MMF group (median: 7 vs. 2, P = 0.03). Neuroendocrine aggregates were present in the GVHD (N = 12) and GVHD vs. MMF (N = 4) groups while absent in the MMF group. The MMF group had a higher semi-quantitative eosinophil score and a higher automated eosinophil count as detected by the deep learning CNN (median eos/HPF: MMF 19.2, GVHD vs. MMF 3.6, GVHD 3.4, P < 0.001).

Conclusions: Lower eosinophil counts, higher apoptotic counts and neuroendocrine cell aggregates favour the diagnosis of GVHD. AI models for eosinophil quantification may serve as an ancillary tool for assessing this differential diagnosis. Given the rarity of MMF-induced colitis in SCT patients, pathologists should have a high threshold for making this diagnosis in this population.