Main pancreatic duct (MPD) dilatation in patients with intraductal papillary mucinous neoplasms (IPMN) is a known risk factor for malignancy, yet its predictive value remains debated, especially in non-resected patients. We aimed to evaluate whether endoscopic ultrasound (EUS) features of the MPD can predict malignancy in patients with cyst-associated MPD dilatation.

We retrospectively analyzed 231 patients who underwent EUS for pancreatic cysts with MPD dilatation (≥5 mm). Malignancy was defined as high-grade dysplasia (HGD) or invasive carcinoma (IC) in resected patients, or progression to cancer/metastases during ≥12 months of follow-up. EUS features (diameter, wall thickening, content, course, nodules) were reviewed by two blinded endosonographers. Statistical analysis included logistic regression, ROC curves, and Kaplan–Meier survival estimates.

Among 231 patients, 88 underwent surgical resection and 141 were managed with surveillance. Malignancy was diagnosed in 70 patients (67 surgical, 3 during follow-up). Malignant patients were younger than non-malignant ones (65.2 ± 10 vs 68.7 ± 9.6 years, p=0.023). On univariate analysis, several EUS features were significantly associated with malignancy: thickened MPD walls (30% vs 16%, p=0.034), inhomogeneous ductal content (54% vs 31%, p=0.002), tortuous ductal course (56% vs 37%, p=0.014), and presence of nodules (23% vs 7%, p=0.003). MPD diameter was higher in malignant cases (8.2 ± 3.3 mm vs 7.5 ± 4.4 mm), but not statistically significant (p=0.242). In multivariate analysis, inhomogeneous content (OR=2.10, p=0.054) and nodules (OR=2.53, p=0.086) showed trends toward independent association with malignancy. The logistic regression model incorporating EUS features yielded an area under the ROC curve (AUC) of 0.783 (95% CI: 0.556–1.00; p=0.014), indicating good discriminative ability. In the surveillance subgroup, 3 patients progressed to advanced PDAC during follow-up. Kaplan–Meier analysis showed a gradual decline in progression-free survival, with approximately 30% of patients experiencing progression at 36 months.

EUS features such as inhomogeneous MPD content and nodules were associated with malignancy in IPMN patients with ductal dilatation. These findings suggest that detailed ductal morphology may enhance risk stratification beyond duct diameter alone, supporting its integration into clinical decision-making.