Rare malignant liver tumors (RMLTs) comprise a diverse group of neoplasms with distinct imaging features and significant diagnostic challenges due to their low prevalence and overlap with more common hepatic lesions. This review highlights the main radiologic characteristics of selected RMLTs-including fibrolamellar hepatocellular carcinoma, hepatic lymphoma, hepatocellular carcinoma in non-cirrhotic liver, mucinous cystic neoplasm, intraductal papillary neoplasm of the bile duct, epithelioid hemangioendothelioma, angiosarcoma, malignant hepatic adenoma, neuroendocrine tumor, hepatocholangiocarcinoma, hepatoblastoma, undifferentiated embryonal sarcoma, and infantile hepatic hemangioendothelioma-focusing on their presentation in CT and MRI. Recognizing specific imaging findings, such as arterial hyperenhancement, biliary communication, target and lollipop signs, and tumor morphology, can help narrow differential diagnoses and guide appropriate clinical management. Despite advancements in imaging, histopathologic confirmation is often required due to nonspecific features. Improved radiologic awareness of these rare entities is essential to facilitate early diagnosis and individualized treatment planning.

Intraductal papillary neoplasms of the bile duct (IPNBs) have a high propensity for malignant transformation; therefore, surgical resection remains the standard first-line treatment. In cases where hepatic lobectomy is not feasible, however, controlling biliary drainage can be challenging. We present herein a case of unresectable IPNB complicated by jaundice and cholangitis due to mucin production by the tumor. Stereotactic body radiation therapy (SBRT) has been used as a treatment modality, resulting in favorable outcomes. An 80-year-old male patient presented to the emergency room with symptoms of cholangitis, for which he had previously undergone endoscopic lithotripsy for the removal of choledochal stones. The persistent symptoms and viscous bile led to suspicions of IPNB; therefore, the patient underwent a peroral cholangioscopy with biopsy to confirm the diagnosis. Due to his compromised cardiac function, however, surgical resection was not deemed a viable option, and biliary drainage was attempted instead. Unfortunately, frequent mucin-induced obstructions of the catheter made it difficult to control the cholangitis; therefore, SBRT was administered to achieve local tumor control and reduce mucin production. The radiation was delivered using a 10 MV beam with a volumetric-modulated arc therapy, fiducial gold markers, and suspended exhalation. A total dose of 60 Gy was administered across eight fractions (planning target volume D95), and one month post-SBRT, the biliary dilation and cholangitis had resolved. No local tumor regrowth or recurrent cholangitis occurred for at least one year after treatment, nor were any significant adverse effects related to the SBRT observed. According to the Surveillance, Epidemiology, and End Results (SEER) database, SBRT has been performed for IPNB; however, only a few case reports have been identified, all of which were cases in which brachytherapy was performed. To our knowledge, this is the first case report detailing a treatment regimen of SBRT with a definite radiation dose. This case suggests that SBRT may be of value as an alternative therapy for cases in which surgical resection is not an option.

Benign tumors of the liver and biliary tract are rare entities, and some of them require surgical management to prevent their malignant transformation. Tumors from the biliary tract with malignant potential are treated either by hepatic resection, for mucinous cystic neoplasm and ciliated hepatic foregut cysts, or by biliary resections, for biliary papillary neoplasm and type I and IV choledochal cysts. The pathologies requiring prophylactic cholecystectomy are polyps larger than 10 mm, porcelain gallbladder and pancreaticobiliary maljunction. Finally, hepatocellular adenoma over 5cm, occurring in male patients, or exon 3 mutated beta-catenin, should lead to prophylactic resection by hepatic segmentectomy. This article describes these different pathologies and their management.

Intraductal papillary neoplasm of the bile duct (IPNB) is a biliary neoplasm characterized by intraductal papillary growth and varying degrees of malignant transformation. This study aimed to identify effective prognostic factors (PFs) for predicting the prognosis of IPNB after surgical resection, addressing the gap in the higher level evidence. We systematically searched databases from their inception to October 10, 2023. Data on 12 predetermined PFs were collected and subjected to a meta-analysis. Forest plots were used to summarize the findings. Fifteen studies with a total of 2311 patients were included. Among the PFs examined, extrahepatic tumor location (HR, 2.97; 95% CI 1.68-5.23), subclassification type 2 (HR, 2.62; 95% CI 1.45-4.76), R1 resection (HR, 2.47; 95% CI 1.73-3.51), elevated CA19-9 level (HR, 3.25; 95% CI 1.91-5.54), tumor multiplicity (HR, 2.65; 95% CI 1.40-5.02), and adjacent organ invasion (HR, 3.17; 95% CI 2.01-5.00) were associated with a poorer prognosis. Additionally, the combined HR values indicated that lymph node metastasis and poor tumor differentiation were linked to a worse prognosis, although both exhibited significant heterogeneity. Our study offers valuable insights for enhancing postoperative prognostication and treatment decision-making for IPNB patients with IPNB. These findings warrant further validation in future prospective studies.

Intrahepatic cholangiocarcinoma (iCCA) has been subclassified by its gross morphology into the mass-forming (MF), periductal-infiltrating (PI), and intraductal growth (IG) types and their combinations. This classification correlates well with clinical features; for example, MF-iCCA has less lymph-node metastasis and a better prognosis than PI-iCCA. According to the recently accumulated evidence from histological investigations, the WHO classification endorsed a subclassification scheme in which iCCA cases are classified into small- and large-duct types. Small-duct iCCA is considered to originate from septal or smaller bile ducts and is characterized by less frequent lymph-node metastasis, a favorable prognosis, and an MF appearance. Large-duct iCCA arises around the second branch of the biliary tree and has more aggressive biology and distinct genetic abnormalities. According to the practice guidelines for iCCA from the Liver Cancer Study Group of Japan and the National Comprehensive Cancer Network, upfront surgery is recommended for iCCA without distant metastasis regardless of the morphological subtype, based on clinical experience. In consideration of the biological heterogeneity of iCCA, the treatment strategy for iCCA needs to be reconsidered based on the WHO subtypes.

To establish a classification system which differentiates cystic intraductal papillary neoplasm of the bile duct (cystic IPNB) from hepatic mucinous cystic tumors (MCN) based on their radiological difference.

A total of 75 patients pathologically diagnosed as MCN and IPNB in two major hospitals from 2015 to 2024 were enrolled. Radiological features were recorded and compared between these two tumors. Variables with significant differences were included in multivariate logistic regression (LR) analysis. A decision model was built and simplified based on importance ranking of variables. K-nearest-neighbor (KNN) model was introduced to learn distribution of individuals in main dimensions based on multiple correspondence analysis (MCA) and predicted diagnosis. The diagnostic efficacy of the classification system and the KNN model was compared.

Significant differences existed in Dmax-IVC angle, septation, mural nodule, upstream and downstream biliary dilatation, communication with bile duct between MCN and cystic IPNB. Downstream biliary dilatation and communication with bile duct were highly specific for IPNB (specificity, 97.9 % and 100 %, respectively), which could independently diagnose IPNB. Among four significant indicators in LR analysis, upstream biliary dilatation and Dmax-IVC angle were used for a simplified decision model to attain good applicability. The KNN model based on MCA data achieved highest accuracy (0.910) when K = 11. Overall, the classification system achieved an AUC of 0.882 (0.95CI: 0.797-0.966), compared with 0.911 (0.95CI: 0.818-1.000) in the KNN model, which demonstrated no significant difference (p = 0.655) in differential performance.

The classification system combining four important indicators had equivalent performance to KNN model in discrimination, which was simple and applicable for clinical practice, and also accessible on unenhanced examinations.

There are several types of microvasculature supplying neoplasms: "newly formed blood vessels" (neoangiogenesis), which are a component of the tumor microenvironment (TME) of invasive carcinoma with wound healing-like reaction; and "pre-existing blood vessels", which are used as tumor-supplying vessels by neoplasms (co-option vessels) and are likely to develop in hypervascularized organs. We herein review the microvasculature of neoplasms of biliary tract with reference to pre-existing vessels and vessel co-options. In the hepatobiliary system, intrahepatic large and extrahepatic bile ducts (large bile ducts) and the gallbladder as well as hepatic lobules are highly vascularized regions. In large bile ducts, the biliary lining epithelia and underlining capillaries (peribiliary capillary plexus [PCP]) form the biliary epithelia-PCP alignment, whereas the hepatocyte-sinusoid alignment composes hepatic lobules. Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are the main biliary tract carcinomas. CCA is subdivided into distal (d/CCA), perihilar (pCCA), and intrahepatic (iCCA), and iCCA is subdivided into small duct type (SD-iCCA) and large duct type (LD-iCCA). High-grade biliary intraepithelial neoplasm (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN) have recently been proposed as the precursors of LD-iCCA, p/dCCA, and GBC. In the large bile ducts and gallbladder, all cases of high-grade BilIN and PGA, about half of IPNB, and one-third of ICPN with less-complicated structure were found to have hijacked the PCP as their supporting vessels (vessel co-option), while p/dCCA, LD-iCCA, and GBC were supplied by neo-angiogenetic vessels associated with fibrous stroma. The intraluminal components of the remaining cases of ICPN and IPNB with complicated structure presented sparse capillaries without fibrous stroma, a unique microvasculature different from that of co-option or neoangiogenesis. Regarding iCCA showing invasion into the hepatic lobules, some SD-iCCAs replaced hepatocytic cords and used pre-existing sinusoids as co-opted vessels. Visualization of pre-existing vessels could be a new pathological tool for the evaluation of malignant progression and of vascular supply in CCAs and its precursors.

The intraductal papillary neoplasm of the bile duct is a rare tumor considered one of the precursor lesions of cholangiocarcinoma. It is characterized by papillary growth within the bile duct lumen, occurring anywhere in the biliary tree. We report a case of a 70-year-old man who presented with a six-month history of weight loss and occasional choluria. An abdominal ultrasound showed a marked dilatation of the biliary tree with a polypoid intraluminal lesion. Computed tomography and magnetic resonance imaging confirmed the presence of these findings and did not reveal any secondary lesions. The patient underwent a cephalic duodenopancreatectomy yielding a diagnosis of intraductal papillary neoplasm with high-grade dysplasia.

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 5 mm oval defect in region B6 and two 8 mm semicircular defects in the hilar bile duct. Endoscopic ultrasound revealed a 3.5 mm 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.

Intraductal papillary neoplasm of bile duct (IPNB), as a precancerous lesion of cholangiocarcinoma, is a rare biliary tract tumor. A 66-year-old female patient was found to have a bile duct mass by routine examination. The liver function tests and tumor markers were normal. Imaging findings revealed a 2.6 cm mass in the common hepatic duct, accompanied by dilatation of both intrahepatic and extrahepatic bile ducts. The patient underwent open extrahepatic bile duct resection, cholecystectomy and Roux-en-Y hepaticojejunostomy. We also conducted a literature review to summarize the clinicopathological features and surgical treatments of IPNB.

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 ≥ 2.5 cm (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.

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 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.

Intracholecystic papillary neoplasm (ICPN) of the gallbladder is a macroscopically visible premalignant lesion protruding into the gallbladder lumen, with infrequent association with invasive adenocarcinoma. Intraductal papillary neoplasm of the bile ducts (IPNB) is a non-invasive lesion characterized by intraductal papillary or villous architecture. Both ICPN and IPNB are rare findings in the gallbladder and biliary tract pathology. Diagnosis relies on clinical manifestations, imaging techniques, and comprehensive histological examination. Here, we present two cases: a 63-year-old male with mild abdominal pain found to have a gallbladder mass, diagnosed histologically as ICPN with associated invasive carcinoma; and a 65-year-old female with chronic jaundice and a large tumor mass in the common bile duct, histologically diagnosed as IPNB with associated invasive carcinoma. These cases highlight the importance of a careful and thorough microscopic examination to rule out differential diagnoses and to reveal any potential invasive carcinoma associated with these uncommon lesions.

Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB.

A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan.

A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions.

Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

Most precursor lesions and early cancerous changes in the gallbladder and bile ducts present as clinically/grossly inapparent lesions. Low-grade dysplasia is difficult to define and clinically inconsequential by itself; however, extra sampling is required to exclude accompanying significant lesions. For high-grade dysplasia ('carcinoma in situ'), a complete sampling is necessary to rule out invasion. Tumoral intramucosal neoplasms (ie, intracholecystic and intraductal neoplasia) form radiologically/grossly visible masses, and they account for (present in the background of) about 5% to 10% of invasive cancers of the region. These reveal a spectrum of papilla/tubule formation, cell lineages, and dysplastic transformation. Some subtypes such as intracholecystic tubular non-mucinous neoplasm of the gallbladder (almost never invasive) and intraductal oncocytic or intraductal tubulopapillary neoplasms of the bile ducts (may have a protracted clinical course even when invasive) are to be noted separately. Other types of intracholecystic/intraductal neoplasia have a high frequency of invasive carcinoma and progressive behavior, which often culminates in mortality.

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.

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.

Hepatic and biliary masses, should be considered to diagnose IPNB. Prompt surgery and vigilant follow-up are crucial in determining prognosis.

Intraductal papillary neoplasm of the bile ducts is a rare tumor. Characteristic features include bile duct dilatation, cystic lesions with communication to the bile ducts, and intraluminal solid nodules arising from the bile duct wall. As in pancreatic intraductal papillary mucinous neoplasia, intestinal, pancreaticobiliary, gastric, and oncocytic types are described. Intraductal papillary neoplasm of the bile ducts has a high potential for malignancy, and patients should be surgically resected when possible. In this review, the complex imaging diagnosis is presented. The main focus is on contrast-enhanced ultrasound, an established method for many other indications whose potential on the biliary system should be better exploited. In the present article, typical contrast-enhanced ultrasound findings in intraductal papillary neoplasm of the bile ducts are demonstrated.

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 (IPNB) is a relatively rare disease and is known as one of the premalignant lesions in the biliary tract. The concept of IPNB has changed through numerous studies and is still evolving. As a lesser studied clinical entity compared with its pancreatic counterpart, intraductal papillary mucinous neoplasm, IPNB has been described in many similar terms, including biliary papillomatosis, biliary intraductal papillary-mucinous neoplasm, and papillary cholangiocarcinoma. This is based on the diversity of histopathological spectrum of IPNB.

This review investigated previous studies including original articles, case studies, and expert opinions. Recently, two types of IPNB (types 1 and 2) have been proposed and validated based on the content first established in the WHO 2010 criteria.

This review provides a comprehensive analysis of existing literature, summarizing the clinical, radiological, morphological, and pathological characteristics of IPNB.

Given the ongoing ambiguity and controversies surrounding IPNB, future research, including large population-based studies and molecular investigations, is essential to enhance understanding of this disease.

An intraductal papillary mucinous neoplasm of the biliary tract (BT-IPMN) in the caudate lobe of the liver is a rare tumor originating from the bile duct. Approximately 40% of the intraductal papillary neoplasms of the biliary tract (IPNB) secrete mucus and can grow in the intrahepatic or extrahepatic bile ducts. A 65-year-old woman presented with recurrent episodes of right upper pain. She developed her first episode 8 years ago, which resolved spontaneously. The frequency of symptoms has increased in the last 2 years. She underwent laparoscopic hepatectomy and choledochal exploration and was pathologically diagnosed with a rare BT-IPMN of the caudate lobe after admission. Here, we review studies on IPNB cases and systematically describe the pathological type, diagnosis, and treatment of IPNB to provide a valuable reference for hepatobiliary surgeons in the diagnosis and treatment of this disease.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease in Western countries. The main aim of this study was to characterize current surgical strategies and outcomes in the mainly European participating centers.

A multi-institutional retrospective series of patients with a diagnosis of IPNB undergoing surgery between 1 January 2010 and 31 December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association. The textbook outcome (TO) was defined as a non-prolonged length of hospital stay plus the absence of any Clavien-Dindo grade at least III complications, readmission, or mortality within 90 postoperative days.

A total of 28 centers contributed 85 patients who underwent surgery for IPNB. The median age was 66 years (55-72), 49.4% were women, and 87.1% were Caucasian. Open surgery was performed in 72 patients (84.7%) and laparoscopic in 13 (15.3%). TO was achieved in 54.1% of patients, reaching 63.8% after liver resection and 32.0% after pancreas resection. Median overall survival was 5.72 years, with 5-year overall survival of 63% (95% CI: 50-82). Overall survival was better in patients with Charlson comorbidity score 4 or less versus more than 4 ( P =0.016), intrahepatic versus extrahepatic tumor ( P =0.027), single versus multiple tumors ( P =0.007), those who underwent hepatic versus pancreatic resection ( P =0.017), or achieved versus failed TO ( P =0.029). Multivariable Cox regression analysis showed that not achieving TO (HR: 4.20; 95% CI: 1.11-15.94; P =0.03) was an independent prognostic factor of poor overall survival.

Patients undergoing liver resection for IPNB were more likely to achieve a TO outcome than those requiring a pancreatic resection. Comorbidity, tumor location, and tumor multiplicity influenced overall survival. TO was an independent prognostic factor of overall survival.

Intraductal papillary neoplasm of the bile duct (IPNB) is a premalignant neoplasm that can involve both the intrahepatic and extrahepatic bile ducts. Owing to the low incidence and confusing nomenclature, its clinicopathological features remain controversial. Additionally, only a few studies have reported on the long-term prognosis of IPNB to date. Therefore, the present study aimed to clarify the clinicopathological characteristics and prognosis of IPNB.

Medical records of patients with IPNB treated at our hospital between August 2000 and October 2021 were retrospectively reviewed. A database of demographic characteristics, test results, surgical details, pathological findings, and follow-up information was constructed for analysis. Patients were divided into intrahepatic and extrahepatic groups, and dysplasia and invasive carcinoma groups for comparison. Differences between study groups were analyzed using the χ2 test, Fisher's exact test, t-test, or Mann-Whitney U test, as appropriate. Cumulative survival rates were estimated using the Kaplan-Meier method.

In total, 43 patients (21 men and 22 women) with IPNB were included in the study. The median age at diagnosis was 62 (54-69) years. Thirty-eight patients underwent surgery. The mean operation time was (269.5 ± 94.9) min. Five patients underwent endoscopic retrograde cholangiopancreatography for biopsy. Twenty-one and 22 patients had intrahepatic and extrahepatic lesions, respectively. The extrahepatic group had more patients with intraluminal masses (p = 0.021) and abnormal bilirubin levels (p = 0.001), but fewer patients with hepatolithiasis (p = 0.021). The operation time was longer in patients with extrahepatic lesions (p = 0.002). Twenty patients had dysplasia and 23 had invasive carcinoma. The invasive carcinoma group had a longer operation time than the dysplasia group (p = 0.004). As of March 2022, 39 patients were followed up, with a mean follow-up time of (56.2 ± 38.2) months. Fifteen patients survived without tumors, two survived with tumors, and 22 patients died. The 1-, 3-, 5-, and 10-year cumulative overall survival rates were 86.9%, 65.8%, 49.8%, and 32.0%, respectively.

IPNB is a rare bile duct disease that occurs mainly in patients with advanced age. Surgery is the primary treatment strategy. Intrahepatic and extrahepatic lesions, as well as dysplasia and invasive carcinoma have their own unique characteristics. The long-term prognosis of IPNB is generally poor.

This study aimed to investigate the clinicopathological findings of intraductal papillary neoplasm of the bile duct (IPNB) in patients with occupational cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane to elucidate the development of IPNB to cholangiocarcinoma. The clinicopathological findings of 17 IPNB lesions according to the size (1.5-20 mm in diameter) and their comparison between type 1 (n = 9) and type 2 IPNBs (n = 8) were investigated. An IPNB of <5 mm in size was classified as micro IPNB (n = 7), while those ≥5 mm in size were classified as ordinary IPNB (n = 10). Both types 1 and 2 IPNBs were observed in micro IPNB, and their proportions were not different between micro and ordinary IPNBs. The clinicopathological characteristics of types 1 and 2 IPNBs were fundamentally similar to those previously reported. IPNB with invasive carcinoma was only found in ordinary IPNB although the proportions of low-grade and high-grade epithelium were not different between micro IPNB and ordinary IPNB. All IPNB exhibited γH2AX and S100P, indicating the occurrence of DNA injury and malignant transformation in micro and ordinary IPNBs. These results indicate that the carcinogens may induce micro IPNB with types 1 or 2 at the initiation and then develop ordinary IPNB with types 1 or 2, subsequently, progressing to IPNB with invasive carcinoma in patients with occupational cholangiocarcinoma.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare premalignant neoplasm that can progress to invasive adenocarcinoma. In this retrospective study, cases of IPNB were reviewed to examine cytomorphologic and molecular features.

IPNB cytology cases with histopathologic confirmation were retrieved from the pathology archives. The cytomorphologic features such as cellularity, architecture, cell type, and cellular details were analyzed.

The cohort included 13 cases (six brushings, six fine-needle aspirations [FNA], and one combined brushing and FNA). The lesions involved common bile duct in nine cases (69%) and hepatic duct in four cases (31%). Original cytological diagnoses included adenocarcinoma (five, 38%), suspicious for adenocarcinoma (one, 8%), neoplasm (three, 23%), atypical (three, 23%), and reactive (one, 8%). The cytomorphologic features included moderate/high cellularity (12, 92%), papillary and/or complex papillary architecture (10, 77%), columnar cells (11, 85%), vacuolated cytoplasm (12, 92%), enlarged nuclei (13, 100%), and fine granular chromatin (12, 92%). Background mucin, necrosis and acute inflammation were seen in four (31%), four (31%), and two (15%) cases, respectively. KRAS testing was performed in nine cases with mutant KRAS found in five (56%).

Our study demonstrated that IPNB cytology specimens were relatively cellular with a wide spectrum of cytomorphology; however, most cases harbored adenocarcinoma or high-grade dysplasia. The characteristic cytomorphologic features included papillary/complex papillary clusters of columnar cells with vacuolated cytoplasm, enlarged nuclei, and fine granular chromatin in relatively cellular specimens. KRAS mutations identified may have potential diagnostic and therapeutic implications.

This chapter provides a comprehensive background from basic to applied knowledge of surgical anatomy which is necessary for the surgical treatment of cholangiocarcinoma (CCA) patients. Significant advances that have been made in the surgical treatment of CCA were examined. For instance, in-depth details are provided for appropriate preoperative assessment and treatment to optimize patient status and to improve the outcome of surgical treatment(s). Comprehensive details are provided for the surgical techniques and outcomes of treatments for each type of CCA with clear illustrations and images. This chapter also describes the role of minimally invasive surgery and liver transplantation in CCA treatment.

Although KRAS mutations are the major driver of intrahepatic cholangiocarcinoma (ICC), their role remains unexplored. This study aimed to elucidate the prognostic effects, association with clinicopathologic characteristics and potent functions of KRAS mutations in ICC.

A hundred and seven resected stage I-III ICCs were analysed for KRAS mutation status and its link with clinicopathological features. An independent validation cohort (n = 138) was included. In vitro analyses using KRAS-mutant ICC cell lines were performed.

KRAS mutation was significantly associated with worse overall survival in stage I-III ICCs, which was validated in an independent cohort. Recurrence-free survival did not significantly differ between cases with and without KRAS mutations, but if limited to recurrence with extrahepatic metastasis, KRAS-mutant cases showed significantly worse distant metastasis-free survival than KRAS-wild cases showed. KRAS mutations were associated with frequent tumour budding with reduced E-cadherin expression. In vitro, KRAS depletion caused marked inhibition of cell growth and migration together with E-cadherin upregulation in KRAS-mutant ICC cells. The RNA-sequencing assay revealed that KRAS depletion caused MYC pathway downregulation and interferon pathway upregulation.

Our observations suggest that KRAS mutations are associated with aggressive behaviour of ICC, especially the development of extrahepatic metastasis. Mutant KRAS is likely to change the adhesive status of ICC cells, affect the responsiveness of tumour cells to interferon immune signals, and consequently promote extrahepatic metastasis. KRAS mutation status, which predicts the prognoses of patients with ICC after surgical resection, is expected to help stratify patients better for individual postoperative treatment strategies.

Intraductal papillary neoplasm of the bile duct (IPNB) has a wide range of histopathology and intra- and extrahepatic tumor locations.

This retrospective single-center study evaluated the clinicopathological features and long-term outcomes of 146 patients with IPNB of the liver (IPNB-L) who underwent hepatic resection between January 2002 and June 2019.

The 146 patients included 97 (66.4%) men and 49 (33.6%) women, of mean age 64.3 ± 8.0 years. Seventy-two (49.3%) patients were incidentally diagnosed, with no specific symptoms, and 18 (12.3%) were found to have hepatolithiasis. Sixty-one (41.8%) and two (1.4%) patients underwent concurrent bile duct resection and pancreaticoduodenectomy, respectively, and 130 (89.0%) underwent R0 resection. Low-grade and high-grade intraepithelial neoplasia, and invasive carcinoma were identified in 26 (17.8%), 50 (34.2%), and 70 (47.9%) patients, respectively. Five-year tumor recurrence and patient survival rates were 8.4% and 93.9%, respectively, in patients with high-grade neoplasia; and 41.5% and 72.3%, respectively, in patients with invasive carcinoma. CA19-9 > 37 U/mL and R1 resection were independent risk factors for tumor recurrence and reduced survival in patients with carcinoma. The combination of hypermetabolic fluorodeoxy-glucose-positron emission tomography (FDG-PET) or elevated CA19-9 showed a sensitivity of 91.8% and a specificity of 61.9% for the prediction of IPNB-L with high-grade neoplasia and carcinoma.

IPNB-L is a rare type of intrahepatic biliary neoplasm that can range histologically from benign disease to invasive carcinoma. Surgical curability is the most important prognostic factor, thus aggressive resection is highly recommended to achieve R0 resection.

Recently, "polypoid invasive carcinoma (PICA)" showing grossly visible polypoid, invasive carcinoma with no adenoma component was proposed as a neoplastic polyp of the gallbladder. Herein, we report four cases of PICA of the bile duct. PICA cases of bile duct showed single, sessile polypoid growth grossly, and polypoid components were composed of invasive carcinoma of papillary/tubular patterns with active desmoplasia, and invaded directly and continuously into the bile duct wall and periductal tissue. While PICA and other intraductal papillary neoplasm of bile duct (IPNB) shared several features, PICA showed an invasive carcinoma growing in the duct lumen and also invading into the bile duct wall, thus different from IPNB which is the intraluminal polypoid, preinvasive epithelial neoplasia with back-to-back epithelial units. Taken together, PICA and IPNB could be differentiated from each other.

An 82-year-old man presented to the emergency department with abdominal pain and febrile symptoms that had been present for 4 days. Blood tests showed elevated liver enzymes and white blood cell count, and abdominal contrast-enhanced CT revealed a 35 mm cystic lesion in the left lateral liver lobe. On closer examination, the cystic lesion was found to have contiguous bile duct dilatation and internal nodules. Furthermore, mucus production was observed during endoscopic retrograde cholangiopancreatography, which led to the diagnosis of intraductal papillary neoplasm of the bile duct (IPNB), with cystic infection. Although the patient was an older adult, there was no background disease that would have prevented surgery, and resection was performed. Pathological examination revealed type 1 IPNB, with invasive carcinoma. The number of reports of IPNB is expected to increase with an increasing older population in Asia, and we report the findings of this case.

Pyloric gland adenoma (PGA) of the gallbladder is a polypoid, preinvasive epithelial neoplasm composed of uniform back-to-back, pyloric glands in a tubular configuration. Intracholecystic papillary neoplasm (ICPN), another preinvasive grossly visible neoplasm of the gallbladder, is subdividable into four subtypes, including gastric subtype. In this study, PGA was reappraised referring to gastric subtype of ICPN (gICPN).

PGA and gICPN pathologically defined by WHO 2019 classification were surveyed in a total of 104 cases of gallbladder epithelial neoplasms of our Hospital (2002 January to 2021 May) and were pathologically and immunohistochemically compared.

PGA (7 cases) was characterized by i) a well-demarcated, polypoid lesion and ii) packed tubular components resembling pyloric glands. gICPNs (14 cases) were subdivided into i) pyloric gland predominant (2 cases), ii) foveola predominant (6 cases) and iii) mixed foveola and pyloric gland type (6 cases). gICPNs were also divided into a solitary, polypoid lesion with well demarcation from the surrounding mucosa (5 cases) and a conglomerated polypoid and granular lesions with poor demarcation (9 cases). PGA shared gross and histologic features with solitary, polypoid gICPNs, and PGA could be regarded as solitary gICPN predominantly composed of pyloric glands. Nuclear expression of β-catenin was found in 6 of 7 PGA, but absent in gICPN, including solitary, polypoid gICPN.

PGA could correspond to a solitary gICPN mainly composed of pyloric glands, but may undergo a different molecular pathway from gICPN.

Cystic hepatobiliary neoplasms with mucin-producing epithelium-mucinous cystic neoplasm of the liver (MCN) and intraductal papillary neoplasm of the bile duct (IPNB)-are rare and distinct entities that have unique clinical, pathologic, and imaging features. They are differentiated pathologically by the presence of subepithelial ovarian-like hypercellular stroma (OLS), which is the defining histopathologic feature of MCN. MCN is commonly a benign, large, solitary, symptomatic, multiloculated cystic mass without biliary communication that occurs in middle-aged women. On the other hand, IPNBs are a heterogeneous spectrum of tumors, which are commonly associated with invasive carcinoma, occur in older patients, and can be differentiated from MCN by communication with the biliary tree, intraductal masses, associated biliary ductal dilatation, and absent OLS. Understanding of these rare neoplasms has grown and evolved over time and continues to today, but uncertainty and controversy persist, related to the rarity of these tumors, relatively recent designation as separate entities, inherent clinicopathologic heterogeneity, overlapping imaging features, and the fact that many prior studies likely included MCN and cystic IPNB together as a single entity. Confusion regarding these neoplasms is evident by historical inconsistencies and nonstandardized nomenclature through the years. Awareness of these entities is important for the interpreting radiologist to suggest a particular diagnosis or generate a meaningful differential diagnosis in the appropriate setting, and is of particular significance as MCN and cystic IPNB have overlapping imaging features with other more common hepatobiliary cystic masses but have different management and prognosis. Online supplemental material is available for this article. Work of the U.S. Government published under an exclusive license with the RSNA.

A 73-year-old man with mixed-type intraductal papillary mucinous neoplasm of the pancreas body was followed up for 14 years. Based on imaging findings, the intraductal papillary mucinous neoplasm of the pancreas met the high-risk stigmata, and new hepatic masses were suspected to be intraductal papillary neoplasms of the bile duct. With a diagnosis of intraductal papillary mucinous neoplasm of the pancreas and intraductal papillary neoplasm of the bile duct, the patient had undergone left lateral hepatectomy and distal pancreatectomy. Based on pathology, the pancreatic specimen was diagnosed as a high-grade intraductal papillary mucinous neoplasm of the pancreas, and the hepatic specimen was diagnosed as an intraductal papillary neoplasm of the bile duct and hepatocellular carcinoma. The intraductal papillary neoplasms of the bile duct and hepatocellular carcinoma were adjacent to each other. Fifteen months after surgery, recurrence in the remnant pancreas was detected. The patient had undergone residual total pancreatectomy, with no recurrence thirty months after the second resection. This case demonstrates that second surgery for metachronous high-risk lesions in the remnant pancreas of patients with intraductal papillary mucinous neoplasm of the pancreas and intraductal papillary neoplasm of the bile duct may also be considered to improve survival.

Because of new and improved imaging techniques, cystic/intraductal pancreatobiliary tract lesions are increasingly being discovered, and brushings or endoscopic ultrasound/computed tomography/magnetic resonance imaging-guided fine-needle aspiration biopsies from these lesions have become an integral part of pathologists' daily practice. Because patient management has become increasingly conservative, accurate preoperative diagnosis is critical. Cytologic distinction of low-risk (pseudocysts, serous cystadenoma, lymphoepithelial cysts, and squamoid cysts of the pancreatic duct) from high-risk pancreatic cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) requires incorporation of clinical, radiologic, and cytologic findings, in conjunction with chemical and molecular analysis of cyst fluid. Cytopathologists must ensure appropriate specimen triage, along with cytologic interpretation, cyst classification, and even grading of some (mucinous) cysts. Epithelial atypia in mucinous cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) has transitioned from a 3-tiered to a 2-tiered classification system, and intraductal oncocytic papillary neoplasms and intraductal tubulopapillary neoplasms have been separately reclassified because of their distinctive clinicopathologic characteristics. Because these lesions may be sampled on brushing or fine-needle aspiration biopsy, knowledge of their cytomorphology is critical.

To use an integrated, multidisciplinary approach for the evaluation of cystic/intraductal pancreatobiliary tract lesions (incorporating clinical, radiologic, and cytologic findings with [chemical/molecular] cyst fluid analysis and ancillary stains) for definitive diagnosis and classification.

Review of current literature on the cytopathology of cystic/intraductal pancreatobiliary tract lesions.

Our knowledge/understanding of recent updates in cystic/intraductal pancreatobiliary lesions can ensure that cytopathologists appropriately triage specimens, judiciously use and interpret ancillary studies, and incorporate the studies into reporting.

Intracholecystic papillary neoplasm (ICPN) is a recently proposed gallbladder neoplasm. Its prevalence and pathologies remain to be clarified. A total of 38 ICPN cases (28 ICPNs identified among 1904 cholecystectomies (1.5%) and in 100 surgically resected primary gallbladder neoplasms (28%) in Fukui Prefecture Saiseikai Hospital, Japan, and other 10 ICPNs) were examined pathologically and immunohistochemically. They were composed of 21 males and 17 females with a mean age of 75 years old, and presented intraluminal growth of papillary lesions with fine fibrovascular stalks. ICPNs were relatively frequent in the fundus (n = 11) and body (n = 9). Grossly, the conglomerated sessile type (n = 30) was more frequent than the isolated polypoid type (n = 8). All cases were classified as high-grade dysplasia, and they were further divided into 22 cases presenting irregular structures and 16 cases presenting regular structures. The former showed frequent complicated lesions and stromal invasion (54.5%) compared to the latter (12.5%). Twenty-four cases showed predominantly either of four subtypes (11 gastric, 7 intestinal, 4 biliary and 2 oncocytic subtype), while the remaining14 cases showed mixture of more than two subtypes. In conclusion, ICPN presented unique preinvasive neoplasm with characteristic histopathologies. Irregular histologies and complicated lesions of ICPN were related to stromal invasion.

Evidence regarding intraductal papillary neoplasm of the bile duct (IPNB) as a type of precancerous lesion of cholangiocarcinoma is limited. Moreover, a reproducible in vivo model is lacking, and IPNB pathogenesis remains unclear. Here, we use a doxycycline-inducible tetracycline (Tet)-on mice model to control fibroblast growth factor 10 (FGF10) expression, which regulates branching and tubule formation. FGF10-induced IPNB mimics the multifocal and divergent human IPNB phenotypes via the FGF10-FGF receptor 2 (FGFR2)-RAS-extracellular-signal-regulated kinase (ERK) signaling pathway. A paracrine/autocrine growth factor is sufficient to initiate and maintain IPNB originating from the peribiliary glands, including biliary stem/progenitor cells. With Kras^G12D, p53, or p16 mutations or both, Fgf10-induced IPNB shows stepwise carcinogenesis, causing associated invasive carcinoma. Fgf10-induced papillary changes and progression are suppressed by the inhibition of the FGF10-FGFR2-RAS-ERK signaling pathway, demonstrating that the signal is a therapeutic target for IPNB and associated carcinoma.

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.