Year: 2025
Type: article
Abstract: Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly. // Methods: We analyzed 20 tumor samples by histology, RNA Next-Generation Sequencing, DNA-methylation profiling, copy number analyses, and single nucleus RNA sequencing (snRNA-seq). Clinical data, including age, sex, and disease progression, were collected. MRI series were included when available. // Results: All cases with tissue available for histology review (n=13) were morphologically consistent with intracerebral schwannoma, but differed in their extent of GFAP staining. All (n=20) shared DNA-methylation profiles distinct from other CNS tumors, as well as from VGLL-altered peripheral nerve sheath tumors. Most cases (n=14/17) harbored fusions of either VGLL3 or VGLL1 (CHD7::VGLL3 (n=9/17) and EWSR1::VGLL1 (n=5/17)). In two cases the presence of a VGLL3 fusion was also confirmed by CNA analyses (n=2/17). MRI (n=4) showed well-defined, nodular tumors with strong, homogeneous enhancement and no diffusion restriction. Tumors were located throughout the neuroaxis [supratentorial (n=15), infratentorial (n=4), and spinal (n=1)]. snRNA-seq of a VGLL1-fused tumor indicated VGLL1 upregulation in 28.6% of tumor cells (n=1). During median follow-up of 1.8 years (range 3 months-9 years), none of the tumors recurred (n=10). // Conclusions: We identify and define a new benign tumor class, designated VGLL-altered intraparenchymal CNS schwannomas. These tumors feature VGLL alterations and a specific DNA-methylation profile, with schwannoma-like histopathology and CNS localization, akin to previously classified intracerebral schwannomas.
Authors: Schmid, Simone, Mirchia, Kanish, Tietze, Anna, Liu, Ilon, Siewert, Christin, Nückles, Jakob, Schittenhelm, Jens, Behling, Felix, Snuderl, Matija, Hartmann, Christian, Brandner, Sebastian, Paine, Simon ML, Korshunov, Andrey, Hasselblatt, Martin, Coras, Roland, Epari, Sridhar, Stadelmann, Christine, Zechel, Sabrina, Simon, Michèle, Wilson, Yelena, Gianno, Francesca, Calixto-Hope, G Lucas, Zherebitskiy, Viktor, Kaimaktchiev, Vassil B, Robinson, Lorraina, Aldape, Kenneth, Hoving, Eelco W, Tops, Bastiaan BJ, Perera, Ashwyn Augustine, Göller, Pauline, Hernáiz Driever, Pablo, Wesseling, Pieter, Koch, Arend, Perry, Arie, Sahm, Felix, Jones, David TW, Capper, David
Institutions: German Cancer Research Center, Humboldt-Universität zu Berlin, Deutsches Konsortium für Translationale Krebsforschung, Charité - Universitätsmedizin Berlin, University of Tübingen, Hertie Institute for Clinical Brain Research, NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, Medizinische Hochschule Hannover, University College London Hospitals NHS Foundation Trust, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, Nottingham University Hospitals NHS Trust, University of Nottingham, Queen's Medical Centre, National Center for Tumor Diseases, University Hospital Münster, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, ERN EpiCARE, Homi Bhabha National Institute, Tata Memorial Hospital, Universitätsmedizin Göttingen, University of Göttingen, Akron Children's Hospital, Hospital for Sick Children, University of Utah, National Cancer Institute, Center for Cancer Research, Princess Máxima Center, Hopp Children's Cancer Center Heidelberg, University Hospital Heidelberg, Amsterdam University Medical Centers, Amsterdam UMC Location Vrije Universiteit Amsterdam
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G8790832697
OpenAlex ID: W6988058644
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