Evidence map›Paper›PMID 39899075›Full record

ArticleActa neuropathologica2025

IDH-mutant astrocytomas with primitive neuronal component have a distinct methylation profile and a higher risk of leptomeningeal spread.

Felix Hinz, Dennis Friedel, Andrey Korshunov, Franziska M Ippen, Henri Bogumil, Rouzbeh Banan, Sebastian Brandner, Martin Hasselblatt, Henning B Boldt, Vaidas Dirse and 40 more

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Article in Acta neuropathologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

50 authors.

Felix HinzDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Dennis FriedelDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Andrey KorshunovDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Franziska M IppenClinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Henri BogumilDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Rouzbeh BananDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Sebastian BrandnerDivision of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London, UK.
Martin HasselblattInstitute of Neuropathology, University Hospital Münster, Münster, Germany.
Henning B BoldtDepartment of Pathology, Odense University Hospital, Odense, Denmark.
Vaidas DirseHematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.
Hildegard DohmenInstitute of Neuropathology, Justus-Liebig University Giessen, Giessen, Germany.
Eleonora AronicaDepartment of Pathology, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Michael BrodhunDepartment of Neurosurgery, Helios Clinic Erfurt, Erfurt, Health and Medical University, Erfurt, Germany.
Marike L D BroekmanDepartment of Neurosurgery, Haaglanden Medical Center and Leiden University Medical Center, Leiden, The Netherlands.
David CapperDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Asan CherkezovInstitute of Neuropathology, University Hospital Münster, Münster, Germany.
Maximilian Y DengNational Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
Vera van DisDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Jörg FelsbergInstitute of Neuropathology, Medical Faculty, and University Hospital Düsseldorf, Heinrich Heine University, and German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany.
Stephan FrankInstitute of Pathology, Division of Neuropathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Pim J FrenchDepartment of Neurology, Brain Tumor Center at ErasmusMC Cancer Institute, Rotterdam, The Netherlands.
Rüdiger GerlachDepartment of Neurosurgery, Helios Clinic Erfurt, Erfurt, Health and Medical University, Erfurt, Germany.
Kirsten GöbelDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Eric GooldInstitute for Experimental Pathology, ARUP Laboratories, Salt Lake City, UT, USA.
Jürgen HenchInstitute of Pathology, Division of Neuropathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Sven KantelhardtDepartment of Neurosurgery, Vivantes Klinikum im Friedrichshain, Berlin, Germany.
Patricia Kohlhof-MeineckeDepartment for Pathology, Katharinenhospital Stuttgart, 70174, Stuttgart, Germany.
Sandro KriegDepartment of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
Christian MawrinDepartment of Neuropathology and Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, and Center of Behavioral Brain Science, Magdeburg, Germany.
Gillian MorrisonCentre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
Angelika MühlebnerDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Koray OzdumanDepartment of Neurosurgery, School of Medicine, Acibadem University, 34752, Istanbul, Turkey.
Stefan M PfisterHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Pietro Luigi PolianiPathology Unit, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy.
Marco PrinzSignalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
Guido ReifenbergerInstitute of Neuropathology, Medical Faculty, and University Hospital Düsseldorf, Heinrich Heine University, and German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany.
Markus J RiemenschneiderDepartment of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
Roman SankowskiInstitute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Daniel SchrimpfDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Martin SillHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Matija SnuderlNYU Langone Health, New York, NY, USA.
Robert M VerdijkDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Mathew R VoisinPrincess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
Pieter WesselingDepartment of Pathology, Amsterdam University Medical Centers, Amsterdam and Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Wolfgang WickDepartment of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
David E ReussDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Andreas von DeimlingDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Felix SahmDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Sybren L N Maas *Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Abigail K Suwala *Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. Abigail.Suwala@med.uni-heidelberg.de.

Funding

Bundesministerium für Bildung und Forschung 01EO2103Deutsche Forschungsgemeinschaft 259373024Deutsche Forschungsgemeinschaft 532594103
6 · The paper itself

Abstract

IDH-mutant astrocytomas are diffuse gliomas that are defined by characteristic mutations in IDH1 or IDH2 and do not have complete 1p/19q co-deletion. The established grading criteria include histological features of brisk mitotic activity (grade 3) and necrosis and/or microvascular proliferation (grade 4). In addition, homozygous deletion of the CDKN2A/B locus has recently been implemented as a molecular marker for grade 4 IDH-mutant astrocytomas. Here, we describe a subgroup of high-grade IDH-mutant astrocytomas characterised by a primitive neuronal component based on histology and a distinct DNA methylation profile (n = 51, ASTRO PNC). Misinterpretation as carcinoma metastasis was common, since GFAP expression was absent in the primitive neuronal component, whereas TTF-1 expression was detected in 15/19 cases (79%) based on immunohistochemistry. Apart from mutations in IDH1, TP53, and ATRX, we observed enrichment for alterations in RB1 (n = 19/51, 37%) and MYCN (n = 14/51, 27%). Homozygous CDKN2A/B deletion (n = 1/51, 2%) and CDK4 amplification (n = 3/51, 6%) were relatively rare events. Clinical (n = 31 patients) and survival data (n = 23 patients) indicate a clinical behaviour similar to other CNS WHO grade 4 IDH-mutant astrocytomas, however with an increased risk for leptomeningeal (n = 7) and extra-axial (n = 2) spread. Taken together, ASTRO PNC is defined by a distinct molecular and histological appearance that can mimic metastatic disease and typically follows an aggressive clinical course.

Indexed as

AstrocytomaBrain NeoplasmsDNA MethylationIsocitrate DehydrogenaseMeningeal NeoplasmsAdolescentAdultAgedCyclin-Dependent Kinase Inhibitor p16FemaleHumansMaleMiddle AgedMutationYoung AdultCyclin-Dependent Kinase Inhibitor p16IDH1 protein, humanIDH2 protein, humanIsocitrate DehydrogenaseAstrocytomaDNA methylationIDH-mutantMYCNPrimitive neuronal componentRB1

Identifiers

PMID39899075
PMCPMC11790679

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