Histologic Features in Colon Biopsies Can Discriminate Mycophenolate From GVHD-induced Colitis.
ABSTRACT Mycophenolate mofetil (MMF) is a T-cell inhibitor frequently used in the treatment of acute allograft rejection. MMF may cause colitis that clinically and histologically resembles graft-versus-host disease (GVHD). 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 significant features on a cohort of bone marrow transplant patients who were also taking MMF as part of their immunosuppressive regimen and developed a diarrheal illness due to colitis. Routinely processed colonic biopsies from 17 patients with MMF colitis and 40 patients with GVHD-induced colitis were evaluated for the overall grade of colitis (grades 1 to 4) and histologically for a wide range of inflammatory, epithelial, and architectural changes in a blinded manner. Statistically significant features were then tested in a cohort of 20 bone marrow transplant patients who also received MMF, and later developed a diarrheal illness. Both univariate and multivariate analyses (including receiver operating characteristic analysis) were performed. Morphologic features shown to be independently associated with MMF include the presence and quantity of lamina propria eosinophils and endocrine cell aggregates and the presence and quantity of apoptotic microabscesses, hypereosinophilic (degenerated) crypts, and crypt distortion. Eosinophils were present in all MMF patients, but apoptotic microabscesses were present in none and endocrine cell aggregates in only 1 case. When a grade-by-grade comparison was made between MMF and GVHD, grade 1 or 2 MMF also showed an increased prevalence rate and quantity of lamina propria neutrophils in comparison with grade 1 or 2 GVHD. By receiver operating characteristic analysis, a combination of lamina propria eosinophils >15 per 10 HPF, combined with a lack of endocrine cell aggregates and apoptotic microabscesses, revealed sensitivity, specificity, and positive and negative predictive values of 76%, 93%, 81%, and 90%, respectively, for identification of MMF colitis. On the basis of these data, we conclude that a variety of histologic features, in particular, eosinophils >15 per 10 HPF, lack of endocrine cell aggregates in the lamina propria, and lack of apoptotic microabscesses, can be used by pathologists to help separate MMF from GVHD-induced colitis in routine clinical practice.
SourceAvailable from: Joel K Greenson[Show abstract] [Hide abstract]
ABSTRACT: The 2005 National Institute of Health (NIH) Consensus Conference outlined histopathological diagnostic criteria for the major organ systems affected by both acute and chronic graft-versus-host disease (GVHD). The 2014 Consensus Conference led to this updated document with new information from histopathological studies of GVHD in the gut, liver, skin and oral mucosa and expanded discussion of GVHD in the lungs and kidneys. The recommendations for final histological diagnostic categories have been simplified from 4 categories to 3: no GVHD, possible, and likely GVHD based on better reproducibility achieved by combining the previous categories of consistent with and definite GVHD into the single category of likely GVHD. Issues remain in the histopathological characterization of GVHD, particularly with respect to the threshold of histological changes required for diagnostic certainty. Guidance is provided for the incorporation of biopsy information into prospective clinical studies of GVHD, particularly with respect to biomarker validation. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2015; 21(4). DOI:10.1016/j.bbmt.2014.12.031 · 3.35 Impact Factor
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ABSTRACT: Many drugs and chemical agents can cause enteritis and colitis, producing clinical gastrointestinal side effects, the most common of which are diarrhoea, constipation, nausea and vomiting. Significant histological overlap exists between some patterns of medication or chemical injury and various disease entities. A particular medication may cause multiple patterns of injury and may mimic common entities such as coeliac disease, Crohn's disease, infectious enteritis and colitis. Thus, given the common absence of specific histopathological features, the diagnosis often relies upon thorough clinicopathological correlation. This review concentrates on selected examples of medication-induced injury of the intestinal tract in which the pathology can be recognized, particularly on biopsies, with a focus on newly described medication-induced gastrointestinal effects.Histopathology 01/2015; 66(1). DOI:10.1111/his.12598 · 3.30 Impact Factor
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ABSTRACT: The assessment of gastrointestinal (GI) specimens from transplant patients is complicated by the wide range of, potentially rare, pathologies that may be found in this clinical setting. Acute GI graft versus host disease (GvHD) is characterised by epithelial cell apoptosis, although there is increasing recognition that acute and/or chronic inflammation may also be present. By contrast, there are thus far no histological features known to be specific to chronic GI GvHD. Mycophenolate mofetil colitis may mimic both GvHD and inflammatory bowel disease, whereas both CMV and adenovirus infections can cause gland apoptosis. Post-transplant lymphoproliferative disorder should be considered if a Crohn's like histological picture is seen, and granulomas in biopsies from umbilical cord blood recipients should raise a suspicion of cord colitis syndrome. Finally, the GI tract may be involved directly or indirectly by the disease that originally required haematopoietic stem cell or liver transplantation. This article is protected by copyright. All rights reserved.Histopathology 09/2014; 66(4). DOI:10.1111/his.12542 · 3.30 Impact Factor