Molecular Analysis of Pancreatic Cyst Fluid for the Management of Intraductal Papillary Mucinous Neoplasms

Pancreatic cancer is one of the most lethal human cancers. Early detection and diagnosis of precursor lesions for pancreatic malignancy is essential to improve the morbidity and mortality associated with this diagnosis. Of the cystic precursor lesions, branch duct intraductal papillary mucinous neoplasm (IPMN) is the most frequently identified lesion and has a wide range of malignant potential. Currently, Carcinogenic embryonic antigen (CEA) levels in the cyst fluid and cytology are the two most often utilized tools to diagnose these lesions; however, their diagnostic and risk stratification capabilities are somewhat limited. Within the last decade, the use of endoscopic ultrasound-guided fine-needle aspiration has opened the door for molecular analysis of cystic fluid as an option to enhance both the diagnosis and risk stratification of these lesions. The first step is to differentiate branch duct IPMNs from other lesions. KRAS and GNAS alterations have been shown to be accurate markers for this purpose. Following cyst type identification, mutational analysis, telomere fusion, microRNAs, long non-coding RNA, and DNA methylation have been identified as potential targets for stratifying malignant potential using the cystic fluid. In this review, we will examine the various targets of cyst fluid molecular analysis and their utility in the diagnosis and risk stratification of branch duct IPMNs.