Journal of Clinical Pathology最新文献

{"title":"Deep learning predicts microsatellite instability status in colorectal carcinoma in an ethnically heterogeneous population in South Africa.","authors":"Alessandro Pietro Aldera, Didem Cifci, Gregory Patrick Veldhuizen, Wan-Jung Tsai, Komala Pillay, Adam Boutall, Hermann Brenner, Michael Hoffmeister, Jakob Nikolas Kather, Raj Ramesar","doi":"10.1136/jcp-2025-210053","DOIUrl":"https://doi.org/10.1136/jcp-2025-210053","url":null,"abstract":"<p><strong>Background: </strong>Deep learning (DL) models are effective pre-screening tools for detecting mismatch repair deficiency (dMMR) in colorectal carcinoma (CRC). These models have been trained and validated on large cohorts from the Northern Hemisphere, without representation of African samples. We sought to determine the performance of a DL model in an ethnically heterogeneous cohort of patients from South Africa.</p><p><strong>Methods: </strong>Our cohort comprised 197 CRC resection specimens, with scanned whole slide images tessellated and inputted into a transformer-based DL model trained on large international cohorts. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC), sensitivity and specificity. The maximal Youden's J index was calculated to determine the optimal cut-off threshold for the model prediction score.</p><p><strong>Results: </strong>Our model yielded an AUROC of 0.91 (±0.05). Using a prediction score threshold of 0.620 produced an overall sensitivity of 85.7% (95% CI 73.3% to 92.9%) and a specificity of 82.4% (95% CI 75.5% to 87.7%). The false negative cases were predominantly left-sided (71.4%) and did not show the typical dMMR/microsatellite instability-high histological phenotype. Sensitivity was lower (50%-75%) in cases showing isolated PMS2 or MSH6 loss of staining. Calibrating the classification threshold to 0.470, the sensitivity was optimised to 95.6% (95% CI 86.3% to 98.9%) with a specificity of 69.6% (95% CI 61.8% to 76.4%). This would have resulted in excluding 103 cases (52.3%) from downstream immunohistochemical (IHC) or molecular testing.</p><p><strong>Conclusions: </strong>Following appropriate region-specific calibration, we have shown that this model could be employed to accurately prescreen for dMMR in CRC, thereby reducing the burden of downstream IHC and molecular testing in a resource-limited setting.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111051","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":"https://doi.org/10.1136/jcp-2024-210025","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-16","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":"Improving transparency in publishing: gaps in standardised reporting across surgical pathology and laboratory medicine journals.","authors":"Griffin Hughes, Cameron O'Brien, Reece Anderson, Matt Vassar","doi":"10.1136/jcp-2024-209858","DOIUrl":"https://doi.org/10.1136/jcp-2024-209858","url":null,"abstract":"<p><strong>Aims: </strong>Research reporting checklists are itemised writing standards to improve transparency and facilitate reproducibility. Previous assessments of their recommendation or requirement have demonstrated improved checklist adherence across medical specialties and study designs. Here, we investigated the endorsement of reporting checklists within pathology, laboratory medicine and forensic science journals.</p><p><strong>Methods: </strong>We queried Google Scholar Metrics and the Scopus CiteScore tool to identify top pathology and forensic medicine journals. Two authors independently assessed for the mention, recommendation or requirement or checklists-derived from the Enhancing the Quality and Transparency Of Health Research (EQUATOR) network-as well as study preregistration within each journal's aims and instructions for authors. Journal editors were contacted by one author every 3 weeks to confirm whether or not certain study designs would be considered for publication.</p><p><strong>Results: </strong>Of the 88 journals evaluated, most did not mention or endorse the EQUATOR Network (73.9%) or International Committee of Medical Journal Editors reporting standards (51.1%). The most commonly reported checklists included Animal Research: Reporting of In Vivo Experiments (38.6%), Consolidated Standards of Reporting Trials (28.4%) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (25.0%). The CARE reporting checklist for case reports was required most often by five journals (5.7%). The final email response from journal editors and contacts was 9.1%.</p><p><strong>Conclusions: </strong>Reporting checklists were suboptimally mentioned and rarely required. Even with many basic and diagnostic science reporting checklists and initiatives, endorsement remains low. We recommend that authors, reviewers and editors become familiar with relevant reporting checklists for their fields and publishing spaces to improve checklist visibility and adherence for scientific transparency, reproducibility and rigour.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078351","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":"<i>SOX17</i>: a new therapeutic target for immune evasion of colorectal cancer.","authors":"Avash Das, Omer Yilmaz, Osman Yilmaz, Vikram Deshpande","doi":"10.1136/jcp-2024-209878","DOIUrl":"https://doi.org/10.1136/jcp-2024-209878","url":null,"abstract":"<p><p>Despite advances in cancer immunotherapies across various cancers, survival outcomes in colorectal cancer (CRC) with these agents remain largely unsatisfactory despite the high tumour burden. Colorectal stem cells (CSCs), especially <i>LGR5</i>+ CSCs, are the significant drivers in CRC initiation, progression and resistance to conventional therapies. Although native immune surveillance is sufficient to combat early tumour formation, CRC evades early immune detection with its well-documented adenoma-to-carcinoma sequence. The exact mechanism underlying this phenomenon still needs to be better understood. SRY-related HMG box gene 17 (<i>SOX17</i>), a transcription factor that specifies embryonic gut formation, is increasingly recognised as a significant factor in CRC tumourigenesis. However, its role as a tumour suppressor or oncogene is still debated. Evidence from a recent study highlighted the critical role of <i>SOX17</i> in reshaping the tumour immune ecosystem through the simultaneous inhibition of CD8+ T cells and selective suppression of <i>LGR5</i> expression in CSCs through transcriptional repression, thereby facilitating disease progression. Given its role in immune evasion, <i>SOX17</i> could be a promising marker in personalised therapy. Additionally, <i>SOX17</i> could play a role in the diagnostic arena, potentially identifying dysplasia in the gastrointestinal tract. Future clinical, basic and genetic studies focusing on <i>SOX17</i> are needed to ascertain its mechanistic role in tumour immunomodulation in CRC and diagnosing preneoplastic lesions in the gastrointestinal tract.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023492","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":"Fifth edition WHO classification: precursor lymphoid neoplasms, acute leukaemias of mixed or ambiguous lineage, myeloid/lymphoid neoplasms, and histiocytic and dendritic cell neoplasms, including strategies for application <b>in resource-limited settings</b>.","authors":"Prashant Tembhare, Xueyan Chen, John K C Chan, Brent Wood, Kikkeri N Naresh","doi":"10.1136/jcp-2025-210135","DOIUrl":"https://doi.org/10.1136/jcp-2025-210135","url":null,"abstract":"<p><p>The fifth edition of the WHO classification of haematolymphoid tumours (WHO-HEM5) introduces significant updates to the classification of acute lymphoblastic leukaemia, ALAL (including mixed phenotype acute leukaemia (MPAL)), myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), and histiocytic and dendritic cell neoplasms, reflecting the advances in the understanding of the genetic basis of these diseases. This review provides an overview of these changes, highlighting a shift to a more refined molecular-genetic approach. The incorporation of newly recognised genetic subtypes into the classification scheme underscores the evolving landscape of these entities. Challenges in diagnosing ALAL/MPAL and MLN-TK are discussed, along with recent insights into histiocytic and dendritic cell neoplasms, including newly defined entities such as ALK-positive histiocytosis.The review also explores the practical implications of WHO-HEM5, particularly in resource-limited settings, where comprehensive molecular testing may be unavailable. While morphology and immunohistochemistry remain essential diagnostic tools, strategic use of flow cytometry and targeted fluorescence in situ hybridisation can facilitate risk-adapted classification and improve survival in regions with limited resources and therapeutic options. Future large-scale studies are necessary to establish the diagnostic and prognostic value of these newly genetically defined entities for diverse healthcare environments, and to standardise guidelines in refining disease classification and optimising patient outcomes.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994495","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":"<i>GLI1</i> amplification and fusion in <i>MDM2</i>-amplified low-grade osteosarcoma.","authors":"Lan Li, Ming Zhang, Xiaoqi Sun, Yuzi Zhang, Yongbin Su, Rongfang Dong, Tingting Zhang, Ziyi Wang, Yi Ding","doi":"10.1136/jcp-2024-209813","DOIUrl":"https://doi.org/10.1136/jcp-2024-209813","url":null,"abstract":"<p><strong>Aims: </strong>Glioma-associated oncogene homologue 1 (<i>GLI1</i>) was recently shown to be coamplified with mouse double minute 2 (<i>MDM2</i>), cyclin-dependent kinase 4 (<i>CDK4</i>) and some other adjacent genes in a significant subset of <i>GLI1</i>-altered mesenchymal tumours and well-differentiated/dedifferentiated liposarcomas, which are characterised by <i>MDM2</i> amplification. Given that <i>MDM2</i> is also amplified in low-grade osteosarcoma (LGOS), we investigated the prevalence of <i>GLI1</i> amplifications/fusions in a series of 15 cases of <i>MDM2</i>-amplified LGOS, an area that has not been previously explored.</p><p><strong>Methods: </strong>This study conducted a retrospective analysis and examined <i>GLI1</i> amplifications/fusions in 15 cases of <i>MDM2</i>-amplified LGOS and 46 cases of other bone tumours and tumour-like lesions using fluorescence in situ hybridisation with a <i>GLI1</i> amplification probe and a <i>GLI1</i> break-apart probe. Six cases of LGOS were also tested by next-generation sequencing.</p><p><strong>Results: </strong>Fluorescence in situ hybridisation analysis revealed that 13 of 15 (87%) LGOS cases exhibited <i>GLI1</i> amplification; no fusion gene was found. Next-generation sequencing revealed that all six tested cases showed <i>GLI1</i> amplification and one case had both <i>GLI1</i> amplification and <i>GLI1</i> gene fusion (<i>PPM1H::GLI1</i>). All 46 cases of other bone tumours and tumour-like lesions were negative for <i>GLI1</i> amplification and <i>GLI1</i> fusion.</p><p><strong>Conclusion: </strong>These results indicate that <i>GLI1</i> amplification is common in LGOS, and <i>GLI1</i> fusion could occur in LGOS.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967791","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":"Prognostic value of PRAME expression in uveal melanoma: a meta-analysis.","authors":"Manuel Perez-Perez, Carmen García de Sola-Llamas, Gonzalo Mariscal, Laura Macías-García","doi":"10.1136/jcp-2024-210032","DOIUrl":"https://doi.org/10.1136/jcp-2024-210032","url":null,"abstract":"<p><strong>Introduction: </strong>Overexpression of Preferentially Expressed Melanoma Antigen (PRAME) is associated with melanoma progression. In the case of uveal melanoma (UM), PRAME expression was identified as conferring a metastatic risk.</p><p><strong>Aim: </strong>This study aimed to review the available evidence regarding the prognostic value of PRAME expression in UM.</p><p><strong>Methods: </strong>This study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included cohort studies and randomised clinical trials. The methodological quality of the studies was assessed by the Methodological Index for Non-Randomised Studies (MINORS). The meta-analysis was performed using Review Manager V.5.4. Heterogeneity was checked with the I2 test. If there was no heterogeneity, a fixed-effects model was adopted.</p><p><strong>Results: </strong>Nine studies were included. The PRAME+ group showed significant differences in the development of metastases OR (M-H, Fixed, 95% CI): 3.46 (2.84, 4.22). The PRAME+ group had a significantly shorter time to metastasis MD (IV, Random, 95% CI): -28.31 (-55.41, -1.22) and a significantly lower percentage metastasis-free survival at 5-year follow-up MD (IV, Fixed, 95% CI): -21.67 (-25.74,-17.61). PRAME expression was an independent marker for the development of metastatic disease at any follow-up HR (IV, Fixed, 95% CI): 2.00 (1.60, 2.49). In addition, PRAME+tumours were significantly larger than PRAME-tumours MD (IV, Random, 95% CI): 0.22 (0.01, 0.42).</p><p><strong>Conclusions: </strong>PRAME is a good prognostic marker in UM. We believe that further studies are needed to determine the most cost-effective method for reporting PRAME overexpression.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982263","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":"Patients review their pathology reports before their treating physician: heading towards patient autonomy? Focus on prostate cancer.","authors":"Rodolfo Montironi, Alessia Cimadamore, Antonio Lopez-Beltran, Eamonn T Rogers, Liang Cheng","doi":"10.1136/jcp-2025-210200","DOIUrl":"https://doi.org/10.1136/jcp-2025-210200","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020302","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":"Nancy histological index in ulcerative colitis: an interobserver study.","authors":"Melissa C Hutchings, Adrian C Bateman","doi":"10.1136/jcp-2025-210129","DOIUrl":"https://doi.org/10.1136/jcp-2025-210129","url":null,"abstract":"<p><p>The Nancy histological index (NHI) is a measure of disease activity within colorectal biopsies and a predictor of clinical outcome in ulcerative colitis (UC). We measured interobserver agreement (IOA) during NHI scoring of 20 colorectal biopsies in UC by 13 pathologists of varying grade and experience. The level of IOA was measured using Fleiss' kappa statistic. The degree of IOA was moderate, with kappa scores of 0.53 (SE 0.01) for the whole group (n=13), 0.50 (SE 0.05) for the consultants (n=4) and 0.54 (SE 0.019) for the trainees (n=9). Normal biopsies or those showing a mild increase in lamina propria chronic inflammation were graded most reproducibly. Subjectivity existed at NHI grade boundaries, particularly identification of mild acute inflammation (AI), assessment of AI severity and identification of ulceration. An education programme for pathologists or an artificial intelligence tool may improve IOA in the future.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023493","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":"Morphology combined with <i>HER2</i> D-DISH ploidy analysis to diagnose partial hydatidiform mole: an evaluation audit using molecular genotyping.","authors":"Caroline M Joyce, Geoffrey J Maher, Susan Dineen, Nirosha Suraweera, Tommie V McCarthy, John Coulter, Keelin O'Donoghue, Michael J Seckl, Brendan Fitzgerald","doi":"10.1136/jcp-2023-209269","DOIUrl":"10.1136/jcp-2023-209269","url":null,"abstract":"<p><strong>Aims: </strong>A hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to confirm a morphologically suspected PHM diagnosis. This study sought to evaluate the clinical accuracy of PHM diagnosis using morphological assessment supported by <i>HER2</i> dual-colour dual-hapten in situ hybridisation (D-DISH) ploidy determination.</p><p><strong>Methods: </strong>Over a 2-year period, our unit examined 1265 products of conception (POCs) from which 103 atypical POCs were diagnosed as PHM or non-molar conceptuses with the assistance of <i>HER2</i> D-DISH ploidy analysis. We retrospectively audited a sample of 40 of these atypical POCs using short tandem repeat genotyping. DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped using 24 polymorphic loci. Parental alleles in placental villi were identified by comparison to those in maternal decidua. To identify triploid PHM cases, we sought three alleles of equal peak height or two alleles with one allele peak twice the height of the other at each locus.</p><p><strong>Results: </strong>Thirty-six of the 40 cases (19 PHM and 17 non-molar) were successfully genotyped and demonstrated complete concordance with the original diagnosis. All PHMs were diandric triploid of dispermic origin. In two non-molar diploid cases, we identified suspected trisomies (13 and 18), which potentially explains the pregnancy loss in these cases.</p><p><strong>Conclusions: </strong>This study validates the use of <i>HER2</i> D-DISH ploidy analysis to support the diagnosis of a morphologically suspected PHM in our practice.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"327-334"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329835","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}