Serous cystadenoma (SCA): SCAs make up about 16% of all resected pancreatic cysts [2]. They tend to present as isolated lesions. Classic SCAs are composed of multiple cysts with a “honeycomb” appearance and a characteristic central fibrotic scar [2, 4]. These cysts occur in patients over 60 years of age, and they have a male predominance if macrocystic and female predominance if microcystic [4]. SCAs are usually hypervascular [4] and lined by cuboidal epithelium [2]. They can occasionally present with abdominal pain, but most frequently they are asymptomatic. A small fraction of SCAs are secondary to mutation in VHL (von Hippel Lindau gene). SCAs generally require resection only if they are causing symptoms due to size rather than concern for malignancy [2]. See Figs. 5.3 and 5.4.

Solid pseudopapillary neoplasia (SPN): These are rare (3% of all resected pancreatic cysts) tumors found almost exclusively in women in their 20s and 30s who are symptomatic on presentation with abdominal pain or, less frequently, jaundice or pancreatitis. Risk of malignancy is 10–20% and warrants surgical resection [2, 4]. Five-year postoperative survival is 80%, with rare recurrences noted up to a decade after initial presentation [2]. See Figs. 5.5 and 5.6.

Cystic pancreatic endocrine neoplasm (CPEN): Rarely, pancreatic neuroendocrine tumors may be cystic rather than solid. These tumors generally occur after age 50 and are found equally in women and in men. They are associated with multiple endocrine neoplasia (MEN-1) syndrome and the MEN-1 gene mutation. On imaging they reveal enhancement of the cyst wall. Cyst fluid positive for chromogranin A and synaptophysin is both a sensitive and specific finding in these patients. Once disease is confirmed, most patients undergo resection with survival rate of over 87% at 5 years. Risk of malignancy with these tumors is 11–14% [2].

Based on the findings in our patient, her most likely diagnosis is BD-IPMN, although an MCN or a serous cyst (SCA, CPEN) cannot be excluded. Of note, lack of history of pancreatitis makes a pseudocyst unlikely.

Our patient underwent an abdominal MRI as part of her initial workup. Abdominal imaging with an MRI (with or without contrast) or with a pancreas protocol CT is the first step in both characterizing and risk stratifying the lesion [1–6]. If the diagnosis is still uncertain based on clinical and imaging findings, or if there are additional risk factors, an endoscopic ultrasound with fine needle aspiration (EUS/FNA) may be pursued. Risk factors that prompt further workup include symptomatic initial presentation with obstructive jaundice or pancreatitis, main duct dilation (diameter of 5–9 mm is considered worrisome, while >10 mm is high risk), cyst size >3 cm, and a mural nodule within the cyst [1, 2, 5, 6]. According to the 2012 International Association of Pancreatology guidelines, one risk factor is sufficient to recommend EUS, while the 2015 American Gastroenterological Association guidelines require at least two risk factors [1]. In the case of our patient, her cyst size and possible mural nodule warrant a referral for EUS/FNA.

EUS/FNA can help visualize the cyst better, evaluate possible connections to the pancreatic ducts, visualize a potential mural nodule, and sample the cyst fluid for cytology. EUS/FNA results are still largely operator dependent [1, 5]. Findings on FNA may also vary significantly; thus, the presence of a marker can help classify cysts better, but the absence of one is more difficult to interpret. A useful finding on FNA is the presence of a “string sign” (when cystic fluid stretches between two surfaces over 1 cm), which is highly specific for mucinous cysts [1, 4]. Low amylase levels in the fluid rule out a pseudocyst; however, high levels of amylase are seen in both pseudocysts and in mucinous cysts [1, 4]. CEA levels on cytology are helpful if elevated over 192–200 ng/ml in identifying mucinous cyst (MCN or IPMN), as they are typically low in serous cysts or pseudocysts; CEA is not a predictor of malignancy, however [1, 2, 4–6]. Further, while cytology findings are rare, they can be highly specific, especially if atypical epithelial cells are found [1, 5]. Mutations in GNAS or KRAS are very specific for IPMNs (>90%, with one of the two mutations present in over 95% of all IPMNs), but these findings have not been fully validated and are not used on a daily basis [1, 4–7]. Finally, work is underway to identify additional markers within the cyst fluid, such as miRNAs and VEGF [2, 5, 7].