Evidence map›Paper›PMID 42034799›Full record

ArticleActa neuropathologica2026

Loss of meningothelial identity and mesenchymal fate switching in NF2-mutant meningiomas.

Ramin Rahmanzade, Leonille Schweizer, Simone Schmid, Tereza Lausová, Gianluca Sigismondo, Mozhgan Esmaeili Benvidi, Rushda Patel, Aras Fuat Kaan, Rouzbeh Banan, David Reuss and 22 more

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Article in Acta neuropathologica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

The trial behind it

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

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

32 authors.

Ramin RahmanzadeDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Leonille SchweizerDepartments of Neuropathology, Edinger Institute, Institute of Neurology, University of Frankfurt Am Main, Heidelberg, Germany.
Simone SchmidDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin Institute of Health (BIH), Charitéplatz 1, 10117, Berlin, Germany.
Tereza LausováDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Gianluca SigismondoDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Mozhgan Esmaeili BenvidiDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Rushda PatelDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Aras Fuat KaanDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Rouzbeh BananDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
David ReussDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Natalie JägerDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Marie-Theresa ForsterFrankfurt Cancer Institute (FCI), Frankfurt Am Main, Heidelberg, Germany.
Viktoria ZellerDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Patricia Kohlhof-MeineckeInstitute of Pathology, Klinikum Stuttgart, Kriegsbergstrasse 60, 70174, Stuttgart, Germany.
Annette Fisseler-EckhoffDepartment of Pathology, Helios HSK Wiesbaden, 65199, Wiesbaden, Germany.
Barbara CarlDepartment of Neurosurgery, University of Marburg, Marburg, Germany.
Patrick N HarterCenter for Neuropathology and Prion Research, LMU Munich, Munich, Germany.
Katrin LamszusDepartment of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
Ulrich SchüllerInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany.
Michal ZapotockySecond Faculty of Medicine, Prague Brain Tumor Research Group, Charles University and University Hospital Motol, V Uvalu 84, 15006, Prague 5, Czech Republic.
Till AckerFaculty of Health, Institute of Neuropathology, Justus Liebig University Giessen, Giessen, Germany.
C O HanemannPeninsula Medical School, University of Plymouth, PlymouthDevon, PL6 8BU, UK.
Jens SchittenhelmDepartment of Neuropathology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Eva BrackDivision of Pediatric Hematology/Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Uta FluckeDepartment of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
Gunhild MechtersheimerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Luca BerteroPathology Unit, Department of Laboratory Medicine, City of Health and Science University Hospital of Turin, Turin, Italy.
Christine HaberlerDivision of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.
David CapperDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin Institute of Health (BIH), Charitéplatz 1, 10117, Berlin, Germany.
Andreas von DeimlingDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Philipp SieversDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Felix SahmDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. Felix.sahm@med.uni-heidelberg.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intracranial sarcomas can arise secondarily from primary brain tumors, including gliomas and meningiomas, either spontaneously or following radiotherapy. The current WHO classification recognizes sarcomatous transformation in several tumor entities; however, sarcomas arising from meningiomas remain poorly characterized and are regarded as a possible histological manifestation within the spectrum of anaplastic meningiomas. We analyzed nine matched meningioma-sarcoma pairs using integrated histopathological assessment and molecular profiling, including DNA methylation analysis, next-generation sequencing, copy number profiling, and proteomics. Although recurrent sarcomatous tumors were clonally related to their meningioma precursors-sharing identical NF2 alterations and overlapping chromosomal aberrations-they demonstrated pronounced divergence at the histological, immunophenotypic, and epigenetic levels. Importantly, sarcomatous transformation occurred in four cases without prior radiotherapy. Sarcomatous recurrences exhibited loss of meningothelial markers and acquired expression of cytokeratin and myogenic markers. DNA methylation profiling revealed a shift away from canonical meningioma signatures toward profiles resembling non-meningothelial mesenchymal tumors. Proteomic analysis showed consistent upregulation of SOX2 in sarcomatous tumors compared with their primary counterparts, suggesting acquisition of stem-like features during lineage divergence. Clinically, these tumors were associated with aggressive growth, early recurrence, and extracranial metastases, resembling malignant sarcomas more closely than anaplastic meningiomas. In addition, analysis of an institutional cohort of NF2-mutant intracranial tumors (n = 316) suggests that sarcomas with inactivating NF2 mutations may originate from meningiomas even in the absence of a clinically recognized precursor. Together, these findings suggest that sarcomatous transformation represents a rare evolutionary endpoint in NF2-mutant meningiomas, marked by clonal continuity but pronounced biological divergence. These results highlight limitations of morphology-based classification and emphasize the value of integrated molecular diagnostics in distinguishing these tumors from conventional high-grade meningiomas. Given their sarcoma-like behavior despite a meningioma ancestry, these tumors may not be adequately captured by current meningioma grading schemes.

Indexed as

Meningeal NeoplasmsMeningiomaNeurofibromin 2SarcomaAdultAgedCell Transformation, NeoplasticDNA MethylationFemaleHumansMaleMiddle AgedMutationNeoplasm Recurrence, LocalNeurofibromin 2NF2 protein, humanAnaplastic meningiomaLineage plasticityNF2SarcomaSOX2

Identifiers

PMID42034799
PMCPMC13110230

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.