Pathology最新文献

{"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}

{"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}

{"title":"The number of potential gateways determines prognostic value of tumour deposits in colon cancer.","authors":"Ayse Selcen Oguz Erdogan, Nelleke P M Brouwer, Valentina Angerilli, Natasja Rutgers, Gina Brown, Femke Simmer, Iris D Nagtegaal","doi":"10.1016/j.pathol.2024.12.635","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.12.635","url":null,"abstract":"<p><p>Tumour deposits (TD) are a crucial biomarker in colorectal cancer, closely associated with nearby structures such as blood vessels, lymphatic vessels, and peripheral nerves. These anatomical structures serve as pathways that facilitate the spread of tumour cells throughout the body. This study aims to investigate how TD access these anatomical gateways and how these variations impact patient survival. We analysed colon carcinoma patients who underwent surgery at Radboud University Medical Centre between 1986 and 2012 for the presence of TD. Using serial sections and immunohistochemistry with four different antibodies (CD34, D2-40, S100, and elastic van Gieson), we examined the presence and distribution of TD access to surrounding anatomical structures, including blood vessels, lymphatic vessels and peripheral nerves. In 127 patients, 280 TD were examined. Of these, 112 TD (40%) had multiple access points, 109 TD (39%) had a single access point, and 59 TD (21%) had no discernible access point. More than half of the TD (57%) demonstrated haematovascular invasion. Patients with TD featuring a single access point had a better prognosis compared to those with multiple access points (5-year overall survival, p=0.025; 5-year disease-free survival, p=0.005). TD are a heterogeneous biomarker characterised by various access points, with haematovascular invasion being the most common. Our study highlights a direct correlation between the number of TD access points and patient outcomes, indicating that an increase in access points is linked to a poorer prognosis.</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":"143658130","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":"Progression to invasive carcinoma: cellular activities and immune-related pathways define the lepidic and acinar subtypes of lung adenocarcinoma.","authors":"Ethan N Okoshi, Shiro Fujita, Kris Lami, Yuka Kitamura, Ryuta Matsuda, Andrey Bychkov, Takuro Miyazaki, Keitaro Matsumoto, Takeshi Nagayasu, Junya Fukuoka","doi":"10.1016/j.pathol.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.pathol.2025.01.001","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is the most frequent subtype of thoracic malignancy, which is itself the largest contributor to cancer mortality. The lepidic subtype is a non-invasive tumour morphology, whereas the acinar subtype represents one of the invasive morphologies. This study investigates the transition from a non-invasive to an invasive subtype in the context of LUAD. Patients with pathologically confirmed mixed subtype LUAD consented to analysis of RNA sequencing data extracted from each subtype area separately. The study included 17 patients with tumours found to exhibit a lepidic-acinar transition. Eighty-seven genes were found to be differentially expressed between the lepidic and acinar subtypes, with 44 genes significantly upregulated in lepidic samples ​and 43 genes significantly upregulated in acinar samples. Gene Ontology analysis showed that many of the genes upregulated in the acinar subtype were related to immune response, whereas for the lepidic subtype, genes responsible for cellular activities were upregulated. Immune deconvolution analysis showed that there was a significantly higher proportion of M1 macrophages and total B cells in acinar areas. Immunohistochemistry showed that B cells were mainly localised to tertiary lymphoid structures in the tumour area. This is the first study to investigate the molecular features of mixed subtype lepidic-acinar transitional tumours. Immunological dynamics are presumed to be involved in this transition from lepidic to acinar subtype. Further research should be conducted to elucidate the progression of disease from non-invasive to invasive morphologies.</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":"143812111","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":"Frequent PIK3CA and GNAQ mutations in solitary pulmonary capillary haemangioma and pulmonary cavernous haemangioma: genetic link to vascular malformations.","authors":"Yi-Chen Yeh, Ping-Yuan Chu, Chia-I Lin, Shu-Ying Wang, Shin-Ying Lin, Hsiang-Ling Ho, Min-Shu Hsieh","doi":"10.1016/j.pathol.2024.11.016","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.11.016","url":null,"abstract":"<p><p>Pulmonary haemangiomas are rare diseases with unclear pathogenesis. The molecular alterations underlying these conditions have not yet been identified. In this study, we sought to investigate the genetic alterations in the two most common types of pulmonary haemangiomas: solitary pulmonary capillary haemangiomas (SPCH) and pulmonary cavernous haemangiomas. This study included six patients with SPCH and four patients with pulmonary cavernous haemangioma. Utilising a customised next-generation sequencing panel, we identified a high frequency of PIK3CA hotspot mutations-five of six SPCH cases and three of four pulmonary cavernous haemangiomas, totalling 80%. Additionally, GNAQ mutations were detected in one SPCH and one pulmonary cavernous haemangioma. Overall, nine of 10 (90%) of the pulmonary haemangiomas in our study harboured mutations in either the PIK3CA or GNAQ genes. The variant allele frequencies of these mutations were relatively low, ranging from 4.2% to 15.5%, which complicates detection using Sanger sequencing due to its lower sensitivity. Our study identified a high frequency of PIK3CA mutations and occasional GNAQ mutations in SPCH and pulmonary cavernous haemangioma. The high prevalence of PIK3CA mutations in pulmonary haemangiomas suggests a potential link to the vascular malformation category in the International Society for the Study of Vascular Anomalies (ISSVA) classification where PIK3CA mutations are recognised as significant causative genetic events. The findings from this research represent the first documented evidence of the molecular alterations underlying these pulmonary haemangiomas.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743580","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":"Molecular testing of lung cancer in Australia: consensus best practice recommendations from the Royal College of Pathologists of Australasia in collaboration with the Thoracic Oncology Group of Australasia.","authors":"Wendy A Cooper, Benhur Amanuel, Caroline Cooper, Stephen B Fox, Jon W A Graftdyk, Peter Jessup, Sonja Klebe, Wei-Sen Lam, Trishe Y-M Leong, Zarnie Lwin, Rachel Roberts-Thomson, Benjamin J Solomon, Rebecca Y Tay, Rebecca Trowman, Janney L Wale, Nick Pavlakis","doi":"10.1016/j.pathol.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.pathol.2025.02.001","url":null,"abstract":"<p><p>Molecular testing plays a critical role in guiding optimal treatment decisions for lung cancer patients across a variety of clinical settings. While guidelines for biomarker testing exist in other jurisdictions, to date no best practice guidelines have been developed for the Australian setting. To address this need, the Royal College of Pathologists of Australasia collaborated with the Thoracic Oncology Group of Australasia to identify state-based pathologists, oncologists and consumer representatives to develop consensus best practice recommendations. Sixteen recommendations were established encompassing appropriate biomarkers, lung cancer subtype, tumour stage, specimen types, assay selection and quality assurance protocols that can inform and standardise best practice in molecular testing of lung cancer. These multidisciplinary evidence-based recommendations are designed to standardise and enhance molecular testing practices for lung cancers and should help ensure laboratories provide high-quality molecular testing of lung cancer for all Australians, including those from regional or remote communities.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658129","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":"Further case and literature review of the novel epithelioid vascular bone lesion associated with NFATC1/2 fusions.","authors":"Hannah Blaikie, Claudia Di Bella, Lisa Orme, John L Slavin, Penelope A McKelvie","doi":"10.1016/j.pathol.2024.11.015","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.11.015","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606144","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":"SS18-SSX and SSX c-terminus antibodies for identification of specific fusion oncoprotein in mesenchymal neoplasms.","authors":"Iva Brčić, Theresa Marie Godschachner, Jasminka Igrec, Susanne Scheipl, Anna Maria Smolle, Andreas Leithner, Joanna Szkandera, Bernadette Liegl-Atzwanger","doi":"10.1016/j.pathol.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.11.013","url":null,"abstract":"<p><p>Chromosomal rearrangement can be identified by direct methods or by using immunohistochemistry for a component of the fusion oncoprotein as a surrogate marker. Our aim was to gain insights into the staining profile using novel SS18-SSX and SSX c-terminus antibodies in SS18 fusion tumours and to investigate their potential use in soft tissue tumours harbouring SSX fusion partner outside the spectrum of synovial sarcoma. A retrospective analysis of 310 soft tissue sarcomas [via tissue microarray (TMA)] diagnosed at our Institution between 1999 and 2019 was performed. As controls, whole tissue sections from 14 genetically confirmed synovial sarcomas and one EWSR1::SSX2 rearranged sarcoma diagnosed between 2020 and 2023 were included. Two different antibodies for SSX locus were used: SSX c-terminus and SS18-SSX. Twenty-one of 310 (6.8%) and 25 of 310 (8.1%) sarcomas on the TMA showed nuclear staining with SS18-SSX and SSX, respectively. From the 24 synovial sarcomas, 17 (70.8%) stained positive for both antibodies, and in five of these cases, nuclear staining for SSX was weak. In four (16.7%) cases, only SS18-SSX was positive, and in three (12.5%) cases, only SSX staining was found. Furthermore, SSX nuclear expression was only found in four of 62 (6.5%) myxofibrosarcomas. In the control cohort, 11 of 14 synovial sarcomas (78.6%) showed positive staining for both antibodies. The remaining three cases were negative for SS18-SSX, but demonstrated at least focally strong positivity for SSX. The EWSR1::SSX2 rearranged sarcoma showed strong nuclear positivity for SSX. SS18-SSX and SSX c-terminus antibodies are reliable diagnostic markers that can be used as a surrogate marker for identification of a specific fusion. The SS18-SSX antibody is more specific and shows strong nuclear staining in synovial sarcomas, whereas SSX can present with weak staining and is less specific. However, the latter can be used in soft tissue tumours harbouring SSX fusion partner outside the spectrum of synovial sarcoma.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701008","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":"Can residual proliferative cancer burden predict long-term outcomes following neoadjuvant chemotherapy in breast cancer?","authors":"Imen Zawati, Yousra Troujette, Olfa Adouni, Maroua Manai, Meriem Nouira, Karim Mekki, Mohamed Manai, Khaled Rahal, Amor Gamoudi","doi":"10.1016/j.pathol.2024.11.014","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.11.014","url":null,"abstract":"<p><p>Residual proliferative cancer burden (RPCB) has been suggested as a strong predictor model of long-term outcomes in breast cancer undergoing neoadjuvant chemotherapy (NACT). In our study, we aimed to compare the prognostic value of multiple post-NACT classifications for assessing residual disease. Archival surgical specimens of 97 patients with primary breast cancer who underwent NACT were evaluated for residual cancer burden (RCB). The post-operative Ki-67 proliferation index was quantified using immunohistochemistry on post-treatment surgical excision specimens with residual disease. Then, we calculated the RPCB scores by combining the anatomical RCB index with the biological post-therapeutic Ki-67 using the Cox proportional hazard model for each parameter. Using the Kaplan-Meier method, RCBIII showed an unfavourable prognosis with worse relapse-free survival (RFS) (estimated 5-year RFS rate of 38%) than RCBI, which displayed a similarly good prognosis as pathological complete response (equal to RCB0) (estimated 5-year RFS rates of 80% and 100%, respectively) (p=0.012). The RCBII showed an intermediate prognosis (estimated 5-year RFS rate of 79%). A higher post-NACT Ki-67 (greater than cut-off 20%) had a negative impact on the overall survival and RFS (p<0.0001 for both) using the Kaplan-Meier method. In multivariate analysis, the histological residual tumour size, number of affected lymph nodes, and RCB index remained independent prognostic factors for RFS. In addition, RPCBIII showed the worst prognosis (with an estimated 5-year RFS rate of 38%) compared to RPCBI (estimated 5-year RFS rate of 83%) (p=0.039) by the Kaplan-Meier method. The area under the curve of the RCB index was 0.82 compared to 0.62 for the RPCB model in terms of RFS prediction. Our study highlighted the potential stratification of RCBII cases based on the RPCB classification. Further studies with larger cohorts will be needed to validate whether the RCPB adds value to residual disease assessment.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693090","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":"Paroxysmal cold haemoglobinuria with peculiar peripheral blood film finding.","authors":"Shatha Sharaf, Nahlah AlGhasham","doi":"10.1016/j.pathol.2024.12.634","DOIUrl":"https://doi.org/10.1016/j.pathol.2024.12.634","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639758","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}