Presumed Intraductal Papillary Mucinous Neoplasms in Individuals at High Risk for Pancreatic Cancer
Tommaso Dall’Olio, Gabriele Capurso, Maria Terrin, Raffaele De Luca, Chiara Coluccio, Valentina Arcangeli, Anna Caterina Milanetto, Giovanni Butturini, Alberto Fantin, Luca Barresi, Giulia De Marchi, Andrea Galli, Marco Di Marco, Francesco Panzuto, Romano Sassatelli, Claudio Ricci, Francesco Maria Di Matteo, Elide Spinelli, Arianna Dal Buono, Margherita Patruno, Giulia Martina Cavestro, Elisa Venturini, Paolo Giorgio Arcidiacono, Roberto Salvia, Massimo Falconi, Silvia Carrara, Livia Archibugi, Salvatore Paiella, , Andrea Anderloni, Francesca Bergamo, Chiara Cristofori, Angelo De Padova, Nicolò De Pretis, Fabrizio Di Benedetto, Giulio Donato, Isabella Frigerio, Mattia Garutti, Paola Ghiorzo, Carlo Ingaldi, Alberto Larghi, Valeria Grazia Malagnino, Matteo Marasco, Claudio Pasquali, Marta Puzzono, Gabriele Rancatore, Erica Secchettin, Giuliana SereniImportance
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.
Objective
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.
Design, Setting, and Participants
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.
Exposure
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
Main Outcomes and Measures
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.
Results
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: χ
2
= 14.4;
Conclusions and Relevance
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.