Original ArticlesHistologic Correlates of Clinical and Endoscopic Severity in Children Newly Diagnosed With Ulcerative ColitisBoyle, Brendan MD, MPH*; Collins, Margaret H. MD†; Wang, Zhu PhD‡; Mack, David MD§; Griffiths, Anne MD∥; Sauer, Cary MD¶; Markowitz, James MD#; LeLeiko, Neal MD**; Keljo, David MD††; Rosh, Joel MD‡‡; Baker, Susan S. MD§§; Pfefferkorn, Marian MD∥∥; Heyman, Melvin MD¶¶; Patel, Ashish MD##; Baldassano, Robert MD***; Noe, Joshua MD†††; Rufo, Paul MD‡‡‡; Kugathasan, Subra MD¶; Walters, Thomas MD∥; Denson, Lee MD†; Hyams, Jeffrey MD‡ on behalf of the PROTECT Study GroupAuthor Information *Nationwide Children’s Hospital, Columbus †Cincinnati Children’s Hospital Medical Center, Cincinnati, OH ‡Connecticut Children’s Medical Center, Hartford, CT §Children’s Hospital of Eastern Ontario, Ottawa ∥Hospital for Sick Children, Toronto, ON, Canada ¶Emory Children’s Center, Atlanta, GA #Cohen Children’s Medical Center, New Hyde Park ‡‡Goryeb Children’s Hospital/Atlantic Health, Morristown §§Women & Children’s Hospital of Buffalo WCHOB, Buffalo, NY **Hasbro Children’s Hospital, Providence, RI ††Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA ∥∥Riley Children’s Hospital Indiana University School of Medicine, Indianapolis, IN ¶¶University of California, San Francisco, CA ##UT Southwestern, Dallas, TX ***Children’s Hospital of Philadelphia, Philadelphia, PA †††Medical College of Wisconsin, Milwaukee, WI ‡‡‡Boston Children’s Hospital, Boston, MA The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflicts of Interest and Source of Funding: Supported by the National Institutes of Health (NIH) (DK 095745-01); the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), U01DK095745 and P30DK078392 (Integrative Morphology Core). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Brendan Boyle, MD, MPH, Nationwide Children’s Hospital, Columbus, OH 43205 (e-mail: firstname.lastname@example.org). The American Journal of Surgical Pathology: November 2017 - Volume 41 - Issue 11 - p 1491-1498 doi: 10.1097/PAS.0000000000000939 Buy Metrics Abstract To characterize rectal histology in an inception cohort of children newly diagnosed with ulcerative colitis (UC) and to explore its relationship with clinical indices of disease severity. The PROTECT (Predicting Response to Standardized Pediatric Colitis Therapy) Study enrolled children 17 years of age and younger newly diagnosed with UC. Baseline rectal biopsies were evaluated for acute and chronic inflammation, eosinophilic inflammation (peak eosinophil count > 32 eosinophils/high powered field, eosinophilic cryptitis or abscesses), and architectural/nonarchitectural chronic changes. Correlation with clinical indices including Mayo endoscopy subscore and Pediatric Ulcerative Colitis Activity Index was performed. Rectal biopsies from 369 patients (mean age, 12.9±3.1 y, 50% female) were reviewed. Cryptitis was found in 89%, crypt abscesses in 25%, and eosinophilic inflammation in 58%. Crypt distortion/atrophy was present in 98% of specimens. Higher grades of acute and chronic inflammation were associated with the presence of basal plasmacytosis (P<0.0001), basal lymphoid aggregates (P<0.0001), and surface villiform changes (P<0.0001). A severe Mayo endoscopy subscore was most common among those with severe acute and chronic inflammation, although this relationship was not linear. Severe Pediatric Ulcerative Colitis Activity Index scores were associated with the absence of or only mild eosinophilic inflammation (<32 eosinophils/high powered field) (P<0.03) and the presence of surface villiform changes (P<0.005). Acute and chronic inflammation, eosinophilic inflammation and chronic changes are common in children newly diagnosed with UC. The clinical and biological implication of low to absent eosinophilic inflammation and the presence of surface villiform changes requires further study. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.