Neuroendocrine neoplasms diagnosed in the setting of inflammatory bowel disease: A systematic review and proposed management algorithm.
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BACKGROUND: Patients with inflammatory bowel disease (IBD) are at higher risk of developing malignancies, including neuroendocrine neoplasms, but the specifics of that are not well known. We reviewed the existing literature to map the evidence surrounding this phenomenon. METHODS: Following PRISMA 2020 guidelines, we searched PubMed from inception to September 2024 for patients with gastrointestinal neuroendocrine neoplasms (NENs) and either Crohn disease (CD) or ulcerative colitis (UC). Eligible studies included case reports, case series, and larger retrospective IBD cohorts. We extracted demographic and clinical data including tumor grade, location, metastatic status, and mode of detection. Comparative analyses between UC and CD were performed using Fisher exact test, chi-square test, and independent t-tests. RESULTS: We identified 67 case studies with data available for a total of 108 patients (61.1% male), ranging from 14 to 87 years of age. The median duration from IBD diagnosis to NEN detection was 13 years. Fifty-five (50.9%) patients had CD and 53 (49.1%) had UC. UC patients were older at NEN diagnosis (mean 49 vs 40 years, P = .004) and had a higher metastatic rate (39.6% vs 18.2%, P = .019). Most NENs were low-grade (69.4%), while 20.4% were high-grade and 8.3% were mixed. The most common tumor locations were the rectum (29.6%) and appendix (27.8%), with rectal and colonic NENs more prevalent in UC and small bowel or appendiceal NENs more common in CD. At diagnosis, 71.3% of patients had localized disease. For high-grade NENs, 86.4% of cases were metastatic, compared to 9.3% for low-grade tumors. Only 10.2% of NENs were detected via endoscopic surveillance. CONCLUSIONS: NENs in IBD show distinct patterns by IBD type, with significant differences in tumor location, grade, and metastatic rates between UC and CD. These hypothesis-generating observations suggest heightened vigilance after approximately 10 years of IBD or around age 44, focusing on rectal lesions in UC and small bowel/appendiceal lesions in CD. Validation in prospective, population-based studies is needed before these findings can inform clinical practice.