Papillary Neoplasm Of Bile Duct Research Articles

Multiple intraductal papillary neoplasms of bile duct diagnosed based on endoscopic ultrasonography and peroral cholangioscopy findings.

A man in his 30s was referred to our department for evaluation of bile duct stricture and removal of an intrahepatic bile duct stone. Five years before his presentation, he underwent left hepatectomy for a giant hepatic hemangioma. There were no abnormalities in blood biochemical tests. Magnetic resonance cholangiopancreatography showed one 5mm oval defect in region B6 and two 8mm semicircular defects in the hilar bile duct. Endoscopic ultrasound revealed a 3.5mm hypoechoic focal raised lesion in the hilar bile duct. Oral cholangioscopy revealed his two lesions in the hilar bile duct as white papillary elevations with mucus production. The pathological diagnosis of intraductal papillary neoplasm was determined (low-grade dysplasia, type 1, gastric type). After 1 and a half years, no expansion of the bile duct lesion was observed. Initially, it was thought to be a benign stenosis after liver resection, but based on the results of endoscopic ultrasound, we suspected a tumorous lesion, and we were able to make an accurate diagnosis, including histological type, using transoral cholangioscopy.

The Native Flip-Flop-Intrahepatic Papillary Neoplasm of Bile Duct

Intrahepatic papillary neoplasm of bile duct configures as a papillary neoplasm with a distinct fibro-vascular stalk layered by variant epithelium pervading intrahepatic bile ducts with cystic dilatation. Neoplasm configures as a premalignant lesion associated with low grade, intermediate grade or high grade intraepithelial neoplasia. Tumour progression is concordant with preliminary inactivation of TP53 and p16, antecedent activating mutations within KRAS and delayed loss of SMAD4/ DPC4 gene. Cogent clinical symptoms arising due to biliary obstruction as hyper-bilirubinaemia or abdominal pain may emerge. Cytological smears are hyper-cellular and comprised of broad, double layered sheets and aggregates of columnar epithelial cells enmeshed within a fine stroma commingled with complex, three dimensional, branching papillary configurations. Morphologically, complex tubulovillous structures or micropapillary articulations appear to distend bile ducts or enlarged, multi-locular cysts are layered by pancreaticobiliary, intestinal, gastric or oncocytic epithelium.

Focal Intrahepatic Duct Dilatation (FIDD): a Finding That Mandates Further Evaluation That May Amount to Liver Resection

AbstractThe increasing use of imaging has led to incidental findings in the liver. The Western experience of managing focal intrahepatic duct dilatation (FIDD) is not well recorded. We present our experience based on a large prospectively maintained database at a tertiary hepatobiliary surgical unit. We identified patients with liver resection for focal incidental duct dilatation from January 2003 to December 2019 from the liver unit database. We recorded the demographics, symptomatology, blood test results, imaging, type of liver resection, morbidity, mortality and histology of resected specimens. Nine patients had focal intrahepatic duct dilatation among 994 liver resections performed (0.9%). Six patients were asymptomatic, 2 upper abdominal pain and 1 recurrent gram-negative sepsis. Liver function tests were normal in all patients. Two patients had cholangiocarcinoma (CCA), 4 intrahepatic stones, 1 intraductal papillary neoplasm of bile duct (IPN-B) and 2 benign strictures. Focal incidental duct dilatation is rare in the Western population. Most patients are asymptomatic with an incidental finding of intrahepatic duct dilatation on cross-sectional imaging. Differentiating benign and malignant pathology is difficult warranting liver resection, in fit patients, to resolve the diagnosis. Liver resection is safe and can be potentially curative in patients with a neoplasm, which can occur in 30% of patients with focal intrahepatic duct dilatation.

Intraductal papillary neoplasm of the bile duct: diagnostic value of MRI features in differentiating pathologic subclassifications-type 1 versus type 2.

To identify MRI features for differentiating type 2 from type 1 intraductal papillary neoplasms of bile duct (IPNB) and assessing malignant potential of IPNB. This retrospective study included 60 patients with surgically proven IPNB who had undergone preoperative MRI between January 2007 and December 2020. All surgical specimens were reviewed retrospectively to classify types 1 and 2 IPNBs and assess tumor grade. Significant MRI features for differentiating type 2 (n = 40) from type 1 IPNB (n = 20); and for IPNB with an associated invasive carcinoma (n = 43) from intraepithelial neoplasia (n = 17) were determined using logistic regression analysis. An associated invasive carcinoma was more frequently found in type 2 than in type 1 IPNB (85.0% [34/40] vs. 45.0% [9/20], p = 0.003). At univariable analysis, MRI features including extrahepatic location, no dilatation of tumor-bearing segment of bile duct, isolated upstream bile duct dilatation, and single lesion were associated with type 2 IPNB (all p ≤ 0.012). At multivariable analysis, significant MRI findings for differentiating type 2 from type 1 IPNB were extrahepatic location and no dilatation of tumor-bearing segment of bile duct (odds ratio [OR], 7.24 and 46.40, respectively). At univariable and multivariable analysis, tumor size ≥ 2.5cm (OR, 8.45), bile duct wall thickening (OR, 4.82), and irregular polypoid or nodular tumor shape (OR, 6.44) were significant MRI features for differentiating IPNB with an associated invasive carcinoma from IPNB with intraepithelial neoplasia. MRI with MR cholangiopancreatography may be helpful in differentiating type 2 IPNB from type 1 IPNB and assessing malignant potential of IPNB. Preoperative MRI with MR cholangiopancreatography may be helpful in differentiating type 2 intraductal papillary neoplasms of bile duct (IPNB) from type 1 IPNB and assessing malignant potential of IPNB. • In terms of tumor grade, the incidence of invasive carcinoma was significantly higher in type 2 intraductal papillary neoplasm of the bile duct (IPNB) than in type 1 IPNB. • At MRI, extrahepatic location and no dilatation of tumor-bearing segment are significant features for differentiating type 2 IPNBs from type 1 IPNBs. • At MRI, large tumor size, bile duct wall thickening, and irregular polypoid or nodular tumor shape are significant features for differentiating IPNB with an associated invasive carcinoma from IPNB with intraepithelial neoplasia.

Interobserver agreement of pathologic classification and grading of tumoral intraductal pre-invasive neoplasms of the bile duct

Current WHO terminology and recent publications have classified tumoral (grossly visible) intraductal pre-invasive neoplasms of bile duct (TIDN) into three categories: intraductal papillary neoplasm of bile duct (IPNB), intraductal papillary oncocytic neoplasm (IOPN), and intraductal tubulopapillary neoplasm (ITPN). A total of 227 cases of TIDN and related lesions ≥3 mm in height were examined by 10 biliary pathologists referring to these 3 categories and two pathologic gradings: two-tiered system (low- and high-grade dysplasia) and modified types 1 and 2 subclassification. Among them, IPNB was the most frequent (183 cases), followed by IOPN (28 cases), while ITPN was rare (2 cases), and interobserver agreement in this classification was “substantial” (κ-value, 0.657). The interobserver agreement of two-tiered grading system of TIDN was “slight” (κ-value, 0.201), while that of modified types 1 and 2 subclassification was “moderate” (κ-value, 0.515), and 42 % were of type 1, and 58 % were of type 2. Type 1 TIDN showed occasional stromal invasion (6.7 %), whereas type 2 TIDN was frequently associated with stromal invasion (49.6 %) (p < 0.01). In conclusion, the classification of TIDN into three categories and modified types 1 and 2 subclassification are a practically applicable classification and grading system for TIDN.

Large duct intrahepatic cholangiocarcinoma arising from intraductal papillary neoplasm of bile duct: A rare case report

Large duct intrahepatic cholangiocarcinoma arising from intraductal papillary neoplasm of bile duct: A rare case report

Pathological survey of precursor lesions in cholangiocarcinoma.

To clarify the pathological significance of two precursors (high-grade biliary intraepithelial neoplasm [BilIN] and intraductal papillary neoplasm of bile duct [IPNB]) in cholangiocarcinomas (CCAs). Ninety-one cases of CCA (47 distal CCAs [dCCAs], 31 perihilar CCAs [pCCAs] and 13 intrahepatic CCAs of large duct type [LD-iCCAs]) were examined for their association with precursors. Neoplastic intraepithelial lesions without underlying infiltrating carcinoma in the surrounding mucosa of CCAs were considered to reflect high-grade BilIN. High-grade BilIN and IPNB were subdivided into gastric, biliary, intestinal and oncocytic subtypes, while CCAs were subdivided into gastrobiliary, intestinal and oncocytic subtypes. The postoperative overall survival (OS) was examined. Fifty-four and 8 of 91 CCAs were associated with high-grade BilIN and IPNB, respectively, while these precursors were unidentifiable in the remaining CCAs. A majority of CCAs were of the gastrobiliary subtype, while the intestinal subtype was occasionally detected, and the oncocytic subtype was rare. CCAs with high-grade BilIN showed a similar postoperative OS to CCAs without precursors, while CCAs with IPNB showed a favorable postoperative OS compared to CCAs without precursors. CCAs were frequently associated with precursors; high-grade BilIN may be a major precursor and IPNB a minor one. CCAs with IPNB showed a favorable postoperative OS compared to CCAs with high-grade BilIN.

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.

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.

P-67 Comparison of the malignant predictors in intrahepatic and extrahepatic intraductal papillary neoplasm of bile duct

Intraductal papillary neoplasm of the bile duct (IPNB) is a precancerous lesion of cholangiocarcinoma, for which surgical resection is the most effective treatment. We evaluated the predictors of malignancy in IPNB according to anatomical location and the prognosis without surgery. A total of 196 IPNB patients who underwent pathologic confirmation by surgical resection or endoscopic retrograde cholangiography or percutaneous transhepatic cholangioscopic biopsy were included. Clinicopathological findings of IPNB with invasive carcinoma or mucosal dysplasia were analyzed according to anatomical location. Of the 116 patients with intrahepatic IPNB (I-IPNB) and 80 patients with extrahepatic IPNB (E-IPNB), 62 (53.4%) and 61 (76.3%) were diagnosed with invasive carcinoma, respectively. Multivariate analysis revealed that mural nodule > 12 mm (p=0.043) in I-IPNB and enhancement of mural nodule (p=0.044) in E-IPNB were predictive factors for malignancy. Pathology discrepancy before and after surgery, IPNB has 71.2% of sensitivity and 82.3% of specificity. In the non-surgical IPNB group, composed of nine I-IPNB and seven E-IPNB, 43.7% progressed to IPNB with invasive carcinoma within 876 days. E-IPNB has a higher rate of malignancy than I-IPNB. The predictive factor for malignancy is mural nodule > 12 mm in I-IPNB and mural nodule enhancement in E-IPNB.

Pancreaticoduodenectomy for recurrence of intraductal papillary neoplasm of bile duct at seven years after curative resection

Pancreaticoduodenectomy for recurrence of intraductal papillary neoplasm of bile duct at seven years after curative resection

Cystic and Intraductal Neoplasms of the Pancreatobiliary Tract.

The Pancreatobiliary Pathology Society (PBPS) would like to thank Alain C. Borczuk, MD, and the Archives of Pathology &amp; Laboratory Medicine for again highlighting our society by publishing 4 review articles based on the presentations at the PBPS companion society symposium at the 2020 United States and Canadian Academy of Pathology (USCAP) meeting. Our mission is to educate surgical pathologists and cytopathologists on the importance of the advances in this complex area and hopefully transform the way we practice pancreatobiliary pathology. The PBPS fosters excellence and international collaboration in education, research, and the global practice of pancreatobiliary pathology. PBPS became an official society in 2016 and a USCAP companion society in 2018, but the sharing of knowledge, enthusiasm, and ideas in pancreatobiliary pathology started more than 20 years ago as an annual “Pancreas Club” luncheon held during the USCAP meeting, which grew over the years and became the PBPS. The first advisory council members of the Pancreas Club were Volkan Adsay, MD; Ralph Hruban, MD; David Klimstra, MD; Günter Klöppel, MD; and Giuseppe Zamboni, MD. Thanks to their dedication to pancreatobiliary pathology and contagious enthusiasm, many other pathologists interested in pancreatobiliary pathology were attracted to join and motivated the transformation into the official 501c3 society that it is today (PBPath.org).The 2020 PBPS Companion Society Symposium was entitled “Cystic and Intraductal Neoplasms of the Pancreatobiliary Tract” and consisted of 5 outstanding presentations entitled (1) “Preoperative Molecular Assessment of Pancreatic Cysts and Intraductal Lesions,” (2) “Cytologic Assessment of Cystic/Intraductal Lesions of the Pancreatobiliary Tract,” (3) “Mucinous Cystic and Intraductal Neoplasms of the Pancreatobiliary Tract,” (4) “Nonmucinous Cystic Lesions of the Pancreas,” and (5) “Management Algorithms for Pancreatic Cysts and Intraductal Neoplasms: The Surgeon's Perspective.” These topics represented a 360-degree expert evaluation of cystic and intraductal pancreatobiliary lesions and were given in the same stepwise manner in which they are often encountered, from the cytomorphologic and molecular characteristics to their histomorphology, and finally to management from a surgeon's perspective.Four of the presentations from the 2020 companion meeting have been converted into review articles in this issue of Archives of Pathology &amp; Laboratory Medicine. In the first article, Michelle Reid, MD, MS, reviews the cytologic features of cystic and intraductal pancreatobiliary tract lesions. Dr Reid emphasizes the use of an integrated, multidisciplinary approach for the evaluation of cystic/intraductal pancreatobiliary tract lesions, incorporating clinical, radiologic, and cytologic findings with chemical and molecular cyst fluid analysis as well as ancillary studies for definitive diagnosis and classification (and, where applicable, grading) of mucinous and nonmucinous cystic lesions. She also describes the cytologic features of tumoral intraepithelial neoplasms, intraductal oncocytic papillary neoplasms (IOPNs), intraductal tubulopapillary neoplasms (ITPNs), and intraductal papillary neoplasm of bile duct (IPNB), which may be sampled by bile duct brushing or fine-needle aspiration biopsy. The second article examines recent advances in mucinous cystic and intraductal neoplasms of the pancreatobiliary tract and is written by David Klimstra, MD, along with his colleague Kerem Ozcan, MD. In this article Drs Klimstra and Ozcan explore the clinicopathologic, genetic, and prognostic features of cystic and intraductal mucinous neoplasms of the pancreas, including mucinous cystic neoplasms and pancreatic intraductal neoplasms, intraductal papillary mucinous neoplasm (IPMN), IOPN, and ITPN. Additionally, the histologic features of preinvasive mass-forming neoplasms of the bile duct IPNB, IOPN, and ITPN are described, along with similarities and differences compared with their pancreatic counterparts. Recently described aspects of morphology, grading, classification, and genomic alterations in these neoplasms are emphasized. The third article is on nonmucinous cystic lesions of the pancreas and is by Irene Esposito, MD, and her colleague Lena Haeberle, MD. In this article Drs Esposito and Haeberle examine the spectrum of nonmucinous cystic lesions of the pancreas and their different biological behaviors. They review serous cystic neoplasms, solid-pseudopapillary neoplasms, cystic neuroendocrine tumors, and pancreatitis-associated pseudocysts, and discuss their epidemiology and clinical and gross features as well as their histomorphology, immunohistochemistry, molecular profile, and prognostic associations. The fourth and final article is entitled “Management Algorithms for Pancreatic Cystic Neoplasms: The Surgeon's Perspective” and is written by Jin-Young Jang, MD, PhD, along with his colleague Hyeong Seok Kim, MD. Drs Jang and Kim review the current status of pancreatic cystic neoplasms including IPMNs, their epidemiology, malignancy risk, and treatment-related factors. They also discuss optimal management algorithms for IPMNs, which require thoughtful assessment to determine the indication for resection. The use of nomograms, surveillance, and other management strategies in customizing IPMN management is explored, along with more tailored approaches to surgical intervention versus surveillance.We are extremely proud of our society and the continued contributions of its members to the field of pancreatobiliary pathology. We hope that you will enjoy these review articles exploring a unique, 360-degree (cytopathologist's, surgical pathologist's, and surgeon's) perspective on cystic and intraductal neoplasms of the pancreatobiliary tract.

A Review of Mucinous Cystic and Intraductal Neoplasms of the Pancreatobiliary Tract.

Although most pancreatic and bile duct neoplasms are solid, mucinous cystic neoplasms and intraductal neoplasms have been increasingly recognized even when clinically silent, thanks to the increased use of sensitive imaging techniques. Cystic and intraductal neoplasms of the pancreas are often resectable and curable and constitute about 5% of all pancreatic neoplasms. Owing to their preinvasive nature and different biology, recognition of these entities remains a major priority. Mucinous cystic neoplasms are histologically and clinically distinct from other cystic pancreatic neoplasms. Pancreatic intraductal neoplasms encompass 3 major entities: intraductal papillary mucinous neoplasm, intraductal oncocytic papillary neoplasm, and intraductal tubulopapillary neoplasm. Intraductal papillary neoplasms of bile ducts are also preinvasive mass-forming neoplasms with both similarities and differences with their pancreatic counterparts. All of these pancreatobiliary neoplasms have diverse and distinctive clinicopathologic, genetic, and prognostic variations. To review the clinical, pathologic, and molecular features of mucinous cystic and intraductal neoplasms of the pancreatobiliary tract. Literature review, diagnostic manuals, and guidelines. This review will briefly describe well-known clinical and pathologic features and will focus on selected recently described aspects of morphology, grading, classification, and genomic alterations of cystic and intraductal neoplasms of the pancreatobiliary tract.

Strategy for Discriminating Intraductal Papillary Neoplasm of the Bile Duct (IPNB) in Different Anatomical Locations Based on Clinicopathological Features and Outcomes

Introduction: In the statement by the Japan-Korea expert pathologists, it was described that Intraductal papillary neoplasm of bile duct (IPNB) can be subclassified into two types. Each of these two types has a different tendency in the anatomical location and invasiveness. The present study assessed the clinical features and outcomes of intra-/extra- hepatic IPNB to establish optimal therapeutic strategies for IPNB. Method: The present study included 28 cases who were pathologically diagnosed with IPNB. These cases were classified by the anatomical location where it arises (intrahepatic-IPNB 7 cases/ extrahepatic-IPNB 21 cases). Furthermore, we attempted to further clarify the characteristics of intrahepatic IPNB by comparing with intrahepatic cholangiocarcinoma (ICC). Results: Superficial extension was significantly more frequent in extrahepatic type with 17 cases (p=0.003). Pathologically, lymphatic invasion was significantly more frequent in the extrahepatic type (p=0.033), and mucus production tended to be more frequent in intrahepatic type (p=0.063). In terms of prognosis, recurrence was observed in 9 cases of extrahepatic type. As compared with 26 cases of ICC, preoperative intrahepatic (p=0.026) and extrahepatic (p<0.01) biliary dilatation and histological mucus production (p<0.01) were significantly found in primary hepatic IPNB. ICC group significantly showed CA19-9 >100 (p=0.043), portal invasion (p<0.01) and recurrence (p<0.01). Conclusions: Preoperative diagnosis of intrahepatic IPNB is possible because of the relatively common and characteristic imaging findings. However, considering the malignant potential in patients with high tumor markers and portal vein invasion, as well as the characteristics of horizontal extension of IPNB, systematic hepatectomy with adequate bile duct resection are recommended.

Incidental Focal Intrahepatic Duct Dilatation (FIDD) - A Finding that Mandates Further Investigation that May Include a Liver Resection

Introduction: The increasing use of imaging has led to incidental findings in the liver. The Western experience of managing focal intrahepatic duct dilatation (FIDD) is not well recorded. We present our experience based on a large prospectively maintained database at a tertiary hepatobiliary surgical unit. Methods: Patients with liver resection for FIDD between January 2003-December 2019 were retrospectively identified from the liver unit database. The demographics, symptomatology, blood test results, imaging, type of liver resection, morbidity, mortality, and histology of resected specimens were recorded. Results: 9 patients had FIDD among 994 liver resections performed (0.9%). Median age 64 (52-82). 6 patients were asymptomatic, 2 upper abdominal pain and 1 recurrent gram-negative sepsis. Liver function tests were normal in all patients. The operations were 4 right hepatectomy, 3 Left hepatectomy, 1 Left lateral sectionectomy and 1 Right anterior sectionectomy. No mortality and 1 patient had subphrenic collection needing drainage. Two patients had cholangiocarcinoma (CCA), 4 intrahepatic stones, 1 intraductal papillary neoplasm of bile duct (IPN –B) and 2 benign strictures. Median follow up 5 years (1-16). 2 patients with CCA and one with intrahepatic stones died during follow up. Conclusion: FIDD is rare in the Western population. Most patients are asymptomatic with an incidental finding of FIDD on cross-sectional imaging. Differentiating benign and malignant pathology is difficult warranting liver resection in fit patients to resolve the diagnosis. Liver resection is safe and can be potentially curative in patients with a neoplasm, which can occur in 30% of patients with FIDD.

Hepatobiliary mucinous cystic neoplasms and mimics.

This review will provide an overview of hepatobiliary mucinous cystic neoplasms and their mimics such as complex appearing benign cysts, intraductal papillary neoplasm of bile ducts, choledochal cysts, infectious cysts, and other cystic neoplasms. Preoperative imaging, particularly abdominal MRI with MRCP, plays a key role in differentiating these entities which differ widely in management. Familiarity with the differentiating imaging features of mucinous cystic neoplasms and their mimics allows radiologists to provide management-guiding reports.

A Mouse Model of Cholangiocarcinoma Uncovers a Role for Tensin-4 in Tumor Progression.

Earlier diagnosis and treatment of intrahepatic cholangiocarcinoma (iCCA) are necessary to improve therapy, yet limited information is available about initiation and evolution of iCCA precursor lesions. Therefore, there is a need to identify mechanisms driving formation of precancerous lesions and their progression toward invasive tumors using experimental models that faithfully recapitulate human tumorigenesis. To this end, we generated a mouse model which combines cholangiocyte-specific expression of KrasG12D with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced inflammation to mimic iCCA development in patients with cholangitis. Histological and transcriptomic analyses of the mouse precursor lesions and iCCA were performed and compared with human analyses. The function of genes overexpressed during tumorigenesis was investigated in human cell lines. We found that mice expressing KrasG12D in cholangiocytes and fed a DDC diet developed cholangitis, ductular proliferations, intraductal papillary neoplasms of bile ducts (IPNBs), and, eventually, iCCAs. The histology of mouse and human IPNBs was similar, and mouse iCCAs displayed histological characteristics of human mucin-producing, large-duct-type iCCA. Signaling pathways activated in human iCCA were also activated in mice. The identification of transition zones between IPNB and iCCA on tissue sections, combined with RNA-sequencing analyses of the lesions supported that iCCAs derive from IPNBs. We further provide evidence that tensin-4 (TNS4), which is stimulated by KRASG12D and SRY-related HMG box transcription factor 17, promotes tumor progression. We developed a mouse model that faithfully recapitulates human iCCA tumorigenesis and identified a gene cascade which involves TNS4 and promotes tumor progression.

407 Incidental Focal Intrahepatic Duct Dilatation (FIDD) – A Finding That Mandates Further Investigation That May Include Liver Resection

Abstract Background The increasing use of imaging has led to incidental findings in the liver. The Western experience of managing focal intrahepatic duct dilatation (FIDD) is not well recorded. We present our experience based on a large prospectively maintained database at a tertiary hepatobiliary surgical unit. Method Patients with liver resection for FIDD between January 2003-December 2019 were retrospectively identified from the liver unit database. The demographics, symptomatology, blood test results, imaging, type of liver resection, morbidity, mortality, and histology of resected specimens were recorded. Results 9 patients had FIDD among 994 liver resections performed (0.9%). 6 patients were asymptomatic, 2 upper abdominal pain and 1 recurrent gram-negative sepsis. Liver function tests were normal in all patients. Two patients had cholangiocarcinoma (CCA), 4 intrahepatic stones, 1 intraductal papillary neoplasm of bile duct (IPN –B) and 2 benign strictures. Conclusions FIDD is rare in the Western population. Most patients are asymptomatic with an incidental finding of FIDD on cross-sectional imaging. Differentiating benign and malignant pathology is difficult warranting liver resection in fit patients to resolve the diagnosis. Liver resection is safe and can be potentially curative in patients with a neoplasm, which can occur in 30% of patients with FIDD.

Reappraisal of pathological features of intraductal papillary neoplasm of bile duct with respect to the type 1 and 2 subclassifications

The pathological spectrum of intraductal papillary neoplasm of bile duct (IPNB) remains to be clarified. A total of 186 IPNBs were pathologically examined using the type 1 and 2 subclassifications proposed by Japanese and Korean biliary pathologists incorporating a two-tiered grading system (low-grade and high-grade dysplasia), with reference to four subtypes (intestinal [i], gastric [g], pancreatobiliary [pb], and concocytic [o] subtype). IPNBs were classifiable into type 1 composed of low-grade dysplasia and 'high-grade dysplasia with regular structures' (69 IPNBs), and type 2 of 'high grade dysplasia with irregular structures and complicated lesions' (117 IPNBs). Type 1 was more common in the intrahepatic bile duct (78%), whereas type 2 was frequently located in the extrahepatic bile duct (58%). Mucin hypersecretion was more common in type 1 (61%) than in type 2 (37%). IPNBs were classifiable into the four subtypes: 86 iPNBs, 40 gIPNBs, 31 pbIPNBs, and 29 oIPNBs. The four subtypes were histologically evaluable with reference to the type 1 and 2 subclassifications. iIPNB and pbIPNBs were frequently classified as type 2, whereas types 1 and 2 were observed at similar rates in gIPNB and oIPNB. Stromal invasion was almost absent in type 1, irrespective of subtype, but was found in 66 of 117 type 2 IPNBs (P<.01), and postoperative outcome was favorable in IPNBs without invasion compared with IPNBs with invasion (P<.05). The type 1 and 2 subclassifications with reference to the four subtypes may provide useful information for understanding IPNB.