Current clinical and research fluid biomarkers to aid risk stratification of pancreatic cystic lesions

Pancreatic cystic lesions (PCL) are composed of a heterogeneous group of entities that are increasingly diagnosed, generally as incidental findings in asymptomatic patients. In conjunction with this growing incidence, the potential for malignant transformation of mucin-producing cysts makes PCL a challenging clinical conundrum for the clinician, patient, and healthcare system. Cyst characterization based on morphology is often difficult and inaccurate, therefore several intracystic fluid biomarkers have been evaluated as ancillary testing to enhance the difficult balance between sparing a patient from an unnecessary high-risk pancreatic surgery and missing the opportunity to prevent or diagnose pancreatic adenocarcinoma at an early disease stage. There are two questions that are key to guide the care of patients with PCL: 1) is it a non-mucinous cyst that does not require any follow-up? and 2) if mucinous, does the cyst harbor advanced neoplasia (high-grade dysplasia or invasive carcinoma) that requires surgical resection, or is it a low-risk lesion that will benefit from a surveillance program? The purpose of this review is to give a general and practical overview of the different cyst fluid biomarkers that have been studied to address these specific questions, from classic biochemical markers to include carcinoembryonic antigen to novel genetic and epigenetic markers, such as microRNA or intracystic bacterial DNA.