Journal of Clinical Pathology最新文献

{"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":"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":"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}

{"title":"Fusions in salivary gland neoplasms: a review of practical diagnostic applications.","authors":"Justin A Bishop","doi":"10.1136/jcp-2024-209859","DOIUrl":"10.1136/jcp-2024-209859","url":null,"abstract":"<p><p>There is an ongoing explosion of new information regarding the underlying molecular alterations driving a variety of salivary gland neoplasms. The volume of this emerging data makes it difficult to keep up with and may cause pathologists to believe that salivary gland neoplasms cannot be diagnosed without genetic analysis. This review focuses on the practical diagnostic applications of molecular tools in surgical pathology specimens.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"289-297"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557963","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":"Diagnostic utility of ERG immunostaining in dermatofibroma: be aware of ERG expression in cellular neurothekeoma.","authors":"Fleur Cordier, Liesbeth Ferdinande, Jo Van Dorpe, David Creytens","doi":"10.1136/jcp-2024-209913","DOIUrl":"10.1136/jcp-2024-209913","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"359-360"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949545","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":"Combined analysis of albumin in situ hybridisation and C reactive protein immunohistochemistry for the diagnosis of intrahepatic cholangiocarcinoma: towards a molecular classification paradigm.","authors":"Thomas Albrecht, Annik Rossberg, Fabian Rose, Kai Breuhahn, Eva-Marie Baumann, Marcell Tóth, Fritz Brinkmann, Alphonse Charbel, Monika Nadja Vogel, Bruno Köhler, Arianeb Mehrabi, Markus Wolfgang Büchler, Stephan Singer, Wiebke Solass, Beate Straub, Peter Schirmacher, Stephanie Roessler, Benjamin Goeppert","doi":"10.1136/jcp-2024-209429","DOIUrl":"10.1136/jcp-2024-209429","url":null,"abstract":"<p><strong>Aims: </strong>Intrahepatic cholangiocarcinoma (iCCA) is a diagnosis of exclusion that can pose a challenge to the pathologist despite thorough clinical workup. Although several immunohistochemical markers have been proposed for iCCA, none of them reached clinical practice. We here assessed the combined usage of two promising diagnostic approaches, albumin in situ hybridisation (Alb-ISH) and C reactive protein (CRP) immunohistochemistry, for distinguishing iCCA from other adenocarcinoma primaries.</p><p><strong>Methods: </strong>We conducted Alb-ISH and CRP immunohistochemistry in a large European iCCA cohort (n=153) and compared the results with a spectrum of other glandular adenocarcinomas of different origin (n=885). In addition, we correlated expression patterns with clinicopathological information and mutation data.</p><p><strong>Results: </strong>Alb-ISH was highly specific for iCCA (specificity 98.8%) with almost complete negativity in perihilar CCA and only rare positives among other adenocarcinomas (sensitivity 69.5%). CRP identified the vast majority of iCCA cases (sensitivity 84.1%) at a lower specificity of 86.4%. Strikingly, the combination of CRP and Alb-ISH boosted the diagnostic sensitivity to 88.0% while retaining a considerable specificity of 86.1%. Alb-ISH significantly correlated with CRP expression, specific tumour morphologies and small or large duct iCCA subtypes. Neither Alb-ISH nor CRP was associated with iCCA patient survival. 16 of 17 recurrent mutations in either IDH1, IDH2 and FGFR2 affected Alb-ISH positive cases, while the only KRAS mutation corresponded to an Alb-ISH negative case.</p><p><strong>Conclusions: </strong>In conclusion, we propose a sequential diagnostic approach for iCCA, integrating CRP immunohistochemistry and Alb-ISH. This may improve the accuracy of CCA classification and pave the way towards a molecular-guided CCA classification.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"307-316"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945040","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":"Novel scoring system provides high separation of diploidy and triploidy to aid partial hydatidiform mole diagnosis: an adaption of <i>HER2</i> D-DISH for ploidy analysis.","authors":"Caroline M Joyce, Susan Dineen, Julie Deane, Niamh Conlon, Paula M O'Shea, Paul Corcoran, John Coulter, Keelin O'Donoghue, Brendan Fitzgerald","doi":"10.1136/jcp-2023-209265","DOIUrl":"10.1136/jcp-2023-209265","url":null,"abstract":"<p><strong>Aims: </strong>Diagnosis of hydatidiform mole or molar pregnancy based on morphology alone can be challenging, particularly in early gestation, necessitating the use of ancillary techniques for accurate diagnosis. We sought to adapt the VENTANA <i>HER2</i> dual-colour dual-hapten in-situ hybridisation (D-DISH) assay by using the internal chromosome 17 enumeration probe to determine ploidy status.</p><p><strong>Methods: </strong>We selected 25 products of conception, consisting of molar and non-molar cases, to validate the <i>HER2</i> D-DISH assay. These cases had prior morphological assessment by a perinatal pathologist and ploidy analysis using molecular cytogenetics. Three independent observers, blinded to the original histopathological and genetic diagnosis, scored 10 representative areas on each slide. Interobserver variability was assessed by comparing the total scores of each observer using analysis of variance (ANOVA) and the kappa statistic.</p><p><strong>Results: </strong>Our ploidy scoring system accurately determined the correct number of diploid and triploid conceptuses, demonstrating complete concordance with pre-existing ploidy status and the initial diagnosis. Interobserver agreement between three independent scorers was robust: ANOVA (p=0.36) and kappa statistic (0.812, p<0.001). We achieved clear separation of average nuclear signals for diploid and triploid conceptuses, which was statistically significant (p<0.05). Employing our innovative scoring system, known as the 'rule of 5', we established ploidy decision thresholds for all 25 cases.</p><p><strong>Conclusions: </strong>Our modified <i>HER2</i> D-DISH ploidy assay simplifies the process of ploidy determination and improves the accuracy of morphological diagnosis of molar pregnancy. The <i>HER2</i> D-DISH assay was selected for ploidy analysis due to the widespread availability of in-situ hybridisation in pathology laboratories.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"320-326"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329836","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":"von Meyenburg complexes are more frequently associated with cholangiocarcinoma.","authors":"Dhanpat Jain, Binny Khandakar, Pu Ni, Barton Kenney, Lihui Qin, Vikram Deshpande, Maria Isabel Fiel","doi":"10.1136/jcp-2024-209572","DOIUrl":"10.1136/jcp-2024-209572","url":null,"abstract":"<p><strong>Aim: </strong>There is some evidence that von Meyenburg complexes (VMCs) can progress to cholangiocarcinoma (CC). This study aimed to evaluate the prevalence of VMCs in CC cases.</p><p><strong>Methods: </strong>All hepatic resections and explants with intra-hepatic CC (I-CC) and hilar-CC (H-CC) from 1985 to 2020 were studied. Hepatic resections (n=68) for benign lesions or metastatic colonic carcinoma and 15 cases with cirrhosis without any cancer were used as controls.</p><p><strong>Results: </strong>A total of 118 cases of CC (88 I-CC, 30 H-CC) were identified. Of these, 61 (52%) patients had no known background liver disease, and 20 (17%) had cirrhosis. Associated liver disorders included metabolic dysfunction-associated steatohepatitis (23), chronic viral hepatitis B or C (13), biliary disease (primary or secondary sclerosing cholangitis) (8), polycystic kidney disease (6), cryptogenic cirrhosis (5) and others miscellaneous disorders (7). VMCs were present in 34 (39%) of 88 I-CC cases and 7 (23%) of 30 H-CC cases. VMCs were present within the tumour (20 cases), outside the cancer (21 cases) or at both locations (10 cases). VMCs with dysplasia/carcinoma in situ were seen in 19 of 41 (46%) cases with CC and VMCs. In addition, bile duct adenomas were identified in 6 (5%) of CC. 7% of controls showed the presence of VMCs compared with 35% of CC cases (p<0.05).</p><p><strong>Conclusions: </strong>VMCs are seen far more frequently in patients with CC than in the control group. The findings support the hypothesis that VMCs could represent a precursor of CC or a marker for a higher risk of developing CC.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"300-306"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904131","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: myeloid neoplasms.","authors":"Xueyan Chen, Nikhil Patkar, Prashant Tembhare, Subramanian Papagudi, Cecelia Yeung, Rashmi Kanagal Shamanna, Sumeet Gujral, Brent Wood, Kikkeri N Naresh","doi":"10.1136/jcp-2024-210022","DOIUrl":"10.1136/jcp-2024-210022","url":null,"abstract":"<p><p>The fifth edition of the WHO classification of haematolymphoid tumours (WHO-HEM5) introduces significant advancements in the understanding and diagnosis of myeloid neoplasms, emphasising molecular and genetic insights. This review highlights key updates from the revised fourth edition (WHO-HEM4R), particularly the integration of genetic criteria for disease classification. Many entities are now defined by specific genetic abnormalities, enhancing diagnostic precision and prognostic assessment. Notably, the elimination of the 20% blast threshold for acute myeloid leukaemia (AML) with specific defining genetic alterations reflects a shift towards genomic-driven diagnostics. Additional updates include the refined subclassification of myelodysplastic neoplasms (MDS) and MDS/myeloproliferative neoplasms, as well as the recognition of novel entities such as clonal haematopoiesis and MDS with biallelic TP53 inactivation, further expanding the spectrum of myeloid neoplasms. WHO-HEM5 illustrates the diagnostic utility of morphology, flow cytometry, immunohistochemistry and next-generation sequencing in resource-rich settings. However, its implementation in low-income and middle-income countries (LMICs) remains challenging due to limited access to advanced diagnostic tools. This review explores strategies to optimise diagnosis in resource-constrained environments, where morphology and immunophenotyping remain fundamental. By integrating molecular diagnostics with traditional methods, WHO-HEM5 aims to refine classification and facilitate risk stratification in the era of personalised medicine, providing haematopathologists and clinicians with an essential framework to navigate the complexities of myeloid neoplasms. The emphasis on advancing haematopathology practices worldwide, including in LMICs, demonstrates the ongoing commitment to improving global outcomes in haematological malignancies.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"335-345"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414269","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":"Sunitinib induced glomerular thrombotic microangiopathy in a patient with refractory pancreatic neuroendocrine tumour.","authors":"Aisha Khan, Margarita Consing Gangelhoff, Simon Moubarak, Sandra Herrmann, Karim Nooruddin, Mariam Alexander","doi":"10.1136/jcp-2024-209851","DOIUrl":"10.1136/jcp-2024-209851","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"357-358"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824200","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}