Modern Pathology最新文献

{"title":"Defining NECTIN4 Amplification and Protein Expression in Urothelial Carcinoma and Histologic Subtypes","authors":"John C. Cheville ,&nbsp;Jacob J. Orme ,&nbsp;Sounak Gupta ,&nbsp;Fabrice Lucien-Matteoni ,&nbsp;Robert J. Karnes ,&nbsp;Prabin Thapa ,&nbsp;Abhinav Khanna ,&nbsp;Shruthi Naik ,&nbsp;Vidit Sharma ,&nbsp;Igor Frank ,&nbsp;Lance Pagliaro ,&nbsp;Fernando Quevedo ,&nbsp;Burak Tekin ,&nbsp;Ryan Knudson ,&nbsp;Patricia Greipp ,&nbsp;Carrie Brandt ,&nbsp;Justin Koepplin ,&nbsp;Brian Costello ,&nbsp;Elisabeth Heath ,&nbsp;George Vasmatzis ,&nbsp;Paras H. Shah","doi":"10.1016/j.modpat.2025.100928","DOIUrl":"10.1016/j.modpat.2025.100928","url":null,"abstract":"<div><div>Chromosome 1q23.3 is commonly amplified in metastatic urothelial carcinoma (UC). This region contains <em>NECTIN4</em> that encodes for a membrane protein, and amplification may result in increased NECTIN4 expression. Enfortumab vedotin, an antibody-drug conjugate, targets NECTIN4. The objective of this study was to determine the frequency of <em>NECTIN4</em> amplification by fluorescence in situ hybridization and protein expression by immunohistochemistry in primary UC and subtypes. Tissue microarrays (TMA) were constructed from 841 patients who underwent cystectomy between 2000 and 2020. In 218 patients, TMA were constructed from a concurrent pelvic lymph node metastasis. <em>NECTIN4</em> amplification varied by subtype and was present in 18% of UCs, 13% of UCs with squamous differentiation, 25% of micropapillary carcinoma, 19% of plasmacytoid carcinoma, 17% of high-grade neuroendocrine carcinoma, 8% of pure squamous cell carcinoma, 6% of nested carcinoma, and 6% of sarcomatoid carcinoma. Tumors with <em>NECTIN4</em> amplification had significantly higher H scores compared with nonamplified tumors (<em>P</em> &lt; .0001), and H scores increased with increasing copy number in amplified tumors. <em>NECTIN4</em> amplification was identified in 17% of lymph node metastases, and 70% of amplified primary tumors had an amplified metastasis, which increased to &gt;90% when whole section fluorescence in situ hybridization was performed in discordant TMA cases. There was a moderate agreement between immunohistochemical staining of primary and lymph node metastases (kappa = 0.41). <em>NECTIN4</em> amplifications vary in frequency among UC and subtypes, and amplifications result in higher protein expression. Bladder cancer with <em>NECTIN4</em> amplification may have limited protein expression, whereas nonamplified tumors may show high expression. There was concordance of <em>NECTIN4</em> amplification and protein expression between primary and lymph node metastases, but there were a small number of cases with amplified primary tumors and unamplified metastases, primary tumors with high protein expression, and metastasis with low expression.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100928"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422125","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":"Tumors of the Synovium","authors":"Yee Lin Tang ,&nbsp;Jad Husseini ,&nbsp;G. Petur Nielsen","doi":"10.1016/j.modpat.2025.100913","DOIUrl":"10.1016/j.modpat.2025.100913","url":null,"abstract":"<div><div>The synovium is an integral component of synovial joints, as well as extra-articular structures such as the tenosynovium and bursae. This article reviews normal histology and the immunohistochemical profile of the synovium. It also discusses several common and distinctive intra-articular and extra-articular tumors arising in synovium-lined structures, such as tenosynovial giant cell tumor, synovial chondromatosis, and the recently described chondroid synoviocytic neoplasm. Among these, tenosynovial giant cell tumor and chondroid synoviocytic neoplasm are the only true neoplasms of synoviocytes. An emerging entity, calcified chondroid mesenchymal neoplasm, will also be mentioned. The clinical, radiologic, morphologic, and molecular genetics features of these tumors are discussed, along with their differential diagnoses. In addition, the article addresses other rare lesions, such as lipoma arborescens, a nonneoplastic condition, and synovial hemangioma, which often present as an intra-articular mass. Finally, a brief overview of selected primary intra-articular sarcomas is provided.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100913"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301875","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 Comprehensive Mutational and Histopathological Analysis of STK11-Mutant Non–Small Cell Lung Carcinomas","authors":"Cristiana M. Pineda ,&nbsp;Zoe Guan ,&nbsp;Hyunwoo Kwon ,&nbsp;Deepa Rangachari ,&nbsp;Daniel B. Costa ,&nbsp;Paul A. VanderLaan","doi":"10.1016/j.modpat.2025.100938","DOIUrl":"10.1016/j.modpat.2025.100938","url":null,"abstract":"<div><div>Despite recent advances in the understanding of genomic and immunopathological mechanisms of lung cancer, this disease remains the leading cause of cancer-related deaths in the United States. <em>STK11</em> (<em>LKB1</em>) mutations are present in approximately 20% of non–small cell lung cancers (NSCLCs) and drive tumor progression through disruption of cellular metabolism, polarity, and stress responses, ultimately leading to immune evasion and resistance to cancer therapy. Although these tumors are associated with poor prognoses, the clinicopathological significance of different <em>STK11</em> mutation subtypes and their associations with tumor histology, cellular behavior, metastatic potential, and clinical outcomes remain incompletely understood. In this study, we retrospectively analyzed a large cohort of <em>STK11</em>-mutant and <em>STK11</em> wild-type NSCLCs using a combination of next-generation sequencing, immunologic biomarkers, histopathological characterization, and radiographic imaging. Overall, we demonstrate that <em>STK11</em>-mutant tumors display diverse molecular and morphologic features and are associated with high rates of aggressive histopathological growth patterns, lymphovascular invasion, and spread through the airspaces. Among stage 4 cases, <em>STK11</em> mutations had notable differences in organotropism, with the <em>STK11</em>-loss cohort in particular demonstrating the highest rates of brain metastases at the time of initial diagnosis. Furthermore, among stage 4 cases, whereas all <em>STK11</em> mutation types resulted in decreased overall survival probability compared with the <em>STK11</em> wild-type cohort, the effect appeared most pronounced among the <em>STK11</em>-loss/<em>KRAS</em>-mutant group. These findings underscore the heterogeneity of <em>STK11</em>-mutant NSCLCs and highlight the opportunity for further investigation into specific <em>STK11</em> mutation subtypes in guiding prognosis and therapeutic decision-making for individuals with lung cancer.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100938"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573880","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":"Unraveling Round Cell Sarcomas: A Contemporary Diagnostic Guide Beyond Ewing Sarcoma","authors":"Raul Ezequiel Perret","doi":"10.1016/j.modpat.2025.100914","DOIUrl":"10.1016/j.modpat.2025.100914","url":null,"abstract":"<div><div>Round cell sarcomas represent a continuously evolving category of malignant mesenchymal tumors, currently encompassing 5 main tumor subtypes: Ewing sarcoma, <em>Capicua Transcriptional Repressor</em> (CIC)<em>–</em>rearranged sarcoma, sarcomas with <em>BCL6-corepresso</em>r (<em>BCOR</em><em>)</em>-genetic abnormalities, <em>POZ/BTB and AT hook containing zinc finger 1</em> (<em>PATZ1</em><em>)</em>-rearranged sarcoma, and <em>nuclear factor of activated T cells 2</em> (<em>NFATC2</em><em>)</em>-rearranged sarcoma. These tumors show some degree of histomorphologic overlap, which, coupled with their infrequency, may render their diagnosis challenging for the pathologist. Furthermore, although ancillary techniques like immunohistochemistry and molecular tests can be of diagnostic aid, they are still limited by inherent sensitivity and specificity issues and cannot replace meticulous integration of clinical and radiologic findings. This review is focused on (1) providing a guide for tackling the diagnosis of round cell sarcomas and their mimics using an integrative approach combining demographics, clinicoradiologic data, histomorphology, and ancillary techniques and (2) detailing the most recent information on round cell sarcomas from the latest World Health Organization classification of Bone and Soft Tissue Tumors (fifth edition).</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100914"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301902","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":"Clinical-Grade Interpretable Artificial Intelligence Tool for Automated Detection of Lymph Node Metastasis in Prostate Cancer","authors":"Fatemeh Zabihollahy ,&nbsp;Kangdi Shi ,&nbsp;Collins Wangulu ,&nbsp;Ioannis Prassas ,&nbsp;Mehdi Masoomian ,&nbsp;Rola Saleeb ,&nbsp;Manal Y. Gabril ,&nbsp;Theodorus van der Kwast ,&nbsp;Neil E. Fleshner ,&nbsp;George M. Yousef","doi":"10.1016/j.modpat.2025.100934","DOIUrl":"10.1016/j.modpat.2025.100934","url":null,"abstract":"<div><div>Lymph node metastasis (LNM) is a critical prognostic factor for prostate cancer and is associated with increased mortality and poor clinical outcomes, necessitating modifications to therapeutic strategies. Manual histopathological evaluation of lymphatic tissue on glass slides is labor intensive, subject to interobserver variability, and prone to error. Deep learning approaches offer substantial promise in enhancing the accuracy and efficiency of LNM detection; however, their efficacy is contingent upon the availability of extensive annotated data sets. In this study, we developed a novel artificial intelligence (AI)–driven model leveraging a limited data set of annotated samples. By identifying and incorporating the most informative instances from unlabeled data into the training process, the model optimizes its learning trajectory through iterative error correction. Validation was performed on independent data sets from 3 academic medical centers, comprising 787 whole slide images and &gt;2000 lymph node tissues. On a combined test set of 165 positive and 622 negative cases, the model achieved an area under the receiver operating characteristic curve of 0.94 (95% CI, 0.92-0.96), with slide-level sensitivity and specificity of 96% (95% CI, 92%-99%) and 92% (95% CI, 89%-94%), respectively. Importantly, the AI algorithm identified micrometastases in 17 cases that were initially missed by pathologists. Although pathologists exhibited a 9% miss rate in micrometastasis detection, the AI model demonstrated a significantly lower miss rate of 3% using the institutional data set, highlighting its potential for clinical deployment. This fully autonomous and reproducible method also significantly reduced slide examination times compared with both general and genitourinary pathologists (<em>P</em> &lt; .001). The proposed method demonstrated interpretability by identifying metastasis regions on whole slide images labeled as positive. Ablation studies substantiate the robustness of the proposed methodology for LNM detection.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100934"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505776","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":"Optical Genome Mapping in Pediatric Hematologic Malignancies: High Diagnostic Yield and Unique Insights Across Leukemia Subtypes","authors":"Travis H. Smith ,&nbsp;Jeffrey Jean ,&nbsp;Stephen Phan ,&nbsp;Alexandra E. Kovach ,&nbsp;Karin Miller ,&nbsp;Jennifer Han ,&nbsp;Katherine Ma ,&nbsp;Cindy Fong ,&nbsp;Andrew Doan ,&nbsp;Deepa Bhojwani ,&nbsp;Gordana Raca","doi":"10.1016/j.modpat.2025.100937","DOIUrl":"10.1016/j.modpat.2025.100937","url":null,"abstract":"<div><div>Hematologic neoplasms in pediatric patients have different genomic profiles compared with the same malignancies in adults, with copy number abnormalities (CNAs) and balanced structural variants (SVs) being the most prevalent types of oncogenic drivers. Consequently, we hypothesized that optical genome mapping (OGM), as a new method for genome-wide, high-resolution detection of CNAs and balanced SVs, could represent a powerful testing approach for pediatric leukemias. This study compared the performance of OGM in the detection of clinically significant variants with current standard-of-care (SOC) diagnostic methodologies, including karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray, and a custom pediatric next-generation sequencing panel, OncoKids. In a retrospective review of results from SOC genetic testing and OGM for 100 de novo or relapsed pediatric hematologic neoplasms, full concordance was observed in 71% of cases. A clinically significant finding (tier 1 or 2 based on the Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists guidelines) was missed by OGM in 7 cases, but in 22 cases, OGM identified additional tier 1 or 2 findings missed by SOC testing. The highest increase in diagnostic yield was noted in T-lymphoblastic leukemia/lymphoma (T-ALL), with nearly 40% (9/23) of T-ALL cases having additional tier 1 or 2 findings detected using OGM. The main advantage of OGM was the ability to detect cytogenetically cryptic, balanced rearrangements not targeted by routine FISH probes or OncoKids, whereas its main limitation was low resolution for identifying copy-neutral loss of heterozygosity. As a single assay, OGM detected the majority (92%) of clinically significant variants identified by the combined use of karyotyping, FISH, chromosomal microarray, and OncoKids, and revealed additional tier 1 or 2 variants missed by SOC testing in 22% of the cases. Our study shows that OGM represents a powerful assay for detection of CNAs and balanced SVs in pediatric hematologic neoplasms.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100937"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534644","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":"Diagnostic Utility and Clinicopathologic Associations of Histone H3 Lysine 27 Trimethylation (H3K27me3) Immunohistochemistry for Merkel Cell Carcinoma","authors":"Steve Hrycaj ,&nbsp;May P. Chan ,&nbsp;Sriram Venneti ,&nbsp;Kelly L. Harms ,&nbsp;Paul W. Harms","doi":"10.1016/j.modpat.2025.100945","DOIUrl":"10.1016/j.modpat.2025.100945","url":null,"abstract":"<div><div>Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor that must be distinguished from other cutaneous tumors and metastatic small cell carcinoma (SmCC). Additional diagnostic markers are limited for MCC with immunophenotypic aberrancy. MCC can display immunohistochemical loss of the epigenetic marker histone H3 lysine 27 trimethylation (H3K27me3), but to our knowledge, the diagnostic utility of this observation has not been evaluated. In this study, we investigate H3K27me3 labeling in MCC (n = 195), cutaneous epithelial tumors (n = 48), noncutaneous SmCCs (n = 56), and olfactory neuroblastoma (n = 11), comparing with diagnostic markers, cytokeratin-20, neurofilament, SATB2, and POU4F3. H3K27me3 patterns in MCC included global loss, variable/mosaic labeling, and diffuse labeling. Global loss significantly associated with polyomavirus negativity, squamous atypia, and sarcomatoid change. Tumors with global loss displayed EZHIP expression (9 cases) and <em>SUZ12</em> mutation (1 case). Low but retained H3K27me3 labeling was associated with longer overall and MCC-specific survival. Diagnostically, H3K27me3 labeling in MCC was significantly lower than potential mimics, and global loss of H3K27me3 was highly specific for MCC; stronger H3K27me3 labeling was not informative. Considering reduced/absent H3K27me3 as favoring MCC, diagnostic performance was similar to SATB2. However, H3K27me3 displayed consistent performance in MCC with challenging immunophenotypes, unlike SATB2. In summary, we expand upon descriptions of H3K27me3 labeling in MCC and characterize patterns of H3K27me3 in other tumor types including SmCCs and olfactory neuroblastoma. Our findings support diagnostic utility for the widely available marker H3K27me3 in MCC, with weaker labeling favoring MCC over mimics in challenging cases.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100945"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695738","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":"Updates in Peripheral Nerve Sheath and Adipocytic Tumors","authors":"Sarah Dry","doi":"10.1016/j.modpat.2025.100929","DOIUrl":"10.1016/j.modpat.2025.100929","url":null,"abstract":"<div><div>Certain areas in peripheral nerve sheath and adipocytic neoplasm diagnosis historically were characterized by a lack of clarity and consensus regarding terminology, diagnostic criteria, and prognosis. Recent work has led to important clarifications in diagnostic criteria and/or outcome data for neurofibromas with atypia and MDM2 amplification–negative adipocytic tumors. However, these clarifications remain incompletely recognized by many pathologists, in part due to the paucity of these neoplasms. This paper reviews the history and recent advances in diagnostic criteria, terminology, and understanding of prognosis for neurofibromas with atypia, malignant peripheral nerve sheath tumor (MPNST), malignant melanotic nerve sheath tumor, and atypical spindle cell/pleomorphic lipomatous tumor. Melanoma may be histologically identical to MPNST, and this paper also provides an overview of helpful clinical and molecular features that allow accurate identification of melanoma, including undifferentiated, dedifferentiated, and transdifferentiated melanoma, and their distinction from MPNST.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100929"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438642","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":"Replacing Molecular Testing With Next-Generation Immunohistochemistry: I Can Diagnose That Soft Tissue Tumor With a Single Antibody!","authors":"Jason L. Hornick","doi":"10.1016/j.modpat.2025.100912","DOIUrl":"10.1016/j.modpat.2025.100912","url":null,"abstract":"<div><div>Immunohistochemistry plays a central role in the diagnosis of soft tissue tumors. Conventional immunohistochemistry uses antibodies directed against lineage-restricted antigens, in an attempt to identify a line of differentiation and narrow down the differential diagnosis. However, in most cases, such markers are inadequate to reach a specific diagnosis. Many soft tissue tumors harbor recurrent, often disease-defining molecular genetic alterations. Increasingly, fluorescence in situ hybridization analysis or next-generation sequencing is employed for identification of such alterations as a diagnostic adjunct. In recent years, immunohistochemistry has been used as a surrogate for such molecular genetic or cytogenetic analysis; this approach can identify the protein correlates of genetic alterations. Numerous next-generation antibodies directed against the protein products of a wide range of genetic alterations (such as gene fusions, amplifications, deletions, and point mutations) have entered our diagnostic armamentarium. In addition, gene expression profiling has uncovered diagnostically useful markers for immunohistochemistry. Finally, epigenetic alterations (eg, methylation) can also be assessed by immunohistochemistry. This review will provide examples of the application of contemporary molecular immunohistochemistry for soft tissue tumor diagnosis.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100912"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292980","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":"Cribriform Tumor of the Skin: Identification of 6q and 9q Loss as a Recurrent Cytogenomic Alteration","authors":"Shira Ronen ,&nbsp;David G. Grand ,&nbsp;Wahab A. Khan ,&nbsp;Michael Michal ,&nbsp;Donald C. Green ,&nbsp;Jennifer S. Ko ,&nbsp;Robert E. LeBlanc ,&nbsp;Jeffrey M. Cloutier","doi":"10.1016/j.modpat.2025.100916","DOIUrl":"10.1016/j.modpat.2025.100916","url":null,"abstract":"<div><div>Cribriform tumor is a rare sweat-gland neoplasm of uncertain malignant potential. Although its histopathologic features are well described, the molecular underpinnings of cribriform tumor remain incompletely characterized. We performed comprehensive molecular profiling of 6 cribriform tumors from 3 institutions using whole-exome sequencing, transcriptome sequencing, and single-nucletide polymorphism array copy number analysis. The cohort included 3 women and 3 men (median age, 54 years; range, 40-66 years), with tumors measuring 0.3 to 2.0 cm. Most arose on the extremities, with one located on the back. The most consistent genomic alteration was arm-level losses of chromosomes 6q and 9q, detected in 5 out of 6 cases. These alterations were validated across independent sequencing and single-nucletide polymorphism array platforms. Whole-exome sequencing identified likely pathogenic variants in 2 tumors (<em>CHEK2</em> p.R145W and <em>NF1</em> p.R1830H). No gene fusions were detected. Taken together, these findings provide independent confirmation that 6q/9q loss represents a consistent cytogenomic alteration in cribriform tumor, supporting its use as a molecular hallmark of this tumor.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100916"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308501","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}