Accurate risk stratification of intraductal papillary mucinous neoplasms ( IPMNs ) remains challenging, particularly in mixed-type lesions without overt high-risk stigmata. In this large multicenter cohort study, cyst fluid next-generation sequencing (NGS) was used to compare molecular profiles of mixed-type and branch-duct IPMNs. Mixed-type IPMNs (main pancreatic duct 5–9 mm) demonstrated significantly higher rates of high-risk mutations —particularly in TP53, SMAD4, and mTOR —and a greater co-occurrence of multiple high-risk alterations compared with branch-duct IPMNs.
Importantly, mixed-type morphology emerged as an independent predictor of high-risk mutations, and preoperative cyst fluid NGS showed excellent diagnostic accuracy for identifying advanced neoplasia, outperforming traditional “worrisome feature” criteria in specificity. These findings highlight the biological…
