A biannual pancreatic cancer surveillance program identifies a high prevalence of intraductal papillary mucinous neoplasms: accelerated malignant transformation in Peutz-Jeghers syndrome

Abstract

Presenter: Yifan Wang MD | McGill University Background: Individuals with a family history of pancreatic adenocarcinoma (PC) or with a germline mutation in a PC susceptibility gene are at higher risk of developing PC. Surveillance of high-risk individuals (HRIs) may allow earlier detection of PC and its precursor lesions. Since advanced-stage PCs have been reported despite annual surveillance, shorter interval surveillance may be justified. Methods: From 2013 to 2020, asymptomatic HRIs were enrolled in a PC surveillance program alternating between magnetic resonance imaging and endoscopic ultrasound every 6 months. Results: Of 75 HRIs enrolled, 43 (57.3%) had a germline mutation in a PC susceptibility gene (GS), and 32 (42.7%) had a familial pancreatic cancer (FPC) pedigree. Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) were identified in 26 (34.7%) individuals, but only 2 developed progressive lesions. Despite biannual surveillance, one patient with Peutz-Jeghers syndrome (PJS) developed locally advanced PC arising from a BD-IPMN. Whole genome sequencing of this patient’s PC and of a second PJS-associated PC from the kindred revealed that both tumours were driven by biallelic inactivation of STK11 in a KRAS-independent manner. From a review of 3,853 patients across two PC registries, we identified one additional PJS patient with PC. Importantly, all 3 PJS patients developed advanced PC consistent with malignant transformation of an underlying BD-IPMN in < 6 months. The other surveillance patient with a progressive lesion had FPC and underwent resection of a mixed-type IPMN which harboured polyclonal KRAS mutations. Furthermore, we found that colloid-type PCs, which develop from IPMNs, display COSMIC signature 17. Conclusion: Biannual PC surveillance identifies a high rate of BD-IPMNs in HRIs, but only a minority of these progress to PC. Our findings suggest that BD-IPMNs in patients with PJS are at risk of rapid malignant transformation. In PJS individuals, a lower threshold for resection of BD-IPMNs may be more effective than shortening surveillance intervals.