Gene Rearrangement and Expression of PRKACA and PRKACB Govern Morphobiology of Pancreatobiliary Oncocytic Neoplasms.

Intraductal oncocytic papillary neoplasms (IOPNs) are distinct from intraductal papillary mucinous neoplasms based on characteristic morphologic and genetic features represented by fusion genes involving PRKACA or PRKACB (PRKACA/B). However, pancreatic and biliary tumors with partial oncocytic features are often encountered clinically, and their molecular features are yet to be clarified. This study included 80 intraductal papillary neoplasms: 32 tumors with mature IOPN morphology (typical), 28 with partial or subclonal oncocytic features (atypical), and 20 without oncocytic features (control). We analyzed PRKACA/B fusion genes, including ATP1B1::PRKACA, DNAJB1::PRKACA, and ATP1B1::PRKACB, by reverse-transcription PCR; mRNA expression of fusion genes and nonrearranged PRKACA/B genes by quantitative reverse-transcription PCR; mutations in KRAS, BRAF, and GNAS by targeted sequencing or droplet digital PCR; and the expression of cyclic adenosine monophosphate (cAMP)-dependent protein kinase catalytic subunits α (PRKACA) and ß (PRKACB), phosphorylated cAMP response element-binding protein, and aberrations of p16, p53, SMAD4, STK11, and ß-catenin by immunohistochemistry. PRKACA/B fusion genes were detected in 100% (32/32) of typical, 46% (13/28) of atypical, and 0% (0/20) of control (P < .05). Expression of PRKACA, PRKACB, and phosphorylated cAMP response element-binding protein was upregulated in neoplasms with PRKACA/B fusion genes (P < .05). mRNA expression of the PRKACA/B fusion genes and protein expression of PRKACA or PRKACB tended to be higher in typical than in atypical cases (mRNA, P = .002; protein expression, P = .054). In some atypical neoplasms with mixed subtypes, PRKACA/B fusion genes were superimposed exclusively on oncocytic components. Typical IOPNs harbored fewer KRAS and GNAS mutations than control samples and fewer alterations in p53 and STK11 than atypical samples (P < .05). In conclusion, PRKACA/B fusion genes not only are the characteristic drivers of IOPNs but also play a crucial role in the development of subclonal oncocytic neoplasms. Moreover, oncocytic morphology is strongly associated with upregulation of PRKACA/B, which may provide clues for potential therapeutic options.

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

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

Lung metastases from intraductal papillary neoplasm of the bile duct: a case report.

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is considered a pre-cancerous biliary lesion and/or an early cancer lesion, although its classification remains unclear. The 2019 revised edition of the World Health Organization Classification of Tumors of the Digestive System proposed type 1 and type 2 as new classification categories, and meta-analyses and/or multi-center cohort studies are beginning to be reported. However, treatment for IPNB recurrence and metastasis remains unclear. CASE PRESENTATION: A 60-year-old man who was referred to our hospital after a suspected liver tumor was diagnosed using abdominal ultrasonography. Imaging findings revealed an irregularly shaped tumor in segment 5 (S5) of the liver (size 20 mm). The S5 lesion was suspected as IPNB, and segmentectomy was performed. The pathological findings revealed invasive carcinoma derived from IPNB, and immunohistochemistry revealed positive expression of MUC1, MUC5AC, and MUC6, but negative expression of CDX2 and MUC2. At 9 months after the surgery, computed tomography revealed a tumor in the right bile duct, which was diagnosed as liver recurrence of IPNB, and right hepatectomy was performed. The histopathological findings were the same as for the first resected specimen (i.e., IPNB). At 45 months after the second surgery, computed tomography revealed nodules in both lungs, which were diagnosed as lung metastases from IPNB and resected in two separate procedures. The pathological findings were metastatic carcinoma from IPNB for both lung lesions. The patient is currently alive and undergoing adjuvant chemotherapy (S-1), which was initiated 64 months after the first resection and 12 months after resection of the lung metastases. CONCLUSION: We encountered a rare case of lung metastases from IPNB, which were diagnosed immunohistologically. Because IPNB is generally a slow-growing tumor, resection may be feasible for IPNB recurrence and/or metastasis, which may be detected during long-term follow-up. Thus, even if resection is performed for primary IPNB, additional surgical treatment may be feasible in this setting.

A Case of High-Dose-Rate Brachytherapy Under Endoscopic Retrograde Cholangiopancreatography (ERCP) for Intraductal Papillary Neoplasm of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) represents a relatively nascent pathological entity, recognized as a precancerous condition within the spectrum of cholangiocarcinoma. Surgical intervention is advocated for all patients with IPNB due to their susceptibility toward obstructive jaundice, cholangitis, and the heightened likelihood of malignant transformation. Nonetheless, the efficacy of radiation therapy for IPNB cases that are either inoperable or refractory remains inadequately substantiated. Herein, we present a case study of an IPNB patient who declined surgery, and a commendable local control was accomplished solely through the implementation of brachytherapy utilizing Ir-192. A septuagenarian Japanese man presented at our medical institution with the chief complaint of jaundice and was subsequently diagnosed with IPNB. The IPNB lesion extensively spanned from the lower intrapancreatic bile duct to the right (extending to B5/B8) and left bile ducts (up to just before B4). The patient underwent weekly endoscopic retrograde cholangiopancreatography (ERCP) sessions. The prescribed treatment regimen encompassed 36 Gy/6 Fr high-dose-rate brachytherapy (HDR-BT) administered once per week during ERCP, with each treatment session adhering to a timeframe not exceeding two hours. Two months following the initiation of treatment, a biliary endoscopy demonstrated complete resolution of the tumor lesion and amelioration of jaundice. The only observed acute adverse event was grade 2 hepatic dysfunctions. To the best of our knowledge, this represents the first documented instance of HDR-BT employed in IPNB management, suggesting its potential as a viable alternative for inoperable or refractory IPNB cases.

MRI features of intraductal papillary mucinous neoplasm of the bile ducts, "The myth about the cyst": A systematic review.

Rationale and objectives: Intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B) is a true pre-cancerous lesion, which shares common features with pancreatic IPMN (IPMN-P). While IPMN-P is a well described entity for which guidelines were formulated and revised, IPMN-B is a poorly described entity.We carried out a systematic review to evaluate the existing literature, emphasizing the role of MRI in IPMN-B depiction. Materials and methods: PubMed database was used to identify original studies and case series that reported MR Imaging features of IPMN-B. The search keywords were "IPMN OR intraductal papillary mucinous neoplasm OR IPNB OR intraductal papillary neoplasm of the bile duct AND Biliary OR biliary cancer OR hepatic cystic lesions". Risk of bias and applicability were evaluated using the QUADAS-2 tool. Results: 884 Records were Identified through database searching. 12 studies satisfied the inclusion criteria, resulting in MR features of 288 patients. All the studies were retrospective. Classic features of IPMN-B are under-described. Few studies note worrisome features, concerning for an underlying malignancy. 50 % of the studies had a high risk of bias and concerns regarding applicability. Conclusions: The MRI features of IPMN-B are not well elaborated and need to be further studied. Worrisome features and guidelines regarding reporting the imaging findings should be established and published. Radiologists should be aware of IPMN-B, since malignancy diagnosis in an early stage will yield improved prognosis.

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

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

Intraductal Papillary Neoplasm of the Bile Duct: A Rare Disease and Presentation.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease that occurs anywhere along the bile duct. The disease predominantly occurs in Far East Asia and is very rarely diagnosed and documented in western countries. IPNB presents similarly to obstructive biliary pathology; however, patients can be asymptomatic. Surgical resection of IPNB lesions is crucial for patient survival because IPNB is precancerous and can transform into cholangiocarcinoma. Although potentially curative by excision with negative margins, patients who are diagnosed with IPNB need close monitoring for de novo recurrence of IPNB or other pancreatic-biliary neoplasms. In this case, we present an asymptomatic non-Hispanic Caucasian male who was diagnosed with IPNB.

Development of intraductal papillary neoplasm of the bile duct in patients with occupational cholangiocarcinoma.

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.

Peroral-cholangioscopy to plan surgery for protruding biliary lesions: report of four cases.

Intraductal biliary lesions can involve the main hepatic confluence. Assessment of the extension of pedunculated biliary lesions during per-oral cholangioscopy (POCS) can optimize and personalize the surgical strategy. Four consecutive cases of pedunculated biliary lesions were analysed. Cholangioscopy was performed with a disposable single-operator cholangioscope. POSC was successfully performed in four patients (three female, mean age 50 years), showing involvement of the main biliary confluence in three of four pedunculated biliary lesions; direct biopsy sampling was diagnostic in two of three cases (in one patient, biopsy were not performed due to the smooth appearance of the intrabiliary lesion). No adverse events occurred after POCS. Surgery required excision of the main hepatic confluence in two of three cases (one patient was not resectable). POCS can diagnose intrabiliary extension of protruding biliary lesions, providing important information to plan the surgical intervention.

Photodynamic therapy for hepatic hilar intraductal papillary neoplasm of the bile duct: a case report.

Video 1Photodynamic therapy for hepatic hilar intraductal papillary neoplasm of the bile duct: a case report.

Intracholecystic papillary neoplasm of the gallbladder diagnosed during follow-up of Menetrier's disease: A case report.

Intracholecystic papillary neoplasm of the gallbladder (ICPN) is a type of intraductal papillary neoplasm of the bile duct that occurs in the gallbladder, and is a relatively newer concept. Therefore, there are few reports regarding ICPN. Menetrier's disease is a rare disease characterized by giant hypertrophy of the gastric folds that causes protein-losing gastroenteropathy (PLG). Although Menetrier's disease is a known risk factor for gastric adenocarcinoma, the association between Menetrier's disease and malignancy other than a malignancy of the stomach is unclear. A 69-year-old man presented to the Hokkaido Social Work Association Obihiro Hospital with gallbladder tumours diagnosed by ultrasonography at a previous institution. In addition, he had previously been diagnosed with PLG due to Menetrier's disease. Abdominal contrast-enhanced computed tomography (CT) revealed an irregular mass with a contrast effect at the fundus of the gallbladder on the free abdominal cavity side. Positron emission tomography-CT showed a tumour with a standard uptake value (SUV) of 8.28 at the fundus of the gallbladder. Cholecystectomy and resection of the gallbladder bed were performed. Based on the microscopy findings, the patient was diagnosed with ICPN. Although he had postoperative ileus, he was discharged 14 days postoperatively due to improvement through conservative treatment. Such cases of ICPN complicated with Menetrier's disease are extremely rare. However, patients with Menetrier's disease may need to be screened for malignancies.

Cystic biliary tumors of the liver: diagnostic criteria and common pitfalls.

With major advancements and frequent use of abdominal imaging techniques, hepatic cysts are increasingly encountered in clinical practice. Although the majority of cysts are benign, a small subset represents neoplastic precursors to cholangiocarcinoma. These cystic precursors include intraductal papillary neoplasms of the bile duct (IPNB) and mucinous cystic neoplasms of the liver (MCN-L), and bear striking pathologic resemblance to corresponding cystic neoplastic precursors within the pancreas. This review examines the salient clinical, gross, microscopic and molecular features of IPNBs and MCN-Ls, and, in particular, provides histopathologic comparison to their pancreatic counterparts. Considering these neoplasms may be diagnostically challenging, we also discuss other hepatic lesions within the differential diagnosis, and the potential for molecular methods to improve their preoperative evaluation and the early detection of cholangiocarcinoma.

Intracholecystic papillary neoplasm arising in the cystic duct and extending into common bile duct: a case report.

An 83-year-old man without specific symptoms was referred to our hospital for further evaluation and treatment of apparent double primary tumors of the cystic duct and common bile duct. Computed tomography showed contrast-enhanced solid tumors in the cystic duct and common bile duct. Magnetic resonance imaging showed that the bile duct tumor was isointense on T1-weighted images and had low intensity on T2-weighted images. In addition, the bile duct tumor showed high intensity on diffusion-weighted images. Endoscopic ultrasonography revealed the tumor of the common bile duct and endoscopic retrograde cholangiopancreatography demonstrated a filling defect in the bile duct. The cystic duct was not identified on endoscopic ultrasonography or endoscopic retrograde cholangiopancreatography. Transpapillary biopsy of the bile duct tumor showed adenocarcinoma. The patient was diagnosed with double primary tumors of the cystic duct and the common bile duct and underwent subtotal stomach-preserving pancreaticoduodenectomy. Microscopic examination with molecular profiling of the tumors revealed a high-grade noninvasive intracholecystic papillary neoplasm of the cystic duct extending into the common bile duct and forming a tubulopapillary neoplasm with invasion of the common bile duct.

Intraductal Papillary Neoplasm of the Bile Duct: A Rare Case of Intrahepatic Space-Occupying Lesion.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare tumor and is considered one of the precursor lesions for cholangiocarcinoma. Though relatively common in the far east countries, it is uncommon in the Indian population. A 67-year-old gentleman presented with vague upper abdominal pain with no history of fever, jaundice, melena, or hematemesis. An abdominal ultrasound showed a solid cystic lesion in the left lobe of the liver with upstream dilatation of bile ducts. Computed tomography and magnetic resonance imaging showed similar findings. With a differential diagnosis of intrahepatic cholangiocarcinoma, intraductal papillary neoplasm, and biliary cystadenoma, he underwent robotic-assisted left hepatectomy. Histopathology was suggestive of IPNB. Following surgery, he had an uneventful recovery and was advised for follow-up visits every six months. A clinical, radiological, and pathological profile of this rare tumor has been described here with a review of the existing literature.

Intraductal papillary neoplasm of the bile duct - A comprehensive review.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts is a rare tumor type. Management decisions are currently based upon a small case series. The authors have large own experience with IPNB. OBJECTIVE: The review aims at reporting on clinicopathological features of IPNB in order to provide guidance for management. METHODS: We searched PubMed, Medline, Microsoft Academic and Embase databases to identify studies of relevance. The analysis of own experience was also included. RESULTS: We analyzed 59 retrospective series and 25 cases from authors' clinical experience. The main sign was jaundice and cholangitis, 33% and 48%, respectively. CT's were performed in 63-76% and MR in 40-56%. Intraductal mass was found in 31-32% and duct dilatation in 27-30%. Endoscopic Retrograde Cholangio-Pancreatography (ERCP) was performed in 48-62%. IPNB with invasive carcinoma was found in 35.7-60% and IPNB with intraepithelial neoplasia in 36-60%. Histopathological confirmation before surgery was rare. The main treatment of IPNB is resection, in our material, both, hepatectomy and hepatectomy plus bile duct resections were performed in 40% of patients. The percentage of postoperative complications was 20%. The 5-year survival rate of all IPNB's patients was 53.6%; in patients with associated invasive carcinoma - 22.2% and without invasive carcinoma - 100% (p â€‹= â€‹0.001). CONCLUSIONS: Early surgery is advisable for radiologically suspected IPNB. The results of treatment depend on histopathology. They are worse at intraductal invasive carcinoma than at neoplasm with neoplasia.

Intraductal papillary neoplasm of the left hepatic duct treated with endoscopic retrograde cholangiopancreatography guided radiofrequency ablation.

Intraductal papillary neoplasm of the biliary tree (IPNB) is a rare non-invasive neoplasm that carries a high potential for progression to malignancy. Typically, these tumors are managed via surgery with total resection being the fundamental goal. Recently, radiofrequency ablation (RFA) has gained momentum as a treatment option for biliary cancers. Prior studies examining the effect of RFA on biliary tumors usually group all tumor types together, leaving few reports looking at sole outcomes in IPNB. We present an elderly woman with advanced dementia who was admitted with obstructive jaundice secondary to intrahepatic IPNB, and underwent Endoscopic Retrograde Cholangiopancreatography (ERCP) with RFA and stenting resulting in objective improvement in both the size of the lesion and laboratory markers. In the right subset of patients, endobiliary RFA can be used as a safe and effective modality of treatment with minimal complications.

A Case in which an Intraductal Papillary Neoplasm of the Bile Duct Was Surgically Resected 12 Years after the Initial Diagnosis.

A 66-year-old Japanese man was referred to our hospital with multiple giant liver cysts. The cysts had already been detected as multiple 3-cm cysts with small nodules at another hospital 12 years prior to this presentation. The cysts were diagnosed as an intraductal papillary neoplasms of the bile duct (IPNB) occupying the right lobe of the liver. Extended right lobectomy was performed. Based on the pathological findings, the tumor was diagnosed to be an oncocytic-type IPNB with minimal invasion. This experience suggests that the progression of IPNBs occur relatively slowly. The present case might provide important information for understanding the natural history of IPNBs.

Planned limited resection of the extrahepatic bile duct in a case of intraductal papillary neoplasm of the bile duct based on preoperative examinations.

Intraductal papillary neoplasm of the bile duct (IPNB) is defined as a non-invasive malignancy; however, since there are disparities in its histological diagnosis, the operative strategy for typical IPNB has not yet been established. A 69-year-old male was diagnosed with a bile duct mass lesion at the confluence of the cystic duct by ultrasonography without clinical symptoms. Liver functional parameters and tumor markers were within normal ranges. Computed tomography showed an enhanced tumor with no findings of ductal invasion or node metastasis. The tumor was exposed in the hepatic duct lumen and biopsy via SpyGlass DS cholangiography revealed that it was a low-grade papillary lesion, indicating type 1 IPNB. Under preoperative diagnostic modalities, limited resection of the extrahepatic bile duct with D2 lymphadenectomy was planned and R0 resection was achieved. The postoperative histological diagnosis was type 1 IPNB without node metastasis. The postoperative course was uneventful and a good prognosis is expected at this stage. In the field of biliary surgery, although extended resection is generally performed for bile duct carcinomas, satisfactory limited surgical resection is possible for type 1 IPNB with lower malignant behavior.

Outcome Determining Factors of Intraductal Papillary Neoplasm of the Biliary Tract (IPNB)-a Single Center Survey and Analysis of Current Literature.

PURPOSE: Intraductal papillary neoplasms of the biliary tract (IPNB) are rare tumors originating from the bile duct epithelium. Metastatic disease of IPNB is extremely rare and only reported in a small number of cases worldwide. Due to this limitation in number, the treatment of IPNB mainly relies on retrospective case series. PATIENTS AND METHODS: We reported three cases of IPNB, one benign, one carcinoma with lymph node metastasis, and one case with histologically proven metachronous pulmonary metastasis. We correlated our findings with the existing data found in the literature. All patients underwent hemihepatectomy and complete tumor resection was achieved. RESULTS: Diagnosis of IPNB can be challenging due to varying presentation. The treatment of choice is surgical oncological resection in an early tumor stage. Long-term outcome highly depends on the underlying grade of dysplasia, multiplicity, and tumor-free margins. Aggressive tumor invasion is reported in up to 72% of cases in IPNB. Furthermore, the recurrence rate of IPNB is high with up to 22%. Further factors associated with an impaired survival are incomplete resection, lymph node involvement, and MUC1 expression. CONCLUSION: High potential for dysplasia and proof of invasive carcinoma upon diagnosis are hallmarks of IPNB. Metastatic disease in IPNB is reported only in small numbers. IPNB is an aggressive tumor entity with impaired long-term outcomes. A drawback for interpretation of current data is the fact that they rely on case series and reports and are not validated through more powerful randomized multicentric trials.

Cytomorphology of intraductal papillary neoplasm of the biliary tract.

Intraductal papillary neoplasms of the bile duct (IPNBs) are papillary epithelial proliferations with delicate fibrovascular cores within dilated bile ducts. They are thought to be premalignant lesions with potential to progress invasive tumors. To our knowledge, there are no prior descriptions of IPNB cytomorphology. A 58-year-old male presented with painless jaundice and elevated liver function tests was found to have an intraluminal mass within the left hepatic duct. A bile duct brushing diagnosed as "atypical cells present" showed a cellular specimen composed of papillary groups and linear strips of mostly cuboidal/columnar cells with mild atypia and vacuolated cytoplasm. A left hepatic lobectomy including extrahepatic bile ducts showed the mass consisted of papillary cores lined by pancreatobiliary-type epithelium with mild-to-severe atypia, consistent with IPNB with a focus suspicious for invasion. The cytomorphologic features described in the current case suggest intraductal papillary neoplasm but may not be specific since similar features could be seen in other bile duct tumors and even in nonneoplastic conditions such as stent or cholelithiasis. However, it is worthwhile to report papillary hyperplasia with atypia in common bile duct brushings in order to avoid a false-negative diagnosis, especially in the context of a filling defect by images which does not appear to be a stone.