Journal of Clinical Pathology最新文献

{"title":"Prognostic implications, genomic and immune characteristics of lung adenocarcinoma with lepidic growth pattern.","authors":"Yue Li, Donglai Chen, Yi Xu, Qifeng Ding, Xuejun Xu, Yongzhong Li, Yedong Mi, Yongbing Chen","doi":"10.1136/jcp-2024-209603","DOIUrl":"10.1136/jcp-2024-209603","url":null,"abstract":"<p><strong>Aims: </strong>Conflicting data were provided regarding the prognostic impact and genomic features of lung adenocarcinoma (LUAD) with lepidic growth pattern (LP+A). Delineation of the genomic and immune characteristics of LP+A could provide deeper insights into its prognostic implications and treatment determination.</p><p><strong>Methods: </strong>We conducted a search of articles in PubMed, EMBASE and the Cochrane Library from inception to January 2024. A domestic cohort consisting of 52 LUAD samples was subjected to whole-exome sequencing as internal validation. Data from The Cancer Genomic Atlas and the Gene Expression Omnibus datasets were obtained to characterise the genomic and immune profiles of LP+A. Pooled HRs and rates were calculated.</p><p><strong>Results: </strong>The pooled results indicated that lepidic growth pattern was either predominant (0.35, 95% CI 0.22 to 0.56, p<0.01) or minor (HR 0.50, 95% CI 0.36 to 0.70, p<0.01) histological subtype was associated with favourable disease-free survival. Pooled gene mutation rates suggested higher EGFR mutation (0.55, 95% CI 0.46 to 0.64, p<0.01) and lower KRAS mutation (0.14, 95% CI 0.02 to 0.25, p=0.02) in lepidic-predominant LUAD. Lepidic-predominant LUAD had lower tumour mutation burden and pooled positive rate of PD-L1 expression compared with other subtypes. LP+A was characterised by abundance in resting CD4+memory T cells, monocytes and γδ T cells, as well as scarcity of cancer-associated fibroblasts.</p><p><strong>Conclusions: </strong>LP+A was a unique histological subtype with a higher EGFR mutation rate, lower tumour mutation burden and immune checkpoint expression levels. Our findings suggested potential benefits from targeted therapy over immunotherapy in LP+A.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"277-284"},"PeriodicalIF":2.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889332","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":"Airway associated inflammation in post-transplant cystic fibrosis patients as a predictor of chronic lung allograft dysfunction (CLAD).","authors":"Tanvi Patel, Bradford Bemiss, Elnaz Panah, Thanchanok Chaiprasit, Austin McHenry, Girish Venkataraman, Vijayalakshmi Ananthanarayanan","doi":"10.1136/jcp-2024-209899","DOIUrl":"10.1136/jcp-2024-209899","url":null,"abstract":"<p><strong>Aims: </strong>In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD.</p><p><strong>Methods: </strong>A retrospective, single-centre observational study of cystic fibrosis LTRs between 2002 and 2021 was performed. Data from biopsy slides, pulmonary function testing and bronchoalveolar lavage fluid microbiology tests were collected. The primary outcome was bronchiolitis obliterans syndrome (BOS) or death after transplant, with an 8-year follow-up period.</p><p><strong>Results: </strong>40 patients were identified with an average age of 35.3 at first transplantation, including 5 redo lung transplants. Fungal infections were correlated with higher rejection scores (p<0.01) and survival status (p=0.027). Fungal and bacterial infection rates were reduced in later transplants (2014-2021) compared with earlier (2002-2014). Fungal infections were associated with significantly worsened outcomes (p≤0.001). Eosinophils in large airways was associated with worse BOS-free survival (p=0.03).</p><p><strong>Conclusions: </strong>Subcategorisation of the inflammatory milieu (particularly noting eosinophils) in surveillance biopsies may help detect CLAD earlier and improve long-term outcomes in cystic fibrosis LTRs.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"251-258"},"PeriodicalIF":2.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949541","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":"Spindle cell carcinoma of the breast resembling pseudoangiomatous stromal hyperplasia.","authors":"Andrew H S Lee, Anne-Marie O'Shea, Ian O Ellis","doi":"10.1136/jcp-2024-209979","DOIUrl":"10.1136/jcp-2024-209979","url":null,"abstract":"<p><p>Pseudoangiomatous stromal hyperplasia (PASH) is commonly present in gynaecomastia, can be seen in some mammary fibroepithelial lesions and in fibrocystic change, and rarely forms a mass. Spindle cell carcinoma of the breast can have a wide range of appearances. This case series describes five spindle cell carcinomas of the breast resembling PASH, a pattern that does not appear to have been reported before. All had bland nuclei like those in fibromatosis-like spindle cell carcinoma. All cases had more close-packed areas, but this was only a very minor component in the index case. Two had associated ductal carcinoma in situ. All were cytokeratin positive with immunohistochemistry. The similarity of the carcinomas in this series to PASH is a diagnostic pitfall particularly in core biopsies as more cellular areas may be only focal.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"285-286"},"PeriodicalIF":2.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189217","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":"Prevalence and clinical outcomes of germline variants among patients with myeloid neoplasms.","authors":"Sunisa Kongkiatkamon, Pimjai Niparuck, Thanawat Rattanathammethee, Sirorat Kobbuaklee, Amornchai Suksusut, Kitsada Wudhikarn, Chupong Ittiwut, Wanna Chetruengchai, Suporn Chuncharunee, Udomsak Bunworasate, Kanya Suphapeetiporn, Ponlapat Rojnuckarin, Chantana Polprasert","doi":"10.1136/jcp-2023-209264","DOIUrl":"10.1136/jcp-2023-209264","url":null,"abstract":"<p><strong>Aims: </strong>Myeloid neoplasms (MNs) with germline predisposition have been recognised as a distinct entity. Emerging evidence suggests that sporadic myelodysplastic syndromes may also harbour undetected germline predispositions. We investigated germline alterations in a cohort of 122 adult Thai MNs.</p><p><strong>Methods: </strong>MN patients were recruited and tested for germline variants using deep targeted next-generation sequencing. The germline variant was filtered using American College of Medical Genetics classifications and then evaluated for the association with clinical characteristics and outcomes.</p><p><strong>Results: </strong>Our findings revealed pathogenic/likely pathogenic germline alterations in 12 (10%) of the patients. These germline lesions were commonly found in the DNA damage response pathway (n=6, 50%). We also identified novel deleterious <i>FANCA</i> ^{A1219GfsTer59} variants in two patients diagnosed with secondary acute myeloid leukaemia (sAML) from aplastic anaemia and AML with myelodysplasia related. Among sAML, individuals with germline mutations had inferior overall survival compared with those with wild-type alleles (2 months vs 12 months) with HR 4.7 (95% CI 1.0 to 20), p=0.037. Therefore, the presence of pathogenic or likely pathogenic mutations may be linked to inferior survival outcomes.</p><p><strong>Conclusions: </strong>Our study highlighted that the prevalence of germline predisposition in Southeast Asian populations is comparable to that in Caucasians. This underscores the importance of germline genetic testing within the Asian population.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"259-265"},"PeriodicalIF":2.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081560","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":"Histone antibodies in primary Sjögren's disease.","authors":"Adrian Y S Lee","doi":"10.1136/jcp-2024-209803","DOIUrl":"10.1136/jcp-2024-209803","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"287-288"},"PeriodicalIF":2.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621417","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":"Formulation of workplace-based assessments (WBAs) and entrustable professional activities (EPAs) for postgraduate medical trainees in clinical biochemistry.","authors":"Tahir S Pillay, Lena Jafri, Rivak Punchoo","doi":"10.1136/jcp-2024-209796","DOIUrl":"10.1136/jcp-2024-209796","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"240-250"},"PeriodicalIF":2.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818195","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":"The fifth edition of the WHO classification of mature T cell, NK cell and stroma-derived neoplasms.","authors":"Ayoma D Attygalle, Kennosuke Karube, Yoon Kyung Jeon, Wah Cheuk, Govind Bhagat, John K C Chan, Kikkeri N Naresh","doi":"10.1136/jcp-2025-210074","DOIUrl":"10.1136/jcp-2025-210074","url":null,"abstract":"<p><p>The fifth edition of the WHO Classification of Haematolymphoid Tumors (WHO-HAEM5) introduces significant advancements in the understanding and diagnosis of mature T cell and NK cell, and stroma-derived neoplasms, and incorporates molecular and genetic data/findings accrued over the past years. The classification has been reorganised using a hierarchical system, employed across the fifth edition of the WHO classification of tumours of all organ systems. This review highlights recent developments, evolving concepts, and key updates since the revised fourth edition (WHO-HAEM4R). It enumerates the minimal/essential criteria necessary for diagnosis and classification, constituting not only the importance of clonality analysis in the workup of certain T cell neoplasms and the detection of infectious agents and specific genetic alterations in a subset of entities but also the applicability of these criteria in resource-constrained settings. 'Stroma-derived neoplasms of lymphoid tissues discussed in this review is a new category introduced in HAEM5 that encompasses mesenchymal tumours occurring exclusively in lymph nodes and spleen and mesenchymal dendritic cell neoplasms previously classified as 'histiocytic/dendritic cell neoplasms'.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"217-232"},"PeriodicalIF":2.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449108","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":"Preoperative liquid biopsy for <i>EGFR</i>-mutated detection at diagnostic in early-stage non-small cell lung cancer: real-world experience of a single centre.","authors":"Christophe Bontoux, Jonathan Benzaquen, Valérie Taly, Aurélia Baurès, Maryline Allegra, Caroline Lacoux, Virginie Tanga, Guylène Rignol, Jean-Philippe Berthet, Charles-Hugo Marquette, Virginie Lespinet-Fabre, Olivier Bordone, Samantha Goffinet, Marius Ilie, Veronique Hofman, Paul Hofman","doi":"10.1136/jcp-2024-209941","DOIUrl":"https://doi.org/10.1136/jcp-2024-209941","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656929","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}