Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.     

Cyst fluid glucose: An alternative to carcinoembryonic antigen for pancreatic mucinous cysts

Pancreatic cystic lesions(PCLs) have been increasingly recognized in clinical practice. Although inflammatory cysts(pseudocysts) are the most common PCLs detected by cross-sectional imaging modalities in symptomatic patients in a setting of acute or chronic pancreatitis, incidental pancreatic cysts with no symptoms or history of pancreatitis are usually neoplastic cysts. For these lesions,it is imperative to identify mucinous cysts(intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) due to the risk of their progression to malignancy. However, no single imaging modality alone is sufficient for a definitive diagnosis of all PCLs. The cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration provides additional information for the differential diagnosis of PCLs. Current recommendations suggest sending cyst fluid for cytology evaluation and measurement of carcinoembryonic antigen(CEA) levels. Unfortunately, the sensitivity of cytology is greatly limited, and cyst fluid CEA has demonstrated insufficient accuracy as a predictor of mucinous cysts. More recently, cyst fluid glucose has emerged as an alternative to CEA for distinguishing between mucinous and nonmucinous lesions. Herein, the clinical utility of cyst fluid glucose and CEA for the differential diagnosis of PCLs was evaluated.     

Molecular biomarkers have the potential to improve the diagnostic work-up of pancreatic cystic lesions

Pancreatic cysts are increasingly diagnosed due to the widespread use of cross-sectional imaging, and some of these lesions harbor malignant potential. Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are the major premalignant cystic neoplasms of the pancreas. A variety of diagnostic tools are used to predict the malignant potential of these cysts, but specificity and sensitivity are limited. Thus, many patients undergo unnecessary operations for benign cysts. Balancing the risks of watchful waiting with those of operative management is key in managing these lesions. During the last decade, genetic changes of pancreatic cysts have been examined extensively to estimate their malignant potential. In this review, we provide an overview of the latest molecular and genetic aspects of pancreatic cysts and how they may contribute to the differential diagnosis in patients with pancreatic cystic neoplasms.     

Updates in diagnosis and management of pancreatic cysts

Incidental pancreatic cysts are commonly encountered with some cysts having malignant potential. The most common pancreatic cystic neoplasms include serous cystadenoma, mucinous cystic neoplasm and intraductal papillary mucinous neoplasm. Risk stratifying pancreatic cysts is important in deciding whether patients may benefit from endoscopic ultrasound (EUS) or surgical resection. Surgery should be reserved for patients with malignant cysts or cysts at high risk for developing malignancy as suggested by various risk features including solid mass, nodule and dilated main pancreatic duct. EUS may supplement magnetic resonance imaging findings for cysts that remain indeterminate or have concerning features on imaging. Various cyst fluid markers including carcinoembryonic antigen, glucose, amylase, cytology, and DNA markers help distinguish mucinous from nonmucinous cysts. This review will guide the practicing gastroenterologist in how to evaluate incidental pancreatic cysts and when to consider referral for EUS or surgery. For presumed low risk cysts, surveillance strategies will be discussed. Managing pancreatic cysts requires an individualized approach that is directed by the various guidelines.     

Magnetic resonance imaging in the detection of pancreatic neoplasms

Recently, with the rapid scanning time and improved image quality, outstanding advances in magnetic resonance (MR) methods have resulted in an increase in the use of MRI for patients with a variety of pancreatic neoplasms. MR multi-imaging protocol, which includes MR cross-sectional imaging, MR cholangiopancreatography and dynamic contrast-enhanced MR angiography, integrates the advantages of various special imaging techniques. The non-invasive all-in-one MR multi-imaging techniques may provide the comprehensive information needed for the preoperative diagnosis and evaluation of pancreatic neoplasms. Pancreatic neoplasms include primary tumors and pancreatic metastases. Primary tumors of the pancreas may be mainly classified as ductal adenocarcinomas, cystic tumors and islet cell tumors (ICT). Pancreatic adenocarcinomas can be diagnosed in a MRI study depending on direct evidence or both direct and indirect evidence. The combined MRI features of a focal pancreatic mass, pancreatic duct dilatation and parenchymal atrophy are highly suggestive of a ductal adenocarcinoma. Most cystic neoplasms of the pancreas are either microcystic adenomas or mucinous cystic neoplasms. Intraductal papillary mucinous tumors are the uncommon low-grade malignancy of the pancreatic duct. ICT are rare neoplasms arising from neuroendocrine cells in the pancreas or the periampullary region. ICT are classified as functioning and non-functioning. The most frequent tumors to metastasize to the pancreas are cancers of the breast, lung, kidney and melanoma. The majority of metastases present as large solitary masses with well-defined margins.     

Precursor lesions of pancreatic cancer: molecular pathology and clinical implications.

BACKGROUND: Pancreatic cancer is a lethal disease, with near uniform 5-year mortality rates. The key to improving survival of pancreatic cancer rests upon early detection of this neoplasm at a resectable, and hence potentially curable, stage. METHODS: We review the current state of the literature vis-à-vis the three common precursor lesions of pancreatic adenocarcinoma: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. We also discuss two clinical scenarios of emerging importance, namely asymptomatic pancreatic cysts ('pancreatic incidentalomas') and the significance of precursor lesions in familial pancreatic cancer kindreds. RESULTS: Pancreatic intraepithelial neoplasias are the microscopic precursor lesions of pancreatic adenocarcinomas, while intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are macroscopic, cystic precursor lesions. All three noninvasive entities demonstrate a multistep morphologic and genetic progression that culminates in frank invasive adenocarcinoma. Despite these commonalities, each precursor lesion harbors a unique repertoire of clinicopathologic and genetic characteristics that has an impact on natural history and prognosis of these lesions. Due to improvements in radiological techniques, asymptomatic pancreatic cysts are being increasingly discovered in the general population; intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are the most common underlying histology in resected incidentalomas of the pancreas. Pancreatic asymptomatic cysts present an enormous challenge in terms of accurate diagnosis and management stratification. Incorporating molecular signatures of cystic precursor lesions into the diagnostic algorithm will likely become a standard of care for asymptomatic pancreatic cysts. High-risk individuals from familial pancreatic cancer kindreds are another group of individuals where knowledge of precursor lesions has had a therapeutic impact; sensitive imaging technologies have enabled the identification and subsequent resection of pancreatic cancer precursors in these high-risk individuals, preventing the progression to invasive cancer. CONCLUSIONS: Precursor lesions of pancreatic adenocarcinomas represent a unique opportunity for diagnosis and intervention for a malignancy with near uniform lethality. Further studies on these precursors will enable the development of rational early detection and therapeutic strategies in order to ameliorate pancreatic cancer survival.     

Pancreatic Cysts and Guidelines

Pancreatic cysts, especially incidental asymptomatic ones seen on noninvasive imaging such as CT or MR imaging, remain a clinical challenge. The etiology of such cysts may range from benign cysts without any malignant potential such as pancreatic pseudocysts and serous cystadenomas to premalignant or frankly malignant cysts such as mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, cystic degeneration associated with solid tumors such as pancreatic ductal adenocarcinoma or pancreatic endocrine neoplasms, and solid pseudopapillary neoplasms. The clinical challenge in 2017 is to accurately preoperatively diagnose them and their malignant potential before deciding about surgery, surveillance or doing nothing. This review will focus on the currently available clinical guidelines for doing so.     

Endosonography in the diagnosis and management of pancreatic cysts

Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying riskof malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound(EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration(FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUSFNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUSguided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance.     

Role of endoscopic ultrasonography in pancreatic cystic neoplasms: Where do we stand and where will we go?

We increasingly encounter pancreatic cystic neoplasms (PCN) in clinical practice and the differential diagnoses vary widely from benign to malignant. There is no ‘one and only’ diagnostic procedure for PCN. Multiple modalities including computed tomography, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound (EUS) are widely used, but EUS has the advantage of anatomical proximity to the pancreas and upper gastrointestinal tract. In addition, EUS‐guided fine‐needle aspiration (EUS‐FNA) provides both cytological evaluation and cyst fluid analysis. Although the role of EUS‐FNA for PCN is established, the sensitivity of cytology is low and cyst fluid analysis is only useful for differentiation between mucinous and non‐mucinous cysts. Recently, novel through‐the‐needle imaging under EUS‐FNA, such as confocal laserendomicroscopy, is expected to attribute to a better diagnostic yield. Moreover, feasibility of cyst ablation has been reported and the role of EUS has expanded from diagnosis to treatment. However, clinical impact of cyst ablation in terms of safety, efficacy and cost‐effectiveness should be validated further. In summary, EUS and EUS‐guided intervention does and will play a central role in the management of PCN from surveillance to treatment, but many clinical questions remain unanswered, which warrants well‐designed prospective clinical trials.     

Precursors to pancreatic cancer

Infiltrating ductal adenocarcinoma of the pancreas is believed to arise from morphologically distinct noninvasive precursor lesions. These precursors include the intraductal papillary mucinous neoplasm, the mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia. Intraductal papillary mucinous neoplasms are grossly visible mucin-producing epithelial neoplasms that arise in the main pancreatic duct or one of its branches. The cysts of mucinous cystic neoplasms do not communicate with the major pancreatic ducts, and these neoplasms are characterized by a distinct ovarian-type stroma. Pancreatic intraepithelial neoplasia is a microscopic lesion. This article focuses on the clinical significance of these three important precursor lesions, with emphasis on their clinical manifestations, detection, and treatment.     

Surgical Management of Pancreatic Cysts: A Shifting Paradigm Toward Selective Resection

Due to the widespread use of high-quality cross-sectional imaging, pancreatic cystic neoplasms are being diagnosed with increasing frequency. Clinicians are therefore asked to counsel a growing number of patients with pancreatic cysts diagnosed incidentally at an early, asymptomatic stage. Over the last two decades, accumulating knowledge on the biologic behavior of these neoplasms along with improved diagnostics through imaging and endoscopic cyst fluid analysis have allowed for a selective therapeutic approach toward these neoplasms. On one end of the management spectrum, observation is recommended for typically benign lesions (serous cystadenoma), and on the other end, upfront resection is recommended for likely malignant lesions (main duct IPMN, mucinous cystadenoma, solid pseudopapillary tumor, and cystic pancreatic neuroendocrine tumors). In between, management of premalignant lesions (branch duct IPMN) is dictated by the presence of high-risk features. In general, resection should be considered whenever the risk of malignancy is higher than the risk of the operation. This review aims to describe the evolution and current status of evidence guiding the selection of patients with pancreatic cystic neoplasms for surgical resection, along with a specific discussion on the type of resection required and expected outcomes.     

Endoscopic diagnosis and treatment of pancreatic cysts

Pancreatic cystic neoplasms have emerged as an important new opportunity for many disciplines to participate in the diagnosis and management of early pancreatic neoplasia. With an increase in an understanding of these lesions and their potential for malignant transformation, there has been a dramatic increase in the frequency of diagnosis. We critically examined the literature on diagnostic methods for pancreatic cystic lesions over the past 5 years. The methods of endoscopic pancreatic pseudocyst drainage and clinical outcomes are also discussed. Morphologic studies of cystic lesions using cross-sectional imaging or endoscopic ultrasound have a low diagnostic rate. Cyst fluid analysis with the use of tumor markers (eg, carcinoembryonic antigen) increases the accuracy of diagnosis. The management of cystic lesions is heavily dependent on the type of cyst, the neoplastic potential, and the risk of surgery. The traditional therapy is pancreatic resection and not cyst enucleation. In contrast to cystic neoplasms, pseudocysts are localized collections of inflammatory fluid that mimic cystic neoplasms. The fluid collections arise from chronic pancreatitis and ductal leaks. Because pseudocysts have no neoplastic potential, they can be drained rather than resected. Drainage can be safely accomplished with external catheters or endoscopically with internal catheters. As we learn more about the pathophysiology of the various cystic lesions, treatment will be tailored to the specific cyst lesion. Endoscopic ultrasound has an important role in the characterization of pancreatic cystic lesions and helps in selection of the optimal treatment modality.     

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of pancreatic cysts by combined cytopathology and cystic content analysis

Recent advances in imaging technology have resulted in an increase in incidental discoveries of pancreatic cystic lesions. Pancreatic cysts comprise a wide variety of lesions and include non-neoplastic cysts and neoplastic cysts. Because some pancreatic cysts have more of a malignant potential than others, it is absolutely essential that an accurate diagnosis is rendered so that effective care can be given to each patient. In many centers, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has emerged as the modality of choice that enables one to distinguish between mucinous and non-mucinous lesion, diagnose malignancy and collect cyst fluid for further diagnostic studies, such as pancreatic enzyme levels, molecular analysis and other tumor biomarkers. The current review will focus on EUS-guided FNA and the cytological diagnosis for pancreatic cysts.     

Presentation and management of pancreatic cystic neoplasms

Pancreatic cystic neoplasms are less frequent than other pancreatic tumors, but because of the wide availability and improvement of modern imaging methods, these neoplasms are being recognized with increasing frequency and it is often possible to be differentiated preoperatively not only from other cystic pancreatic disorders but also from one another. Most patients have no symptoms while clinical signs are not really useful in the clinical work up, and when they are present, they never help us to identify the type of pathology. Treatment differs with the diagnosis. Serous cystic neoplasms are uniformly benign and usually do not mandate resection unless this lesion is symptomatic. In contrast, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms have a premalignant or malignant tendency, and therefore should be managed aggressively by pancreatic resection; in the absence of invasive disease, prognosis is excellent after appropriate surgery, but the presence of invasive malignancy signifies a poor prognosis. Solid pseudopapillary neoplasms have nonaggressive behavior and their management is related to the extension of the disease. The purpose of this article is to review the types of pancreatic cystic neoplasms, their diagnosis, indications for surgical treatment, and outcome.     

Macrocystic type of serous cystadenoma with a communication between the cyst and pancreatic duct

A 42-year-old woman with a cystic lesion in the head of the pancreas was evaluated by using abdominal ultrasonography, a computed tomographic scan, magnetic resonance imaging and endoscopic retrograde pancreatography. Multiple cystic lesions, 5 cm in diameter, which had papillary protrusion inside the cyst in the head of the pancreas and had the communication between the cysts and pancreatic duct, were determined. Pylorus-preserving pancreaticoduodenectomy was performed under the diagnosis of mucinous cystic neoplasm of the pancreas. Although the cut surface of the tumor showed a macrocystic tumor of 3 cm in diameter, part of the cyst wall was cavernous. A histopathological examination showed single-layered cuboidal cells, which lead to the diagnosis as being serous cystadenoma of the pancreas. Serous cystadenoma is a rare, almost benign pancreatic tumor. The macrocystic subtype of serous cystadenoma is even more rare. We describe a patient who had this macrocystic subtype of serous cystadenoma with a communication between the cyst and pancreatic duct. This case illustrates the difficulty in the diagnosis of cystic lesions in the pancreas, and might support the single category of cystic lesions of the pancreas.     

Frequent multiple c‐ki‐ras oncogene activation in pancreatic juice from patients with benign pancreatic cysts

Background: We detected benign pancreatic cysts in more than half of 12 cases of in situ pancreatic cancer. A few investigators, having detected K‐ras mutation in pancreatic juice before the clinical diagnosis of pancreatic cancer, have suggested that this mutation might be an early event in pancreatic oncogenesis. Therefore, in the present study, we evaluated whether benign pancreatic cysts are a precancerous condition as reflected by K‐ras mutation in pancreatic juice. Methods: Pancreatic juice was collected through endoscopic cannulation of the pancreatic duct. Analysis of the mutations was performed using the polymerase chain reaction–preferential homoduplex formation assay. Results: The frequencies and types of K‐ras point mutations and the rate of multiplicity of K‐ras mutations in patients with benign pancreatic cyst were the same as those with pancreatic cancer. Conclusions: Multiple K‐ras codon 12 mutations in the pancreatic juice of patients with benign pancreatic cysts are present as frequently as those with pancreatic cancer. These results indicate that patients with benign cysts may be at a high‐risk for the development of pancreatic cancer.     

The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology.

BACKGROUND & AIMS: Current methods to detect malignancy in mucinous cystic neoplasms of the pancreas remain inadequate. The role of detailed molecular analysis in this context was investigated. METHODS: Endoscopic ultrasound-guided pancreatic cyst aspirates were prospectively collected during a period of 19 months and studied for cytology, carcinoembryonic antigen level, and molecular analysis. Molecular evaluation incorporated DNA quantification (amount and quality), k-ras point mutation, and broad panel tumor suppressor linked microsatellite marker allelic loss analysis by using fluorescent capillary electrophoresis. The sequence of mutation acquisition was also calculated on the basis of a clonal expansion model, and comparison was made to the final pathology. RESULTS: Thirty-six cysts with confirmed histology were analyzed. There were 11 malignant, 15 premalignant, and 10 benign cysts. Malignant cysts could be differentiated from premalignant cysts on the basis of fluid carcinoembryonic antigen level (P=.034), DNA quality (P=.009), number of mutations (P=.002), and on the sequence of mutations acquired (P<.001). Early k-ras mutation followed by allelic loss was the most predictive of a malignant cyst (sensitivity, 91%; specificity, 93%). CONCLUSIONS: Malignant cyst fluid contains adequate DNA to allow mutational analysis. A first hit k-ras mutation followed by allelic loss is most predictive of the presence of malignancy in a pancreatic cyst. This approach should serve as an ancillary tool to the conventional work-up of pancreatic cysts. Cumulative amount and timing of detectable mutational damage can assist in diagnosis and clinical management.     

Evaluation and management of cystic pancreatic tumors: emphasis on the role of EUS FNA.

Cystic lesions of the pancreas are increasingly recognized and usually represent pseudocysts or cystic pancreatic tumors (CPTs), but also include congenital cysts, acquired cysts, extrapancreatic cysts, or cystic degeneration of solid tumors. It is important to distinguish CPT lesions given their varied prognosis and therapy. Mucinous varieties of CPTs (mucinous cystic neoplasms and intraductal papillary mucinous tumors) are premalignant or malignant, and surgical resection is generally recommended in good operative candidates. In contrast, nonmucinous CPTs include serous cystadenomas with a very low malignant potential, or pseudocysts, which are always benign. As a result, nonmucinous CPTs are generally resected only when inducing symptoms or complications. Review of the clinical, imaging, laboratory, and pathology information may clarify the specific tumor type. The relatively limited accuracy of any one modality requires that we consider the combined results when making management decisions.     

Management of pancreatic ductal leaks and fistulae

Pancreatic duct leaks can occur as a result of both acute and chronic pancreatitis or in the setting of pancreatic trauma. Manifestations of leaks include pseudocysts, pancreatic ascites, high amylase pleural effusions, disconnected duct syndrome, and internal and external pancreatic fistulas. Patient presentations are highly variable and range from asymptomatic pancreatic cysts to patients with severe abdominal pain and sepsis from infected fluid collections. The diagnosis can often be made by high‐quality cross‐sectional imaging or during endoscopic retrograde cholangiopancreatography (ERCP). Because of their complexity, pancreatic leak patients are best managed by a multidisciplinary team comprised of therapeutic endoscopists, interventional radiologists, and surgeons in the field of pancreatic interventions. Minor leaks will often resolve with conservative management while severe leaks will frequently require interventions. Endoscopic treatments for pancreatic duct leaks have replaced surgical interventions in many situations. Interventional radiologists also have the ability to offer therapeutic interventions for many leak patients. The mainstay of endotherapy for pancreatic leaks is transpapillary pancreatic duct stenting with a stent that bridges the leak if possible, but varies based on the manifestation and clinical presentation. Fluid collections that result from leaks, such as pseudocysts, can often be treated by endoscopic transluminal drainage with or without endoscopic ultrasound or by percutaneous drainage. Endoscopic interventions have been shown to be effective and have an acceptable complication rate.     

Combination of cyst fluid CEA and CA 125 is an accurate diagnostic tool for differentiating mucinous cystic neoplasms from intraductal papillary mucinous neoplasms

Background/objectivesDespite advances in imaging techniques, diagnosis and management of pancreatic cystic lesions still remains challenging. The objective of this study was to determine the utility of cyst fluid analysis (CEA, CA 19-9, CA 125, amylase, and cytology) in categorizing pancreatic cystic lesions, and in differentiating malignant from benign cystic lesions.MethodsA retrospective analysis of 68 patients with histologically and clinically confirmed cystic lesions was performed. Cyst fluid was obtained by surgical resection (n = 45) or endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) (n = 23). Cyst fluid tumor markers and amylase were measured and compared between the cyst types.ResultsReceiver operating characteristic (ROC) curve analysis of the tumor markers demonstrated that cyst fluid CEA provided the greatest area under ROC curve (AUC) (0.884) for differentiating mucinous versus non-mucinous cystic lesions. When a CEA cutoff value was set at 67.3 ng/ml, the sensitivity, specificity and accuracy for diagnosing mucinous cysts were 89.2%, 77.8%, and 84.4%, respectively. The combination of cyst fluid CEA content >67.3 ng/ml and cyst fluid CA 125 content >10.0 U/ml segregated 77.8% (14/18) of mucinous cystic neoplasms (MCNs) from other cyst subtypes. On the other hand, no fluid marker was useful for differentiating malignant versus benign cystic lesions. Although cytology (accuracy 83.3%) more accurately diagnosed malignant cysts than CEA (accuracy 65.6%), it lacked sensitivity (35.3%).ConclusionsOur results demonstrate that cyst fluid CEA can be a helpful marker in differentiating mucinous from non-mucinous, but not malignant from benign cystic lesions. A combined CEA and CA 125 approach may help segregate MCNs from IPMNs.