Intraductal Papillary Neoplasm Research Articles

A Case Report of Intraductal Papillary Neoplasm Associated with an Extrahepatic Bile Ducts

Choledochal cysts are congenital cystic dilations of the extrahepatic and/or intrahepatic bile ducts and are rare. Adults with choledochal cysts are at risk of developing biliary carcinoma. Our case is a 31-year-old female patient who presented with right upper quadrant pain. In magnetic resonance imaging/magnetic resonance cholangiopancreatography, there was a fusiform enlargement of the extrahepatic bile duct and cystic duct and it was evaluated as compatible with Type 1 choledochal cyst. Extrahepatic biliary tract excision-cholecystectomy-Roux En Y hepaticojejunostomy procedure was performed. The pathology result was intraductal papillary neoplasm (IPN). IPN is a rare entity in the biliary tract and because it is precancerous, early diagnosis and surgical excision are critical.

Biliary Intraductal Papillary Neoplasm (IPMN-B) and Mucinous Cystic Liver neoplasm with biliary extension: Diagnostic Dilemma

Biliary Intraductal Papillary Neoplasm (IPMN-B) and Mucinous Cystic Liver neoplasm with biliary extension: Diagnostic Dilemma

Use of Intraoperative Cholangioscope in Biliary Resection for Intraductal Papillary Neoplasm of the Bile Duct

Use of Intraoperative Cholangioscope in Biliary Resection for Intraductal Papillary Neoplasm of the Bile Duct

Intraductal Papillary Neoplasms of the Bile Duct. A Comparative Study of Tumor Characteristics, Management Strategies and Outcomes in Europe and Nagoya, Japan

Intraductal Papillary Neoplasms of the Bile Duct. A Comparative Study of Tumor Characteristics, Management Strategies and Outcomes in Europe and Nagoya, Japan

Intraductal oncocytic papillary neoplasm arising in Peutz-Jeghers Syndrome bile duct: a unique case report

BackgroundPeutz-Jeghers syndrome (PJS) is a rare, autosomal dominant disorder caused by germline mutations of STK11/LKB1, with an increased risk of tumors at multiple sites. Intraductal oncocytic papillary neoplasm (IOPN) is a unique subtype of intraductal papillary neoplasm of the bile duct (IPNB) defined by a premalignant neoplasm with intraductal papillary or villous growth of biliary-type epithelium. IOPN has a distinct mutation profile compared with both IPNB and intraductal papillary mucinous neoplasm (IPMN).Case presentationWe herein describe the case of a 44-year-old woman who presented as polyps in the intestinal lumen of sigmoid colon and a 3.1 × 2.1 cm mass in the left lobe of liver. Gross feature revealed a cystic papillary mass and the neoplasm had a clear boundary with the surrounding liver tissue. Histology revealed complex papillary structures, a small amount of fine fibrovascular cores and immunohistochemistry showed extensive positive for MUC5AC, MUC6, CD117. Therefore, histological and immunohistochemical examination of the liver tumor suggested the diagnosis of IOPN. Next-generation sequencing (NGS) revealed other than STK11 germline mutation, the tumor also harbors GNAS somatic mutation at codon 478 and EGFR amplification.ConclusionTo our knowledge, this is the first report of IOPN arising in PJS. This case enlarges the spectrum of PJS related tumors and genetic rearrangements in IOPN.

HPB P41 Pitfalls in establishing a preoperative diagnosis; correlating the radiological and histopathological findings of suspected intraductal papillary neoplasm of the bile duct (IPNB)

Abstract Background Intraductal papillary neoplasm of the bile duct (IPNB) represents a cohort of uncommon biliary tract tumours. It is commonly unrecognised or misdiagnosed in cross sectional imaging of the liver. This rare tumour is of significant clinical importance as it serves as a pre-cursor lesion for Cholangiocarcinoma. The diagnostic work up of a patient with a suspected IPNB remains predominantly based on imaging and as of yet no consensus has been achieved regarding the optimal diagnostic algorithm. The aim of this study was to compare the radiological and clinico-pathological features of patients with confirmed or suspected IPNB managed in a single tertiary center. Methods Retrospective review of a departmental database of consecutive patients with suspected IPNB was performed. Clinical information regarding patient demographics, disease presentation, radiological imaging characteristics and histo-pathological features was analysed. Results Eighteen patients with suspected IPNB were noted, of which histological confirmation was present in eight cases (62%). The most frequent presentation of IPNB was of an incidental finding (50%). The diagnosis of IPNB was made following MRI in 63% of cases. Invasive adenocarcinoma was present in five patients (63%). In the remaining three patients, low grade dysplasia was noted within their IPNB tumours. Conclusions IPNB is frequently associated with concurrent invasive malignancy. Observation alone is insufficient. Radiological assessment of these tumours remains as the fundamental investigation for diagnosis. However, without confirmatory histology perioperatively, the diagnosis cannot be assured therefore the decision for management must be based upon a patient-centered discussion and a careful evaluation of risk.

A Case of Multicystic Biliary Hamartoma with a Marked Peribiliary Gland Component Successfully Treated by Purely Laparoscopic Anatomical Liver Resection

BackgroundMulticystic biliary hamartoma (MCBH) is an extremely rare benign liver lesion characterized by a gross well-circumscribed multicystic honeycomb appearance. This report presents a MCBH case with a marked peribiliary gland component which showed unusual histology.Case PresentationA 63-year-old Japanese male was admitted to our hospital for a detailed examination of a hepatic cystic lesion, which was originally detected 14 years ago and had slowly enlarged. A preoperative imaging study revealed a well-demarcated multicystic lesion without communication to the biliary tracts. The possible clinical diagnoses were mucinous cystic neoplasm (MCN) or MCBH. The lesion was successfully resected by purely laparoscopic right anterior sectionectomy. The cut surfaces of resected specimens grossly exhibited a well-circumscribed multicystic lesion with a thick septum. Histologically, the cyst wall was covered by cuboidal epithelial cells resembling epithelium of the bile duct while abundant small ducts, which morphologically resembled peribiliary glands, were observed among the fibrous stroma of the thick septum. Although possible pathological diagnosis varied, including intrahepatic cholangiocarcinoma, intraductal papillary neoplasm of the bile duct, biliary adenofibroma, MCN and MCBH, the lesion was finally diagnosed as MCBH with a marked peribiliary gland component.ConclusionsMCBH can contain abundant peribiliary glands in the fibrous stroma. A pathologist should be careful not to diagnose such peribiliary glands in MCBH as neoplastic glands.

Chronic expanding hematoma in the liver: a case report

BackgroundA hematoma that gradually increases over a chronic course of months or longer is defined as a chronic expanding hematoma (CEH). CEHs often develop in the limbs and on body surfaces that are susceptible to external stimuli. CEHs in the intrathoracic or intraperitoneal organs are uncommon, with liver CEHs being particularly rare worldwide.Case presentationA 57-year-old woman was previously diagnosed with a giant cyst in the right liver lobe, with a longer axis of approximately 15 cm. Abdominal ultrasonography findings suggested a complex cyst, and she was referred to our hospital for further inspection. Although CEH was suspected, it was difficult to exclude malignant diseases such as intraductal papillary neoplasm of the bile duct and cystadenocarcinoma. There was a possibility of malignant disease and the exclusion of surrounding organs due to tumor growth. Therefore, a right hepatectomy was performed. Pathological examination revealed a pseudocyst containing a clot, which was consistent with CEH.ConclusionsCEH rarely occurs in the liver; however, it is necessary to consider CEH when a slow-growing hepatic mass that shows a mosaic pattern on magnetic resonance imaging is found.

Is a specific T classification needed for extrahepatic intraductal papillary neoplasm of the bile duct (IPNB) type 2 associated with invasive carcinoma?

The necessity of a specific T classification for extrahepatic intraductal papillary neoplasm of the bile duct (IPNB) type 2, one of the precursors of cholangiocarcinoma (CC), remains unclear. Patients who underwent resection for extrahepatic biliary tumors were reviewed. Relapse-free survival (RFS) was compared between IPNB type 2 and CC, stratified by T classification. The cohort involved 443 patients with IPNB type 2 (n=57) and CC (n=386). In 342 patients with perihilar tumors, 5-year RFS of IPNB type 2 and CC group was 49.8% versus 34.5% (p=.012), respectively. The RFS was 54.6% versus 47.2% (p=.110) for pT1-2 tumors and 28.6% versus 22.7% (p=.436) for pT3-4 tumors, respectively. In 92 patients with distal tumors, 5-year RFS was 47.4% versus 42.1% (p=.678). The RFS was 68.2% versus 49.6% (p=.422) for pT1 tumors and 18.8% versus 38.3% (p=.626) for pT2-3 tumors, respectively. Multivariate analysis identified that poor histologic grade (HR, 2.105; p < .001), microscopic venous invasion (HR, 1.568; p=.002), and nodal metastasis (HR, 1.547; p < .001) were independent prognostic deteriorators, while tumor type (IPNB type 2 vs. CC) was not. Prognostic impact of IPNB type 2 was limited, suggesting unnecessity of a specific T classification for IPNB type 2 with invasive carcinoma.

Intraepithelial involvement of non-neoplastic glands in papillary preinvasive neoplasms of the biliary tract: a potential diagnostic pitfall

Intracholecystic papillary neoplasms of the gallbladder (ICPN) and intraductal papillary neoplasms of the bile duct (IPNB) show intramural neoplastic growths in addition to intraluminal papillary or polypoid neoplastic growth. Such intramural growths include intraepithelial involvement of non-neoplastic glands by preinvasive neoplastic epithelia (glandular involvement) as well as stromal invasive carcinoma. A total of 29 ICPN cases and 84 IPNB cases were pathologically examined for their glandular involvement. Glandular involvement was characterized by intramural neoplastic glands (1) showing cytological and phenotypical similarities to intraluminal preinvasive papillary neoplasms and (2) showing reminiscent configurations of non-neoplastic glands, such as (i) a mixture of preinvasive neoplastic epithelia and non-neoplastic epithelia within the same glands, (ii) neoplastic glands close to or within clustered non-neoplastic glands, or (iii) continuous growth of intraluminal preinvasive neoplastic glands into the walls. Such glandular involvement was found in 16 of 29 ICPN and 48 of 84 IPNB, and 15 of the former and 28 of the latter were not associated with invasive carcinoma. Non-invasive ICPN and IPNB with glandular involvement showed a favorable postoperative overall survival (OS). Glandular involvement by preinvasive neoplastic epithelia was frequently found in ICPN and IPNB. Such lesions may be diagnostic pitfalls in ICPN and IPNB referring to invasion. Glandular involvement without invasive carcinoma was not associated with an unfavorable postoperative OS in ICPN and IPNB. Recognition of glandular involvement may thus prevent overestimation of invasive carcinoma in ICPN and IPNB.

Development of extrahepatic bile ducts and mechanisms of tumorigenesis: Lessons from mouse models.

The biliary system is a highly branched tubular network consisting of intrahepatic bile ducts (IHBDs) and extrahepatic bile ducts (EHBDs). IHBDs are derived from hepatic progenitor cells, while EHBDs originate directly from the endoderm through a separate branching morphogenetic process. Traits that are important for cancer are often found to overlap in developmental and other processes. Therefore, it has been suggested that intrahepatic cholangiocarcinomas (iCCAs) and extrahepatic cholangiocarcinomas (eCCAs) have different developmental mechanisms. While much evidence is being gathered on the mechanism of iCCAs, the evidence for eCCA is still very limited. The main reason for this is that there are very few appropriate animal models for eCCA. We can gain important insights from these animal models, particularly genetically engineered mouse models (GEMMs). GEMMs are immunocompetent and mimic human CCA subtypes with a specific mutational pattern, allowing the development of precancerous lesions, that is, biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB). This review provides a summary of the pathogenesis and mechanisms of eCCA that can be revealed by GEMMs. Furthermore, we discuss several clinical questions, such as whether BilIN and IPNB really become malignant, whether the peribiliary gland is the origin of eCCAs, and others.

Pathologies of Precursor Lesions of Biliary Tract Carcinoma.

Carcinomas and precursor lesions of the biliary tract belong to a spectrum of pancreatobiliary neoplasms that share common histology and cell lineages. Over the past two decades, preinvasive precursors to biliary tract carcinomas (BTCs) have been identified such as high-grade biliary intraepithelial neoplasm (high-grade BilIN), intraductal papillary neoplasm of bile duct (IPNB) and intracholecystic papillary neoplasm of the gallbladder (ICPN). While a majority of these precursors may arise from the biliary tract mucosa, some originate from the peribiliary glands and Rokitansky-Aschoff sinuses in the walls of the biliary tract. High-grade BilIN is a microscopically identifiable intraepithelial neoplasm of the biliary tract, whereas IPNB and ICPN are grossly visible intraductal or intraluminal preinvasive neoplasms in the bile duct and gallbladder, respectively. These neoplasms show characteristic histologic features according to four cell lineages and two-tiered grading, and show intraepithelial spreading to the surrounding mucosa and involve non-neoplastic glands in the walls of the biliary tract. These precursors are not infrequently associated with stromal invasion, and high-grade BilIN, in particular, are frequently identified in the surrounding mucosa of BTCs. Taken together, it seems likely that progression from these precursors to invasive carcinoma is a major process in biliary carcinogenesis.

Pathologic patterns of invasive carcinoma associated with intraductal papillary neoplasms of bile duct (IPNB)

The pathologic features of invasive carcinoma associated with IPNB remain to be clarified. By using 82 cases of IPNB, the pathologic spectrum of associated invasive carcinoma and its correlation with their post-operative overall survival (OS) were examined. Invasive carcinoma was found in 52 cases (63 %) of IPNB and was classifiable into three patterns (patterns A, B and C). Pattern A was characterized by microscopic foci of invasive carcinoma in the fibrovascular stalks or confined to the bile duct mucosa and wall beneath the intraluminal pre-invasive neoplastic components of IPNB (23 cases) and pattern B by invasive carcinoma in the periductal connective tissue and in the adjacent organ(s) mainly near or beneath the intraluminal component(s) of IPNB (15 cases). Pattern C showed nodular invasive carcinoma considerably involving the intraluminal pre-invasive components and the bile duct mucosa and wall adjacent to the intraluminal pre-invasive components of IPNB (14 cases). Recognition of these three patterns of invasive carcinoma associated with IPNB may expand the pathologic spectrum of IPNB. IPNBs without invasive carcinoma showed a favorable post-operative-OS compared with those with invasion as a whole and those of pattern B and C, respectively, but showed a similar post-operative-OS to that of pattern A. IPNB of pattern B and C showed an unfavorable post-operative outcome, though there was no difference between pattern B and C. Understanding of the pathologic spectrum of associated invasive carcinoma may facilitate further pathological analysis of IPNB.

Hepatobiliary and Pancreatic: An unusual cause of biliary obstruction.

A 41-year-old man, with no relevant personal history, presented with postprandial fullness, nausea, and weight loss in the last 2 years. On physical examination, he had mild jaundice. Laboratory examination revealed conjugated hyperbilirubinemia (total bilirubin 3.62 mg/dL, conjugated bilirubin 2.60 mg/dL) and cytocholestasis with cholestatic predominance (AST 102 U/L, ALT 144 U/L, FA 330 U/L, GGT 681 U/L). An abdominal computed tomography followed by magnetic resonance cholangiopancreatography (MRCP) showed common bile duct (CBD) stenosis, without mural thickening or intraluminal mass, and intrahepatic and extrahepatic duct dilation. There were no lesions in the hepatic or pancreatic parenchyma (Fig. 1). Endoscopic retrograde cholangiopancreatography (ERCP) showed a heterogeneous filling defect in the distal half of the CBD with upstream dilatation. Biliary sphincterotomy and exploration with a balloon were performed, and tumor tissue fragments with a villous appearance and necrotic areas were obtained. Cholangioscopy allowed the identification of a friable villous vegetative lesion in the middle third of the CBD leading to luminal narrowing (Fig. 2). Biopsies revealed an intraductal tubulopapillary neoplasm with high-grade dysplasia and focal transformation into adenocarcinoma (ADC). Staging exams excluded lymph node or distant metastasis, and, after multidisciplinary discussion, the patient underwent Whipple's cephalic pancreatoduodenectomy with hepaticojejunostomy. The anatomopathological examination of the surgical specimen showed a moderately differentiated ADC in intestinal-type intraductal papillary neoplasm of the bile duct (IPNB) (pT1N0R0) (Fig. 2). There was no indication for adjuvant chemotherapy, but clinical, analytical, and imaging surveillance was recommended. After 1 year of follow-up, the patient remains asymptomatic. IPNBs are rare neoplasms arising from the bile duct considered to be an important precursor of cholangiocarcinoma. They are commonly found in Far East Asia where hepatolithiasis and clonorchiasis are endemic. IPNBs can occur anywhere in the extrahepatic or intrahepatic bile ducts and microscopically are classified into four types: pancreaticobiliary, intestinal, gastric, and oncocytic. Most cases show at time of diagnosis high-grade intraepithelial neoplasia or invasive carcinoma. IPNBs secrete mucin and induce biliary obstruction and dilation, but do not have a typical clinical or imaging presentation, making their early diagnosis a clinical challenge. The major treatment is surgical resection with a better prognosis compared to cholangiocarcinoma.

S1943 An Unusual Liver Tumor

Introduction: Intraductal papillary neoplasm of bile duct (IPNB) is an uncommon premalignant biliary precursor lesion to intrahepatic cholangiocarcinoma (ICC). IPNB can be associated with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Von Meyenburg complexes (VMCs) have a strong association with hepatic fibro-polycystic liver disease. The association of all these rare entities has not been described, thus lending to the singularity of this case. Case Description/Methods: A 69-year-old-male was referred for a 2-month history of right upper abdominal pain and 10-lb weight loss. CT showed left intrahepatic biliary ductal dilation and scattered small hepatic cysts. ERCP showed dilated left intrahepatic bile ducts with suboptimal brushings. MRI/CP (Figure A) revealed dilated left intrahepatic bile ducts with an abrupt cut off of the left hepatic duct and a subtle area of enhancement concerning for an obstructive malignancy. Multiple small side branch pancreatic IPMNs and many renal cysts were noted (Figure B). Due to concern for malignancy, a left hepatectomy was performed (Figure C). Intraoperatively, multiple cystic lesions were noted throughout the liver. Pathology revealed mucinous intestinal type IPNB with multiple VMCs. Tumor likely arose from a predisposing condition because of multiple VMCs, suggestive of fibro-polycystic liver disease in the non-involved liver. Patient did well post operatively. Discussion: Four histologic types of IPNB have been described including pancreatobiliary, intestinal, gastric foveolar and oncocytic. There are 2 general categories of IPNB based on histologic similarities to their pancreatic counterpart. Type 1 shares many features with pancreatic IPMN. It develops in the intrahepatic bile ducts and is characterized by villous architecture, thin fibrovascular cores and frequent mucin production. Type 2 develops in the extrahepatic bile ducts and has complex papillary, polypoid, tubular, solid or cribriform intraductal structures. IPNB is considered premalignant. VMCs are thought to be a part of embryonic ductal plate malformation. Though largely innocuous, there has been a strong association with hepatic fibro-polycystic liver disease and in rare instances histological transformation to ICC. Prior case reports have tied IPNB to pancreatic IPMN, but this is the first case that associates IPNB, pancreatic IPMN, VMCs and cystic lesions of the liver and kidneys all together. We speculate there could be an underlying common pathological pathway that all these entities share.Figure 1.: a. Dilated left intrahepatic bile ducts with an abrupt cut off of the left hepatic duct. b. IPMN pancreas. c. Left hepatectomy showing tumor.

S367 Endoscopic Eversion and Stent-Assisted Strangulation for the Management of an Intraductal Papillary Neoplasm of the Bile Duct: A Minimally Invasive Technique for Non-Surgical Candidates

Introduction: Intraductal papillary neoplasms of the bile duct (IPNB) are uncommon lesions that may accompany risk for malignancy. Management is often surgical and may be associated with significant postoperative morbidity and mortality. Case Description/Methods: An 80-year-old female with a history of hepatocellular carcinoma (HCC) presented for management of jaundice and sepsis after microwave ablation of HCC. Computed tomography (CT) imaging demonstrated intra and extrahepatic biliary ductal dilation with a 19 mm soft tissue density in the distal common bile duct (CBD). Index labs depicted leukocytosis, hyperbilirubinemia, and elevated lactate. Endoscopic ultrasound (EUS) delineated a round, hypoechoic intraductal CBD lesion. The pancreas and ampulla were normal. Endoscopic retrograde cholangiopancreatography (ERCP) confirmed a distal CBD filling defect. Biliary sphincterotomy was performed and balloon sweeping revealed a frond-like partially protruding polypoid lesion suggestive of an IPNB. Due to non-surgical candidacy, we decided to perform a complete eversion with subsequent full prolapse of the lesion by using a biliary extraction balloon. This was followed by the placement of a biliary plastic stent to assist with strangulation of the base of the lesion. Biopsies were consistent with a papillary neoplasm with intestinal differentiation, confirming our findings of an IPNB, without accompanying high-grade dysplasia or carcinoma. Interval surveillance ERCP 3 months later revealed no protruding lesion from the major papilla, no residual filling defects on cholangiogram, and sweeping of the biliary tree uncovered no contents. Cholangioscopy demonstrated segmental mucosal irregularity with mild granular tissue in the mid/distal bile duct wall; however, cholangioscopy-guided intraductal biopsies and brushings showed benign reactive tissue and no recurrent IPNB. At 5 months of follow-up, the patient continues to do well. Discussion: IPNB is a rare biliary lesion. Radical surgical resection has been the mainstay of curative treatment. However, a few recent cases have described endoluminal radiofrequency ablation as an alternative therapy. To the best of our knowledge, this is the first reported case of balloon-assisted eversion combined with stent-assisted strangulation of an IPNB leading to spontaneous removal. In non-surgical candidates, this technique may be advantageous to minimize adverse operative outcomes, improve patient tolerance, and decrease cost. Watch the video at https://tinyurl.com/ACGAbstractS367

S1750 Intraductal Papillary Neoplasm of the Bile Duct Diagnosed Post Liver Transplant in Patient With Recurrent Hepatocellular Carcinoma

S1750 Intraductal Papillary Neoplasm of the Bile Duct Diagnosed Post Liver Transplant in Patient With Recurrent Hepatocellular Carcinoma

S1714 Diagnosis and Management of Intraductal Papillary Neoplasm of the Bile Duct via Endoscopic Ultrasound Evaluation

Introduction: Intrampullary papillary neoplasm (IAPN) is a rare tumor seen in women in their 60s, with an incidence of 0.025 per 100,000. The 5-year survival rate is 33%. It is distinct from an ampullary adenoma, which arises from the duodenal mucosa overlying the ampulla. It is unlikely to be cured by ampullectomy. Case Description/Methods: A 63-year-old woman with prior cholecystectomy was found to have abnormal liver tests (AST 104, AST 233, alkaline phosphatase 290) and mild hyperbilirubinemia (total bilirubin 1.7). Abdominal ultrasound showed diffuse biliary dilatation without obvious stones or stricture. MRCP showed multiple filling defects in the distal common bile duct (CBD). ERCP revealed a prominent ampulla. Digital cholangioscopy done for further investigation showed an exophytic papillary tumor in the distal CBD (Figure) along with excess luminal mucous (Figure). The endoscopic and cholangioscopic findings of a papillary intraluminal mass and mucobilia was suggestive of intraductal papillary neoplasm of the bile duct (IPNB). A 69-year-old woman with a complicated biliary history was seen by her PCP for jaundice and R shoulder pain and was found to have cholelithiasis and choledocholithiasis. She underwent laparoscopic cholecystectomy after MRI showed CBD stones. An ampullary prominence of 1 cm was concerning for an invasive carcinoma. ERCP showed multifocal frond like papillary projections at the left hilum and distal CBD and copious thick mucin through the examined extrahepatic duct and hilum; concerning for IPNB with progression to cholangiocarcinoma. Both patients underwent surgical evaluation. Discussion: IAPN is a rare tumor with poor prognosis. It is unclear if it is a variant of IPNB that also includes the ampulla or if it primarily arises within the ampullary channel and spreads proximally into the bile duct and the pancreatic duct. Diagnosis is established by cholangioscopy with biopsies. Endoscopic ultrasound of the ampulla and pancreas is essential. Cholangioscopy should be undertaken for tumor mapping. Pancreaticoduodenectomy should be treatment of choice for IAPN or IAPN with adenocarcinoma without distant metastases in order to achieve tumor free margins, as seen via pathology tissue. IAPN should be suspected based on endoscopic ampullary features such as a prominent ampulla, prolapse of papillary fronds on sphincterotomy, lack of resolution of cholestasis despite duct clearance. Cholangioscopy should be undertaken establish an early diagnosis.Figure 1.: Photo 1 (top): exophytic papillary tumor in the distal common bile duct; Photo 2 (bottom): excess luminal mucous in common bile duct.

Investigation of -PRKACA/-PRKACB fusion genes in oncocytic tumors of the pancreatobiliary and other systems.

Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreatobiliary system are tumors comprising oncocytic cells, in which three types of fusion genes involving -PRKACA/-PRKACB were recently identified. IOPNs infrequently combine with other histological subtypes of pancreatic intraductal papillary mucinous neoplasms (IPMNs) and intraductal papillary neoplasms of the bile duct (IPNBs). This study aimed to confirm the sensitivity/specificity of the fusion genes for IOPNs and to examine their significance in other oncocytic lesions. An RT-PCR, followed by DNA sequencing, was undertaken to examine the fusions in 18 histologically diagnosed IOPNs, including four combined IOPNs. Moreover, in two IOPN cases, invasive carcinomatous lesions were separately examined on their fusion status. Oncocytic thyroidal (n = 10), renal (n = 10), and salivary gland (n = 3) lesions and IPMNs (n = 9)/IPNBs (n = 4) with focal oncocytic changes were examined as controls. Fluorescence in situ hybridization using PRKACA break-apart probes was conducted for the combined IOPN cases. Target sequencing of KRAS exon2/3 and GNAS exon 8/9 was performed for IOPN cases. Fusions were detected in all IOPN cases including invasive lesions/none of the control cases. The fusion event was confirmed also in non-IOPN component in one of the four combined cases. Regarding mutation events, 5.6%/0% of IOPNs were KRAS-mt/GNAS-mt, respectively, and both components of combined IOPNs were all KRAS-wt/GNAS-wt. In conclusion, our study confirmed the sensitivity and specificity of these fusions for IOPNs. Here, we analyzed the roles of these fusion genes in combined IOPNs, proposing the possibility of IOPN development via IPMNs/IPNBs. Further studies with more combined cases are warranted.

Mucinous cystic neoplasm of the liver with polypoid nodule prolapsing into the bile duct: a case report and review of literature

BackgroundMucinous cystic neoplasm of the liver (MCN-L) is a rare cystic tumor as defined by the 2010 World Health Organization classification. MCN-L usually does not communicate with or grow into the bile duct. Herein, we present a rare case of MCN-L with a polypoid nodule protruding into the bile duct.Case presentationA 69-year-old woman was referred to our hospital for elevated serum liver enzyme levels and obstructive jaundice. The patient also complained of abdominal pain in the right hypochondriac region. Abdominal ultrasonography showed a cystic lesion in segment 4 (S4) of the liver. Computed tomography revealed a 4-cm multilocular cystic lesion with a thick wall and multiple septal formations, showing a cyst-in-cyst appearance in S4. Endoscopic retrograde cholangiography showed a contrast defect between the left hepatic duct and the common bile duct, which was suspected to be a nodular lesion in the bile duct. Bile cytology and biopsy of the nodular lesion showed no malignant findings. Based on these findings, the differential diagnosis in this patient included intraductal papillary neoplasm of the bile duct and MCN-L, which had malignant potential. The patient underwent left hemihepatectomy, including caudate lobe excision with bile duct resection and right hepatocholangiojejunostomy. Macroscopic findings showed a 40 × 29 mm multilocular cystic lesion with a polypoid nodule that protruded into the left intrahepatic bile duct. As an ovarian-like stroma was observed in both cystic and polypoid lesions microscopically, the histopathological diagnosis was MCN-L. The postoperative course was uneventful, and the patient was discharged 24 days after surgery. The patient is currently alive without recurrence 22 months after the surgery.ConclusionAlthough MCN-L rarely communicates with the bile duct, it is necessary to consider that MCN-L could grow into the bile duct, occasionally causing obstructive jaundice.