Virchows Archiv最新文献

{"title":"Balancing innovation and interpretability in histological scoring for penile cancer-letter to the editor.","authors":"Matthias May, Christian Gilfrich, Branko Miladinovic, Maria Cohal, Oliver W Hakenberg","doi":"10.1007/s00428-025-04178-3","DOIUrl":"https://doi.org/10.1007/s00428-025-04178-3","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive molecular profiling of combined hepatocellular carcinoma and cholangiocarcinoma reveals distinct Notch signaling subgroups with prognostic significance.","authors":"Chan Mo Yang, Jaehong Lim, Myung-Giun Noh, Taebum Lee, Sangjoon Choi, Ara Ko, Young-Bae Kim, Dakeun Lee, Seokhwi Kim","doi":"10.1007/s00428-025-04172-9","DOIUrl":"https://doi.org/10.1007/s00428-025-04172-9","url":null,"abstract":"<p><p>Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) is a rare primary liver carcinoma characterized by dual hepatocytic and cholangiocytic differentiation. Accurate diagnosis remains challenging, and the underlying molecular mechanisms that could inform treatment and prognostic predictions are not fully understood. The Notch signaling pathway has been implicated in the carcinogenesis and tumor biology of cHCC-CCA, yet its role has not been comprehensively investigated. In this study, we analyzed 35 cHCC-CCA, 38 hepatocellular carcinoma (HCC), and 32 intrahepatic cholangiocarcinoma (CCA) samples using immunohistochemistry and RNA sequencing. Compared to HCC and CCA, cHCC-CCA exhibited elevated expression of NOTCH1 and its downstream targets (HES5, ASCL1, and HES1). Based on NOTCH1 and HES5 expression levels, cHCC-CCA tumors were stratified into three subgroups: Group 1 (Notch inactivated; low NOTCH1, variable HES5), Group 2 (Notch-responsive; high NOTCH1 and HES5), and Group 3 (Notch-unresponsive; high NOTCH1, low HES5). Notch-responsive tumors (Group 2) displayed the most aggressive biological characteristics, including higher rates of vascular invasion and significantly poorer progression-free survival. Transcriptomic analyses revealed that the molecular profiles of Group 2 cHCC-CCA resembled those of CCA, further confirming Notch signaling activation and identifying enriched pathways associated with increased tumor invasiveness and poor prognosis. These findings highlight the significant heterogeneity within cHCC-CCA and emphasize the potential of NOTCH1 and HES5 as biomarkers for subgroup classification. Moreover, these subgroups offer actionable insights into targeted therapies, including Notch pathway inhibitors, particularly for Notch-responsive tumors.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeat biopsies in membranous lupus nephritis in the era of target antigen identification.","authors":"Elodie Bernhard, Hamza Sakhi, Julie Oniszczuk, Constance Guillaud, Nicolas Limal, Ines Allioua, Narindra Jouan, Stephanie Guillet, Carine Diet, Bertrand Godeau, Philippe Remy, Vincent Audard, Nizar Joher, Anissa Moktefi","doi":"10.1007/s00428-025-04157-8","DOIUrl":"https://doi.org/10.1007/s00428-025-04157-8","url":null,"abstract":"<p><p>In membranous lupus nephritis (LN), positivity for the target antigen exostosin 1/2 (EXT) is associated with a lower chronicity index (CI) at first biopsy and a lower risk of progression to end-stage kidney disease (ESKD) compared to EXT-negative patients. Repeat kidney biopsies (RKB) in LN may reveal increasing CI and class transition with prognostic significance. In a cohort of membranous LN with RKB, we assessed the variation in EXT and neural cell adhesion molecule 1 (NCAM1) expression and their association with class III/IV + V transition and renal outcomes. Thirty patients with 78 biopsies were enrolled. Index biopsies included 60% EXT-NCAM1-, 34% EXT + NCAM1-, 3% EXT-NCAM1 + and 3% EXT + NCAM1 + cases. Target antigen switch occurred in 3 (10%) cases (2 EXT + to EXT-; 1 NCAM1- to NCAM1 +) with favorable renal outcomes. EXT-positive and EXT-negative groups had similar clinico-pathological characteristics at baseline and at the end of follow-up, with comparable numbers of RKB, median CI increase, class transition rates, and renal outcomes. After a median follow-up of 8.8 years, 9 (32%) patients developed ESKD or glomerular filtration rate decrease > 40%. These patients exhibited higher median first biopsy CI (p = 0.04) and higher median serum creatinine level (p = 0.01), higher median CI (p = 0.02), and higher thrombotic microangiopathy (TMA) rate (p = 0.03) at second biopsy. TMA on any follow-up biopsy was more frequent in the adverse outcome group (p = 0.001). Not only EXT but also NCAM1 expression may vary in RKB during membranous LN. EXT-positive and EXT-negative patients had similar presentation and course, while TMA and CI compromised renal outcomes.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-seq of penile squamous cell carcinoma shows ODC1 overexpression is associated with worse overall survival.","authors":"Brian A Keller, Gareth Palidwor, Elena Pastukhova, Zuzanna Gorski, Nicola Schieda, Kevin Hogan, Paul Borowy-Borowski, Harman Sekhon, Trevor A Flood","doi":"10.1007/s00428-025-04166-7","DOIUrl":"https://doi.org/10.1007/s00428-025-04166-7","url":null,"abstract":"<p><p>Penile squamous cell carcinoma (PSCC) is classified into human papillomavirus (HPV)-associated and HPV-independent subtypes. Aggressive and metastatic PSCCs pose significant treatment challenges due to limited effective systemic options. Polyamines are essential intracellular regulators involved in cell proliferation and tumor progression, with ODC1 serving as the rate-limiting enzyme in polyamine metabolism. We used RNA sequencing on 21 PSCC tumors to investigate ODC1 expression. ODC1 overexpression was identified in 10/21 (47.6%) tumors with a higher prevalence in HPV-independent cases (7/12, 58.3%) compared to HPV-associated tumors (3/9, 33.3%). Immunohistochemistry confirmed ODC1 positivity in 5/21 (23.8%) tumors, all of which overexpressed ODC1 and were HPV-independent. Importantly, ODC1 overexpression and positive immunostaining correlated with significantly worse overall survival (p < 0.05). These results indicate that ODC1 overexpression and positive immunostaining are associated with poor prognosis in PSCC, supporting ODC1's value as a prognostic biomarker and highlighting its potential as a novel therapeutic target, given available anti-cancer drugs targeting ODC1 activity.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small cell carcinoma with rhabdomyosarcomatous differentiation of the urinary bladder: an integrated clinicopathological and molecular characterization of five cases.","authors":"Ming Zhao, Ping Zhang, Jiayun Xu, Suying Wang, Yinzhou Shi, Lin Ye, Xiaomin Xu, Xiaodong Teng","doi":"10.1007/s00428-025-04174-7","DOIUrl":"10.1007/s00428-025-04174-7","url":null,"abstract":"<p><p>This study delineates the clinicopathological and molecular features of five rare cases of small cell carcinoma (SmCC) of the urinary bladder with rhabdomyosarcomatous differentiation, distinguishing them from alveolar rhabdomyosarcoma (ARMS). All patients were adult males (median age: 67 years) presenting with hematuria and solitary exophytic bladder masses (mean size: 2.9 cm). Histologically, tumors exhibited predominant SmCC morphology with focal anaplastic features. Focal area showing features suggesting rhabdomyosarcomatous differentiation included scattered cells with eosinophilic cytoplasm and eccentric nuclei resembling rhabdoid or immature skeletal muscle (2/5), and pseudoglandular/alveolar growth patterns mimicking ARMS (2/5). All tumors had coexisting urothelial carcinoma components (accounting for 5-15% of tumor volume). Immunohistochemistry revealed epithelial (AE1/AE3, CAM5.2), neuroendocrine (synaptophysin and/or chromogranin A, INSM1, CD56), and myogenic (desmin, MyoD1, myogenin) marker co-expression within SmCC. Molecular profiling demonstrated universal TP53/RB1 inactivation (5/5), recurrent TERT promoter mutations (4/5), and high tumor mutational burden (mean: 27.4 muts/Mb), while fluorescence in situ hybridization demonstrated the absence of ARMS-defining rearrangements involving PAX3, PAX7, and FOXO1 in all cases. Among four patients with available follow-up (5-19 months), one died of disease at 5 months, one developed multiple bone metastases by 5 months, while two showed no tumor recurrence or metastatic progression (both were treated with radical cystectomy followed by adjuvant etoposide-cisplatin chemotherapy). This study provides the first integrated clinicopathological and molecular characterization of SmCC with rhabdomyosarcomatous differentiation in the bladder. The presence of SmCC-specific alterations (TP53/RB1/TERT) and absence of ARMS-defining fusions support classification as a unique SmCC subtype with divergent rhabdomyosarcomatous differentiation.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histological differentiation of inflammatory bowel disease from \"diverticular colitis\": an actual possibility or the fog is still thick?","authors":"Vincenzo Villanacci, Gabrio Bassotti","doi":"10.1007/s00428-025-04173-8","DOIUrl":"https://doi.org/10.1007/s00428-025-04173-8","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the boundaries between neoplastic and reactive lymphoproliferations: lymphoid neoplasms with indolent behavior and clonal lymphoproliferations-a report of the 2024 EA4HP/SH lymphoma workshop.","authors":"Leticia Quintanilla-Martinez, Jan Bosch-Schips, Gorana Gašljević, Michiel van den Brand, Olga Balagué, Ioannis Anagnostopoulos, Maurilio Ponzoni, James R Cook, Stefan Dirnhofer, Birgitta Sander, Camille Laurent","doi":"10.1007/s00428-025-04168-5","DOIUrl":"https://doi.org/10.1007/s00428-025-04168-5","url":null,"abstract":"<p><p>The boundaries between neoplastic and reactive lymphoproliferations were discussed during the 2024 European Association for Haematopathology/Society for Hematopathology workshop in Dubrovnik, Croatia. Session 5 focused on indolent lymphoid neoplasms and clonal lymphoproliferations. Seventy-two cases were submitted, representing good examples of indolent lymphomas and lymphoproliferative disorders (LPD) and their diagnostic challenges. The morphologic spectrum of primary cutaneous marginal zone lymphoma/lymphoproliferation (PC-MZL/PC-MZLPD) was discussed. PC-MZL/PC-MZLPD is divided in the immunoglobulin heavy chain switched-type and non-switched-type with some clinicopathological differences. The overlapping features between PC-MZL/PC-MZLPD and PC-CD4 + T-cell LPD were highlighted. The criteria for the diagnosis of indolent T-lymphoblastic proliferation (iT-LBP) were reviewed. Indolent T-cell lymphoproliferation of the gastrointestinal tract (iT-LPD-GI) is a rare clonal, non-destructive, and non-epitheliotropic T-cell LPD occurring in adults with a male predominance. The cases submitted to the workshop revealed clinicopathological heterogeneity. Unusual features like infiltration of the complete intestinal wall, mesenteric lymph node involvement, and splenomegaly were observed. A novel group of PD1 + /CD4 + indolent cases with intestinal tropism and dissemination to blood, bone marrow, lymph node, and skin was identified. Other indolent clonal B- and T-cell LPDs were discussed including transient, clonal CD8 + T-cell proliferations, usually the result of immune-mediated cytotoxic T-cell response to virus or neoantigens, and the recently described follicle center lymphoma (FLC) of the lower female genital tract. The increasing awareness of the existence of indolent LPDs should avoid unnecessary treatments. In this report, novel findings, recommendations for diagnosis, open questions, and diagnostic challenges raised by the cases submitted to the workshop will be discussed.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computer-aided tumor cell fraction (TCF) estimation by medical students, residents, and pathologists improves inter-observer agreement while highlighting the risk of automation bias.","authors":"Ana Leni Frei, Amjad Khan, Raphaël Oberson, Stefan Reinhard, Yara Banz, Frédérique Meeuwsen, Andrew Janowczyk, Rainer Grobholz, Heather E Dawson, Alessandro Lugli, Marius Ilié, Jeroen van der Laak, Inti Zlobec","doi":"10.1007/s00428-025-04163-w","DOIUrl":"https://doi.org/10.1007/s00428-025-04163-w","url":null,"abstract":"<p><p>The potential for computer-aided diagnostics (CAD) to augment learning outcomes for medical education in histopathology are vast. However, over-reliance in CAD tools could lead to important errors if the output is inaccurate, such as automation bias. Here, we analyze the influence of a CAD tool for tumor cell fraction (TCF) estimation, named TCFCAD, on medical students with limited histopathological expertise, compared to pathology residents and practicing pathologists. Participants were third-year medical students from the University of Bern (n = 18), residents and pathologists from the European Masters in Molecular Pathology (EMMP; n = 23), and 63 practicing pathologists stratified by < 20 or > 20 years of professional experience (n = 28 and 32, respectively). Each group evaluated 10 colorectal cancer regions of interest (ROI) with and without TCFCAD assistance. The ground truth (GT) was evaluated by a laborious count of all tumor and non-tumor cells per ROI. All groups demonstrated reduced variability in TCF scores with TCFCAD assistance. The standard deviation (SD) of the TCF scores compared to the GT values before and after TCFCAD assistance were 9.09 to 4.95 for medical students, 9.93 to 5.55 for EMMP, and 9.98 to 5.69 and 9.9 to 6.13 for pathologists with < 20 and > 20 years of experience. For one image, both medical students and EMMP participants' scores swayed to the TCFCAD's output despite (1) tool output being inaccurate and (2) participants' original scores without TCFCAD assistance being closer to the GT value. This confirmed a trend of medical students following the tool's recommendation across all ROIs. All groups benefitted most from TCFCAD output for a tumor with marked inflammatory infiltrates. Although TCFCAD improved interobserver agreement, independently of professional experience, there is a demonstrated danger in over-relying on its output. This important bias must be addressed when training students and pathologists on the use of CAD tools.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary mesenchymal cystic hamartoma with EWSR1::CREM fusion: molecular redefinition and diagnostic implications.","authors":"Hao Lei, Xiude Li, Haiqin Zhang, Jing Hu, Xueyue Li, Hongyuan Liao, Xinjian Guo, Xiaofeng Zhou","doi":"10.1007/s00428-025-04165-8","DOIUrl":"https://doi.org/10.1007/s00428-025-04165-8","url":null,"abstract":"<p><p>Pulmonary mesenchymal cystic hamartoma (MCH) is an exceptionally rare benign tumor characterized by cystic-solid architecture and biphasic epithelial-mesenchymal components. We report a 56-year-old woman with a 2.6-cm right lower lobe mass, histologically composed of pseudostratified ciliated epithelium, glandular components, and primitive mesenchymal cells with cartilaginous/adipose differentiation. Tumor cells showed diffuse moderate cytoplasmic BCL-2/CD56 staining, weak-moderate nuclear PR positivity, and a low Ki-67 index (< 2%). RNA sequencing identified a novel EWSR1::CREM fusion, involving exon 13 of EWSR1 and intron 5/exon 6 of CREM. This finding expands the molecular spectrum of FET::CREB-driven tumors and distinguishes MCH from mimics such as glomus tumor and pleuropulmonary blastoma. The patient remained recurrence-free at 4-year follow-up, underscoring the benign nature of this lesion. This study highlights three critical insights: (1) Molecular significance: The EWSR1::CREM fusion suggests shared oncogenic mechanisms with intracranial mesenchymal tumors and primary pulmonary myxoid sarcoma. (2) Diagnostic refinement: Integration of molecular profiling resolves diagnostic ambiguity in cystic lung lesions. (3) Clinical relevance: Routine molecular testing should be considered for ambiguous cystic lung lesions to refine classification. Conservative management is appropriate for molecularly confirmed MCH. Our findings emphasize the necessity of integrating histomorphology, immunohistochemistry, and molecular profiling in diagnosing rare pulmonary entities. Further studies are needed to elucidate the role of EWSR1::CREM in MCH pathogenesis and explore targeted therapeutic strategies.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-center experience using reflex-targeted next-generation sequencing at diagnosis of squamous cell lung carcinoma in daily practice.","authors":"Radu Pirlog, Véronique Hofman, Samantha Goffinet, Christophe Bontoux, Virginie Lespinet, Guylène Rignol, Olivier Bordone, Caroline Lacoux, Virginie Tanga, Christelle Bonnetaud, Sandra Lassalle, Elodie Long-Mira, Davy Lim, Jean Philippe Berthet, Jonathan Benzaquen, Jacques Boutros, Charles Marquette, Simon Heeke, Marius Ilié, Paul Hofman","doi":"10.1007/s00428-025-04147-w","DOIUrl":"https://doi.org/10.1007/s00428-025-04147-w","url":null,"abstract":"<p><p>Patients with lung squamous cell carcinoma (LSCC) rarely benefit from targeted therapies in daily practice. Current and future clinical trials targeting genomic alterations may open up promising therapeutic strategies for this population. We evaluated the usefulness and the clinical added value in the real world of the analysis of LSCC at diagnosis using reflex-targeted next-generation sequencing (NGS) on-site in a single hospital center. Targeted DNA and RNA NGS and diagnostic immunohistochemistry for PD-L1 and c-MET were performed on a consecutive series of 108 LSCC patients. The main genomic alterations included mutations in TP53 [56/102; (51.9%)], PIK3CA [9/108; (8.3%)], PTEN [(8/108 (7.4%)], and KRAS [6/108; (5.6%)]. The genes with the most frequent copy number variants (CNV) were PIK3CA CNV [13/108, (12.0%)], EGFR CNV [7/108, (6.5%)], and FGFR CNV [(7/108, (6.5%)]. The expression of PD-L1 (> 1% in 69% of cases) and c-MET (H-score > 150 in 18% of cases) was independent of the genomic alterations. Rare alterations that can be targeted by tyrosine kinase inhibitors (TKI) were detected in four patients, including EGFR p.Asn771_His773dup, EGFR p.Leu861Gln, KRAS p.Gly12Cys, and MET exon 14 skipping. This study demonstrated the potential clinical utility of developing on-site targeted NGS as reflex testing for LSCC to detect molecular targets for personalised treatment using available drugs or for clinical trials. However, none of the patients in our series received targeted therapy. Most of them were treated with chemotherapy or immuno-chemotherapy according to the PD-L1 status and current standard therapeutic guidelines.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}