Identifying Neoplastic Versus Non-neoplastic Pancreatic Cystic Lesions—What Is the Current Evidence?

The widespread use of modern, high-resolution cross-sectional imaging has led to increased detection of pancreatic cystic lesions (PCLs), which have varying malignant potential. While most require periodic radiographic surveillance, some warrant biopsy or surgical excision. We conducted a narrative review of the literature focusing on the diagnostic accuracy of imaging and the role of endoscopic and molecular tools in PCL evaluation. Cross-sectional imaging correctly classifies cyst type based on morphological features in approximately 50% of cases, with MRI generally outperforming CT. Endoscopic ultrasonography (EUS) is particularly useful when clinical and imaging findings are inconclusive or when high-risk features are present. In selected cases, such features may prompt direct surgical intervention. EUS-guided fine-needle aspiration of cyst fluid for chemical, genetic, and cytological analysis helps differentiate neoplastic mucinous cysts-such as intraductal papillary mucinous neoplasms and mucinous cystic neoplasms-from benign, non-mucinous cysts. Accurate diagnosis of PCLs requires a multimodal approach combining high-quality imaging, EUS evaluation, and cyst fluid analysis. Advances in biomarker development hold promise for improving risk stratification and guiding individualized management strategies.