Pancreatic Cyst

Background

• Majority of pancreatic cysts are typically asymptomatic lesions which may or may not confer risk of malignancy.
• Pancreatic cysts are increasingly detected incidentally due to factors including ubiquitous use of abdominal imaging studies and an increasing population of elderly individuals.
• The prevalence of asymptomatic pancreatic cysts in general population is likely about 1%-3%, but cysts may be found in 2.4%-19.6% (higher in studies with older populations) of all patients examined by abdominal imaging.
• Pancreatic cysts can be divided into nonneoplastic lesions (such as simple cysts, lymphoepithelial cysts, or pseudocysts) and neoplastic lesions. The most common neoplastic lesions include:
  • serous cystic neoplasms (SCNs), which have very low to no risk of malignancy.
  • mucinous cystic neoplasms (MCNs), almost exclusively in women during middle age (mean age 48-55 years old), and which have about a 10%-17% risk of malignancy
  • intraductal papillary mucinous neoplasms (IPMNs), which have a high (but variable) risk of malignancy (up to 68%)
  • solid pseudopapillary neoplasms (SPNs) are primarily found in younger women (mean age 30 years old)
• Early identification and management of mucinous lesions may be associated with improved prognosis.

Evaluation

• 70% of patients may be asymptomatic with lesions found on abdominal imaging.
• Most common signs/symptoms, if reported, are nonspecific and include abdominal pain, weight loss, jaundice, back pain, palpable mass, and postprandial fullness.
• Perform a thorough examination to exclude nonpancreatic etiologies, including more common conditions such as peptic or biliary disease.
• The primary goals of imaging are to characterize the type of cyst and to assess for high-grade dysplasia or pancreatic cancer.
  • Consider magnetic resonance cholangiopancreatography (MRCP) for investigation of pancreatic neoplasms (Weak recommendation), even though it has low ability to diagnose type of cyst (40%-50%) and only moderate ability to distinguish benign from malignant cysts (55%-76%).
  • Consider pancreatic protocol computed tomography (CT) or endoscopic ultrasound (EUS) as alternatives for imaging in patients who are unable to have magnetic resonance imaging (MRI), taking into account risk of radiation exposure or invasiveness of procedure (Weak recommendation).
• Blood tests:
  • Serum amylase and lipase levels are frequently elevated, but may also be normal, in cases of pancreatitis and pseudocyst.
  • Consider testing for serum cancer antigen CA 19-9 in patients with IPMNs if malignancy is suspected (Weak recommendation).
• Consider EUS-guided fine needle aspiration (EUS-FNA) biopsy where diagnosis is unclear and results would alter management (Weak recommendation).
  • Consider it as an adjunct to imaging.
  • Consider it for improving diagnostic accuracy in differentiating mucinous vs. nonmucinous neoplasms, in differentiating malignant vs. benign neoplasms, and in cases where CT or MRI results are unclear (Weak recommendation).
  • EUS-FNA may be also considered if the results are expected to change clinical management, such as the need for, or extent of, surgical resection.
• Cyst fluid analysis, combining carcinoembryonic antigen (CEA) levels with either cytology or molecular testing for KRAS/GNAS mutations, may be considered for differentiating between types of mucinous cysts (Weak recommendation).
• Cytology may also be helpful to differentiate benign neoplasms from those with high-grade dysplasia or cancer (Weak recommendation), but is associated with low diagnostic yield due to low cellularity.

Management

• Management is based on risk of malignancy, which varies by subtype of cyst and by clinical features.
• Management often requires consideration of surgical resection, taking into account numerous factors:
  • Individual life expectancy and risk of death from other factors should be carefully considered prior to decision to perform pancreatic surgery, which itself is associated with significant risk.
  • Initial extent of resection varies by type of cyst and risk profile, but patients should be informed that full pancreatectomy is possible.
  • Further resection is warranted if evidence of cancer or high-grade dysplasias is found on frozen section analysis.
  • On histopathologic examination, features to document include size, uni- or multilocularity, wall thickness, solid areas or mural nodules, cyst content, relationship to ductal system, and appearance of the background pancreas.
• Management by cyst type:
  • Pseudocysts have no malignant potential and do not require surveillance or treatment when asymptomatic (see Pancreatic Pseudocyst for additional information) (Weak recommendation).
  • Consider following asymptomatic patients with SCNs for 1 year, and thereafter only as needed for symptoms (Weak recommendation).
  • MCNs may require surgery, depending on size.
    • Perform surgical resection in patients with MCNs ≥ 40 mm or who have symptomatic MCN or are at high risk irrespective of cyst size (Strong recommendation).
    • Consider follow-up without surgery for MCNs that measure < 30-40 mm with no high-risk features or symptoms (Weak recommendation).
    • Lifelong surveillance is required as long as patient is fit for surgery and should include follow-up every 6 months for first year, then annually thereafter if no changes are observed (Strong recommendation).
  • IPMNs likely require surgery depending on both size and location.
    • Perform surgical resection in all patients with IPMNs > 40 mm, regardless of symptoms or other risk factors, due to increased risk for malignancy (Strong recommendation).
    • Perform surgical resection in all patients with main duct IPMNs who are fit for surgery (Strong recommendation).
    • Consider surveillance in patients with branch duct IPMNs without high-risk features (Weak recommendation).
    • Surgery should be considered in patients with branch duct IPMN patients with high-risk or moderate-risk features as the risk of malignancy increases with the number of these high-risk features.
    • Follow all patients until they are no longer candidates for surgery, as the risk of cyst progression increases with time (Strong recommendation).
  • Rare pancreatic cysts usually require surgery.
    • Perform radical resection of all SPNs (Strong recommendation).
    • Consider surgical resection of cystic pancreatic neuroendocrine (PNEN) tumors > 20 mm (Weak recommendation).
    • Consider surveillance for asymptomatic cysts ≤ 20 mm with no signs of malignant behavior (Weak recommendation).
  • Undefined cysts of unclear etiology typically may require follow-up only.
    • Cysts < 15 mm with no risk factors for malignancy should be reexamined annually; if stable for 3 years, follow every 2 years (Strong recommendation).
    • Cysts ≥ 15 mm should be followed every 6 months during the first year and annually thereafter (Strong recommendation).
    • Lifelong follow-up is required for as long as patient is fit and willing to have surgery or patient is no longer a candidate for surgery (Strong recommendation).
  • Pancreatic pseudocysts have no malignant potential and do not require surveillance or treatment when asymptomatic.
    • Supportive medical care for pseudosymptomatic cysts may involve initiating low-fat diet or pharmacologic therapy including analgesics and/or antiemetics.
    • Interventional pseudocyst drainage is also an option, including endoscopic, percutaneous, and surgical techniques.
    • See Pancreatic Pseudocyst for additional information
• Considerations with follow-up of unresected cysts:
  • Prior to initiating surveillance, clinician should review the patient's risk of developing pancreatic malignancy, calculate approximate life expectancy, consider comorbid conditions, and consider whether patient is a surgery candidate.
  • Most patients who are fit for surgery should be followed (typically with MRI and EUS if necessary) every 6 months to annually, depending on presence of high-risk features and changes that develop.
• Follow-up after surgery with imaging including MRI, MRCP, and/or EUS-guided FNA biopsy may be required depending on cyst type and risk:
  • Noninvasive MCNs may not require surveillance after resection.
  • Surveillance is required for IPMNs and is based on resection margin status.
    • if no residual lesions, repeat examinations at 2 and 5 years may be reasonable.
    • if low- to moderate-grade dysplasia at margin, surveillance consisting of history/physical exam and MRCP ≥ twice a year is suggested.
• Palliative chemotherapy, if required, may be an option for patients with unresectable or recurrent cysts, but there is insufficient evidence to support specific choice of regimen.