Distinctive expression of CD133 between intraductal papillary neoplasms of the bile duct and bile duct adenocarcinomas

Aim: Intraductal papillary neoplasm of the bile duct (IPNB), a novel entity of biliary disease, is recently advocated as the counterpart of pancreatic intraductal papillary mucinous neoplasm (IPMN) because both are in common with a large amount of mucin production and papillary growth. Based on our recent finding that expression of CD133, a cancer stem cell marker, is lacking in pancreatic IPMN, we herein focused on CD133 expression of IPNB in comparison with intrahepatic cholangiocellular carcinoma (IHCCC) or hilar bile duct cancer (HBDC). Methods: Expression of CD133 protein was immunohistochemically determined in patients with IPNB (n = 7), IHCCC (n = 16) or HBDC (n = 8). In addition, morphological and immunohistochemical mucin expression patterns were characterized in IPNB, and clinicopathological features including prognosis were compared between IPNB and other biliary tumors. Results: The IPNB group included significantly more females than the other two groups, and had a longer survival time. While no CD133 expression was observed in IPNB tumor, 16.4% of cancer cells in IHCCC and 17.2% of cells in HBDC expressed CD133. Among seven patients with IPNB, six (86%) were morphologically the pancreatobiliary type and four of six showed mucin expression pattern of the typical pancreatobiliary type (MUC1+/MUC2‐/MUC5AC+). Conclusion: Loss of CD133 expression supports the hypothesis that IPNB is a counterpart of pancreatic IPMN with a differing carcinogenesis from conventional bile duct adenocarcinomas.     

Intraductal papillary neoplasm of the bile duct: A biliary equivalent to intraductal papillary mucinous neoplasm of the pancreas?

Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma characterized by intraductal growth and better outcome compared with the more common nodular-sclerosing type. IPNB is a recognized precursor of invasive carcinoma, but its pathogenesis and natural history are ill-defined. This study examines the clinicopathologic features and outcomes of IPNB. A consecutive cohort of patients with bile duct cancer (hilar, intrahepatic, or distal) was reviewed, and those with papillary histologic features identified. Histopathologic findings and immunohistochemical staining for tumor markers and for cytokeratin and mucin proteins were used to classify IPNB into subtypes. Survival data were analyzed and correlated with clinical and pathologic parameters. Thirty-nine IPNBs were identified in hilar (23/144), intrahepatic (4/86), and distal (12/113) bile duct specimens between 1991 and 2010. Histopathologic examination revealed 27 pancreatobiliary, four gastric, two intestinal, and six oncocytic subtypes; results of cytokeratin and mucin staining were similar to those of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Invasive carcinoma was seen in 29/39 (74%) IPNBs. Overall median survival was 62 months and was not different between IPNB locations or subtypes. Factors associated with a worse median survival included presence and depth of tumor invasion, margin-positive resection, and expression of MUC1 and CEA. Conclusion: IPNBs are an uncommon variant of bile duct cancer, representing approximately 10% of all resectable cases. They occur throughout the biliary tract, share some histologic and clinical features with IPMNs of the pancreas, and may represent a carcinogenesis pathway different from that of conventional bile duct carcinomas arising from flat dysplasia. Given their significant risk of harboring invasive carcinoma, they should be treated with complete resection. (HEPATOLOGY 2012).     

Current status of diagnosis and therapy for intraductal papillary neoplasm of the bile duct

Bile duct epithelial tumours showing papillary neoplasm in the bile duct lumen are present in the intrahepatic and extrahepatic bile ducts. Clinicopathological images of these tumours are distinctive and diverse, including histological images with a low to high grade dysplasia, infiltrating and noninfiltrating characteristics, excessive mucus production, and similarity to intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The World Health Organization Classification of Tumours of the Digestive System in 2010 named these features, intraductal papillary neoplasm of the bile duct (IPNB), as precancerous lesion of biliary carcinoma. IPNB is currently classified into type 1 that is similar to IPMN, and type 2 that is not similar to IPMN. Many of IPNB spreads superficially, and diagnosis with cholangioscopy is considered mandatory to identify accurate localization and progression. Prognosis of IPNB is said to be better than normal bile duct cancer.     

Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin.Consequently,preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular,histological and pathophysiological features.Intraepithelial neoplasms are reported in biliary tract,as biliary intraepithelial neoplasm(BilIN),and in pancreas,as pancreatic intraepithelial neoplasm(PanIN).Both can evolve to invasive carcinomas,respectively cholangiocarcinoma(CCA)and pancreatic ductal adenocarcinoma(PDAC).Intraductal papillary neoplasms arise in biliary tract and pancreas.Intraductal papillary neoplasm of the biliary tract(IPNB)share common histologic and phenotypic features such as pancreatobiliary,gastric,intestinal and oncocytic types,and biological behavior with the pancreatic counterpart,the intraductal papillary mucinous neoplasm of the pancreas(IPMN).All these neoplastic lesions exhibit similar immunohistochemical phenotypes,suggesting a common carcinogenic process.Indeed,CCA and PDAC display similar clinic-pathological features as growth pattern,poor response to conventional chemotherapy and radiotherapy and,as a consequence,an unfavorable prognosis.The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.     

Significance of mucin expression in pancreatobiliary neoplasms

Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis and tumor invasion. We have described, for the first time, that pancreatic ductal adenocarcinomas (PDACs) with an aggressive behavior and a poor outcome expressed MUC1 (pan-epithelial membrane-associated mucin) but did not express MUC2 (intestinal-type secreted mucin), whereas intraductal papillary mucinous neoplasms (IPMNs) with indolent behavior and a favorable outcome did not express MUC1 but did express MUC2. These expression profiles of MUC1 and MUC2 related to the prognoses of the patients were also observed in biliary neoplasms such as intrahepatic cholangiocarcinoma (ICC)-mass-forming type (MF), mucin-producing bile duct tumor (MPBT), and extrahepatic bile duct carcinoma (EHBDC). We also found recently that high expression of MUC4 (tracheobronchial membrane-associated mucin) in PDACs, ICCs-MF, and EHBDCs was a new independent poor prognostic factor, although MUC4 was not expressed in normal pancreatobiliary tissue. High de novo expression of MUC5AC (gastric-type secreted mucin) was observed in many types of pancreatobiliary neoplasms, including all grades of pancreatic intraepithelial neoplasia (PanIN) and biliary intraepithelial neoplasia (BilIN), and all types of IPMNs and MPBTs, as well as PDACs and ICCs-MF, although MUC5AC was not expressed in normal pancreatobiliary tissue. The combined status of MUC1, MUC2, MUC4, and MUC5AC expression may be useful for the early detection of pancreatobiliary neoplasms and evaluation of their malignancy. In regard to the mechanism of mucin expression, we have recently reported that MUC1, MUC2, MUC4, and MUC5AC gene expression is regulated by epigenetics (DNA methylation and histone H3 lysine 9 modification) in cancer cell lines, including PDAC cells. Translational research of mucin gene expression mechanisms, including epigenetics, in pancreatobiliary neoplasms may give us new tools for the early and accurate detection of these neoplasms.     

Intraductal neoplasm of the intrahepatic bile duct: clinicopathological study of 24 cases

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.     

Synchronous pancreatic solid pseudopapillary neoplasm and intraductal papillary mucinous neoplasm

Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm composed of poorly cohesive monomorphic neoplastic cells forming solid and pseudopapillary structures with frequent hemorrhagic-cystic degeneration. Intraductal papillary mucinous neoplasm (IPMN) is a pancreatic exocrine tumor composed of intraductal papillary growth of mucin containing neoplastic cells in the main pancreatic duct or its major branches. In the case presented here, a 53-year-old, Japanese man was found to have multiple cystic lesions and dilatation of the main pancreatic duct in the neck of the pancreas. Histological examination revealed a main-duct and branch-duct type IPMN, of the gastric-type, involving the neck of the pancreas, associated with a 0.5 cm SPN in the caudal side of the IPMN. We diagnosed this case as synchronous SPN and IPMN. As far as we know, only one other case of synchronous SPN and IPMN has been reported. Both the present case and the previously reported case showed abnormal nuclear expression of β-catenin in SPN, whereas IPMN showed no abnormal nuclear expression. These results suggest that β-catenin abnormality is not a common pathogenetic factor of synchronous SPN and IPMN.     

Multistep carcinogenesis of perihilar cholangiocarcinoma arising in the intrahepatic large bile ducts

Flat-type "biliary intraepithelial neoplasia (BilIN)" and papillary-type "intraductal papillary neoplasm of the bile duct (IPN-B)" are proposed as precursors of invasive, perihilar intrahepatic cholangiocarcinoma (ICC). Three carcinogenetic pathways are proposed: BilIN progressing to tubular adenocarcinoma, and IPN-B progressing to tubular adenocarcinoma or to colloid carcinoma. Carcinogenesis via BilIN was characterized by mucin core protein 2-/cytokeratin 20-(MUC2-/CK20-) with MUC1 expression, while carcinogenesis via IPN-B leading to tubular adenocarcinoma was associated with MUC1 expression or that to colloid carcinoma with MUC1-negativity. In both the BilIN and IPNB series, the expression of p21, p53, and cyclin D1 was upregulated with histological progression. Interestingly, p53 expression was upregulated at the invasive stage of BilIN, but was low in noninvasive BilIN, while p53 expression was upregulated in IPN-B1 and reached a plateau in IPN-B2 and invasive ICC. Expression of p16(INK4a), which was frequent in BilIN1, was decreased in BilIN-2/3 and invasive carcinoma. EZH2 expression showed a stepwise increase from BilIN to invasive carcinoma. Membranous expression of β-catenin and E-cadherin was more markedly decreased in ICC with BilIN than in ICC with IPNB. Interestingly, disruption of the membranous distribution of β-catenin and E-cadherin seems to result in the invasion and metastasis of carcinoma cells of BilIN and IPN-B expressing MMP-7 and MT1-MMP. Increased expression of cyclin D1 and c-myc was more frequent in the IPNB lineage than BilIN lineage, possibly related to the Wnt signaling pathway associated with the nuclear accumulation of β-catenin. In conclusion, BilIN and IPN-B progress to invasive ICC through characteristic multistep processes.     

Pathological classification of intrahepatic cholangiocarcinoma based on a new concept

Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic differentiation. To date, ICC was largely classified into adenocarcinoma and rare variants. Herein, we propose to subclassify the former, based on recent progress in the study of ICC including the gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is, ICC is classifiable into the conventional (bile duct) type, the bile ductular type, the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma. Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites, IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB, particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma, mucinous/signet ring cell carcinoma, clear cell type, undifferentiated type, neuroendocrine carcinoma and so on. This classification of ICC may open up a new field of research of ICC and contribute to the clinical approach to ICC.     

Current roles of endoscopy in the management of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by intraductal papillary proliferation of mucin‐producing epithelial cells that exhibit various degrees of dysplasia. IPMN is classified into four histological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) according to its histomorphological and immunohistochemical characteristics. Endoscopic retrograde cholangiopancreatography plays a crucial role in the evaluation of these features of IPMN. Endoscopic ultrasonography (EUS) has proven to be more sensitive than computed tomography or magnetic resonance imaging for early detection of malignancy. The present review addresses the current roles of endoscopy and related techniques in the management of IPMN. The particular focus is on diagnosing IPMN and malignancy within IPMN, detecting pancreatic cancer concomitant with IPMN, differentiating the epithelial subtypes of IPMN, determining the optimal strategy for the management of branch duct IPMN, and discussing innovative endoscopic technology related to IPMN. The disadvantages of endoscopic examinations of IPMN and different attitudes toward EUS‐guided fine‐needle aspiration for IPMN between Japan (negative) and other countries (active) are also discussed.     

Mucin expression profile in pancreatic cancer and the precursor lesions

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.     

Intraductal papillary mucinous neoplasm of the bile duct with gastric and duodenal fistulas

Intraductal papillary mucinous neoplasm (IPMN) of the bile duct is still rare and not yet understood despite of its increased incidence and similar clinicopathologic characteristics compared with IPMN of the pancreas. The fistula formation into other organs can occur in IPMN, especially the pancreatic type. To our knowl-edge, only two cases of IPMN of the bile duct with a choledochoduodenal fistula were reported and we have recently experienced a case of IPMN of the bile duct penetrating into two neighboring organs of the stom-ach and duodenum presenting with abdominal pain and jaundice. Endoscopy showed thick mucin extruding from two openings of the fistulas. Endoscopic suction of thick mucin using direct peroral cholangioscopy with ultra-slim endoscope through choledochoduodenal fis-tula was very difficult and ineffective because of very thick mucin and next endoscopic suction through the stent after prior insertion of biliary metal stent into cho-ledochogastric fistula also failed. Pathologic specimen obtained from the proximal portion of the choledocho-gastric fistula near left intrahepatic bile duct through the metal stent showed a low grade adenoma. The pa-tient declined the surgical treatment due to her old age and her abdominal pain with jaundice was improved af-ter percutaneous transhepatic biliary drainage with the irrigation of N-acetylcysteine three times daily for 10 d.     

Intraductal papillary neoplasm of the bile duct developing in a patient with primary sclerosing cholangitis: A case report

We report a case of intraductal papillary neoplasm of the bile duct (IPNB) that developed in a patient with primary sclerosing cholangitis. A 46-year-old woman was admitted to our hospital with obstructive jaundice. The liver function tests demonstrated increased serum liver enzyme levels. Computed tomography showed dilatation of the intrahepatic bile ducts. Abdominal ultrasonography revealed a highly echoic protruding lesion in the posterior bile duct near the right lobe of the liver. The lesion was suspected to be IPNB, but we were unable to confirm whether it was a carcinoma. A right hepatectomy was performed, and this showed that the dilated bile duct was filled with mucin and contained several yellowish papillary tumors. Histologically, the neoplastic biliary epithelium showed papillary growth in the dilated lumen. The tumor was diagnosed as IPNB, high-grade intraepithelial neoplasia secreting abundant mucin. No recurrence has been detected 3 years after surgery.     

Pathways for the development of multiple epithelial types of intraductal papillary mucinous neoplasm of the pancreas

Journal of Gastroenterology - Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is categorized into four distinct types: the gastric, intestinal, pancreatobiliary, and oncocytic. Each...     

Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas

Recently, attention has been drawn to papillary neoplasm of the pancreatobiliary systems. In the pancreas, the disease entity of intraductal papillary mucinous neoplasm (IPMN-P) is widely recognized. In contrast, the pathological characteristics of biliary papillary tumors, such as biliary papilloma(tosis) and papillary cholangiocarcinoma, have not yet been well documented. In this study, we compared the pathological features and post-operative prognosis among biliary papillary tumors (10 cases of biliary papilloma(tosis) and 22 cases of papillary cholangiocarcinoma), conventional non-papillary cholangiocarcinoma (15 cases), and IPMN-P (31 cases). Macroscopically, all biliary papillary tumors were characterized by the prominent intraductal papillary proliferation, and macroscopic mucin-hypersecretion was seen in 9 of 32 cases (28%). Histologically, biliary papillary tumors consisted of three types of tumor cells (pancreaticobiliary, intestinal and gastric types), whereas only the pancreaticobiliary type was observed in non-papillary cholangiocarcinoma. Immunohistochemically, biliary papillary tumors were characterized by the common expression of MUC2, CDX2 and cytokeratin 20. In addition, biliary papillary tumors could be associated with two types of invasive lesions: tubular adenocarcinoma (9 cases) and mucinous carcinoma (5 cases). Patients with tubular adenocarcinoma had a poor prognosis compared to non-invasive papillary tumor or papillary tumor with mucinous carcinoma. These pathological characteristics and the survival status of biliary papillary tumors were different from those of non-papillary cholangiocarcinoma, and rather closely resembled those of IPMN-P. In conclusion, biliary papillary tumors may be the biliary counterpart (intraductal papillary neoplasm of the bile duct) of IPMN-P.     

Intraductal papillary neoplasm of the bile duct

Intraductal papillary neoplasm of the bile duct(IPNB)is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma.IPNBs are mainly found in patients from Far Eastern areas,where hepatolithiasis and clonorchiasis are endemic.According to the immunohistochemical profiles of the mucin core proteins,IPNBs are classified into four types:pancreaticobiliary,intestinal,gastric,and oncocytic.Approximately 40%-80%of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma,suggesting that IPNB is a disease with high potential for malignancy.It is difficult to make an accurate preoperative diagnosis because of IPNB’s low incidence and the lack of specificity in its clinical manifestation.The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation.Simultaneous proximal and distal bile duct dilation can be detected in some cases,which has diagnostic significance.Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions.However,pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion.Surgical resection is the major treatment.Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved.Staging,histologic subtype,curative resection and lymph node metastasis are factors affecting long-term survival.     

Estrategia ante una neoplasia mucinosa papilar intraductal de páncreas

Intraductal papillary mucinous neoplasm (IPMN) is a premalignant pancreatic entity characterized by papillary growth of the ductal epithelium with rich mucin production and cystic dilatation of the main pancreatic duct and/or its branches. These neoplasms are often multifocal.     

A statement by the Japan‐Korea expert pathologists for future clinicopathological and molecular analyses toward consensus building of intraductal papillary neoplasm of the bile duct through several opinions at the present stage

Intraductal papillary neoplasm of bile duct (IPNB) was described as a preinvasive neoplastic lesion of the biliary tract in the 2010 World Health Organization (WHO) classification. Although a number of studies have since been conducted on IPNBs, controversy remains, particularly regarding the standardization of its definition. Meetings by Japanese and Korean expert pathologists were held twice to resolve the pathological diagnostic aspects of IPNB. Through round‐table discussions and histological reviews, we reached the common understanding that IPNBs diagnosed according to the criteria of WHO 2010 are characterized by intraductal predominant papillary or villous biliary neoplasms covering delicate fibrovascular stalks and are classified into two types pathologically. One type (type 1 IPNB) is histologically similar to intraductal papillary mucinous neoplasms of pancreas, and typically develops in the intrahepatic bile ducts, while the other (type 2 IPNB) has a more complex histological architecture with irregular papillary branching or with foci of solid‐tubular components and typically involves the extrahepatic bile ducts. This report states the diagnostic pathologic features of IPNB proposed by WHO 2010. Since currently, the concept of IPNB is still confusing, the proposed diagnostic pathologic features stated here will be of use for future clinicopathological and molecular analyses toward consensus building of IPNB.     

MUC2 expression and prevalence of high-grade dysplasia and invasive carcinoma in mixed-type intraductal papillary mucinous neoplasm of the pancreas

Background/objectivesMorphological types and mucin protein expressions classify intraductal papillary mucinous neoplasms (IPMNs). Main duct (MD)-IPMN mostly consists of intestinal type (I-type), which expresses MUC2. Branch duct (BD)-IPMN mostly consists of gastric type (G-type), which does not express MUC2. However, the definition of mixed-type IPMN has yet to be clarified and it contains various histological types. The aim of this study was to investigate the relationship between MUC2 expression and the presence of high-grade dysplasia (HGD) and invasive carcinoma, especially in mixed-type IPMN.MethodsThis retrospective study included 101 consecutive patients with surgically resected IPMNs between April 2001 and October 2012. All patients were morphologically classified into four distinct types (I-type, G-type, PB-type: pancreatobilliary, O-type: oncocytic) and immunohistochemical reactivity of various anti-mucin antibodies were investigated.ResultsAccording to the classification of the 2012 international guidelines, the numbers (and histomorphological types: I/G/PB/O) of MD, mixed-type, and BD-IPMNs were 16 (12/4/0/0), 45 (16/28/1/0), and 40 (0/38/1/1). Prevalence of MUC2 expression in MD, mixed-type, and BD-IPMNs were 75% (12/16), 36% (16/45), and 0% (0/40). In mixed-type IPMN, the prevalence of HGD and/or invasive carcinoma in MUC2-positive IPMN was significantly higher than that of MUC2-negative IPMN (HGD + invasive carcinoma: 88% vs. 38%, p = 0.0017; invasive carcinoma: 50% vs. 21%, p = 0.042). Multivariate analysis showed that MUC2 expression is an independent predictive factor of HGD and invasive carcinoma in mixed IPMN (odds ratio 14.6, 95% CI 2.5–87.4, p = 0.003).ConclusionsIn mixed-type IPMN, MUC2 expression clearly identified HGD and invasive carcinoma and may provide most appropriate surgical indication.     

DIRECT PERORAL CHOLANGIOSCOPY AND PANCREATOSCOPY FOR DIAGNOSIS OF A PANCREATOBILIARY FISTULA CAUSED BY AN INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS: A CASE REPORT

Here, we report a case of a pancreatobiliary (PB) fistula caused by an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The PB fistula was suspected after endoscopic retrograde cholangiopancreatography (ERCP) and diagnosed after direct visualization with a direct peroral cholangioscopy and pancreatoscopy by using an ultra‐slim endoscope. No previous reports exist on the precise diagnosis of a PB fistula with direct peroral cholangioscopy and pancreatoscopy. In our case report, a 69‐year‐old man underwent an ERCP because of a pancreatic head mass and biliary tract obstruction. During ERCP, a fistula between the common bile duct (CBD) and main pancreatic duct (MPD) was suspected. After endoscopic sphincterotomy, we examined both the CBD and MPD with an ultra‐slim videoendoscope (GIF‐N260; Olympus Optical Co, Tokyo, Japan) under direct visualization and biopsy of the mass. The analysis of the biopsy specimen confirmed this mass to be an IPMN of the pancreas. When we examined the CBD, one fistula with copious mucin secretion was identified at the distal CBD. In conclusion, direct peroral cholangioscopy and pancreatoscopy using the ultra‐slim endoscope is an efficient tool for diagnosis of PB fistula and pancreatic IPMN.