Significance of Gastrointestinal Histiocytosis: A Case Series and Literature Review

Background and aims Gastrointestinal (GI) histiocytosis is an uncommon and heterogeneous finding that may represent reactive, infectious, medication-related, or neoplastic processes. Because lesions are often identified incidentally on biopsy, their true frequency, etiologic spectrum, and optimal diagnostic approach remain poorly defined. We aimed to characterize GI histiocytosis using a large institutional cohort and contextualize findings using a review of published adult cases. Methods We performed a retrospective case series of adult patients at the Cleveland Clinic Foundation with histiocytic involvement of the GI tract identified on pathology specimens between 2007 and 2022, along with a systematic review of adult cases published on PubMed from 2002 to 2022. Extracted data included demographics, presenting symptoms, indications for endoscopy, anatomic distribution, endoscopic findings, associated conditions, and available immunohistochemical and molecular results. Results The institutional cohort included 108 patients (mean age 63.7 years; 60.2% female), of whom 35% were asymptomatic. Involvement spanned the esophagus to rectum, most commonly affecting the stomach. Endoscopic findings ranged from normal mucosa to polyps, nodules, and ulcerations. Nearly half of cases lacked definitive etiologic classification. Conclusions GI histiocytosis may be more common than previously appreciated but frequently remains incompletely evaluated in routine clinical practice. Integrating clinical context with targeted histologic assessment and selective molecular testing may help distinguish incidental reactive findings from clinically significant histiocytic disorders.