Endobiliary radiofrequency ablation for refractory cholangitis caused by mucin-producing intraductal papillary neoplasm of the bile duct.

Bladder cancer is rare in patients under 40 years of age, and its clinicopathological behavior in this demographic remains a subject of debate. This study aimed to evaluate the histopathological features and prognosis of bladder tumors in patients under the age of 40. This multicenter retrospective study included bladder transurethral resection, biopsy, and cystectomy samples obtained from patients younger than 40 years of age across 20 centers in Turkiye between 2010 and 2025. Among 1,555 biopsies, 445 patients were diagnosed as urothelial neoplasms. After exclusion of 45 patients lacking hematoxylin and eosin stained slides for re-evaluation, 400 urothelial neoplasms were included in the final cohort. All patients were centrally reviewed by three genitourinary pathologists to establish a consensus diagnosis. Demographic characteristics, clinical presentation, tumor localization, pathological stage, and histological subtypes were analyzed. Follow-up data were available for 206 patients and were used to evaluate clinical outcomes. Statistical analyses were performed using chi-square tests with post-hoc analysis based on adjusted standardized residuals. Low-grade papillary urothelial carcinoma (LGPUC) was the most frequent diagnosis, accounting for 233/400 patients (58.3%), followed by papillary urothelial neoplasm of low malignant potential (PUNLMP) in 55/400 patients (13.8%) and high-grade papillary urothelial carcinoma (HGPUC) in 32/400 patients (8.0%). Overall, 340/400 tumors (85.0%) were non-invasive, whereas 60/400 tumors (15.0%) were invasive. Hematuria was the most common presenting symptom, observed in 197/400 patients (49.3%). Diagnostic revisions after central review were identified in 127/400 patients (31.8%), most commonly involving reclassification between PUNLMP and LGPUC. Age-group analysis demonstrated that urothelial neoplasms occurred most frequently in the 31-40-year age group, which showed a significantly higher proportion of HGPUC and invasive tumors (p < 0.001). Subtype histology or divergent differentiation was identified in 4/60 invasive tumors (6.7%). Among the 206 patients with available follow-up data, remission was observed in 159/206 patients (77.2%), recurrence in 41/206 (19.9%), progression in 2/206 (1.0%), and death in 4/206 patients (1.9%). Adverse clinical outcomes were largely confined to invasive tumors. Bladder tumors in patients under 40 years of age typically exhibit low-grade, low-stage characteristics with a favorable prognosis. Consistent with the literature, the 31-40 age group appears to be a biological transition zone with increased risks of high-grade and invasive carcinoma. Long-term follow-up remains essential due to the potential for recurrence and progression in specific subtypes.

Intraductal Papillary Squamous Neoplasm (IPSN) of the Pancreas: Histologic and Molecular Characterization of a Novel and Distinct Intraductal Cancer Precursor.

Intraductal papillary neoplasm of the bile duct (IPNB) is an uncommon biliary tumor with recognized malignant potential and a broad clinicopathological spectrum. Its diagnosis remains challenging, particularly in extrahepatic disease, due to limitations of cross-sectional imaging. We report a consecutive series of five patients diagnosed with IPNB in a tertiary hepatobiliary center, highlighting their clinical, radiologic, endoscopic, and pathological features. Most patients presented with obstructive jaundice or cholangitis, and lesions were predominantly located in the distal bile duct. Cross-sectional imaging showed bile duct dilatation but often yielded inconclusive findings or underestimated intraductal disease, frequently leading to suspicion of cholangiocarcinoma or indeterminate strictures. Cholangioscopy provided additional diagnostic value by enabling direct visualization of characteristic villous or papillary lesions and facilitating targeted biopsies, contributing variably to diagnostic clarification. Histopathology demonstrated high-grade dysplasia in most cases, with one patient harboring invasive carcinoma. All patients required biliary drainage, and most underwent or were considered for surgical resection. These findings highlight the diagnostic discordance between preoperative assessment and definitive pathological diagnosis in IPNB and underscore the limitations of conventional imaging. Cholangioscopy represents a valuable complementary tool in the evaluation of indeterminate biliary strictures, although its findings should be interpreted within a multimodal diagnostic approach.

Intracholecystic papillary-tubular neoplasms (ICPNs) are infrequent preinvasive gallbladder lesions. The literature lacks standard reporting criteria and is limited to single-center series and case reports. This systematic review and meta-analysis aimed to synthesize the available evidence on their epidemiology, pathology, and possible association between high-grade dysplasia and invasive carcinoma. MEDLINE, Scopus, and Web of Science were searched on the June 9, 2025, for "intracholecystic papillary neoplasm" OR "intracholecystic papillary-tubular neoplasm" OR "ICPN" (PROSPERO ID: CRD420250636493). Human studies reporting histologically confirmed ICPNs were included, and case reports, reviews, and animal studies were excluded. Pooled proportions were calculated using generalized linear mixed models with random effects and restricted maximum likelihood. A total of 17 retrospective series, including 15,018 cholecystectomies and 620 ICPN cases, met the criteria. In four studies (13,559 cholecystectomies), the pooled incidence of ICPNs was 1.5% (95% confidence interval [CI] 0.8-2.8). The patients were mainly female (56%), with a mean age of 65 years. Papillary architecture and biliary or gastric phenotypes were also predominant. High-grade dysplasia was observed in the 35.4% of the lesions (six studies) and concomitant gallbladder adenocarcinoma in 26.9% (nine studies). Lymph node metastases were present in 18% of invasive cases, and the 5-year overall survival ranged from 46.7% to 89.7%. ICPNs are uncommon but clinically relevant preinvasive gallbladder neoplasms that frequently harbor high-grade dysplasia or invasive carcinoma. Future research should aim to improve the preoperative diagnostic accuracy, define possible pathological-clinical correlations, and optimize the surgical management.

Intracholecystic Papillary Neoplasia (ICPN) is a pre-invasive gallbladder lesion (< 0.5% of cholecystectomies). A 70-year-old female presented with complaints of abdominal bloating and vomiting. Imaging revealed cholelithiasis with gallbladder neck mass. Diagnostic laparoscopy with extended cholecystectomy and lymphadenectomy was performed. Histopathology revealed ICPN-biliary type with high-grade dysplasia. The 5-day follow-up was uneventful.

Mucinous cystic neoplasm of the liver (MCN-L) is a rare cyst-forming epithelial neoplasm that typically lacks bile duct communication. Intraductal protrusion is uncommon and can mimic cystic intraductal papillary neoplasm of the bile duct (IPNB). A 39-year-old woman undergoing fertility treatment presented with recurrent hyperbilirubinemia and predominantly cholestatic liver test abnormalities. MRI demonstrated a 10.5-cm multilocular cystic lesion in segment 4 of the liver with downstream biliary dilatation, and internal septa were visible within the dilated bile duct on T2-weighted single-shot fast spin-echo (SSFSE) images. Contrast-enhanced computed tomography (CT) revealed enhanced cyst wall and septa, while endoscopic retrograde cholangiography revealed a smooth, oval-shaped filling defect. Endoscopic and intraductal ultrasonography indicated septate cystic components of the bile duct, and biopsy revealed mucin-producing columnar epithelium overlying the ovarian-like stroma, confirming MCN. The patient was treated via extended left hepatectomy with extrahepatic bile duct resection and reconstruction. Pathological examination revealed low-grade intraepithelial neoplasia. The patient remained recurrence-free for 20 months. This case suggests that, although biliary communication usually favors cystic IPNB over MCN-L, identification of intraductal extension of the cyst wall or septa within the dilated bile duct may provide an important clue to the diagnosis of MCN-L.

Papillary renal neoplasm with reverse polarity (PRNRP) is a recently recognized renal tumor characterized by papillary architecture lined by a single layer of low-grade eosinophilic cells with apically located nuclei. In the latest WHO classification, they are not recognized as a distinct entity but rather as a morphological pattern of papillary renal cell carcinoma. To date, limited studies have compared PRNRP with eosinophilic/oncocytic papillary renal cell carcinoma (E/OPRCC), which they are not infrequently confused with, although a few previous comparisons with classic papillary renal cell carcinoma have already identified several distinguishing features. A comparative analysis of 15 of PRNRPs and 16 of E/OPRCC cases was conducted, evaluating their histopathological, immunophenotypic, interphase cytogenetic, and molecular profiles. PRNRPs demonstrated distinctive morphological features, including consistent apical nuclear positioning, absence of foamy macrophages in the papillary cores (p = 0.0001), and a lower nucleolar grade compared to E/OPRCCs (p = < 0.0001). Immunohistochemically, PRNRPs exhibited strong and uniform GATA3 expression and were negative for vimentin, CD10, and CD13, in contrast to E/OPRCCs. Cytogenetically, PRNRPs lacked trisomies of chromosomes 7 and 17, which were present in ~ 40% of E/OPRCCs (p = 0.0262). Notably, all PRNRP cases harbored KRAS mutations, absent in E/OPRCCs (p < 0.0001). Our findings support the classification of PRNRP as a distinct renal tumor entity, separated from both classic papillary renal cell carcinoma and its eosinophilic/oncocytic morphological variant.

Detection of intraductal neoplasms of the bile duct (IN-Bs) remains suboptimal despite various diagnostic modalities. We evaluated the efficacy of digital single-operator cholangioscopy (D-SOC) for screening and surveillance of IN-Bs in patients with bile duct dilatation after stone removal. In a prospective cohort of 181 patients with post-stone removal common bile duct dilatation (> 10mm), screening D-SOC was followed by two rounds of surveillance at 1-year intervals. Outcomes included cumulative incidence of IN-Bs, technical success of D-SOC and D-SOC-guided biopsy, and number needed to screen (NNS) to identify a neoplastic lesion at each round. Technical success of D-SOC was achieved in all patients. Among 181 patients who underwent D-SOC, nine were diagnosed with IN-Bs: cholangiocarcinoma (CCA) (n = 3), intraductal papillary neoplasms of the bile duct (n = 5), and adenoma with dysplasia (n = 1). Curative resection was performed in two patients with CCA. The cumulative incidence of IN-Bs was 6.3% (95% confidence interval, 2.4-10.7%). The NNS values to detect one neoplastic lesion were 29.4, 21.8, and 9.7 at initial screening and 1- and 2-year surveillance. D-SOC can be useful for risk-enriched detection and surveillance of IN-Bs in patients with post-stone-removal biliary dilatation, warranting further evaluation in those with additional CCA risk factors (clinical trial registration number: NCT05600803).

Introduction: Segmental cholangiectasia is a rare cause of focal intrahepatic bile duct dilatation that can mimic congenital, inflammatory or neoplastic conditions, posing diagnostic challenges. Case Presentation: We describe a 58-year-old man with a longstanding cystic lesion in hepatic segment 8 who developed multiple cholangitic episodes. Despite exclusion of infectious, autoimmune and overt neoplastic disease, an elevated carbohydrate antigen 19-9 (CA 19-9) raised concern for intraductal papillary neoplasm of the bile duct (IPNB) and prompted anterior hepatic sectorectomy. Histopathology confirmed segmental cholangiectasia, showing ductal dilatation, bile stasis, cholesterol clefts, fibrosis, and mixed inflammation, without evidence of malignancy or IgG4-related disease. Discussion and Conclusion: Segmental cholangiectasia is a benign yet clinically significant entity that can mimic biliary tumors and prompt major surgery. This case, involving hepatic segment 8, expands the known anatomical spectrum and underscores the importance of multidisciplinary evaluation. Awareness of this condition may prevent misdiagnosis and guide appropriate management, while further studies are needed to better characterize its presentation in Western populations.

Parathyroid carcinoma is an exceptionally rare endocrine malignancy, often functional, manifesting with hypercalcemia and elevated parathyroid hormone (PTH) levels. Non-functional parathyroid carcinoma lacks classical biochemical features, making its diagnosis particularly challenging. Here, we present a case of 60-year-old male with swelling in the anterior aspect of right side of neck. Ultrasound of the neck showed complex cystic nodule suggesting fine needle aspiration cytology (FNAC) to rule out papillary neoplasm. FNAC results were suggestive of hyperplastic colloid nodule. Then the routine blood tests, including serum calcium and thyroid function, were within normal limits and the patient was taken up for total thyroidectomy. Histopathology of the specimen revealed features suggestive of medullary thyroid carcinoma, necessitating IHC. Tumor cells stained strongly positive for GATA3 and PTH, while being negative for calcitonin, MCEA, TTF1, and S100. Focal capsular and lymphovascular invasion was noted and the final diagnosis of parathyroid carcinoma was made. Parathyroid carcinoma is a rare and aggressive tumor that may clinically and radiologically mimic a thyroid nodule, especially in its non-functional form. Diagnosis is extremely difficult and is best confirmed with immunohistochemistry.

Intraductal neoplasms of the pancreas: Current concepts and controversies regarding definitions, evolving classifications, diagnostic challenges and clinical significance.

Multimodal imaging characteristics of intraductal papillary neoplasms of the breast

1539 Long-Term Outcomes of Pancreatic Intraductal Papillary Neoplasms: Impact of Epithelial Subtype and Dysplasia Grade

1533 Characteristics of Intrahepatic Cholangiocarcinomas Misdiagnosed as Intraductal Papillary Neoplasm of the Bile Duct and the Role of Albumin ISH

To investigate the clinicopathological characteristics of intraductal papillary neoplasm of the bile duct (IPNB) and the prognostic factors influencing survival in patients with malignant IPNB. A retrospective analysis was performed on the clinicopathological data and postoperative follow-up records of 62 IPNB patients who underwent surgical treatment at the First Affiliated Hospital of Army Medical University from September 2010 to March 2021. Clinical and pathological characteristics were compared among patients with different histopathological grades (e.g., low-grade vs. high-grade intraepithelial neoplasia) and anatomical subtypes (e.g., intrahepatic, extrahepatic, and diffuse types). Prognostic factors affecting survival in malignant IPNB cases were analyzed using multivariate statistical methods. Based on pathological findings, the 62 IPNB patients were categorized into three groups: low-grade intraepithelial neoplasia (LGIN group, n = 20), high-grade intraepithelial neoplasia (HGIN group, n = 23), and associated invasive carcinoma (IC group, n = 19). The LGIN group exhibited a significantly lower proportion of patients with elevated CA19-9 (> 37 U/mL) compared to the other two groups (p = 0.009). No statistically significant differences were observed in demographic or perioperative parameters among the three groups. Patients in the HGIN and IC groups demonstrated inferior overall survival rates compared to the LGIN group (p = 0.007). After merging HGIN and IC groups into a malignant cohort, the malignant group showed significantly worse overall survival than the LGIN group (p = 0.002). Multivariate Cox regression analysis identified postoperative recurrence, abdominal pain, and non-radical surgery as independent predictors of poor prognosis in the malignant group (p < 0.05). According to the modified anatomical classification system, the 62 patients were stratified into intrahepatic (n = 43), extrahepatic (n = 15), and diffuse (n = 4) subtypes. The intrahepatic group had a significantly higher rate of radical resection compared to the extrahepatic and diffuse groups (p = 0.006). Surgical approaches differed markedly among subtypes: intrahepatic cases predominantly underwent partial hepatectomy (p < 0.001), whereas extrahepatic cases more frequently required extrahepatic bile duct resection (p < 0.001). The modified anatomical classification system provides partial guidance for determining the optimal surgical resection extent in IPNB patients. Radical resection demonstrates superior prognosis compared to palliative treatment. Postoperative recurrence, abdominal pain, and non-radical surgery are identified as independent risk factors for adverse prognosis in malignant IPNB cases. In patients with suspected IPNB, radical resection should be pursued aggressively, especially in those presenting with abdominal pain or elevated CA19-9.

The 6th Edition of the WHO Classification of Digestive System Tumours represents a significant update to the 5th edition. It integrates pathological, new molecular, and clinical insights to refine the taxonomy of digestive system neoplasms. The revised classification continues to emphasise standardisation in terminology, coding, and diagnostic criteria to facilitate global consistency in diagnosis, treatment, epidemiological reporting and research. Structural reorganisation of book chapters describes epithelial tumours by anatomical site, while separating neuroendocrine, mesenchymal and haematolymphoid tumours into dedicated chapters that are aligned with other WHO tumour volumes. Genetic tumour syndromes are classified by mechanisms, pathways and genes, whereas metastatic disease is comprehensively covered under other tumours and metastases. Key structural and diagnostic refinements include consolidation of gastric dysplasia entities; separation of duodenal/ampullary from jejuno-ileal tumours; clearer categorisation of colorectal serrated polyps and novel carcinoma grading; introduction of small- and large-duct intrahepatic cholangiocarcinoma as separate entities, and redefinition of undifferentiated carcinoma to include 'carcinoma with mesenchymal differentiation'. Several new entities are introduced, including oesophageal epidermoid metaplasia, colorectal intramucosal adenocarcinoma, low-grade tubuloglandular adenocarcinoma and lymphoglandular complex-like adenocarcinoma, intraductal tubulopapillary and intraductal oncocytic papillary neoplasms of the bile ducts and sonic hedgehog hepatocellular adenoma. The concept of amphicrine-like carcinoma (ALC) is distinguished from MiNEN and broadens the understanding of tumours with dual neuroendocrine-non-neuroendocrine differentiation. Grading systems are simplified to two-tier classifications (low/high grade) across precursor lesions, with enhanced criteria for neuroendocrine tumour grading. Anal canal neoplasia terminology is harmonised with human papillomavirus (HPV) related Lower Anogenital Squamous Terminology (LAST) and mass-forming biliary and gallbladder cancer precursors share similar terminology. Finally, carcinoma of unknown primary (CUP) is included in a separate section for the first time, classified by molecular and immunophenotypic profiles to guide therapy. Overall, the 6th edition strengthens tumour diagnostic precision and molecular alignment across the digestive system.

To explore the gross classification of gallbladder cancer with primary lesion confined within the gallbladder wall, and its correlation with prognosis and precancerous lesions. A retrospective study was conducted on 123 patients who were admitted to Peking University Third Hospital from January 2006 to December 2020. These patients had preoperative imaging findings suggesting that the primary lesion was confined within the gallbladder wall and had postoperative pathology of adenocarcinoma. Based on CT, MRI, or gross specimens, they were divided into the following four types: Type 1, simple intraluminal lesion: Intraluminal lesions without focal thickening of the gallbladder wall; Type 2, complex intraluminal lesion: Intraluminal lesions associated with focal thickening of the gallbladder wall and/or outer surface dimpling at the tumor base; Type 3, focal wall thickening: Circumferential focal wall thickening with heterogeneous enhancement within 2 continuous parts of the gallbladder; Type 4, diffuse wall thickening: Circumferential diffuse wall thickening extending more than 2 continuous parts of the gallbladder with heterogeneous enhancement. The clinical pathological characteristics, types of precancerous lesions, and survival status were compared among the different types. Both preoperative CT/MRI and intraoperative gross specimens could serve as the basis for gross classification, with gross specimens demonstrating the highest accuracy rate. Among the 123 patients, 13 could not be classified, while the remaining 110 underwent gross classification. The gross classification of gallbladder cancer was strongly or moderately correlated with histopathological parameters such as T-stage (P < 0.001, rs=0.682), lymph node metastasis (P < 0.001, rs=0.478), tissue differentiation degree (P < 0.001, rs=0.484), nerve infiltration (P < 0.001, rs=0.490), and vascular invasion (P < 0.001, rs=0.334). The higher the classification, the more adverse histopathological parameters were observed. Additionally, the gross classification of gallbladder cancer was moderately strongly and highly strongly correlated with residual lesions after surgical treatment (P < 0.001, rs=0.328) and postoperative recurrence (P < 0.001, rs=0.619) in the patients. Survival analysis revealed that the higher the classification, the shorter the median survival time of the patients (Type 1: 96 months, Type 2: 73 months, Type 3: 30 months, Type 4: 14 months, P < 0.001). Multivariate Cox regression indicated that the gross classification of gallbladder cancer was an independent prognostic factor (HR=3.609, 95%CI: 2.177-5.983, P < 0.001). In the patients with the most heterogeneous biological behavior in stage T2, the gross classification of gallbladder cancer was also closely associated with prognosis (median survival times were 72, 70, 29, and 16 months, respectively, P < 0.001). Multivariate Cox regression further demonstrated that the gross classification of gallbladder cancer was an independent prognostic factor (HR=2.723, 95%CI: 1.566-4.736, P < 0.001). In terms of tumor origin, the gross classification of gallbladder cancer was significantly correlated with the type of precancerous lesions: Type 1 mainly originated from intracholecystic papillary neoplasm of the gallbladder, while Types 3 and 4 were mostly high-grade biliary intraepithelial neoplasm or without precancerous lesions. Analysis of the natural history of the tumor suggested that Type 1 progressed slowly, Type 4 progressed rapidly, and Type 2 exhibited greater heterogeneity. The gallbladder cancer with primary lesion confined within the gallbladder wall is closely related to prognosis and precancerous lesions, and can serve as an important reference for surgical decision-making and stratified management.

Background/Objectives: Low-risk non-muscle-invasive bladder cancer (NMIBC) is associated with extremely low rates of progression and cancer-specific mortality. Current surveillance strategies recommend yearly cystoscopic surveillance after the initial 12-month period. Cystoscopic surveillance is costly, leading bladder cancer to be one of the most economically burdensome diseases. We investigated the use of a negative urinary dipstick for haematuria (UDH) in predicting the absence of recurrence. Methods: All patients undergoing flexible cystoscopy at our institution underwent urinary dipstick testing immediately prior to their procedures. We conducted a retrospective analysis of all patients undergoing cystoscopic surveillance for known low-risk NMIBC at our institution between January 2018 and August 2024. All patients had low-risk NMIBC, as defined by American Urological Association (AUA) guidelines, at the time of flexible cystoscopy. Patient demographics, cystoscopy operation records, and subsequent biopsy results were reviewed. Results: A total of 124 patients who underwent 310 cystoscopies were included in the analysis. The overall rate of UDH positivity was 54%. The negative predictive value (NPV) and sensitivity of UDH for the absence of bladder cancer recurrence were 95.7% and 81.2%, respectively. All cases of bladder cancer recurrence with negative UDH were low-grade Ta (n = 5) or papillary urothelial neoplasm of low malignant potential (PUNLMP) (n = 1). There was no difference in the NPV and sensitivity within 12 months of diagnosis (NPV = 95.4%, sensitivity = 83.3%) and 12 months after diagnosis (NPV = 95.8%, sensitivity = 80%). Conclusions: UDH has a high NPV and sensitivity for recurrence in low-risk NMIBC. No cases of high-grade tumors or carcinoma in situ were undetected by UDH in this study. UDH shows promise as an inexpensive adjunct test that can reduce the high economic burden of surveillance of non-muscle-invasive bladder cancer.

Papillary renal neoplasm with reverse polarity shows benign behavior: Results from a 77-case clinicopathological and molecular study.