Clinicopathological Evaluation of Terminal Ileal Nodular Lymphoid Hyperplasia in Adults: A Single-Center Experience

Background/Objectives: Terminal ileal nodular lymphoid hyperplasia (NLH) can mimic Crohn’s disease endoscopically, and data integrating its clinical, laboratory, endoscopic, and histopathological features in adults are limited. We aimed to describe these features and associated conditions. Methods: This retrospective single-center study included adults who underwent colonoscopy between January 2023 and December 2025 with terminal ileal biopsy for endoscopically suspected NLH; histopathological confirmation was required for inclusion. Giardia lamblia (G. lamblia)–positive and –negative patients were compared as a secondary exploratory analysis. Results: Histology confirmed NLH in 50 of 64 biopsied patients (78.1%); 43 with essential inclusion data were analyzed (mean age 35.1 ± 12.0 years; 67.4% male); fecal calprotectin was available in 40. Diarrhea and abdominal pain were leading indications. Findings were predominantly reactive, with no morphological features of lymphoma; one patient with Crohn’s-suggestive features was subsequently diagnosed with Crohn’s disease. No patient had hypogammaglobulinemia or positive celiac serology. G. lamblia infection (10/43, 23.3%) was associated with higher fecal calprotectin (median 36.5 vs. 9.0 µg/g; p = 0.016). Conclusions: On routine histology, adult terminal ileal NLH appears predominantly benign and reactive; however, endoscopic appearance alone was insufficient for diagnosis in one fifth of cases. The G. lamblia–calprotectin association is exploratory and requires confirmation.