Blood and Cyst Fluid Biomarkers in Pancreatic Cystic Lesions

Pancreatic cystic lesions (PCLs) present a diagnostic challenge due to their heterogeneous nature and variable malignant potential. Accurate differentiation between benign and malignant cysts is critical for guiding management and preventing overtreatment. This chapter reviews the current landscape of blood and cyst fluid biomarkers for the risk stratification of PCLs. Blood-based markers such as CA 19-9, CEA, circulating cell-free DNA, and microRNAs offer noninvasive diagnostic options, though their clinical utility remains limited by sensitivity and specificity constraints. Cyst fluid analysis, particularly carcinoembryonic antigen (CEA), glucose, and amylase, continues to play a pivotal role in distinguishing mucinous from nonmucinous cysts. Advances in molecular diagnostics, including next-generation sequencing for KRAS and GNAS mutations, and emerging biomarkers such as Das-1 and microRNA panels, promise improved accuracy in identifying high-risk lesions. Despite these developments, no single biomarker reliably predicts malignancy, underscoring the need for integrated approaches combining imaging, cytology, and molecular analysis. Future research should focus on validating novel biomarkers and developing cost-effective algorithms to enhance preoperative risk stratification and optimize patient management.