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.     

Intraductal oncocytic papillary neoplasm of the bile duct: the first case of peribiliary gland origin

We report herein the first case of intraductal oncocytic papillary neoplasm of the bile duct arising from a peribiliary gland of the left hepatic duct. The patient was a 63-year-old Japanese man. Radiological and cholangioscopic examinations revealed intraductal tumor of the left hepatic duct. After pathological diagnosis of adenocarcinoma by cholangioscopic biopsy, a surgical hepatobiliary resection was performed. Pathological examination revealed papillary tumor in the left hepatic duct. Histologically, the tumor was identified as papillary neoplasm comprising oncocytic cells and delicate fibrovascular cores. Interestingly, this tumor originated from the cystic space in the bile duct wall. This cystic space was histologically identified as a cystically dilated peribiliary gland. Carcinoma in situ was observed in this cystic peribiliary gland at the bottom of the tumor, but not on any areas of biliary epithelium. This case suggests that intraductal papillary neoplasm can arise from both biliary epithelium and peribiliary glands.     

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 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.     

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.     

Endoscopic diagnosis of intraductal papillary mucinous neoplasm of the bile duct

Background/Purpose

Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is considered an uncommon tumor. The purpose of this study was to evaluate the diagnostic utility of endoscopic cholangiography (ERC) with subsequent peroral cholangioscopy (POCS) and/or intraductal ultrasonography (IDUS) for this tumor.

Methods

From December 1991 to November 2006, a retrospective analysis was made of eight patients with IPMN-B. Their clinical features and the endoscopic diagnostic strategy for POCS and IDUS were reviewed.

Results

In all the patients, ERC failed to show papillary tumors, due to coexisting mucin or biliary sludge. POCS was carried out after ERC and it showed the presence and locations of papillary tumors in all patients, except for one with a tumor in the peripheral intrahepatic bile duct (B3). IDUS was performed in seven of the eight patients; in five of these patients, intraductal protruding tumors were clearly visualized, whereas flat tumors were not identified in the remaining two patients. In one of the eight patients, endoscopic nasobiliary drainage did not remove the huge amount of mucin. Hence, this patient required subsequent percutaneous biliary drainage. Six of the eight patients underwent surgical treatment; five patients underwent a hepatic resection with or without extrahepatic bile duct resection and one underwent a pancreaticoduodenectomy. Five of the six operated patients are still alive; one patient died of gastric cancer 90 months after the operation (mean follow-up period, 45.3 months). The two remaining patients, who were considered inoperable due to major medical comorbidities, died of liver failure and cholangitis 3 and 6 months, respectively, after stent placement.

Conclusion

ERC failed to delineate intraductal papillary tumors, due to coexisting mucin. The presence and location of papillary tumors were correctly diagnosed by both POCS and IDUS, but POCS may be better than IDUS to diagnose the extent of the tumor.     

Surgical strategy for mucin-producing bile duct tumor

Tumors with copious mucin production within the intra- or extrahepatic bile ducts have been reported as mucin-producing bile duct tumors (MPBTs). Because mucin produced by these tumors causes recurrent cholangitis and obstructive jaundice, surgical resection should be indicated even if these tumors are regarded as benign. In order to choose the appropriate surgical procedure, exact preoperative assessment of tumor location and cancer extension is important, especially evaluation of the extent of superficial spreading through cholangioscopic observation and biopsy. In principle, MPBTs should be resected in a manner similar to that employed for other types of bile duct carcinomas. That is, major hepatectomy with or without extrahepatic bile duct resection or pancreaticoduodenectomy should be chosen as the surgical procedure, and intraoperative frozen section at the stumps of the bile duct is essential. On the other hand, when precise diagnosis is completed preoperatively and the lesion is diagnosed as adenoma or carcinoma with invasion confined to the ductal wall and limited superficial spreading, limited resections preserving organ functions as much as possible can be considered as a choice among surgical procedures. All ten patients with MPBT resected at our institution according to these strategies are still alive without tumor recurrence, with a median survival of 48.0 months.     

Intraductal papillary mucinous neoplasm of the pancreas with a bifid pancreatic duct

A bifid pancreatic duct presenting a major bifurcation in the main pancreatic duct is one of the anatomical variations of the pancreatic ducts. We encountered a 71-year-old female with a 5-cm-diameter branch duct intraductal papillary mucinous neoplasm of the pancreas in whom preoperative endoscopic retrograde pancreatography demonstrated an anomalous bifurcation of the main pancreatic duct at the body of the pancreas. We performed a distal pancreatectomy, instead of a middle pancreatectomy, with a cutting line at the downstream pancreas to the duct bifurcation point. Intraoperative ultrasonography was useful to confirm the exact location of the pancreatic duct bifurcation as well as the tumor extension. The procedure resulted in a favorable outcome without any postoperative complications. Although a bifid pancreatic duct is an unusual anomalous condition, this case should alert surgeons to be aware of such anatomical variants when performing pancreatic resection, otherwise, incurable pancreatic complications may occur postoperatively.     

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.     

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.     

Intraductal papillary neoplasm of the bile duct: Assessment of invasive carcinoma and long-term outcomes using MRI

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Intraductal ultrasonography for the diagnosis of proximal invasion in extrahepatic bile duct cancer

Intraductal ultrasonograpy (IDUS) was performed on 22 patients with extrahepatic bile duct cancer, using the percutaneous transhepatic approach. Intraductal ultrasonograpy images of the proximal invasion of the bile duct cancer were defined. In addition, three patients were examined through the peroral approach, to try to diagnose whether or not the cancer invaded to the bifurcation of the hepatic duct. Intraductal ultrasonograpy images obtained through the percutaneous approach could be classified into three patterns, types 1, 2 and 3, according to the features of the interior surface of the bile duct and the thickness of the bile duct wall. Type 1 images, which did not show protrusions into the bile duct lumen and had a bile duct wall of even thickness, were not likely to show bile duct cancer. Type 2 images showed protrusions of the tumour into the bile duct lumen and the surfaces of the protrusions were irregular. Type 3 images showed single or multiple low echoic papillary masses in the bile duct. Using the peroral technique, we considered all three cases to be type 1 and could diagnose that cancer had not invaded to the bifurcation of the hepatic ducts. From the results of this study, we suggest that proximal invasion of extrahepatic bile duct cancer can be diagnosed using IDUS.     

Intraductal papillary neoplasm of the bile ducts: A case report and literature review

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare bile duct neoplasm mostly found in far eastern nations where hepatolithiasis and clonorchiasis infections are endemic. In western countries, it is very rare and the etiology is unknown. In this article, we report the first IPNB patient we encountered in our clinic and a literature review. The patient is a 38-year-old female with a history of choledocholithiasis who presented with obstructive jaundice. She was found to have a papillary mass at the junction of the right hepatic duct and common hepatic duct with six masses in the liver parenchyma. The immunophenotypic and histologic features of the tumor are consistent with IPNB, gastric subtype. The patient had a partial hepatectomy and has been receiving palliative chemotherapy. In a search of PubMed database, we collected 354 IPNB patients reported in 22 articles. In these patients, 52.8% were from Japan and 27.7% were from western countries including the United States (11.0%). The age of the patients ranged from 35 to 80 years old with an average of 64.6. Male/female ratio was 1.5. Macroscopically, 57.5% of the tumors were in the left lobe and 29.5% were in the right lobe. The average size of the tumor were 4.2 cm at the time of diagnosis. Histologically, pancreato-biliary subtype accounted for 41.8%, intestinal 28.0%, gastric 13.5% and oncocytic 16%. An invasive component is most often present in the pancreato-biliary and gastric subtypes. Despite recent advanced technologies, diagnosis of IPNB is still challenging, especially in western countries due to its rarity. Defined clinico-pathologic features are in demand for the accurate diagnosis and proper treatment.     

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.     

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.     

Intraductal papillary mucinous neoplasm of the biliary tract with cardiac metastasis: A case report

Introduction:Intraductal papillary mucinous neoplasm of the biliary tract (IPNB) is a rare, low-grade neoplasm limited to the bile duct mucosa. The malignant transformation rate is low, and there have been limited reports of metastasis to other organs. Herein, we presented a rare case of a patient who was diagnosed with IPNB concurrent with invasive adenocarcinoma after surgery and was diagnosed with cardiac metastasis 6 months later.Patient concerns:A 61-year-old male patient presented with abdominal pain to a local clinic. He was diagnosed with intrahepatic cholangiocarcinoma with pancreatitis and transferred to our hospital.Diagnosis:Diagnostic testing (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, positron emission tomography-computed tomography) revealed a papillary neoplasm and invasive adenocarcinoma with papillary neoplasm in the periampullary lesion.Interventions:Pancreaticoduodenectomy, right hemihepatectomy, and left lateral sectionectomy of the liver were performed. After surgery, we planned gemcitabine-based adjuvant chemotherapy.Outcomes:Upon completion of the sixth gemcitabine chemotherapy cycle, a hyperechoic, oval-shaped mass (1.3 × 2.6 cm) was found on the outer wall of the right atrium. Resection of a cardiac tumor in the right atrium and patch repair were performed.Conclusion:To our knowledge, no other case of cardiac metastasis found during observation after surgery for an IPNB has been described. IPNBs are known to be less aggressive and to have a lower metastasis rate than intraductal papillary mucinous neoplasms; therefore, the number of case reports describing metastasis after surgery is relatively low. Our case suggests that close observation is necessary in patients diagnosed with an IPNB.