PathologyPub Date : 2025-03-05DOI: 10.1016/j.pathol.2024.12.644
Man-Kwan Yip , Hoi Kevin Chin , Man Au Yeung , Wing-Tat Poon
{"title":"Novel mutation in acaeruloplasminaemia: a rare case of neurodegeneration mimicking normal pressure hydrocephalus","authors":"Man-Kwan Yip , Hoi Kevin Chin , Man Au Yeung , Wing-Tat Poon","doi":"10.1016/j.pathol.2024.12.644","DOIUrl":"10.1016/j.pathol.2024.12.644","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":"57 4","pages":"Pages 521-524"},"PeriodicalIF":3.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796124","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}
PathologyPub Date : 2025-03-04DOI: 10.1016/j.pathol.2024.12.639
Anne Rullier , Samuel Amintas , Maxime Marques , Brigitte Le Bail , Geneviève Belleannée , Pierre Dubus , Rémi Vergara , Noelle Bernard
{"title":"Recycled formalin: a new tool to mitigate the environmental impact of surgical pathology in routine practice","authors":"Anne Rullier , Samuel Amintas , Maxime Marques , Brigitte Le Bail , Geneviève Belleannée , Pierre Dubus , Rémi Vergara , Noelle Bernard","doi":"10.1016/j.pathol.2024.12.639","DOIUrl":"10.1016/j.pathol.2024.12.639","url":null,"abstract":"<div><div>Formalin is universally acknowledged as the gold standard for tissue fixation. However, it is a dangerous toxic chemical without any realistic substitute. Therefore, decreasing its use seems to be the only way to reduce its environmental impact. We assessed the feasibility of an innovative formalin recycling circuit based on the reuse of formalin following biopsy removal and paper filtration. We also assessed the efficiency of a policy of less formalin use in routine practice without compromising work quality and security. The recycled formalin was equivalent to new formalin in terms of its chemical and molecular properties, as well as the fixation, analysis, and storage of tissue samples. Moreover, its use for fixation did not affect molecular analyses. We calculate that our process would have decreased the total consumption of formalin in 2022 by 26% compared to 2021. This corresponds to financial savings of €4620, a 2434 kg CO<sub>2</sub> equivalent reduction in greenhouse gases, and substantial decreases in toxicity to humans and freshwater. Our recycled formalin circuit is a simple, easy-to-implement, efficient way to mitigate the environmental impact of formalin in surgical pathology without compromising the quality of analysis and the safety of the pathology staff.</div></div>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":"57 4","pages":"Pages 437-442"},"PeriodicalIF":3.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788744","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}
PathologyPub Date : 2025-03-03DOI: 10.1016/j.pathol.2025.01.002
Wayne Dimech, Patricia Mitchell, Giuseppe Vincini
{"title":"Cost-benefit analysis of two quality control approaches for infectious disease testing.","authors":"Wayne Dimech, Patricia Mitchell, Giuseppe Vincini","doi":"10.1016/j.pathol.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.pathol.2025.01.002","url":null,"abstract":"<p><p>The traditional methods for monitoring quality control (QC) results of using the mean and standard deviation of 20 external QC results to establish acceptance criteria have been widely accepted in medical pathology. The use of Westgard rules to monitor assay performance has been used by clinical chemists for decades and is now applied to infectious disease testing. However, previous reports have indicated this approach creates frequent 'false rejections' leading to a waste of time and resources. This study evaluated the true cost of false rejections in a single laboratory by mapping the QC activities over a 5-month period. From January 2023 to May 2023 inclusive, a laboratory logged all QC results that failed Westgard rules using Bio-Rad Unity software. All activities arising from those QC failures were logged and the cost calculated in Australian dollars. The costs included the cost of reagents, external quality control (EQC), kit control and calibrators, and the staff time. As each laboratory has different pricing structures, certain assumptions were made. The laboratory used the traditional methods for patient result release. Over the same period, the EQC results were submitted to EDCNet software and subjected to National Serology Reference Laborator-developed QConnect Limits. At the end of the period, the outcomes of the traditional approach to EQC monitoring were compared with QConnect Limits. The senior scientist identified which QC rejections were 'true rejections'.Over the 5-month period, there were a total of 70 flags raised across 15 of the 23 test kits used on two different test platforms. All but one of the 70 episodes resulted in repeat testing of the EQC sample. On 17 occasions, the QC sample was tested more than three times. Recalibration of the assay occurred 12 times, and the results were referred to the senior scientist six times. The acceptance criteria for the EQC were re-set seven times. After ensuing investigations, only one of the 70 flags was deemed to be a 'real error' by the senior scientist. This was also detected by QConnect Limits. The cost of EQC flag investigations over the 5-month period was calculated to be just under $12,000 for 5 months. Extrapolating this to a 12-month period, the additional cost to the laboratory for EQC follow-up was estimated to be approximately $28,700 or about $2,400 per month. Delays in the release of patient results occurred in 42 of 70 episodes. In total, over the 5-month period, the accumulated delay in patients' reports was 68 h or 816 min per month. The use of traditional methods for the monitoring EQC is not fit for purpose of infectious disease testing. This is because frequent, normal reagent lot-to-lot variation is expected in serology tests. These changes cause frequent 'false rejections' if the acceptance criteria are too tight, as is the case when using 20 data points to establish limits. The consequences of false rejections are the waste of resources and staff time, ad","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743594","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}
PathologyPub Date : 2025-03-01DOI: 10.1016/j.pathol.2024.12.637
Fernanda Caramella-Pereira, Qizhi Zheng, Jessica L Hicks, Sujayita Roy, Tracy Jones, Martin Pomper, Lizamma Antony, Alan K Meeker, Srinivasan Yegnasubramanian, Angelo M De Marzo, W Nathaniel Brennen
{"title":"Overexpression of fibroblast activation protein (FAP) in the stroma of proliferative inflammatory atrophy (PIA) and primary adenocarcinoma of the prostate.","authors":"Fernanda Caramella-Pereira, Qizhi Zheng, Jessica L Hicks, Sujayita Roy, Tracy Jones, Martin Pomper, Lizamma Antony, Alan K Meeker, Srinivasan Yegnasubramanian, Angelo M De Marzo, W Nathaniel Brennen","doi":"10.1016/j.pathol.2024.12.637","DOIUrl":"10.1016/j.pathol.2024.12.637","url":null,"abstract":"<p><p>Fibroblast activation protein (FAP) is a serine protease upregulated at sites of tissue remodelling and cancer that represents a promising therapeutic and molecular imaging target. In prostate cancer, studies of FAP expression using tissue microarrays are conflicting, such that its clinical potential is unclear. Furthermore, little is known regarding FAP expression in benign prostatic tissues. Here we demonstrated, using a novel iterative multiplex immunohistochemistry assay in standard tissue sections, that FAP was nearly absent in normal regions but was increased consistently in regions of proliferative inflammatory atrophy (PIA). In carcinoma, FAP was expressed in all cases but was highly heterogeneous. High FAP levels were associated with increased pathological stage and cribriform morphology. We verified that FAP levels in cancer correlated with CD163+ M2 macrophage density. In this first report to quantify FAP protein in benign prostate and primary tumours, using standard large tissue sections, we clarify that FAP is present in all primary prostatic carcinomas, supporting its potential clinical relevance. The finding of high levels of FAP within PIA supports the injury/regeneration model for its pathogenesis and suggests that it harbours a protumourigenic stroma, yet high levels of FAP in benign regions could lead to false-positive FAP-based molecular imaging results in clinically localised prostate cancer.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788728","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}
PathologyPub Date : 2025-03-01DOI: 10.1016/j.pathol.2024.12.638
Christopher R McEvoy, Catherine Mitchell, Owen W J Prall, Huiling Xu, Andrew P Fellowes, David Y Choong, Evangeline Buela, Roxane Legaie, Jiaan Yu, Richard Lupat, Christopher M Angel, Christine Khoo, Jia-Min Pang, Cameron Snell, Stephen B Fox, Jeremy Lewin
{"title":"The implementation of an RNA-based gene fusion assay into a diagnostic oncology department: an Australian perspective.","authors":"Christopher R McEvoy, Catherine Mitchell, Owen W J Prall, Huiling Xu, Andrew P Fellowes, David Y Choong, Evangeline Buela, Roxane Legaie, Jiaan Yu, Richard Lupat, Christopher M Angel, Christine Khoo, Jia-Min Pang, Cameron Snell, Stephen B Fox, Jeremy Lewin","doi":"10.1016/j.pathol.2024.12.638","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.12.638","url":null,"abstract":"<p><p>Accurate detection of oncogenic gene fusions is important for histological diagnosis of a subset of tumours. Some fusions are also the target of precision therapies. We describe our validation and early diagnostic results for the detection of fusions using the commercially available Illumina TruSight RNA Fusion Panel (TRFP) and the Arriba fusion detection algorithm. Retrospective validation showed that this assay demonstrated high accuracy (94% positive predictive agreement) for a wide variety of fusions. Prospective diagnostic data comprised a cohort of 131 clinical samples (102 mesenchymal tumours, 29 epithelial tumours), of which 80 were excisional specimens and 51 were small specimens, predominantly core biopsies. The test failure rate was 10.7%. We detected 64 (54.7%) clinically-actionable fusions in passed samples, including 12 (10.3%) that either changed or were critical for the diagnosis and 14 (12.0%) that were potentially therapeutically targetable. Most samples (89.7%) fulfilled criteria for partial reimbursement by the Australian Government Medical Benefits Scheme. In addition to describing the utility of an RNA-based fusion assay in cancer diagnostics, it is hoped that this study will provide practical advice for other laboratories considering introducing such a test.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743595","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}
PathologyPub Date : 2025-02-22DOI: 10.1016/j.pathol.2024.12.636
Ravin Hettiarachchi, Julie Allerton, Christopher McIver, Dianne Rafferty, Peter Taylor, Robert Stevens
{"title":"A comparison of phenotypic methods to demonstrate penicillin susceptibility in Staphylococcus aureus.","authors":"Ravin Hettiarachchi, Julie Allerton, Christopher McIver, Dianne Rafferty, Peter Taylor, Robert Stevens","doi":"10.1016/j.pathol.2024.12.636","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.12.636","url":null,"abstract":"<p><p>The aim of this study was to assess the performance of phenotypic methods to demonstrate penicillin susceptibility in Staphylococcus aureus isolates using polymerase chain reaction (PCR) as a reference. A total of 126 S. aureus isolates were categorised as penicillin-susceptible S. aureus (PSSA), methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) using blaZ and mecA PCR. The minimum inhibitory concentration (MIC) of penicillin for each isolate was determined by broth microdilution (BMD) and agar dilution (AD) methods. Qualitative susceptibility was determined by blinded disc diffusion testing using Calibrated Dichotomous Sensitivity (CDS), Clinical Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) methods. Categorical agreement (CA) rate, major error (ME) rate and very major error (VME) rate were calculated. These isolates were characterised into 66 PSSA, 38 MSSA and 22 MRSA by molecular testing. High rates of VME (9.6%) were encountered using BMD and AD, with 20% of penicillin-resistant S. aureus isolates having a penicillin MIC ≤0.125 mg/L. There was no VME using disc diffusion methods with high level of agreement of interpretation by three separate plate readers. CA rate using CLSI was 98.6% with 1.4% ME rate, for CDS CA rate was 97.6% with 2.4% ME rate, and for EUCAST CA rate was 93.8% with 6.2% ME rate. All methods improved with consensus reporting after considering interpretation by the plate readers. Laboratories can confidently report penicillin susceptibility in the majority of clinical S. aureus isolates based on disc diffusion testing using CLSI, EUCAST or CDS methodologies. Consensus reporting by independent plate readers may improve CA of disc diffusion testing. Penicillin MIC determination should not be used to demonstrate penicillin susceptibly in S. aureus isolates without confirmation by disc diffusion or molecular methods.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743572","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}