Presumed Intraductal Papillary Mucinous Neoplasms in Individuals at High Risk for Pancreatic Cancer

Pancreatic cystic lesions are common during surveillance of individuals at hereditary risk for pancreatic cancer, but whether their incidence and progression differ across genetic risk groups remains uncertain.

To compare the incidence, morphologic characteristics, and progression of presumed intraductal papillary mucinous neoplasms (IPMNs) in individuals at high risk of PC across hereditary risk groups.

This multicenter cohort study was conducted from January 2016 to December 2025 at 25 centers participating in the Italian Registry of Families at Risk of Pancreatic Cancer. Participants were individuals undergoing pancreatic surveillance with magnetic resonance imaging with cholangiopancreatography and/or endoscopic ultrasonography.

Familial pancreatic cancer without pathogenic germline variants vs pathogenic germline variant (PGV) carrier status, further grouped into 3 predefined categories: PGV1 (Peutz-Jeghers syndrome or CDKN2A sequence variant carriers), PGV2 (BRCA2 or ATM variant carriers), and PGV3 (Lynch syndrome-associated genes or BRCA1 or PALB2 variant carriers).

Cumulative incidence of presumed IPMNs, longitudinal changes in index cyst diameter and main pancreatic duct diameter, and progression to worrisome features or high-risk stigmata. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) for incident IPMNs, adjusted for hereditary risk, age, sex, body mass index, tobacco smoking status, and diabetes.

Among 1688 high-risk individuals (median age, 56 years [IQR, 50-64 years]; 1055 women [62.5%]), 496 (29.4%) had a presumed IPMN. Median follow-up from enrollment was 17 months (IQR, 0-36 months). A total of 1298 participants (76.9%) did not have a presumed pancreatic cyst at baseline, and 124 (9.6%) of these participants developed an incident lesion during follow-up. In the complete-case multivariable analysis of 1245 participants and 123 events, PGV1 (adjusted HR [AHR], 1.82; 95% CI, 0.97-3.43), PGV2 (AHR, 0.81; 95% CI, 0.45-1.45), and PGV3 (AHR, 0.70; 95% CI, 0.34-1.44) were not associated with incident cyst development compared with FPC, whereas older age was associated with higher incidence (AHR per year, 1.04; 95% CI, 1.02-1.05). Longitudinal trajectories of cyst growth (time × group interaction: χ2 = 14.4; df = 15; P = .49) and main pancreatic duct diameter (time × group interaction: χ2 = 4.35; df = 15; P > .99) did not differ significantly across groups, and progression to worrisome features or high-risk stigmata was infrequent (13 patients [2.6%]).

In this multicenter cohort study of individuals at high risk of PC who were undergoing pancreatic surveillance, the incidence and short-term progression of presumed IPMNs did not differ significantly across hereditary risk groups, whereas older age was associated with incident cyst development. Longer follow-up appears to be needed to assess potential gene-specific differences.