Introduction
Presumed branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs), are the most frequent abnormal finding during pancreatic surveillance of high-risk individuals (HRIs). However, whether their prevalence and behavior differ according to hereditary background remains unclear.
Aims & Methods
We compared the prevalence, morphologic characteristics, and progression patterns of suspected IPMNs between genetically tested familial pancreatic cancer (FPC) individuals and carriers of pathogenic germline variants (PGVs) enrolled in the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC). This multicenter observational study included HRIs undergoing surveillance with MRI/MRCP and/or endoscopic ultrasound (EUS) at 25 sites joining IRFARPC from 2016 to 2025. FPC individuals testing negative for PGVs were compared with PGV carriers, further grouped into three predefined categories. Baseline clinical and imaging features were analyzed descriptively. The cumulative incidence of incident IPMN was assessed using the Kaplan-Meier method and age-adjusted Cox regression. Longitudinal changes in index cyst diameter and main pancreatic duct (MPD) diameter were modeled using mixed-effects spline models. The occurrence of worrisome features/high-risk stigmata (WF/HRS) was evaluated using cumulative incidence analysis.
Results
Among 1,672 HRIs, 496 (29.7%) individuals with suspected IPMN were included (364, 73.4% FPCs, and 132, 26.6%, PGVs). Baseline demographic, clinical, and cyst characteristics were similar between the groups, although prior cancer history and EUS use were more common among PGV carriers. In the at-risk cohort of 1,298 individuals free of suspected IPMN at baseline, 124 (9.5%) developed a suspected IPMN during follow-up, with no significant between-group differences in cumulative incidence. In the age-adjusted analysis, no PGV subgroup showed a significantly higher risk than FPC, whereas increasing age was independently associated with incident cyst development (HR 1.03, 95% CI 1.02-1.05; p<0.001). Longitudinal trajectories of index cyst diameter and MPD diameter did not differ significantly across hereditary groups, and progression to WF/HRS was infrequent overall. Only two patients underwent surgery, revealing one invasive IPMN-associated carcinoma (PGV patient) and one mixed-type IPMN with low-grade dysplasia (FPC patient).
Conclusion
In this multicenter surveillance cohort, suspected IPMNs showed similar baseline characteristics and short- to mid-term imaging behavior across hereditary risk groups. Age appeared more relevant than genetic subgroup in incident lesion development, supporting surveillance strategies primarily guided by imaging phenotype and interval changes.
