American journal of clinical pathology最新文献

{"title":"Optimizing electronic health records: Integration of human factors engineering for enhanced pathology report display and accessibility.","authors":"Ethan P Larsen, Mohammad Jalloul, Moira P Larsen","doi":"10.1093/ajcp/aqaf024","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf024","url":null,"abstract":"<p><strong>Objective: </strong>The integration of human factors engineering (HFE) into electronic health records (EHRs) is essential to enhance the display and accessibility of pathology reports. Pathology testing is central to clinical decision-making, yet the current EHR interfaces present challenges in test ordering and result interpretation, contributing to diagnostic errors. This study explores the application of HFE principles to redesign EHR visual displays, specifically for HIV and urine toxicology testing.</p><p><strong>Methods: </strong>By involving pathologists and clinicians in the design process, we developed user-centric templates that improve result clarity and accessibility. We also describe case examples of one successful template prototype implementation and one where technical barriers highlight limitations of applying user-centered design within the constraints of EHR and Laboratory Information System applications. The redesigned reports emphasize critical information through standardized color codes and organized data presentation, making nonstandard findings more prominent.</p><p><strong>Discussion: </strong>These interventions have the potential to create improved clinician comprehension and workflow efficiency, ultimately supporting better patient care. The study highlights the importance of incorporating HFE principles into EHR design and advocates for broader adoption to enhance usability and safety in health care settings.</p><p><strong>Conclusions: </strong>Further collaboration with regulatory bodies could establish standardized guidelines, fostering more effective EHR systems across the industry.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAS may facilitate transformation of chronic lymphocytic leukemia to histiocytic sarcoma with indeterminate dendritic cell features.","authors":"Farhan Hassan, Hailing Zhang, Dietrich Werner Idiaquez, Nagehan Pakasticali, Elizabeth Hyjek, Mohammad Hussaini","doi":"10.1093/ajcp/aqaf041","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf041","url":null,"abstract":"<p><strong>Objective: </strong>We sought to investigate the molecular mechanism underlying transformation of chronic lymphocytic leukemia (CLL) to histiocytic sarcoma (HS) with indeterminate dendritic cell (IDC) features.</p><p><strong>Methods: </strong>Extensive NGS-based genomic profiling was performed on samples of a patient who had CLL, secondary HS with IDC features, and CMML. Clonotypic evaluation of VDJ rearrangement status was performed to confirm clonal relatedness.</p><p><strong>Results: </strong>HS is a rare proliferation of malignant tissue histiocytes that is usually primary, although secondary HS exists and often demonstrates mutations in the Ras/Raf/MAPK or PI3K/AKT/mTOR pathways, but HS with indeterminate dendritic cell (IDC) features has not been previously reported. A 77-year-old man with chronic lymphocytic leukemia (CLL) presented with an oropharyngeal mass. Biopsy specimen showed large atypical histiocytic cells with oval-to-irregular indented nuclei. They were positive for CD33, CD4, CD68 (subset, weak), CD163 (subset, weak), BCL6, S100 (subset), CD1a, cyclin D1 (subset), and lysozyme (weak) but negative for Langerin, BRAF V600E, CD21, CD23, CD35, CD123, TCF4, TCL1, MPO, CD20, CD79a, CD10, MUM1, and BCL2. The patient was diagnosed with secondary HS with IDC features as well as chronic myelomonocytic leukemia (CMML) in the bone marrow. Careful genomic dissection of all 3 types of malignant cells showed that SF3B1 p.E622D was present in both CLL and HS but not CMML. In addition, the HS acquired KRAS p.G13D, which we hypothesize drove the transdifferentiation of CLL to HS. Moreover, next-generation sequencing (NGS) clonotypic evaluation of variable-diversity-joining (VDJ) rearrangements in both the HS and CLL established relatedness but not the CMML.Conclusion: This is the first report of secondary HS with IDC features arising from CLL. We establish by both IGH NGS analysis and mutational profiling that the CLL and HS are clonally-related and posit that acquisition of KRAS p.G13D drove transdifferentiation. This has therapeutic implications for targeting the RAS-BRAF-MAPK-ERK pathway.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic characteristics of lymphoproliferative disorders involving the kidney.","authors":"Kotaro Takeda, Haiming Tang, Deepika Kumar, Adebowale J Adeniran, Guoping Cai","doi":"10.1093/ajcp/aqaf023","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf023","url":null,"abstract":"<p><strong>Objective: </strong>Lymphoproliferative disorders can involve the kidney, which is associated with a worse prognosis. The objective of this study was to review the clinical and histologic characteristics of patients with lymphoproliferative disorders involving the kidneys.</p><p><strong>Methods: </strong>Cases with lymphoproliferative disorders showing renal involvement were retrieved from the institutional pathology database for the past 20 years. Data regarding patient demographics, clinical presentations, lymphoma subtypes, history of lymphoma, treatments received, chemotherapy regimens, and patient outcomes were extracted.</p><p><strong>Results: </strong>The cohort included 48 cases of non-Hodgkin lymphoma with renal involvement, comprising 35 men and 13 women, with a median age of 71.5 years. Most lymphomas were mature B-cell neoplasms, accounting for 42 (87.5%) cases, with diffuse large B-cell lymphoma as the leading subtype in 18 (42.9%) cases. A renal mass was the initial presentation in 33 (68.8%) patients, while the remaining 15 (31.2%) had medical renal complications. Approximately half of the renal mass cases were de novo aggressive lymphomas, while most with renal complications had systemic involvement of previously diagnosed low-grade lymphomas. Chemotherapy, frequently R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), was the primary treatment. Patients with a kidney mass tended to show a worse prognosis than those with medical renal complications, but statistical significance was not reached (P = .347).</p><p><strong>Conclusions: </strong>The study demonstrates that renal mass is a crucial presentation of lymphoma, in some cases even without history, highlighting the importance of renal biopsy to triage patients for proper treatment and avoid unnecessary nephrectomy.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid clinical deployment of UBA1 testing in patients with VEXAS syndrome.","authors":"Paul A Wadsworth, Simon B Chen, Lauren Lawrence, Chandler C Ho, Joseph E Le, Paolo Libiran, Peter C Grayson, Marcela A Ferrada, David B Beck, Carlos J Suarez","doi":"10.1093/ajcp/aqaf051","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf051","url":null,"abstract":"<p><strong>Objective: </strong>VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described autoinflammatory syndrome caused by pathogenic variants in UBA1. However, there is a dearth of widely available UBA1 testing aside from large, expensive sequencing studies. Thus, we sought to rapidly develop, validate, and clinically deploy a cost-effective assay for detecting the most common UBA1 variants.</p><p><strong>Methods: </strong>We developed, validated, and implemented a single base extension mass spectrometry assay for detecting pathogenic UBA1 variants at the c.121, c.122, and c.118-1 positions in patients with suspected VEXAS syndrome. Assay performance characteristics were assessed using peripheral blood and bone marrow samples from patients with (n = 8) and without (n = 36) VEXAS.</p><p><strong>Results: </strong>The assay demonstrated a lower limit of detection (LOD) of 10% variant allele fraction for each mutation. The analytical accuracy, sensitivity, and specificity were each demonstrated to be 100% at the LOD, with excellent intra- and interrun reproducibility. Based on literature review of reported UBA1 variants associated with VEXAS, to date, this assay detects the most prevalent variants, with a clinical sensitivity of 97% or more.</p><p><strong>Conclusions: </strong>A cost-effective, mass spectrometry-based assay with high analytical and clinical performance can feasibly be implemented in hospital laboratories for diagnosis of VEXAS syndrome.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4 antigen loss in bronchoalveolar lavage fluid with neutrophilia and infectious organisms: A diagnostic pitfall when analyzing T-cell subsets by flow cytometry.","authors":"Lianqun Qiu, Jason E Love, William Simonson, Jonathan R Fromm, Sindhu Cherian","doi":"10.1093/ajcp/aqaf048","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf048","url":null,"abstract":"<p><strong>Objective: </strong>Flow cytometric T-cell subtyping is an important component of bronchoalveolar lavage (BAL) analysis with diagnostic value in routine practice.</p><p><strong>Methods: </strong>BAL fluid was collected for differential and standard 4-color panel T-cell subtype analysis using flow cytometry, followed by a 10-color comprehensive T-cell panel to confirm CD4 T-cell antigen loss.</p><p><strong>Results: </strong>Here, we report 4 BAL cases that were incidentally identified during our daily practice over the past 5 years and showed apparent loss of detectable surface CD4 on CD3+ T cells by 2 different anti-CD4 clones. Each of these BAL fluids was rich in neutrophils and had infectious microorganisms identified on microbiological examination, including Pseudomonas aeruginosa, Haemophilus influenzae, and Mycobacterium avium complex. The dual CD4- and CD8-negative CD3+ T cells were confirmed to express α/β but not γ/δ T-cell receptor in 1 case.</p><p><strong>Conclusions: </strong>CD4 antigen loss on CD3+ T cells may be seen in neutrophil-predominant BAL fluid specimens that contain infectious microorganisms. The underlying mechanism for CD4 antigen loss is unclear but may involve proteolytic cleavage by protease and/or elastase of either neutrophilic or microbial origin, or possibly chronic antigenic stimulation. Awareness of this diagnostic pitfall is important in clinical practice to avoid misinterpretation of a falsely low CD4/CD8 ratio or a population of T cells lacking expression of CD4 and CD8 in BAL samples.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of TP53 mutations by immunohistochemistry in acute myeloid leukemia varies with interpreter expertise and mutation status.","authors":"Lee P Richman, Brianna F Waller, Scott B Lovitch, Ashwini Jambhekar","doi":"10.1093/ajcp/aqaf047","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf047","url":null,"abstract":"<p><strong>Objective: </strong>TP53 mutations, including missense and inactivating (frameshift, splice site, and nonsense) mutations, occur in approximately 10% of myeloid neoplasms and confer adverse outcomes. Classification of myeloid neoplasms by World Health Organization and International Consensus Classification standards recognizes the importance of early detection of TP53 mutations. p53 immunohistochemistry (IHC) is a widely accessible method used to detect mutations; however, previous studies have demonstrated variable accuracy, especially for inactivating TP53 mutations. Recently, sequencing using targeted panels has seen increased use. Although highly accurate, sequencing is resource intensive and not universally available.</p><p><strong>Methods: </strong>Using 134 bone marrow samples from patients with acute myeloid leukemia evaluated for TP53 mutation by sequencing, we assessed the concordance of p53 IHC with sequencing as well as the interrater-reliability for IHC intensity and percent positivity.</p><p><strong>Results: </strong>Consistent with previous studies, we found that p53 IHC was strongly specific and modestly sensitive for missense mutations and that overall performance improved with dedicated hematopathology training. We also found that IHC performed poorly for inactivating mutations and was even variable between cases harboring identical amino acid changes. Low predicted transcriptional activity of p53 missense proteins correlated with a mutant pattern of IHC staining. The status of the second allele and variant allele frequency also affected the accuracy of p53 IHC as a surrogate for TP53 allele status.</p><p><strong>Conclusion: </strong>Cases of acute myeloid leukemia with TP53 mutations predicted to have low transcriptional activity showed reduced overall survival. Our results demonstrate limited practical utility of p53 IHC for accurate evaluation of TP53 mutation status because of multifactorial confounders.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A critical analysis of CellaVision systems in the modern hematology laboratory.","authors":"Brydon Panozzo, Jaineel Ramnarain, Song Chen, Hiu Lam Agnes Yuen, Maciej Tatarczuch, Shahla Vilcassim, Christopher Chang-Yew Leow, Chris Barnes","doi":"10.1093/ajcp/aqaf045","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf045","url":null,"abstract":"<p><strong>Objective: </strong>This review aims to provide a comprehensive analysis of the current literature regarding the use of CellaVision digital morphology systems and to assess the emerging applications, their potential to supplement current diagnostic pathways, and-importantly-appreciate their practical and perceived limitations.</p><p><strong>Methods: </strong>A manual literature review was conducted to identify relevant journal articles and published abstracts as they relate to the application of CellaVision systems to hematology laboratory practice in human patients.</p><p><strong>Results: </strong>CellaVision systems can characterize cellular morphology with overall a high degree of accuracy-in particular, for neutrophils; lymphocytes; and common red blood cell changes, including target cells. Challenges remain, however, with the detection of particular important findings, including immature granulocytes and red blood cell agglutination. The application of CellaVision systems to emerging areas such as telepathology and parasitology are evolving, with an increasing volume of literature highlighting the technology's utility.</p><p><strong>Conclusion: </strong>CellaVision systems and associated digital technologies are poised to play an increasingly important role in hematology laboratories, with promises of enhanced accuracy and improved workflows. Several critical deficiencies highlight the necessity for continued research to support their transition into routine clinical practice.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic ultrasound-guided pancreatic core-needle/microforceps biopsy is a valuable diagnostic tool for pancreatic lesions: Experience from a large academic institution.","authors":"Saba Shafi, Wendy L Frankel, Zaibo Li, Dan Jones, Somashekar G Krishna, Ashwini K Esnakula, Martha Yearsley, Shaoli Sun, Giovanni Lujan, Jennifer Vazzano, Wegahta Weldemichael, Peter Lee, Hamza Shah, Jordan Burlen, George Papachristou, Wei Chen","doi":"10.1093/ajcp/aqaf050","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf050","url":null,"abstract":"<p><strong>Objective: </strong>Endoscopic ultrasound (EUS)-guided, fine-needle core biopsy (FNB), and through-the-needle microforceps biopsy (TTNB) are latest tools for evaluating pancreatic lesions. We aim to provide subspecialty surgical pathologists' experience with EUS-FNB/TTNB in diagnosing pancreatic lesions at a large academic center.</p><p><strong>Methods: </strong>A 3-year review identified 101 EUS pancreatic specimens submitted for surgical pathology: 87 biopsy specimens (FNB = 58, TTNB = 29) and 14 fine-needle aspirations (FNAs). Diagnoses were compared with cytology and resection specimens when available.</p><p><strong>Results: </strong>Of the 101 cases, 10 had previous EUS-FNA cytology with inconclusive diagnoses. Rebiopsy with EUS-FNB/TTNB provided definitive diagnoses in 9 cases. Thirty-five cases (18 cystic and 17 solid lesions) had concurrent surgical pathology and cytology specimens. The diagnostic yield of EUS-FNB/TTNB biopsy specimens (69%) was significantly higher than that of cytology specimens (26%, P = .0017), as was the diagnostic accuracy (P = .0012). This diagnostic advantage was statistically significant in cystic lesions (FNB/TTNB [83.3%] vs cytology [16.7%] for achieving a specific diagnosis, P = .0002) but not in solid lesions (61.5% vs 46.2%, P = .6951). Only in 1 case did cytology (adenocarcinoma) provide a more definitive diagnosis than surgical pathology (high-grade dysplasia cannot exclude adenocarcinoma).</p><p><strong>Conclusions: </strong>The EUS-FNB/TTNB methods complement EUS-FNA cytology in diagnosing pancreatic lesions, and they often outperforms concurrent cytology specimens, particularly in cystic lesions.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53abn high-risk endometrial cancer with PPP2R1A mutation might not benefit from adjuvant chemotherapy.","authors":"Qingxia Zhang, Yue Wang, Dan He, Jingyun Sun, Xin Li, Dong Li, Ying Dong, Yan Zhang, Suxia Wang","doi":"10.1093/ajcp/aqaf039","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf039","url":null,"abstract":"<p><strong>Objectives: </strong>Recent studies have found that high-risk endometrial cancer frequently harbors mutations in tumor suppressor genes PPP2R1A and FBXW7. This study aimed to explore the prognostic utility of these genes and their potential to predict benefit from adjuvant treatment.</p><p><strong>Methods: </strong>Tissue samples of 121 patients with high-risk endometrial cancer were collected. PPP2R1A, FBXW7, and POLE exonuclease domain mutations were detected using Sanger sequencing, while mismatch repair proteins and p53 expression were tested by immunohistochemistry.</p><p><strong>Results: </strong>PPP2R1A and FBXW7 mutations were detected in 11.6% and 21.5% of tumors, respectively. PPP2R1A mutations occurred more frequently in nonendometrioid, high-grade, and advanced-stage tumors and were strongly correlated with poor prognosis. Importantly, PPP2R1A mutations were more frequent in the p53 abnormal (p53abn) subgroup than in the other 3 molecular subgroups (P = .011). In addition, patients with p53abn, PPP2R1A-mutated tumors showed poor prognosis regardless of whether they received adjuvant chemotherapy. In contrast, patients with p53abn, PPP2R1A wild-type tumors exhibited statistically significantly longer survival after adjuvant chemotherapy (P = .022). Similar associations were observed in the patients with p53abn, FBWX7 wild-type tumors.</p><p><strong>Conclusions: </strong>PPP2R1A and FBXW7 status may be related to the current adjuvant chemotherapy outcome, particularly in endometrial cancer with the p53abn subtype. Thus, incorporating PPP2R1A and FBXW7 detection in the stratification and treatment decision-making process may be helpful.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interobserver agreement in scoring HER2-negative and HER2-low immunohistochemistry in breast cancer: Reasons for discordance and impact of a single training session.","authors":"Yun-An Tseng, Steffanie Tamayo, Evi Abada, Shivali Marketkar, Linda C Hanley, Katrine Hansen, M Ruhul Quddus, C James Sung, Kamaljeet Singh","doi":"10.1093/ajcp/aqaf043","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf043","url":null,"abstract":"<p><strong>Objective: </strong>In the DESTINY-Breast04 trial, human epidermal growth factor receptor 2 (HER2) low (HER2-L) is defined as an HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative fluorescence in situ hybridization. Limited data report poor agreement in scoring HER2-0 vs 1+. We aim to investigate the HER2 IHC concordance rate, with focus on HER2-0 vs HER2-L groups. We evaluate the impact of a single training session on concordance.</p><p><strong>Methods: </strong>Nine breast pathologists from the same institution reviewed 60 HER2 IHC stains on breast biopsy specimens in 2 rounds of 30 cases each. An educational slide review session was provided between the 2 rounds. Interobserver Cohen κ values were computed and compared.</p><p><strong>Results: </strong>Overall complete agreement for HER2 IHC was noted in 37 (62%) of 60 cases, with similar agreement in the first round (19/30 [63%]) and second round (18/30 [60%]). For all 60 cases, κ values ranged from .517 to .895, with 92% of κ values in substantial agreement or better range. For combined HER2-0 and HER2-L cases, κ values ranged from .298 to .826, with only 45% of κ values in substantial agreement or better range. In HER2-L only cases, 50% of the scorer pairs of κ values were 0 or less (no agreement), and only 14% of pairs showed substantial or better agreement. The educational session did not improve the κ values. Faint and heterogeneous HER2 expression, cytoplasmic blush, dislodged cells, and in situ component led to poor concordance in HER2-0 vs HER2-L.</p><p><strong>Conclusions: </strong>Poor concordance on HER2-0 vs HER2-L and lack of improvement after a training session likely suggest ineffective HER2 IHC expression range in HER2 low spectrum.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}