S3556 Duodenal Fistulization of Main Duct IPMN: A Rare Indicator of Invasive Transformation

Introduction: Main duct intraductal papillary mucinous neoplasms (MD-IPMNs) are a subtype of pancreatic cystic neoplasms with a well-established potential for malignant transformation. Although a rare finding, spontaneous fistulization of IPMNs into the gastrointestinal (GI) tract may indicate advanced histologic progression. We present a case of an MD-IPMN fistulizing into the duodenum, ultimately found to be invasive mucinous adenocarcinoma following surgical resection. Case Description/Methods: A 70-year-old man with a known history of pancreatic cystic lesion presented with abdominal pain, nausea and weight loss. Computed tomography imaging showed a heterogeneous 5.5 × 3.8 × 4.5 cm cystic mass lesion with pancreatic duct dilation (up to 12 mm), parenchymal atrophy, and scattered calcifications within the pancreatic body, likely due to chronic pancreatitis. Endoscopic ultrasound was performed, and a 4.1 × 3.3 cm heterogeneous cystic lesion was identified in the pancreatic head with ill-defined borders and communication with the pancreatic duct. Fine-needle aspiration (FNA) revealed a mucinous neoplasm with low- to intermediate-grade dysplasia. Furthermore, a 2 cm excavated area containing mucinous material was seen endoscopically in the distal duodenal bulb. Biopsy of this area showed mucinous columnar epithelium with papillary architecture and low-grade dysplasia, concerning for MD-IPMN with spontaneous fistulization. Patient underwent a Whipple procedure. Final pathology showed moderately differentiated invasive mucinous adenocarcinoma arising from IPMN. At 6-month follow-up, he remained asymptomatic and was tolerating adjuvant chemotherapy. Discussion: Fistula formation of MD-IPMNs into adjacent organs may signal more aggressive disease biology and is often associated with high-grade dysplasia or invasive carcinoma. Proposed mechanisms for fistula formation include mucin hypersecretion, chronic inflammation, and enzymatic autodigestion. Presence of tumor cells near the fistula tract may reflect direct invasion and a worse prognosis. Extended resection, such as pancreaticoduodenectomy, is often necessary for margin clearance. This case highlights the importance of recognizing GI fistulization as a marker of advanced MD-IPMN, warranting early evaluation for surgical resection even when cytology from FNA suggests low or intermediate-grade dysplasia.