American Journal of Surgical Pathology最新文献

{"title":"NTRK Fusions in Xanthogranuloma, a Clinicopathologic and Molecular Analysis of 23 Cases.","authors":"Brandon Umphress, Aofei Li, Matthew Kuhar, Rachel Kowal, Ahmed K Alomari, LeeAnn Baldridge, Anthony J Ross, Simon J Warren","doi":"10.1097/PAS.0000000000002394","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002394","url":null,"abstract":"<p><p>Xanthogranuloma is the most common category of histiocytic neoplasia, with a range of clinical behaviors from solitary cutaneous lesions to multiple cutaneous lesions and less frequent cases with evolution to disseminated disease. Solitary lesions make up 78% to 81% of total cases. We encountered 2 consecutive index patients with solitary cutaneous xanthogranuloma with NTRK overexpression by immunostaining and confirmed the presence of an NTRK1 fusion with both RNA and DNA sequencing. We screened 55 additional patients by pan-TRK immunostain, and found that 26 of 48 (54%) with solitary xanthogranulomas had TRK overexpression, whereas 0 of 7 (0%) multifocal or disseminated xanthogranulomas had TRK overexpression. We sequenced a subset of 23 patients with solitary xanthogranuloma. In all 16 patients with a positive pan-TRK immunostain, we confirmed the presence of an NTRK1 fusion using RNA and DNA sequencing. In all 7 patients that were negative by immunostain we identified no NTRK fusion by sequencing. All patients with a fusion identified by sequencing had overexpression of the NTRK1 RNA transcript relative to wild-type tumors with a mean 58-fold increase over wild-type tumors (P=8.77e-15). Further, all cases with fusions had a loss of the extracellular portion of NTRK1, and fusion partners were limited to TPM3, PRDX1, IRF2BP2, LRRIP1, and SQSTM1. DNA sequencing identified additional recurrent loss of function mutations in DNA methylation genes DNMT3A, KDM5D, and SETD2, as well as the MTOR-PI3K pathway gene FLCN. Recurrent copy number gains were detected in MTOR-PI3K pathway genes PIK3CG, IL10Ra, as well as transcriptional regulator PAX8. The frequency of NTRK1 fusions appears markedly higher in solitary compared with multifocal and disseminated xanthogranuloma (54% vs. 0%). The reduced proportion of NTRK1 fusions in disseminated cases relative to solitary cases suggests that NTRK1 fusions are less efficient than MAP kinase pathway point mutations at driving tumor evolution towards disseminated disease. As NTRK1 fusions are uncommon in other histiocytoses, pan-TRK immunostain may have utility to confirm the diagnosis of xanthogranuloma in a histiocytic lineage tumor and to screen for low-risk xanthogranuloma.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDKN2A Chromogenic In Situ Hybridization for Separating Benign From Malignant Mesothelial Proliferations.","authors":"Andrew Churg, Tara Spence, Karina C Martin, Janine Senz, Stephen Yip, Julia R Naso","doi":"10.1097/PAS.0000000000002395","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002395","url":null,"abstract":"<p><p>CDKN2A FISH is a standard method for separating mesotheliomas from reactive mesothelial proliferations, but FISH requires specialized equipment and technical expertise for interpretation. Here, we show that a commercially available CDKN2A CISH probe provides equivalent information but can be easily scored using an ordinary light microscope and does not require specialized training.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of HER2 Scoring Systems in Endometrial Cancer: Toward Optimization of HER2-Directed Therapies.","authors":"Ekaterina Menshikova, Kristin Deeb, Elizabeth M Genega, Krisztina Hanley, Gulisa Turashvili","doi":"10.1097/PAS.0000000000002392","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002392","url":null,"abstract":"<p><p>Endometrial carcinomas (EC) show variable HER2 protein expression or gene amplification and may be eligible for HER2-directed therapy (trastuzumab or antibody-drug conjugates (ADCs) such as trastuzumab-deruxtecan). HER2 testing is currently recommended in advanced-stage/recurrent serous carcinomas and carcinosarcomas. However, no universally adopted reporting guidelines exist, and institutional practices vary. We aimed to analyze our experience with HER2 testing and compare gynecologic (GyC), gastric (GaC), and breast (BrC) criteria. We identified ECs with available HER2 immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) results where applicable. HER2 IHC was reassessed using GyC, GaC, and BrC. The overall HER2-positivity rates were 31% by GyC and BrC, and 35.7% by GaC. The scoring systems significantly differed, with 69.8% concordance between GaC and GyC (P<0.001) and 99.2% concordance between BrC and GyC. Our results emphasize the importance of using the appropriate HER2 scoring criteria depending on the type of intended HER2-directed therapy as well as comprehensive yet perspicuous reporting of HER2 status to ensure optimal clinical outcomes in EC patients.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Significance of Different Histology and High-Risk HPV Types in Neuroendocrine Carcinomas of the Cervix.","authors":"Seung Jun Lee, Seokhyun Lee, Ilias P Nikas, Misong Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Haeryoung Kim, Sumi Yun, Kyung-Ah Hwang, Se Ik Kim, Cheol Lee","doi":"10.1097/PAS.0000000000002391","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002391","url":null,"abstract":"<p><p>This study aimed to investigate the impact of different histologic and high-risk (HR) human papillomavirus (HPV) types on the clinicopathologic characteristics and survival of patients with neuroendocrine carcinoma of the cervix (NEC). We retrospectively reviewed the medical records of patients with NEC diagnosed and treated at the Seoul National University Hospital between January 2000 and December 2021. Two pathologists specializing in gynecologic oncology thoroughly examined the slides. To determine the type of HPV infection, microarray analysis and next-generation sequencing were conducted. In addition, the impact of several variables on progressoin-free survival (PFS) and overall survival (OS) was investigated. In total, 47 patients with NEC were included in this analysis. Small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) were identified in 36 (76.6%) and 11 (23.4%) patients, respectively. Whereas 31 (66.0%) patients had a pure NEC, 16 (34.0%) were diagnosed with a mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN). Of the 32 NEC patients whose HPV infection status was confirmed, HR-HPV infection was found in 30 of them (93.8%). Nineteen patients were infected with HPV 18. Between patients infected with HPV 16 or 18 and HR-HPV other than 16 or 18, there was no significant difference in most clinicopathologic characteristics such as histology (P=0.311). However, HR-HPV type other than 16 or 18 was associated with pelvic lymph node metastasis (P=0.044) and advanced stage (P=0.035). In the Kaplan-Meier analysis and the Cox regression analyses, no significant difference in PFS and OS was observed between LCNEC and SCNEC, pure NEC and MiNEN, and HPV 16 or 18 and HR-HPV other than 16 or 18. High-risk HPV infection, especially from HPV 18, might play a role and impact on NEC pathogenesis. In this study, we did not find evidence that diverse histology and HR-HPV types affect PFS and OS.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights From H3-Wildtype Diffuse Midline Glioma With EZHIP Overexpression.","authors":"Minjun Yan, Bo Wang, Bo Han, Zhuo Li, Xing Liu, Pinan Liu","doi":"10.1097/PAS.0000000000002388","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002388","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CK17 Immunohistochemistry Is a Useful Adjunct in the Diagnosis of HPV-independent, TP53-wild-type Verruciform/Acanthotic Vulvar Intraepithelial Neoplasia (vaVIN).","authors":"Emily M Hartsough, Rosalynn M Nazarian, Jaclyn C Watkins","doi":"10.1097/PAS.0000000000002383","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002383","url":null,"abstract":"<p><p>Verruciform/acanthotic vulvar intraepithelial neoplasia (vaVIN) is a rare, recently defined HPV-independent, TP53-wild type lesion of the vulva that predisposes to vulvar squamous cell carcinoma (VSCC). VaVIN encompasses a variety of histomorphologic subtypes, including verruciform lichen simplex chronicus (vLSC), differentiated exophytic vulvar intraepithelial lesion (DEVIL), and vulvar acanthosis with altered differentiation (VAAD). Given the rarity of the lesion, subtle histopathologic features, and overlap with other preneoplastic entities and benign dermatoses, vaVIN is a diagnostic challenge. Therefore, immunohistochemistry (IHC) may be a helpful diagnostic adjunct in differentiating vaVIN from mimickers. Cytokeratin 17 (CK17) immunohistochemistry has been previously described as a useful diagnostic tool in diagnosing differentiated vulvar intraepithelial neoplasia (dVIN) and VSCC and has only recently been applied to vaVIN. In this study, we identified a total of ten cases of vaVIN, including four classified as vLSC, five classified as DEVIL, and one classified as VAAD. CK17 was expressed by all vaVIN lesions, with superficial to suprabasal expression in the vLSC subtype and uniform suprabasal expression in the DEVIL and VAAD subtypes. The pattern of CK17 expression may be helpful in differentiating vaVIN subtypes, notably demonstrating only superficial expression in some cases of the least aggressive phenotype, vLSC. Suprabasal expression corresponds to the more aggressive phenotypes of DEVIL and VAAD. However, additional confirmatory studies in a larger cohort are needed to validate these findings.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Claudin-18 and Mutation Surrogate Immunohistochemistry in Gastric-type Endocervical Lesions and their Differential Diagnoses.","authors":"Lawrence Hsu Lin, Harsimar Kaur, David L Kolin, Marisa R Nucci, Carlos Parra-Herran","doi":"10.1097/PAS.0000000000002342","DOIUrl":"10.1097/PAS.0000000000002342","url":null,"abstract":"<p><p>Gastric-type endocervical adenocarcinomas (GAS) are aggressive HPV-independent neoplasms with molecular alterations in TP53 , STK11 , CDKN2A , and SMAD4 . Claudin-18 (CLDN18) has emerged as a useful marker to distinguish GAS from HPV-associated neoplasia. Its role in separating GAS from benign proliferations and exuberant endocervical glands is unknown. We studied the utility of immunohistochemistry for CLDN18, progesterone receptor (PR), and mutation surrogate stains (P53, STK11/LKB1, MTAP, SMAD4/DPC4) in 46 GAS, 12 benign gastric-type endocervical lesions, 54 benign Mullerian endocervical populations, and 11 HPV-associated endocervical adenocarcinomas. PD-L1 and HER2 immunostains were evaluated in GAS. Gastric-type lesions were more often positive for CLDN18 (100% benign, 78% GAS, most often well to moderately differentiated) compared to benign Mullerian endocervical specimens (all negative) and HPV-associated neoplasia (18%, always focal). Conversely, PR was negative in all gastric-type lesions and positive in 92% of benign Mullerian endocervical populations. GAS revealed aberrant/mutant expression of P53 in 35%, STK11/LKB1 in 25%, MTAP in 23%, and SMAD4/DPC4 in 9% of cases. Abnormal staining in at least one of these 4 mutation surrogate markers was present in 63% of GAS. HER2 score of 3+ was seen in 25% of GAS, and PD-L1 was positive in 37% based on a combined positive score. CLDN18 is a sensitive and highly specific marker of gastric-type benign and malignant endocervical lesions. Once a gastric-type phenotype is confirmed, mutation surrogate immunostains can be used to support a diagnosis of GAS. PD-L1 and HER2 expression is seen in a subset of GAS offering therapeutic options for this aggressive tumor.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"206-216"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal Juxtaglomerular Cell Tumors Exhibit Distinct Genomic and Epigenomic Features and Lack Recurrent Gene Fusions: Comprehensive Molecular Analysis of a Multi-institutional Series.","authors":"Kvetoslava Michalova, Petr Martinek, Roman Mezencev, Sounak Gupta, Sean Williamson, Matthew Wasco, Sambit Mohanty, Cristina Magi-Galluzzi, Sofia Cañete-Portillo, Manju Aron, Shivani Kandukuri, João Lobo, Güliz A Barkan, Irem Kilic, Andrea Strakova-Peterikova, Kristyna Pivovarcikova, Michael Michal, Michal Michal, Thomas M Ulbright, Andres M Acosta","doi":"10.1097/PAS.0000000000002344","DOIUrl":"10.1097/PAS.0000000000002344","url":null,"abstract":"<p><p>Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6 . The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"217-226"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Profiling of Sinonasal Adenoid Cystic Carcinoma: Canonical and Noncanonical Gene Fusions and Mutation.","authors":"Alena Skálová, Martina Bradová, Abbas Agaimy, Jan Laco, Cécile Badual, Stephan Ihrler, Ivan Damjanov, Niels J Rupp, Carlos E Bacchi, Sarina Mueller, Sami Ventelä, Da Zhang, Eva Comperat, Petr Martínek, Radek Šíma, Tomas Vaněček, Petr Grossmann, Petr Steiner, Veronka Hájková, Inka Kovářová, Michal Michal, Ilmo Leivo","doi":"10.1097/PAS.0000000000002349","DOIUrl":"10.1097/PAS.0000000000002349","url":null,"abstract":"<p><p>Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB , or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC. We have searched the authors' registries and selected all AdCCs arising in the sinonasal tract. The tumors were examined histologically, immunohistochemically, by next generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) looking for MYB/MYBL1 and/or NFIB gene fusions or any novel gene fusions and/or mutations. In addition, all tumors were tested for HPV by genotyping using (q)PCR. Our cohort comprised 88 cases of sinonasal AdCC, predominantly characterized by canonical MYB::NFIB (49 cases) and MYBL1::NFIB (9 cases) fusions. In addition, noncanonical fusions EWSR1::MYB ; ACTB::MYB; ESRRG::DNM3 , and ACTN4::MYB were identified by NGS, each of them in 1 case. Among nine fusion-negative AdCCs, FISH detected rearrangements in MYB (7 cases) , NFIB (1 case), and EWSR1 (1 case). Six AdCCs lacked fusions or gene rearrangements, while 11 cases were unanalyzable. Mutational analysis was performed by NGS in 31/88 (35%) AdCCs. Mutations in genes with established roles in oncogenesis were identified in 21/31 tumors (68%), including BCOR (4/21; 19%), NOTCH1 (3/21; 14%), EP300 (3/21; 14%), SMARCA4 (2/21; 9%), RUNX1 (2/21; 9%), KDM6A (2/21; 9%), SPEN (2/21; 9%), and RIT1, MGA, RB1, PHF6, PTEN, CREBBP, DDX41, CHD2, ROS1, TAF1, CCD1, NF1, PALB2, AVCR1B, ARID1A, PPM1D, LZTR1, GEN1 , PDGFRA , each in 1 case (1/21; 5%). Additional 24 cases exhibited a spectrum of gene mutations of uncertain pathogenetic significance. No morphologic differences were observed between AdCCs with MYBL1::NFIB and MYB::NFIB fusions. Interestingly, mutations in the NOTCH genes were seen in connection with both canonical and noncanonical fusions, and often associated with high-grade histology or metatypical phenotype, as well as with poorer clinical outcome. Noncanonical fusions were predominantly observed in metatypical AdCCs. These findings emphasize the value of comprehensive molecular profiling in correlating morphologic characteristics, genetic landscape, and clinical behavior in AdCC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"227-242"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraductal Polypoid Neoplasm in the Intrahepatic Large Bile Ducts of Small Duct-type Intrahepatic Cholangiocarcinoma May Result From Cancerization of Ducts.","authors":"Yasuni Nakanuma, Yuko Kakuda, Hiroyuki Matsubayashi, Takashi Sugino","doi":"10.1097/PAS.0000000000002347","DOIUrl":"10.1097/PAS.0000000000002347","url":null,"abstract":"<p><p>To survey and characterize intraductal polypoid neoplasms in the intrahepatic large bile ducts of small duct-type intrahepatic cholangiocarcinoma (small duct-iCCA), a total of 121 cases of small duct-iCCA presenting mass-forming growth were surveyed for intraductal polypoid neoplasms that were compared with mass-forming tumors in individual cases and with intraductal papillary neoplasm of bile duct (IPNB) (20 cases). Polypoid neoplasms were found in intrahepatic bile ducts in 8 (6.6%) of 121 cases of small duct-iCCA. They showed cast-like growth involving several adjoining bile ducts adjacent to or in the peripheries of mass-forming tumors as well as well-differentiated papillary or tubular/cribriform patterns and no stromal invasion. Intraductal polypoid neoplasms were histologically and immunohistochemically similar to mass-forming tumors in individual cases, and both components were of biliary subtype. There was an abrupt transition between these polypoid neoplasms and normal lining epithelia in the affected bile ducts, suggesting that intraductal polypoid neoplasms reflect the cancerization of ducts. IPNB presented with biliary (5 cases), intestinal (8 cases), gastric (5 cases), and oncocytic subtypes (2 cases), and about half of IPNBs were noninvasive, thus differing from intraductal polypoid neoplasms of small duct-iCCA. In conclusion, small duct-iCCA occasionally presents as intraductal polypoid neoplasms in adjoining bile ducts, reflecting the cancerization of ducts. These intraductal polypoid neoplasms should be considered in the differential diagnosis of heterogeneous intraductal tumors of bile ducts.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"284-293"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}