Journal of Clinical Pathology最新文献

{"title":"Time trends in Gleason score distribution among Gleason score 8 and 9-10 cancers.","authors":"Lars Egevad, Chiara Micoli, Brett Delahunt, Hemamali Samaratunga, Hans Garmo, Pär Stattin, Martin Eklund","doi":"10.1136/jcp-2025-210062","DOIUrl":"https://doi.org/10.1136/jcp-2025-210062","url":null,"abstract":"<p><p>Reporting of prostate cancer grade has drifted to higher reported grades over the past decades. In prostate cancers diagnosed on needle biopsy of 1 72 112 men reported to The National Prostate Cancer Register of Sweden 2000-2020, we also noted a grade shift among high-grade cancers. We applied multinomial logistic regression to assess time trends. Among International Society of Urological Pathology (ISUP) grade 4 cancers, Gleason score 3+5 increased from 8% in 2000 to 22% in 2020, while Gleason score 4+4 decreased from 88% to 77%. Among ISUP grade 5, Gleason score 4+5 and 5+4 cancers increased from 85% to 93%, while Gleason score 5+5 decreased from 15% to 7%. This may be explained by a reluctance to assign Gleason scores composed of a uniform grade following recommendations to include minimal components of higher grade in the scores. These changes are obscured by merging Gleason scores into ISUP grades.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624863","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":"Carcinoma arising in microglandular adenosis of the breast: clinicopathological and genetic analysis.","authors":"Qiang Zhang, Yanping Li, Bao-Hua Yu, Rui Bi, Xiaoli Xu, Yufan Cheng, Wentao Yang, Ruohong Shui","doi":"10.1136/jcp-2024-209833","DOIUrl":"https://doi.org/10.1136/jcp-2024-209833","url":null,"abstract":"<p><strong>Aims: </strong>To study the clinicopathological, immunohistochemical and molecular features of carcinoma arising in microglandular adenosis (MGACA) of the breast.</p><p><strong>Methods: </strong>Clinicopathological features of 13 cases of MGACA were analysed. All tumours were molecular subtype by immunohistochemistry (IHC) of AR, CD8, FOXC1 and DCLK1 expression. Next-generation sequencing including 511 genes was analysed.</p><p><strong>Results: </strong>All tumours showed a histological spectrum ranging from microglandular adenosis (MGA) to atypical MGA (AMGA), ductal carcinoma in situ (DCIS) and MGACA. Invasive components in 10 of 13 tumours were invasive carcinoma of no special type (NST), 3 were metaplastic carcinoma with mesenchymal differentiation (including two cases of matrix-producing carcinoma) mixed with NST. All lesion-associated epithelial cells were triple negative (TNBC) and positive for S-100. Reticulin staining showed the presence of basement membrane in MGA, AMGA and DCIS, and its absence in invasive carcinoma. According to IHC-based TNBC molecular subtyping, 10 tumours were basal-like immune-suppressed (BLIS), 2 were luminal androgen receptor and 1 was immunomodulatory. 10 patients had gene mutations. Pathogenic germline mutations of the <i>BRCA1</i> and <i>BRCA2</i> genes were detected in four tumours (30.7%) and one tumour (7.7%). Somatic mutation rate of the <i>TP53</i> gene was 69.2%. Amplification rates of <i>MYC</i>, <i>FGFR2</i>, <i>JAK2</i> and <i>MCL1</i> genes in our cohort were 46.2%, 15.4%, 15.4% and 7.7%, respectively.</p><p><strong>Conclusion: </strong>MGACA is a rare breast carcinoma, with distinct morphological, immunohistochemical and molecular features. Most MGACA were BLIS molecular subtype of TNBC. <i>TP53</i> and <i>BRCA1</i> gene mutation and <i>MYC</i> gene amplification were the most common genetic changes in MGACA.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624860","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":"Patterns of HER2 expression and genomic correlates in lung cancer, with a focus on preanalytical variables impacting immunohistochemical staining results.","authors":"Cristiana M Pineda, Lauren O'Loughlin, Heather L Benjamin, Deepa Rangachari, Hollis Viray, Page C Widick, Zoe Guan, Jason A Beattie, Kai E Swenson, Mihir S Parikh, Adnan Majid, Daniel B Costa, Paul A VanderLaan","doi":"10.1136/jcp-2025-210095","DOIUrl":"https://doi.org/10.1136/jcp-2025-210095","url":null,"abstract":"<p><strong>Aims: </strong>Fam-trastuzumab deruxtecan-nxki (T-DXd) was recently approved for advanced stage or metastatic solid tumours with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) 3+ staining. Data on HER2 IHC testing and knowledge of genomic correlates in lung cancer are scarce. This study analyses genomic characteristics of HER2-expressing tumours and addresses issues with preanalytical variables for lung cancer specimens.</p><p><strong>Methods: </strong>HER2 IHC staining was performed on selected archival cytology and surgical pathology lung cancer specimens for patients eligible for T-DXd therapy. Patient and tumour characteristics and next-generation sequencing (NGS) data were correlated with HER2 IHC results.</p><p><strong>Results: </strong>166 patients with thoracic tumour samples had HER2 expression assessed: 46% were IHC 0, 28% IHC 1+, 13% IHC 2+ and 13% IHC 3+. HER2 IHC scores were overall lower for cytology cell blocks as compared with surgical pathology specimens; 79% of cases with paired specimens had a decrease in their HER2 IHC score from their surgical specimen to their paired cytology specimen. Of specimens with HER2 IHC 3+ and NGS available, only 14% (3/21) had concomitant ERBB2 alterations. Among all specimens, ERBB2 point mutations were noted in 4% (4/110) and ERBB2 amplification in 3% (3/110). The majority of HER2 3+ cases with paired NGS (17/21, 81%) had non-<i>ERBB2</i> genomic alterations, including: <i>KRAS</i>, <i>TP53,</i> and <i>STK11</i> mutations.</p><p><strong>Conclusions: </strong>HER2 IHC 3+ is seen in a small but clinically significant proportion of samples and is associated with a variety of co-occurring non-ERBB2 genomic alterations. Preanalytical variables including specimen fixation can significantly impact the assessment of HER2 expression via immunohistochemistry.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624862","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":"Re-evaluating the relevance of extensive intraductal component (EIC) in modern breast cancer management.","authors":"Seyed Reza Taha, Fouad Boulos","doi":"10.1136/jcp-2024-209973","DOIUrl":"https://doi.org/10.1136/jcp-2024-209973","url":null,"abstract":"<p><p>The concept of extensive intraductal component (EIC), currently defined by the presence of a prominent ductal carcinoma in situ (DCIS) component within an invasive tumor and extending beyond its margins, was introduced in the 1980s as a predictor of local recurrence following breast-conserving therapy for invasive breast carcinoma. At the time, surgical excision to negative margins was not the standard of care, making EIC a valuable tool for identifying patients at risk of recurrence. However, with modern oncologic and surgical advancements, its clinical relevance has diminished. Despite its continued inclusion as a mandatory entry in the CAP synoptic checklist, studies have shown that EIC does not independently predict local recurrence when margins are negative. Instead, objective parameters such as DCIS size and nuclear grade more accurately correlate with margin status and recurrence risk. While EIC may still be useful in preoperative biopsy assessments for evaluating disease extent among other things, its routine reporting in resection specimens appears less informative. Given its vague definition and limited prognostic value, we propose that EIC reporting should be discretionary rather than mandatory, with emphasis placed on more objective and clinically relevant metrics.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567335","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":"Leadership and emotional intelligence: an early-career pathologist's perspective on the laboratory medical director role.","authors":"Maryam Asif","doi":"10.1136/jcp-2025-210057","DOIUrl":"https://doi.org/10.1136/jcp-2025-210057","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567334","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":"Clinical utility of 'Shaken' biopsies for whole-genome sequencing.","authors":"Rachel Nelan, Martina Mijuskovic, Martina Hughes, Jennifer Becq, Zoya Kingsbury, Eleni Tsogka, Miao He, Dunja Vucenovic, Clare Craig, Greg Elgar, Pauline Levey, Tamara Suaris, Emma Walsh, Mark Ross, J Louise Jones","doi":"10.1136/jcp-2024-209781","DOIUrl":"https://doi.org/10.1136/jcp-2024-209781","url":null,"abstract":"<p><strong>Aims: </strong>Whole-genome sequencing (WGS) is beginning to be applied to cancer samples in the clinical setting. This ideally requires high-quality, minimally degraded DNA of high tumour cell content, while retaining sufficient tissue with excellent morphology for histopathological diagnosis and immunohistochemistry. The aim of this study was to investigate alternative ways of handling cancer samples to fulfil both diagnostic and molecular requirements.</p><p><strong>Methods: </strong>Ex vivo biopsies were taken to investigate the feasibility of using cancer cells 'shaken' from the surface of a biopsy for WGS, while maintaining the tissue biopsy for histological diagnosis. WGS from the shaken cells was compared with the gold standard of a fresh-frozen (FF) biopsy. The procedure was piloted in the real-world setting for breast cancer samples.</p><p><strong>Results: </strong>Cells shaken from ex vivo biopsies can yield DNA of sufficient quantity and quality for WGS, while having no discernible impact on quality of tissue morphology. WGS data showed good coverage, comparable variant calls and generally higher tumour content in shaken cell samples compared with the control FF samples. For real-world biopsies, DNA yields were lower, but WGS data were of excellent quality for the cases analysed.</p><p><strong>Conclusions: </strong>Shaken biopsy sampling allows genomic sequencing from patients with cancer who may otherwise not receive a genome sequence due to limited sample availability. It represents a way of overcoming the logistics of obtaining and storing FF tissue making it a suitable technique for wider scale implementation in the clinical setting.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542179","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":"If you provide them, they will come: an observational study of online pathology report access by patients at a large, academic, tertiary care hospital in Canada.","authors":"Jacob Ranot, Pedram Noghani, Deanna Rothwell, Jason K Wasserman","doi":"10.1136/jcp-2025-210065","DOIUrl":"https://doi.org/10.1136/jcp-2025-210065","url":null,"abstract":"<p><strong>Aims: </strong>Patients of The Ottawa Hospital (TOH) are given immediate access to their pathology reports via an online patient portal. The purpose of this study was to determine how often patients accessed their reports, the sociodemographic and pathologic variables associated with access and the latency between sign out and access.</p><p><strong>Methods: </strong>This retrospective cross-sectional observational study was conducted on the first 250 consecutive pathology reports published in 2023 from 10 different subspecialties in anatomical pathology at TOH. Data regarding date/time of report publication and access, as well as demographic data, and variables related to the individual report contents were extracted from the hospital's electronic health records.</p><p><strong>Results: </strong>Of the 2500 patients included in this study, 1315 (52.6%) accessed their report online. Patients under 65 years of age, female patients and those residing within Ottawa were more likely to access their reports. Biopsies and reports with malignant diagnoses were accessed at higher rates than resections and benign cases, respectively. 463 (36.0%) patients accessed their reports within 24 hours; 822 (68.5%) accessed them within the first week. In 53% of cases, the patient accessed their report before the treating physician.</p><p><strong>Conclusions: </strong>These findings highlight that while over half of patients accessed their pathology reports online, significant differences in access rates were observed based on age, gender, location and report type. The high proportion of patients reviewing their reports before their treating physician underscores the need for patient-centred strategies to enhance understanding and support timely communication of results.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523393","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":"Revealing <i>RB1</i> loss in an emerging entity: report of two cases of PRRX1-rearranged mesenchymal tumours.","authors":"Fleur Cordier, Sharareh Fadaei, Liesbeth Ferdinande, Frederick Dochy, Lieve Vanwalleghem, Karolien Van Den Bossche, Siebe Loontiens, Joni Van der Meulen, Nadine Van Roy, Jo Van Dorpe, David Creytens","doi":"10.1136/jcp-2023-209267","DOIUrl":"10.1136/jcp-2023-209267","url":null,"abstract":"<p><strong>Aims: </strong><i>PRRX1</i>-rearranged mesenchymal tumours are a recently identified and rare subgroup of soft tissue neoplasms with distinct morphological features and genetic alterations. This study aims to further investigate the immunohistochemical profile and underlying genetic alterations in these tumours in order to get more insight on their underlying biology and the unique profile of these tumours.</p><p><strong>Methods: </strong>Two new molecular confirmed cases of <i>PRRX1</i>-rearranged mesenchymal tumours were thoroughly studied with immunohistochemical stainings (RB1, CD34, ALK and pan-TRK), fluorescence in situ hybridisation (FISH) <i>RB1/13q12</i> and RNA-based next-generation sequencing.</p><p><strong>Results: </strong>Both cases exhibited typical morphological and molecular features, confirming the diagnosis of <i>PRRX1</i>-rearranged mesenchymal tumours. Immunohistochemistry revealed RB1 loss in both cases, which was subsequently confirmed through FISH analysis. Additionally, one case showed focal positivity for CD34, ALK and pan-TRK on immunohistochemistry.</p><p><strong>Conclusions: </strong>We identified loss of <i>RB1</i> in two cases of PRRX1-rearranged mesenchymal tumours. This could suggest a potential association with <i>RB1</i>-deficient soft tissue tumours, although further research is necessary. Furthermore, the finding of focal positivity for CD34, ALK and pan-TRK on immunohistochemistry enriches the immunohistochemical profile of these tumours.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"154-160"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058387","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":"Indian childhood cirrhosis: a retrospective study -redefining the older myths!","authors":"Surbhi Goyal, Akanksha Singh, Shivanshu Gangwar, Aditi Goyal, Puja Sakhuja, Seema Kapoor","doi":"10.1136/jcp-2023-208934","DOIUrl":"10.1136/jcp-2023-208934","url":null,"abstract":"<p><strong>Aims: </strong>This retrospective study emphasises the need of awareness for clinicopathological attributes of Indian childhood cirrhosis (ICC) in order to enable timely diagnosis and management.</p><p><strong>Methods: </strong>This study was done on liver archival tissue of our department from the period of January 2016 to December 2022. Of these, cases of copper overload on paediatric biopsies were retrieved. The histopathological features were scrutinised independently by three pathologists, correlating with their clinico-radiological investigations.</p><p><strong>Results: </strong>Five children in infancy to middle childhood presented with features of chronic liver disease in the form of jaundice and abdominal distention, were included in the study. Characteristic firm hepatomegaly with sharp margins and transaminitis was noted in all cases. Autoimmune, viral and metabolic workup were negative in all these patients except one which showed positive autoimmunity and another whose Coomb's test was positive. Normal ceruloplasmin levels and unremarkable slit lamp examination excluded the possibility of Wilson's disease. The histological features of marked ballooning degeneration with diffuse Mallory Denk, pericellular fibrosis, absence of steatosis and panlobular copper deposits clinched the diagnosis of ICC.</p><p><strong>Conclusions: </strong>ICC once believed to be extinct has still not vanished and remains underdiagnosed in routine practice. It is a rapidly fatal disease with a debatable pattern of inheritance and controversial role of copper as etiological agent. The clinical presentation is often deceptive and lack of awareness leads to misdiagnosis. Histopathological attributes are pathognomonic and possibility of ICC should be kept in all cases of cryptogenic cirrhosis.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"161-168"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403111","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":"In triple-negative breast cancer, fibrotic focus, the mitotic activity index and tumour-infiltrating lymphocytes have independent prognostic value: an observational population-based cohort study with very long follow-up.","authors":"Umay Kiraz, Emma Rewcastle, Kirsten B Pettersen, Desmond M Abono, Sadia H Raghe, Einar G Gudlaugsson, Jan P A Baak, Emilius A M Janssen","doi":"10.1136/jcp-2024-209855","DOIUrl":"https://doi.org/10.1136/jcp-2024-209855","url":null,"abstract":"<p><strong>Aims: </strong>Triple-negative breast cancer (TNBC) is prognostically and therapeutically heterogeneous. The mitotic activity index (MAI) and fibrotic focus (FF) have been established as predictors in non-TNBC but not in TNBC. Late distant metastases occur in TNBC, but previous studies had short follow-up. High stromal tumour-infiltrating lymphocytes (sTILs) are prognostically favourable, but prognostic sTILs-thresholds are not well assessed. We evaluated prognostic/predictive characteristics in an observational population-based cohort of 231 consecutive TNBC patients with long follow-up.</p><p><strong>Methods: </strong>MAI, FF, sTILs and other characteristics were analysed with standard receiver operating characteristic curve analysis, percentile-derived prognostic thresholds, univariate and multivariate survival methods. A TNBC index and decision tree were assessed for distant metastasis-free survival.</p><p><strong>Results: </strong>Long follow-up was decisive: 7% of patients developed late distant metastases. In agreement with the aggressive nature of TNBC, the strongest prognostic MAI-threshold was 5 (p=0.001), lower than that for non-TNBC phenotypes. Lymph-node (LN) status (p=0.0003), FF (p=0.002), MAI5 (p=0.009) and sTILs (threshold 40%, p=0.003) were multivariable based significant and independent prognosticators, but no other characteristics (age, tumour size and grade). LN status was the strongest prognosticator, followed by FF, MAI5 and sTILs40. Subgroup analyses of patients undergoing adjuvant chemotherapy (ACT) showed that only FF and sTILs had significant prognostic value, while LN-positivity and the combination of LN-positivity and MAI≥5 could be a predictive factor for ACT outcome.</p><p><strong>Conclusions: </strong>LN status, MAI5, FF and sTILs40 are prognostic factors in TNBC patients. In TNBC patients who have undergone ACT, the combination of LN-positivity and MAI5 is predictive for response to treatment.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449107","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}