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Guideline review
Pancreatic cystic lesions: risk stratification and management based on recent guidelines
  1. Benjamin M Stutchfield1,
  2. Manu Nayar2,
  3. Ian D Penman3
  1. 1 Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK
  2. 2 Department of Gastroenterology, The Freeman Hospital, Newcastle, UK
  3. 3 Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, UK
  1. Correspondence to Benjamin M Stutchfield, Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK; ben.stutchfield{at}


Pancreatic cystic lesions (PCLs) can present complex diagnostic and management challenges with uncertainty as to the most appropriate investigations, interventions and surveillance. Guidelines have been developed to aid decision making, including the European Study Group, American College of Gastroenterology and International Study Group guidelines. This paper presents issues relating to risk stratification and the appropriate management of patients with PCLs, reviewing these recently published guidelines. While there are similarities across these expert guidelines, there are notable differences in terms of features associated with increased risk of malignant transformation, the most appropriate imaging modality and timing of interval imaging. Where variations exist, this reflects differing interpretations of a limited evidence base, and decision making will likely evolve further as experience with these guidelines develops.

  • pancreas
  • pancreatic tumours

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The prevalence of pancreatic cystic lesions (PCL) is increasing, associated with the increasing use of CT and MRI to investigate potential intra-abdominal pathology and possibly related to an ageing population. PCLs may be detected in up to 3% of patients undergoing contrast-enhanced CT and up to 45% of patients undergoing MRI/magnetic resonance cholangiopancreatography.1 Most are asymptomatic, but if symptoms are present they are generally non-specific. PCLs represent a spectrum of disease from benign to malignant potential, to frankly malignant lesions. They may occur as solitary lesions or in association with disorders such as polycystic kidney disease or von Hippel-Lindau syndrome.

While incidental detection of a likely malignant or premalignant PCL may be fortuitous, surgical intervention to remove a PCL which is subsequently found to be benign may expose the patient to considerable unnecessary risk. Characterisation and risk stratification of PCLs can be challenging, necessitating multimodality investigation which may include cross-sectional imaging, endoscopic ultrasound (EUS) and tissue sampling. Recognising these diagnostic and management difficulties, guidelines have recently been developed in an attempt to aid decision making.

The International Consensus Guidelines, published in 2012, were ‘consensus-based’, rather than ‘evidence-based,’ guidelines and were updated in 2017.2 3 More recently, both the American College of Gastroenterology (ACG) and the European Study Group (ESG) on Cystic Tumours of the Pancreas have provided evidence-based guidance centred on systematic review of the literature, using criteria for assessment of study quality in addition to expert opinion.4 5

The aim of this review is to highlight the key points from these guidelines, including differences and controversies, to assist in PCL decision making and the development of local protocols.

Classification of PCLs

PCLs can be defined as (1) inflammatory fluid collections; (2) non-neoplastic; or (3) neoplastic (table 1). A history of pancreatitis should always be sought during the initial work-up of a patient with a PCL. Non-neoplastic pancreatic cysts do not require resection unless symptomatic. Of the neoplastic pancreatic cysts, mucinous, intraductal papillary mucinous, solid pseudopapillary and neuroendocrine lesions have malignant potential, and resection should be considered dependent on the risk of malignant transformation balanced against the risks of intervention or continued surveillance.6 Serous cystic tumours are a benign entity and resection is only indicated if symptomatic. Figure 1 shows example images for serous cystadenoma, intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasms (MCN).

Table 1

Pancreatic cystic lesions

Figure 1

Pancreatic cystic lesions. (A) EUS image showing serous cystadenoma (microcystic variant); (B) EUS image showing main duct intraductal papillary mucinous cystadenoma; (C) EUS image showing malignant mucinous cystadenoma. EUS, endoscopic ultrasound.


Following identification of a PCL, subsequent investigations should proceed in a stepwise fashion. Inflammatory fluid collections are often clearly defined based on patient history and imaging findings, although an underlying pancreatic lesion should be considered. In terms of true PCLs, CT and MRI have similar reported accuracy for identifying the specific type, 40%–95% and 40%–81%, respectively.4 Across the guidelines MRI is recommended as the preferred investigation for PCLs, with MRI best demonstrating communication with ductal system, internal septations or mural nodules without the radiation exposure of CT and interventional risks associated with EUS.4 5 Differentiating cyst type is problematic, with MRI and other imaging modalities showing 40%–50% accuracy in determining cyst type and 55%–76% in identifying malignancy.5 CT can provide further information when performed in addition to MRI where there is diagnostic uncertainty, to detect features of chronic pancreatitis, to differentiate pseudocysts from true PCLs and where there is suspicion of a malignant PCL or pancreatic cancer, although this is based on low-quality evidence.

Recommendation 1: cross-sectional imaging

MRI is the preferred investigation for pancreatic cystic lesions. CT should be performed in addition to MRI if differentiation of inflammatory cystic lesions from true cystic lesions is required, to detect features of chronic pancreatitis and where malignant lesions are suspected.

Where there are clinical or radiological features of concern, EUS is recommended as an adjunct to cross-sectional imaging. However, if patients are deemed not fit for surgery, then further investigation for incidental cysts would not be appropriate. While EUS is helpful at identifying the different features of PCLs, the guidelines acknowledge that EUS remains imperfect at identifying the exact type of PCL. Contrast-enhanced EUS should be considered to assess mural nodules and can help identify vascularity within the PCL. Hyperenhancement raises suspicion for malignant transformation, and in these cases tissue sampling should be considered. EUS-fine needle aspiration (FNA) increases diagnostic accuracy when considering mucinous versus non-mucinous PCLs, especially when combined with cyst fluid carcinoembryonic antigen (CEA), lipase levels and cytology. Although EUS-FNA is a relatively safe procedure, complications such as pancreatitis and infection can occur, with one study reporting an adverse event rate of 6%.7 There is a lack of evidence regarding the utility of brush cytology and forceps biopsy at EUS, but these techniques may find a role as experience with different methods of tissue sampling develops. Endoscopic retrograde cholangiopancreatography does not have a role in the characterisation of PCLs, although pancreatoscopy may be helpful in differentiating chronic pancreatitis from main duct-IPMN.4

Recommendation 2: endoscopy

Endoscopic ultrasound (EUS) is recommended where there are radiological features of concern or diagnostic uncertainty. Contrast-enhanced EUS can aid assessment of vascularity of the lesion and guide tissue sampling. Fine needle aspiration improves diagnostic accuracy.

While cyst fluid analysis is recommended, interpretation of results may be challenging with limited sensitivity and accuracy. When differentiating mucinous from non-mucinous lesions, cytological analysis of cyst fluid has a sensitivity as low as 40%, with cyst fluid CEA level having a sensitivity between 50% and 80%.4 However, specificity is reportedly higher, with 99% specificity for cytological analysis and 60%–90% specificity for a cyst fluid CEA level ≥192 ng/mL.4 No serum markers are currently available for routine use, although CA 19.9 levels may be elevated in the context of malignant transformation. Mutational analysis of cyst fluid appears promising but remains investigational at present.

Risk of malignancy

IPMN is the most common mucinous lesion occurring, with equal male to female ratio in their 50s–70s, either incidentally, on a background of pancreatitis or related to malignancy. IPMN can be defined as either main duct (MD-IPMN), branch duct (BD-IPMN) or mixed type (MT-IPMN) based on the cyst’s communication with the pancreatic ductal system. MD-IPMN and MT-IPMN display similar, relatively high, propensity for malignant transformation (30%–91% of lesions where the main pancreatic duct was ≥5 mm).4 BD-IPMN has a lower risk of high-grade dysplasia or malignancy (3%–47% at >30 mm maximum cyst diameter), but features predictive of malignancy and high-risk features are the same (table 1).4 Risk of malignancy is lower for mucinous cystic neoplasm, although still significant (11%–38%).8 9 Mucinous neoplasms are found predominantly in women aged 50–70 years old presenting with abdominal pain, as an incidental finding or in relation to malignancy. Table 2 provides an indication of malignant risk associated with the type of lesion. It is important to note that this reflects pathological assessment of these lesions following resection and so cannot be used to estimate malignant risk prior to surgery.

Table 2

Risk of malignancy in pancreatic cystic lesions

The ESG, International Consensus Group (ICG) and ACG guidelines have defined features indicating high risk for malignancy and/or high-grade dysplasia for mucinous lesions including IPMN and mucinous cystic neoplasm (table 3). The ESG describes a separate set of ‘high risk factors’ for both IPMN and mucinous cystic neoplasia, while the ICG and ACG consider both subtypes together as ‘mucinous lesions’. While there is general consistency across the guidelines, there are some key differences, such as cut-off values for cyst size, growth rate and associated features. Where there are differences this has resulted from different interpretations of a limited literature base without sufficient evidence to support one approach over another. Across the guidelines the most concerning features include obstructive jaundice occurring secondary to the cyst, presence of a mural nodule or solid component, and main pancreatic duct dilatation. The correct balance of risk will become apparent as experience with these recently published guidelines expands.

Table 3

High-risk features of mucinous cysts (IPMN and mucinous) according to the guideline

There are limited data regarding risk of malignancy in solid pseudopapillary neoplasms (SPN), although two series have reported that approximately 15% of resected SPNs were malignant.10 11 Cystic pancreatic neuroendocrine tumours have approximately 20% risk of malignancy, although when ≤20 mm they usually are considered low risk.12

Management: resection

Indications for resection of PCLs can be categorised as absolute, relative or ‘no surgery indicated’. While minimally invasive techniques are increasingly being used for pancreatic resections, risks remain considerable, with approximately 40% of patients undergoing distal pancreatectomy experiencing a degree of leak from the pancreatic stump.13 The incidence of new-onset insulin-dependent diabetes mellitus (8%), pancreatic fistula (5%), intra-abdominal abscess (4%) and postoperative bleed (4%) are not insignificant.14 It is therefore essential to ensure indications for surgery are appropriate and the risk/benefit ratio is considered.

The guidelines vary regarding indications for surgery, ranging from offering specific advice to recommending the patient is referred to the pancreatic multidisciplinary team. For IPMN, the ESG regards one or more of the ‘Features highly predictive of malignancy’ as an absolute indication for surgery, with relative indications defined as ‘Features associated with an increased risk of high-grade dysplasia or cancer’ (table 3). The ESG guidelines go on to suggest that patients who have one or more relative indications for surgery and no significant comorbidity should undergo resection, patients with one ‘relative indication’ plus one ‘significant-comorbidity’ should undergo intensive surveillance, while those with ‘significant comorbidity’ and two or more relative indications should undergo surgery. The implementation of this approach would be problematic given ‘significant comorbidity’ is not defined and there is insufficient evidence to suitably risk-stratify patients prior to surgery. The ACG does not provide guidance on whether a specific lesion should be resected or not, rather they recommend referral to a pancreatic multidisciplinary team (MDT) for further discussion if there are ‘high risk characteristics’ present (table 3). The ICG recommends proceeding straight to surgery if clinically appropriate in the presence of ‘high risk stigmata’ for mucinous cystic lesions and proceeding to EUS in the presence of ‘worrisome features’ (table 3). If at EUS there is a definite mural nodule, main duct features suspicious for involvement or suspicious/malignant cytology, then surgery is recommended, otherwise the patient should undergo interval imaging (see next section).

With regard to mucinous cystic neoplasms, the ESG recommends that cysts which are symptomatic, ≥40 mm, have mural nodules or show high growth rate should be resected. The ACG does not provide specific guidance regarding surgery, while the ICG recommends that all fit patients undergo resection of MCNs. The ICG acknowledges that although MCNs less than 4 cm are low risk, these lesions generally occur in the distal pancreas, so are amenable to resection which avoids surveillance.

The guidelines agree that all SPNs should be resected. The ESG recommends that pancreatic neuroendocrine tumours >20 mm and those that are ≤20 mm but are symptomatic or show signs of malignant behaviour should be resected, the ACG does not comment on surgery for neuroendocrine tumours, and the ICG does not comment on neuroendocrine PCLs.

The surgical approach to IPMN and mucinous cystic neoplasm should be an oncological resection with standard lymphadenectomy. For MD-IPMN and MT-IPMN with main duct dilatation running the length of the pancreas, intraoperative frozen section of the resection margin is recommended. For the majority of BD-IPMN, an oncological resection with standard lymphadenectomy is recommended. There may be a role for parenchymal sparing pancreatectomy (resection of the lesion and minimal pancreatic tissue) for lesions with very low probability of malignancy, but the morbidity is similar to standard resections and benefits are yet to be demonstrated. Given the rarity of SPN, guidance for appropriate interventions is limited, although even in cases of locally advanced disease, metastatic or recurrent SPN an aggressive surgical approach can be considered. For pancreatic neuroendocrine tumours, surgery should proceed according to tumour localisation (pancreatoduodenectomy, distal pancreatectomy or enucleation).

Recommendation 3: surgical resection

Surgical approach should be tailored to the presence of high-risk features for malignancy or high-grade dysplasia. An oncological resection with standard lymphadenectomy is preferred.

Management: surveillance and follow-up

While there is general consistency between guidelines regarding the highest risk PCL features, there is variation in the approach to small undefined PCLs (table 4), which constitute the majority of cases. The ESG considers EUS, CT or MRI as appropriate investigations, the ACG favours MRI, while the ICG considers MRI or CT appropriate for smaller cysts, with EUS in addition for larger lesions. Evidence to support one strategy over another is lacking, and therefore follow-up strategies may be designed according to local resources. By way of consolidation, MRI would seem most appropriate as the surveillance imaging of choice given the radiation exposure associated with CT and interventional risks of EUS. If the initial investigation was CT, then small cysts do not necessarily require repeat imaging in the form of MRI or EUS at the initial stage. If patients cannot tolerate MRI, then CT or EUS may also be acceptable forms of surveillance.

Table 4

Follow-up for undefined cystic lesions of the pancreas according to guideline

For patients who have undergone resection of IPMN, the length of follow-up should be tailored to the individual concerned and includes perceived cancer risk, comorbidity and patient preference. All guidelines recommend following local PDAC (pancreatic ductal adenocarcinoma) protocols where invasive cancer is found and 6-monthly follow-up imaging initially where high-grade dysplasia is evident in the resected specimen (table 5). It is important to note that patients who develop pancreatic cystic neoplasia have a tendency to develop further lesions which can recur over 10 years following resection of the first lesion.15 Indeed in a series of 130 patients, 62% had developed another IPMN by 10 years (4% at 1 year, 25% at 5 years).16 For this reason all guidelines recommend that follow-up should be continued as long as the patient is considered a surgical candidate.

Table 5

Follow-up for intraductal papillary mucinous neoplasia according to guideline

There is good evidence that resected mucinous cystic neoplasia in the absence of invasive malignancy do not recur, and the guidelines agree that postoperative surveillance is not required for these patients.2–5

Recommendation 4: surveillance

All guidelines advocate surveillance imaging for undefined pancreatic cystic lesions regardless of size. Following resection of IPMN surveillance should continue while the patient remains a surgical candidate. Surveillance is not required following resection of mucinous cystic neoplasm. Appropriate imaging modality varies according to guideline; however, MRI represents a good balance between risk and benefit of the investigation. Surveillance may not be appropriate in frail or elderly patients or those with significant comorbidities.


PCLs present a range of complex diagnostic and management dilemmas. Expert working groups have aided decision making through the development of guidelines addressing the key issues. While there is some consistency as to the features associated with high risk of cancer or high-grade dysplasia, the limited evidence base has resulted in variation in recommendations regarding indications for surgery or surveillance and the modalities and frequency of surveillance. Ultimately, the various guidelines are iterative and will hopefully converge with more experience and review of large patient series.


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  • Contributors All authors contributed to the design of the work and approved the final manuscript. BMS and MN drafted and revised the article, and IDP contributed to revising the article. MN and IDP contributed images to the manuscript. All conceived the study, did literature search, reviewed and edited the paper. BMS and MN wrote the paper.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.