A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct

Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas.These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010.In 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 IPNBs.IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis.From a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs.The histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin.Due to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging features.Surgical resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

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.

Percutaneous transhepatic cholangioscopy-assisted biliary polypectomy for local palliative treatment of intraductal papillary neoplasm of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a premalignant biliarytype epithelial neoplasm with intraductal papillary or villous growth.Currently reported local palliative therapeutic modalities,including endoscopic nasobiliary drainage,stenting and biliary curettage,endoscopic biliary polypectomy,percutaneous biliary drainage,laser ablation,argon plasma coagulation,photodynamic therapy,and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages.We have applied percutaneous transhepatic cholangioscopy(PTCS)-assisted biliary polypectomy(PTCS-BP)technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010.AIM To assess the technical feasibility,efficacy,and safety of PTCS-BP for local palliative treatment of IPNB.METHODS Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included.PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire,and the tumor was snared and resected with electrocautery.The primary outcome was its feasibility,indicated by technical success.The secondary outcomes were efficacy,including therapeutic success,curative resection,and clinical success,and safety.RESULTS Five patients(four with mucin-hypersecreting cast-like type and one with polypoid type IPNB)were included.Low-and high-grade intraepithelial neoplasia(HGIN)and recurrent IPNB with invasive carcinoma were observed in one,two,and two patients,respectively.Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB.All five patients achieved technical success of PTCS-BP.Four patients(three with mucin-hypersecreting cast-like type and one with polypoid type IPNB)obtained therapeutic success;one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors.All four patients with mucin-hypersecreting IPNB achieved clinical success.The patient with polypoid type IPNB achieved curative resection.There were no PTCS-BP-related serious adverse events.CONCLUSION PTCS-BP appears to be feasible,efficacious,and safe for local palliative treatment of both mucin-hypersecreting cast-like and polypoid type IPNB.

Surgically treating a rare and asymptomatic intraductal papillary neoplasm of the bile duct:A case report

BACKGROUND Intraductal papillary neoplasms of the bile duct(IPNBs)are rare and characterized by papillary growth within the bile duct lumen.IPNB is similar to obstructive biliary pathology.In this report,we present an unexpected case of asymptomatic IPNB and consolidate our findings with the relevant literature to augment our understanding of this condition.Integrating relevant literature contributes to a more comprehensive understanding of the disease.CASE SUMMARY A 66-year-old Chinese male patient was admitted to our hospital for surgical intervention after gallstones were discovered during a routine physical examination.Preoperative imaging revealed a lesion on the left side of the liver,which raised the suspicion of IPNB.A laparoscopic left hemihepatectomy was performed,and subsequent histopathological examination confirmed the diagnosis of IPNB.At the 3-mo postoperative follow-up,the patient reported good recovery and no metastasis.IPNB can manifest both latently and asymptomatically.Radical surgical resection is the most effective treatment for IPNB.CONCLUSION Hepatic and biliary masses,should be considered to diagnose IPNB.Prompt surgery and vigilant follow-up are crucial in determining prognosis.

Simultaneous intraductal papillary neoplasms of the bile duct and pancreas treated with chemoradiotherapy

Some authors have suggested that intraductal papillary mucinous neoplasms of the bile duct(IPMN-B) could be the the biliary counterpart of IPMN of the pancreas(IPMN-P) since they share several clinical-pathological features.These include prominent intraductal papil-lary proliferation pattern,a gastrointestinal phenotype,frequent mucin hyper-secretion and progression to mu-cinous carcinoma.To date there are just four reported cases of patients with synchronous IPMN-B and IPMN-P all of which were treated surgically.We hereby report the case of a 76-year-old woman who was incidentally diagnosed with both an asymptomatic 3 cm bulky uid lesion obstructing the bile duct lumen,diagnosed as a malignant IPMN-B,and synchronous multiple pancreatic cystic lesions(10-13 mm) communicating with an irreg-ular Wirsung,diagnosed as branch duct IPMN-P.Since surgery was ruled-out because of the patient's age and preferences,she underwent a conservative manage-ment regimen comprising both chemotherapy and radio-therapy.This was effective in decreasing the mass size and in resolving subsequent jaundice.This is also the f irst reported case of IPMN-B successfully treated with chemoradiotherapy.Clinicians should consider medical treatment as an option in this clinical scenario,in pa-tients who may be unf it for surgery.

Diagnosis of bile duct hepatocellular carcinoma thrombus without obvious intrahepatic mass

AIM:To study the diagnosis of hepatocellular carcinoma(HCC)presenting as bile duct tumor thrombus with no detectable intrahepatic mass.METHODS:Six patients with pathologically proven bile duct HCC thrombi but no intrahepatic mass demonstrated on the preoperative imaging or palpated intrahepatic mass during operative exploration,were collected.Their clinical and imaging data were retrospectively analyzed.The major findings or signs on comprehensive imaging were correlated with the surgical and pathologic findings.RESULTS:Jaundice was the major clinical symptom of the patients.The elevated serum total bilirubin,direct bilirubin and alanine aminotransferase levels were in concordance with obstructive jaundice and the underlying liver disease.Of the 6 patients showing evidence of viral hepatitis,5 were positive for serum alpha fetoprotein and carbohydrate antigen 19-9,and 1 was positive for serum carcinoembryonic antigen.No patient was correctly diagnosed by ultrasound.The main features of patients on comprehensive imaging were filling defects with cup-shaped ends of the bile duct,with large filling defects presenting as casting moulds in the expanded bile duct,hypervascular intraluminal nodules,debris or blood clots in the bile duct.No obvious circular thickening of the bile duct walls was observed.CONCLUSION:Even with no detectable intrahepatic tumor,bile duct HCC thrombus should be considered in patients predisposed to HCC,and some imaging signs are indicative of its diagnosis.

Gd-EOB-DTPA-enhanced magnetic resonance imaging for bile duct intraductal papillary mucinous neoplasms

AIM: To investigate gadolinium-ethoxybenzyldiethylenetriamine-pentaacetic acid(Gd-EOB-DTPA)-enhanced magnetic resonance imaging(MRI) of intraductal papillary mucinous neoplasms of the bile duct(IPMN-B). METHODS: The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography(CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented.RESULTS: Conventional imaging showed diffusedilatation of bile ducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bile ducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bile ducts in the hepatobiliary phase. GdEOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomographyCT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology. CONCLUSION: Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bile ducts in invasive cases.

Non-image diagnosis of bile duct injury during laparoscopic cholecystectomy

Objective: To evaluate the role of simple non-imagetechnique in intraoperative diagnosis of bile duct in-jury (BDI).Methods: BDI was highly suspected at the original la-paroscopic cholecystectomy (LC) when the following 3abnormal findings were noted: the 'cystic duct' stump(the common bile duct stump actually) markedly re-tracted down to the duodenum; bile leakage from theporta hepatis; abnormal mucosal patch attached to the'cystic duct' stump of the removed gallbladder. Allcases of suspected BDI were converted to have laparo-tomy. Image techniques such as intraoperative cholan-giography or ultrasonography were not utilized forrecognition of BDI in all 9 patients.Results: BDI in 4 of the 9 patients was suspected ac-cording to 1-3 abnormal intraoperative findings de-scribed above. The four patients were subjected imme-diately to converted laparotomy. Abnormal findingswere not observed or misinterpreted in the other 5misdiagnosed patients.Conclusions: Timely recognizing whether BDI occursshould be considered as a routine procedure ofLC. Negligence of operators to the abnormalities of theoriginal LC, is the main cause of misdiagnosis forBDL. Simple non-image approaches such as close ob-servation of these abnormalities can make timely diag-nosis for most BDIs during the original LC.

Intraoperative frozen section diagnosis of bile duct margin for extrahepatic cholangiocarcinoma

AIM To evaluate the usefulness of frozen section diagnosis(FSD) of bile duct margins during surgery for extrahepatic cholangiocarcinoma(CCA). METHODS We retrospectively analyzed 74 consecutive patients who underwent surgery for extrahepatic CCA from 2012 to 2017, during which FSD of bile duct margins was performed. They consisted of 40 distant and 34 perihilar CCAs(45 and 55 bile duct margins, respectively). The diagnosis was classified into three categories: negative, borderline(biliary intraepithelial neoplasia-1 and 2, and indefinite for neoplasia), or positive. FSD in the epithelial layer, subepithelial layer, and total layer was compared with corresponding permanent section diagnosis(PSD) postoperatively.Then, association between FSD and local recurrence was analyzed with special reference to borderline.RESULTS Analysis of 100 duct margins revealed that concordance rate between FSD and PSD was 68.0% in the total layer, 69.0% in the epithelial layer, and 98.0% in the subepithelial layer. The extent of remaining biliary epithelium was comparable between FSD and PSD, and more than half of the margins lost > 50% of the entire epithelium, suggesting low quality of the samples. In FSD, the rate of negative margins decreased and that of borderline and positive margins increased according to the extent of the remaining epithelium. Diagnostic discordance between FSD and PSD was observed in 31 epithelial layers and two subepithelial layers. Alteration from borderline to negative was the most frequent(20 of the 31 epithelial layers). Patients with positive margin in the total and epithelial layers by FSD demonstrated a significantly worse local recurrence-free survival(RFS) compared with patients with borderline and negative margins, which revealed comparable local RFS. Patients with borderline and negative margins in the epithelial layer by PSD also revealed comparable local RFS. These results suggested that epithelial borderline might be regarded substantially as negative. When classifying the status of the epithelial layer either as negative or positive, concordance rates between FSD and PSD in the total, epithelial, and subepithelial layers were 95.0%, 93.0%, and 98.0%, respectively.CONCLUSION During intraoperative assessment of bile duct margin, borderline in the epithelial layer can be substantially regarded as negative, under which condition FSD is comparable to PSD.

Epidemiology and outcome of individuals with intraductal papillary neoplasms of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare distinct subtype of precursor lesions of biliary carcinoma.IPNB is considered to originate from luminal biliary epithelial cells,typically displays mucin-hypersecretion or a papillary growth pattern,and results in cystic dilatation[1].IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts,and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma.IPNBs have similar phenotypic changes in the occurrence and development of all subtypes,and the prognosis is significantly better than that of traditional(nonpapillary)cholangiocarcinoma.AIM To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment.METHODS Invasive IPNB,invasive intraductal papillary mucinous neoplasm of the pancreas(IPMN),and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.Annual percentage changes(APCs)in the incidence and incidence-based(IB)mortality were calculated.We identified the independent predictors of overall survival(OS)and cancer-specific survival(CSS)in indivi duals with invasive IPNB.RESULTS The incidence and IB mortality of invasive IPNB showed sustained decreases,with an APC of-4.5%(95%CI:-5.1%to-3.8%)and-3.3%(95%CI:-4.1%to-2.6%)(P<0.001),respectively.Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma.Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma.A total of 1635 individuals with invasive IPNB were included in our prognosis analysis.The most common tumor sites were the pancreaticobiliary ampulla(47.9%)and perihilar tract(36.7%),but the mucin-related subtype of invasive IPNB was the main type,intrahepatically(approximately 90%).In the univariate and multivariate Cox regression analysis,age,tumor site,grade and stage,subtype,surgery,and chemotherapy were associated with OS and CSS(P<0.05).CONCLUSION Incidence and IB mortality of invasive IPNB trended steadily downward.The heterogeneity of IPNB comprises site and the tumor’s mucin-producing status.

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.

Common bile duct lesions-how cholangioscopy helps rule out intraductal papillary neoplasms of the bile duct:A case report

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare variant of bile duct tumors,characterized by an exophytic growth exhibiting a papillary mass within the bile duct lumen and it can be localized anywhere along the biliary tree,with morphological variations and occasional invasion.CASE SUMMARY We present a patient with obstructive jaundice who was diagnosed with IPNB using cholangioscopy during endoscopic retrograde cholangio-pancreatography.Using the SpyGlass DS Ⅱ technology,we were able to define tumor extension and obtain targeted Spy-byte biopsies.After multidisciplinary evaluation,the patient was scheduled for surgical resection of the tumor,which was radically removed.CONCLUSION Cholangioscopy appears to be crucial for the rapid and clear diagnosis of lesions in the bile duct to achieve radical surgical resection.

Diagnosis and treatment of trauma of hepatic portal bile duct

Objective To investigate the diagnosis and treatment of trauma of hepatic portal bile duct. Methods Eight cases of trauma of the hepatic portal bile duct were reviewed. All short-term splits were treated with repair plus drainage with supporting tube. In 7 cases, there were combined injuries of 2 or more than 2 organs. The combined injuries were respectively treated. Long-term complication of bile duct stenosis was managed with internal drainage. Results Five cases were found during operation. Of these 5 patients, 3 were with the traumatic split less than 50% diameter and 2 with that more than 50% diameter. After repair,1 of the former 3 died and 2 remained in good condition. However, 1 of the latter 2 died and 1 was reoperated on due to bile duct stricture after the repair. Other 3 cases were found due to postoperative bile leakage. They were treated with internal drainage and good results achieved. Conclusion It is difficult to make a definite diagnosis of traumatic injury of hepatic protal bile

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.

Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma

We present the first case of an intraductal papillary neoplasm of the bile duct(IPNB) accompanying a mixed adenoneuroendocrine carcinoma(MANEC).A 74-yearold woman presented with fever of unknown cause.Laboratory data revealed jaundice and liver injury.Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct,which exhibited early enhancement and papillary growth.Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater,characterized by its protruding and dilated orifice.Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct,but no invasive region was suggested by diagnostic imaging.Therefore,the initial diagnosis was IPNB.After endoscopic nasobiliary drainage,a pylorus-preserving pancreaticoduodenectomy was performed.Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia,indicating pancreaticobiliary-type IPNB.In addition,solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident.Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component,diagnosing it as a neuroendocrine tumor(NET).Furthermore,the MIB-1 proliferation index of NET was higher than that of IPNB,and microinvasion of the NET component was found,indicating neuroendocrine carcinoma(NET G3).This unique case of MANEC,comprising IPNB and NET,provides insight into the pathogenesis of biliary NET.

Successful endoscopic treatment of an intraductal papillary neoplasm of the bile duct

We present a case of a 76-year-old man with right upper quadrant abdominal pain and weight loss,who was found to have an intraductal papillary neoplasm of the bile duct(IPNB)of the pancreaticobiliary subtype,deemed curatively resectable.The patient declined surgery and opted for endoscopic therapy.He underwent two sessions of endoscopic retrograde cholangiopancreatography(ERCP)-guided radiofrequency ablation(RFA).Ten months later,no evidence of recurrence was identified on repeat ERCP.To our knowledge,this is the first reported case of successful use of RFA as a primary treatment modality for resectable IPNB.

Unexpected metastasis of intraductal papillary neoplasm of the bile duct without an invasive component to the brain and lungs:A case report

BACKGROUND Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct(IPNB),distant metastasis remains unexplained especially in cases of carcinoma in situ.In the present study,we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain.CASE SUMMARY A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma.Laboratory tests on admission reported a mild elevation of alkaline phosphatase,γ-glutamyl transpeptidase,and total bilirubin in serum.Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct(CBD)extending to the left hepatic duct.Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern.Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis.Therefore,a diagnosis of IPNB cT1N0M0 was established.Left hepatectomy with bile duct reconstruction was performed.Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement.The patient was monitored carefully by regular examinations.However,at 32 mo after the operation,a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level.Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated.In addition to histopathological results,a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer.CONCLUSION This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.

Intraductal papillary neoplasm of the bile duct:The new frontier of biliary pathology

Intraductal papillary neoplasms of the bile duct(IPNBs)represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen.Since their first description in 2001,several classifications have been proposed,mainly based on histopathological,radiological and clinical features,although no specific guidelines addressing their management have been developed.Bile duct neoplasms generally develop through a multistep process,involving different precursor pathways,ranging from the initial lesion,detectable only microscopically,i.e.biliary intraepithelial neoplasia,to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma.Complex and advanced investigations,mainly relying on magnetic resonance imaging(MRI)and cholangioscopy,are required to reach a correct diagnosis and to define an adequate bile duct mapping,which supports proper treatment.The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB,as well as their natural evolution with a particular focus on prognosis and survival.Aggressive surgical resection,including hepatectomy,pancreaticoduodenectomy or both,represents the treatment of choice,yielding optimal results in terms of survival,although several endoscopic approaches have been described.IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential.The novel subclassification of types 1 and 2 defines the histological and clinical aspects,prognosis and survival.Diagnosis is mainly based on MRI and cholangioscopy.Surgical resection represents the mainstay of treatment,although endoscopic resection is currently applied to nonsurgically fit patients.New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB,to identify targeted therapies.

Intraductal papillary neoplasm of the bile duct in liver cirrhosis with hepatocellular carcinoma

A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hospital with recurrent HCC. Laboratory data showed that levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were elevated. He died of progressive hepatic failure. At autopsy,in addition to HCCs,an intraductal papillary proliferation of malignant cholangiocytes with fibrovascular cores was found in the dilated large bile ducts in the left lobe,and this papillary carcinoma was associated with an invasive mucinous carcinoma (invasive IPNB). Interestingly,extensive intraductal spread of the cholangiocarcinoma was found from the reactive bile ductular level to the interlobular bile ducts and septal bile ducts and to the large bile ducts in the left lobe. Neural cell adhesion molecule,a hepatic progenitor cell marker,was detected in IPNB cells. It seems possible in this case that hepatic progenitor cells located in reactive bile ductules in liver cirrhosis may have been responsible for the development of the cholangiocarcinoma and HCC,and that the former could have spread in the intrahepatic bile ducts and eventually formed grossly visible IPNB.

A case of asymptomatic intraductal papillary neoplasm of the bile duct without hepatolithiasis

A 65-year-old woman was found to have dilatation of the intrahepatic bile duct in the right anterior segment during a general health. Laboratory data were within normal ranges and no solid mass was detected in her abdominal computer tomography (CT) or nuclear magnetic resonance imaging (MRI). However, endoscopic retrograde cholangiopancreatography (ERCP) demonstrated an obstruction of the right bile duct. Intraoperative cholangiography showed stenosis of the intrahepatic bile duct in the anterior inferior segment (B5) and narrowness of the intrahepatic bile duct in the anterior superior segment (B8), so that we strongly suspected intrahepatic cholangiocarcinoma (ICC). Histologically, surgically resected liver specimens, without tumor mass by macroscopic observation, showed intraductal papillary proliferation with fibrovascular cores and intraductal spreading of carcinoma in situ throughout a considerable area, especially in bile ductules around the peripheral small portal area. Furthermore, the immunohistochemical profile of the tumor (MUC5AC+/CK7+) was compatible with an intraductal papillary neoplasm of the bile duct (IPN-B). Consequently, this case was diagnosed as IPN-B with spreading CIS, stageⅠ(pT1, pN0, P0, H1, M0). We report a case of IPN-B with interesting histopathologicalfindings and emphasize that cholangiography is especially helpful for the diagnosis of bile duct dilatation due to infiltration of carcinoma cells.