Pancreatic Cysts
Written by Djuna Cahen
Pancreatic cystic lesions are common. Their prevalence ranges from 2% to 15% on imaging studies, but autopsy findings suggest it may be as high as 50%. The two most prevalent benign lesions, pseudocysts and serous cystadenomas (SCA), account for 15 to 25% of these cysts. The dominant lesions with malignant potential are the two mucinous cyst types: intraductal papillary mucinous neoplasms (IPMN), which account for about half of the cysts, and the less common mucinous cystic neoplasms (MCN).1-4
During the last decades various cyst guidelines have been published, which were mostly based on expert opinions. They emphasize the importance of identifying high-risk cysts and performing timely surgery before cancer develops. However, distinguishing between high-risk and low-risk or benign cysts is a challenge.3, 5, 6
Diagnostic process and risk stratification
Cyst types
Pseudocysts: These benign cysts form after acute or chronic pancreatitis and typically appear as unilocular cysts that may contain debris. They are often connected to the pancreatic duct, although this is difficult to confirm. If a pancreatic cyst is found at the onset of pancreatitis, one should consider it to be the cause rather than the consequence of the condition. Most pseudocysts resolve on their own and intervention is only needed for symptomatic cases.1
Serous Cystadenomas: These benign, slow-growing cysts mostly affect women aged 50-70 years. They typically appear as microcystic (honeycomb) lesions, but can also be solid, macrocystic, or unilocular. A central scar is a distinctive feature, but is only seen in 30% of cases. While they are mostly asymptomatic, larger cysts can cause symptoms like pain, pancreatitis, or biliary obstruction. 1
Mucinous Cystic Neoplasms (MCNs): Less common than IPMNs, MCNs primarily affect women in their 40s to 60s. They are single, thick-walled, unilocular cysts found in the distal pancreas, which do not communicate with the pancreatic ducts, unlike IPMNs. Rare peripheral (egg-shell) calcifications are a hallmark. The risk of cancer in MCNs is typically 5-15%, despite earlier reports suggesting higher risks.1
Intraductal Papillary Mucinous Neoplasms (IPMNs): IPMNs are the most common mucinous cysts having a peak incidence in the 50s-70s7. They are classified into main-duct, branch-duct, or mixed-type IPMNs. Main-duct IPMNs cause dilatation of the main duct and are characterized by a “fish-mouth papilla” on endoscopy. Branch-duct IPMNs often form clusters of branch-duct dilatation, while the mixed-type involves both main- and branch ducts. IPMNs are usually asymptomatic, but a small percentage may cause pain or pancreatitis. The risk of malignancy varies, with branch-duct IPMNs ranging from 1-38% and main-duct types between 33% and 85%.1
Solid Pseudopapillary Neoplasms (SPNs): These rare lesions predominantly affect young women, typically in their 20s or 30s. They can occur throughout the pancreas and appear as well-demarcated lesions with both solid and cystic components, sometimes with irregular calcifications. On histology, 10-15% of SPNs are solid pseudopapillary carcinoma, but these have a low risk of metastasis.1
Cystic Pancreatic Endocrine Neoplasms (CPENs): These lesions arise from pancreatic endocrine cells and are considered cystic versions of pancreatic neuroendocrine tumors. They usually present with a thick, enhancing wall on imaging and have low but variable metastatic potential.1
Differentiation between cyst types
Adapted with approval from N Engl J Med 2024;391:832-843
Risk stratification
First, dedicated pancreatic imaging should be performed, preferably a contrast-enhanced MRCP. Cysts are categorized based on their malignancy risk into benign, low-risk, and higher-risk cysts (intermediate and high). Low-risk cysts are typically smaller BD-IPMNs with little to no risk of malignancy. Intermediate-risk cysts present a minimal risk of current cancer, but have the potential of future malignant progression, while high-risk cysts have a significant chance of advanced neoplasia, including high-grade dysplasia or invasive cancer.5
For benign cysts like SCAs and pseudocysts, no further evaluation is necessary. For other cysts, it is essential to assess whether high-risk stigmata (HRS) or worrisome features (WF) are present. HRS like biliary obstruction, mural nodules, or pancreatic duct dilation greater than 10 mm strongly suggest the presence of advanced neoplasia. Worrisome features, such as cyst size over 3 or 4 cm (depending on the guideline), mild duct dilation, or lymphadenopathy also indicate an increased risk, but are not as strongly predictive as HRS.5
The presence of symptoms is associated with malignancy, although most cysts are asymptomatic. Jaundice is considered a high-risk feature, while pancreatitis and abdominal pain are intermediate risk factors. In addition, elevated serum CA19-9 and new-onset diabetes are worrisome according to the latest guidelines.5
Adapted with approval from N Engl J Med 2024;391:832-843
Role of endoscopy
Endoscopic ultrasound (EUS) is used in select cases to improve risk assessment, particularly for intermediate-risk cysts. It is also helpful for confirming a diagnosis in low-risk cases and establishing a preoperative diagnosis in high-risk cases. EUS has higher accuracy than MRI for detecting ductal communication and smaller mural nodules, and it can identify the “fish mouth papilla”, a key sign of IPMN. Contrast-enhanced EUS is particularly useful for identifying epithelial nodules, which are strong indicators of malignancy.5
Fine needle aspiration (FNA) of cyst fluid is a safe procedure, but its diagnostic yield is low. Cyst fluid analysis can help diagnose the cyst type. DNA analysis can detect mutations linked to specific cyst types but can also aid in risk assessment.5
Mucinous Cysts
Mediators of progression to pancreatic cancer
The assessment of cancer risk
Adapted with approval from N Engl J Med 2024;391:832-843
For mucinous cysts, management options include surgery, surveillance, or no further action. Factors such as the risk of malignancy, overall health, existing risk of pancreatic cancer, and the patient’s preference must be considered.1, 5
High-risk cysts generally require surgical resection, with the most common procedure being limited segmental pancreatectomy. For main or mixed-duct IPMN, it is important to locate the at-risk portion of the pancreas, though this can be challenging. A more aggressive approach like total pancreatectomy carries high morbidity, so segmental resection is preferred. Even after resection, continued surveillance of the remaining pancreas is necessary, as IPMNs are typically multifocal. 1, 5
For intermediate-risk mucinous cysts, the decision is more complex, and tools like EUS and cyst fluid analysis can aid in determining whether surgery or intensified surveillance is needed.1, 5
In some cases, low-risk cysts may be resected based on factors such as patient preference, the cyst’s location, or the desire to avoid ongoing surveillance. MCNs, for example, are typically found in younger patients, and resection may be considered to prevent the need for long-term follow-up. Although smaller lesions carry a very low risk of malignancy, removing them may offer peace of mind and avoid recurrence. 1, 5
Management of presumed mucinous cystic lesions
Adapted with approval from N Engl J Med 2024;391:832-843
For most low-risk cysts, surveillance is recommended. Follow-up imaging (preferably by MRCP) is performed every six months for the first year and annually thereafter, but the frequency can be adjusted based on stability. Monitoring for symptoms, elevated CA19-9 or new-onset diabetes is also important. Cyst stability is defined as less than a 20% increase in size or less than 2.5mm growth per year. If a cyst shows significant growth or develops new high-risk features, further intervention like EUS or surgery may be necessary.1, 5
Although there is no strong evidence for discontinuing surveillance in low-risk cysts, those that have been stable for years present minimal risk, and it may be reasonable to stop monitoring. Also, regular reassessment of the patient’s health status is essential to adjust management goals accordingly.1, 5, 8
Suggested follow-up durations
Adapted with approval from N Engl J Med 2024;391:832-843
Citations:
- Gonda Tamas A. Cahen DL, Farrell James J. Pancreatic Cysts. New England Journal of Medicine 2024.
- Levink IJM, Bruno MJ, Cahen DL. Management of Intraductal Papillary Mucinous Neoplasms: Controversies in Guidelines and Future Perspectives. Current Treatment Options in Gastroenterology 2018;16:316-332.
- Elta GH, Enestvedt BK, Sauer BG, et al. ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts. Official journal of the American College of Gastroenterology | ACG 2018;113.
- Vege SS, Ziring B, Jain R, et al. American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts. Gastroenterology 2015;148:819-822.
- Ohtsuka T, Fernandez-del Castillo C, Furukawa T, et al. International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas. Pancreatology 2024;24:255-270.
- The European Study Group on Cystic Tumours of the P. European evidence-based guidelines on pancreatic cystic neoplasms. Gut 2018;67:789.
- Kromrey M-L, Bülow R, Hübner J, et al. Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study. Gut 2018;67:138.
- Meziani J, Sprij MLJA, Fuhler GM, et al. Small cyst size and lack of growth as negative predictors of malignant transformation in low-risk intraductal papillary mucinous neoplasms of the pancreas: A systematic review and meta-analysis. United European Gastroenterology Journal 2024.
Sponsored by:
This website was developed with the support of an educational grant by Abbott EPD
Pancreas Academy is owned and managed by the European Pancreatic Club (EPC)
Address:
House of European Gastroenterology
Wickenburgg. 1, 1080 Vienna, Austria