Abstract Background Benign and malignant lesions can be found in the anus or at the anorectal junction. Pinch biopsies obtained during endoscopy enhance our understanding of disease and facilitate scientific advancement. However, due to concerns about pain and bleeding from mucosa-adjacent hemorrhoidal vessels, many endoscopists have been trained not to biopsy below the anorectal junction. A better understanding of the safety and tolerability of endoscopic anal biopsies is critical to improve the diagnostic yield of endoscopy and to facilitate further research. Methods We recruited 124 patients with inflammatory bowel disease (114 with Crohn’s disease (CD) and 10 with ulcerative colitis) who presented for standard-of-care (SOC) colonoscopy as part of an ongoing multi-’omic study of perianal CD. All procedures were performed with propofol-based sedation. Forward and retroflexed views of the anorectal junction were obtained under standard high-definition white light and narrow band imaging (Figure 1). Two biopsies each were obtained from the distal rectum and anus and were stored for future analysis. In addition, all patients had a SOC biopsy of the rectum, and 17 patients had a biopsy of the anus to confirm proper targeting of biopsies and to evaluate for histopathological variations in the mucosa. Patients were systematically assessed for perianal pain or bleeding prior to discharge from the procedure unit and again by phone call 24 hours later. Results All rectal biopsies were confirmed to contain rectal mucosa when evaluated by expert gastrointestinal (GI) pathologists. Additionally, 16/17 (94.12%) anal biopsies contained squamous mucosa (one biopsy contained only mucin). Transitional epithelium was identified in 2 patients. Two of 124 (1.61%) patients noted transient pain and bleeding that resolved without intervention. This rare adverse event did not occur in the patients that had 3 anal biopsies and could not be definitively linked to study-related sampling of the anal mucosa. Conclusion Office-based sedated endoscopic biopsy of the anal mucosa is safe and well tolerated. Our study confirmed that the anal canal contains predominantly squamous mucosa. However, we identified a short segment of transitional mucosa in two of 17 patients, highlighting heterogeneity in this region that should be further defined and accounted for in studies evaluating the anal transcriptome in health and disease1. Given the safety findings of this study of sedated patients, we believe that endoscopists can sample anal mucosa when clinically appropriate or for research purposes. Reference: 1. Tanaka E, Noguchi T, Nagai K, et al. Morphology of the epithelium of the lower rectum and the anal canal in the adult human. Méd Mol Morphol 2012;45:72–79. Conflict of interest: McDonald, Benjamin: Consultant for Iterative Health Klein, Jeremy: None Capucci, Lauren: No conflict of interest Liu, Cambrian: No conflict of interest Alpert, Lindsay: No conflict of interest Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx.
McDonald et al. (2026) studied this question.