Human pathology最新文献

{"title":"Tumor infiltrating lymphocytes in breast cancer: A narrative review with focus on analytic validity, clinical validity, and clinical utility","authors":"Brian S. Finkelman ,&nbsp;Huina Zhang ,&nbsp;David G. Hicks ,&nbsp;David L. Rimm ,&nbsp;Bradley M. Turner","doi":"10.1016/j.humpath.2025.105866","DOIUrl":"10.1016/j.humpath.2025.105866","url":null,"abstract":"<div><div>Since Dr. Stephen Paget first proposed the “seed and soil” hypothesis in 1889, the tumor microenvironment has been recognized as a crucial component of tumor growth, progression, and metastasis. Tumor-infiltrating lymphocytes (TILs) are an important part of the tumor microenvironment, as well as an important prognostic and predictive biomarker for many cancers. This narrative review aims to summarize the current literature on the analytic validity, clinical validity, and clinical utility of TILs in breast cancer, including discussion of all major clinical subtypes. We summarize the current recommendations of the International Immuno-Oncology Biomarker Working Group on Breast Cancer for pathologist assessment and reporting of TILs, the state of the evidence justifying their usefulness as a biomarker in breast cancer, particularly for triple-negative and HER2+ breast cancer, as well as ongoing challenges and areas of future development, such as automated TIL scoring algorithms. Based on currently available evidence as well as ongoing clinical trials, we expect that TILs will increasingly become a cost-effective, easily available, and widely utilized biomarker in breast cancer, helping to guide treatment selection and optimization of therapy for many patients.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105866"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen receptor-low positive breast cancer: Historical perspective and recent advancements","authors":"Huina Zhang ,&nbsp;Madhurya Ramineni ,&nbsp;Xiaoxian Li","doi":"10.1016/j.humpath.2025.105820","DOIUrl":"10.1016/j.humpath.2025.105820","url":null,"abstract":"<div><div>The assessment of estrogen receptor<span><span> (ER) expression in breast cancer, has traditionally been performed using ligand-binding assays, followed by immunohistochemistry<span>, and is widely used to predict tumor response to endocrine therapy. ER-low positive breast cancer, formally defined in the 2020 ASCO/CAP testing guidelines, represents a small subset of invasive breast cancers characterized by 1 %–10 % of ER staining. Emerging evidence suggests that ER-low positive tumors constitute a heterogeneous group in terms of clinicopathologic features, molecular profiles, prognosis, and responsiveness to endocrine therapy. These tumors frequently behave more like ER-negative cancers, often displaying a more aggressive </span></span>clinical course compared to classic ER-positive tumors. The clinical benefit of endocrine therapy in this subset remains uncertain, posing a significant challenge in determining the optimal treatment strategies. This review offers both a historical perspective and a comprehensive, up-to-date analysis of recent advancements in the understanding of ER-low positive breast cancer, with a focus on tumor biology, pathological evaluation, and clinical implications.</span></div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105820"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in papillary tumors of breast","authors":"Raza S. Hoda ,&nbsp;Hannah Y. Wen","doi":"10.1016/j.humpath.2025.105759","DOIUrl":"10.1016/j.humpath.2025.105759","url":null,"abstract":"<div><div>This review addresses common diagnostic challenges associated with papillary breast tumors—a rare but significant category of breast lesions. Despite their low incidence, papillary tumors are frequently encountered in breast pathology consultation practice due to their overlapping terminology and perplexing immunohistochemical results. Issues regarding assessment of invasive carcinoma in the setting of solid papillary carcinoma and encapsulated papillary carcinoma are covered. Emerging entities, such as tall cell carcinoma with reversed polarity and invasive lobular carcinoma mimicking solid papillary carcinoma, are discussed. Additionally, pragmatic guidance is provided for managing papillary breast tumors on needle core biopsy. Herein, we aim to provide clarity and confidence to surgical pathologists dealing with papillary breast tumors—mammary Medusa—equipping them with practical knowledge to better navigate this complex area of breast pathology.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105759"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updates on utility of immunohistochemistry in diagnosis of metastatic breast cancer","authors":"Hongxia Sun,&nbsp;Aysegul A. Sahin,&nbsp;Qingqing Ding","doi":"10.1016/j.humpath.2025.105821","DOIUrl":"10.1016/j.humpath.2025.105821","url":null,"abstract":"<div><div><span>Accurate diagnosis of metastatic breast carcinoma is essential for effective clinical management. </span>Immunohistochemistry<span> plays a pivotal role in confirming or excluding a breast origin. In this review, we discuss both traditional and newly identified breast cancer markers, with a particular focus on studies related to TRPS1, and share our experience in applying this marker. Additionally, we explore the challenges associated with using these markers to differentiate metastatic breast cancer from malignancies of other origins.</span></div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105821"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Best pathology practices for HER2 testing interpretation, including HER2-low and ultralow, in the era of HER2-directed antibody drug conjugates (ADCs), aligned with the 2018 CAP/ASCO HER2 guidelines","authors":"Monalyn Marabi,&nbsp;Gary M. Tse","doi":"10.1016/j.humpath.2025.105818","DOIUrl":"10.1016/j.humpath.2025.105818","url":null,"abstract":"<div><div>With the emergence of studies showing clinical response to novel human epidermal growth factor receptor 2(HER2)-targeted treatments among HER2-low and HER2-ultralow metastatic breast cancer patients, this gives hope to patients failing to respond to conventional treatment. Hence, the interest in identifying these group of patients is becoming important. Pathologists' interpretation and scoring of HER2 immunohistochemistry (IHC) was challenged from a dichotomous way to a ternary way of reporting. But HER2 IHC testing is affected by a number of pre-analytic, analytic and post-analytic challenges that could affect interpretation at the lower HER2 protein expression range. Interobserver variability among pathologists and inter-assay variabilities likewise posses a challenge since prior guidelines’ emphasis were focused on recognizing HER2-overexpressed from HER2-non-overexpressed tumours. In consideration of these clinical trials, the American Society of Clinical Oncologists and College of American Pathologists (ASCO/CAP) updated and reaffirmed the guideline on HER2 testing in 2018 and in 2023, with the criteria for HER2 categories redefined. Here, we reviewed the definition and differences among HER2-low, HER2-ultralow and HER2-null breast cancer cases as well as the different challenges on HER2 IHC testing encountered and reported, including best pathology practice recommendations to avaoid or minimize these challenges.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105818"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updates and controversies in breast pathology","authors":"Yan Peng ,&nbsp;Lori A. Erickson","doi":"10.1016/j.humpath.2025.105864","DOIUrl":"10.1016/j.humpath.2025.105864","url":null,"abstract":"<div><div>In the rapidly evolving molecular era, this special issue on breast pathology aims to provide a timely update on recent advancements and to foster thoughtful discussion on current controversies across the diverse landscape of breast lesions. Particular attention is given to the integration of morphology, immunophenotypic profiles, and molecular alterations, all of which have significant implications for patient management and prognosis. This issue aspires to serve as an evidence-based, and problem-solving reference to support and enhance best pathology practices.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105864"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging molecular Therapeutic targets in breast Cancer: Pathologic identification and clinical implications","authors":"Aysegul A. Sahin ,&nbsp;Hui Chen ,&nbsp;Huang Xiao ,&nbsp;Damodaran Senthil ,&nbsp;Funda Meric-Bernstam","doi":"10.1016/j.humpath.2025.105881","DOIUrl":"10.1016/j.humpath.2025.105881","url":null,"abstract":"<div><div>Breast carcinoma represents a biologically heterogeneous group of malignancies with diverse clinical behaviors, highlighting the need for robust molecular markers to support accurate diagnosis, prognosis, and therapeutic decision-making. Histopathologic evaluation and assessment of established biomarkers, including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, remain central to clinical management, yet these biomarkers do not fully capture the disease complexity. Advances in genomics have enabled identification of intrinsic breast cancer subtypes, improving risk stratification and personalization of therapy. New molecular technologies such as next-generation sequencing and liquid biopsy approaches have uncovered actionable genomic alterations and allow for real-time monitoring. Emerging biomarkers such as cyclin E overexpression, <em>BRCA1/2</em> mutations, and mismatch repair deficiency provide additional prognostic and predictive value, especially in guiding targeted therapies. The tumor microenvironment, including immune cell infiltration and stromal composition, has also gained recognition for its role in modulating tumor progression and therapeutic response. Liquid biopsy tools, including analysis of circulating tumor DNA, circulating tumor cells, and exosomes, offer promising non-invasive methods for disease surveillance and early detection of resistance. High-throughput techniques such as spatial transcriptomics and multiplex immunofluorescence are accelerating biomarker discovery with potential clinical application. Despite these advances, challenges remain in standardization, reproducibility, and clinical validation. This review summarizes current and emerging breast cancer biomarkers, emphasizing their role in advancing precision oncology. Continued translational research and methodological refinement are essential for successful integration of new biomarkers into clinical practice and for improving patient outcomes.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105881"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Information for Authors","authors":"","doi":"10.1016/S0046-8177(25)00185-6","DOIUrl":"10.1016/S0046-8177(25)00185-6","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105898"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current concepts and controversies in post-neoadjuvant breast pathology","authors":"Gregory R. Bean ,&nbsp;Benjamin C. Calhoun","doi":"10.1016/j.humpath.2025.105825","DOIUrl":"10.1016/j.humpath.2025.105825","url":null,"abstract":"<div><div><span>This review aims to be a helpful guide for pathologists in summarizing the current concepts and controversies in the reporting of post-neoadjuvant </span>breast carcinoma specimens. It is structured to chronologically detail the relevant points from the initial diagnosis in the pretreatment biopsy to the gross and microscopic evaluation of the posttreatment surgical specimen, with pertinent digressions related to imaging, representative sampling, staging systems, prognostic biomarker testing, and clinical implications of reporting residual disease.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105825"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple-negative lobular breast cancer: focus on pathology and clinical challenges","authors":"Fulvio Borella ,&nbsp;Niccolò Gallio ,&nbsp;Mariausilia Giurdanella ,&nbsp;Giulia Capella ,&nbsp;Paola Cassoni ,&nbsp;Isabella Castellano","doi":"10.1016/j.humpath.2025.105871","DOIUrl":"10.1016/j.humpath.2025.105871","url":null,"abstract":"<div><div><span>Triple-negative invasive lobular carcinoma is a rare and under-characterized subtype of breast cancer, distinct from the more common triple-negative </span>invasive ductal carcinoma<span>. While triple-negative invasive ductal carcinoma<span> is generally recognized for its aggressive clinical behavior and lack of targeted treatment<span> options, triple-negative invasive lobular carcinoma presents unique histopathological and molecular features that may influence its prognosis and therapeutic responsiveness. Despite these differences, triple-negative invasive lobular carcinoma remains poorly studied, leading to a reliance on treatment strategies adapted from ductal histotype, which may not fully address its biological complexities.</span></span></span></div><div>This review aims to provide a comprehensive overview of triple-negative invasive lobular carcinoma by analyzing its clinicopathological characteristics, prognostic factors<span><span><span>, and emerging therapeutic approaches. We explore the genetic alterations commonly observed in triple-negative invasive lobular carcinoma, their potential implications for treatment selection, and the challenges in current management strategies. Furthermore, we discuss the need for specialized research efforts and </span>clinical trials to define treatment paradigms better. As precision </span>oncology continues to evolve, understanding the biological distinctions of triple-negative invasive lobular carcinoma will be essential for optimizing patient outcomes and developing more effective treatment strategies.</span></div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105871"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}