Modern Pathology最新文献

{"title":"Meningiomas With Chromosomal Polysomies Reveal Nonrandom Gain of Chromosomes, Distinct Methylation Signature, and Lower Risk of Recurrence","authors":"Erica Vormittag-Nocito ,&nbsp;Drew Duckett ,&nbsp;Rudolph J. Castellani ,&nbsp;Jared T. Ahrendsen ,&nbsp;Xinyan Lu ,&nbsp;Lawrence J. Jennings ,&nbsp;Rimas V. Lukas ,&nbsp;Stephen T. Magill ,&nbsp;Lucas Santana-Santos ,&nbsp;Daniel J. Brat ,&nbsp;Pouya Jamshidi ,&nbsp;Madina Sukhanova","doi":"10.1016/j.modpat.2025.100775","DOIUrl":"10.1016/j.modpat.2025.100775","url":null,"abstract":"<div><div>Meningiomas are the most common primary central nervous system tumors in adults. Although the majority of meningiomas are benign, certain clinical and histopathological factors are associated with an increased risk of tumor progression and recurrence. Advances in genomic characterization of brain tumors have revealed that certain molecular characteristics such as <em>TERT</em> promoter mutation and chromosomal losses on 1p, 6p/q, 9p, 10p/q, 14q, and 18p/q as genomic markers are associated with aggressive behavior. However, the significance of chromosomal polysomies in meningiomas is not clear. We performed a comparative analysis of clinical, cytogenomic, and methylation profiles of a series of 25 meningioma cases with gains of multiple chromosomes and compared with 2 low-risk groups with either no copy number alterations or isolated monosomy 22. No high-risk morphologic subtypes of meningioma were linked to the polysomy group, and there were no differences in the World Health Organization Grade or progression-free survival between the study groups. Noteworthy was a nonrandom pattern of chromosomal gains, with most cases showing tetrasomy of chromosomes 5 and 20 with concurrent trisomy of chromosomes 12 and 17. Methylation profiling showed that meningiomas with polysomies had a distinct methylation signature and were predominantly Merlin-intact meningiomas. These results suggest that meningiomas with multiple polysomies are an uncommon subclass of benign meningioma that have a low rate of progression after resection and a unique genetic architecture.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 7","pages":"Article 100775"},"PeriodicalIF":7.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907876","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":"Corrigendum to \"Pan-Cancer Molecular Biomarkers: Practical Considerations for the Surgical Pathologist\" [Modern Pathology 38 (2025) 100752].","authors":"Pari Jafari, Megan E Forrest, Jeremy Segal, Peng Wang, Melissa Yuwono Tjota","doi":"10.1016/j.modpat.2025.100773","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100773","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100773"},"PeriodicalIF":7.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079114","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":"Longitudinal Analysis Reveals Dynamic Changes in Histopathologic Features in Responders to Neoadjuvant Treatment in a Stage III BRAF-Mutant Melanoma Cohort","authors":"Jorja Braden ,&nbsp;Alison Potter ,&nbsp;Robert V. Rawson ,&nbsp;Nurudeen A. Adegoke ,&nbsp;Serigne N. Lo ,&nbsp;Jordan W. Conway ,&nbsp;Alexander M. Menzies ,&nbsp;Matteo S. Carlino ,&nbsp;George Au-Yeung ,&nbsp;Robyn P.M. Saw ,&nbsp;Andrew J. Spillane ,&nbsp;Kerwin F. Shannon ,&nbsp;Thomas E. Pennington ,&nbsp;Sydney Ch’ng ,&nbsp;David E. Gyorki ,&nbsp;Julie R. Howle ,&nbsp;James S. Wilmott ,&nbsp;Richard A. Scolyer ,&nbsp;Georgina V. Long ,&nbsp;Ines Pires da Silva","doi":"10.1016/j.modpat.2025.100776","DOIUrl":"10.1016/j.modpat.2025.100776","url":null,"abstract":"<div><div>Despite advances in systemic therapies, cutaneous melanoma remains a highly deadly disease. Patients with high-risk stage III melanoma have a significant likelihood of recurrence following surgery. Although adjuvant immunotherapy has been the standard of care, recent evidence demonstrates that neoadjuvant immunotherapy is more effective for higher-risk stage III patients, showing superior survival outcomes compared with adjuvant immunotherapy. This has led to an immediate paradigm shift in clinical practice toward neoadjuvant therapy for this cohort. The NeoTrio clinical trial assessed the efficacy of sequential or combination <em>BRAF</em>-targeted therapy with anti–programmed cell death-1 in the neoadjuvant setting. However, research on longitudinal histopathologic changes during this treatment period remains limited. Analysis of hematoxylin and eosin slides from 60 patients across 4 matched neoadjuvant timepoints revealed dynamic changes in a number of treatment response features. Females achieved significantly higher rates of major pathologic response (<em>P</em> = .002) and displayed higher levels of inflammatory fibrosis (<em>P</em> = .04) and hyalinized fibrosis (<em>P</em> = .01). The presence of tertiary lymphoid structures (<em>P</em> = .013) and plasma cells (<em>P</em> = .02) at resection was significantly associated with response. Combination scoring of histopathologic features (composite score and the immune-related pathologic response [irPR] score) was significantly associated with response early during the neoadjuvant period (composite score at week 2 on-treatment, <em>P</em> = .03; high irPR score at week 2 on-treatment, <em>P</em> = .01). A high irPR score at week 2 on-treatment was also found to be significantly associated with a lower chance of recurrence at this early neoadjuvant timepoint (<em>P</em> = .02). Other features associated with a lower likelihood of recurrence included increased hyalinized fibrosis (<em>P</em> = .015) and the presence of extensive lymphocyte density score (<em>P</em> = .01), tertiary lymphoid structures (<em>P</em> = .03), and plasma cells (<em>P</em> = .01). This study deepens our understanding of treatment response markers and their dynamic changes during neoadjuvant therapy. It underscores the significance of these features, particularly given their early emergence and strong associations with response and recurrence.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100776"},"PeriodicalIF":7.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924240","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":"Cytogenomic and Clinicopathologic Comparison of MYC-Positive and MYC-Negative High-Grade B-Cell Lymphoma With 11q Aberration in the Context of Other Aggressive Lymphomas With MYC Rearrangement","authors":"Beata Grygalewicz ,&nbsp;Lukasz M. Szafron ,&nbsp;Laura A. Szafron ,&nbsp;Renata Woroniecka ,&nbsp;Joanna Parada ,&nbsp;German Ott ,&nbsp;Heike Horn ,&nbsp;Barbara Pienkowska-Grela ,&nbsp;Jolanta Rygier ,&nbsp;Natalia Malawska ,&nbsp;Katarzyna Wojtkowska ,&nbsp;Zbigniew Bystydzienski ,&nbsp;Katarzyna Blachnio ,&nbsp;Beata Nowakowska ,&nbsp;Grzegorz Rymkiewicz","doi":"10.1016/j.modpat.2025.100774","DOIUrl":"10.1016/j.modpat.2025.100774","url":null,"abstract":"&lt;div&gt;&lt;div&gt;According to the 2022 World Health Organization Classification, high-grade B-cell lymphoma with 11q aberration (HGBCL-11q) is a &lt;em&gt;MYC&lt;/em&gt;-negative lymphoma with 11q duplication and terminal deletion as specific chromosomal aberrations for this neoplasm. However, there is a growing number of reports defying this definition, describing cases with the co-occurrence of 11q aberration and &lt;em&gt;MYC&lt;/em&gt; rearrangement (HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R). This research has 2 aims. First, to compare the unique HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R group of 9 cases with 26 HGBCL-11q cases on chromosomal, mutational, and clinicopathological levels. The second objective was to investigate the association of the new HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R group with HGBCL-11q and 2 other closely related &lt;em&gt;MYC-&lt;/em&gt;positive aggressive lymphoma subtypes: Burkitt lymphoma (BL) (n = 17) and HGBCL, not otherwise specified with &lt;em&gt;MYC&lt;/em&gt;R (n = 10). Genetic results were obtained by classical cytogenetics, fluorescence in situ hybridization, microarrays, and whole exome sequencing. In parallel histopathologic/immunohistochemical analyses (HP/IHC)with flow cytometry (FCM), in conjunction with clinical presentation and treatment outcomes, are presented. Our findings reveal that HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R exists as an independent nosologic entity, distinct from BL and HGBCL-11q at the cytogenetic, molecular, and clinicopathological levels, although it contains common features of both lymphoma subtypes. Common features with BL include following: &lt;em&gt;MYC&lt;/em&gt;R with the immunoglobulin (Ig) genes, patterns of secondary chromosomal aberrations like dup(1q), del(17p), and high number of &lt;em&gt;MYC&lt;/em&gt; and &lt;em&gt;CCND3&lt;/em&gt; mutations. Other BL features are: frequent extranodal abdominal presentation, morphology, germinal center B-cell-like cell of origin determined by IHC and FCM, immunophenotypical features such as MYC(+)/LMO2(–) detected by following flow cytometric features: CD45(+)&lt;sup&gt;weaker&lt;/sup&gt;, more cases with CD43(+) and CD44(–) expression, only expression of IgD and IgM heavy chain, and CD38(+)&lt;sup&gt;higher&lt;/sup&gt; overexpression, which correlates with &lt;em&gt;MYC&lt;/em&gt;R assessed by FCM. Similarity to HGBCL-11q includes the existence of 11q aberration, presence of &lt;em&gt;DDX3X&lt;/em&gt;, &lt;em&gt;ETS1&lt;/em&gt;, &lt;em&gt;GNA13&lt;/em&gt;, &lt;em&gt;NFRKB&lt;/em&gt;, and &lt;em&gt;KMT2D&lt;/em&gt;&lt;em&gt;,&lt;/em&gt; and the lack of &lt;em&gt;TCF3&lt;/em&gt; and &lt;em&gt;ID3&lt;/em&gt; mutations. Additionally, frequent nodal and tonsillar presentation, morphology, germinal center B-cell-like cell of origin, and immunophenotypical features, including CD56(+) expression measured using FCM, are observed, which are associated with &lt;em&gt;NCAM&lt;/em&gt; duplication/amplification on 11q, and pathogenesis not associated with Epstein-Barr virus infection. The distinctive chromosomal change of HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R was the gain or amplification of 3q29. Our cohort of patients with HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R had similar relapse-free survival to that of patients with HGBCL-11q and BL, if treated with BL-direct","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100774"},"PeriodicalIF":7.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924241","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":"The Histologic Spectrum of Rituximab-Associated Common Variable Immunodeficiency-Like Enteropathy","authors":"Pari Jafari ,&nbsp;David Hakimian ,&nbsp;Maria Westerhoff ,&nbsp;Jerome Cheng ,&nbsp;Wenqing Cao ,&nbsp;Mehran N. Kohnehshahri ,&nbsp;Won-Tak Choi ,&nbsp;Gertruda Evaristo ,&nbsp;Rondell P. Graham ,&nbsp;Xiaoyan Liao ,&nbsp;Xiuli Liu ,&nbsp;Rish K. Pai ,&nbsp;Marcela A. Salomao ,&nbsp;Lei Zhao ,&nbsp;John Hart ,&nbsp;Dejan Micic ,&nbsp;Carol E. Semrad ,&nbsp;Lindsay Alpert","doi":"10.1016/j.modpat.2025.100770","DOIUrl":"10.1016/j.modpat.2025.100770","url":null,"abstract":"<div><div>Rituximab (RTX) is a monoclonal anti-CD20 antibody widely used to treat B-cell neoplasms and autoimmune conditions. RTX has recently been linked to an enteropathy characterized by diarrhea, malabsorption, and hypogammaglobulinemia, closely resembling common variable immunodeficiency (CVID) enteropathy. We present the first dedicated histopathologic assessment of RTX-associated CVID-like enteropathy. Study inclusion criteria were the presence of diarrhea, weight loss, or other gastrointestinal symptoms in the setting of current/prior RTX use and associated hypogammaglobulinemia. Twenty-two patients (15 male:7 female; mean age at biopsy/resection, 63.4 years) across 9 tertiary medical centers met inclusion criteria and had small bowel (N = 20) and/or colon (N = 17) specimens (biopsies/resections) available for review; 71.4% of specimens dated from ≤5 years of last RTX dose. Cases were systematically evaluated by gastrointestinal pathologists at each institution. Key histologic features in the small bowel included sparse/absent lamina propria plasma cells (N = 10; 50%), intraepithelial lymphocytosis (N = 12; 60%), villous atrophy (N = 11; 55%), increased crypt apoptotic bodies (N = 6; 30%), and active inflammation (N = 5; 25%). Common features in the colon included sparse/absent plasma cells (N = 7; 41.2%), increased crypt apoptotic bodies (N = 7; 41.2%), active inflammation (N = 5; 29.4%), and intraepithelial lymphocytosis (N = 4; 23.5%). Goblet cell loss was appreciated in small bowel and/or colon specimens from 2 patients. Follow-up biopsies (interval, 2 months to 4 years) were available for 7 patients and largely recapitulated the histology of the index specimens, though 1 patient demonstrated improvement in villous blunting and intraepithelial lymphocytosis. In summary, the histologic spectrum of post-RTX CVID-like enteropathy encompasses lamina propria plasma cell depletion, increased crypt apoptotic bodies, small bowel villous atrophy, and goblet cell loss. While the underlying pathophysiology remains uncertain, the clinicopathologic picture may reflect post-RTX B-cell/plasma cell impairment. Although histologic findings may be subtle and variable, pathologists should be aware of this entity and should seek a history of RTX use in patients whose biopsies exhibit these CVID enteropathy-like features.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100770"},"PeriodicalIF":7.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906934","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":"Spatial Mapping of Gene Signatures in Hematoxylin and Eosin-Stained Images: A Proof of Concept for Interpretable Predictions Using Additive Multiple Instance Learning","authors":"Miles Markey,&nbsp;Juhyun Kim,&nbsp;Zvi Goldstein,&nbsp;Ylaine Gerardin,&nbsp;Jacqueline Brosnan-Cashman,&nbsp;Syed Ashar Javed,&nbsp;Dinkar Juyal,&nbsp;Harshith Pagidela,&nbsp;Limin Yu,&nbsp;Bahar Rahsepar,&nbsp;John Abel,&nbsp;Stephanie Hennek,&nbsp;Archit Khosla,&nbsp;Amaro Taylor-Weiner,&nbsp;Chintan Parmar","doi":"10.1016/j.modpat.2025.100772","DOIUrl":"10.1016/j.modpat.2025.100772","url":null,"abstract":"<div><div>The relative abundance of cancer-associated fibroblast (CAF) subtypes influences a tumor’s response to treatment, especially immunotherapy. However, the gene expression signatures associated with these CAF subtypes have yet to realize their potential as clinical biomarkers. Here, we describe an interpretable machine learning approach, additive multiple instance learning (aMIL), to predict bulk gene expression signatures from hematoxylin and eosin-stained whole-slide images, focusing on an immunosuppressive LRRC15+ CAF-enriched TGFβ-CAF signature. aMIL models accurately predicted TGFβ-CAF across various cancer types. Tissue regions contributing most highly to slide-level predictions of TGFβ-CAF were evaluated by machine learning models characterizing spatial distributions of diverse cell and tissue types, stromal subtypes, and nuclear morphology. In breast cancer, regions contributing most to TGFβ-CAF-high predictions (“excitatory”) were localized to cancer stroma with high fibroblast density and mature collagen fibers. Regions contributing most to TGFβ-CAF-low predictions (“inhibitory”) were localized to cancer epithelium and densely inflamed stroma. Fibroblast and lymphocyte nuclear morphology also differed between excitatory and inhibitory regions. Thus, aMIL enables a data-driven link between histologic features and transcription, offering biological interpretability beyond typical black-box models.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100772"},"PeriodicalIF":7.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941833","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":"Artificial Intelligence–Based Single-Cell Analysis as a Next-Generation Histologic Grading Approach in Colorectal Cancer: Prognostic Role and Tumor Biology Assessment","authors":"Vincenzo Mitchell Barroso ,&nbsp;Zhilong Weng ,&nbsp;Lennert Glamann ,&nbsp;Marcus Bauer ,&nbsp;Claudia Wickenhauser ,&nbsp;Thomas Zander ,&nbsp;Reinhard Büttner ,&nbsp;Alexander Quaas ,&nbsp;Yuri Tolkach","doi":"10.1016/j.modpat.2025.100771","DOIUrl":"10.1016/j.modpat.2025.100771","url":null,"abstract":"<div><div>The management of colorectal carcinoma (CRC) relies on pathological interpretation. Digital pathology approaches allow for development of new potent artificial intelligence–based prognostic parameters. The study aimed to develop an artificial intelligence–based image analysis platform allowing fully automatized, quantitative, and explainable tumor microenvironment analysis and extraction of prognostic information from hematoxylin and eosin–stained whole-slide images of CRC patients. Three well--characterized, multi-institutional patient cohorts were included (patient n = 1438, whole-slide image n &gt; 2400). The developed image analysis platform implements quality control and established algorithms to segment tissue and detect cell types. It enabled systematic analysis of immune infiltrate, assessing its prognostic relevance, intratumoral heterogeneity, and biological concepts across multiple survival end points. Analyzing single-cell types and their combinations reveals independent, prognostic parameters, highlighting significant intratumoral heterogeneity, especially in the biopsy setting, which must be accounted for. A key morphologic concept related to tumor control by the immune system is described, resulting in a capable, independent prognostic parameter (tumor “out of control”). Our findings have direct clinical implications and can be used as a foundation for updating the existing CRC grading systems.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 7","pages":"Article 100771"},"PeriodicalIF":7.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904171","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":"Undifferentiated Pleomorphic Sarcoma in Children and Young Adults: A Comprehensive Clinicopathologic, Genomic, and Epigenetic Comparison With Adult Counterparts","authors":"Carla Saoud ,&nbsp;Gunes Gundem ,&nbsp;Chad M. Vanderbilt ,&nbsp;Leonard H. Wexler ,&nbsp;Damon R. Reed ,&nbsp;William Tap ,&nbsp;Samuel Singer ,&nbsp;Liliana B. Villafania ,&nbsp;Elli Papaemmanouil ,&nbsp;Jamal Benhamida ,&nbsp;Tejus A. Bale ,&nbsp;Cristina R. Antonescu","doi":"10.1016/j.modpat.2025.100769","DOIUrl":"10.1016/j.modpat.2025.100769","url":null,"abstract":"<div><div>Undifferentiated pleomorphic sarcoma (UPS) occurs primarily in older adults and remains a diagnosis of exclusion due to its lack of differentiation and specific molecular alterations. Its occurrence in children is rare and controversial, with an unclear relationship to its adult counterpart. In this study, we aimed to investigate a cohort of 6 pediatric undifferentiated pleomorphic sarcoma (P-UPS, mean 10 years old) and 19 young-adult undifferentiated pleomorphic sarcoma (YA-UPS, mean 30 years old) cases by conducting a comprehensive comparative analysis of their clinicopathologic, genomic, and epigenetic features relative to their adult undifferentiated pleomorphic sarcoma counterparts (A-UPS, n = 100). Histologically, P-UPS and YA-UPS exhibited broad morphologic spectrum. The most frequent alterations across all groups were <em>TP53</em>, <em>CDKN2A/B</em>, and <em>ATRX,</em> with no significant differences among subsets. Notably, <em>RB1</em> alterations were absent in P-UPS, although representing the second most common alteration in YA-UPS (32%) and A-UPS (41%). <em>PTEN</em> alterations were significantly more prevalent in YA-UPS (26%) compared with that in P-UPS (0%) and A-UPS (6%). Deletions in chromosomes 10, 16q, and 13q, along with amplification of 20q, were the most common across all groups. Except for a higher frequency of 17q amplification in P-UPS (33%) and YA-UPS (26%) compared with that in A-UPS (6%), no other arm-level differences were observed. P-UPS showed a lower mean fraction genome altered compared with YA-UPS and A-UPS, whereas all UPS age groups showed a low tumor mutational burden (mean &lt;10 mut/MB). Pathogenic germline variants of high clinical significance (<em>TP53</em>, <em>NF1</em>, <em>MLH1</em>, <em>CHEK2</em>, and <em>BARD1</em>) were observed only in YA-UPS (31%) and A-UPS (12%) cases. By T-distributed stochastic neighborhood embedding and hierarchical clustering of DNA methylation, the majority of P-UPS and a small subset of YA-UPS grouped in a distinct cluster, characterized by a lower genomic index compared to A-UPS. In contrast, most UPS occurring in young adults genomically parallel their older adults’ counterparts. P-UPS and YA-UPS cases exhibited a better disease-specific and progression-free survival, compared with A-UPS cases.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100769"},"PeriodicalIF":7.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917344","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":"Pathology Asks for Global Regulations in Artificial Intelligence Employment","authors":"Massimo Rugge ,&nbsp;Matteo Fraschini ,&nbsp;Alessandro D’Amuri ,&nbsp;Gavino Faa","doi":"10.1016/j.modpat.2025.100754","DOIUrl":"10.1016/j.modpat.2025.100754","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100754"},"PeriodicalIF":7.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807594","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":"Spatially Resolved Single-Cell Morphometry of Benign Breast Disease Biopsy Images Uncovers Quantitative Cytomorphometric Features Predictive of Subsequent Invasive Breast Cancer Risk","authors":"Mustapha Abubakar ,&nbsp;Shaoqi Fan ,&nbsp;Alyssa Klein ,&nbsp;Ruth M. Pfeiffer ,&nbsp;Scott Lawrence ,&nbsp;Karun Mutreja ,&nbsp;Teresa M. Kimes ,&nbsp;Kathryn Richert-Boe ,&nbsp;Jonine D. Figueroa ,&nbsp;Gretchen L. Gierach ,&nbsp;Maire A. Duggan ,&nbsp;Thomas E. Rohan","doi":"10.1016/j.modpat.2025.100767","DOIUrl":"10.1016/j.modpat.2025.100767","url":null,"abstract":"<div><div>Currently, benign breast disease (BBD) pathologic classification and invasive breast cancer (BC) risk assessment are based on qualitative epithelial changes, with limited utility for BC risk stratification for women with lower-risk category BBD (ie, nonproliferative disease [NPD] and proliferative disease without atypia [PDWA]). Here, machine learning–based single-cell morphometry was used to characterize quantitative changes in epithelial nuclear morphology that reflect functional/structural decline (ie, increasing nuclear size, assessed as epithelial nuclear area and nuclear perimeter), altered DNA chromatin content (ie, increasing nuclear chromasia), and increased cellular crowding/proliferation (ie, increasing nuclear contour irregularity). Cytomorphologic changes reflecting chronic stromal inflammation were assessed using stromal cellular density. Data and pathology materials were obtained from a case-control study (n = 972) nested within a cohort of 15,395 women diagnosed with BBD at Kaiser Permanente Northwest (1971-2012). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations of cytomorphometric features with risk of subsequent BC were assessed using multivariable logistic regression. More than 55 million epithelial and 37 million stromal cells were profiled across 972 BBD images. Cytomorphometric features were individually predictive of subsequent BC risk, independently of BBD histologic classification. However, cytomorphometric features of epithelial functional/structural decline were statistically significantly predictive of low-grade but not high-grade BC following PDWA (OR for low-grade BC per 1-SD increase in nuclear area and nuclear perimeter, 2.10; 95% CI, 1.26-3.49, and 2.22; 95% CI, 1.30-3.78, respectively), whereas stromal inflammation was predictive of high-grade but not low-grade BC following NPD (OR for high-grade BC per 1-SD increase in stromal cellular density, 1.53; 95% CI, 1.13-2.08). Associations of nuclear chromasia and nuclear contour irregularity with subsequent tumor grade were context specific, with both features predicting low-grade BC risk following PDWA (OR per 1-SD, 1.58; 95% CI, 1.06-2.35, and 2.21; 95% CI, 1.25-3.91, for nuclear chromasia and nuclear contour irregularity, respectively) and high-grade BC following NPD (OR per 1-SD, 1.47; 95% CI, 1.11-1.96, and 1.29; 95% CI, 1.00-1.70, for nuclear chromasia and nuclear contour irregularity, respectively). The results indicate that cytomorphometric features on BBD hematoxylin-eosin–stained images might help to refine BC risk estimation and potentially inform BC risk reduction strategies for BBD patients, particularly those currently designated as low risk.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 7","pages":"Article 100767"},"PeriodicalIF":7.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882593","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}