Journal of Pathology Clinical Research最新文献

{"title":"Characterisation and impact of intratumoural stroma in melanoma and carcinoma brain metastases","authors":"Dave Bandke,&nbsp;Serge Weis,&nbsp;Andreas Gruber,&nbsp;Petar Noack,&nbsp;Ognian Kalev,&nbsp;Karoline Ornig,&nbsp;Rupert Langer","doi":"10.1002/2056-4538.70061","DOIUrl":"10.1002/2056-4538.70061","url":null,"abstract":"<p>Research on the tumour microenvironment in brain metastases (BM) has predominantly focused on the immune response, while the presence, morphological patterns, and potential clinical relevance of intratumoural stroma remain less intensively investigated. We retrospectively analysed 604 BM (529 carcinomas, 75 melanomas) from 556 patients. Intratumoural stroma was histomorphologically classified into absent/unclear (Group 0), present without desmoplasia (Group 1) or with desmoplasia (Group 2). Associations with histological features, clinical parameters, and survival were evaluated. Intratumoural stroma was absent in 63.2% of tumours (<i>n</i> = 382), was present without desmoplasia in 14.9% (<i>n</i> = 90), and was desmoplastic in 21.9% (<i>n</i> = 132). Desmoplasia was most frequent in metastases from breast carcinomas and pulmonary squamous cell carcinomas. No significant associations were found between stroma groups and age, sex, brain location, PD-L1 expression, oncogenic mutations in lung carcinoma, or breast-cancer molecular subtype. Independent predictors of poorer survival were increasing age (HR = 1.029, 95% CI: 1.018–1.039, <i>p</i> &lt; 0.001), male sex (HR = 1.492, 95% CI: 1.204–1.849, <i>p</i> &lt; 0.001), and infratentorial location (HR = 1.402, 95% CI: 1.125–1.748, <i>p</i> = 0.003). Stroma groups showed no independent prognostic value in the overall cohort. However, subgroup analysis of non-small cell lung cancer revealed a U-shaped relationship, with Group 1 stroma linked to better survival (<i>p</i> = 0.020). In summary, intratumoural stroma in BM is a carcinoma-specific phenomenon, absent in melanoma. Patient outcomes, however, were primarily determined by demographic and anatomical factors rather than stromal morphology in the overall cohort but may have clinical relevance in particular tumour subgroups.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148064154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a decision tree diagram for classifying study designs in tumour pathology research: a multidisciplinary approach","authors":"Oana M Craciun,&nbsp;Ester García-Ovejero,&nbsp;Fiona Campbell,&nbsp;Marina Montes-Mota,&nbsp;Stefan Holdenrieder,&nbsp;Inga Trulson,&nbsp;Karolina Worf,&nbsp;Sophie Gabriel,&nbsp;Magdalena Kowalewska,&nbsp;Irmina Michalek,&nbsp;Kateryna Maslova,&nbsp;Lukasz Taraszkiewicz,&nbsp;Javier del Águila,&nbsp;Richard Colling,&nbsp;Puay Hoon Tan,&nbsp;Gabrielle Goldman-Lévy,&nbsp;Christine Giesen,&nbsp;Ramon Cierco Jimenez,&nbsp;Dilani Lokuhetty,&nbsp;Ian A Cree,&nbsp;Iciar Indave,&nbsp;Beatriz Pérez Gómez,&nbsp;Magdalena Chechlińska,&nbsp;Marina Pollán Santamaría,&nbsp;Elena Plans-Beriso,&nbsp;WCT EVI MAP Project Team","doi":"10.1002/2056-4538.70056","DOIUrl":"10.1002/2056-4538.70056","url":null,"abstract":"<p>The World Health Organization (WHO) Classification of Tumours: A Living Evidence Gap Map by Tumour Type (WCT EVI MAP) project aims to develop Evidence Gap Maps of the available evidence, primarily to inform the WHO Classification of Tumours. The project, covering all tumour types, faces the challenge of reviewing a huge number of studies by reviewers from multiple backgrounds. The aim was to develop a decision tree (DT) diagram for classifying study designs reporting on tumour pathology studies, in order to support the decision-making process when assigning evidence levels across various disciplines. A modified consensus process, incorporating stakeholder workshops, was conducted in three phases: (1) development of the initial DT diagram draft (literature review and expert evaluation); (2) iterative reviews with project partners; and (3) testing the advanced DT diagram version with several sets of references to refine critical points. A total of 368 records were used for training throughout the entire process. Consensus was achieved when classifications could categorise studies consistently without causing discordance in new example sets. A DT diagram and its Glossary of Operational Definitions with 27 decision nodes and 26 categories were developed. The DT diagram is organised into six sections: WCT EVI MAP selection criteria, evidence synthesis, basic research related studies, descriptive studies, observational and experimental studies, and diagnostic test studies. The DT diagram is a valuable tool for the project's needs, successfully integrating diverse disciplinary perspectives for classifying evidence in tumour pathology research according to study design. It lays the foundation for future advancements in evidence mapping and classification within tumour pathology and related disciplines.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding UTROSCT heterogeneity: systematic clinicopathological evaluation combined with molecular profiling","authors":"Jing Yang,&nbsp;Jinku Zhang,&nbsp;Jinmei Li,&nbsp;Yan Liu,&nbsp;Yuxiang Wang,&nbsp;Ajin Hu,&nbsp;Congrong Liu","doi":"10.1002/2056-4538.70055","DOIUrl":"10.1002/2056-4538.70055","url":null,"abstract":"<p>Uterine tumor resembling ovarian sex cord tumor (UTROSCT) constitutes an exceptionally rare histological subset of uterine mesenchymal neoplasms. While most cases have benign clinical behavior, a subset of UTROSCTs exhibits clinically aggressive behavior characterized by recurrence and metastasis. Here, we present a cohort of 25 UTROSCT cases molecularly confirmed by recurrent fusion gene detection, including <i>ESR1::NCOA3</i> (<i>n</i> = 12), <i>GREB1::NCOA1</i> (<i>n</i> = 6), <i>ESR1::NCOA2</i> (<i>n</i> = 3), <i>GREB1::NCOA2</i> (<i>n</i> = 2), <i>GREB1::SS18</i> (<i>n</i> = 1), and <i>GREB1::CTNNB1</i> (<i>n</i> = 1). Notably, six cases (6/25, 24%) demonstrated recurrence/metastasis: two cases showed intrauterine recurrence (harboring <i>ESR1::NCOA3</i> and <i>GREB1::NCOA1</i> fusions), while four developed extrauterine metastases (carrying <i>ESR1::NCOA3</i>, <i>ESR1::NCOA2, GREB1::NCOA1,</i> and <i>GREB1::NCOA2</i> fusions), with one fatality. To dissect the biological basis of UTROSCT aggressiveness, we performed integrated clinicopathologic, immunohistochemical, and molecular profiling. Multivariate analysis identified tumor size &gt;5 cm, FIGO stage IB, and lymphovascular space invasion (LVSI) as independent predictors of recurrence/metastasis, whereas histologic features, proliferation index, and fusion gene subtypes lacked prognostic significance. Multi-omics analysis of primary versus metastatic tumors revealed striking copy number variations (CNVs) exclusively in metastatic lesions. Specifically, heterozygous losses of <i>SMARCB1</i> (2/4 metastatic cases) and <i>ATRX</i> (1/4 metastatic cases) were identified; both play critical roles in chromatin remodeling. These genetic alterations were conspicuously absent in primary tumors, suggesting their potential role in metastatic progression. Our findings represent the first demonstration of CNV-driven oncogenic evolution in UTROSCTs, particularly implicating SWI/SNF complex dysregulation in metastatic competence.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The road to therapy for myeloid sarcoma: navigating the complexities of subclonal MAPK/ERK mutations and clonal evolution","authors":"DuJiang Yang,&nbsp;Jiexiang Yang,&nbsp;GuoYou Wang","doi":"10.1002/2056-4538.70063","DOIUrl":"10.1002/2056-4538.70063","url":null,"abstract":"&lt;p&gt;The recent seminal work by Nann and colleagues, ‘Myeloid sarcoma shows a high frequency of mutations activating the MAPK/ERK pathway and association with clonal hematopoiesis’ provides a crucial genomic framework for this rare and aggressive malignancy [&lt;span&gt;1&lt;/span&gt;]. By rigorously demonstrating the high prevalence of &lt;i&gt;KRAS&lt;/i&gt;, &lt;i&gt;NRAS&lt;/i&gt;, and &lt;i&gt;PTPN11&lt;/i&gt; mutations and linking a subset of cases to clonal hematopoiesis (CH), the authors have rightly shifted the paradigm for understanding myeloid sarcoma (MS) pathogenesis. While these findings are undoubtedly significant, a critical appraisal reveals several profound biological and clinical challenges that must be addressed to translate this genetic atlas into therapeutic progress.&lt;/p&gt;&lt;p&gt;First, the functional and clinical implications of subclonal MAPK/ERK mutations demand a more nuanced interpretation than presented. While the high frequency (44%) is striking, the subclonal nature of many of these mutations suggests they may not be the universal founding oncogenic event. A critical, unanswered question is whether MAPK/ERK activation is a &lt;i&gt;bona fide&lt;/i&gt; driver of extramedullary tropism or merely a passenger event that confers a proliferative advantage within a permissive niche. The study's data, while correlative, cannot distinguish between these possibilities. If these mutations are indeed key to tissue invasion, why do we not observe universal, clonal dominance? This heterogeneity poses a direct threat to the efficacy of targeted therapies. MEK or ERK inhibitor monotherapy, as successfully deployed in other rat sarcoma (RAS)-pathway-driven cancers [&lt;span&gt;2&lt;/span&gt;], would likely select for the outgrowth of pre-existing, MAPK-wild-type subclones, leading to rapid clinical resistance. Therefore, the therapeutic strategy for MS may need to pivot towards rational combinations that target a more fundamental dependency of the MS-initiating cell, such as BCL-2 inhibition [&lt;span&gt;3&lt;/span&gt;], concurrently with MAPK pathway suppression to prevent escape.&lt;/p&gt;&lt;p&gt;Second, the provocative association with CH requires stringent validation and mechanistic exploration. The authors propose a compelling ‘two-hit’ model where CH provides the initial pre-leukemic clone, with subsequent MAPK/ERK mutation triggering overt MS. However, the phylogenetic relationship between the CH clone and the dominant MS clone remains largely inferential from the data shown. Definitive proof requires single-cell DNA sequencing of MS lesions and paired bone marrow to reconstruct the precise evolutionary trajectory. Furthermore, the immunological consequences of this trajectory are entirely unexplored. CH is known to create a pro-inflammatory bone marrow milieu and can remodel the immune system, potentially fostering a permissive environment for secondary oncogenic events [&lt;span&gt;4&lt;/span&gt;]. It is plausible that CH-derived MS represents a distinct immunobiological entity compared to &lt;i&gt;de novo&lt;/i&gt; MS. Characterizing the tumor micr","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145543373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authors' reply: Re: Yang et al. The road to therapy for myeloid sarcoma: navigating the complexities of subclonal MAPK/ERK mutations and clonal evolution","authors":"Dominik Nann,&nbsp;Falko Fend","doi":"10.1002/2056-4538.70064","DOIUrl":"10.1002/2056-4538.70064","url":null,"abstract":"&lt;p&gt;Reply to Yang &lt;i&gt;et al&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;We thank the authors for their interest in our recent paper ‘Myeloid sarcoma shows a high frequency of mutations activating the MAPK/ERK pathway and association with clonal hematopoiesis’ [&lt;span&gt;1&lt;/span&gt;], which appeared in the September issue of &lt;i&gt;The Journal of Pathology, Clinical Research&lt;/i&gt;. In their letter to the Editor, Dr. Yang and his colleagues raise some important issues, which point the way for further studies on myeloid sarcoma (MS) and its development [&lt;span&gt;2&lt;/span&gt;]. These include subclonal mutations in the MAPK pathway, the association with clonal hematopoiesis and the importance of the microenvironment.&lt;/p&gt;&lt;p&gt;Nevertheless, we want to clarify a few points raised by Dr. Yang and colleagues concerning our results. They state that the frequent subclonal nature of many MAPK/ERK mutations in our MS samples suggests they may not be the universal founding oncogenic event. Although we agree with this statement in principle, since activating mutations of &lt;i&gt;NRAS, KRAS&lt;/i&gt; and/or &lt;i&gt;BRAF&lt;/i&gt; were observed in only 53% of our MS cases and other acquired mutations, namely &lt;i&gt;NPM1&lt;/i&gt;, mutated in 38% of cases, are alternative candidate drivers, we want to point out that &lt;i&gt;NRAS/KRAS&lt;/i&gt; mutations constitute minor, subclonal events in only 2/18 cases. In case 27, the bone marrow showed a &lt;i&gt;KRAS&lt;/i&gt; mutation with 7% variant allele frequency (VAF), which was present at 2% and 3% VAF, respectively, in the two MS from this patient. In case 31, the &lt;i&gt;NRAS&lt;/i&gt; mutation was present in the bone marrow at 28% VAF and at only 0.4% VAF in the MS. In these cases, the MAPK/ERK mutations most likely represent a subclone and are not responsible for MS development. In the remaining 15/18 cases with &lt;i&gt;NRAS/KRAS&lt;/i&gt; mutations; however, these showed a high VAF (mean 41.7%, range 19–92%). In the cases with available pre-transplant bone marrow (BM) biopsy, the majority of &lt;i&gt;NRAS/KRAS&lt;/i&gt; mutations were acquired in MS or showed a significant increase in VAF in the MS in comparison to the BM biopsy. In some cases with mutations in other genes with higher VAF, this is indicative of a bi-allelic event rather than subclonality of the &lt;i&gt;RAS&lt;/i&gt; mutation, as for example in case 33 with a &lt;i&gt;TP53&lt;/i&gt; mutation with 83% VAF and the &lt;i&gt;EZH2&lt;/i&gt; mutation in case 18 with 89% (scrotal) and 99% (penis) VAF, respectively, in two different locations. In summary, the high VAFs and the frequent &lt;i&gt;de novo&lt;/i&gt; acquisition of &lt;i&gt;NRAS/KRAS&lt;/i&gt; mutations in many MS cases, together with the clear evidence for upregulation of the MAPK/ERK signaling cascades (supplementary material, Figure S3 in our paper [&lt;span&gt;1&lt;/span&gt;]) detected by comparative gene expression profiling clearly point to a role in MS development, although functional studies will be necessary to corroborate these findings. Of interest is case 10, which showed acquired identical mutations of &lt;i&gt;BRAF&lt;/i&gt; and &lt;i&gt;KRAS&lt;/i&gt; in both MS samples, but not in the BM. Given the fact that both ","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145543336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B lymphocytes and tertiary lymphoid structures have a prognostic impact on penile squamous cell carcinoma","authors":"Nicolette Zavillová,&nbsp;Petr Waldauf,&nbsp;Michaela Kendall Bártů,&nbsp;David Čapka,&nbsp;Jan Hojný,&nbsp;Zuzana Prouzová,&nbsp;Radoslav Matěj,&nbsp;Roman Zachoval,&nbsp;Jan Hrudka","doi":"10.1002/2056-4538.70059","DOIUrl":"10.1002/2056-4538.70059","url":null,"abstract":"<p>Several prognostic markers, including tumor-infiltrating lymphocytes, which have been recently identified in penile squamous cell carcinoma (pSCC), have focused mostly on T cells. The prognostic role of B cells and tertiary lymphoid structures (TLSs) has not yet been sufficiently described. We examined whole tissue sections histopathologically for TLSs and immunohistochemically for CD20 and CD138. The B-cell immunoscore (B-IS) divided the cohort into five categories based on the expression of these two B-cell/plasma cell markers (CD20 and CD138, respectively). Patients with fewer TLSs had worse overall survival (OS) [hazard ratio (HR) = 2.17; 95% CI: 0.94–5; <i>p</i> = 0.069]. A significant association was identified between a high TLS diameter and the presence of a lymphocytic infiltrate [odds ratio (OR) = 2.2442; 95% CI: 1.1022–4.55; <i>p</i> = 0.0208]. Patients with low B-IS (HR = 1.89, 95% CI: 1.18–3.03, <i>p</i> = 0.008), a low number of CD20⁺ cells in the tumor center (HR = 1.67, 95% CI: 1.04–2.7, <i>p</i> = 0.035), and a low number of CD20⁺ cells at the tumor invasion front (HR = 1.69, 95% CI: 1.06–2.78; <i>p</i> = 0.028) had significantly worse OS. High B-ISs were strongly associated with a mutated p53 profile detected by immunohistochemistry (OR = 4.76, 95% CI: 1.32–25, <i>p</i> = 0.011), low T-cell immunoscores (OR = 0.49; 95% CI: 0.23–1.03; <i>p</i> = 0.051), and brisk lymphocytic infiltration (OR = 2.0417, 95% CI: 1.01–4.76; <i>p</i> = 0.037). High CD20⁺ cell counts at the invasion front were associated with histological grade 3 disease (OR = 2.44, 95% CI 1.15–5.26, <i>p</i> = 0.015). An association was also observed between low B-IS and mutations in <i>KMT2D</i> (OR 0.31, 95% CI: 0.07–1.21, <i>p</i> = 0.057) and <i>EGFR</i> (OR = ∞, 95% CI: 0.86–∞, <i>p</i> = 0.053). In conclusion, high numbers of tumor-infiltrating B cells within TLSs represent a favorable prognostic marker in pSCC. These findings emphasize the need to identify novel microscopic prognostic markers during pathological assessment to guide early and appropriate therapeutic strategies.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secretory breast carcinoma: morphologic and molecular heterogeneity with indicators of aggressive potential in a cohort of 29 cases","authors":"Huayan Ren,&nbsp;Wanting Tong,&nbsp;Jiayue Ma,&nbsp;Xinyan Chen,&nbsp;Huifen Huang,&nbsp;Na Wei,&nbsp;Yuqiong Liu,&nbsp;Minglei Yang,&nbsp;Lan Zhang,&nbsp;Huixiang Li","doi":"10.1002/2056-4538.70060","DOIUrl":"10.1002/2056-4538.70060","url":null,"abstract":"<p>Secretory breast carcinoma (SBC) is a rare tumour defined by <i>ETV6-NTRK3</i> rearrangement, but its clinicopathological spectrum and potential for aggressive behaviour remain incompletely characterised. We retrospectively reviewed 29 SBCs diagnosed between 2014 and 2024, including 28 females and one male aged 12–63 years (median 44). Twenty-eight tumours arose in the breast parenchyma and one in axillary accessory breast tissue. Histologically, microcystic and tubular patterns predominated and carcinoma <i>in situ</i> was common. Most tumours were nuclear grade 1 with rare mitoses (0–1/10 high-power fields, HPF). A single patient with distant metastasis harboured a solid-predominant tumour showing nuclear grade 2–3, brisk mitoses (6/10 HPF), and multifocal necrosis. All tumours demonstrated diffuse S100 and pan-TRK expression. Oestrogen and/or progesterone receptor staining was observed in 16 of 29 cases (2–30% of tumour cells), and all were HER2 negative or low (0–1+). Ki-67 ranged from 3% to 20% (mean 7%). Fluorescence <i>in situ</i> hybridisation (FISH) was positive in 17 of 17 tested tumours (14 <i>ETV6-NTRK3</i> dual-fusion; 3 <i>NTRK3</i> break-apart). In the metastatic case, RNA sequencing confirmed canonical <i>ETV6-NTRK3</i> fusion, while targeted DNA sequencing identified additional variants of uncertain significance (VUS) – <i>RANBP2</i> p.S1843R, <i>NUP107</i> p.K382Q, <i>NCOR1</i> p.A1947V (missense), and <i>PREX2</i> p.G606G (synonymous). All patients underwent surgery, and 14 received adjuvant chemotherapy. During follow-up ranging from 6 to 135 months (median 76), one patient developed lung metastasis and was alive with disease at 88 months; the remaining 28 patients were alive without recurrence or metastasis. In summary, SBC is typically indolent and characterised by <i>ETV6-NTRK3</i> rearrangement with diffuse pan-TRK/S100 positivity. A solid-predominant pattern with increased cytological atypia, mitotic activity, and necrosis may indicate aggressive potential. Routine <i>NTRK</i> testing supports diagnosis and may help identify patients who could benefit from TRK-inhibitor therapy in advanced disease.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffuse glioma with FGFR3-TACC3 fusion in adults is not a homogenous clinicopathological and molecular entity","authors":"Xiaoli Su,&nbsp;Jiawen Wu,&nbsp;Pingling Wang,&nbsp;Liwen Hu,&nbsp;Yupeng Chen,&nbsp;Caihong Ren,&nbsp;Fangling Song,&nbsp;Hangrui Lin,&nbsp;Chenlin Ji,&nbsp;Yucheng xie,&nbsp;Xingfu Wang","doi":"10.1002/2056-4538.70057","DOIUrl":"10.1002/2056-4538.70057","url":null,"abstract":"<p>Adult diffuse gliomas with <i>FGFR3-TACC3</i> (F3T3) fusion are rare and highly heterogeneous central nervous system (CNS) tumors. Current research on the biological behavior of these tumors is limited, especially regarding whether histopathologically low-grade tumors are indolent or represent early-stage high-grade tumors, thereby posing challenges for grading. In this single-center study of 17 patients with adult <i>F3T3</i> fusion diffuse gliomas (F3T3 gliomas), both low- and high-grade F3T3 gliomas presented distinctive recurrent histopathological features, such as oligodendrocyte-like cells, branched vessels and frequent calcifications. Molecularly, <i>TERT</i> promoter mutations and 7+/10− chromosomal alterations were common; one patient with recurrent glioma with histopathological features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) had additional <i>CDK4</i> and <i>MDM2</i> amplifications. Methylation profiling of 3 samples revealed varied results. A patient whose tumor had histopathological features consistent with PLNTY and a methylation subtype classified as the mesenchymal subtype of glioblastoma (GBM) experienced tumor recurrence 8 months after surgery. After 5–62 months of follow-up, seven patients relapsed, and six died; the primary tumors of the three patients with recurrence presented histopathological characteristics of low-grade glioma (LGG). GBM patients had worse overall survival than LGG patients (<i>p</i> = 0.035) but similar progression-free survival (<i>p</i> = 0.47), indicating that LGG patients may experience recurrence. For adults with tumors with histopathological features of PLNTY, further molecular and methylation analyses are needed for grading. If <i>TERT</i> promoter mutations are present, even with a PLNTY methylation profile, these tumors can still exhibit the biological behavior of high-grade gliomas.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145402356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context is key: how diagnostic and prognostic markers are reshaping gynecologic pathology","authors":"Martin Köbel,&nbsp;Anthony N Karnezis","doi":"10.1002/2056-4538.70058","DOIUrl":"10.1002/2056-4538.70058","url":null,"abstract":"<p>The field of gynecologic pathology is undergoing a transformative change. The translation of molecular findings from large-scale genomic studies into clinical practice has been facilitated by robust surrogate assays, particularly immunohistochemistry (IHC). These tools provide scalable molecular proxies with short turnaround times, enabling molecular subclassification and conclusive prognostic biomarker studies. This commentary highlights how prognostic markers now refine diagnoses in challenging borderline areas, where an abnormal result can help exclude benign or precursor entities. However, the utility of these markers is highly context-dependent, modified by histotype and molecular subtype. Furthermore, the confident diagnosis of rare entities and the study of their precursors have been advanced by defining specific molecular and IHC profiles, opening new avenues for research and therapy. The integration of morphology with molecular features is increasing the robustness of diagnoses and dictating oncology management as never before.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145402371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}