Abstract
A precise diagnosis of the nature of pancreatic cystic neoplasm (PCN) is crucial since it determines the patients in need of rapid surgical resection as well as those who can be followed up, and, accordingly, the frequency and modalities of surveillance. Endoscopic ultrasound (EUS) and especially fine needle aspiration (FNA) are invasive methods, with specific adverse events occurring in 2.7-5%. Thus, they should only be used as a third-line tool in the absence of characteristic radiographic features on computed tomography (CT) scan and magnetic resonance imaging (MRI). The most difficult aspects of differential diagnosis are: intraductal papillary mucinous neoplasm (IPMN) versus chronic pancreatitis; unifocal IPMN versus serous cystic neoplasm (SCN); macrocystic SCN versus mucinous cystic neoplasm (MCN); cystic neuroendocrine tumors versus MCN; solid serous cystadenoma versus neuroendocrine tumors versus small solid pseudopapillary tumors; pseudocyst versus MCN; low-grade, high-grade, or invasive IPMN. When classical radiological and EUS features are not conclusive, EUS-FNA may be helpful by analyzing cytological, chemical, and/or molecular data. The addition of EUS-FNA to CT scan and MRI increased the overall accuracy for diagnosing PCN by 36 and 54%, respectively. Analysis of molecular markers in pancreatic cyst fluid might increase the limited accuracy of EUS-FNA by using cytology and chemical and/or tumor marker analysis alone. Current evidence suggests that contrast-enhanced EUS (CH-EUS) is highly accurate for distinguishing non-neoplastic cysts from neoplastic cysts. CH-EUS might also be useful for distinguishing mural epithelial nodules from mucinous clots. Needle-based confocal laser endomicroscopy (nCLE) images a target tissue at a subcellular level of resolution, providing real-time in-vivo optical biopsy. nCLE is feasible during EUS-FNA and allows in-vivo diagnosis of PCN with high accuracy. In conclusion, EUS is a third-line tool in the diagnosis of PCN. Clinical context as well as careful evaluation of CT scan and magnetic resonance cholangiopancreatography images by specialized radiologists are crucial in the diagnosis process. Nowadays it is inconceivable to skip these steps.