Pathobiology最新文献

{"title":"Myeloid Neoplasms with Evidence of the Additive/Cumulative Effect of Molecular Genetic Alterations That \"Pave the Way\" to a Specific Disease Category or Entity: Lessons Learned from Cases Submitted to the 22nd Meeting of the European Association for Haematopathology/Society of Hematopathology Bone Marrow Workshop Organized by the European Bone Marrow Working Group, Dubrovnik 2024.","authors":"Alexandar Tzankov, Anna Green, Roos Leguit, Leonie Saft, Olga K Weinberg, Alexandra Traverse-Glehen","doi":"10.1159/000548829","DOIUrl":"10.1159/000548829","url":null,"abstract":"","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"160-185"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280921","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":"Assessing Tumour Budding in Lung Squamous Cell Carcinoma: A Comparative Analysis of Digital Whole-Slide Imaging and Light Microscopy.","authors":"Mark Keyter, Stefano Lucà, Marie Maillard, Solange Peters, Thorsten Krueger, Sabina Berezowska","doi":"10.1159/000549728","DOIUrl":"10.1159/000549728","url":null,"abstract":"<p><p><p>Introduction: Tumour budding (TB) is an emerging prognostic marker in solid cancers and has recently been endorsed by the IASLC as a component of grading in lung squamous cell carcinoma (LUSC). With the growing adoption of digital pathology, the reproducibility of TB assessment on whole-slide images (WSIs) warrants evaluation.</p><p><strong>Methods: </strong>We assessed the utility of WSI for TB evaluation in a retrospective cohort of 204 resected LUSC cases. Peritumoral budding (PTB) and intratumoural budding (ITB) were independently scored by two pathologists, applying the International Tumour Budding Consensus Conference (ITBCC) criteria established for colorectal cancer and endorsed by the IASLC for use in LUSC. A total of 816 TB hotspot regions were analysed.</p><p><strong>Results: </strong>Substantial intraobserver reliability was observed, with strong correlations between absolute bud counts in WSI and conventional light microscopy (CLM; R = 0.845, p < 0.001; R = 0.880, p < 0.001). Interobserver agreement was moderate for both PTB and ITB across platforms (Cohen's κ: CLM 0.582 [PTB], 0.570 [ITB]; WSI 0.593 [PTB], 0.423 [ITB]). Discordance mainly occurred in lower TB categories due to differences in hotspot selection and morphological mimics. When applying the recently proposed IASLC two-tier cutoff (0-9 buds vs. ≥10 buds), interobserver agreement for PTB improved modestly (κ = 0.49 for CLM; κ = 0.53 for WSI), with overall agreement exceeding 93%.</p><p><strong>Conclusion: </strong>These findings support the feasibility and reproducibility of TB assessment using WSI and highlight its potential for standardizing LUSC TB evaluation in digital pathology workflows. WSI also demonstrated practical advantages, including easier field selection and annotation. </p>.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"135-146"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12788830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596905","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":"Erratum.","authors":"","doi":"10.1159/000550993","DOIUrl":"10.1159/000550993","url":null,"abstract":"<p><p>In the article \"Assessing Tumour Budding in Lung Squamous Cell Carcinoma: A Comparative Analysis of Digital Whole-Slide Imaging and Light Microscopy\" [Pathobiology. 2025; https://doi.org/10.1159/000549728] by Keyter et al., the 3rd author's name should read \"Marie Maillard.\"The original online article has been updated to reflect this.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"186"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639539","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":"Malignant Progression of Subependymal Giant Cell Astrocytoma-Imitating Fibrous Meningioma in a Child Carrying a Germline <italic>CHEK2</italic> Mutation.","authors":"Bartosz Szmyd, Marcin Braun, Agata Pastorczak, Dariusz Jan Jaskólski, Joanna Madzio, Karolina Miarka-Walczyk, Zuzanna Urbańska, Wiesława Grajkowska, Joanna Trubicka, Dariusz Adamek, Dobromiła Barańska, Wojciech Młynarski, Joanna Trelińska","doi":"10.1159/000550591","DOIUrl":"10.1159/000550591","url":null,"abstract":"<p><strong>Introduction: </strong>The subependymal giant cell astrocytoma (SEGA) predominantly occurs in patients with tuberous sclerosis. Here, we present an unusual aggressive transformation of SEGA-imitating fibrous meningioma in a child carrying a germline CHEK2 mutation.</p><p><strong>Methods: </strong>This case study was conducted at a tertiary pediatric oncology center in accordance with current diagnostic and therapeutic standards. Tumor classification followed WHO CNS5 criteria and was complemented by genome-wide DNA methylation profiling. Comprehensive molecular workup included germline and somatic whole exome sequencing, copy number analysis, and RNA sequencing.</p><p><strong>Results: </strong>An 8.5-year-old girl presented with an intraventricular tumor initially diagnosed as SEGA based on imaging and partial resection histology. Treatment with an mTOR inhibitor led to 4 years of stability before rapid progression and death due to postoperative brain edema. Re-examination of both specimens revealed transformation into an aggressive anaplastic meningioma, while the initial lesion was reclassified as fibrous meningioma. Whole exome and microarray analyses excluded germline TSC1/TSC2 defects but identified a pathogenic germline CHEK2 variant (c.1466del, p.Asn489ThrfsTer23). Somatic alterations involving NF1 and TP53 were found in the primary tumor.</p><p><strong>Conclusions: </strong>Constitutional CHEK2 mutations combined with somatic NF1 defect may have promoted the malignant progression of SEGA-imitating fibrous meningioma and its favorable initial response to mTOR inhibitors.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"246-254"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146065872","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":"Unravelling the Tumourigenesis Mechanisms of Oncocytic Cell Tumours: Discoveries from a Comparative Omics Study.","authors":"Sule Canberk, Marta Ferreira, Arnaud Da Cruz Paula, Luísa Pereira, Carla Oliveira, Hugo Osório, Paula Soares, Valdemar Máximo","doi":"10.1159/000548985","DOIUrl":"10.1159/000548985","url":null,"abstract":"<p><strong>Introduction: </strong>Oncocytic cell tumours (OCTs), previously referred to as Hürthle cell tumours of the thyroid, are a subset of thyroid and endocrine neoplasms that pose diagnostic and therapeutic challenges owing to their unpredictable clinical behaviour. The transcriptomic and proteomic landscapes of OCTs remain poorly characterized compared with those of mitochondrion-rich neoplasms (MRNs: thyroid tumours with ≥75% oncocytic cells that share similar morphology but harbour nuclear driver mutations consistent with their respective histotypes rather than mitochondrial alterations).</p><p><strong>Methods: </strong>We performed RNA and protein sequencing on 12 OCT samples and 6 MRNs. This study was prompted by the understanding that oncocytic morphology alone does not necessarily predict tumour behaviour.</p><p><strong>Results: </strong>RNA sequencing analysis identified 47 downregulated and 38 upregulated differentially expressed genes (DEGs) in OCTs relative to MRNs, with significant enrichment in pathways related to heme metabolism. Protein sequencing further revealed 20 under-expressed and 64 over-expressed differentially expressed proteins (DEPs) in OCTs. Notably, all oncocytic carcinomas formed a distinct cluster separate from the MRNs, indicating a unique proteomic profile.</p><p><strong>Conclusion: </strong>Most of the DEPs were involved in three key cellular pathways: epigenetic regulation, the tumour microenvironment, and protein biogenesis, suggesting that these processes may underlie the distinctive morphology and behaviour of OCTs. These findings highlight the need for continued research into these molecular mechanisms to improve the diagnostic accuracy and develop targeted therapies for patients with OCTs.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"109-122"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145392147","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":"Expression of Far Upstream Element-Binding Protein in Gastrointestinal Stromal Tumors and Its Regulation of Cell Proliferation, Migration, and Invasion.","authors":"Zhigao Zhang, Fucheng Zhang, Shubao Zhang, Xiaoling Song, Yonghong Xu, Yaojun Wang","doi":"10.1159/000547278","DOIUrl":"10.1159/000547278","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to observe the expression of far upstream element-binding protein 1 (FUBP1) in gastrointestinal stromal tumors (GISTs) and explore its impact on the biological behavior of GIST cells.</p><p><strong>Methods: </strong>Fifty patients with GIST who underwent surgical resection were selected, and cancer tissues and adjacent normal tissues were gathered. The expression level of FUBP1 and its correlation with clinicopathological data and prognosis in patients with GISTs were assessed. GIST-T1 cell lines in the logarithmic growth phase were transfected with lentiviruses overexpressing FUBP1, small hairpin RNA targeting FUBP1, and their respective negative controls. FUBP1 expression levels in each group, cell biological behavior were tested, and the effect of FUBP1 on tumor growth in vivo were tested.</p><p><strong>Results: </strong>Compared to adjacent normal tissues, FUBP1 expression level was elevated in GIST cancer tissues and was concerned with tumor size, NIH risk category, and tumor metastasis in patients. Knockdown of FUBP1 inhibited cell malignant behaviors and promoted cell apoptosis, while overexpression of FUBP1 had the opposite effects. FUBP1 facilitated the growth of GIST cells in vivo.</p><p><strong>Conclusion: </strong>FUBP1 is upregulated in GISTs and facilitates the invasion, migration, and proliferation of GIST cells. This provides a new perspective for understanding the pathogenesis of GIST and lays a foundation for developing potential therapeutic strategies targeting FUBP1.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"23-33"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964272","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 Power of MUC2 in Mucinous Adenocarcinomas.","authors":"Kemal Behzatoğlu","doi":"10.1159/000550592","DOIUrl":"10.1159/000550592","url":null,"abstract":"<p><p><p>Background: In cancers, key prognostic determinants such as clinical stage and mutational load are well recognized. However, mucinous adenocarcinomas (MACs) display distinct biological behavior as a large proportion of their tumor volume consists of extracellular mucin, predominantly the MUC2 protein, rather than neoplastic cells. MUC2 provides a protective barrier for cancer cells against external factors, including chemotherapeutic agents and cytotoxic lymphocytes, while its anti-inflammatory and tumor-suppressive properties paradoxically support tumor persistence and immune evasion. Summary: Excessive mucin secretion and its viscoelastic properties facilitate rapid local expansion and dissemination into adjacent tissues. These effects are particularly significant in organs that open into body cavities, such as the colon and appendix, whereas they are less pronounced in confined organs such as the breast. In ductal organs, overexpression of MUC2 may promote early invasion through pressure-induced disruption of ductal structures. Key Messages: Consequently, in MACs, tumor location and organ architecture, alongside clinical stage and mutational profile, are critical determinants of biological behavior. Accurate differential diagnosis and therapeutic approaches should address both organ-specific pathways and MUC2-related mechanisms, including its structural, anti-inflammatory, and tumor-suppressive functions. MUC2-targeted therapies may thus represent a promising adjunct to conventional, organ-based treatment strategies. </p>.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"232-245"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011577","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":"Increased Infiltration of Tissue-Resident Memory T Cells Predicts a Good Response to Anti-PD-L1 Immunotherapy in Extrahepatic Cholangiocarcinoma.","authors":"Yoshiyuki Tagayasu, Rin Yamada, Kosuke Kanemitsu, Yoshihiko Kondo, Yukio Fujiwara, Takumi Tanizaki, Rumi Itoyama, Yuki Kitano, Hiromitsu Hayashi, Yoshihiro Komohara, Masaaki Iwatsuki","doi":"10.1159/000547222","DOIUrl":"10.1159/000547222","url":null,"abstract":"<p><strong>Introduction: </strong>Extrahepatic cholangiocarcinoma (eCCA) is an aggressive malignancy with a poor prognosis. Immune checkpoint inhibitors (ICIs) targeting PD-L1 enhance antitumor immunity, but reliable predictive biomarkers remain unclear. This study investigated tumor-infiltrating immune cells, including T cells and macrophages, as potential biomarkers for ICI efficacy in eCCA.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 15 eCCA patients who received durvalumab for recurrent or unresectable disease after surgery. Immunohistochemical staining assessed PD-L1, HLA-class I/II, CD8, and CD103 expression in resected tumor specimens. ICI response was evaluated using RECIST 1.1 criteria and classified as partial response (PR), stable disease (SD), or progressive disease (PD). Correlations between immune cell infiltration and clinical outcomes were analyzed.</p><p><strong>Results: </strong>Five patients achieved PR, five SD, and five PD. CD8+ and CD103+ T-cell infiltration within tumor nests was significantly higher in PR and SD groups than in PD (p = 0.032, p = 0.0147). High HLA-class I expression correlated with response, while PD-L1 and HLA-class II showed no significant association. Patients with increased CD8+CD103+ T cells demonstrated better disease control.</p><p><strong>Conclusion: </strong>Intratumoral CD8+ and CD103+ T cells may serve as predictive biomarkers for ICI efficacy in eCCA, highlighting tissue-resident immune cells as therapeutic targets.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-11"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732642","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":"Expression of ENPP1 in Testicular Germ Cell Tumors: Exploring Its Role in the Pathobiology of Distinct Histotypes and in Prognosis.","authors":"Miguel Bernardo Alves, Nuno Tiago Tavares, Fernanda Fernandes-Pontes, Alexandra Lapa, Rita Guimarães, Paula Lopes, Isaac Braga, Joaquina Maurício, Carmen Jerónimo, Rui Henrique, João Lobo","doi":"10.1159/000547655","DOIUrl":"10.1159/000547655","url":null,"abstract":"<p><strong>Introduction: </strong>Testicular germ cell tumors (TGCTs) are the most common solid malignancies among young men. Despite good response to cisplatin-based chemotherapy, side effects negatively affect quality of life. Recent development of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors opens opportunity for targeted therapy, but ENPP1 expression in TGCTs has not been characterized. We aimed to assess ENPP1 immunoexpression in a cohort of primary and metastatic TGCTs, and in normal testicular parenchyma, looking into differential immunoexpression patterns among subtypes and clinicopathological correlations.</p><p><strong>Methods: </strong>Overall, 90 TGCT individual tumor components from 63 patients diagnosed and treated at a comprehensive cancer center were assessed, using immunohistochemistry to ascertain biomarker expression (combined score of stained tumor cells percentage and intensity). In silico analysis of The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) datasets was performed for additional validation.</p><p><strong>Results: </strong>Significant differences in ENPP1 expression across TGCT subtypes were disclosed. Seminomas and embryonal carcinomas (ECs) showed significantly higher ENPP1 expression compared to other subtypes, the highest levels being found in EC, which was confirmed with in silico analysis of TCGA and HPA. Expression in metastatic samples was overall lower compared to primary TGCTs. ENPP1 was not expressed in germ cells of healthy testicular parenchyma.</p><p><strong>Conclusion: </strong>We demonstrate that ENPP1 is expressed in TGCTs, mostly EC (a frequently aggressive tumor subtype), followed by seminoma (the most common TGCT subtype), suggesting potential responsiveness to novel ENPP1 inhibitors. Absent expression in germ cells of healthy testicular parenchyma suggest cancer cells specificity and low probability of fertility-related toxicity.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"12-22"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732641","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":"Mechanistic Underpinnings of Lung Cancer Initiation in Patients with Human Immunodeficiency Virus Infection.","authors":"Omar Bushara, Charles Crepy D Apos Orleans, Yash Kadakia, Rucha Alur, David DeVaro, Sunil Singhal","doi":"10.1159/000546745","DOIUrl":"10.1159/000546745","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the leading cause of cancer related death in the USA. A proven risk factor for the development and progression of lung cancer is human immunodeficiency virus (HIV).</p><p><strong>Summary: </strong>HIV persists within the lung in alveolar macrophages and bronchial epithelial cells, reducing mucociliary function and decreasing epithelial integrity. This persistence yields chronic inflammation by way of matrix metalloproteinases, which causes pulmonary injury. Over time, this progresses to pulmonary disease and allows for the development of superimposed pulmonary infections and chronic inflammatory states. This injury is a risk factor for the development of dysplasia, and chronic pulmonary disease and infections further increase the risk for developing lung cancer. HIV persistence and chronic inflammation also lead to CD8+ T cell exhaustion and alterations to macrophages and dendritic cells that blunt the physiologic antitumor response. As such, HIV infection promotes initial dysplasia and allows for progression on preinvasive lesions to frank malignancy.</p><p><strong>Key messages: </strong>The purpose of this review is to highlight HIV as an under-appreciated risk factor and summarize the biologic and immunologic role of HIV in lung cancer initiation and progression. Further research regarding risk reduction and surveillance in this population and the potential increased role of immunotherapy is warranted.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"48-62"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732643","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}