Original ArticlesPediatric Gastrointestinal Histopathology in Patients With Tetratricopeptide Repeat Domain 7A (TTC7A) Germline Mutations A Rare Condition Leading to Multiple Intestinal Atresias, Severe Combined Immunodeficiency, and Congenital EnteropathyDannheim, Katelyn MD*; Ouahed, Jodie MDCM, MMSc, FRCPC, FAAP†,‡; Field, Michael BS†; Snapper, Scott MD, PhD†; Raphael, Bram P. MD§; Glover, Sarah C. DO∥; Bishop, Phyllis R. MD∥; Bhesania, Natalie MD∥; Kamin, Daniel MD†,‡; Thiagarajah, Jay MD, PhD†,‡; Goldsmith, Jeffrey D. MD‡,¶ Author Information *Department of Pathology, Rhode Island and Hasbro Children’s Hospitals, Providence, RI †Division of Gastroenterology, Hepatology, and Nutrition ¶Department of Pathology ‡Congenital Enteropathy Program, Boston Children’s Hospital, Boston §Takeda Pharmaceuticals USA, Cambridge, MA ∥Division of Digestive Diseases and Division of Pediatric Gastroenterology, University of Mississippi Medical Center, Jackson, MS This work was presented in part at the 2019 Annual Meeting of the United States and Canadian Academy of Pathology, National Harbor, Maryland. This work was funded by a Career Development Award from the Office of Faculty Development at Boston Children’s Hospital, Boston, MA and by the National Institute of Health Grant K08DK122133 (J.O.) and National Institute of Health Grant RC2DK118640 (J.T., J.D.G.). Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Jeffrey D. Goldsmith, MD, Boston Children’s Hospital, Department of Pathology, BCH 3027, 300 Longwood Avenue, Boston, MA 02115 (e-mail: [email protected]). The American Journal of Surgical Pathology: June 2022 - Volume 46 - Issue 6 - p 846-853 doi: 10.1097/PAS.0000000000001856 Buy Metrics Abstract Mutations in the tetratricopeptide repeat domain 7A (TTC7A) gene are a rare cause of congenital enteropathy that can result in significant morbidity. TTC7A deficiency leads to disruption of the intestinal epithelium. The histopathology of this condition has been partly described in case reports and clinical studies. This manuscript describes an in-depth investigation of the pediatric gastrointestinal pathology of the largest histologically examined cohort with confirmed TTC7A mutations reported to date and, for the first time, compared the findings to age-matched and sex-matched control patients with intestinal atresia not thought to be associated with TTC7A mutations. Hematoxylin and eosin–stained slides of endoscopically obtained mucosal biopsies and surgical resection specimens from 7 patients with known TTC7A mutations were examined retrospectively. The microscopic findings were found to be on a spectrum from atresia-predominant to those with predominantly epithelial abnormalities. Several unique histopathologic characteristics were observed when compared with controls. These included neutrophilic colitis and prominent lamina propria eosinophilia throughout the gastrointestinal tract. Striking architectural abnormalities of the epithelium were observed in 4 of the 7 patients. The 5 patients with intestinal atresia demonstrated hypertrophy and disorganization of the colonic muscularis mucosae accompanied by bland spindle cell nodules within the intestinal wall. The components of the latter were further elucidated using immunohistochemistry, and we subsequently hypothesize that they represent obliterated mucosa with remnants of the muscularis mucosae. Finally, atrophic gastritis was noted in 4 patients. In conclusion, the unique histopathologic characteristics of TTC7A mutation-associated enteropathy described herein more fully describe this novel disease entity in infants who present with congenital enteropathy or enterocolitis. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.