Pancreatic cystic neoplasms and how to avoid them

Computed tomography (CT) scanning, magnetic resonance imaging and cholangiopancreatography (MRI/MRCP) are accurate methods for the detection of PCN, with MRI and MRCP being used most often. However, the accuracy of these methods remains relatively low for identifying the specific type of PCN.^4–9 If a specific diagnosis is not established by cross-sectional imaging, further investigations are not indicated if the results will not change clinical management (e.g. if there is a clear indication or contraindication for surgery, or in cases where there are small cysts with no indication for surgery).³

Although cyst fluid carcinoembryonic antigen (CEA) and cyst fluid amylase or lipase increase the accuracy of endoscopic ultrasonography (EUS) for differentiating mucinous from nonmucinous PCN, the diagnostic accuracy of these biomarkers is too low to establish the specific PCN type.^10–16 In addition, cyst fluid CEA does not allow the differentiation of mucinous cystic neoplasms (MCN) from intraductal papillary mucinous neoplasms (IPMN), nor benign mucinous cysts from those with high-grade dysplasia or cancer.¹⁷ Therefore, cyst fluid CEA is not reliable for the diagnosis of the specific type of PCN, and the CEA level should be considered only as an adjunct to imaging and the cytological features of the cystic lesion.

EUS-FNA (fine-needle aspiration) is only indicated when there are unclear CT and MRI findings and the EUS-FNA result is expected to change clinical management.³ Cyst fluid analysis should include amylase or lipase, CEA and cytology. Compared with EUS alone, cyst fluid cytology after EUS-FNA increases the accuracy for differentiating mucinous from nonmucinous and benign from malignant PCN; however, cytology is highly specific but insensitive in this setting.^11,12,18

Surveillance of PCN is determined by the risk of progression to cancer. Patients who have a definite diagnosis of serous PCN do not require surveillance owing to the benign nature of these lesions.^19,20 By contrast, the risk of progression of mucinous PCN—both MCN and IPMN—to high-grade dysplasia and cancer increases over time. Therefore, if there is no indication for surgery, patients who have MCN or IPMN should be subject to long-term follow-up. Nevertheless, long-term surveillance is not indicated in patients who have MCN or IPMN if they are not fit for surgery because they have comorbidities.^21–24 

A multiphasic pancreas protocol CT scan is highly accurate for the characterization of PCN. To qualify as a multiphasic pancreatic protocol CT, an examination requires inclusion of thin reconstruction images (≤ 2.5-mm slice thickness) obtained during the pancreatic parenchymal phase. Despite that, MRI/MRCP is preferred for surveillance to avoid repeated exposure to radiation during long-term follow-up. In addition, MRI/MRCP is more sensitive than CT scanning for the identification of relevant PCN features, such as mural nodules (which are associated with a high risk of high-grade dysplasia or cancer), internal cyst septations (that may be of help for the specific diagnosis of PCN), and the presence of multiple cysts (supporting the diagnosis of multiple side-branch IPMN).^7,25–27 

Figure 1 | Indications for surgery in patients who have IPMN and are fit for surgery.

As the risk of IPMN or MCN progressing to high-grade dysplasia or cancer increases over time, the chance of developing indications for surgery (whether they are clinical or based on imaging) also increases over time. Surveillance of patients who have IPMN or MCN but no indication for surgery should, therefore, not be interrupted as long as they are fit for surgery, even if no significant change is observed after 3–5 years.^3,21–23,30 

As the risk of cancer associated with IPMN is high for patients who have absolute or relative indications for surgery, resection of IPMN in those patients should not be delayed. By contrast, although malignancy cannot be definitively excluded before histological examination of a surgical specimen, the risk of high-grade dysplasia or cancer in patients with IPMN is low in the absence of risk factors.²¹ On that basis, and as a general rule, patients who have no indication for surgical resection (i.e. small cysts with no risk factors for malignancy) should not be operated on unless they develop an indication for surgery during follow-up. In this context, factors such as life expectancy, the patient’s compliance and wishes, and the surgical risk are important for appropriate clinical decision making.

A parenchyma-sparing pancreatectomy is a nononcological procedure and has a morbidity comparable to, or even higher than, that of an oncological pancreatic resection.^31,32 The procedure should not be carried out in patients who have a surgical indication for IPMN because of their risk of cancer or high-grade dysplasia. The surgical approach for IPMN should be an oncological resection with standard lymphadenectomy ^3,31,32 

After an appropriate diagnostic work-up, small cysts may remain undefined in terms of their specific type. Despite that, an undefined cyst could be mucinous and the risk of malignant transformation may increase over time. For this reason, criteria for surgical resection or surveillance of undefined cysts may follow the same general rules defined for branch duct IPMN (BD-IPMN). Undefined small pancreatic cysts are, however, frequent and often have no effect on a patient’s survival in the absence of any risk factor for malignancy.³³ On that basis, the European Study Group on Cystic Tumours of the Pancreas recommends that, in the absence of risk factors for malignancy, undefined cysts <15 mm in size should be re-examined every year—if they are stable for 3 years, the follow-up may be extended to every 2 years as long as the patient remains fit for surgery.^3,34 When there are no risk factors for malignancy and the undefined cysts measure ≥15 mm, they should be followed up at 6-month intervals for the first year and annually thereafter.^3,21