Archives of pathology & laboratory medicine最新文献

{"title":"A Machine-Learning Approach to Predicting Adenoma Detection and Surveillance Impact of Deeper Sections in Colorectal Polypectomy Specimens.","authors":"Taofic Mounajjed, Andrew Geiser, Paul Dambowy","doi":"10.5858/arpa.2025-0311-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0311-OA","url":null,"abstract":"<p><strong>Context.—: </strong>In the routine practice of pathology, cutting deeper levels into paraffin blocks of colorectal polypectomy specimens that do not show a lesion on initial hematoxylin-eosin sections is common. However, this practice lacks standardization, and data are limited on the predictability of adenoma detection and the impact on surveillance intervals and resource use.</p><p><strong>Objective.—: </strong>To develop machine learning models that predict which polyps and encounters are most likely to reveal clinically significant lesions on deeper levels and influence patient surveillance intervals.</p><p><strong>Design.—: </strong>We performed a retrospective study of 94 888 patients (145 405 colonoscopies; 392 130 polyps) from 2007 to 2024. Polyp characteristics, deeper-level requests, and clinical/endoscopic features were analyzed. Machine learning models were developed to predict (1) adenoma detection in single polyps with deeper levels and (2) impact on surveillance intervals per encounter.</p><p><strong>Results.—: </strong>Deeper levels were requested in 26 067 jars (11%) and 21 232 encounters (15%), revealing adenomas in 7946 single polyps examined (51%). Predictive models showed high performance: logistic regression for single-polyp conversion (area under the receiver operating characteristic curve 0.88, accuracy 81%) and gradient boosting classifier for surveillance interval impact (area under the receiver operating characteristic curve 0.90, accuracy 83%). Important predictors included polyp size, location, total polyps, and artificial intelligence-assisted colonoscopy.</p><p><strong>Conclusions.—: </strong>Deeper-level sectioning contributes significantly to adenoma detection and influences surveillance intervals. Machine learning provides a practical framework to optimize deeper-level requests, enhancing diagnostic precision and resource allocation.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examination of Pathologist-Artificial Intelligence Interactions and Their Impact on Pathologist Accuracy Using Artificial Intelligence-Assisted Scoring of Immunohistochemistry for Human Epidermal Growth Factor Receptor 2.","authors":"John Shamshoian, Zahil Shanis, Ryan Cabeen, Limin Yu, Shreya Chakraborty, Marc Thibault, Blake Martin, Harshith Padigela, Dinkar Juyal, Syed Ashar Javed, William Qian, Juhyun Kim, Ylaine Gerardin, Beckett Rucker, Jacqueline Brosnan-Cashman, Harsha Pokkalla, Jimish Mehta, Amaro Taylor-Weiner, Eric Walk, Andrew Beck, Michael C Montalto, Ben Glass, Santhosh Balasubramanian","doi":"10.5858/arpa.2025-0262-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0262-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Advances in computer vision have fueled the development of artificial intelligence (AI)-based algorithms for pathology. AI-assisted approaches may streamline the diagnostic workflow and reduce variability.</p><p><strong>Objective.—: </strong>To assess the impact of an AI-assist model for human epidermal growth factor receptor 2 (HER2) scoring on pathologist reproducibility and accuracy and to understand pathologist-model interactions.</p><p><strong>Design.—: </strong>An AI-Assist algorithm for HER2 scoring, AI-Measurement of HER2 (AIM-HER2), was developed to generate slide-level scores of HER2 immunohistochemistry (IHC) aligned with guidelines from the American Society of Clinical Oncology/College of American Pathologists. AIM-HER2 was assessed in a retrospective reader study wherein HER2-trained pathologists (n = 20) scored breast cancer cases (n = 200) with and without model assistance using a 2-cohort crossover design with a 3-week washout. A separate panel of expert pathologists (n = 5) provided manual reference scores.</p><p><strong>Results.—: </strong>As an AI-assist tool, AIM-HER2 improved interrater agreement both overall and at the 0/1+ and 1+/2+ cutoffs and significantly increased positive percentage agreement at the 0/1+ and 1+/2+ cutoffs. Pathologists displayed a wide range of model override rates, and the quality of these overrides was correlated with each pathologist's manual accuracy. Measurements of AIM-HER2 accuracy were highly dependent on reference panel composition.</p><p><strong>Conclusions.—: </strong>The use of AI-assist tools, such as AIM-HER2, for scoring HER2 IHC in breast cancer may improve pathologist reproducibility and accuracy, particularly at the 0/1+ and 1+/2+ cutoffs. However, improved consistency of pathologist interpretation of AI-assisted IHC scoring guidance may be necessary for AI-assist tools to reach their full potential.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Innovative Diagnostic Strategy for Malignant Pleural Effusion Using Discontinuous Gradient Centrifugation.","authors":"Jin-Xin Zhu, Lei Yuan, Yong-Tao Zhan, Ying-Jie Li, Hao-Ming Xia, Ming Jiang, Xiang Ao, Jie Zhou, Qian Wang, Dong-Hui Zhang, Zhi-Jie Zhang, Hong-Sheng Li, Ni Qiu","doi":"10.5858/arpa.2025-0442-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0442-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Malignant pleural effusion (MPE) is a common cancer metastatic complication, and distinguishing it from benign effusions is critical for treatment. Cytology is central to MPE diagnosis, but inflammatory and reactive mesothelial cells often obscure malignant cells, limiting accuracy. Although liquid-based cytology (LBC) improves specificity over conventional smears, its use is constrained by specialized equipment requirements.</p><p><strong>Objective.—: </strong>To investigate a novel discontinuous gradient centrifugation (DGC) technique for improving the diagnostic efficiency of MPE.</p><p><strong>Design.—: </strong>We prospectively analyzed 55 pleural effusion samples (September 2021-April 2023) using DGC and LBC, with cytoblock paraffin embedding and immunohistochemistry as the reference standard.</p><p><strong>Results.—: </strong>Immunohistochemical staining classified 24 cases as benign and 31 as malignant. Class IA was found in 27 (49.09%), IB in 2 (3.64%), IC in 0 (0%), II in 2 (3.64%), and III in 24 (43.64%) cases via DGC; with LBC, class IA was in 9 (16.36%), IB in 7 (12.73%), IC in 8 (14.55%), and II in 8 cases. (14.55%). DGC had 1 false-positive and 3 false-negative results, whereas LBC had 2 false positives and 9 false negatives. Compared with LBC, DGC showed significantly higher sensitivity (90.32% versus 70.97%, P = .001), negative predictive value (88.46% versus 70.97%, P = .003), and overall accuracy (92.72% versus 80.0%, P = .007). Receiver operating characteristic curve analysis revealed a significantly larger area under the curve for DGC (0.931 [95% CI, 0.873-0.989] versus 0.813 [95% CI, 0.704-0.922]).</p><p><strong>Conclusions.—: </strong>DGC is an innovative, highly accurate method for MPE detection, outperforming LBC in clinical practice.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing Ferritin Levels in Healthy Older Adults: Updated Reference Ranges and Associated Health Outcomes.","authors":"Sultana Monira Hussain, John K Olynyk, Hans G Schneider, Paul Lacaze, Chenglong Yu, Lawrence J Beilin, Andrew M Tonkin, Daniel Clayton-Chubb, Cammie Tran, David Clark, Amanda J Rickard, Robyn L Woods, Rowan G Walker, John J McNeil","doi":"10.5858/arpa.2025-0503-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0503-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Ferritin is used as a biomarker for iron storage, but levels vary significantly among individuals.</p><p><strong>Objective.—: </strong>To define a ferritin reference range in older adults and explore its associations with health outcomes.</p><p><strong>Design.—: </strong>A post hoc analysis included 5247 men and 6075 women aged 70 years or older from the Aspirin in Reducing Events in the Elderly trial. At enrollment, participants had no diagnosed cardiovascular disease (CVD), dementia, physical disability, or life-threatening illness. Longitudinal data on mortality, CVD morbidity, and serious hemorrhage were linked to baseline ferritin levels. Ferritin levels were analyzed in quintiles (Q) (Q1-Q5), with Q2 through Q4 as the reference category.</p><p><strong>Results.—: </strong>Median ferritin concentrations were 190 μg/L for men and 125 μg/L for women, measured with the Abbott Alinity platform. Sex-specific reference ranges derived using the Clinical and Laboratory Standards Institute guidelines were 23 to 741 μg/L and 19 to 440 μg/L (2.5th-97.5th percentiles), respectively. No relationship was found between ferritin levels and disability-free survival, mortality, or CVD outcomes. However, men with the lowest ferritin levels had increased future incidence of major hemorrhage (hazard ratio [HR], 1.51; 95% CI, 1.10-2.07), gastrointestinal (GI) bleeding (HR, 2.03; 95% CI, 1.12-3.60), and GI cancer (HR, 1.27; 95% CI, 1.04-1.54).</p><p><strong>Conclusions.—: </strong>A suggested reference range for ferritin in older adults using the Abbott Alinity platform is 25 to 740 μg/L for men and 20 to 440 μg/L for women. Low ferritin levels were associated with increased risks of GI bleeding and GI cancer in older men.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Utility of Dysmorphic Erythrocyte Identification Using the Atellica 1500 Automated Urinalysis System in the Evaluation of Glomerular Hematuria.","authors":"Yongjung Park, Beom Jin Lim, John Hoon Rim, Sang-Guk Lee, Jeong-Ho Kim","doi":"10.5858/arpa.2025-0396-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0396-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Dysmorphic red blood cells (dRBCs) in urine are useful noninvasive markers for distinguishing glomerular hematuria.</p><p><strong>Objective.—: </strong>To assess the diagnostic utility of dRBC identification, using image data from the Atellica 1500 Automated Urinalysis System (Siemens Healthineers).</p><p><strong>Design.—: </strong>We retrospectively evaluated 162 patients from Severance Hospital (n = 46; August 2019-February 2024) and Yongin Severance Hospital (n = 116; between March 2020 and February 2024) who underwent renal, urinary, and/or urogenital biopsies during periods when the same Atellica 1500 Automated Urinalysis System was in use. dRBCs were evaluated by trained medical technologists following recent literature criteria. Inclusion requires hematuria (≥2+ on dipstick) and dRBC testing within 3 months before biopsy. From biopsy, imaging, and clinical findings, patients were classified as having glomerular hematuria (n = 90) or nonglomerular diseases (n = 72).</p><p><strong>Results.—: </strong>The area under the receiver operating characteristic curve (AUROC) for %dRBC in diagnosing glomerular disease was 0.766. At cutoffs of 17% and 28% dRBCs, sensitivity was 32.2% and 21.1% with specificity of 95.8% and 97.2%, respectively. %G1-dRBC yielded an AUROC of 0.636, with sensitivities of 31.1% and 26.7% at 1% and 2% cutoffs, respectively, for corresponding specificities. In immunoglobulin A nephropathy (n = 67), %G1-dRBC was higher in cases with segmental glomerulosclerosis (n = 53). Multivariate analysis identified that younger age, higher %dRBC, lower dipstick blood/leukocyte esterase, and higher dipstick protein grades were independent predictors of glomerular diseases.</p><p><strong>Conclusions.—: </strong>dRBC identification using digital urine sediment analyzer provides high specificity and positive predictive value for glomerular hematuria, with advantages in efficiency, reproducibility, and image archiving.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Claudin 18.2 Expression Concordance in Paired Cytology and Surgical Specimens of Gastric and Gastroesophageal Junction Adenocarcinomas.","authors":"Ruimeng Yang, Harsimar Kaur, Minhua Wang, Xi Wang, Xuchen Zhang, Guoping Cai","doi":"10.5858/arpa.2025-0466-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0466-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Claudin 18.2 (CLDN18.2) is a clinically actionable target in gastric and gastroesophageal junction adenocarcinomas, with patient selection guided by CLDN18.2 immunohistochemistry assay. While surgical specimens are standard for testing, the reliability of cytology specimens for CLDN18.2 assessment remains unclear.</p><p><strong>Objective.—: </strong>To assess the concordance of CLDN18.2 expression between cytology and surgical specimens and to explore the possible causes of discrepancy.</p><p><strong>Design.—: </strong>CLDN18.2 immunohistochemistry was performed on paired cytology and surgical specimens. The diagnostic performance at the cutoff of 75% or greater was evaluated across clinicopathologic variables.</p><p><strong>Results.—: </strong>Positive CLDN18.2 expression was seen in 35% (13 of 37) of surgical and 32% (12 of 37) of cytology cases. Overall, 86% (32 of 37) of pairs were concordant (either positive or negative). At the cutoff of 75% or greater, cytology achieved 77% sensitivity, 92% specificity, 83% positive predictive value, and 88% negative predictive value. Subgroup analysis showed that specimen origin was the strongest determinant of accuracy: concordance was greatest when both cytology and surgical specimens were obtained from gastric primary tumor, with perfect agreement (prevalence-adjusted, bias-adjusted κ [PABAK] = 1.00). In contrast, cases where one or both specimens were derived from metastatic sites showed lower agreement (PABAK = 0.68; bootstrap P < .01).</p><p><strong>Conclusions.—: </strong>Cytology specimens could serve as a reliable source for CLDN18.2 biomarker testing when interpreted at the threshold of 75% or above. Although discrepancies occur in some cases, the findings support the incorporation of cytology into biomarker testing workflows to expand access to CLDN18.2-targeted therapies for patients lacking surgical specimens.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature-Dependent Long-term and Short-term Stability of Human Epidermal Growth Factor 2 Antigenicity on Pathology Slides.","authors":"Liam Scott, Julia Benanto, Charles J Robbins, Katherine Bates, Mengni He, Nay Nwe Nyein Chan, David L Rimm","doi":"10.5858/arpa.2025-0447-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0447-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Immunohistochemistry-based assessment of human epidermal growth factor receptor 2 (HER2) is increasingly useful for clinical decision-making in breast, gastroesophageal, and other cancers. Retroactive use of cancer tissue for research purposes is increasing alongside increased understanding of HER2's role in determining cancer outcomes. Best practices for formalin-fixed, paraffin-embedded (FFPE) tissue handling are addressed in guidelines for diagnostic and scientific activities; however, preanalytic variables arising after tissue embedding and sectioning are minimally discussed.</p><p><strong>Objective.—: </strong>To quantify the loss of HER2 antigenicity that occurs on sectioned FFPE slides over long- and short-term timescales, in both room-temperature and freezer conditions.</p><p><strong>Design.—: </strong>Surplus FFPE microarray slides from years-prior experiments, stored either at room temperature or in a -80°C freezer, were paired with block-matched, freshly cut slides for analysis of postsectioning epitope degradation. To evaluate short-term changes in epitope availability, a set of FFPE slides was serially stained by immunofluorescence during a 2-month period, using standardization to mass spectrometry values to enable standardized quantification of antigen in amol (attomoles)/mm2.</p><p><strong>Results.—: </strong>Significant degradation of HER2 antigen on FFPE slides occurs over a period of years when slides are stored at room temperature, but not when stored at -80°C. In either condition, the amount of degradation that occurs within a 2-month timescale is negligible compared to variation attributable to tumor heterogeneity and interrun variability.</p><p><strong>Conclusions.—: </strong>Room-temperature storage of FFPE slides appears to be safe for HER2 measurement when staining will occur within 2 months. The \"shelf life\" of slides stored at -80°C is at least 1 year.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total Versus Ionized Calcium: Valid Index of Calcium Status in Critically Ill Patients.","authors":"Madhumita Das, Argha Baruah","doi":"10.5858/arpa.2025-0488-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0488-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Accurate evaluation of calcium status is essential in critically ill patients. However, reliance on total calcium (tCa) and albumin-corrected calcium often leads to misclassification, influencing clinical decisions.</p><p><strong>Objective.—: </strong>To compare various calcium measurement methods with ionized calcium (iCa), the gold standard, and evaluate their diagnostic and prognostic relevance in intensive care unit (ICU) patients.</p><p><strong>Design.—: </strong>A cross-sectional study was conducted for 1 year in 145 ICU patients at a tertiary care center. Measured parameters included tCa, iCa, albumin, total protein, and pH. Derived indices included albumin-corrected calcium (CtCa), calculated iCa (CiCa), pH-adjusted iCa (pHiCa), nonionized calcium (NiCa), and the iCa:CtCa ratio. Correlations, sensitivity/specificity, classification accuracy, and receiver operating characteristic (ROC) analyses were performed.</p><p><strong>Results.—: </strong>Abnormal iCa levels were observed in 82.07% (119 of 145) of patients, with hypercalcemia being rare. tCa, CtCa, CiCa, and NiCa significantly underestimated hypocalcemia when compared to iCa (P ≤ .01). Among methods, pHiCa showed the best diagnostic performance (95.2% accuracy; 86.3% sensitivity) and strongest correlation with iCa (r = 0.983). The iCa:CtCa ratio reflected physiological changes such as alkalosis and hypoalbuminemia, particularly in postoperative and septic patients. ROC analysis indicated poor prognostic value of iCa for prolonged ICU stay. The calculated areas under the curve for ICU stay and mortality were 0.51 and 0.54, respectively.</p><p><strong>Conclusions.—: </strong>Conventional calcium measurement methods frequently misclassify calcium status in critically ill patients. pHiCa demonstrated superior diagnostic accuracy and agreement with iCa. While iCa lacks prognostic utility for ICU outcomes, it remains indispensable for precise calcium assessment.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computer-Aided Quantitative Image Analysis of Multiple Human Epidermal Growth Factor Receptor 2 Immunohistochemistry Assays in Breast Carcinoma.","authors":"Mélissande Cossutta, Birgit Truumees, Alexandre Papine, Heidi Lykke Kristoffersen, Ekaterina Tatarinova, Lise Emanuelsen, Charles Homsy, Françoise Soussaline, Søren Nielsen","doi":"10.5858/arpa.2025-0316-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0316-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Quantitative image analysis (QIA) is increasingly applied for immunohistochemistry (IHC)-based biomarker assessment in pathology. With the introduction of drugs targeting breast carcinomas (BCs) with low human epidermal growth factor receptor 2 (HER2) expression levels, a need for more accurate and reproducible HER2 scoring is warranted. QIA has the potential to increase HER2 IHC scoring reproducibility. However, QIA reproducibility should be agnostic and uninfluenced by different IHC assays.</p><p><strong>Objective.—: </strong>To compare HER2 scoring accuracy and reproducibility by expert pathologists and QIA in BCs analyzed with different IHC assays.</p><p><strong>Design.—: </strong>Algorithm parameters of the QIA method were developed by using 183 slides from 6 Nordic immunohistochemical Quality Control (NordiQC) HER2 runs. The QIA method was then validated on 409 slides from 2 other runs. HER2 scores obtained by visual scoring, following 2023 European Society for Medical Oncology and American Society of Clinical Oncology/College of American Pathologists guidelines or by QIA, were compared.</p><p><strong>Results.—: </strong>Visual scoring and QIA reached 86% (κ = 0.81) overall scoring agreement for tissue cores in the final validation material. QIA showed 98% (95% CI, 97.8%-99.0%) sensitivity and 84% (95% CI, 80.3%-87.6%) specificity for the distinction between HER2 0 (no drug candidate) and HER2 1-3+ (drug candidates) scores. Ninety-nine percent (95% CI, 98.7%-99.9%) sensitivity and 100% (95% CI, 99.8%-100%) specificity were obtained for the separation between HER2 2-3+ in situ hybridization (ISH)-positive cores (HER2 classical overexpression) and HER2 0-2+ ISH-negative cores (HER2-low expression range).</p><p><strong>Conclusions.—: </strong>Our QIA method can be beneficial to use as a reliable HER2 scoring tool for HER2 classical overexpression and HER2-low in BCs. It was found to be agnostic and provided same accuracy irrespective of IHC assay applied.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mast Cell Activation Syndrome: Quantification of Mast Cells Across Conditions Reveals Limited Diagnostic Utility of Mast Cell Counts and Tryptase Depletion Index.","authors":"Christoph Geisenberger, Solveig Kuss, Hans-Peter Horny, Susanna Müller","doi":"10.5858/arpa.2025-0007-OA","DOIUrl":"https://doi.org/10.5858/arpa.2025-0007-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Mast cell enumeration in gastrointestinal biopsies is commonly requested to diagnose mast cell activation syndrome (MCAS) or systemic mastocytosis (SM) with gastrointestinal (GI) involvement. However, mast cell numbers can be elevated in various disorders and quantities do not reflect functional states. A novel measure, the tryptase depletion index (TDI), was recently proposed as a surrogate measure for mediator release and mast cell activation.</p><p><strong>Objective.—: </strong>To evaluate the diagnostic utility of the TDI and mast cell counts for differentiating between MCAS, SM, and inflammatory disorders in GI biopsies.</p><p><strong>Design.—: </strong>GI biopsy samples from patients with SM or MCAS (n = 64), inflammatory disorders (n = 26), and healthy controls (n = 38) were examined. All sections were immunostained for c-Kit/CD117 and tryptase, and mast cells were quantified within the lamina propria. Testing for KIT D816V mutation and CD25 immunohistochemistry were performed for all cases with suspected SM or MCAS.</p><p><strong>Results.—: </strong>Infiltrates of atypical, CD25+ mast cells were confirmed in SM. Mast cell numbers were elevated in SM, MCAS, and inflammatory disorders as compared to healthy tissue. The TDI did not differ significantly among the groups, and fluctuations in TDI can be explained by measurement noise from counting performed on subsequent tissue sections. Receiver operating characteristic analysis showed low sensitivity and specificity for TDI or mast cell enumeration in diagnosing MCAS.</p><p><strong>Conclusions.—: </strong>While SM can be substantiated with markers such as CD25/CD30 or KIT mutations, counting mast cells appears of limited utility.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}