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.

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.

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.

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.

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.

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.

Update on mucinous cystic neoplasm of the pancreas:a narrative review

Mucinous cystic neoplasm(MCN)of the pancreas is an exocrine cystic tumor with a potential of harboring malignancy.The latest World Health Organization classification of tumors of digestive system designates malignant MCN as MCN with associated invasive carcinoma(MCN-AIC).Since its separation from other pancreatic cystic tumors in 1978,much progress has been made in our understanding of MCN in epidemiology,clinical and pathological features,biological behavior,as well as prognostic characteristics.This review aims to summarize the current knowledge of MCN and MCN-AIC.

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.

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.

Difficulty with diagnosis of malignant pancreatic neoplasms coexisting with chronic pancreatitis

Chronic pancreatitis is a relatively common disease. We encountered two different cases of belatedly demonstrated pancreatic carcinoma featuring underlying chronic pancreatitis. The first case was one that was highly suspected as that of a malignancy based upon imaging study, but unfortunately, it could not be confirmed by intra-operative cytology at that time. Following this, the surgeon elected to perform only conservative bypass surgery for obstructive biliary complication. Peritoneal carcinomatosis was later noted and the patient finally died. The second case, a malignant mucinous neoplasm,was falsely diagnosed as a pseudocyst, based upon the lesion's sonographic appearance and associated elevated serum amylase levels. After suffering repeated hemoptysis,the patient was found to exhibit lung metastasis and peritoneal seeding. We reviewed some of the literature,including those studies discussing chronic pancreatitis predisposing to a malignant change. These two case analyses illustrate clearly that the diagnosis for such conditions, which is simply based upon imagery or pathological considerations may end up being one of a mistaken malignancy. Some of our suggestions for the treatment of such malignancies as revealed herein include,total pancreatomy for univocal mass lesion, and needle aspiration of lesion-contained tissue for amylase, CA199and CEA levels for a suspicious cystic pancreatic mass.

Recent advances in the diagnostic evaluation of pancreatic cystic lesions

Pancreatic cystic lesions(PCLs)are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population.It has become crucial to identify these PCLs and subsequently risk stratify them to guide management.Given the high morbidity associated with pancreatic surgery,only those PCLs at high risk for malignancy should undergo such treatment.However,current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs.Therefore,research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy.Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing.While cyst fluid glucose has reemerged as a potential biomarker,cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs.Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs.While most of these recent diagnostics are only practiced at selective tertiary care centers,they hold a promise that management of PCLs will only get better in the future.

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.

Pancreatic cystic neoplasms:a review of preoperative diagnosis and management

Pancreatic cystic neoplasms(PCNs) are a diverse group of neoplasms in the pancreas,and are more increasingly encountered with widespread abdominal screening and improved imaging techniques.The most common types of PCNs are serous cystic neoplasms(SCNs),mucinous cystic neoplasms(MCNs),and intraductal papillary mucinous neoplasms(IPMNs).Clinicians frequently feel bewildered in the differential diagnosis and subsequent management among the various types of lesions in the pancreas,which may lead to overtreatment or delayed treatment.The current review provides recent developments in the understanding of the three most common types of PCNs,the latest modalities used in preoperative diagnosis and differential diagnosis,as well as the most up to date management.Suggestions for diagnosis and differential diagnosis of SCNs,MCNs,and IPMNs are also provided for young surgeons.Better understanding of these neoplasms is essential for clinicians to make accurate diagnosis and to provide the best management for patients.

An analysis of clinico-pathologic features of intraductal papillary mucinous neoplasm of the pancreas

The natural history and clinical manifestation of resected intraductal papillary mucinous neoplasm(IPMN)of the pancreas were elucidated,and based on this,a retrospective pancreatic database was reviewed to identify patients with IPMN who were surgically managed in our department from 1999 to June 2006.Pathologic rereview of each case was performed,and the clinico-pathologic features were examined.Student’s T test and x2 analysis were used to identify factors associated with malignancy.Fifty-one patients were identified.There were 33 males and 18 females.One patient’s pancreas was unresectable,two patients underwent a total pancreatectomy,42 patients had a pancreatecoduodenectomy and five patients had distal pancreatectomy.Main-duct type carcinoma was identified in 24 patients;branch-duct type in 15 patients,and mixed type in 12 patients.Invasive carcinoma was present in 35 patients.Weight loss and jaundice occurred more commonly in the invasive group.The average serum CA19-9 level was significantly higher in the invasive group(1542μ vs 94.5μ).The average diameter of the pancreatic duct was also wider in the invasive group(8.7 mm vs 4.3 mm).Significant predictors of malignant IPMNs included weight loss,jaundice,a high level of serum CA19-9,a large pancreatic duct and main-duct type carcinoma.

A bibliometric study on pancreatic cystic disease research

Pancreatic cystic disease is being increasingly identified in patients,and many relevant papers have been published in this field.A bibliometric analysis was previously performed to identify the most influential studies in many subject areas,and the top 100 most cited papers on pancreatic cystic disease were analyzed in this study.The Web of Science database was searched for all papers related to pancreatic cystic disease on June 9,2018.The top 100 most cited papers were selected and listed in descending order based on the total number of citations(TCs).The author,journal,institution,country of origin,and research focus were further analyzed.The most cited papers were published between 1975 and 2015.Intraductal papillary mucinous neoplasm was the most commonly studied subtype(36%),followed by pancreatic pseudocyst(16%),solid pseudopapillary neoplasm(9%),and mucinous cystic neoplasm(7%).The average number of TCs was 282,and the average citation index value was 21.Thirty-eight journals published the top 100 papers;Annals of Surgery(n=14)and Gastrointestinal Endoscopy(n=11)published the most papers.Most papers were published in the United States of America(59%),with the majority from Johns Hopkins Medical Institution(15%).Canto MI from Johns Hopkins Medical Institution authored the largest number of most cited papers(n=8).This study reviews the significant achievements and developmental trends in pancreatic cystic disease.Abbreviations:CI=citation index,IPMN=intraductal papillary mucinous neoplasm,MCN=mucinous cystic neoplasm,PP=pancreatic pseudocyst,SCN=serous cystic neoplasm,SPN=solid pseudopapillary neoplasm,TC=total number of citation.

Pancreatic cystic tumors:an update

Pancreatic cystic tumors(PCTs)comprise a heterogeneous group of entities,accounting for 2%to 10%of pancreatic lesions.The most common types are intraductal papillary mucinous neoplasms(IPMNs),mucinous cystic neoplasm(MCN),and serous cystic neoplasm(SCN),which account for approximately 90%of PCTs.This review discusses updates in pathologic features,malignant transformation,biologic behavior,and molecular evolution of PCTs.IPMN includes main duct and branch duct types.These can also be classified into 4 histologic subtypes based on cell lineages of differentiation,and may be associated with different tumorigenic pathways and clinicopathologic characteristics.The gastric type is the most common and is rarely associated with carcinomas,whereas the pancreatobiliary type is significantly more associated with invasive carcinoma.MCN is a mucinous cystic lesion with the presence of ovarian-type pericystic stroma.Prognosis of the resected non-invasive MCN is excellent,but the long-term survival of MCNs with invasive carcinoma may be poor.SCN includes microcystic adenoma,macrocystic adenoma,and solid variant serous adenoma.Serous cystadenocarcinoma is defined by the presence of distant metastases,which is rare in literature.Intraductal tubulopapillary neoplasm is characterized by uniformly high-grade dysplasia and ductal differentiation without overt production of mucin,with high risk for developing invasion.Acinar cell cystadenoma is a rare benign lesion with acinar differentiation.In addition,some pancreatic neuroendocrine tumors may assume a cystic configuration,sometimes referred to as cystic pancreatic endocrine neoplasm tumor,with a lower pathologic stage.Solid pseudopapillary tumor is composed of poorly cohesive monomorphic epithelial cells forming solid and pseudopapillary structures,with excellent prognosis.