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      Clinical, Histologic, and Immunophenotypic Features of Serrated Polyps in Patients With Inflammatory Bowel Disease

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          Abstract

          Background

          Colorectal serrated polyps (SP), which include hyperplastic polyps (HP), sessile serrated adenomas/polyps (SSA/P), and traditional serrated adenomas, are not uncommon and have been implicated to play a role in the pathogenesis in a subset of sporadic colorectal carcinomas; however, their significance in patients with prolonged inflammatory bowel disease (IBD) remains unclear.

          Methods

          We retrospectively studied the clinicopathologic features, BRAF and β-catenin immunohistochemistry staining patterns in 36 SPs from 28 patients with IBD compared with 40 SPs in patients without IBD.

          Results

          Eleven SSA/Ps and 25 HPs from IBD and site-matched controls were included. SSA/Ps in the study group were slightly more commonly seen in males (55% vs. 41%, P = 0.7) and older patients (55.2 vs. 47.8 years, P = 0.2) compared to patients with HP. They were moderately larger (7.13 mm vs. 4.83 mm, P = 0.14) and more likely located on the right (63.6% vs. 32%, P = 0.46). Smaller percentage of SSA/Ps showed BRAF staining compared to controls (55.6% vs. 73.3%, P = 0.41) and HPs showed similar features (52.0% vs. 54.2%, P = 1). β-catenin was negative in all cases. During follow-up, only one patient in the SSA/P group developed carcinoma 42 months after at the same site and two developed adenoma-like low-grade dysplasia but no patients with HPs had such findings.

          Conclusions

          Our findings show that SPs in IBD share similar clinicodemographic and immunophenotypical features with sporadic SPs. However, patients with SSA/Ps may have a slight increase in risk of developing dysplasia compared to patients with HPs in IBD.

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          Most cited references25

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          CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer.

          Aberrant DNA methylation of CpG islands has been widely observed in human colorectal tumors and is associated with gene silencing when it occurs in promoter areas. A subset of colorectal tumors has an exceptionally high frequency of methylation of some CpG islands, leading to the suggestion of a distinct trait referred to as 'CpG island methylator phenotype', or 'CIMP'. However, the existence of CIMP has been challenged. To resolve this continuing controversy, we conducted a systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology, involving 295 primary human colorectal tumors and 16,785 separate quantitative analyses. We found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset, encompassing almost all cases of tumors with BRAF mutation (odds ratio = 203). Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors.
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            Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications.

            Assessment of epithelial dysplasia in ulcerative colitis has been hindered by inconsistencies in and disagreements about nomenclature and interpretation. To resolve these issues, pathologists from ten institutions participated in three exchanges of multiple slides and, following each exchange, in discussions of the results. A classification system for the epithelial changes that occur in ulcerative colitis was developed, which should be applicable to other forms of inflammatory bowel disease as well. The classification makes use of standardized terminology, addresses specific problem areas, and offers practical solutions. The reproducibility of the system was studied by means of examinations of both inter- and intra-observer variations. The clinical implications of the findings were incorporated into suggestions for patient management. The basis of the classification is that the term "dysplasia" is reserved for epithelial changes that are unequivocally neoplastic and may therefore give rise directly to invasive carcinoma. Specimens are categorized as negative, indefinite, or positive for dysplasia. The negative category includes all inflammatory and regenerative lesions and indicates that only continued regular surveillance is required. The indefinite category is applied to epithelial changes that appear to exceed the limits of ordinary regeneration but are insufficient for an unequivocal diagnosis of dysplasia or are associated with other features that prevent such unequivocal diagnosis. Clinically, it indicates that early repeat biopsy is often required to assess the changes more accurately. The positive category is divided into two subcategories: 1) high-grade dysplasia, for which colectomy should be strongly considered after confirmation of the diagnosis, and 2) low-grade dysplasia, which also requires confirmation and early repeat biopsy or colectomy, depending on other findings.
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              Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study.

              Although inflammation is presumed to contribute to colonic neoplasia in ulcerative colitis (UC), few studies have directly examined this relationship. Our aim was to determine whether severity of microscopic inflammation over time is an independent risk factor for neoplastic progression in UC. A cohort of patients with UC undergoing regular endoscopic surveillance for dysplasia was studied. Degree of inflammation at each biopsy site had been graded as part of routine clinical care using a highly reproducible histologic activity index. Progression to neoplasia was analyzed in proportional hazards models with inflammation summarized in 3 different ways and each included as a time-changing covariate: (1) mean inflammatory score (IS-mean), (2) binary inflammatory score (IS-bin), and (3) maximum inflammatory score (IS-max). Potential confounders were analyzed in univariate testing and, when significant, in a multivariable model. Of 418 patients who met inclusion criteria, 15 progressed to advanced neoplasia (high-grade dysplasia or colorectal cancer), and 65 progressed to any neoplasia (low-grade dysplasia, high-grade dysplasia, or colorectal cancer). Univariate analysis demonstrated significant relationships between histologic inflammation over time and progression to advanced neoplasia (hazard ration (HR), 3.0; 95% CI: 1.4-6.3 for IS-mean; HR, 3.4; 95% CI: 1.1-10.4 for IS-bin; and HR, 2.2; 95% CI: 1.2-4.2 for IS-max). This association was maintained in multivariable proportional hazards analysis. The severity of microscopic inflammation over time is an independent risk factor for developing advanced colorectal neoplasia among patients with long-standing UC.
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                Author and article information

                Journal
                Gastroenterology Res
                Gastroenterology Res
                Elmer Press
                Gastroenterology Research
                Elmer Press
                1918-2805
                1918-2813
                October 2018
                1 October 2018
                : 11
                : 5
                : 355-360
                Affiliations
                [a ]Department of Pathology, Yale School of Medicine, New Haven, CT, USA
                [b ]Peoria Tazewell Pathology Group, Peoria, IL, USA
                [c ]Baylor University Medical Center, Baylor Scott and White Center for Inflammatory Bowel Diseases, Dallas, TX, USA
                Author notes
                [d ]Corresponding Author: ILKe Nalbantoglu, Department of Pathology/Surgical Pathology-EP2-608B, 310 Cedar Street, New Haven, CT 06515, USA. Email: ilke.nalbantoglu@ 123456yale.edu
                Article
                10.14740/gr1064w
                6188039
                80d4c5a8-af24-47ad-bae0-b554781240cb
                Copyright 2018, Yang et al.

                This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 July 2018
                : 30 July 2018
                Categories
                Original Article

                serrated,polyps,inflammatory bowel disease,braf,β-catenin
                serrated, polyps, inflammatory bowel disease, braf, β-catenin

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