Modern Pathology最新文献

{"title":"Whole-Slide Imaging and Radiological Features Predict Clinical Outcomes in Patients With Neuroendocrine Tumors of the Lung","authors":"Sevinj Yolchuyeva ,&nbsp;Leyla Ebrahimpour ,&nbsp;Yannick Lemaréchal ,&nbsp;Philippe Joubert ,&nbsp;Steve Bilodeau ,&nbsp;Philippe Després ,&nbsp;Venkata SK. Manem","doi":"10.1016/j.modpat.2025.100897","DOIUrl":"10.1016/j.modpat.2025.100897","url":null,"abstract":"<div><div>Neuroendocrine tumors are rare and heterogeneous cancers that vary in clinical presentation, biology, and treatment response. They exhibit slow growth with varying levels of aggressiveness, highlighting the need for reliable biomarkers to guide personalized treatment. This study aims to develop predictive models for overall survival (OS) and progression-free survival (PFS) using computed tomography scans, whole-slide images, and clinical data. This retrospective analysis included 83 patients. Predictive models were developed using radiomics features from computed tomography scans and morphologic or pathomics features from whole-slide images. The Cox model was trained using the most significant features from both radiomics and pathomics. By integrating these features with clinical data, we built predictive models combining clinical-radiomics and clinical-pathomics information. We also assessed how image harmonization across different acquisition parameters affects model performance. The radiomics model’s concordance indices (C-indices) for predicting OS and PFS in the validation cohort were 0.64 ± 0.06 (95% CI, 0.55-0.73) and 0.60 ± 0.05 (95% CI, 0.52-0.67), respectively. Combining radiomics with clinical data slightly improved performance, with C-indices of 0.643 ± 0.04 (95% CI, 0.58-0.70) for OS and 0.61 ± 0.04 (95% CI, 0.54-0.68) for PFS. For the pathomics model, combining morphologic features with clinical data also showed better improvements, with C-indices for OS increasing from 0.65 ± 0.08 (95% CI, 0.53-0.76) to 0.70 ± 0.03 (95% CI, 0.57-0.82), and for PFS from 0.60 ± 0.15 (95% CI, 0.39-0.81) to 0.68 ± 0.08 (95% CI, 0.57-0.80). Harmonizing radiomics features did not significantly enhance the model’s performance for predicting survival outcomes. This study developed and validated models that integrate radiomics and pathomics with clinical data, improving prognostic accuracy for OS and PFS. These multimodal approaches, supported by large data sets, offer significant potential for enhancing patient risk stratification. Further multi-institutional validation is needed, but these imaging-driven biomarkers could ultimately refine therapeutic strategies and optimize survival outcomes.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100897"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138209","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":"Predicting the Probability of Residual Axillary Nodal Metastases in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy","authors":"Thaer Khoury ,&nbsp;Haiying Zhan ,&nbsp;Xiao Huang ,&nbsp;Farhad Ghasemi ,&nbsp;Fareed Rajack ,&nbsp;Guangwei Yuan ,&nbsp;Han Yu ,&nbsp;Janie Theriot ,&nbsp;Ryan Bragiel ,&nbsp;Kanako Okamoto ,&nbsp;Muhammad Ali","doi":"10.1016/j.modpat.2025.100902","DOIUrl":"10.1016/j.modpat.2025.100902","url":null,"abstract":"<div><div>In patients with breast cancer treated with neoadjuvant chemotherapy (NACT), a positive sentinel lymph node (SLN) usually requires completion axillary lymph node dissection (ALND). To enable de-escalation of this traumatic surgery, we aimed to develop a model to accurately estimate the likelihood of axillary disease after a positive SLN biopsy in the NACT setting. We retrospectively analyzed clinicopathological data from 237 patients composed of a training set of 150 patients from a single institution and a validation set of 87 patients from 2 other institutions. Variables that were collected included the histologic type, lymphovascular invasion, the number of lymph nodes (LNs) (SLN and non-SLN), positive and negative, with and without treatment effect, extranodal extension, and the calculated residual cancer burden of the largest SLN metastasis. Residual axillary disease was defined as ≥1 positive LNs in the completion ALND specimen. Univariable and multivariable statistical analyses were performed. Then, a formula for the risk of predicted probability of residual axillary disease was created using a stepwise feature selection based on the Akaike Information Criterion to select variables in the model. Residual axillary disease was identified in 120 out of 237 (50.6%) cases (73 [48.7%] in the training set and 47 [54%] in the validation set). Independent predictors of residual axillary disease in the multivariable model included the greatest dimension of the largest SLN metastasis, lymphovascular invasion, greater number of positive LNs with no treatment effect, greater number of positive LNs with treatment effect, greater number of negative LNs with treatment effect, and fewer number of negative LNs. These variables along with residual cancer burden of the largest SLN metastasis and histologic type were incorporated into the final model by stepwise feature selection. The predictive formula achieved an area under the curve of 77.6% for the training set and 69.7% for the validation set. A predicted probability value of ≤20% yielded a negative predictive value of 86.5% in the training set and 64.7% in the validation set. This corresponds to 37 (25.3%) patients who could be spared ALND in the training set and 17 (19.5%) in the validation set. Using the formula, a subset of patients treated with NACT could be spared unnecessary ALND.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100902"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225609","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":"Human Epidermal Growth Factor Receptor 2 (HER2)-Ultralow Breast Cancer: Incidence, Clinicopathologic Features, and Need for Refined Scoring System","authors":"Doaa Morrar,&nbsp;Edi Brogi,&nbsp;Christopher J. Schwartz,&nbsp;Fresia Pareja,&nbsp;Hannah Y. Wen,&nbsp;Dara S. Ross","doi":"10.1016/j.modpat.2025.100901","DOIUrl":"10.1016/j.modpat.2025.100901","url":null,"abstract":"<div><div>Patients with metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC), defined as immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization negative, have demonstrated clinical benefit from antibody-drug conjugates, such as trastuzumab deruxtecan. The DESTINY-Breast06 trial further demonstrated that patients with hormone receptor-positive, HER2-ultralow (UL) metastatic BC also benefit from HER2-targeted therapies. This study aimed to evaluate the incidence, staining characteristics, and clinicopathologic features of HER2-UL BC. We retrospectively analyzed scanned HER2 IHC slides (PATHWAY anti-HER2/neu 4B5) from 400 primary BC cases diagnosed between January and March 2024. Two breast pathologists reevaluated and recategorized HER2 IHC results into HER2-positive, HER2-low, HER2-UL, and HER2-null (N). HER2-UL was defined as incomplete or weak membranous staining in ≤10% of tumor cells, whereas HER2-N showed complete absence of membranous staining. Staining was analyzed by distribution, location, and quality. Clinicopathologic comparisons were performed across HER2-negative groups. Original HER2 classification based on the 2023 American Society of Clinical Oncology and College of American Pathologists guidelines included HER2 IHC 0 (146, 37%), HER2 IHC 1+ (188, 47%), HER2 IHC 2+/fluorescence in situ hybridization negative (33, 8%), and HER2-positive (HER2 IHC 2+/fluorescence in situ hybridization positive or 3+) (33, 8%). Upon rereview, with HER2-low, HER2-UL, and HER2-N incorporated into the classification framework, 63 cases (16%) were HER2-N, 118 (29%) HER2-UL, 186 (47%) HER2-low, and 33 (8%) HER2-positive. In HER2-UL cases, median membranous staining was 3% (range, 1%-9%). Nonspecific staining patterns, such as granular cytoplasmic staining, cytoplasmic blush, edge staining, and dot-like peritumoral staining, were frequently observed in recategorized cases. No significant clinicopathologic differences were found among HER2-N, HER2-UL, and HER2-low groups, except for higher invasive lobular carcinoma frequency in HER2-N (<em>P</em> = .034) and older age in HER2-UL patients. Notably, 55% (80/146) of initial HER2 IHC 0 cases were categorized as HER2-UL. As HER2-targeted therapies expand to HER2-UL tumors, accurate classification is critical. Implementation of a refined scoring system could improve diagnostic accuracy and therapeutic targeting.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100901"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206848","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 Evaluation and Prognostic Significance of V-Domain Immunoglobulin Suppressor of T-Cell Activation (VISTA) in Human Resectable Cervical Carcinoma: Implications for Immune Activation and Suppression","authors":"Qingshen Xie ,&nbsp;Jinqing Li ,&nbsp;Jieyao Li ,&nbsp;Chaoqun Liu ,&nbsp;Yangyang Li ,&nbsp;Hong Zeng ,&nbsp;Jingwei Yu ,&nbsp;Yingchen Wu ,&nbsp;Kaiqian Chen ,&nbsp;Zhaonan Zhang ,&nbsp;Bo Wang","doi":"10.1016/j.modpat.2025.100851","DOIUrl":"10.1016/j.modpat.2025.100851","url":null,"abstract":"<div><div>V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a promising next-generation immune checkpoint target. This study investigated the distribution and clinical significance of VISTA expression in cervical carcinoma. Using a cohort of 290 patients from Sun Yat-sen Memorial Hospital, we assessed VISTA expression in tumor cells, endothelial cells, and immune cells (ICs) through immunohistochemistry, and found that it was expressed in tumor cells (18.6%), endothelial cells (38.3%), and ICs (100%). Higher infiltration of VISTA⁺ ICs was observed in the stromal region compared with that in the intratumoral region of resectable cervical carcinoma. Among the ICs, macrophages showed the highest VISTA expression compared with that by T cells and neutrophils. High intratumoral VISTA expression was an independent marker of favorable prognosis. Robust infiltration of VISTA⁺ ICs and CD8⁺ T cells in the tumor microenvironment correlated with the best clinical outcomes. In addition, in an independent cervical carcinoma cohort (<em>n</em> = 48), VISTA⁺ ICs in both intratumoral and stromal regions were positively associated with CD8⁺ T cells, CD103⁺ T cells, and effector molecules, such as granzyme B. Elevated VISTA expression was also associated with an enriched immunosuppressive profile, including Foxp3⁺ regulatory T cells and molecules such as TGF-β1, PD-1, LAG-3, TIM-3, and TIGIT. Moreover, multiplex staining and correlation analysis revealed a positive association between VISTA⁺ TGF-β1⁺ ICs and FOXP3⁺ regulatory T cells in tumor tissues. These findings establish a strong connection between intratumoral VISTA⁺ ICs and a regulatory immune contexture involving both activation and suppression signatures, with a skew toward activation dominance. Our study results suggest that VISTA can be employed as a potential prognostic biomarker for cervical carcinoma.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100851"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732311","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":"Analysis of Oncogene Mutations in Odontogenic Myxoma","authors":"Jintana Pankam ,&nbsp;Nakarin Kitkumthorn ,&nbsp;Siribang-on Piboonniyom Khovidhunkit ,&nbsp;Dusit Bumalee ,&nbsp;Puangwan Lapthanasupkul","doi":"10.1016/j.modpat.2025.100856","DOIUrl":"10.1016/j.modpat.2025.100856","url":null,"abstract":"<div><div>Odontogenic myxoma (OM) is a rare, benign mesenchymal odontogenic tumor. Presently, the molecular mechanisms underlying OM remain unclear, and no diagnostic markers have been identified. This study aimed to investigate gene mutations related to the MAPK/ERK, PI3K/mTOR, and β-catenin/Wnt pathways in OM, including <em>KRAS</em>, <em>PIK3CA</em>, and <em>CTNNB1</em>, and their associated proteins. Additionally, the association between gene mutations and their associated protein expression was also investigated. DNA was extracted from 11 formalin-fixed, paraffin-embedded OM tissues for PCR. PCR-positive samples using <em>KRAS</em>, <em>PIK3CA</em>, and <em>CTNNB1</em> primers were sent for DNA sequencing to investigate mutations in <em>KRAS</em> exon 2 codons 12 and 13, <em>PIK3CA</em> exon 9 codons 542 to 549, and <em>CTNNB1</em> exon 3 codons 32 to 45. Proteins associated with these pathways, including p-ERK1/2, p-mTOR, and β-catenin, were examined using immunohistochemistry. We found that 2 of 11 cases (18.18%) had <em>KRAS</em> mutation (G12V), with almost all cases (90.91%) expressing p-ERK1/2 in the spindle-shaped tumor cells. Only 1 of 9 cases (11.11%) possessed <em>PIK3CA</em> mutation (Q546E), although all cases variably expressed p-mTOR in the tumor cells. None of the case showed <em>CTNNB1</em> mutation and β-catenin expression. Statistical analysis indicated no significant association between gene mutations and their associated proteins in OM (<em>P</em> &gt; .05). In conclusion, the presence of <em>KRAS</em> and <em>PIK3CA</em> mutations, along with p-ERK1/2 and p-mTOR expression in a subset of OM, suggests that the pathogenesis of this tumor may involve the MAPK/ERK and PI3K/mTOR signaling pathways. In contrast, the absence of <em>CTNNB1</em> mutations and β-catenin expression indicates no association between OM pathogenesis and the β-catenin/Wnt signaling pathway. However, further studies with larger sample sizes are needed to confirm these findings.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100856"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753813","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":"Analytical and Clinical Performance of the VENTANA CLDN18 (43-14A) RxDx Assay in Gastric and Gastroesophageal Junction Adenocarcinoma Tissue Samples in SPOTLIGHT and GLOW","authors":"Steven P. Stratton ,&nbsp;Lizhen Pang ,&nbsp;Judith Pugh ,&nbsp;Margarita Kouzova ,&nbsp;Drew Baldwin ,&nbsp;Jannine McDonald ,&nbsp;Rebecka Lawrence-Glaze ,&nbsp;Sean Moran ,&nbsp;Abraham Guerruero ,&nbsp;Diarmuid Moran","doi":"10.1016/j.modpat.2025.100844","DOIUrl":"10.1016/j.modpat.2025.100844","url":null,"abstract":"<div><div>New therapies are needed to treat patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Zolbetuximab is a monoclonal antibody that targets the tight junction protein claudin 18 isoform 2 (CLDN18.2) in gastric or gastroesophageal junction (G/GEJ) adenocarcinoma cells. We describe the analytical and clinical performance of the VENTANA CLDN18 (43-14A) RxDx Assay (Roche Diagnostics Solutions) as a companion diagnostic immunohistochemistry assay for treatment with zolbetuximab. Analytical performance was assessed in commercially available G/GEJ adenocarcinoma samples. Clinical performance was assessed in the context of 2 phase 3 trials (SPOTLIGHT, NCT03504397; GLOW, NCT03653507) of first-line zolbetuximab plus chemotherapy in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma, whose tumors were CLDN18.2 positive (≥75% of viable tumor cells demonstrating moderate-to-strong membrane CLDN18 staining). Staining acceptability rates were assessed in patients whose tumors were tested for CLDN18.2 status using the VENTANA CLDN18 (43-14A) RxDx Assay and who met enrollment eligibility criteria not related to CLDN18.2 status. Progression-free survival and overall survival were evaluated in the enrolled patients. Analytical performance: positive and negative percent agreement compared with immunohistochemistry reference scoring was 100% for between-antibody, between-detection kit, between-instrument, between-day, and within-run precision studies. Interlaboratory reproducibility exceeded 90% average positive and negative agreement between sites and 94% average positive and negative agreement between readers across 3 sites. Clinical performance: among 3783 patient tumor samples, staining acceptability rates exceeded 94%. Patients identified for eligibility using the VENTANA CLDN18 (43-14A) RxDx Assay demonstrated statistically significant improvement in progression-free survival and overall survival with zolbetuximab plus chemotherapy in both phase 3 trials. The VENTANA CLDN18 (43-14A) RxDx Assay demonstrated robust, reproducible analytical performance and clinical utility as a companion diagnostic for first-line zolbetuximab plus chemotherapy in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma, whose tumors were CLDN18.2 positive.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100844"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668000","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 Predicts Survival Across Squamous Tumor Entities From Routine Pathology: Insights From Head and Neck, Esophagus, Lung, and Cervical Cancer.","authors":"Verena Bitto, Xiaofeng Jiang, Michael Baumann, Jakob Nikolas Kather, Ina Kurth","doi":"10.1016/j.modpat.2025.100845","DOIUrl":"10.1016/j.modpat.2025.100845","url":null,"abstract":"<p><p>Computational pathology-based models are becoming increasingly popular for extracting biomarkers from images of cancer tissue. However, their validity is often only demonstrated on a single unseen validation cohort, limiting insights into their generalizability and posing challenges for explainability. In this study, we developed models to predict overall survival using hematoxylin and eosin slides from formalin-fixed paraffin-embedded samples in head and neck squamous cell carcinoma. By validating our models across diverse squamous tumor entities, including head and neck (hazard ratio [HR], 1.58; 95% CI, 1.17-2.12; P = .003), esophageal (nonsignificant), lung (HR, 1.31; 95% CI, 1.13-1.52; P < .001), and cervical (HR, 1.39; 95% CI, 1.10-1.75; P = .005) squamous cell carcinomas, we showed that the predicted risk score captures relevant information for survival beyond head and neck squamous cell carcinoma. Correlation analysis indicated that the predicted risk score is strongly associated with various clinical factors, including human papillomavirus status, tumor volume, and smoking history, although the specific factors vary across cohorts. These results emphasize the relevance of comprehensive validation and in-depth assessment of computational pathology-based models to better characterize the underlying patterns they learn during training.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100845"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668003","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":"Head-to-Head Comparison of 2 Artificial Intelligence Tools for Detecting Lymph Node Metastases in Whole-Slide Pathology Images Within and Beyond Their Intended Use","authors":"Rachel N. Flach,&nbsp;Milan Samuels,&nbsp;Natalie D. ter Hoeve,&nbsp;Nikolas Stathonikos,&nbsp;Trudy G.N. Jonges,&nbsp;Jan E. Freund,&nbsp;Gerben E. Breimer,&nbsp;Willeke A.M. Blokx,&nbsp;Frans Schutgens,&nbsp;Tri Q. Nguyen,&nbsp;Paul J. van Diest,&nbsp;Carmen van Dooijeweert","doi":"10.1016/j.modpat.2025.100905","DOIUrl":"10.1016/j.modpat.2025.100905","url":null,"abstract":"<div><div>The increasing diagnostic workload in pathology, driven by rising cancer incidences, highlights the need for scalable, cost effective solutions. Artificial intelligence (AI) has shown promise in supporting lymph node (LN) metastasis detection, a key prognostic factor in cancer staging. However, the current Conformité Européene In Vitro Diagnostics--certified AI tools are often limited to specific tumor types, reducing their cost efficiency and clinical use. This study evaluates the performance of 2 Conformité Européene In Vitro Diagnostics-certified AI tools—Visiopharm Metastasis Detection App (VMD) and DeepPath LYDIA (DPL)—for multipurpose LN metastasis detection across 6 tumor types, both within and beyond their intended use. We retrospectively analyzed whole-slide images from 455 patients with LN metastases from melanoma, colorectal, head and neck, lung, vulvar, and breast cancer. Both sentinel and nonsentinel LNs were included, with expert pathologists establishing the reference standard, according to clinical practice. Sensitivity was calculated per case and stratified based on metastasis size. False-positive alerts (FPAs) were assessed in 1012 tumor-negative slides. Both applications demonstrated excellent sensitivity for macrometastases across tumor types. DPL showed slightly higher sensitivity for micrometastases and isolated tumor cells compared with VMD, particularly in lung cancer and melanoma. FPA rates were substantial for both tools, with VMD generally producing more alerts, especially in lung and breast cancer. Our findings suggest that a single AI tool may be suitable for LN metastasis detection across multiple tumor types, even beyond its intended use. However, high FPA rates—particularly in lung cancer (inside intended use for DPL)—may limit practical use. Prospective studies are needed to confirm workflow efficiency gains and define optimal implementation strategies. These results support a broader, pragmatic approach to AI validation and regulatory approval, potentially improving the business case for AI adoption in pathology laboratories.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100905"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275388","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 and Molecular Genetic Features of Spindle Cell Rhabdomyosarcoma Harboring ZFP64::NCOA2/3 Fusions: A Series of 14 Cases","authors":"Carina A. Dehner ,&nbsp;Baptiste Ameline ,&nbsp;Fernanda Amary ,&nbsp;John M. Gross ,&nbsp;Ying Zou ,&nbsp;Michael Michal ,&nbsp;Zdenek Kinkor ,&nbsp;Jorge Torres-Mora ,&nbsp;Faizan Malik ,&nbsp;Erica Y. Kao ,&nbsp;Robert W. Ricciotti ,&nbsp;Nasir Ud Din ,&nbsp;Ivy John ,&nbsp;Brendan C. Dickson ,&nbsp;Elizabeth G. Demicco ,&nbsp;Abbas Agaimy ,&nbsp;Konstantinos Linos ,&nbsp;Meera R. Hameed ,&nbsp;Andrew L. Folpe ,&nbsp;Daniel Baumhoer","doi":"10.1016/j.modpat.2025.100906","DOIUrl":"10.1016/j.modpat.2025.100906","url":null,"abstract":"<div><div>Spindle cell rhabdomyosarcomas (SCRMS), recognized by the 2020 <em>World Health Organization Classification of Tumors of Soft Tissue and Bone</em> as a distinct entity, comprise a family of malignant skeletal muscle tumors sharing spindle cell morphology. To date, members of this family include (1) MyoD1-mutated SCRMS/sclerosing rhabdomyosarcomas (RMS), (2) intraosseous SCRMS with FET::<em>TFCP2</em> or <em>MEIS1::NCOA2</em> fusions, and (3) infantile/congenital SCRMS harboring <em>NCOA1/2</em> or <em>VGLL3</em> rearrangements. A rare, emerging subtype of SCRMS has been reported to harbor recurrent <em>ZFP64::NCOA3</em> fusions. We studied 14 cases of this rare SCRMS subtype. The tumors presented in 11 men and 3 women (median age, 39.5 years; range, 22-69 years) and involved the thigh (4), lower leg (2), gluteal soft tissues (2), abdominal wall (1), mediastinum (1), subperiosteal surface of third rib (1), glottis (1), prostate (1), and pelvis (1). Morphologically, 11 tumors showed uniform spindle cell morphology with a fascicular architecture, whereas the remaining 3 tumors demonstrated focal or predominant round cell morphology. Extensive chondro-osseous differentiation was seen in 2 cases. By immunohistochemistry, tumors were variably positive for both desmin and MyoD1 (6 tumors), desmin, MyoD1, and myogenin (1 tumor), desmin alone (3 tumors of which only 1 was also tested for MyoD1), or MyoD1 alone (3 tumors). Smooth muscle actin was noted in 6 of 10 tested cases, and 2 of 5 tested cases showed ALK expression. A <em>ZFP64::NCOA3</em> fusion was detected in 8 tumors, and a <em>ZFP64::NCOA2</em> fusion was detected in 6 tumors. Methylation studies showed all but 1 tested tumor to form a tight cluster, clearly separate from other RMS subtypes and non-RMS morphologic mimics. Clinical follow-up (10/14 cases; median, 35 months; range, 3-108 months) demonstrated local recurrence in 2 patients and distant metastases in 5 patients (median, 12 months; range, at presentation - 106 months). At the time of last follow-up, 5 patients were alive without evidence of disease, 3 patients were alive with disease, and 2 patients died of disease at 34 and 108 months. We conclude that SCRMS with <em>ZFP64::NCOA2/3</em> fusions represents a distinct, clinically aggressive sarcoma characterized by fascicular and sometimes round cell morphology, occasional chondro-osseous differentiation, and variable skeletal muscle marker expression. Recognition of this emerging subtype of SCRMS may have prognostic and therapeutic implications.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100906"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275323","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 “Magnetic Resonance Imaging (MRI)–Adapted Prostate Cancer Risk Tool Incorporating Cribriform and Intraductal Carcinoma” (Modern Pathology 2025 Dec;38(12):100852)","authors":"Ngoc-Nhu Jennifer Nguyen ,&nbsp;Kristen Liu ,&nbsp;Katherine Lajkosz ,&nbsp;Rui Bernardino ,&nbsp;Leyi Bellinda Yin ,&nbsp;Eva Hollemans ,&nbsp;Lisa J. Kroon ,&nbsp;Neil Fleshner ,&nbsp;Geert J.L.H. van Leenders ,&nbsp;Kenneth A. Iczkowski ,&nbsp;Theodorus H. van der Kwast ,&nbsp;Michelle R. Downes","doi":"10.1016/j.modpat.2025.100893","DOIUrl":"10.1016/j.modpat.2025.100893","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100893"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251822","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}