BACKGROUND & AIMS: Inflammatory bowel disease (IBD) may increase risk of small bowel cancer (SBC). However, little is known of the characteristics and features of IBD-SBC, due to a low number of cases worldwide. We performed a population-based study of IBD and SBC to calculate risk and increase our understanding of clinical characteristics and histopathological and molecular features.

METHODS: The study population consisted of all individuals aged 16 years or older living in Denmark during 1978-2010. Through linkage between national registers and subsequent scrutiny of medical records and pathology descriptions, we identified 40 cases of IBD-SBC. Risk was calculated by standardized incidence ratio (SIR) (observed/expected); patient characteristics were derived from medical files, and surgery specimens were obtained from hospitals nationwide for histopathological and molecular analyses.

RESULTS: During 241,620 person-years of follow-up, 23 patients with Crohn's disease developed small bowel adenocarcinoma (SIR, 14.38; 95% confidence interval, 8.78-22.20) and 9 developed neuroendocrine tumors (SIR, 6.83; 95% confidence interval, 3.13-12.97). No significantly increased risk of SBC was found among patients with ulcerative colitis. Most patients with SBC had moderate-to-severe Crohn's disease with small bowel and upper gastrointestinal involvement. Assessment of surgical specimens of small bowel adenocarcinomas revealed a clear transition from inflammation to dysplasia and cancer, whereas no tumors had evidence of microsatellite instability.

CONCLUSIONS: In a population-based study of patients in Denmark with IBD and SBC, we found risk of adenocarcinomas and neuroendocrine tumors to be increased among persons with Crohn's disease. Most patients with IBD-SBC had extensive IBD of moderate-to-severe activity. Adenocarcinomas appeared to develop via an inflammation-dysplasia-carcinoma pathway, but differed from IBD-related colorectal adenocarcinomas in their molecular features.