Modern Pathology最新文献

{"title":"Population-Specific Immunogenomic Alterations in Gallbladder Cancer and Prognostic Significance","authors":"Yan Zhu ,&nbsp;Luisa Maren Solis Soto ,&nbsp;Shubham Pant ,&nbsp;Eduardo A. Vega ,&nbsp;Eduardo Vinuela ,&nbsp;Behnaz Bozorgui ,&nbsp;Jean-Nicolas Vauthey ,&nbsp;Gloria Aguayo ,&nbsp;Zhonglin Wang ,&nbsp;Wei Lu ,&nbsp;Xinyue Chen ,&nbsp;Barbara Mino ,&nbsp;Lakshmi Kakarala ,&nbsp;Jianliang Dai ,&nbsp;Suyu Liu ,&nbsp;Khalida M. Wani ,&nbsp;Alexander J. Lazar ,&nbsp;Fernando Carapeto ,&nbsp;Sunyoung Lee ,&nbsp;Ignacio Wistuba ,&nbsp;Lawrence N. Kwong","doi":"10.1016/j.modpat.2025.100824","DOIUrl":"10.1016/j.modpat.2025.100824","url":null,"abstract":"<div><div>Gallbladder carcinoma is a deadly disease with a poor prognosis, and recent clinical data suggest only a modest benefit of PD1/PDL1 inhibitors in this disease. Optimizing immunotherapeutic approaches will require a detailed understanding of the immunogenomic landscape of this disease worldwide. We combined targeted next-generation sequencing and immunohistochemistry to create detailed immunogenomic landscapes from 2 cohorts of gallbladder cancer cases from the United States (n = 60) and Chile (n = 62). Mutations in <em>TP53</em>, <em>SMAD4</em>, <em>KRAS</em>, <em>PIK3CA</em>, <em>ARID2</em>, <em>ARID1A</em>, <em>ATM</em>, <em>FBXW7</em>, <em>ERBB2</em>, and <em>NF1</em> were found in both the US and Chilean primary cohorts, as well as amplifications in ERBB2, <em>CCNE1</em>, <em>MDM2</em>/<em>CDK4</em>, and <em>CCND1</em>. Despite similar mutation profiles, the immune profiles were distinct, with the Latin American cohort having higher densities of biomarkers associated with CD4+ T cells and PD-1 but lower densities of CD68+ macrophages compared with the North American cohort. Clustering and correlation analyses suggest novel immune subgroups and clinical associations independently of any specific mutations. Additionally, supported by multiplexed single-cell imaging technology, we identified low CD4 and high V-domain Ig suppressor of T cell activation as a candidate biomarker pair of poor outcomes. In summary, our findings highlight the importance of sensitivity to geographic location when considering therapeutic developments and pave a path for further immune investigations of this understudied disease.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100824"},"PeriodicalIF":7.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336746","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":"Comprehensive Molecular, Pathological, and Clinical Characterization of Clear Cell Adenocarcinoma of the Urinary Tract","authors":"Rayan Rammal ,&nbsp;Florestan J. Koll ,&nbsp;Ziyu Chen ,&nbsp;Jacob E. Tallman ,&nbsp;Syed Muneeb Alam ,&nbsp;Jordan E. Eichholz ,&nbsp;Walid Chatila ,&nbsp;Tejiri Agbamu ,&nbsp;Andrew T. Lenis ,&nbsp;Merve Basar ,&nbsp;Cansu Yol ,&nbsp;Jie-Fu Chen ,&nbsp;Judy Sarungbam ,&nbsp;Ying-Bei Chen ,&nbsp;Anuradha Gopalan ,&nbsp;Samson W. Fine ,&nbsp;Satish K. Tickoo ,&nbsp;Cristina R. Antonescu ,&nbsp;Britta Weigelt ,&nbsp;Nadeem R. Abu-Rustum ,&nbsp;Hikmat Al-Ahmadie","doi":"10.1016/j.modpat.2025.100821","DOIUrl":"10.1016/j.modpat.2025.100821","url":null,"abstract":"<div><div>Clear cell adenocarcinoma of the urinary tract (utCCA) is a rare, Müllerian-type tumor typically arising in the urethra of female patients with poorly understood pathogenesis. Here, we report the clinical, pathologic, and molecular characterization of a cohort of utCCA treated at a tertiary referral center. Cases were centrally reviewed, and immunohistochemistry and whole exome and targeted sequencing were performed. The landscape of somatic alterations was compared with ovarian and uterine clear cell carcinoma, and urothelial carcinoma. Among 35 utCCA, most patients were female (86%), and the most common primary tumor site was the urethra (83%) in association with urethral diverticula (51%). Median disease-free and overall survival rates were 42 and 65 months, respectively. The most common mutations were in <em>ARID1A</em> and <em>TP53</em>. Mutations in <em>TERT</em> promoter and other chromatin-modifying genes were rare. Phylogenic analysis suggested that utCCA arises from a dysplastic clear cell precursor developing within the diverticular lining. Although this is the largest study of utCCA to date, the study is limited by its small sample size, retrospective design, and clinical heterogeneity of the cohort. Molecular analysis of utCCA, including multiregion sequencing of tumor and adjacent urethral and diverticular lining, supports a potential mechanism of disease pathogenesis in which most utCCA arise from regions of clear cell dysplasia, possibly resulting from chronic inflammation in the setting of urinary stasis, and not through a progression from intestinal metaplasia or divergent differentiation of a precursor urothelial carcinoma.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 10","pages":"Article 100821"},"PeriodicalIF":7.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485100","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":"HER2, HER3, and Mismatch Repair Protein Expression in Stage IV Small Bowel Adenocarcinoma: Results From a Multicenter Series","authors":"Alessandro Vanoli ,&nbsp;Tommaso Colella ,&nbsp;Paola Parente ,&nbsp;Giuseppe De Lisi ,&nbsp;Federica Grillo ,&nbsp;Erica Quaquarini ,&nbsp;Salvatore Corallo ,&nbsp;Rondell Patrell Graham ,&nbsp;Marc Ferrante ,&nbsp;Annick Moens ,&nbsp;Gert De Hertogh ,&nbsp;Camilla Guerini ,&nbsp;Roberta Riboni ,&nbsp;Paola Alberizzi ,&nbsp;Luca Mastracci ,&nbsp;Matteo Fassan ,&nbsp;Paolo Pedrazzoli ,&nbsp;Marco Vincenzo Lenti ,&nbsp;Catherine Klersy ,&nbsp;Marco Paulli ,&nbsp;Antonio Di Sabatino","doi":"10.1016/j.modpat.2025.100825","DOIUrl":"10.1016/j.modpat.2025.100825","url":null,"abstract":"<div><div>Small bowel adenocarcinoma (SBA) is a rare and aggressive malignancy. One-third of SBA cases are diagnosed at an advanced stage, often with limited treatment options. Recent clinical trials have underscored the importance of testing predictive biomarkers for therapy response in advanced solid tumors, particularly with respect to antibody-drug conjugates and immunotherapy. However, few studies have investigated the expression of mismatch repair (MMR) proteins, HER2, and HER3 in metastatic SBA. In this study, the immunohistochemical expression of MMR proteins, HER2 (using gastric cancer scoring criteria), and HER3 was assessed in a multicentric series of 26 stage IV SBAs. In 7 cases, tissues from both the primary tumor and paired distant metastasis were tested for all biomarkers, and any discordance in biomarker expression (ie, spatial heterogeneity) was recorded. For comparison, a cohort of 47 stage III SBA patients was also evaluated.</div><div>MMR deficiency (MMRd), HER2 positivity (score 3+ or 2+ with gene amplification), and HER3 positivity were identified in 11.5%, 7.7%, and 40% of stage IV SBAs, respectively, with limited overlap among the biomarkers. One stage IV SBA showed heterogeneous MMR status, with a distinct subclone lacking MSH6 expression. When stage III SBAs were compared with stage IV SBAs, MMRd was more frequent (31.9%) among stage III SBAs. In 1 case (14%), the primary tumor was MMR-proficient, HER2-negative, and HER3-negative, whereas the metachronous distant metastasis was MMR-deficient, HER2-negative, and HER3-positive. The percentage of MMRd and HER2 positivity observed in stage IV SBAs highlights the need to assess HER2 and MMR status in these rare tumors. Our findings also suggest that evaluating the response of SBAs to anti-HER3 therapies should be considered in future clinical trials. Additionally, evidence of spatial heterogeneity in biomarker expression emphasizes the importance of assessing biomarkers in metastatic tissue to identify actionable alterations that may not be present in the primary tumor.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100825"},"PeriodicalIF":7.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336744","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":"Myeloid Neoplasms With Oligomonocytosis Exhibit Heterogenous Pathologic and Genetic Features","authors":"Vandana Baloda ,&nbsp;Raniah Al Amri ,&nbsp;Pranav P. Patwardhan ,&nbsp;Sara A. Monaghan ,&nbsp;Erika M. Moore ,&nbsp;Bryan Rea ,&nbsp;Miroslav Djokic ,&nbsp;Nidhi Aggarwal ,&nbsp;Grant C. Bullock ,&nbsp;Yen-Chun Liu ,&nbsp;Svetlana Yatsenko ,&nbsp;Nathanael G. Bailey","doi":"10.1016/j.modpat.2025.100823","DOIUrl":"10.1016/j.modpat.2025.100823","url":null,"abstract":"<div><div>The criteria used to classify patients with myeloid neoplasms and monocytosis have changed in the fifth edition of the World Health Organization classification (WHO5) and the International Consensus Classification (ICC). Although both classifications have reduced the absolute monocyte count threshold for chronic myelomonocytic leukemia (CMML) to 0.5 × 10⁹/L, the ICC has also introduced new morphologic criteria for CMML. We studied the effect of these changes on a large cohort of myeloid neoplasms with white blood cell count &lt; 13 × 10⁹/L and blasts &lt;20% that were previously classified using the fourth revised edition of the WHO classification of hematologic malignancies (WHO4r). The lower monocyte threshold might reclassify approximately 20% of WHO4r-defined myelodysplastic syndrome as myelodysplastic-type CMML (MD-CMML) in the new classifications. This change led to an 84% increase in MD-CMML by WHO5 criteria. The number of MD-CMML cases in the cohort decreases from 107 by WHO5 criteria to 40 by ICC criteria because of the morphologic criteria. New ICC criteria remove 55% of WHO4r-defined MD-CMML patients from the category, and these and other patients (13% of our cohort) are not classifiable by ICC criteria. ICC-defined CMML enriches for CMML-like genetic signatures, but we find that genetic classification and genetically informed risk models predict outcome better than monocyte counts or morphologic features.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 10","pages":"Article 100823"},"PeriodicalIF":7.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336745","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":"Clinicopathologic, Immunohistochemical, and Molecular Analysis of Primary Ovarian Carcinoid Tumors With Correlation of Ki67 Proliferation Index With Patient Outcomes","authors":"Madeline Fitzpatrick ,&nbsp;Ekaterina Olkhov-Mitsel ,&nbsp;Yutaka Amemiya ,&nbsp;Arun Seth ,&nbsp;Bojana Djordjevic ,&nbsp;Carlos Parra-Herran ,&nbsp;Jelena Mirkovic","doi":"10.1016/j.modpat.2025.100822","DOIUrl":"10.1016/j.modpat.2025.100822","url":null,"abstract":"<div><div>Primary ovarian carcinoid tumors (pOCTs) are a rare subset of ovarian neoplasms resembling well-differentiated neuroendocrine tumors (NETs) arising in the gastrointestinal tract. Unlike NETs at other anatomic sites, the use of proliferation markers, such as mitotic count and Ki67 proliferation index, is not well established in the classification of these tumors. In this study, we describe the clinicopathologic, immunohistochemical, and molecular characteristics of pOCTs and correlate mitotic count and Ki67 index with patient outcomes. In our series of 23 pOCTs, most cases were associated with at least 1 other ovarian neoplasm (19/23; 82.6%), most often a mature teratoma or struma ovarii (each 43.5%; 10/23). All 23 cases (100%) expressed synaptophysin, whereas 87.0% (20/23) expressed chromogranin. Frequent staining with TTF-1 and CDX2 (33.3% and 83.3%, respectively) was also observed. Targeted exome sequencing was performed in 14 cases, which identified no recurrent NET-associated mutations or novel mutations in pOCTs. Most pOCTs presented as stage IA disease (13/23; 56.5%), of which 6 had Ki67 indices &gt;3% (46.2%; 6/13). There were 6 cases of stage IC disease (26.0%), which exhibited a variable Ki67 index (range: 1.2%-35.6%). Extraovarian spread was noted in 4 cases (17.4%), with 3 cases having Ki67 indices &gt;3% (range: 1.0%-58.8%). Local recurrence occurred in 1 case (4.3%) with pelvic sidewall involvement at diagnosis and a Ki67 index of 58.8%. Follow-up, ranging from 3 to 153 months (median: 55.5 months), showed no disease-related deaths. We combined our findings with 16 previously published cases of pOCTs and found that cases with &gt;20 mitoses per 2 mm² had the highest rate of recurrence. Cases with Ki67 indices ≥ 7.5% were associated with worse overall and disease-free survival. Overall, our findings reaffirm the indolent nature of most pOCTs, although disease recurrence and aggressive behavior can occur, particularly in cases with elevated proliferation indices.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100822"},"PeriodicalIF":7.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485099","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":"Genetic analysis of early neoplasia in the breast: Next-generation sequencing of flat epithelial atypia and associated ductal and lobular lesions.","authors":"Gregor Krings, Eliah R Shamir, E Shelley Hwang, Yunn-Yi Chen","doi":"10.1016/j.modpat.2025.100820","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100820","url":null,"abstract":"<p><p>The molecular features of invasive breast cancers (IBC) have been well-characterized, but less is known about earlier stages of neoplasia, including oncogenic drivers in early intraductal lesions. Flat epithelial atypia (FEA) is considered the earliest recognized precursor in the low-grade neoplasia pathway, but its mutational repertoire has not been studied, and drivers of the transition to morphologically more advanced lesions are unknown. Herein, we utilized next-generation sequencing to analyze 39 synchronous lesions from 13 patients, including FEA (n=12) or predominantly FEA with early atypical ductal hyperplasia (FEA/early ADH, n=5), and associated ADH (n=2), ductal carcinoma in situ (DCIS, n=11), lobular carcinoma in situ (LCIS, n=3), and/or IBC with ductal and/or lobular differentiation (n=6). Aside from 1 DCIS sample, all sequenced lesions in each patient were clonally related to one another. Recurrent alterations in FEA and FEA/early ADH included PIK3CA (69%), NCOR1 (31%), CBFB (31%), RUNX1 (15%), and GATA3 (23%). The mutational repertoire of FEA was similar to TCGA luminal IBC, except CBFB and NCOR1 mutations, which were more frequent in FEA and (along with PIK3CA, FOXA1, CDKN1B) not always identified in paired morphologically advanced lesions. Compared to FEA, DCIS had more mutations and chromosomal copy number changes, including aberrations in PI-3 kinase pathway, transcription factors, chromatin remodeling genes, and TP53. CDH1 mutations identified in LCIS were absent in paired FEA. Analysis of cases with ductal and lobular heterogeneity, including Rosen's triad, confirmed shared clonality of the ductal and lobular components with features of genetic divergence. IBC of no special type were genetically similar to DCIS, and tubular carcinomas were similar to FEA. The results reveal the mutational repertoire of FEA and the genetics of early breast neoplasia, highlighting clonal relationships of FEA to ductal and lobular carcinomas. Luminal breast cancer-associated genetic alterations are present at the earliest morphologically recognized stages of neoplasia.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100820"},"PeriodicalIF":7.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485101","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":"NUTM1/NUTM2B-Rearranged Intra-Abdominal Sarcomas: A Distinct Entity from Sarcomas with ESR1 Overexpression as a Therapeutic Target.","authors":"Ziyad Alsugair, Marie Karanian, Alexandra Meurgey, Isabelle Treilleux, Caroline Renard, Simon Phelinas, Olivier Glehen, Vahan Kepenekian, Pierre Meeus, Brice Thamphya, Daniel Pissaloux, Franck Tirode, Nazim Benzerdjeb","doi":"10.1016/j.modpat.2025.100816","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100816","url":null,"abstract":"<p><p>Emerging evidence reports that NUTM1 rearrangements also occur in non-carcinomas, including skin tumors, leukemias, and high-grade sarcomas. Recently, a distinct subset of NUTM1-rearranged sarcomas was identified intra-abdominally, mainly of colonic origin, differing molecularly, based on limited methylation analysis. This study aimed to further explore 5 patients with NUTM1/NUTM2-rearranged intra-abdominal sarcomas at clinical, histological, immunohistochemical, and transcriptomic levels. The included patients were all females without prior history of cancer; their mean age was 51.6 years (range 29-73). Tumors were located intra-abdominally, including the sigmoid colon, the vesico-uterine ligament, and the submucosa of the ascending colon. Three patients experienced disease progression despite chemotherapy, resulting in death within 1 to 8 month from diagnosis. Diverse histological patterns were observed, including epithelioid proliferation, cohesive and dyscohesive areas, rhabdoid cells, and spindle cell fascicles. Immunohistochemically, most markers were negative; all cases were positive for estrogen receptors, while NUT was positive only in NUMT1-rearranged cases. MXD4::NUTM1 fusions were identified in 3 cases, in the other cases NUTM2B fusions were identified with either MXD4 or MXI1. UMAP clustering analysis demonstrated that NUTM1/NUMT2B-rearranged intra-abdominal sarcomas clustered together, apart from other neoplasms. The hierarchical clustering dendrogram displayed a greater separation of NUTM1/NUMT2B-intra-abdominal rearranged sarcomas from NUTM1-rearranged carcinomas and NUTM1-rearranged porocarcinomas, from MGA::NUTM1-sarcomas and NUTM1-rearranged endometrial stromal sarcomas. ESR1 expression was significantly higher in NUTM1/NUMT2B-rearranged intra-abdominal sarcomas. NUTM1/2B-rearranged intra-abdominal sarcomas herein represent an emerging entity distinct from the sarcomatous lineage at the transcriptomic level, and characterized by its overexpression of estrogen receptors, which could be an indication for another therapeutic option.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100816"},"PeriodicalIF":7.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302490","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":"Whole Slide Imaging-Free Supporting Tool for Cytotechnologists in Cervical Cytology","authors":"Yuki Kurita ,&nbsp;Shiori Meguro ,&nbsp;Yuki Sugiura ,&nbsp;Sanshiro Togo ,&nbsp;Yukimi Kouda ,&nbsp;Isao Kosugi ,&nbsp;Yasunori Enomoto ,&nbsp;Hideya Kawasaki ,&nbsp;Takeji Saitoh ,&nbsp;Makoto Suzuki ,&nbsp;Junichi Sakane ,&nbsp;Daisuke Suzuki ,&nbsp;Osamu Ishidou ,&nbsp;Kazuya Shinmura ,&nbsp;Toshihide Iwashita","doi":"10.1016/j.modpat.2025.100817","DOIUrl":"10.1016/j.modpat.2025.100817","url":null,"abstract":"<div><div>Cervical cytology is a crucial method for detecting cancerous and precancerous lesions. However, traditional workflows rely heavily on manual microscopic observations by cytotechnologists, making the process time-consuming and labor-intensive. Although several artificial intelligence (AI)-assisted cytology systems have been developed, most approaches require whole slide images, which entails costly scanning equipment, extensive data storage, and additional processing time. These factors hinder real-time diagnosis and are often impractical in resource-limited settings. In this study, we developed cytology-all-in-one (CYTOLONE), a novel AI model designed to support cytotechnologists in cervical cytology. CYTOLONE was constructed using a model based on OpenAI’s contrastive language-image pretraining framework and fine-tuned using a hierarchical labeling structure. This approach enabled the model to effectively learn the relationship between low-magnification images and cytologic features. By integrating the microscope directly with an Apple Silicon Mac and using an iPhone camera for image capture, CYTOLONE offers real-time evaluation, processing each image in under 0.5 seconds. The evaluation results demonstrated that CYTOLONE achieved superior classification accuracy compared with both contrastive language-image pretraining-ViT-B/16 and GynAIe-B16-10k. The model maintained high Anomaly detection accuracy (95.8%) and significantly improved accuracy in Malignancy (92.8%), Bethesda (61.5%), and Diagnosis (57.5%) categories. Furthermore, feature space visualization revealed clearer boundaries between diagnostic categories, reflecting CYTOLONE’s improved performance. The proposed workflow seamlessly integrates traditional cytology practices, allowing cytotechnologists to receive AI support during real-time specimen observation. This innovative workflow eliminates the need for costly whole slide image scanners, improves diagnostic efficiency, and is well-suited for resource-limited environments. Our findings suggest that CYTOLONE can enhance the efficiency of cytotechnologists and improve diagnostic accuracy, offering a practical solution to the existing limitations in AI-assisted cytology systems.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 10","pages":"Article 100817"},"PeriodicalIF":7.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302491","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":"Characterization of Cholangiocarcinomas With Tubulocystic Morphology Associated With Biliary Adenofibroma or Biliary Adenofibroma-Like Lesions","authors":"Xiaoyan Liao ,&nbsp;Diana Agostini-Vulaj ,&nbsp;Rena X. Li ,&nbsp;Xuchen Zhang","doi":"10.1016/j.modpat.2025.100815","DOIUrl":"10.1016/j.modpat.2025.100815","url":null,"abstract":"<div><div>Hepatic biliary adenofibroma (BAF) is a benign neoplasm composed of tubuloglandular and microcystic structures within a fibrous stroma, resembling von Meyenburg complexes or ductal plate malformation (DPM). Intrahepatic cholangiocarcinoma (iCCA) with a DPM pattern (iCCA-DPM) is an established variant of iCCA, whereas adenofibroma-like tubulocystic carcinoma (AL-TCC) is a newly proposed iCCA variant associated with BAF-type lesions. We hypothesize that BAF, AL-TCC, and iCCA-DPM form a tumorigenic spectrum. Ten cases of surgically resected iCCAs with BAF (n = 1) or BAF-like (n = 9) lesions compatible with AL-TCC were analyzed and compared with 7 iCCA-DPM and 26 unspecified small duct iCCA (SD-iCCA). The AL-TCC cohort (6 women and 4 men) had a median age of 62 years. Tumors were often multifocal (70%), averaging 5.5 cm in size, with frequent lymphovascular invasion (40%), but no perineural invasion. Comparisons between AL-TCC and iCCA-DPM revealed no significant differences in age, sex, tumor size, focality, lymphovascular invasion, perineural invasion, or outcomes. When AL-TCC and iCCA-DPM were grouped together (n = 17) and compared with other unspecified SD-iCCA, the combined AL-TCC/iCCA-DPM cohort showed a stronger association with von Meyenburg complexes, biliary cysts, and/or bile duct adenomas (7/17 [41%] vs 0/26, <em>P</em> &lt; .001), less perineural invasion (<em>P</em> = .027), more frequent ARID1A loss (11/17 [65%] vs 3/26 [12%], <em>P</em> &lt; .001), and better patient outcomes (<em>P</em> = .036). Kaplan-Meier analysis revealed that ARID1A loss significantly improved patient survival (<em>P</em> = .046). In summary, AL-TCC with BAF or BAF-like lesions shares clinicopathologic and histogenetic characteristics with iCCA-DPM, suggesting that they are related and likely represent a continuum of tumorigenesis, distinct from other SD-iCCA.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 10","pages":"Article 100815"},"PeriodicalIF":7.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302489","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":"First Cases of NUT Carcinoma Harboring NUTM2 Gene Rearrangements","authors":"Mark G. Evans ,&nbsp;Sara O. Vargas ,&nbsp;Adam Bedeir ,&nbsp;Tolulope Adeyelu ,&nbsp;Hassan Ghani ,&nbsp;David A. Bryant ,&nbsp;Mathew J. Oberley ,&nbsp;Jawhar Rawwas ,&nbsp;Christopher A. French","doi":"10.1016/j.modpat.2025.100796","DOIUrl":"10.1016/j.modpat.2025.100796","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 7","pages":"Article 100796"},"PeriodicalIF":7.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270214","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}