Pathology最新文献

{"title":"Neuropathology meets chemical and genetic pathology head-on: a personal perspective.","authors":"Colin L Masters","doi":"10.1016/j.pathol.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.11.001","url":null,"abstract":"<p><p>Medical science has made revolutionary discoveries around the nosology and aetiology of the neurodegenerative diseases. Dementia is the second leading cause of death in Australia. My colleagues and I are now looking at therapeutics which potentially can delay or prevent the onset of Alzheimer's disease (AD). Advances in diagnosis allow detection of preclinical AD. Neuropathologists working closely with chemical and genetic pathologists have a major role to play in pushing diagnostics and therapeutics to the forefront of clinical management of these diseases.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved costs and turnaround time for Treponema pallidum detection utilising a real-time PCR assay developed for the Hologic Panther Fusion system.","authors":"Radhika Nagappan, Erasmus Smit, Saed Miri Nargesi, Gary McAuliffe","doi":"10.1016/j.pathol.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.09.011","url":null,"abstract":"<p><p>The aims of this study were to evaluate the performance and workflow characteristics of a laboratory-developed test to detect Treponema pallidum on the Hologic Panther Fusion system compared with an existing commercial assay. A Hologic Panther Fusion-based real-time polymerase chain reaction assay was optimised for T. pallidum (TP RT-PCR) using previously published primer and probe sequences and validated with a simplified preprocessing protocol. A total of 124 clinical and external quality assurance (EQA) samples were tested in parallel by the new method and the Viasure T. pallidum RT-PCR (Certest Biotech). Cross reactivity, limit of detection, PCR efficiency and coefficient of variation (CV) were measured. Simplified preprocessing methods involving either concentration or vortexing were compared with the existing overnight chemical/enzymatic preprocessing method for a subset of positive samples. Workflow impacts were assessed before and after implementation. The Panther Fusion T. pallidum assay correctly detected 65 of 65 (100%) positive clinical and EQA samples and 33 of 33 (100%) negative samples. No cross reactivity was observed for 45 of 45 (100%) samples. The limit of detection was 15 copies/reaction, and intrarun CV was <1.66%. The simplest preprocessing protocol detected 34 of 34 (100%) positive samples with an average Δ cycle threshold (Ct) <0.82 compared with the Viasure workflow. The new workflow reduced median turnaround time from 3.83 to 1.73 days (p<0.001) and estimated costs from US$35,004.96 to US$19,390.15 in the 3 months post-implementation. The laboratory-developed Panther Fusion T. pallidum assay is a sensitive and specific method for detection of syphilis and a cost-effective option to help improve workflow and turnaround time in a diagnostic laboratory.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain crisis complicating severe bone marrow necrosis during induction for acute promyelocytic leukaemia.","authors":"Elizabeth Goodall, Aditya Tedjaseputra, Cathryn Hui, Patricia Walker, Jake Shortt","doi":"10.1016/j.pathol.2024.09.012","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.09.012","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the detection of congenital syphilis: reviewing test utility and adherence to recommendations.","authors":"Selina M J Lim, Hannah Gooding, Andrew Walczak, Justin Morgan, Eun Hye Grace Lee, Briony Hazelton, Tim Ford, Carolien Giele, Suzanne P McEvoy, Michelle Porter, David A Foley","doi":"10.1016/j.pathol.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.09.010","url":null,"abstract":"<p><p>Western Australia (WA) has experienced a resurgence of congenital syphilis. Appropriate microbiology testing of the neonate is recommended to confirm infection, including syphilis immunoglobulin M (IgM), rapid plasma reagin (RPR) paired with a maternal sample, and polymerase chain reaction (PCR) on placenta and nasal swabs. We examined the performance of microbiology tests in confirmed congenital syphilis cases and the adherence to testing recommendations in those assessed as high risk. We reviewed the microbiology results of confirmed congenital syphilis cases in WA between 1 January 2018 and 31 December 2023. In addition, microbiology testing of neonates from metropolitan Perth identified as being at a high risk of congenital syphilis between 1 January 2021 and 31 October 2023 was reviewed. Eighteen congenital syphilis cases were identified; data were unavailable for a case born interstate. Of the 17 included cases, the case fatality rate was 35% (6/17; five stillbirths and one perinatal death). Placenta tissue PCR was positive in all stillbirths. Of the 12 live births, 83% were symptomatic at delivery. Perinatal testing was performed in 11 live births (11/12); IgM was detected in 55% (6/11). Placenta tissue PCR was positive in 88% (7/8 tested). Nasal swab PCR was positive in 57% (4/7 tested). There were 22 neonates classified as being at a high risk for congenital syphilis infection; all had IgM and RPR testing. Syphilis PCR was performed on placenta tissue samples in 64% (14/22) and on nasal swabs in 64% (14/22) of cases. Comprehensive microbiological testing, including syphilis IgM and placenta tissue PCR, is required to confirm congenital syphilis infection. Continuous evaluation of testing will be crucial for individual case detection and monitoring of the ongoing outbreak. Given the risk of incomplete specimen collection, our data support ​the adoption of a risk-based approach for neonates at risk of congenital syphilis, with management guided by maternal serology and treatment history.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation sequencing RNA fusion panel for the diagnosis of haematological malignancies.","authors":"Trung Quang Ngo, Anna Fong Na Goh, Pranav Dorwal, Emmanuel Leong, Jake Shortt, Pasquale L Fedele, Michael Gilbertson, Chun Yew Fong, Naranie Shanmuganathan, Beena Kumar, Paul Yeh","doi":"10.1016/j.pathol.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.09.009","url":null,"abstract":"<p><p>Haematological malignancies are being increasingly defined by gene rearrangements, which have traditionally been detected by karyotype, fluorescent in situ hybridisation (FISH) or reverse-transcriptase polymerase chain reaction (RT-PCR). However, these traditional methods may miss cryptic gene rearrangements and are limited by the number of gene rearrangements screened at any one time. A next-generation sequencing (NGS) RNA fusion panel is an evolving technology that can identify multiple fusion transcripts in a single molecular assay, even without prior knowledge of breakpoints or fusion partners. We explored the utility of the TruSight RNA Fusion Panel for use in haematological malignancies by sequencing 30 peripheral blood or bone marrow aspirate samples. Secondary and tertiary analyses were performed using the Illumina DRAGEN RNA pipeline and PierianDx Clinical Genomics Workspace platform. Our RNA fusion panel was able to reliably detect known fusion transcripts, such as BCR::ABL1, ETV6::RUNX1 and KMT2A::AFF1, in acute lymphoblastic leukaemia (ALL), KMT2A::MLLT3, KMT2A::MLLT6, PML::RARA and CBFB::MYH11 in acute myeloid leukaemia (AML), and FIP1L1::PDGFRA in myeloid/lymphoid neoplasm with eosinophilia (MLN-Eo). In addition, it was able to detect rare KAT6A::CREBBP and CHIC2::ETV6 fusions, which could not be confirmed by traditional methods. The assay had a transcript limit of detection of approximately 5-10% of positive controls. These findings confirm the unique utility of the NGS-based RNA fusion panel as a diagnostic tool to identify gene rearrangements that drive haematological malignancies. It can identify novel and rare gene rearrangements to assist with diagnosis, prognostication and treatment decisions.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell division cycle 6 ​is an independent prognostic biomarker in breast cancer.","authors":"Yousif A Kariri, Mansour Alsaleem, Abdulbaqi Al-Kawaz, Bader Y Alhatlani, Nigel P Mongan, Andrew R Green, Emad A Rakha","doi":"10.1016/j.pathol.2024.09.006","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.09.006","url":null,"abstract":"<p><p>Cell division cycle 6 (CDC6) is a cell cycle protein involved in cell cycle control, DNA replication and cancer cell apoptosis. This study investigated the prognostic value of CDC6 in breast cancer (BC) utilising large well-characterised cohorts of early-stage ​BC. CDC6 messenger RNA (mRNA) was assessed using the Molecular Taxonomy of the Breast Cancer International Consortium (n=1980), the Cancer Genome Atlas (n=854) and Kaplan-Meier plotter (n=4,929) cohorts. CDC6 protein expression was evaluated using immunohistochemistry in a large (n=951) well-characterised Nottingham BC cohort. The associations between CDC6, clinicopathological parameters, molecular features and patient outcomes were assessed. High CDC6 expression positively correlated with dysregulation of key BC-related genes, including gene involved in cell cycle, DNA damage repair, epithelial cell migration, ​and tumour microenvironment control, as well as with markers characteristic of the basal-like phenotype (CK5, CK14 and CK17). High CDC6 mRNA and protein expression were associated with clinicopathological parameters characteristic of aggressive behaviour, including high tumour grade, large tumour size, the presence of lymphovascular invasion and hormone receptor negativity. High CDC6 protein expression was an independent predictor of poor outcome [p=0.007; hazard ratio (HR)=1.3; 95% confidence interval (CI) 1.2-1.9). This study indicates that CDC6 is an independent prognostic biomarker in BC. These results warrant further functional validation for CDC6 as a potential therapeutic target in BC.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current concepts and molecular pathology of neurodegenerative diseases.","authors":"Shelley L Forrest, Gabor G Kovacs","doi":"10.1016/j.pathol.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.10.006","url":null,"abstract":"<p><p>Neurodegenerative diseases are a pathologically, clinically and genetically diverse group of diseases characterised by selective dysfunction, loss of synaptic connectivity and neurodegeneration, ​and are associated with the deposition of misfolded proteins in neurons and/or glia. Molecular studies have highlighted the role of conformationally altered proteins in the pathogenesis of neurodegenerative diseases and have paved the way for developing disease-specific biomarkers that capture and differentiate the main type/s of protein abnormality responsible for neurodegenerative diseases, some of which are currently used in clinical practice. These proteins follow sequential patterns of anatomical involvement and disease spread in the brain and may also be detected in peripheral organs. Recent studies suggest that glia are likely to have an important role in pathological spread throughout the brain and even follow distinct progression patterns from neurons. In addition to morphological and molecular approaches to the classification of these disorders, a further new stratification level incorporates the structure of protein filaments detected by cryogenic electron microscopy. Rather than occurring in isolation, combined deposition of tau, amyloid-β, α-synuclein and TDP-43 are frequently observed in neurodegenerative diseases and in the ageing brain. These can be overlooked, and their clinicopathological relevance is difficult to interpret. This review provides an overview of disease pathogenesis and diagnostic implications, recent molecular and ultrastructural classification of neurodegenerative diseases, how to approach ageing-related and mixed pathologies, ​and the importance of the protein-based classification system for practising neuropathologists and clinicians. This review also informs general pathologists about the relevance of ongoing full body autopsy studies to understand the spectrum and pathogenesis of neurodegenerative diseases.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A diagnostic dilemma for a patient with skin lesions and marked leukocytosis: mixed-phenotype acute leukaemia or blastic plasmacytoid dendritic cell neoplasm with aberrant cytoplasmic CD3 expression?","authors":"Zhihong Hu, C Cameron Yin, Xiaoping Sun, Xin Han, Wei Wang, Sa Wang, M James You","doi":"10.1016/j.pathol.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.09.008","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The utility of postmortem radiological imaging in forensic neuropathology practice.","authors":"Linda Iles","doi":"10.1016/j.pathol.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.10.005","url":null,"abstract":"<p><p>The integration of postmortem computed tomography (PMCT) into forensic pathology practice has been the discipline's most important advance over the past 25 years. Likewise, postmortem radiological imaging has enhanced forensic neuropathology practice. The strengths and weaknesses of PMCT as applied to forensic neuropathology practice will be discussed.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological spectrum of sporadic Creutzfeldt-Jakob disease.","authors":"Diane L Ritchie, Colin Smith","doi":"10.1016/j.pathol.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.09.005","url":null,"abstract":"<p><p>Human prion diseases are a rare group of transmissible neurodegenerative conditions which are classified according to their aetiology as sporadic, genetic or acquired forms. Creutzfeldt-Jakob disease (CJD) is the most common form of human prion disease, with the sporadic form accounting for ∼85% of all reported cases. While advances have been made in the development of clinical tools and biomarkers in the diagnosis of prion disease, allowing greater diagnostic certainty for surveillance purposes, definitive diagnosis requires neuropathological examination of the brain at postmortem. Since the 1990s, efforts have been made to develop a classification system for sporadic CJD (sCJD) based on observed differences in the clinical features and the pathological phenotype (the nature and degree of spongiform vacuolation, neuronal loss, astrogliosis and misfolded prion protein accumulation in the brain), also referred to as the 'histotype'. Six major clinicopathological subtypes of sCJD are internationally recognised, largely correlating with the combination of the two distinct types of the protease-resistant prion protein (PrP^res type 1 or 2) and the methionine (M)/valine (V) polymorphism at codon 129 of the prion protein gene (PRNP): MM1/MV1, MM2-cortical, MM2-thalamic, MV2, VV1 and VV2. This classification system has been extended to recognise sCJD cases demonstrating both mixed PrP^res types or mixed histotypes in the brain of the same individual, as well as including atypical or novel pathological phenotypes. In this review, we will provide an up-to-date overview of the current classification of sCJD based on the prominent neuropathological features. In addition, with levels of infectivity at their highest in the brain, we will also discuss the additional precautions that are recommended when handling and examining postmortem tissues from patients with suspected prion disease.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}