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

Germline pathogenic variants grouped into three risk categories (Peutz-Jeghers syndrome or CDKN2A; BRCA2 or ATM; Lynch syndrome genes, BRCA1 or PALB2), compared with familial pancreatic cancer without a germline pathogenic variant

Pancreatic cystic lesions are common during surveillance of individuals at hereditary risk of pancreatic cancer, but whether their incidence and progression differ across genetic risk groups remained uncertain. This multicentre cohort study, conducted from January 2016 to December 2025 at 25 centres of the Italian Registry of Families at Risk of Pancreatic Cancer, compared familial pancreatic cancer without a germline pathogenic variant with three categories of germline pathogenic variant carriers: PGV1 (Peutz-Jeghers syndrome or CDKN2A variants), PGV2 (BRCA2 or ATM) and PGV3 (Lynch syndrome genes, BRCA1 or PALB2). Among 1,688 high-risk individuals (median age 56 years, 62.5% women), 496 (29.4%) had a presumed intraductal papillary mucinous neoplasm (IPMN), and 124 of the 1,298 participants without a cyst at baseline (9.6%) developed an incident lesion over a median follow-up of 17 months. In a complete-case multivariable analysis (1,245 participants, 123 events), PGV1 (adjusted HR 1.82; 95% CI 0.97-3.43), PGV2 (0.81; 0.45-1.45) and PGV3 (0.70; 0.34-1.44) were not associated with incident cyst development compared with familial pancreatic cancer, whereas older age was (adjusted HR per year 1.04; 1.02-1.05). Trajectories of cyst growth and main pancreatic duct diameter did not differ across groups, progression to worrisome features or high-risk stigmata was infrequent (13 patients, 2.6%), and the authors consider longer follow-up necessary to assess potential gene-specific differences.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This is chiefly a negative result: neither cyst incidence nor cyst growth differs significantly across genetic risk categories, and only age is associated with the appearance of a cyst (adjusted HR 1.04 per year). It reassures on the rarity of short-term progression (13 patients, 2.6%), but it does not prove the absence of a difference: median follow-up is only 17 months, the PGV1 interval (adjusted HR 1.82; 95% CI 0.97-3.43) comes close to significance, and the abstract does not give the number of carriers in each category. It therefore does not justify adapting surveillance to the genetic category now, the authors themselves awaiting longer follow-up to detect any gene-specific differences.

Analysis by Dr Thibaut Benquey