Diagnosis and treatment of biliary mucinous cystic neoplasms: A single-center experience

Background: Biliary mucinous cystic neoplasms(BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and prognosis of BMCNs in a large single center. Methods: We analyzed 49 patients with BMCNs confirmed by postoperative pathology at the First Afflliated Hospital, Zhejiang University School of Medicine between January 2007 and December 2021. Results: Among the 49 patients, 37 were female(75.5%), and the average age was 57.04 years. Common symptoms included abdominal discomfort, jaundice and fever, while 22 patients(44.9%) had no symptoms. Serum carbohydrate antigen(CA) 19-9 and CA125 concentrations were elevated in 34.8% and 19.6% of patients, respectively. Forty-eight patients had tumors in the intrahepatic bile ducts and only one had a tumor in the extrahepatic bile duct. Forty-eight patients with noninvasive intrahepatic BMCNs were further analyzed in terms of pathological features: 34(70.8%) had low-grade intraepithelial neoplasms(LGINs), and 14(29.2%) had high-grade intraepithelial neoplasms(HGINs). The potential immunohistochemical markers of BMCNs were cytokeratin(CK) 19, CK7, estrogen receptor and progesterone receptor. Follow-up data for 37 patients with intrahepatic BMCNs were obtained. The median overall survival(OS) of BMCNs was not reached. The longest survival time was 137 months.The 5-and 10-year OS rates were 100% and 85.4%, respectively. The 5-and 10-year recurrence-free survival(RFS) rates were 93.9% and 80.2%, respectively. Conclusions: BMCNs are rare cystic neoplasms that commonly occur in middle-aged females. BMCNs can only be diagnosed and classified by postoperative pathology, as there are no specific clinical presentations, serological indicators or imaging modalities for preoperative diagnosis. Complete surgical resection is necessary for BMCNs, and the postoperative prognosis is favorable.

Malignancy risk factors and prognostic variables of pancreatic mucinous cystic neoplasms in Chinese patients

BACKGROUND Pancreatic mucinous cystic neoplasms(MCNs)represent one of the precursor lesions of pancreatic ductal adenocarcinoma,and their detection has been facilitated by advances in preoperative imaging.Due primarily to the rarity of MCNs,however,there is limited knowledge regarding the prognostic variables and high-risk factors for malignant transformation.A more comprehensive and nuanced approach is necessary to fill this gap and provide a basis for improved treatment decisions and patient outcomes.AIM To investigate the high-risk factors associated with malignant MCNs and to explore the prognostic factors of MCN with associated invasive carcinoma(MCNAIC).METHODS All cases of resected MCNs from a single high-volume institution between January 2012 and January 2022 were retrospectively reviewed.Only cases with ovarian-type stroma verified by progesterone receptor staining were included.Preoperative features,histological findings and postoperative course were documented.Multivariate logistic regression was employed to investigate variables related to malignancy.Survival analysis was performed using the Kaplan-Meier curve,and the prognostic factors were assessed to evaluate the postoperative course of patients with MCN-AIC.RESULTS Among the 48 patients,36 had benign MCNs,and 12 had malignant MCNs(1 high-grade atypical hyperplasia and 11 MCN-AIC).Age,tumour size,presence of solid components or mural nodules and pancreatic duct dilatation were identified as independent risk factors associated with malignancy.The follow-up period ranged from 12 mo to 120 mo,with a median overall survival of 58.2 mo.Only three patients with MCN-AIC died,and the 5-year survival rate was 70.1%.All 11 cases of MCN-AIC were stage I,and extracapsular invasion was identified as a prognostic factor for poorer outcomes.CONCLUSION The risk factors independently associated with malignant transformation of MCNs included age,tumour size,presence of solid components or mural nodules,and pancreatic duct dilatation.Our study also revealed that encapsulated invasion was a favourable prognostic factor in MCN-AIC patients.

Management of mucinous cystic neoplasms of the pancreas

The purpose of this study was to investigate the actual management of mucinous cystic neoplasm (MCN) of the pancreas. A systematic review was performed in December 2009 by consulting PubMed MEDLINE for publications and matching the "pancreatic mucinous cystic neoplasm", "pancreatic mucinous cystic tumour", "pancreatic mucinous cystic mass", "pancreatic cyst", and "pancreatic cystic neoplasm" to identify English language articles describing the diagnosis and treatment of the mucinous cystic neoplasm of the pancreas. In total, 16 322 references ranging from January 1969 to December 2009 were analysed and 77 articles were identified. No articles published before 1996 were selected because MCNs were not previously considered to be a completely autonomous disease. Definition, epidemiology, anatomopathological findings, clinical presentation, preoperative evaluation, treatment and prognosis were reviewed. MCNs are pancreatic mucinproducing cysts with a distinctive ovarian-type stroma localized in the body-tail of the gland and occurring in middle-aged females. The majority of MCNs are slow growing and asymptomatic. The prevalence of invasive carcinoma varies between 6% and 55%. Preoperative diagnosis depends on a combination of clinical features, tumor markers, computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound with cyst fluid analysis, and positron emission tomography-CT. Surgery is indicated for all MCNs.

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging (MRI)/magnetic resonance cholangio pancreatography (MRCP) and computer tomography (CT) scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms (IPMN). While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.

Pancreatic endometrial cyst mimics mucinous cystic neoplasm of the pancreas

Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are exceedingly rare lesions that are difficult to diagnose pre-operatively. This report describes the findings in a 43-year-old patient with a recent episode of acute pancreatitis who presented with a large cyst in the tail of the pancreas. Imaging demonstrated a loculated pancreatic cyst, and cyst fluid aspiration revealed an elevated amylase and carcinoembryonic antigen. The patient experienced an interval worsening of abdominal pain, fatigue, diarrhea, and a 15-pound weight loss 3 mo after the initial episode of pancreatitis. With concern for a possible pre-malignant lesion, the patient underwent a laparoscopic distal pancreatectomy with splenectomy, which revealed a 16cm×12cm×4cm lesion. Final histopathology was consistent with an intra-pancreatic endometrial cyst. Here we discuss the overlapping imaging and laboratory features of pancreatic endometrial cysts and mucinous cystic neoplasms of the pancreas.

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct:A case report

Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

Mucinous cystic neoplasm of the liver: A case report

BACKGROUND Mucinous cystic neoplasm of the liver(MCN-L)is a cyst-forming epithelial neoplasm.The most distinguishing feature is the ovarian-type subepithelial stroma on pathological examination.CASE SUMMARY An abdominal ultrasound incidentally revealed a liver tumor in a 32-year-old woman.Physical and laboratory examination results did not reveal any abnormalities.Enhanced abdominal computed tomography(CT)revealed a cystic space measuring 7.2 cm×5.4 cm in the liver.Subsequent CT showed an increase in tumor size.Thus,we performed surgical resection of the tumor and gallbladder.Postoperative histopathological examination confirmed the diagnosis of MCN-L.At the 6-mo of follow-up,no recurrence was observed on ultrasound or CT.CONCLUSION Since preoperative diagnosis of MCN-L is difficult,active surgery is recommended and helpful for the diagnosis and treatment of MCN-L.

Anaplastic carcinoma associated with a mucinous cystic neoplasm of the pancreas during pregnancy:Report of a case and a review of the literature

Oncogenesis of anaplastic carcinoma of the pancreas is a subject of controversy, because it shows sarcomatous nature with extremely poor prognosis. We herein report an unusual case of anaplastic carcinoma occurring with a recurrent mucinous cystic neoplasm in a 38-year-old female. A 10-cm retroperitoneal cystic mass was pointed out in the first pregnancy and a probable diagnosis of mucinous cystic neoplasm was made in October 2000. She refused surgery first and delivered her baby uneventfully. During her second pregnancy in 2002, however, she presented hematemesis and underwent urgent distal pancreatectomy, splenectomy and partial resection of the gastric wall where the tumor perforated. A diagnosis of borderline-type mucinous cystic neoplasm with ovarian-like stroma was made. Nine months later, CT visualized a recurrent cystic tumor near the pancreatic stump, which was subsequently resected. Pathology revealed that the tumor was composed of two different components of borderline-type mucinous cystic neoplasm and anaplastic carcinoma. The latter was intensely positive for vimentin, CD68, p53 and focally for cytokeratin, suggesting both sarcomatous and carcinomatous differentiation. She survived four years after the second surgery without tumor recurrence. Although the origin of anaplastic carcinoma has not been determined yet, it should be remembered that anaplastic carcinoma can occur in association with mucinous cystic neoplasm of more benign histology.

Validation of serum tumor biomarkers in predicting advanced cystic mucinous neoplasm of the pancreas

BACKGROUND Early detection of advanced cystic mucinous neoplasms[(A-cMNs),defined as high-grade dysplasia or malignancy]of the pancreas is of great significance.As a simple and feasible detection method,serum tumor markers(STMs)may be used to predict advanced intraductal papillary mucinous neoplasms(IPMNs)and mucinous cystic neoplasms(MCNs).However,there are few studies on the usefulness of STMs other than carbohydrate antigen(CA)19-9 for early detection of A-cMNs.AIM To study the ability of five STMs-CA19-9,carcinoembryonic antigen(CEA),CA125,CA724,and CA242 to predict A-cMNs and distinguish IPMNs and MCNs.METHODS We mainly measured the levels of each STM in patients pathologically diagnosed with cMNs.The mean levels of STMs and the number of A-cMN subjects with a higher STM level than the cutoff were compared respectively to identify the ability of STMs to predict A-cMNs and distinguish MCNs from IPMNs.A receiver operating characteristic curve with the area under curve(AUC)was also created to identify the performance of the five STMs.RESULTS A total of 187 patients with cMNs were identified and 72 of them showed AcMNs.We found that CA19-9 exhibited the highest sensitivity(SE)(54.2%)and accuracy(76.5%)and a moderate ability(AUC=0.766)to predict A-cMNs.In predicting high-grade dysplasia IPMNs,the SE of CA19-9 decreased to 38.5%.The ability of CEA,CA125,and CA724 to predict A-cMNs was low(AUC=0.651,0.583,and 0.618,respectively).The predictive ability of CA242 was not identified.The combination of STMs improved the SE to 62.5%.CA125 may be specific to the diagnosis of advanced MCNs.CONCLUSION CA19-9 has a moderate ability,and CEA,CA125,and CA724 have a low ability to predict A-cMNs.The combination of STM testing could improve SE in predicting A-cMNs.

Large mucinous cystic neoplasm of the pancreas associated with pregnancy

Mucinous cystic neoplasms (MCNs) of the pancreas occur mostly in females and are potentially sex hormone-sensitive. However, a MCN occurring during pregnancy is quite rare. A 30-year-old woman in the tenth week of pregnancy was referred to us because of a rapid increase in left hypochondrial distending pain. On ultrasound, the patient had a large intra-abdominal cystic lesion. She was thereafter diagnosed with missed abortion and a computed tomography scan showed that the lesion was a cystic tumor 18 cm in diameter originating from the pancreatic tail. The patient subsequently underwent tumor resection with distal pancreatectomy, sparing the spleen. Histopathological analysis of the specimen revealed a pancreatic MCN with moderate dysplasia. Immunohistochemically, the tumor was positive for both estrogen and progesterone receptors. To our knowledge, this is the first reported case of pancreatic MCN with moderate dysplasia in association with pregnancy. Our case strongly indicates that pancreatic MCN is female-hormone dependent.

Imaging pitfalls of pancreatic serous cystic neoplasm and its potential mimickers

The aim of this article is to clarify diagnostic pitfalls of pancreatic serous cystic neoplasm(SCN) that may result in erroneous characterization. Usual and unusual imaging findings of SCN as well as potential SCN mimickers are presented. The diagnostic key of SCN is to look for a cluster of microcysts(honeycomb pattern), which may not be always found in the center. Fibrosis in SCN may be mistaken for a mural nodule of intraductal papillary mucinous neoplasm(IPMN). The absence of cyst wall enhancement may be helpful to distinguish SCN from mucinous cystic neoplasm. However, oligocystic SCN and branch duct type IPMN may morphologically overlap. In addition, solid serous adenoma, an extremely rare variant of SCN, is difficult to distinguish from neuroendocrine tumor.

Diagnostic and therapeutic endoscopic approaches to intraductal papillary mucinous neoplasm

Pancreatic cystic lesions are increasingly identified on routine imaging.One specific lesion,known as intraductal papillary mucinous neoplasm(IPMN),is a mucinous,pancreatic lesion characterized by papillary cells projecting from the pancreatic ductal epithelium.The finding of mucin extruding from the ampulla is essentially pathognomonic for diagnosing these lesions.IPMNs are of particular interest due to their malignant potential.Lesions range from benign,adenomatous growths to highgrade dysplasia and invasive cancer.These mucinous lesions therefore require immediate attention to determine the probability of malignancy and whether observation or resection is the best management choice.Unresected lesions need long-term surveillance monitoring for malignant transformation.The accurate diagnosis of these lesions is particularly challenging due to the substantial similarities in morphology of pancreatic cystic lesions and limitations in current imaging technologies.Endoscopic evaluation of these lesions provides additional imaging,molecular,and histologic data to aid in the identification of IPMN and to determine treatment course.The aim of this article is to focus on the diagnostic and therapeutic endoscopic approaches to IPMN.

Pancreatic intraductal papillary mucinous neoplasms:Current diagnosis and management

Intraductal papillary mucinous neoplasms(IPMNs)represent approximately 1%of all pancreatic neoplasms and 25%of cystic neoplasms.They are divided into three types:main duct-IPMN(MD-IPPMN),branch duct-IPMN(BD-IPMN),and mixed type-IPMN.In this review,diagnostics,including clinical presentation and radiological investigations,were described.Magnetic resonance imaging is the most useful for most IPMNs.Management depends on the type and radiological features of IPMNs.Surgery is recommended for MD-IPMN.For BD-IPMN,management involves surgery or surveillance depending on the tumor size,cyst growth rate,solid components,main duct dilatation,high-grade dysplasia in cytology,the presence of symptoms(jaundice,new-onset diabetes,pancreatitis),and CA 19.9 serum level.The patient’s age and comorbidities should also be taken into consideration.Currently,there are different guidelines regarding the diagnosis and management of IPMNs.In this review,the following guidelines were presented:Sendai International Association of Pancreatology guidelines(2006),American Gastroenterological Association guidelines,revised international consensus Fukuoka guidelines(2012),revised international consensus Fukuoka guidelines(2017),and European evidence-based guidelines according to the European Study Group on Cystic Tumours of the Pancreas(2018).The Verona Evidence-Based Meeting 2020 was also presented and discussed.

Treatment of a giant low-grade appendiceal mucinous neoplasm:A case report

BACKGROUND Low-grade appendiceal mucinous neoplasm(LAMN)is extremely rare and easily misdiagnosed before surgery.CASE SUMMARY We report the treatment of an asymptomatic case of LAMN diagnosed by magnetic resonance imaging(MRI)and surgical findings.A 70-year-old woman presented with an adnexal mass found by physical examination in July 2020.Gynecologic ultrasonography revealed a cystic mass in the right adnexa,and computed tomography showed a cystic mass in the pelvic cavity.All tumor markers were normal.A further MRI examination suggested mucinous neoplasm in the right pelvic cavity,excluding the possibility of adnexal cyst.Laparoscopic exploration found a huge cystic mass of about 10 cm×7 cm that originated from the apex of the appendix,with spontaneous rupture.LAMN was confirmed by pathological examination.As of May 2021,no disease recurrence occurred after an open appendectomy.CONCLUSION This case indicates that we should pay more attention to female patients who are clinically diagnosed with an adnexal mass at admission,.The physical examination should be done carefully,and the laboratory and imaging examination results should be comprehensively analyzed to avoid misdiagnosis and to ensure prompt diagnosis and treatment,and to improve prognosis.MRI may be a better option for the diagnosis of appendiceal mucinous neoplasm.

Needle-based confocal endomicroscopy in the discrimination of mucinous from non-mucinous pancreatic cystic lesions

BACKGROUND Pancreatic cystic lesions(PCLs)are considered a precursor of pancreatic cancer.Needle-based confocal endomicroscopy(nCLE)is an imaging technique that enables visualization of the mucosal layer to a micron resolution.Its application has demonstrated promising results in the distinction of PCLs.This study evaluated the utility of nCLE in patients with indeterminate PCLs undergoing endoscopic ultrasound fine-needle aspiration(EUS-FNA)to distinguish mucinous from non-mucinous lesions.AIM To evaluate the accuracy of nCLE in indeterminate PCLs undergoing EUS-FNA to distinguish mucinous from non-mucinous lesions.METHODS Patients who required EUS-FNA between 2015 and 2017 were enrolled prospectively.During EUS-FNA,confocal imaging,analyses of the tumor markers carcinoembryonic antigen and amylase,and cytologic examination were conducted.All patients were followed for at least 12 mo and underwent laboratory testing and computed tomography scanning or magnetic resonance imaging.nCLE videos were independently reviewed by 6 observers to reach a final diagnosis(mucinous vs non-mucinous)based on criteria derived from previous studies;if there was disagreement>20%,a final diagnosis was discussed after consensus re-evaluation.The sensitivity,specificity,and accuracy of nCLE were calculated.Adverse events were recorded.RESULTS Fifty-nine patients were included in this study.Final diagnoses were derived from surgery in 10 patients,cytology in 13,and imaging and multidisciplinary team review in 36.Three patients were excluded from final diagnosis due to problems with nCLE acquisition.Fifty-six patients were included in the final analysis.The sensitivity,specificity,and accuracy of nCLE were 80%[95%confidence interval(CI):65-90],100%(95%CI:72-100),and 84%(95%CI:72-93),respectively.Postprocedure acute pancreatitis occurred in 5%.CONCLUSION EUS-nCLE performs better than standard EUS-FNA for the diagnosis of indeterminate PCL.

Natural history of intraductal papillary mucinous neoplasia:How much do we really know?

Information on the natural history of intraductal papillary mucinous neoplasia(IPMN) is currently inadequate due to a lack of carefully orchestrated long-term followup on a large cohort of patients with asymptomatic disease.Based on the available data,one can draw the conclusions that main duct IPMN is commonly associated with malignancy and an aggressive operative stance should be taken with resection being offered to most patients who are suitable operative candidates.In contrast,the majority of branch type IPMN with a diameter of less than 3 cm can be safely followed with routine surveillance imaging provided they lack the high-risk covariates of age,symptomatology,nodularity or wall thickness.

Pancreatic cystic neoplasms:a comprehensive approach to diagnosis and management

Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years.Accurate diagnosis is crucial,as errors occur in approximately one-third of resected cysts discovered incidentally.Various imaging modalities such as computed tomography,magnetic resonance imaging,and endoscopic techniques are available to address this challenge.However,risk stratification remains problematic,with guideline inconsistencies and diagnostic accuracy varying according to cyst type.This review proposed a stepwisemanagement approach,considering patient factors,imaging results,and specific features.This patient-centered model offers a structured framework for optimizing the care of individuals with pancreatic cystic neoplasms.

Prevalence and outcomes of pancreatic cystic neoplasms in liver transplant recipients

AIM To determine the prevalence,characteristics and clinical course of pancreatic cystic neoplasms(PCNs) in liver transplantation(LT) recipients.METHODS We retrospectively studied consecutive patients who underwent LT between January 1998 to April 2016. Clinical and laboratory data were obtained from patient medical records. Imaging findings on computed tomography and magnetic resonance cholangiopancreatography were reviewed by two radiologists.RESULTS During the study period,872 patients underwent cadaveric LT. Pancreatic cysts were identified in 53/872(6.1%) and 31/53(58.5%) were PCNs [28 intraductal papillary mucinous neoplasm(IPMN),2 mucinous cystic neoplasm(MCN),1 serous cystadenoma]. Patients with PCNs exhibited less male predominance(55% vs 73%,P = 0.03) compared to patients without pancreatic cysts. Thirteen patients(42%) were diagnosed with PCN pre-LT while 18 patients(58%) developed PCN post-LT. The median size of PCNs was 13 mm [interquartile range(IQR) 10-20 mm]. All IPMNs were side-branch type. Most PCNs were found in the head and body of pancreas(37% each),followed by the tail(25%). Five patients underwent further evaluation with endoscopic ultrasound. Progress imaging was performed on 81% of patients. PCNs remained stable in size and number in all but 2 patients. During a median follow up of 39 mo(IQR 26-58 mo),the 2(6%) patients with MCN underwent pancreatectomy. No PCN patient developed pancreatic adenocarcinoma,while 5 died from illnesses unrelated to the PCN. Among patients without PCN,1/841(0.1%) developed pancreatic adenocarcinoma.CONCLUSION The prevalence of PCNs in LT recipients was similar to the general population(3.6%,31/872). Side-branch IPMNs do not appear to have accelerated malignant potential in post-LT patients,indicating the current surveillance guidelines are applicable to this group.

Diagnosis and management of relapsing pancreatitis associated with cystic neoplasms of the pancreas

One of the most important causes of relapsing pancreatitis is a cystic neoplasm of the pancreas. These low grade malignancies may cause pancreatitis by obstructing or communicating with a pancreatic duct. Patients with relapsing pancreatitis and a focal fluid fluid collection should be investigated for the possibility of a mucinous cystic neoplasm. Cross sectional imaging can provide a diagnosis with the imaging findings of a low attenuation cystic lesion containing mural calcification (CT scanning) or a lobular T2 enhancing lesion (MRCP). Endoscopic ultrasound can provide more detailed imaging with the ability to guide fine needle aspiration of the cyst fluid. Cyst fluid analysis can provide a diagnosis of a mucinous cystic lesion with the combination of cytology (mucinous epithelium), elevated carcinoembryonic antigen (CEA), and the presence of DNA mutations. Management of these patients consists of surgical resection and monitoring in patients not able to withstand surgery.

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions

BACKGROUND Pancreatic cystic lesions(PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions.AIM To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen(CA)19-9, CA72-4], carcinoembryonic antigen(CEA), serine protease inhibitor Kazal-type 1(SPINK1), interleukin 1 beta(IL1-β), vascular endothelial growth factor A(VEGF-A), and prostaglandin E2(PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions.METHODS This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound(EUS) and EUS-fine needle aspiration(EUS-FNA) for characterization and sampling of different PCLs.RESULTS The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance(59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively(P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance(P < 0.0001). In contrast, IL-1β, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions.CONCLUSION EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.