The aim is to propose and prospectively validate a diagnostic approach and model for prediction of mucinous versus non-mucinous, and malignant versus non-malignant pancreatic cysts using a combination of clinical, radiologic, and biomarker characteristics.

This combined cross-sectional and prospective single center clinical and translational study involves a collaborative multidisciplinary team composed of gastroenterologists, surgeons, radiologists, and basic scientists. Eligible patients with solitary or multiple pancreatic cysts referred for diagnostic evaluation and/or surgical treatment will undergo initial radiographic imaging with high-resolution CT, MRI/MRCP, and EUS/FNA as part of standard medical care at Johns Hopkins Hospital. This is a three-phase study.

In Phase I, eligible patients with pancreatic cysts will undergo initial radiographic imaging (high-resolution CT, MRI/MRCP, endoscopic ultrasonography (EUS) with fine needle aspiration (FNA)) as part of standard care at the Johns Hopkins Hospital. Patients will be categorized according to the presence of symptoms referable to the cyst or imaging features concerning for malignancy based on the initial radiographic assessment. Symptomatic patients, or those with concerning features, will be referred for surgical resection. The pathologic features and final diagnosis of resected pancreatic cysts will be compared with preoperative clinical, radiologic, and cyst fluid test results.

Asymptomatic patients with low-risk features at baseline radiographic and endoscopic imaging will enter Phase II. Patients will be followed on a prospective periodic surveillance schedule according the consensus clinical guidelines with either CT or MRI to monitor for new or metachronous cystic neoplasms. Those who develop symptoms or concerning features will have a repeat EUS/FNA as well as imaging with the opposite axial imaging modality, and will be referred for surgery if a suspicious lesion is detected.

Patients who have surgery either during Phase I or Phase II, will enter post-surgical surveillance (Phase III). Patients will be followed using a prospective periodic surveillance schedule according the consensus clinical guidelines with either CT or MRI to monitor for new or metachronous cystic neoplasms. Those who undergo surgery after surveillance in Phase II will continue with the imaging modality they were originally evaluated with prior to surgery.. Patients who develop symptoms or high-risk features on imaging will have a repeat EUS/FNA as well as imaging with the opposite axial imaging modality and will be referred for surgery if a suspicious lesion is detected. Samples will be collected prospectively for biomarker analysis. Cyst fluid, pancreatic juice and blood will be collected during EUS and blood will be collected yearly during the outpatient clinic visit. Patients will be followed for three years.

Inclusion Criteria:

1. Adult patients age 18 years and older
2. Referred for assessment of one or more pancreatic cyst.

Exclusion Criteria:

1. Medically ill patients with ASA class 4 or greater.
2. History of chronic kidney disease with a serum creatinine > 2.0 mg/dl or estimated glomerulofiltration rate (eGFR) < 30 ml/min, dialysis patients, acute renal failure, cirrhosis of the liver, chronic hepatitis, prior nephrectomy or kidney or liver transplantation.
3. History of moderate (generalized hives) or severe (facial swelling, airway reaction) reaction to intravenous radiographic contrast material.
4. History of obstruction in the upper GI tract such as esophageal or pyloric stricture, which would not allow passage of an endoscope.
5. Bleeding diathesis (clotting problems) or a history of thrombocytopenia (low platelet count <50,000).
6. Inability to provide informed consent.
7. Pregnancy or lactation.

Patients referred to Johns Hopkins for evaluation of pancreatic cysts