Human pathologyPub Date : 2025-08-01DOI: 10.1016/j.humpath.2025.105759
Raza S. Hoda , Hannah Y. Wen
{"title":"Challenges in papillary tumors of breast","authors":"Raza S. Hoda , 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}
Human pathologyPub Date : 2025-08-01DOI: 10.1016/j.humpath.2025.105821
Hongxia Sun, Aysegul A. Sahin, Qingqing Ding
{"title":"Updates on utility of immunohistochemistry in diagnosis of metastatic breast cancer","authors":"Hongxia Sun, Aysegul A. Sahin, 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}
Human pathologyPub Date : 2025-08-01DOI: 10.1016/j.humpath.2025.105818
Monalyn Marabi, Gary M. Tse
{"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, 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}
Human pathologyPub Date : 2025-08-01DOI: 10.1016/j.humpath.2025.105864
Yan Peng , Lori A. Erickson
{"title":"Updates and controversies in breast pathology","authors":"Yan Peng , 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 , Hui Chen , Huang Xiao , Damodaran Senthil , 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}
Human pathologyPub Date : 2025-08-01DOI: 10.1016/j.humpath.2025.105825
Gregory R. Bean , Benjamin C. Calhoun
{"title":"Current concepts and controversies in post-neoadjuvant breast pathology","authors":"Gregory R. Bean , 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 , Niccolò Gallio , Mariausilia Giurdanella , Giulia Capella , Paola Cassoni , 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}
Human pathologyPub Date : 2025-08-01DOI: 10.1016/j.humpath.2025.105801
Lan Zheng , Lin Jonathan He , Hui Chen , Qingqing Ding , Justin Bishop , Yan Peng
{"title":"CIC-rearranged sarcoma in the breast: A series of 3 rare cases with literature review","authors":"Lan Zheng , Lin Jonathan He , Hui Chen , Qingqing Ding , Justin Bishop , Yan Peng","doi":"10.1016/j.humpath.2025.105801","DOIUrl":"10.1016/j.humpath.2025.105801","url":null,"abstract":"<div><div><span>Capticua transcriptional repressor (</span><em>CIC</em><span><span>)-rearranged sarcoma represents a distinct highly aggressive, undifferentiated round </span>cell sarcomas, which most commonly affects young adults. The tumor typically arises in the deep soft tissues of the limbs and trunk, followed by the head and neck region, and is rarely found in visceral organs. </span><em>CIC</em>-rearranged sarcoma originating in the breast is extremely rare with only one case having been reported in the literature. We report three cases of <em>CIC</em><span><span>-rearranged sarcoma in the breast, all occurring in young females and exhibiting aggressive clinical behavior. Microscopically, all three cases showed diffuse or lobular growth of small round blue tumor cells with vesicular nuclei, prominent </span>nucleoli<span>, and clear cytoplasm. Focal reticular growth pattern and myxoid stroma were also observed. The diagnosis of </span></span><em>CIC</em><span><span>-rearranged sarcoma was confirmed through either fluorescence in situ hybridization (FISH) or </span>RNA sequencing; two of the three cases were confirmed to harbor </span><em>CIC</em>::<em>DUX4</em> fusion. This case series, to the best of our knowledge, represents the largest report of <em>CIC</em><span>-rearranged sarcoma in the breast. It highlights the importance of recognizing this rare entity in the breast due to its aggressive clinical course, poor response to chemotherapy, and high tendency for metastasis. It also emphasizes the utility of molecular studies in distinguishing </span><em>CIC</em>-rearranged sarcoma from poorly differentiated carcinoma, as <em>CIC</em>-rearranged sarcoma has significantly worse prognosis than poorly differentiated carcinoma of breast.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105801"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119416","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}
Human pathologyPub Date : 2025-08-01DOI: 10.1016/j.humpath.2025.105835
Hua Guo , Shi Wei
{"title":"Prognostic models for breast cancer: A narrative review","authors":"Hua Guo , Shi Wei","doi":"10.1016/j.humpath.2025.105835","DOIUrl":"10.1016/j.humpath.2025.105835","url":null,"abstract":"<div><div>Cancer prognostic models use a combination of risk factors to estimate the probability of patients' clinical outcomes, allowing the physicians to categorize patients into risk groups to guide clinical decision making. An ideal prognostic model would accurately predict patient survival and/or recurrence risk, taking into account a combination of clinical and pathological parameters that are readily available in the standard of care practice, thus can be widely utilized and continuously calibrated. To date, there have been many prognostic models for breast cancer proposed. These models differ in the methods of development and validation, the composition of predicting factors, the projected clinical outcomes, and their utilities. The identification of prognostic factors heavily relies on accurate assessment of pathologic characteristics of tumors, for which the pathologists’ role is essential. Therefore, it is crucial to understand prognostic models in pathology practice to provide more accurate and personalized patient care. Herein, we present a narrative review of commonly used breast cancer prognostic models in clinical practice.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"162 ","pages":"Article 105835"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293672","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}