Presenter: Samer AlMasri MD | University of Pittsburgh Medical Center Background: The uncinate process of the pancreas has a dominant drainage ductal system that can either empty into the accessory or main pancreatic ducts. Although several autopsy series have outlined the anatomical footprints for this independent drainage system, current international consensus guidelines of intraductal papillary mucinous neoplasms (IPMNs) still consider it as a branch duct, even though it is the main drainage system for a once independent portion of the pancreas. We hypothesized that, in addition to the well-defined high-risk criteria of IPMNs, dilation of the “dominant” uncinate duct (UDD) is associated with advanced neoplasia (high grade dysplasia /invasive cancer = HGD/IC) on final resection pathology, and may therefore be classified as an independent high-risk criterion. Methods: A retrospective review of patients who underwent surgical resection of a pancreatic IPMNs between 2008-2019 at our institution was performed. Preoperative imaging studies (pancreas protocol CT and /or MRI) were reviewed by an abdominal radiologist who was blinded to the final pathological Results. In addition to the Fukuoka criteria, we recorded whether there was any UDD irrespective of the location of the primary lesion. Using multivariate logistic regression, the pathological significance of UDD was determined. Results: A total of 260 patients were identified. The mean age at diagnosis was 67.9 years and 49.2% were females. Of the entire cohort, 122 (47%) had HGD/IC and 138 (53%) had non-invasive (low/intermediate grade dysplasia) disease in the surgical specimen. UDD was noted in 59 (22.7%) patients, of which 36 (61%) had invasive disease on pathological evaluation (P < 0.003). On multivariate logistic regression for the entire cohort, adjusting for size, main duct dilation, presence of enhancing mural nodule, bilirubin level and demographics, UDD was an independent predictor of invasive disease (OR= 2.99, P < 0.04). Subgroup analysis was performed on patients with main/mixed duct IPMNs and branch duct IPMNs with high risk criteria confined to the dorsal pancreas (n=170, 66.4%) in order to determine the pathological significance of UDD in these remote lesions. Even in this subgroup of patients, UDD was a significant predictor of HGD/invasive cancer (OR= 7.6, P < 0.004), suggesting it may be associated with an aggressive field effect. Conclusion: This is the largest study to date evaluating the significance of uncinate “dominant” duct dilation in IPMNs, and shows it to be a high-risk feature associated with HGD/IC. This association persisted for IPMNs limited to the dorsal pancreas, suggesting UDD may be associated with an aggressive “field effect”. Although these findings warrant validation with larger prospective studies, we recommend this feature be considered an additional high-risk criterion in IPMN, irrespective of the location of the cystic lesion.