Cases Of IPNB Research Articles

Pathologic characterization of precursors and cholangiocarcinoma referring to peribiliary capillary plexus: a new pathologic approach to bile duct neoplasm.

The peribiliary capillary plexus (PCP) regularly and densely lines the basal side of the lining epithelia of normal bile ducts. To determine the pathology of the PCP in high-grade biliary intraepithelial neoplasms (BilINs) and intraductal papillary neoplasms of the bile duct (IPNBs), a precursor of cholangiocarcinoma (CCA), and CCA. Seventy-six cases of surgically resected high-grade BilIN and 83 cases of IPNB were histopathologically examined using endothelial immunostaining of PCP; all cases of high-grade BilIN and 40 cases of IPNB were associated with invasive CCA. Invasive and preinvasive neoplasms were pathologically examined referring to a two-layer pattern composed of biliary lining epithelia and underlying PCP unique to the bile duct. All high-grade BilIIN cases had an underlying single layer of capillaries, similar to PCP (PCP-like capillaries). In 43% of the 83 cases of IPNB, these capillaries were regularly distributed in almost all stalks and intervening stroma of intraluminal neoplastic components, while in the remaining 57% of IPNB, capillaries were sparsely or irregularly distributed in intraluminal components showing cribriform or solid growth patterns composed of striking atypical neoplastic epithelia. Invasive carcinomas associated with high-grade BilIN and IPNB were not lined with capillaries. The loss of PCP-like capillaries underlying high-grade BilIN and in stalks or stroma of IPNB may be involved in the malignant progression of these precursors. Immunostaining of PCP could be a new pathological tool for the evaluation of malignant progression and vascular supply in CCA and its precursors.

Intraductal Implantation of Biliary Neoplasms: A Potential Cause of "Multifocal" Tumors.

Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS , GNAS , APC , BRAF , CTNNB1 , SMAD4 , TP53 , or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension.

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.

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.

Intraductal papillary neoplasm of the bile duct: Cytomorphologic and molecular features.

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.

Intraductal papillary neoplasm of the bile duct: two case reports and review of the literature

Background: Intraductal Papillary Neoplasm of the Bile Duct (IPNB) is a rare disease that is characterized by papillary lesions in the intra and extrahepatic biliary tree. Traditional imaging studies may show biliary dilation and/or filling defects. Endoscopic retrograde cholangiopancreatography can demonstrate diffuse bile duct dilatation as well as amorphous filling defects, however visualization of the biliary system can be limited by obstruction by the papillary lesions or mucin. Digital single operator cholangioscopy can be used to aid in diagnosis.Case Presentation: We report two elderly Caucasian males that presented with fatigue and obstructive jaundice. In both cases, the diagnosis of IPNB of was made. In one case, digital single operator cholangioscopy was used successfully to make the diagnosis.Conclusions: We present two cases of IPNB as well as a review of the clinical characteristics of IPNB and the utility of digital single operator cholangioscopy to aid in diagnosis. In IPNB, timely diagnosis is paramount. Traditional imaging studies can be inadequate, digital single operator cholangioscopy allows for quick diagnosis and, if indicated, further intervention.

Clinicopathological Aspects and Diagnostic Problems in Patients with Intraductal Papillary Neoplasm of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is defined as a non-invasive malignancy and disparity of its histological diagnosis with related diseases remains. Twenty-six cases of IPNB and 12 of papillary adenocarcinomas (PAC) at two Institutes were investigated. The prevalence of biliary dilatation and mucin secretion in the group with IPNB was significantly higher compared to the group with PAC (p<0.01). IPNB was predominantly located in the proximal bile duct compared to the location of PAC (p<0.01). Mis-matching of a second histological diagnosis was observed in 27% of IPNB and 25% of PAC, respectively. The prevalence of tumor relapse was significantly higher in PAC than in IPNB (p<0.05), and the overall survival was significantly better in IPNB than in PAC (p<0.01). Although IPNB is currently defined under histological criteria, morphologies were various and disparity in histological diagnosis for IPNB remains problematic when the clinical strategy is contemplated.

Clinicopathological features of intraductal papillary neoplasms of the bile duct: a comparison with intraductal papillary mucinous neoplasm of the pancreas with reference to subtypes.

Intraductal papillary epithelial neoplasms of the pancreatobiliary system (intraductal papillary neoplasm of the bile duct (IPNB) and intraductal papillary mucinous neoplasm (IPMN)) seem to share many clinicopathological features; however, IPNB has not been fully characterized. In order to understand the clinicopathological/immunohistochemical features of IPNB better, we compared 52 cases of IPNB with 42 cases of IPMNs with mural nodules. The IPNB cases were divided into two groups according to their histological similarity and according to five key histological findings. All IPNB and IPMN cases mainly affected middle-aged to elderly people, predominantly men. Mucin hypersecretion was less frequent in IPNB compared to IPMN. Group 2 IPNB more frequently had a higher histopathological grade and more extensive stromal invasion than IPMN. Group 1 IPNB and IPMN were further classified into four subtypes (gastric, intestinal, pancreatobiliary, and oncocytic). Although each subtype of IPNB and IPMN showed similar histology, the immunohistochemical results were different. The gastric type of IPNB was less frequently positive for CDX2, and intestinal IPNB was more frequently positive for MUC1 and less frequently positive for MUC2, MUC5AC, and CDX2 compared to each subtype of IPMN, respectively. In conclusion, IPNB and IPMN have some clinicopathological features in common, but mucin hypersecretion was less frequent both in IPNBs than in IPMN. Group 2 IPNB differed from IPMN in several parameters of tumor aggressiveness. Additional clinicopathological and molecular studies should be performed with respect to the subtypes of IPNB and IPMN.

Gallbladder papillary neoplasms share pathological features with intraductal papillary neoplasm of the bile duct.

Intraductal papillary neoplasm of the bile duct (IPNB) has been widely recognized. However, the knowledge of intracystic papillary neoplasm of the gallbladder (IPNG) including papillary adenoma and adenocarcinoma is not well defined. In this study, we compared the clinicopathological and immunohistochemical features between 32 IPNG cases and 32 IPNB cases. IPNG-1 (low-high grade dysplasia) exhibited an earlier onset age, smaller tumor size and lower level of CK20 expression compared to IPNG-2 (invasive carcinoma). Histologically, pancreaticobiliary and intestinal subtype accounted for nearly half of IPNG or IPNB (44.4% and 48.1% vs. 44.0% and 44.0%), respectively. Immunohistochemically, 88.9% of IPNG and 92.0% of IPNB cases were positive for MUC1, and 96.3% and 92.0% for CK7, respectively. CDX2 and MUC2 were more highly expressed in the intestinal subtype than in other subtypes. CK20 expression increased in parallel with tumor progression. In addition, 53.1% of IPNG cases and 68.6% of IPNB cases exhibited invasive carcinoma, and showed significant survival advantages to conventional gallbladder adenocarcinoma and cholangiocarcinoma, respectively. In conclusion, papillary adenoma and adenocarcinoma of the gallbladder can be recognized as different pathological stages of IPNG, and they share pathological features with IPNB.

Intraductal papillary neoplasms of intrahepatic bile duct: a clinicopathologic study of 25 cases

To study the clinicopathologic and immunohistochemical features of intraductal papillary neoplasms of the bile duct (IPNB) of the intrahepatic bile duct. The clinical findings, morphologic features and immunophenotype of 25 cases of IPNB were investigated. Of the 25 cases of IPNB, 18 were in the left lobe, 6 were in the hilar bile duct, and 1 was in the right lobe. The average age was 60.6 (26-73) years. The presenting symptom was abdominal pain in 15 cases. Imaging results were variable, including multilobular cysts, mass lesions within the dilated ducts, cholangiolithiasis with dilated bile duct, and solid mass. Gross examinations were concordant with imaging findings. Microscopically, all the IPNB could be divided into four papillary patterns, including 12 gastric type, 8 intestinal type, 4 pancreatobiliary type and 1 oncocytic type. Five IPNB showed mild to moderate atypia, 10 showed high-grade atypia and 10 IPNB were associated with carcinomas.The invasive IPNB were mainly bile duct adenocarcinomas(9 cases), and rarely colloid carcinoma (1 case). Immunohistochemically, IPNB expressed MUC5AC (96.0%, 24/25), MUC2 (32.0%, 8/25), MUC6 (40.0%, 10/25) and MUC1 (12.0%, 3/25). The different MUC expression was commonly associated with specific histological subtype. IPNBs are rare cystic and premalignant neoplasms of the liver. The imaging features vary, but show a common feature of dilated bile duct. The pathologic types and classifications are similar to intraductal papillary mucinous neoplasm of the pancreas. The MUC stains are helpful in diagnosis and histological subtyping.

Impact of radiation and surgery for intraductal papillary neoplasm of the bile duct: A population-based analysis.

363 Background: Intraductal Papillary Neoplasm of the Bile Duct (IPNB), either in-situ or invasive, is a histological variant with better prognosis then the more common adenocarcinoma. This study’s purpose is to use the Surveillance Epidemiology and End Results (SEER) database to evaluate prognostic factors: histology, stage, location, extent of surgery and the use of radiation therapy (RT). Methods: Cases from 1973-2011 were acquired. Inclusion criteria included intrahepatic (IHD), extrahepatic bile duct (EHD) or ampulla of vater (AoV) locations, first primary, extent of surgery and RT history. Kaplan-Meier and Log-Rank methods measured overall survival (OS) and disease specific survival (DSS) in months (m) and their medians (MOS, MDSS). Cox multivariate regression computed hazard ratios (HR) controlling for stage, treatment, surgical extent and histology. Results: . For non-invasive cases, 14% were IPNB (n = 31). Survival was similar for EHD &amp; AoV cases. Surgery was associated with prolonged MOS of 120m compared to 8m without surgery or RT. A trend suggested better survival with lesser extent of surgery for EHD &amp; AoV cases (p &lt; 0.16, n = 8 at both sites). For invasive cases, 5% were IPNB (n = 1309). For cases not receiving surgery, RT was associated with prolonged OS &amp; DSS from 3 to 7m (p = 0.026) and 4 to 8m (p = 0.074). In T1N0M0 EHD cases, surgery with and without RT had similar OS &amp; DSS. Cox analysis observed similar OS &amp; DSS for surgery with and without RT for EHD and AoV cases. Mucin-producing IPNB was less likely local stage disease (10% vs 39%, p &lt; 0.01), with shorter OS 5m vs 23 m (p &lt; 0.01) and DSS 6m vs 28m (p &lt; 0.01), and for EHD cases, with HR = 2.0 (p &lt; 0.01) compared to papillary type IPNB. Conclusions: For non-invasive IPNB, surgery with less extensive resections was associated with better prognosis. For invasive IPNB cases not amenable to surgery, RT improved short term survival. If high-risk factors such as suboptimal surgical margins, which are not recorded in SEER, correlated with the use of RT, then the outcomes in EHD &amp; AoV locations could be explained by an imparted benefit. As well, mucin-associated IPNB, was associated with worse survival than papillary type. Further work is necessary to validate these findings.

Diagnostic performance of CT and MRI in distinguishing intraductal papillary neoplasm of the bile duct from cholangiocarcinoma with intraductal papillary growth.

We aimed to evaluate the diagnostic performance of CT and MRI for distinguishing intraductal papillary neoplasm of the bile duct (IPNB) from cholangiocarcinoma (CC) with intraductal papillary growth (IPG). Forty-two patients with either IPNB or CC with IPG proven by histopathology were independently reviewed in retrospect. Strict criteria for diagnosis of IPNB included presence of the designated imaging features as follows: local dilatation of the bile duct, nodule within the dilated bile duct, growing along the interior wall of bile duct. Any lesion that was not consistent with the criteria was classified as CC with IPG. Sensitivity, specificity, positive and negative predictive values for characterization of IPNB were calculated, and k test was used to assess the level of agreement. Two imaging reviewers correctly identified 21 of 26 (80.8%) and 22 of 26 (84.6%) IPNB cases, respectively. Alternatively, they correctly identified 14 of 16 (87.5%) and 15 of 16 (93.8%) CC with IPG, respectively. Agreement between the two reviewers was perfect (k = 0.81) for the diagnosis of IPNB and differentiation from CC with IPG. By using our designated diagnostic criteria of CT and MRI, IPNB can be accurately identified and possible to be distinguished from CC with IPG. • IPNB can accurately be identified by using defined diagnostic criteria at CT/MRI. • IPNB has some characteristic CT and MR imaging features. • IPNB is a rare entity; up until now it might have been misdiagnosed.

Intraductal papillary neoplasms and mucinous cystic neoplasms of the hepatobiliary system: demographic differences between Asian and Western populations, and comparison with pancreatic counterparts

To improve the characterization of intraductal papillary neoplasm of the bile duct (IPNB) and mucinous cystic neoplasm of the liver (MCN-L). A retrospective review of pathology archives (1999-2011) in our three institutions identified cases of IPNB (n=138) and MCN-L (n=54). The IPNB/MCN-L ratio was 5.7:1 at Samsung Medical Centre in Seoul, which was significantly higher than those at the University of Washington Medical Center in Seattle (1:3.0) and King's College Hospital in London (1:6.3). This difference was mainly attributable to the considerably larger number of patients with IPNB in Seoul (n=131) than in Seattle and London (n=7). Western patients with IPNB were all non-Asian in ancestry. IPNB differed from pancreatic intraductal papillary neoplasm in its higher histological grade, more advanced stage of an associated invasive cancer, and worse prognosis. In contrast, MCN-L showed significantly lower histological grade than its pancreatic counterpart (P=0.022). Unlike in pancreatic mucinous cystic neoplasm, malignant transformation was very rare in MCN-L (10% versus 2%). This study demonstrated demographic differences in IPNB and MCN-L among regions. IPNB and MCN-L differ from their pancreatic counterparts in the risk of malignant transformation and patients' prognosis.

Intraductal papillary neoplasms of the bile duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas. IPNBs display a spectrum of premalignant lesion towards invasive cholangiocarcinoma. The most common radiologic findings for IPNB are bile duct dilatation and intraductal masses. The major treatment of IPNB is surgical resection. Ultrasonography, computed tomography, magnetic resonance image, and cholangiography are usually performed to assess tumor location and extension. Cholangioscopy can confirm the histology and assess the extent of the tumor including superficial spreading along the biliary epithelium. However, pathologic diagnosis by preoperative biopsy cannot always reflect the maximum degree of atypia, because IPNBs are often composed of varying degrees of cytoarchitectural atypia. IPNBs are microscopically classified into four epithelial subtypes, such as pancreatobiliary, intestinal, gastric, and oncocytic types. Most cases of IPNB are IPN with high-grade intraepithelial neoplasia or with an associated invasive carcinoma. The histologic types of invasive lesions are either tubular adenocarcinoma or mucinous carcinoma. Although several authors have investigated molecular genetic changes during the development and progression of IPNB, these are still poorly characterized and controversial.

Intraductal papillary neoplasm of the bile duct: clinicopathological study of 10 cases

Background and aims Intraductal papillary neoplasm of the bile duct (IPNB) is a new entity of biliary neoplasm that is characterized by predominant intraductal papillary growth with various degrees of malignant transformation. It has better prognosis compared with conventional cholangiocarcinoma. Although IPNB has been recently added to the WHO classification, preoperative diagnosis is still challenging and the classification system might need refinements. Methods We retrospectively reviewed clinicopathological features of 10 surgically resected cases of IPNB, which were previously diagnosed as intraductal cholangiocarcinoma or papillary adenocarcinoma of the bile duct from 2008 to 2014. Histologic features are classified into intestinal, gastric, pancreaticobiliary, and oncocytic types as described in the literature, together with invasive growth pattern and immunohistochemistry. Results Eight tumors (80%) were invasive IPNB and two (20%) were non-invasive. All of the non-invasive cases are IPNB with high-grade dysplasia. Three cases (30%) were cystic type which having a communication to the bile duct lumen. Discussion Intraductal growth type cholangiocarcinoma (invasive IPNB) showed a worse prognosis than IPNB with high-grade dysplasia. Curative resection is the major treatment and an important favorable factor for long-term survival, especially in patients with early-stage. Due to its rarity, a mechanism of histopathogenesis remains to be studied.

Dynamic contrast-enhanced MSCT findings of intraductal papillary neoplasm of the bile ducts

To investigate the findings of contrast-enhanced multislice computed tomography (MSCT) that characterize intraductal papillary neoplasms of bile ducts (IPNB). The MSCT findings and clinical data of 16 cases of IPNB proven by surgical pathology were reviewed retrospectively. Among the 16 cases, nine were adenoma (multi-lesions, n = 5; single lesions, n = 4) and seven were adenocarcinoma (multi-lesions, n = 4; single lesions, n = 3). Among the nine adenoma cases, seven showed nodules or masses in the expanding intrahepatic bile ducts with asymmetrical low density on plain scan, and two showed obvious expansion of biliary ducts and the inner wall of bile ducts was rough. All seven of the adenocarcinoma cases showed nodules or masses in the expanding intrahepatic bile ducts with asymmetrical low density-like adenoma. When contrast enhancement was applied, the nine adenoma cases manifested slight-to-moderate degrees of asymmetrical enhancement. For the seven adenocarcinoma cases, two showed asymmetrical enhancement similar to that of the adenoma cases and five showed continued enhancement; one case showed malignant infiltration of the bile duct and evident damage in the adjacent hepatic tissue. The CT plain scan findings for the two groups (adenoma and adenocarcinoma) were not significantly different (t = -1.17, P = 0.2632). Significantly different findings were obtained with the MSCT imaging analysis for the arterial phase (t = 6.53, P less than 0.01) and the portal vein phase (t = 5.63, P less than 0.01). All cases showed asymmetrical expansion of intrahepatic biliary ducts, diffuse or local, and four cases showed moderate expansion of the common bile duct. One adenocarcinoma case showed intumescence in the celiac lymph node by moderate asymmetrical enhancement. MSCT is helpful for the differential diagnosis of IPNB from other hepatic lesions.

Long-term clinical outcome of the surgically resected intraductal papillary neoplasm of the bile duct

Intraductal papillary neoplasm of the bile duct (IPNB) is a biliary neoplasm with predominant intraductal papillary growth and various degrees of malignant transformation. Although IPNB has been recently added to the WHO classification, the classification system needs refinements. We retrospectively reviewed 93 non-invasive and invasive IPNB cases, surgically resected from 1996 to 2006. To further characterize their biologic behavior, we modified the WHO classification into a 4-tier category system in which non-invasive IPNB cases with complex fused or cribriform papillae were separately designated. Epithelial types such as intestinal, gastric, pancreatobiliary, and oncocytic type were determined by morphology and mucin core protein immunohistochemistry. Resection margins were classified based on their microscopic appearances. The prognostic values of mucinous histology and MUC1 protein expression were also determined. IPNB with complex fused or cribriform papillae showed a worse prognosis than IPNB with simple papillae and one such case showed a metachronous metastasis. In addition, a positive surgical margin including dysplasia was associated with worse outcomes. Among the invasive IPNB cases, MUC1-positive tumors were more aggressive than MUC1-negative tumors. We propose that non-invasive IPNB with complex fused or cribriform papillae might be better classified as mucosa-confined cholangiocarcinoma rather than IPNB with high grade dysplasia. In addition, aggressive further resection is recommended when a positive surgical margin including dysplasia is reported during intraoperative histopathological evaluation.

Morphology of intraductal papillary neoplasm of the bile ducts: radiologic–pathologic correlation

Intraductal papillary neoplasm of the bile duct (IPN-B) is known as a premalignant lesion of invasive cholangiocarcinoma. The purpose of this study was for radiologic-pathologic correlation of morphologic features of IPN-B and to correlate the subclassifications with biological behavior in regard to the bile duct wall invasion. A pathologist classified gross morphology of 75 cases (44 men and 31 women, age range, 39-85) of histopathologically proven IPN-B into polypoid, cast-like, superficial-spreading, and cyst-forming type. Preoperative images were retrospectively reviewed by two observers independently and classified the gross appearance of intraductal tumors into the four types. The pathologist classified macroscopic appearances of 75 cases of IPN-B into polypoid type in 26, cast-like intraductal growth in 17, superficial-spreading growth in 21, and cyst-forming type in 11. Two observers classified image findings in accordance with pathologist's classification in 58 and 57 (77% and 76%) among the 75 cases of IPN-B, respectively; 18 and 19 of 26 cases of polypoid type, 14 and 14 of 17 cases of cast-like growth type, 16 and 19 of 21 cases of superficial-spreading type, 10 and 5 of 11 cases of cyst-forming type, respectively. Interobserver agreement for subclassification of tumor morphology was in the category of good agreement (k = 0.651). There was no correlation between morphological subclassification and tendency to invasive cholangiocarcinoma. IPN-Bs can be classified morphologically into polypoid, cast-like growth, superficial-spreading, and cystic type, but there is no correlation between the types and tendency to invasive cholangiocarcinoma.

Tumorigenesis and phenotypic characteristics of mucin‐producing bile duct tumors: an immunohistochemical approach

Intraductal papillary neoplasm of the bile duct (IPNB) is characterized by exophytic proliferation of neoplastic epithelial cells with fibrovascular stalks in bile duct lumen, mucin hypersecretion, and considerable dilatation or multilocular changes of the affected bile ducts. A mucin-producing bile duct tumor is an IPNB with excessive mucin production and clinical symptoms. Herein, the phenotypes as well as the tumorigenesis and progression of IPNB are reviewed with immunohistochemical assistance. The tumors are subdivided into three phenotypes: pancreatobiliary, intestinal, and gastric. About half of IPNB cases are of the pancreatobiliary type, and the remaining half are of the intestinal type. Aberrant expression of CDX2 with MUC2 and CK20 is related to the development of intestinal metaplasia. Inactivation of P16INK4a and nuclear expression of beta-catenin are related to the development of IPNB. Decreased expression of membranous beta-catenin and E-cadherin and aberrant expression of MMP-7 and -9 and of MUC1 are related to invasion of IPNB with tubular adenocarcinoma, whereas MUC2 is involved in the invasion of IPNB with mucinous carcinoma. IPNB can be regarded as a counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, particularly the main duct type. More comparative studies between IPNB and pancreatic IPMN are recommended for further analysis of these papillary neoplasms.

Intraductal papillary neoplasm of the bile duct associated with Clonorchis sinensis infection

Intraductal papillary neoplasm of bile duct (IPNB) is one of the precursor lesions of cholangiocarcinoma. Although hepatolithiasis has been extensively studied in its association with IPNBs, there had been no comprehensive study of IPNBs with Clonorchis sinensis infection. Twelve IPNBs were selected from 20 surgically resected cholangiocarcinomas, positive for C. sinensis tests (60%) and compared with eight IPNBs, selected from 51 resected cholangiocarcinomas, negative for C. sinensis tests (16%), by histologic and immunohistochemical studies of mucin core proteins and cytokeratin panels. The predominant immuno-phenotype of IPNB cases with Clonorchiasis was pancreatobiliary type (MUC1+/MUC2-/CDX2-; 9/12 cases), while that of IPNB cases with negative for C. sinensis was intestinal type (MUC1-/MUC2+/CDX2+; 6/8; p = 0.04). The prevalence of IPNBs was higher when patients with cholangiocarcinoma had Clonorchiasis. IPNBs with Clonorchiasis tended to have a more pancreatobiliary phenotype, which suggests IPNBs with Clonorchiasis may have a different tumorigenesis pathway from IPNBs with other etiologies.