Virchows Archiv最新文献

{"title":"Hepatocyte nuclear factor 4 alpha defines a distinct subtype of lung carcinoid with therapeutic potential targeting somatostatin receptor 2.","authors":"Toshinori Otani, Yuuki Nishimura, Eijitsu Ryo, Taisuke Mori, Takashi Ohtsuka, Masayuki Shimoda","doi":"10.1007/s00428-026-04720-x","DOIUrl":"https://doi.org/10.1007/s00428-026-04720-x","url":null,"abstract":"<p><p>Lung neuroendocrine neoplasms (NENs) range from low-grade carcinoids to high-grade aggressive neuroendocrine carcinomas (NECs). While studies have identified molecular subtypes of NEC driven by lineage-defining transcription factors, the molecular classification of lung carcinoids (LCs) remains poorly understood. Here, we investigated the molecular and clinicopathological characteristics of LC, focusing on hepatocyte nuclear factor 4α (HNF4α), a transcription factor expressed in certain NECs. Using a publicly available transcriptomic dataset comprising 30 carcinoid tumors, we identified a distinct HNF4A-high LC subtype, in which HNF4A expression was almost mutually exclusive with NK2 Homeobox 1 (NKX2-1), which encodes thyroid transcription factor-1 (TTF-1), and Achaete-Scute family BHLH transcription factor 1 (ASCL1), showing a trend toward central/endobronchial locations. Immunohistochemical analysis of 15 surgically resected LCs revealed that HNF4α-positive LCs accounted for 46.7% (7/15) and HNF4α-negative LCs and tumorlets were mostly TTF-1-positive. RNA sequencing of representative HNF4α-positive and -negative cases demonstrated that the HNF4α-positive subtype possesses a distinctive molecular signature. Differentially expressed genes identified across two independent transcriptome datasets revealed that HNF4α-positive/HNF4A-high and HNF4α-negative/HNF4A-low LCs were enriched for genes related to the digestive and pulmonary neuroendocrine systems, respectively, suggesting distinct cells of origin. Furthermore, somatostatin receptor 2 (SSTR2) was significantly upregulated in the HNF4α-positive/HNF4A-high subtype, as validated by immunohistochemistry. Taken together, HNF4α-positive LC represents a unique subtype characterized by a specific neuroendocrine phenotype, mutually exclusive with TTF-1 and ASCL1 expression, and SSTR2 may serve as a potential therapeutic target for this subtype.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040925","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":"The indolent nature of gastroblastoma. Report of an illustrative case with 28 years of follow-up showing previously unreported immunohistochemical and molecular features.","authors":"Stefano La Rosa, Federica Branca, Giovanna Finzi, Laura Libera, Monica Leutner, Christoph Schubart, Abbas Agaimy","doi":"10.1007/s00428-026-04729-2","DOIUrl":"https://doi.org/10.1007/s00428-026-04729-2","url":null,"abstract":"<p><p>We report the clinical, morphological, ultrastructural, and molecular features of a gastroblastoma diagnosed in a 27-year-old male describing some unreported findings that can help to better understand this very rare tumor. The clinical course lasting 28 years confirms the indolent nature of gastroblastoma, although the disease was metastatic to local lymph nodes and peritoneum at the time of diagnosis. The tumor displayed a predominant monophasic appearance, being composed of epithelial cells with only very rare spindle mesenchymal cells, confirmed at ultrastructural examination. Thorough immunohistochemical investigation demonstrated coexpression of cytokeratins (AE1/AE3, CAM5.2, CK8/18), podoplanin (D2-40), CD56, and NSE in absence of synaptophysin, chromogranin A, DOG1, CD117, CD34, SMA, desmin, vimentin, and S100. In addition, the expression of somatostatin receptor 2 A associated with positive octreoscan and ⁶⁸Ga-DOTATOC PET imaging may suggest the use of this nuclear medicine approach for the staging of the tumor and to select patients for possible therapy with somatostatin analogues. The tumor was mismatch repair proteins proficient and did not show any mutation in all 60 genes investigated. Interestingly, targeted RNA sequencing identified a previously unreported TAC3::GLI1 fusion that expands the spectrum of genetic aberrations of gastroblastoma.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031422","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":"Immunohistochemical expression of p53 is a helpful surrogate marker in the differential diagnosis of primary ovarian mucinous tumors: a large study of 181 cases of mucinous borderline tumor and carcinoma.","authors":"Pavel Dundr, Isabela Töltési, Michaela Kendall Bártů, Jana Drozenová, Pavel Fabian, Oluwole Fadare, Jitka Hausnerová, Jan Laco, Sigurd F Lax, Radoslav Matěj, Ivana Stružinská, Zuzana Špůrková, Barbora Weberová, Simona Stolnicu, Marián Švajdler, W Glenn McCluggage, Romana Vránková, Kristýna Němejcová","doi":"10.1007/s00428-026-04724-7","DOIUrl":"https://doi.org/10.1007/s00428-026-04724-7","url":null,"abstract":"<p><p>Primary ovarian mucinous tumors represent a group of tumors in which the diagnosis can be difficult in some cases. The most problematic aspect is the distinction between mucinous borderline tumor (MBT) and mucinous carcinoma (MC) with expansile type of invasion. Ancillary markers to help this distinction would be beneficial, but due to the overlapping immunohistochemical and molecular features, no markers are currently widely used in this scenario. However, a recent study showed that the immunohistochemical expression of p53 with a discriminatory cut-off of 30% tumor cells with strong nuclear expression can be used as a surrogate, but this finding has not been validated in an independent series of ovarian mucinous tumors. In our study, we analyzed 181 ovarian mucinous tumors (MBT, MC or equivocal), focusing on the practical significance of p53 expression in differential diagnosis, including assessment of the value of the proposed 30% strong expression cut-off. Of the tumors included in the study, 23/109 (21.1%) cases of MBT, 42/60 (70%) cases of MC, and 8/12 (66.7%) of mucinous tumors classified as equivocal (overlap between MBT and MC) showed an abnormal p53 staining pattern, including cases with expression in ≥ 30% of tumor cells, cases with complete negativity, and cases with abnormal cytoplasmic staining. In conclusion, the results of our study confirm that p53 immunohistochemical staining can be of practical use in the differential diagnosis of ovarian mucinous tumors. Our receiver operating characteristics (ROC) analyses demonstrated that although cut-offs lower than 30% yielded slightly higher overall discriminatory performance, the predefined ≥ 30% threshold provided substantially higher specificity, which is likely more relevant in routine diagnostic practice. In the setting of morphologically equivocal ovarian mucinous tumors, higher specificity may reduce the risk of overdiagnosing MBT as MC, while still identifying a substantial subset of malignant tumors.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026076","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":"Sinonasal POU2AF3 (COLCA2)-rearranged carcinomas: a study of 11 aggressive tumors with findings supporting classification as solid adenoid cystic carcinoma.","authors":"Sintawat Wangsiricharoen, Kelly E Craven, Kristina M Wakeman, James E Davis, Lindsey O Lowder, Evan Raps, Tiffany G Baker, Morgan Blakely, Ross J Taliano, Sara Amin, Mena Mansour, Gerben E Breimer, Abbas Agaimy, Justin A Bishop","doi":"10.1007/s00428-026-04716-7","DOIUrl":"https://doi.org/10.1007/s00428-026-04716-7","url":null,"abstract":"<p><p>POU class 2 homeobox associated factor (POU2AF3) is a gene that has been associated with increased risk of colon cancer. Recently, colleagues have reported recurrent EWSR1/FUS::POU2AF3 fusions in undifferentiated spindle cell/round cell sarcomas with a predilection for the sinonasal tract. We report 11 sinonasal POU2AF3-rearranged carcinomas that are distinct from the EWSR1/FUS::POU2AF3 sarcomas. The tumors affected mostly in men (median age: 46 years) and arose in the sinonasal tract (median size: 6 cm). Clinical follow-up on 9 patients showed 6 patients developed distant metastases with a latency from the time of presentation to 16 months. Four patients died of disease, 4 were alive with disease, and 1 was alive with no evidence of disease. Most tumors showed histologic features consistent with solid adenoid cystic carcinoma (AdCC), comprising basaloid cells growing in solid nests or sheets. All showed varying extent of duct formation. Pankeratin, CK7, CD117, and CK5/6 were expressed in all tested tumors; most were also positive for S100 protein and SOX10. RNA sequencing revealed EP300::POU2AF3 (n = 6), EWSR1::POU2AF3 (n = 3), CREBBP::POU2AF3 (n = 1), and CHD7::POU2AF3 (n = 1). Most also harbored NOTCH1 mutations (6/9). MYB RNA expression was elevated by RNA sequencing and/or RNA in situ hybridization in 7/7 tested cases. Our findings support that a subset of sinonasal solid AdCC harbors POU2AF3 rearrangements, and these tumors pursue an aggressive clinical course. Diffuse expressions of pankeratin, S100 protein, SOX10, CK7, and/or CD117 provide a useful immunoprofile that reflects the diffuse overgrowth of neoplastic ductal cells in AdCC and distinguishes them from the EWSR1/FUS::POU2AF3 sarcomas.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031373","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":"Anal canal neoplasms in the modern era: integrating HPV biology, LAST terminology, and evolving molecular classification.","authors":"Kathleen Byrnes, Lysandra Voltaggio","doi":"10.1007/s00428-026-04719-4","DOIUrl":"https://doi.org/10.1007/s00428-026-04719-4","url":null,"abstract":"<p><p>Anal canal neoplasia comprises a heterogeneous and evolving group of precursor lesions and invasive malignancies whose classification increasingly depends on integrating morphology, human papillomavirus association, immunophenotype, and molecular alterations. This review summarizes current concepts in the pathology of anal canal neoplasms, with emphasis on practical application of Lower Anogenital Squamous Terminology, distinction between low-grade and high-grade squamous intraepithelial lesions, and the role of ancillary testing in diagnostically challenging cases. We discuss the expanding spectrum of invasive neoplasms, including human papillomavirus-driven and human papillomavirus-independent squamous cell carcinoma, anorectal neuroendocrine carcinoma, and anal adenocarcinoma, highlighting recently described subtypes and their clinicopathologic significance. Attention is given to emerging molecular correlates, including alterations in TP53, CYLD, and other oncogenic pathways, which may refine classification and prognostic stratification. The review also addresses unresolved issues, including precursor lesions for human papillomavirus-independent disease, evolving terminology for glandular and mixed lesions, and controversy regarding staging of anal adenocarcinoma. By combining contemporary terminology with morphologic, immunohistochemical, and molecular findings, this review provides a practical framework for pathologists navigating an uncommon but increasingly complex diagnostic area.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025921","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":"Clinical Interchangeability of 22C3 and 28 - 8 PD-L1 assays for patient selection in esophageal squamous cell carcinoma.","authors":"Halim Song, Ji-Seon Jeong, Uiree Jo, Young Soo Park, Joon Seon Song","doi":"10.1007/s00428-026-04722-9","DOIUrl":"https://doi.org/10.1007/s00428-026-04722-9","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) comprises 84% of esophageal cancers, with a poor prognosis due to late diagnosis and limited treatment. Immunotherapy targeting programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) has improved survival outcomes; however, variability in PD-L1 testing platforms and scoring methods poses challenges. This study evaluated concordance between the PD-L1 immunohistochemistry assays, specifically 22C3 and 28 - 8, in ESCC using tumor proportion score (TPS) and combined positive score (CPS) methodologies to address inconsistencies in testing approaches. PD-L1 expression in 198 ESCC cases was assessed using biopsy or surgical resection specimens. Two standardized PD-L1 assays (Dako 22C3 pharmDx and Dako 28 - 8 pharmDx) were evaluated according to the manufacturer's protocols. Staining was independently scored by two pathologists using TPS and CPS with cutoffs of ≥ 1%, ≥ 10%, and ≥ 50%. Among 198 ESCC cases, PD-L1 expression assessed by the 22C3 and 28 - 8 assays showed comparable positivity rates across TPS and CPS cutoffs. Inter-assay concordance was high, with intraclass correlation coefficients (ICC) of 0.82 and 0.81 for TPS and CPS, respectively. Cohen's kappa and Gwet's AC1 showed substantial agreement across clinical cutoffs. Inter-observer reproducibility was excellent (ICC, 0.95‒0.97) for both assays. Higher T stage was associated with CPS positivity at the CPS ≥ 1 cutoff (p = 0.012 for 22C3; p = 0.045 for 28 - 8). Notable concordance was observed between the 22C3 and 28 - 8 assays, suggesting their potential interchangeability in selecting patients with ESCC for PD-1 inhibitor therapy.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026018","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":"KRAS-mutated endometrial carcinomas: a comprehensive analysis of clinicopathological and molecular profiles across histological subtypes.","authors":"Wen-Qi Li, Hai-Xia Wu, Han-Bo Li, Qing Zhang, Jing-Wen Si, Shu-Jie Pang, Yan Shen","doi":"10.1007/s00428-026-04723-8","DOIUrl":"https://doi.org/10.1007/s00428-026-04723-8","url":null,"abstract":"<p><p>The Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations represent oncogenic drivers in endometrial carcinoma (EC), while their clinicopathological and genomic features across EC histological subtypes have not been fully defined. In a cohort of 612 ECs subjected to targeted sequencing were retrospectively enrolled and cases were screened for KRAS hotspot mutations. Clinicopathological characteristics and genomic landscapes were systematically analyzed. KRAS hotspot mutations were identified in 119 (19.4%) EC cases, including 9 mesonephric-like adenocarcinomas (MLA), 98 endometrioid carcinomas (EEC), and 12 other histological types. Although MLA patients were younger than EECs, they showed significantly advanced FIGO stage (P < 0.0001), along with distinct patterns of myometrial invasion and lymph node metastasis. The overall dominant KRAS variants were G12D (35.3%), G12V (21.8%), and G13D (21.0%). Notably, EECs with mucinous differentiation (MD) possessed a distinct mutational spectrum dominated by G12D (83.3%), which differed significantly from other subgroups (P < 0.0001). All MLA cases displayed microsatellite stability, with only one KRAS/PTEN and three KRAS/PIK3CA co-mutations. Mismatch repair deficiency (MMRd) was observed in 31 cases (31.6%) of EECs. All EECs with MD and/or squamous differentiation harbored KRAS-PTEN/PIK3CA co-mutations, whereas KRAS were mutually exclusive with TP53 and CTNNB1 alterations. KRAS-mutated ECs display prominent subtype-specific clinicopathological and genomic heterogeneity. The unique molecular signatures may provide novel insights to improve diagnostic accuracy and facilitate the development of targeted treatment strategies.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012943","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":"Comment on: \"deep learning augmented pathological grading and intraductal carcinoma of the prostate signatures improve recurrence prediction after intensity-modulated radiation therapy\".","authors":"Lu Wang, Xiaohu Sun","doi":"10.1007/s00428-026-04725-6","DOIUrl":"https://doi.org/10.1007/s00428-026-04725-6","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009161","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":"High-risk human papillomavirus infection and immunohistochemical expression patterns of p16 and Rb in primary and metastatic squamous cell carcinoma of the lung.","authors":"Fumiya Narutomi, Hidetaka Yamamoto, Mikiko Hashisako, Kayo Ijichi, Rina Jiromaru, Ryosuke Kuga, Yoshinao Oda","doi":"10.1007/s00428-026-04547-6","DOIUrl":"https://doi.org/10.1007/s00428-026-04547-6","url":null,"abstract":"<p><p>The prevalence of high-risk human papillomavirus (HR-HPV) infection in lung squamous cell carcinoma (SCC) remains controversial. Moreover, distinguishing primary lung SCC from metastatic SCC is challenging. HPV-associated cancers, including oropharyngeal and cervical carcinomas, exhibit typical p16 overexpression and Rb partial loss pattern in both primary sites and lymph node metastases. However, their diagnostic utility in pulmonary lesions remains unclear. The clinicopathological features of 114 cases of primary lung SCC and 11 of pulmonary metastatic SCC were analyzed. HR-HPV infection was assessed using RNA in situ hybridization and immunohistochemistry for p16 and Rb. HR-HPV was not detected in any primary lung SCC cases, whereas it was detected in 9 of 11 metastatic SCC cases. All nine cases of HPV-positive metastatic SCCs showed p16 positivity and Rb loss (partial loss, n = 8; complete loss, n = 1). Among the primary lung SCC cases, 31 (27.2%) cases were positive for p16, and 48.4% showed preserved Rb expression and 51.6% showed complete loss of Rb expression. The p16 or Rb expression status did not influence the prognostic difference in primary SCCs. HR-HPV infection was not observed in primary lung SCC, suggesting a lower prevalence than previously reported. The p16+/Rb partial loss pattern was exclusively associated with metastatic HPV-related SCC, whereas primary lung SCC demonstrated distinct p16 and Rb expression profiles. However, cases with a p16+/Rb complete loss pattern require HPV-specific testing. The combination of p16 and Rb IHC with HPV-specific testing may help differentiate primary lung SCC from metastatic SCC.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002649","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":"Clinicopathological factors potentially relevant to pulmonary intravascular fibrin organisation in patients with COVID-19: an autopsy-based study.","authors":"Manuel Meneses-Flores, Brenda S Zúñiga-Ascencio, Jose S Lopez-Gonzalez, Saray Santos-Torres, Francina Bolaños-Morales, Dolores Aguilar-Cazares, Cesar Luna-Rivero","doi":"10.1007/s00428-026-04721-w","DOIUrl":"https://doi.org/10.1007/s00428-026-04721-w","url":null,"abstract":"<p><p>Microvascular thrombosis is a hallmark of severe COVID-19, but the structural organisation of fibrin within these thrombotic formations remains poorly characterized. We previously identified a distinctive radial fibrin pattern in pulmonary and renal microvessels; however, factors potentially relevant to its formation were not explored. The objective of this study was to identify clinicopathological variables potentially relevant to the formation of the radial fibrin pattern. In a retrospective observational cohort of 307 patients with COVID-19, clinical and laboratory parameters were compared between survivors and non-survivors to contextualize findings in a subset of 40 autopsied patients. Within this autopsied subset, cases were stratified according to the presence and architecture of intravascular fibrin. Clinical and laboratory parameters were evaluated across groups, and immunohistochemical studies were performed to detect platelets and endothelial-associated factors within intravascular fibrin. The radial pattern of intravascular fibrin was observed in areas of severe tissue injury. Immunohistochemistry demonstrated CD61-positive platelets within these structures, with Factor VIII and von Willebrand factor positivity. Cases with a radial pattern of intravascular fibrin showed significantly lower calcium levels and higher procalcitonin concentrations, together with trends toward increased inflammatory and coagulation markers, consistent with the broader cohort analysis in which nonsurvivors exhibited higher inflammatory and coagulation parameters. These findings suggest that, in severe COVID-19, intravascular fibrin with a radial pattern may arise in a hypercoagulable setting marked by systemic inflammation, in which hypocalcaemia appears to be a relevant variable.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002671","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}