Modern Pathology最新文献

{"title":"Lymphovascular Space Invasion in Endometrial Cancer: Does it Matter Where and How Much to Sample? A Macroscopic Study of 208 Hysterectomies","authors":"Deniz Ates ,&nbsp;Sevilay Karahan ,&nbsp;Aleyna Oruç ,&nbsp;Alp Usubutun","doi":"10.1016/j.modpat.2025.100885","DOIUrl":"10.1016/j.modpat.2025.100885","url":null,"abstract":"<div><div>Lymphovascular space invasion (LVSI) is a key prognostic factor in endometrial cancer, guiding adjuvant treatment decisions. This retrospective study analyzed 208 hysterectomy specimens with confirmed LVSI to determine optimal sampling strategies for detecting substantial LVSI. Samples/blocks from tumor infiltration fronts were reviewed microscopically, and LVSI foci were counted per slide and summed across all slides. Cutoffs of ≥5, ≥4, and ≥3 LVSI foci were evaluated. Only the ≥5 threshold significantly correlated with lymph node metastasis (<em>P</em> = .038) compared with &lt;5 LVSI. Both patients with ≥5 LVSI foci either on a single slide or those reaching this threshold by summing across slides were associated with nodal metastasis (<em>P</em> = .023). However, significantly worse overall survival was observed only in patients with ≥5 foci on a single slide, not in those reaching the threshold by summing across multiple slides (<em>P</em> &lt; .001). Focal LVSI (&lt;5 foci) showed no significant overall survival compared with substantial LVSI. Increased sampling from the tumor infiltration front improved LVSI detection rates (<em>P</em> &lt; .001), but gains in detecting substantial LVSI plateaued after 7 samples/blocks. Higher LVSI levels were associated with deep LVSI and cervical/endocervical LVSI (<em>P</em> &lt; .001). Deep LVSI was linked to reduced overall survival compared with superficial LVSI (<em>P</em> &lt; .001), whereas cervical/endocervical LVSI showed no significant association with overall survival (<em>P</em> = .273). Tumor grade, deep LVSI, and cervical involvement predicted nodal metastasis, whereas the microcystic, elongated, and fragmented pattern did not. These findings support using a threshold of ≥5 LVSI foci on at least 1 slide—as opposed to summing across slides—as a marker of worse overall survival. For optimal evaluation, at least 7 tumor infiltration front samples/blocks should be taken, including deep myometrium and cervical/endocervical canal, to ensure adequate assessment and identify patients at higher risk of nodal spread.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100885"},"PeriodicalIF":5.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054747","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":"DNA Methylation-Based Classification of Kidney Neoplasms","authors":"Antonios Papanicolau-Sengos ,&nbsp;Omkar Singh ,&nbsp;Kyung Park ,&nbsp;Matija Snuderl ,&nbsp;Maria Tretiakova ,&nbsp;Maria Merino ,&nbsp;Bradley Stohr ,&nbsp;Jeff Simko ,&nbsp;Fang-Ming Deng ,&nbsp;Emily Chan ,&nbsp;Jasper Wu ,&nbsp;Jairo Barreto ,&nbsp;Rohit Gupta ,&nbsp;Brian Park ,&nbsp;Rust Turakulov ,&nbsp;Zied Abdullaev ,&nbsp;David A. Solomon ,&nbsp;Kenneth Aldape","doi":"10.1016/j.modpat.2025.100884","DOIUrl":"10.1016/j.modpat.2025.100884","url":null,"abstract":"<div><div>Renal neoplasms are morphologically and molecularly heterogeneous, with their diagnosis often hindered by interobserver variability and overlapping microscopic features. A subset of cases is unclassifiable despite immunohistochemical, mutation, and cytogenetic-based diagnostic workup. Through examination of the genome-wide DNA methylation signatures of over 2000 renal neoplasms, we identified 23 coherent groups that correlate with known neoplasm types and identified novel clinically relevant subtypes of existing neoplasm types. We used machine learning models to develop and validate a classifier trained on DNA methylation profiles of 1284 samples. The classifier was tested on an external data set of 287 renal neoplasms with &gt;90% concordance between expected neoplasm type and high-score DNA methylation-based classification. Discordance between the original histologic label and methylation class led to potential reclassification of some cases. This work demonstrates proof of principle for the feasibility of a DNA methylation classifier as a clinically useful tool to assist in the diagnosis of renal neoplasms.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100884"},"PeriodicalIF":5.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054754","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":"PolyPath: Adapting a Large Multimodal Model for Multislide Pathology Report Generation","authors":"Faruk Ahmed,&nbsp;Lin Yang,&nbsp;Tiam Jaroensri,&nbsp;Andrew Sellergren,&nbsp;Yossi Matias,&nbsp;Avinatan Hassidim,&nbsp;Greg S. Corrado,&nbsp;Dale R. Webster,&nbsp;Shravya Shetty,&nbsp;Shruthi Prabhakara,&nbsp;Yun Liu,&nbsp;Daniel Golden,&nbsp;Ellery Wulczyn,&nbsp;David F. Steiner","doi":"10.1016/j.modpat.2025.100886","DOIUrl":"10.1016/j.modpat.2025.100886","url":null,"abstract":"<div><div>The interpretation of histopathology cases underlies many important diagnostic and treatment decisions in medicine. Notably, this process typically requires pathologists to integrate and summarize findings across multiple slides per case. Existing vision-language capabilities in computational pathology have so far been largely limited to small regions of interest, larger regions at low magnification, or single whole-slide images (WSIs). This limits interpretation of findings that span multiple high-magnification regions across multiple WSIs. By making use of Gemini 1.5 Flash, a large multimodal model with a 1-million token context window, we demonstrate the ability to generate bottom-line diagnoses from up to 40,000 image patches of size 768 × 768 pixels from multiple WSIs at 10× magnification. This is the equivalent of up to 11 hours of video at 1 fps. Expert pathologist evaluations demonstrate that the generated report text is clinically accurate and equivalent to or preferred over the original reporting for 68% (95% CI, 60%-76%) of multislide examples with up to 5 slides. Although performance decreased for examples with ≥6 slides, this study demonstrates the promise of leveraging the long-context capabilities of modern large multimodal models for the uniquely challenging task of medical report generation where each case can contain thousands of image patches.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100886"},"PeriodicalIF":5.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054078","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":"Methylation Signatures Identify Two Distinct Clusters of Uterine Leiomyosarcoma With Unique Histologic and Clinical Behaviors","authors":"Christopher Felicelli,&nbsp;Drew Duckett,&nbsp;Zachary Coty-Fattal,&nbsp;Yue Feng,&nbsp;Farres Obeidin,&nbsp;Borislav A. Alexiev,&nbsp;Lucas Santana dos Santos,&nbsp;Lawrence Jennings,&nbsp;Jian-Jun Wei","doi":"10.1016/j.modpat.2025.100883","DOIUrl":"10.1016/j.modpat.2025.100883","url":null,"abstract":"<div><div>Uterine leiomyosarcoma (uLMS) is a rare and deadly gynecologic malignancy. uLMS is histologically heterogeneous and presents with a wide spectrum of tumor differentiation, with a broad range of genomic DNA instability, which can make the diagnosis and prognosis of uLMS challenging. Methylation has emerged as a useful molecular tool in tumor classification and diagnosis in certain neoplasms. We initiated this study to investigate the role of global methylation in the differential diagnosis of uLMS from its mimics in correlation with pathologic characteristics and clinical outcomes. In this study, we performed array-based global methylation profiling analysis in a total of 71 uLMS and compared the methylation signatures of uLMS with several other uterine mesenchymal tumors and soft tissue leiomyosarcoma. We found that uLMS demonstrated distinct methylation patterns differing from all other tumor types. Notably, methylation profiling defines 2 distinct subgroups of uLMS with differing copy number alterations, resulting in unique histologic and clinical behaviors, further emphasized by differences in methylation pathway analysis. This study is the first to report methylation profiling as a useful diagnostic tool in differentiating uLMS from mimics and defines 2 subtypes of uLMS based on methylation signatures.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100883"},"PeriodicalIF":5.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008393","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":"Epstein-Barr Virus–Associated Gastric Cancer: A Histopathologic Study With Comprehensive Molecular Profiling","authors":"Valentina Angerilli ,&nbsp;Jessica Gasparello ,&nbsp;Antonio Collesei ,&nbsp;Carlotta Ceccon ,&nbsp;Francesca Bergamo ,&nbsp;Marianna Sabbadin ,&nbsp;Paola Parente ,&nbsp;Alessandro Vanoli ,&nbsp;Monia Niero ,&nbsp;Claudio Luchini ,&nbsp;Roberta Gafà ,&nbsp;Angelo Paolo Dei Tos ,&nbsp;Federica Grillo ,&nbsp;Luca Mastracci ,&nbsp;Sara Lonardi ,&nbsp;Matteo Fassan","doi":"10.1016/j.modpat.2025.100881","DOIUrl":"10.1016/j.modpat.2025.100881","url":null,"abstract":"<div><div>A subset of gastric cancers (GCs) is linked to Epstein-Barr virus (EBV) infection. This study aims to characterize the histopathological and molecular features of EBV-associated GCs (EBVaGCs), focusing on predictive biomarkers and genomic and transcriptomic analysis. A total of 35 primary EBVaGCs were considered. The presence of EBV was confirmed with in situ hybridization. Immunohistochemical analyses for HER2, PD-L1, claudin 18.2, and mismatch repair proteins were performed. Genomic and transcriptomic profiles were assessed using AmoyDx Master Panel, which can identify single-nucleotide variants, InDels, and copy number variations on 571 hot genes, as well as microsatellite status, tumor molecular burden, and homologous recombination deficiency at the DNA level; however, at the RNA level, it identifies rearrangements/fusions in 45 genes and also quantifies the expression of 2396 cancer-related transcripts. The following histotypes were identified: carcinoma with lymphoid stroma (CLS; 69%), tubular (20%), and mixed (11%). Most cases were associated with atrophic gastritis (71%), and only 11% with dysplasia. The vast majority (94%) of EBVaGCs expressed EBV-encoded RNA in all tumor cells. Mismatch repair deficiency and HER2 overexpression were each observed in 6% of cases, whereas all tumors had a PD-L1-combined positive score ≥10. Sixty-six percent of cases showed moderate/strong claudin 18.2 expression in ≥75% of cancer cells. The most frequently altered genes were <em>PIK3CA</em> (41%) and <em>ARID1A</em> (17%). Transcriptomic analysis revealed substantial differential gene expression between EBVaGCs and EBV-negative controls, with upregulation of genes involved in antigen presentation, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction in EBVaGCs. Within EBVaGC, CLS showed higher expression of immune-related transcripts and higher PD-L1 expression than other histotypes. This study establishes EBVaGC as a distinct molecular class, with a distinctive profile of genomic alterations and expression of predictive biomarkers, and also with a unique immune microenvironment with enhanced cytotoxic activity. The findings highlight EBV’s role in early tumor development and EBVaG-CLS as a distinct subgroup within EBVaGC, characterized by unique morphologic features and a pronounced immune activation profile.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100881"},"PeriodicalIF":5.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006358","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":"Deep Learning-Assisted System Improves Practical Effects in Cervical Cytopathology Diagnosis: A Comparative Study of Reading Modes","authors":"Zichen Ye ,&nbsp;Peiyu Zhang ,&nbsp;Ronggan Wei ,&nbsp;Haiyan Niu ,&nbsp;Hongxia Li ,&nbsp;Mingjuan Wang ,&nbsp;Sara Lu Riggs ,&nbsp;Peng Xue","doi":"10.1016/j.modpat.2025.100882","DOIUrl":"10.1016/j.modpat.2025.100882","url":null,"abstract":"<div><div>Deep learning (DL) has significantly improved the diagnostic accuracy and efficiency of cytopathologists. However, current DL-assisted reading modes have yet to be fully evaluated, and there is limited evidence regarding cytopathologists’ preferences and experiences. This study employs a randomized, controlled, 4-way crossover design to assess the effectiveness of 4 distinct cytopatholog reading modes. This study included retrospectively collected 1620 cervical slides between 2021 and 2022. These slides were read by 108 certified cytopathologists with varying expertise using the 4 reading modes: unassisted, concurrent, second, and triage mode. A questionnaire survey was conducted to gather the cytopathologists’ adoption of each mode, including mode score and their confidence and preferences. Compared with unassisted, all DL-assisted modes improved the cytopathologists’ diagnostic performance. The unassisted mode had a sensitivity of 66.2% and a specificity of 72.5%. The second, concurrent, and triage modes all improved on these metrics: sensitivity increased by 20.2%, 17.3%, and 16.7%, respectively, whereas specificity increased by 13.2%, 10.8%, and 22.3%, respectively. The median reading time per slide was prolonged in second mode from 200 to 235 seconds but substantially reduced to 130 seconds in triage mode, and 53 seconds in concurrent mode (<em>P</em> &lt; .0001 for all). Moreover, the questionnaire survey showed that &gt;90% of cytopathologists agreed that the DL-assisted mode was useful in improving diagnostic confidence, and they preferred the concurrent mode, whereas the triage mode achieved the highest performance in the mode score. The second mode stands out for its heightened sensitivity, the triage mode boasts superior specificity, and the concurrent mode leads in efficiency when assisting cytopathologists. These findings provide useful information for choosing appropriate DL-assisted modes in cytopathological practice.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100882"},"PeriodicalIF":5.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008396","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":"Digital Spatial Profiling Demonstrates Differences Between Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans and Its Conventional Counterparts","authors":"Nicholas Frazzette ,&nbsp;Suvrajit Maji ,&nbsp;Nada Mohamed ,&nbsp;Austin Jones ,&nbsp;Ata S. Moshiri ,&nbsp;Robert W. Ricciotti ,&nbsp;Shreeram Akilesh ,&nbsp;Jose G. Mantilla","doi":"10.1016/j.modpat.2025.100879","DOIUrl":"10.1016/j.modpat.2025.100879","url":null,"abstract":"<div><div>Dermatofibrosarcoma protuberans (DFSP) is a neoplasm of the dermis with a tendency for aggressive local growth and recurrence. A minority of DFSP cases may transform into higher-grade sarcoma (fibrosarcomatous transformation [FST]) (DFSP-FST), which is associated with more aggressive behavior and risk of metastasis. The histologic diagnosis of DFSP-FST may be challenging, particularly in small biopsies. Currently, there are no specific markers to reliably support the diagnosis of DFSP-FST. We identified 33 DFSP from 32 patients, including 9 patients with FST and 1 distant metastasis. Tissue microarrays (TMAs) were created using representative areas of all cases, including DFSP-FST, conventional regions from DFSP-FST, and pure conventional DFSP. Digital spatial profiling of the entire transcriptome was performed on the TMAs using the Nanostring GeoMx platform. Expression data were queried to identify differentially expressed genes specific to the regions of transformation in DFSP. Immunohistochemistry for PReferentially expressed Antigen in MElanoma (PRAME) was subsequently performed using a clinically validated protocol. Digital spatial profiling demonstrated significant gene expression differences between DFSP-FST and conventional DFSP. Genes that were overexpressed in DFSP-FST include <em>PRAME</em>, <em>CTAG1B</em>, and <em>MMP11</em>. Immunohistochemical analysis for PRAME showed positive expression in 7 of 10 DFSP-FST (70%) and 1 of 23 conventional DFSP (4%) (<em>P</em> &lt; .0001). Gene expression profiling shows significant upregulation of <em>PRAME</em> and <em>CTAG1B</em> in DFSP-FST compared with conventional DFSP, a finding that was validated by immunohistochemistry for PRAME. Therefore, immunohistochemistry for PRAME may be useful to support the diagnosis of FST, especially in small biopsies. Increased expression of CTAG1B (NY-ESO-1) in DFSP-FST may also offer future therapeutic potential.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100879"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992943","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":"Cover","authors":"","doi":"10.1016/S0893-3952(25)00168-1","DOIUrl":"10.1016/S0893-3952(25)00168-1","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 9","pages":"Article 100870"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094832","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":"Cross-Platform Methylation-Based Site of Origin Classification for Squamous Cell Carcinomas","authors":"Allen W. Zhang ,&nbsp;Vahid Akbari ,&nbsp;Andrew Galbraith ,&nbsp;Zoe Kore ,&nbsp;YuQi Li ,&nbsp;Samuel Leung ,&nbsp;Jennifer X. Ji ,&nbsp;Kristy Dever ,&nbsp;Julie MacIsaac ,&nbsp;Hilary Brewis ,&nbsp;Diane Pan ,&nbsp;Cornelius Kürten ,&nbsp;Andrew Ajisebutu ,&nbsp;Alberto Contreras-Sanz ,&nbsp;Alireza Moeen ,&nbsp;Jeffrey A. Zuccato ,&nbsp;Vikas Patil ,&nbsp;Peter C. Black ,&nbsp;Wan Lam ,&nbsp;Erin Pleasance ,&nbsp;Julia R. Naso","doi":"10.1016/j.modpat.2025.100878","DOIUrl":"10.1016/j.modpat.2025.100878","url":null,"abstract":"<div><div>Squamous cell carcinomas (SCCs) are one of the most common cancer types and can arise at nearly any anatomic site. Because SCCs are one of the most common metastases, do not have reliable site-specific morphologic or genomic features, and have considerable morphologic and immunohistochemical overlap with urothelial carcinomas, distinguishing between primary and metastatic squamous-appearing tumors can be challenging. This distinction can be critical to clinical management. We present <em>Squa</em>mous cell carcinoma <em>M</em>ethylation for <em>O</em>rigin <em>S</em>ite (SquaMOS), a methylation-based classifier to predict site of origin of squamous-appearing carcinomas. Trained on publicly available array-based methylation data from 1062 primary SCCs (from lung, head and neck, cervix, and esophagus) and urothelial carcinomas, SquaMOS predicted site of origin in primary tumors with 96.1% accuracy in an internal test set (n = 458) and 97.4% accuracy in an external test set from 3 institutions (n = 78). On metastatic tumors (n = 51), SquaMOS predictions were 96.1% accurate. SquaMOS was directly applicable to shallow Nanopore sequencing data (CpG probe site coverage, 0.25-2.88×) with an accuracy of 91.7% (n = 36; 100% accurate for high-confidence predictions). When tested on SCCs outside the training set types (n = 15, including 3 metastases to lung), no cases were misclassified as of lung origin, supporting accuracy of lung vs nonlung origin classification for diverse SCC types. Overall, we demonstrate highly accurate performance of the SquaMOS classifier on primary and metastatic tumors from multiple data sources, robust to suboptimal tumor purity. We illustrate transferability of our array-based classifier to low-depth Nanopore sequencing data, a potentially rapid means of site of origin determination in a clinical setting.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100878"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992905","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":"HNF1A-inactived Hepatocellular Adenomas in Fibropolycystic Kidney and Liver Disease Are Associated With Germline HNF1B Variant","authors":"Catherine E. Hagen ,&nbsp;Dipti M. Karamchandani ,&nbsp;Luisa Ricaurte ,&nbsp;Nagaswaroop Nagaraj ,&nbsp;Vivekananda Sarangi ,&nbsp;Christopher P. Hartley ,&nbsp;Chirag Patel ,&nbsp;Marcela Salomao ,&nbsp;Rish Pai ,&nbsp;Rondell P. Graham","doi":"10.1016/j.modpat.2025.100880","DOIUrl":"10.1016/j.modpat.2025.100880","url":null,"abstract":"<div><div><em>HNF1A</em>-inactivated hepatocellular adenomas are rarely described in patients with hepatorenal fibrocystic disease, and their genetic relationship remains unexplored. This study reports a series of <em>HNF1A</em>-inactivated hepatocellular adenomas with molecular sequencing analysis in patients with fibrocystic kidney and/or liver disease. Cases were retrospectively identified from the pathology archives of 3 institutions. Clinical history was collected from chart review, and hematoxylin-and-eosin–stained slides along with relevant immunohistochemistry were reviewed for liver specimens. Next-generation sequencing was performed on paired lesional hepatocellular adenoma and nonneoplastic tissue. The study group comprised 8 patients (median age, 25 years; male:female, 1:7). Six patients had evidence of congenital hepatic fibrosis, 1 had polycystic liver disease with multiple cysts and bile duct hamartomas, and 1 had an uninvolved background liver but with polycystic kidney disease. Histologic examination revealed that all hepatocellular adenomas showed circumscribed, well-differentiated hepatocellular proliferation with unpaired arterioles and loss of liver fatty acid–binding protein staining via immunohistochemistry. Three patients were found to have novel <em>HNF1B</em> germline variants (c.1430A&gt;C). Our data reveal a new syndromic association for <em>HNF1A</em>-inactivated hepatocellular adenomas. We hypothesize that aberrant interactions between HNF1A and HNF1B may contribute to the pathogenesis of hepatocellular adenomas in these patients. Further studies are necessary to discover additional germline variants that may result in a similar phenotype.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100880"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992955","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}