EP496 - Possible New Polyposis Syndrome: Multiple ileal adenomas and colon polyps with pancreatic neoplasm

Purpose/Background: Small bowel tumors account for approximately 0.5% to 2% of all gastrointestinal tumors with adenomas being the most common. Their reported incidence decreases as you move distally in the small bowel. The ileum is the most uncommon site, and lesions often remain asymptomatic. These lesions are often incidentally discovered during the workup for anemia or nonspecific gastrointestinal complaints. Multiple synchronous ileal adenomas with high-grade dysplasia are exceedingly uncommon and would raise a concern for a hereditary cancer syndrome. The absence of testable pathogenic germline mutations in this case suggests a yet undescribed genetic syndrome.

Methods/Interventions: A 63-year-old woman with a history of iron deficiency anemia, has been undergoing colonoscopies every 3 years due to persistent colonic polyps. In 2024 she underwent a CT enterography due to persistent iron deficiency anemia which was notable for nodular lesions in the distal ileum and pancreatic cystic lesions. She underwent an EGD and colonoscopy which identified two duodenal tubular adenomas and a terminal ileal adenoma with focal high-grade dysplasia. Subsequent MRI confirmed a side-branch intraductal papillary mucinous neoplasm (IPMN). She was discussed in gastrointestinal tumor board and the patient was recommended for ileocolonic resection. In August 2024 the patient underwent a robotic ileocolectomy with intracorporal anastomosis, with final pathology revealing more than 10 tubular and tubulovillous adenomas in the terminal ileum, three with extensive high-grade dysplasia andsmall adenomas noted in both resection margins. Surveillance colonoscopy in January 2025 demonstrated recurrent ileal polyp and in April 2025 she underwent an open ileocolonic resection with intraoperative enteroscopy to determine the proximal resection margin. Tumor markers, including CEA, CA 19-9, and AFP, were within normal limits postoperatively. Due to recurrent adenomas, the patient underwent 76 gene CancerNext-Expanded® genetic testing which revealed no clinically significant variants.

Results/Outcomes: This case illustrates a rare presentation of multifocal ileal adenomas with high-grade dysplasia occurring with pancreatic IPMN and colonic polyps. Small bowel adenomas are well described in hereditary syndromes such as familial adenomatous polyposis (FAP), with a rate of 5%-30%; however, the presence of these polyps was associated with more advanced duodenal polyposis. The specific frequency of ileal adenomas associated with genetic syndromes remains poorly defined, with rates reported in small sample sizes. In this patient, the coexistence of multiple ileal and colonic adenomas, absence of germline mutations, and synchronous pancreatic pathology raises the possibility of a yet-uncharacterized polyposis syndrome. The challenges of surgical management, high recurrence risk, and limited genetic guidance underscore the importance of vigilant endoscopic surveillance.

Conclusion/Discussion: This case highlights the diagnostic and therapeutic complexity of multifocal ileal adenomas with high-grade dysplasia and colon polyps in the absence of identifiable germline mutations. The combination of recurrent ileal adenomas, colonic polyps, and pancreatic IPMN suggests a possible novel polyposis syndrome.