Continuing Education Activity

Pancreatic cysts are often detected in patients undergoing imaging with either computed tomography (CT) or magnetic resonance imaging (MRI) for unrelated reasons. Pancreatic cysts are identified in 2 to 20 percent of patients undergoing CT or MRI; however, these rates may be lower in patients without a history of pancreatitis and may be higher by nearly one-third in high-risk patients with a family history of pancreatic cancer. Pancreatic cysts can be either neoplastic or non-neoplastic. This activity illustrates the evaluation and treatment of pancreatic cysts and reviews the role of interprofessional team members in managing those with this condition.

Objectives:

• Review the presentation of pancreatic cysts.

• Describe the evaluation of pancreatic cysts.

• Explain the management of pancreatic cysts.

• Summarize interprofessional team strategies to improve care coordination and communication to enhance outcomes for patients affected by pancreatic cysts.

Introduction

The pancreas is an important organ in the digestive system that produces enzymes for digestion and releases important hormones into our circulation that helps with metabolism. Pancreatic cysts are often detected in patients undergoing imaging with either CT or MRI for unrelated reasons due to a combination of an aging population and the overall increased use of imaging. Pancreatic cysts are identified in 2% to 20% of patients undergoing CT or MRI; however, these rates can be lower in those with no history of pancreatitis.[1],[2],[3] On the other hand, these rates can increase to nearly one-third of patients in high-risk populations with a family history of pancreatic cancer.[4],[5]

These cysts can be either neoplastic or nonneoplastic. Neoplastic cysts include intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasm, solid pseudopapillary neoplasm, and cystic pancreatic neuroendocrine tumors. IPMNs can be subclassified as main duct IPMN, branch duct IPMN, and mixed IPMN. Nonneoplastic cysts include serous cystic adenoma, simple cysts, lymphoepithelial cysts, and mucinous nonneoplastic cysts. Correct diagnosis is important as management drastically changes if the cyst is neoplastic or nonneoplastic.

Moreover, surgical resection is not always the best option for all pancreatic cysts as resection can be complicated and have many risks associated with it. Depending on the cyst type, growth pattern, and symptoms, surveillance can sometimes be the best option. Moreover, with the ever-growing concern about pancreatic cysts and their risk of malignancy, new advances, such as endoscopic ultrasound, have greatly improved surveillance and proper diagnosis to guide treatment options.

Etiology

The etiology of pancreatic cysts varies widely depending on if they are non-neoplastic or neoplastic. Moreover, they are often found incidentally. As above, a history of pancreatic cancer and/or pancreatitis can increase the risk of developing pancreatic cysts. Neoplastic cysts include IPMN which includes main duct IPMN, branch duct IPMN, and mixed IPMN, mucinous cystic neoplasm, solid pseudopapillary neoplasm, and cystic pancreatic neuroendocrine tumors. Nonneoplastic cysts include serous cystic adenoma, simple cysts, lymphoepithelial cysts, and mucinous nonneoplastic cysts.

Epidemiology

The true frequency and incidence of pancreatic cysts is unknown; however, in a surgical case series of resected pancreatic cysts, the frequency was 26% branch duct IPMN, 25% main duct IPMN, 13% to 23% serous cystadenoma, 11% to 18% mucinous cystic neoplasm, 4% to 7% cystic pancreatic neuroendocrine tumor, and 2% solid pseudopapillary neoplasm.[1],[6],[7]

Pathophysiology

IPMN: The three types of IPMN are main duct, branch duct, and mixed. Main duct IPMN is characterized by segmental or diffuse dilation of the main pancreatic duct to greater than 5 mm in diameter without any other causes of obstruction. Branch duct IPMN is characterized by cysts greater than 5 mm in diameter that communicate with the main pancreatic duct without main duct dilation. Mixed IPMN has cysts that meet criteria for both main duct and branch duct IPMN.[1],[8]

Mucinous cystic neoplasms: Large, mucin-producing cysts that do not communicate with the ductal system.[1] The finding of the ovarian-type stroma is diagnostic for this lesion.[9]

Solid pseudopapillary neoplasm: Large, well-demarcated, mixed cystic and solid tumors.[1]

Cystic pancreatic neuroendocrine tumor: Smaller, more likely nonfunctional, cystic lesions that may be associated with multiple endocrine neoplasia types 1.[1]

Serous cystadenoma: Two subtypes include microcystic type serous cystadenoma and macrocystic serous cystadenoma. Microcystic type serous cystadenoma pathognomonically can be recognized by a honeycomb appearance composed of small septated cysts around a central stellate scar.[1],[10],[11]. Macrocystic serous cystadenomas are radiologically indistinguishable from other pancreatic mucinous lesions.[1],[12]

Simple cyst and lymphoepithelial cyst: Lymphoepithelial cysts have nondysplastic squamous cells with sheets of benign lymphocytes.[13]

Mucinous nonneoplastic cyst: Mucin-producing cyst without malignant potential that is differentiated from mucinous cystic neoplasm by lack of ovarian-type stroma and from IPMN by lack of ductal communication.[1],[14],[15],[16]

History and Physical

Important history would include a history of pancreatitis, a family history of pancreatic cancer, and MEN type 1. Patients are typically asymptomatic; however, they can have abdominal pain, back pain, weight loss, jaundice, steatorrhea, or a palpable mass.[17],[18]. Given the signs and symptoms are nonspecific, a detailed history of other differentials is vital to differentiate the cause. Thus, other notable history would also include alcohol and smoking intake; NSAID use; history of liver, pancreatic, peptic or biliary disease; fevers; or chills.

Evaluation

Pancreatic cysts are usually found incidentally via CT or MRI. The further evaluation depends on findings on these imaging modalities and symptomatology. Moreover, guidelines for the evaluation of pancreatic cysts continue to be modified as advanced diagnostic tests such as endoscopic ultrasound are developed. 

The American Gastroenterology Association has guidelines for patients with asymptomatic, incidental pancreatic cysts.[19],[20] Incidental cysts first should be classified as either high risk or low risk for malignancy on imaging and patient presentation. High-risk features include a symptomatic patient, lymphadenopathy, main pancreatic duct diameter greater than 5 mm, and cyst characteristics that include an abrupt change in the main pancreatic duct caliber, mural nodule, enhancing solid component, thickened walls, and a cyst size of greater than 3 cm.[1] Based on these risk factors, cysts are then split into surveillance only, immediate endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), or surgery. EUS-FNA is warranted if at least two of the following are met: size greater than 3 cm, solid component, or main pancreatic duct dilation.[1] 

For symptomatic pancreatic cysts, surgical resection is the preferred treatment (ACCF/AHA class 1, level B recommendation) as it will provide relief of symptoms but also because pain is associated with a greater likelihood of premalignant or malignant pathology.[1][17][18][21][22]

High-risk pancreatic cysts that have the high-risk features above or a main pancreatic duct dilation, suspected mucinous cystic neoplasm, presumed branch duct IPMN greater than 3 cm are recommended as an ACCF/AHA class 1, level B for resection.[1] 

For low-risk pancreatic cysts such as microcystic serous cystadenoma, they likely can be observed regardless of size as they have very low levels of malignant potential. However, macrocystic serous cystadenomas can be hard to distinguish from mucinous lesions on imaging and require evaluation by EUS-FNA, in which the fluid would be tested for carcinoembryonic antigen level (CEA).[1]

EUS-FNA is a procedure that is gaining ground for further characterizing lesions and prevent misdiagnosis. Cyst fluid can be analyzed for mucin, CEA, and cytology. High CEA levels are correlated with mucinous lesions. Moreover, fluid cytology can help distinguish malignant versus nonmalignant lesions.[1]

Treatment / Management

Management ultimately depends on initial imaging and symptom findings. As per the American Gastroenterological Association, initial management for asymptomatic incidental cysts can be split into three categories: surveillance, need for EUS-FNA, or surgery.[23]. Surveillance is recommended if the cyst is less than 3 cm, no solid component, and no main pancreatic duct dilation. EUS-FNA is recommended if at least two criteria are met from a size greater than 3 cm, solid component, or main pancreatic duct dilation. Surgery is recommended if there is both a solid component and main pancreatic duct dilation or EUS-FNA shows suspicious findings. If surveillance is the treatment, then an MRI should be repeated in 1 year and then every 2 years after that. If there is no change in the cyst, surveillance can be stopped after 5 years. If there is a change, then EUS-FNA should be done. If the initial option was surgical resection and the histology returns as high-grade dysplasia or cancer, then MRI should be performed every 2 years thereafter.[1]

All main duct IPMN, mixed IPMN, and mucinous cystic neoplasms should be resected. Branch duct IPMN resection depends on if the patient is symptomatic, presence of enhancing solid cyst component, main pancreatic duct diameter greater than 5mm, mural nodule, cyst fluid cytology shows suspicious or positive findings of malignancy or a change in main pancreatic duct caliber with distal pancreatic atrophy.[1]

Differential Diagnosis

Given the nonspecific physical exam findings, the differential for pancreatic cysts can be broad. One must rule out pancreatitis, liver, biliary, and peptic diseases. Differentiation can be done via proper history taking, physical exam, laboratory tests, and imaging. Since pancreatic cysts are often found incidentally on imaging, some of these differentials can be ruled out concomitantly.

Prognosis

Depending on the type of the pancreatic cyst, the risk of malignancy varies. Noninvasive diseases typically have a great prognosis.[1]

Five-year survival:

• Resected noninvasive main duct IPMN nearly 100%, however, five-year survival for malignant lesions is around 60%.[1],[24]
• Resected malignant branch duct IPMN around 70%.[1],[25]
• Noninvasive mucinous cystic neoplasm approximately 96% and invasive disease following resection approximately 75%.[1],[26],[27]
• cystic pancreatic neuroendocrine tumor approximately 77%.[1],[28],[29],[30],[31]
• limited data is available for solid pseudopapillary neoplasm due to the rarity of the condition.[1]

Deterrence and Patient Education

It is important to monitor the signs and symptoms described above. If present, seeking medical attention is advised.

Pearls and Other Issues

Differentiating pancreatic cysts can be a difficult endeavor, and EUS-FNA has provided a useful modality to determine the etiologies of these cysts.

Enhancing Healthcare Team Outcomes

Consultation with a gastroenterologist is recommended because the complexity of pancreatic cysts makes management dependent on correct diagnosis and surveillance. Moreover, advanced procedures such as EUS-FNA are required in the diagnosis of the cyst. Once a pancreatic cyst has been diagnosed, an interprofessional team will be needed to guide management. The team can consist of the primary care physician, gastroenterologist, radiologist, pathologist, and surgeon.[1]The outlook for simple pancreatic cysts is good but complex cysts may require a surgical drainage procedure, which also adds to the morbidity. Finally, it is imperative that malignancy always be considered in the differential.