Modern Pathology最新文献

{"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":"2025-10-01","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":"GLUT1 Expression Patterns in Verruciform Acanthotic Vulvar Squamous Intraepithelial Neoplasia, HPV–Independent p53 Wild-Type Squamous Cell Carcinoma and Benign Vulvar Lesions","authors":"Gloria Zhang,&nbsp;Robert A. Soslow,&nbsp;Bin Yang","doi":"10.1016/j.modpat.2025.100900","DOIUrl":"10.1016/j.modpat.2025.100900","url":null,"abstract":"<div><div>Verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN) is a rare type of human papillomavirus (HPV)–independent vulvar squamous cell carcinoma (SCC) precursor lacking aberrant p53 expression. Our recent study demonstrated GLUT1 overexpression in vulvar SCC and identified 2 distinct patterns in HPV-associated high-grade squamous intraepithelial lesions and HPV-independent differentiated vulvar intraepithelial neoplasia. Herein, we expand on our study by assessing GLUT1 expression in 24 cases of vaVIN and 8 cases of associated invasive SCC, compared with 48 cases of benign vulvar squamous lesions, including 40 cases of non-HPV benign vulvar lesions and 8 cases of condyloma associated with low-risk HPV infection. GLUT1 immunohistochemistry (IHC) demonstrated consistent diffuse GLUT1 immunostaining in all vaVIN cases. The GLUT1 immunostaining pattern in vaVIN is characterized by strong membranous staining in the basal layer with suprabasal extension to the full thickness of intermediate layers. In vulvar SCC associated with vaVIN, GLUT1 expression was prominent at the periphery of tumor nests without expression in the central portion. GLUT1 IHC revealed weak peri-papillae or intensified peri-papillae patterns in non-neoplastic vulvar lesions and HPV-related patterns in condyloma. The GLUT1 immunostaining patterns in vaVIN and associated SCC are different from benign mimickers, but similar to those of differentiated vulvar intraepithelial neoplasia and associated SCC, despite distinct molecular alterations and pathways. The latter suggests that upregulation of GLUT1 is likely a common metabolic pathway shared by 2 types of HPV-independent VINs, regardless of p53 status. GLUT1 IHC is highly sensitive in detecting vaVIN. However, the specificity rests on recognizing GLUT1-staining patterns in benign mimickers of vaVIN. Along with HPV chromogenic in situ hybridization and other well-characterized biomarkers, GLUT1 immunochemistry can be a helpful adjunct in assisting the diagnosis of vaVIN.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100900"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206822","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":"2025-09-29","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":"Histopathologic Insights Into Curvularia-Induced Chronic Granulomatous Fungal Sinusitis: A Guide for Surgical Pathologists","authors":"Ashleigh N. Riegler ,&nbsp;Jessica W. Grayson ,&nbsp;Jacob W. Greenway ,&nbsp;Bradford A. Woodworth ,&nbsp;Todd P. McCarty ,&nbsp;Peter G. Pappas ,&nbsp;Sixto M. Leal Jr.","doi":"10.1016/j.modpat.2025.100898","DOIUrl":"10.1016/j.modpat.2025.100898","url":null,"abstract":"<div><div>Chronic granulomatous fungal sinusitis is a rare, debilitating infection characterized by an enlarging mass affecting the orbit, nose, palate, and paranasal sinuses, with occasional intraorbital and intracranial extension. Most cases are reported in subtropical regions, with rare reports from the United States and Europe. Globally, <em>Aspergillus flavus</em> is the primary causative agent in &gt;60% of cases, followed by other <em>Aspergillus</em> species and dematiaceous molds. This study highlights the histopathologic, microbiologic, and molecular diagnostic features of 6 cases with chronic granulomatous fungal sinusitis caused by the emerging pathogen <em>Curvularia</em>, predominantly affecting healthy African Americans in the Southeastern United States. Histopathological examination revealed multinucleated giant cells and noncaseating granulomatous inflammation. Short septate hyphae with bulbous swelling predominated, but there was significant variation in size, shape, and color, with half the cases lacking hyphal pigmentation. Lack of awareness of this emerging entity and variable morphology led to initial misidentification in 3 cases as hyaline septate hyphae <em>(Fusarium</em>), yeasts, and <em>Blastomyces</em>. All cases showed extracellular and intracellular (within multinucleated giant cells) hyphae and round forms with thick refractile cell walls lacking intracellular contents, yielding a characteristic “ghost shell” morphology, indicating fungal nonviability. Consistent with this finding, only 1 culture yielded a live isolate of <em>Curvularia</em>. In addition, 28S rRNA gene sequencing of formalin-fixed paraffin-embedded tissue was required for identification and identified <em>Curvularia lunata</em> (n = 4), <em>Curvularia spicifera</em> (n = 1), and <em>Curvularia</em> spp. (n = 1). One case with 2 hyphal morphologies also grew <em>Aspergillus fumigatus</em>, indicating coinfection. Chronic granulomatous fungal sinusitis, caused by the understudied and persistent pathogen <em>Curvularia</em>, is an emerging threat in immunocompetent hosts, characterized by pathogen persistence in critical facial and cranial structures, despite a significant host response. To accurately diagnose and guide treatment, surgical pathologists must be aware of its expanded geographic range, affected populations, and key histopathologic features, as described herein.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100898"},"PeriodicalIF":5.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176820","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":"Loss of Ribosomal Protein L22 (RPL22) Expression Identifies a Transcriptional Subset of MLH1-Deficient Endometrial Cancers With Lower Numbers of Tumor-Associated Lymphocytes","authors":"Macy L. Osborne-Frazier ,&nbsp;Savannah E. LaBuda ,&nbsp;Molly L. Parrish ,&nbsp;Hannah M. Atkins ,&nbsp;Russell R. Broaddus ,&nbsp;Andrew B. Gladden","doi":"10.1016/j.modpat.2025.100899","DOIUrl":"10.1016/j.modpat.2025.100899","url":null,"abstract":"<div><div>Microsatellite instability-high defines one of the major subsets of endometrial cancer (EC), characterized by defects in DNA mismatch repair, most often by loss of MLH1 protein expression, and sensitivity to immunotherapies. <em>RPL22</em> is selectively mutated in microsatellite instability-high cancers, resulting in loss of protein expression. The significance of this mutation is unknown. An immunohistochemistry assay was developed that reliably detected ECs with ribosomal protein L22 (RPL22) protein loss. With a cohort of ECs, we identified MLH1-deficient cancers with loss of RPL22 expression. Using digital spatial transcriptomics, a subset was identified that was characterized by no expression of RPL22, lower expression of β-2 microglobulin, lack of expression of immune activation pathways, and lower numbers of tumor-associated CD8+ lymphocytes. β-2 Microglobulin, which is necessary for antigen presentation to T lymphocytes, was decreased in EC cell lines with <em>RPL22</em> knocked down. Neither RPL22 expression nor levels of tumor-associated T lymphocytes were associated with tumor mutation burden or PD-L1 expression, 2 biomarkers that are assessed in patients considered for immunotherapies. This study provides the first evidence that RPL22 deficiency is an easily measured indicator of a unique subset of MLH1-deficient ECs that can be characterized as immune low. Our study suggests that patients with RPL22-deficient tumors could represent poor candidates for CD8+ T-cell–based immunotherapies, a current frontline therapy for MLH1-deficient ECs.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100899"},"PeriodicalIF":5.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176843","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":"EWSR1::CREM Tumor of the Kidney With Florid Tubular Proliferation: Expanding the Spectrum of Biphasic Renal Tumors","authors":"Sean R. Williamson,&nbsp;Reza Alaghehbandan,&nbsp;Jesse K. McKenney,&nbsp;Josephine K. Dermawan","doi":"10.1016/j.modpat.2025.100869","DOIUrl":"10.1016/j.modpat.2025.100869","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100869"},"PeriodicalIF":5.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117979","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":"A Distinctive DICER1-Related Wilms-Like Uterine Tumor: A Report of Eight Cases","authors":"Gulisa Turashvili ,&nbsp;Sabrina Croce ,&nbsp;Ben Davidson ,&nbsp;Silke Hausladen ,&nbsp;Olesya Solheim ,&nbsp;Silvestro Carinelli ,&nbsp;Mariano Lombardi ,&nbsp;Diana Lim ,&nbsp;Kyle Devins ,&nbsp;Lawrence Hsu Lin ,&nbsp;Dora Dias-Santagata ,&nbsp;Robert H. Young ,&nbsp;Esther Oliva","doi":"10.1016/j.modpat.2025.100895","DOIUrl":"10.1016/j.modpat.2025.100895","url":null,"abstract":"<div><div>The presence of <em>DICER1</em> mutations associated with overlapping morphologic features in tumors arising at different sites has been suggested to define an emerging category of <em>DICER1</em>-related neoplasms. We undertook a clinicopathologic and molecular characterization of uterine tumors originally diagnosed as Wilms tumors to ascertain if they belong to the spectrum of <em>DICER1</em>-related neoplasms. Of 8 patients with a median age of 36.5 (17-69) years, 5 underwent hysterectomy, 2 endometrial curettings, and 1 polypectomy. Most tumors were centered in the endometrium, and 6 were polypoid with a median size of 8 (3.5-16) cm. All showed a variable admixture of primitive mesenchyme and epithelial-like elements set in a hypocellular, edematous to focally myxoid stroma. The epithelial-like elements were the most extensive component, showing a lobular arrangement, including variably sized and shaped primitive tubules with focal confluent/solid growth and cribriforming, as well as glomeruloid and rosette-like structures. Some primitive tubules had intraluminal projections in 3 tumors, imparting an adenosarcoma-like appearance. Scattered glands with fetal-type epithelium were seen in 7 tumors. Rhabdomyosarcomatous differentiation was present in 6 tumors, and neuroectodermal differentiation and fetal-type cartilage in 3 tumors each (including 2 with both features). <em>DICER1</em> sequencing was successful in 5 of 6 tumors tested, with 4 harboring <em>DICER1</em> mutations, including all 3 with neuroectodermal differentiation and adenosarcoma-like foci. Fetal-type cartilage was present in 2 of 4 <em>DICER1</em>-mutant tumors and 1 tumor with unknown <em>DICER1</em> status. Follow-up was available for 6 patients. The patient with <em>DICER1</em> wild-type tumor (associated with low-grade endometrial endometrioid carcinoma and <em>KRAS</em> mutation) died of disease at 9 months. Of 4 patients with <em>DICER1</em>-mutant tumors, 1 recurred at 7.5 months, 2 were alive without disease at 12 and 38 months, respectively, and 1 was alive with unknown disease status at 31 months. Another patient with unknown <em>DICER1</em> status was alive at 196 months. Uterine tumors diagnosed as Wilms tumors belong to the spectrum of <em>DICER1</em>-related neoplasms at this site and are best described as a “<em>DICER1</em>-related Wilms-like uterine tumor.” These unique tumors are likely part of the larger category of “<em>DICER1</em>-related primitive polyphenotypic neoplasm,” warranting further studies.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100895"},"PeriodicalIF":5.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150130","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":"Integrated Multiomics Analysis of Microsatellite Instability-High Colorectal Cancer Identifies a Subtype With Poor Outcome","authors":"Gangzhi Zhang ,&nbsp;Biting Zhou ,&nbsp;Xiaoxian Xu ,&nbsp;Yang Che ,&nbsp;Wenjie Hong ,&nbsp;Shu Zheng ,&nbsp;Suzhan Zhang ,&nbsp;Wangxiong Hu ,&nbsp;Yanmei Yang","doi":"10.1016/j.modpat.2025.100896","DOIUrl":"10.1016/j.modpat.2025.100896","url":null,"abstract":"<div><div>Up to 50% of patients with metastatic microsatellite instability-high (MSI-H) colorectal cancer (CRC) are resistant to immunotherapy and experience progression or recurrence after treatment. We integrated the genomic, epigenomic, transcriptomic, and proteomic data for 99 patients in a Chinese MSI-H CRC cohort. Proteomic profiling of primary tumors clearly classified MSI-H tumors into 2 subtypes. We found that the 2 subtypes have different mutational signatures, enriched pathways, gene fusion networks, and clinical outcomes. Notably, NCAM1 could serve as a potential biomarker for checkpoint inhibitor response in MSI-H CRC. Thus, there is an urgent need to stratify the MSI-H group into different subtypes and adopt more targeted therapies to prolong patient survival.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100896"},"PeriodicalIF":5.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138299","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 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":"2025-09-22","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":"An Integrated Clinical Genomic and Transcriptomic Subgrouping of Central Chondrosarcoma","authors":"Debora M. Meijer ,&nbsp;Sanne Venneker ,&nbsp;Baptiste Ameline ,&nbsp;Zeynep Erdem ,&nbsp;Sara Cardoso ,&nbsp;Dina Ruano ,&nbsp;Inge H. Briaire-de Bruijn ,&nbsp;Brendy E. van den Akker ,&nbsp;Pauline M. Wijers-Koster ,&nbsp;Claire H.J. Scholte ,&nbsp;Veroniek M. van Praag ,&nbsp;Michiel A.J. van de Sande ,&nbsp;Marieke L. Kuijjer ,&nbsp;Daniel Baumhoer ,&nbsp;Noel F.C.C. de Miranda ,&nbsp;Judith V.M.G. Bovée","doi":"10.1016/j.modpat.2025.100894","DOIUrl":"10.1016/j.modpat.2025.100894","url":null,"abstract":"<div><div>Central conventional chondrosarcoma, a malignant cartilage-producing bone tumor, is the second most common bone sarcoma. Chondrosarcomas are histologically graded, which is so far the best predictor of survival. Early mutations in isocitrate dehydrogenase 1 (<em>IDH1</em>) and <em>IDH2</em> genes are frequent, leading to the production of the oncometabolite D-2-hydroxyglutarate, which affects DNA methylation, resulting in a preferred chondrogenic differentiation over osteogenic differentiation of mesenchymal stem cells, which are currently considered the precursor cells of chondrosarcoma. DNA methylation profiling has previously revealed distinct profiles between <em>IDH</em>-mutant and <em>IDH</em>–wild-type chondrosarcomas, but the presence of further DNA methylation subgroups indicates that classification based solely on <em>IDH</em> status is too simplistic. In this study, we aim to identify biological subgroups in a total of 116 chondrosarcomas by integrating clinical data, <em>IDH</em> mutation status, gene expression, and genome-wide loss of heterozygosity (LOH). Clinical associations were observed between several factors, including sex and histological grade, as well as tumor site and <em>IDH</em> mutation status. RNA sequencing and genome-wide LOH confirmed the distinction between <em>IDH</em>–wild-type and <em>IDH</em>-mutant chondrosarcomas, where the number of chromosome arms affected by LOH was significantly higher in <em>IDH</em>–wild-type tumors than in <em>IDH</em>-mutant tumors. However, no clear subgroups emerged within each <em>IDH</em> group. Further clustering on RNA expression of differentiation markers identified subgroups characterized by chondrogenic, osteogenic, resting chondrocyte, or dedifferentiated profiles. These different subgroups showed a specific clinical presentation and suggest different precursor cells. Instead of a simple dichotomy between <em>IDH</em>-mutant and <em>IDH</em>–wild-type, our integrated approach highlights interconnected clinical, genomic, and transcriptomic patterns that offer a more nuanced view of chondrosarcoma biology and might potentially guide treatment stratification.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100894"},"PeriodicalIF":5.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113777","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}