Journal of Clinical Pathology最新文献

{"title":"Pitfalls in variant interpretation: a critical re-evaluation of somatic versus germline classifications.","authors":"Kok-Siong Poon, Kah Weng Lau","doi":"10.1136/jcp-2026-210689","DOIUrl":"10.1136/jcp-2026-210689","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"498-499"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729159","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":"Population-level evaluation of diagnostic categorisation and cost implications on transitioning from total vitamin B12 to active B12 assay.","authors":"Amro Maarouf, Rachel L Griffiths, Jayne Parkes, Rousseau Mariano Gama, Tejas Kalaria","doi":"10.1136/jcp-2025-210520","DOIUrl":"10.1136/jcp-2025-210520","url":null,"abstract":"<p><p>Transitioning from total to active vitamin B12 testing may influence diagnostic categorisation and costs. In this retrospective population study, a total of 181 794 vitamin B12 results from primary care requests in a UK laboratory were analysed -90 036 using total B12 assay before transitioning, and 91 758 using active B12 assay after transitioning- according to the National Institute for Health and Care Excellence (NICE)-defined thresholds. Compared with total B12, active B12 testing identified proportionately fewer patients as deficient (2.1% vs 6.5%) or indeterminate (37.0% vs 46.2%), and more as deficiency-unlikely (60.9% vs 47.3%). Although active B12 improved classification and may reduce the need for confirmatory testing by classifying fewer individuals as indeterminate, it incurred substantially higher cost, with an estimated 26-fold increase in expenditure to identify one deficient patient based on unit test cost in the NICE guidance. While active B12 may enhance diagnostic precision, its financial impact could limit broader adoption for routine testing unless test costs decrease.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"494-497"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874406","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":"Insights into the prognostic significance of cell division cycle 25A (CDC25A) in breast cancer.","authors":"Yousif A Kariri, Mansour A Alsaleem, Bader Alshamsan, Abdulaziz Algharras, Taher A Kariri, Emad A Rakha","doi":"10.1136/jcp-2026-210688","DOIUrl":"10.1136/jcp-2026-210688","url":null,"abstract":"<p><strong>Background: </strong>Cell division cycle 25A (CDC25A) is a key regulator of cell cycle progression, DNA replication and apoptosis in cancer cells. This study employed multiple well-characterised breast cancer cohorts to evaluate the prognostic significance of CDC25A and to characterise the molecular association linked to its expression in early-stage breast cancer.</p><p><strong>Methods: </strong>CDC25A transcriptomic expression was systematically assessed for statistical associations with key genes and pathways implicated in cell cycle regulation, DNA damage repair, cyclin-dependent signalling, tumour microenvironment and epithelial-mesenchymal transition. Its prognostic relevance was further evaluated through survival analyses. These investigations were conducted across the Molecular Taxonomy of Breast Cancer International Consortium (n=1980), the Cancer Genome Atlas (n=854) and Kaplan-Meier Plotter (n=4929) breast cancer cohorts. Subsequently, this study explored the associations between CDC25A protein expression and established clinicopathological parameters, molecular characteristics and patient outcomes using immunohistochemistry in a large, well-characterised Nottingham breast cancer cohort (n=1045).</p><p><strong>Results: </strong>High CDC25A expression was associated with altered expression of key breast cancer-related genes involved in cell cycle control, DNA damage repair, cyclin-dependent signalling, matrix remodelling and epithelial-mesenchymal transition-related biology. Elevated CDC25A expression at both transcriptomic and proteomic levels was significantly associated with aggressive clinicopathological features, including higher tumour grade, larger tumour size, hormone receptor negativity and lymphovascular invasion. High CDC25A protein expression independently predicted poorer survival outcomes (p=0.027; HR 1.28, 95% CI 1.18 to 1.98).</p><p><strong>Conclusion: </strong>CDC25A is an independent prognostic biomarker of clinical outcome in breast cancer. Further functional studies are warranted to validate CDC25A as a potential prognostic and therapeutic biomarker in breast cancer.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"449-457"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592315","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":"UK participation in the UK National External Quality Assessment Scheme for mismatch repair immunohistochemistry: insights from the last decade.","authors":"Luke Ar Farmkiss, Andrew Dodson, Suzanne Parry, Michelle Charmaine James, Ian M Frayling, Mark Johan Arends","doi":"10.1136/jcp-2026-210695","DOIUrl":"10.1136/jcp-2026-210695","url":null,"abstract":"<p><strong>Aim: </strong>Comparison of immunohistochemical detection of mismatch repair (MMR) proteins within tumours, as deficient MMR is important for (1) the detection of Lynch Syndrome, caused by inherited variants affecting the DNA MMR genes <i>MLH1, MSH2, MSH6</i> and <i>PMS2</i>, (2) aiding MMR gene variant interpretation and (3) deciding on use of immune checkpoint blockade therapy.</p><p><strong>Methods: </strong>This retrospective analysis compares the performance of different MMR immunohistochemistry (IHC) antibody clones, detection systems and automation IHC platforms using a decade of technical data submitted to the UK National External Quality Assessment Scheme (NEQAS) as part of its MMR EQA programme, with calculation of participants' final aggregated scores (FAS) for performance comparison.</p><p><strong>Results: </strong>Between 2011 and 2022, there were 38 MMR assessment runs, with an average of 44.8 submissions per antigen per assessment run. MMR module participation greatly increased over this decade. Average FAS showed a small non-significant upward trend with the lowest scores (14.6) observed in the first half of the decade, with greater concordance between FAS scores (15.1) in the second half of the decade. For MMR IHC, the antibody clones most frequently used were M1 and ES05 (FAS 15.7 and 15.1) for MLH1, G219-1129 and FE11 (FAS 14.8 and 14.1) for MSH2, EP51 and A16-4 (FAS 15.2 and 15.2) for PMS2 and SP93 and EP49 (FAS 16.1 and 15.6) for MSH6. The most common detection systems were Ventana Optiview, Leica BondMax, Leica Bond Refine, Dako FLEX+ and Ventana UltraView.</p><p><strong>Conclusions: </strong>The quality of submitted MMR IHC sections has risen, with recent assessment scores showing lower variability, indicating better antibody clone performance, improved detection systems and IHC automation platform technology, allied to increasing technical competence among participants. UK NEQAS provides insight and feedback relating to MMR IHC protocols that most reliably produce high-quality MMR IHC staining to facilitate accurate reporting of the increasingly important tumour MMR status.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"467-474"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Previously unrecognised gene fusions across diverse solid tumours identified by anchored multiplex RNA sequencing.","authors":"Mariam M Youssef, Xiaojun Feng, Guomiao Shen, Qian Tan, Matija Snuderl, George Jour","doi":"10.1136/jcp-2026-210737","DOIUrl":"10.1136/jcp-2026-210737","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"500-502"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941455","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":"Mucinous carcinoma of the breast: morphological spectrum, diagnostic pitfalls and classification challenges.","authors":"Emad A Rakha, Bara Wazwaz, Stephen B Fox","doi":"10.1136/jcp-2026-210712","DOIUrl":"10.1136/jcp-2026-210712","url":null,"abstract":"<p><p>BackgroundMucinous breast carcinoma (MBC) is a well-recognised special type of invasive breast carcinoma (BC) characterised by abundant extracellular mucin and, in its classical form, a favourable clinical behaviour. However, extracellular mucin production is not unique to classical MBC and extracellular mucin is associated with a spectrum of benign and malignant entities with varying and overlapping morphological patterns but with very different clinical outcomes. Failure to recognise this diversity risks diagnostic imprecision and inappropriate management decisions.This review adopts a clinicopathological and pathogenetic framework centred on BCs associated with extracellular mucin, using classical low-grade MBC as the prototype lesion. The review integrates available molecular data, clinical outcome studies, observations on associated in situ and precursor lesions and accumulated diagnostic experience to generate conceptual models linking morphology, biology and clinical behaviour. Emphasis is placed on reproducible features relevant to routine diagnostic practice to enable pathologists to resolve a differential diagnosis of breast lesions in core biopsies and resections.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"433-444"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930118","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":"Rare case of CD20-positive primary cutaneous T-cell lymphoma, NOS, with an aggressive clinical course.","authors":"Danielle R Rinck, Michael S Chang, Christopher Iriarte, Robert Willim","doi":"10.1136/jcp-2024-210025","DOIUrl":"10.1136/jcp-2024-210025","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"503-504"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086271","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":"TCRbeta1/TCRbeta2 (TRBC1/TRBC2) antibody pair for determining T-cell monotypia as a surrogate for clonality in formalin-fixed paraffin-embedded material.","authors":"Anuradha Kaistha, Jinlong J Situ, Shelley Evans, Margaret Ashton-Key, Graham Ogg, Elizabeth Soilleux","doi":"10.1136/jcp-2026-210684","DOIUrl":"10.1136/jcp-2026-210684","url":null,"abstract":"<p><strong>Aim: </strong>T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates. Clonality testing is frequently required for diagnosis. It lacks the spatial context and is slow and expensive, relying on complex multiplexed PCR reactions, interpreted by scientists or pathologists with specialist molecular training. We set out to make monoclonal antibodies to develop a novel immunohistochemical test for T-cell lymphoma, analogous to the kappa/lambda assay for B-cell and plasma cell neoplasms.</p><p><strong>Methods: </strong>We developed a pair of highly specific monoclonal antibodies against the two alternatively used but very similar T-cell receptor β constant regions, TCRβ1 and TCRβ2 (encoded by the TRBC1 and TRBC2 gene segments). We demonstrate the feasibility of immunohistochemical detection of TCRβ1 and TCRβ2 in formalin-fixed, paraffin-embedded tissue as a novel diagnostic strategy for T-cell lymphomas.</p><p><strong>Results: </strong>Single immunostaining results are presented for 13 T-cell lymphomas and 8 benign T-cell populations, together with illustrative examples of TCRβ1/2 double immunostaining. Finally, we show that this single immunostaining is amenable to automated cell counting, permitting accurate calculation of the TCRβ2:TCRβ1 ratio.</p><p><strong>Conclusion: </strong>This novel assay can be used in a similar way to the kappa/lambda assay for B-cell and plasma cell neoplasms.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"486-493"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility and prognostic value of GATA3 in epithelioid malignant mesothelioma: a practical and cost-effective approach for resource-limited settings.","authors":"Dina Moustafa Thabit, Dalia M Thabet","doi":"10.1136/jcp-2026-210673","DOIUrl":"10.1136/jcp-2026-210673","url":null,"abstract":"<p><strong>Aims: </strong>Distinguishing epithelioid malignant mesothelioma (EMM) from poorly differentiated lung adenocarcinoma (PD-LUAD) remains challenging, particularly when 21.7% of PD-LUADs lack lineage-specific markers (thyroid transcription factor-1 (TTF-1)/Napsin A), creating a diagnostic blind spot. While GATA-binding protein 3 (GATA3) is established in sarcomatoid mesothelioma, its complementary diagnostic value and prognostic relevance in EMM are not well defined.</p><p><strong>Methods: </strong>This retrospective study analysed 115 tissue specimens (55 EMMs; 60 PD-LUADs). Immunohistochemistry for GATA3, calretinin, Wilms' tumour gene 1 (WT-1), TTF-1, Napsin A and pan-cytokeratin was performed. Results were correlated with clinicopathological parameters and overall survival (OS) using Kaplan-Meier and multivariate Cox regression analyses.</p><p><strong>Results: </strong>GATA3 was expressed in 78.2% of EMM but only 6.7% of PD-LUAD cases (p<0.001). Although not specific enough for standalone diagnosis, GATA3 provided meaningful complementary value: in TTF-1/Napsin A-negative PD-LUAD, GATA3 remained negative in 92.3%, helping to exclude EMM when used within a broader panel. Incorporating GATA3 with calretinin and WT-1 improved panel sensitivity to 96.4% while maintaining 100% specificity.High GATA3 expression in EMM correlated significantly with advanced T stage, higher International Mesothelioma Interest Group stage and poor functional status (Karnofsky performance status/Eastern Cooperative Oncology Group). Multivariate analysis identified GATA3 expression (p=0.037), smoking (p=0.041) and clinical T stage (p<0.001) as independent predictors of shorter OS. A qualitative inverse relationship between tumorous GATA3 and GATA3-positive tumour-infiltrating lymphocytes was also noted.</p><p><strong>Conclusions: </strong>GATA3 serves as a useful adjunct within established immunohistochemical panels, particularly in resolving ambiguity in double-negative PD-LUAD. Beyond its supportive diagnostic role, GATA3 demonstrates independent prognostic significance and may reflect underlying immune-microenvironmental features, meriting further exploration in biomarker-guided therapeutic stratification.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"475-485"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941534","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":"Phyllodes tumours of the breast: a 20-year institutional series with emphasis on criteria for malignancy.","authors":"Ping Tang, Alessa Aragao, Mia Yeager, Rachel Gordezky, Nolan Donahue, Lora Xu, Xiuzhen Duan, Emad A Rakha, Puay Hoon Tan","doi":"10.1136/jcp-2026-210626","DOIUrl":"10.1136/jcp-2026-210626","url":null,"abstract":"<p><strong>Background: </strong>Although histological criteria underpin current classification, accurate risk stratification, particularly for borderline and malignant tumours, remains challenging.</p><p><strong>Methods: </strong>We analysed a 20-year institutional series of phyllodes tumours (PTs), integrating clinicopathological data with long-term clinical outcomes. Histological features were extracted from original pathology reports, with slide re-review where archival material was available.</p><p><strong>Results: </strong>Among 111 PTs, 80% were benign, 11% borderline and 9% malignant. The follow-up ranged from 0 to 20 years, with 11.3, 10.3 and 7.6 years for benign, borderline and malignant PT, respectively. Most patients underwent local excision; mastectomy was performed in 22% of malignant PT. Final positive margins were identified in 18% of benign, 8% of borderline and none of the malignant tumours. Adjuvant radiotherapy was administered in 18% of borderline and 67% of malignant PT. Local recurrence occurred in 3%, 11% and 22% of benign, borderline and malignant tumours, respectively. Distant metastases were observed exclusively in malignant PTs (33%, 3/9 cases), two of which were preceded by local recurrence. Notably, two of the three metastatic malignant PTs showed either ≤10 mitoses/10 high-power field or <marked stromal atypia and lack of stromal overgrowth, which are required for diagnosis of malignant PT per WHO 5^th edition recommendation. The low event rate precluded robust multivariable analysis.</p><p><strong>Conclusion: </strong>Our results highlight the biological heterogeneity of malignant PTs and the limitations of rigid histological thresholds. These findings underscore the need for collaborative, multi-institutional prospective studies with standardised tumour sampling and reporting and molecular correlation to refine clinically meaningful risk stratification in PT.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"459-466"},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815809","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}