{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:50:53Z","timestamp":1782607853224,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Meningiomas, the most common primary intracranial tumors, are predominantly benign, but high-grade variants show marked aggressiveness, histo-molecular heterogeneity, and treatment resistance. Although the 2021 WHO CNS classification integrates molecular and histopathologic criteria, substantial inter- and intratumoral variability still limits prognostic accuracy and treatment effectiveness. The goal was to provide insight regarding the histo-molecular intratumoral heterogeneity (ITH) of meningioma and examine its clinical implications. Methods: A narrative review was performed in accordance with PRISMA guidelines. PubMed and Google Scholar were screened for studies on \u201cmeningioma\u201d and \u201cintratumoral heterogeneity\u201d published up to 28 July 2025. Eligible studies included original human research reporting histological or molecular heterogeneity with clinical relevance. Results: Eighteen studies comprising 2952 meningioma patients (mean age 59.4 \u00b1 14.8 years, range 16\u201385) were included. Integrated cytogenetic, molecular, and spatial analyses, including FISH, karyotyping, scRNA-seq, CNV profiling, and spatial transcriptomics, revealed multilayered histo-molecular heterogeneity. Histologically, regional variations in morphology and proliferative index increased with tumor grade. Genomic diversity, marked by recurrent losses of 1p, 14q, and 22q and transcriptionally distinct subclones, defined a complex tumor architecture. Spatial and temporal analyses demonstrated subclonal expansion, stepwise clonal evolution, and therapy resistance, particularly in recurrent tumors. Functionally, SULT1E1+ subclones and COL6A3-mediated macrophage\u2013tumor interactions emerged as potential key drivers of malignancy, recurrence, and radioresistance. Conclusions: Histo-molecular diversity underlies meningioma progression, recurrence, and therapeutic resistance. Standardization of ITH assessment, integration of AI-based spatial analytics, and the development of subclone-specific therapies are essential next steps toward advancing precision neuro-oncology.<\/jats:p>","DOI":"10.3390\/cancers18081206","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:55:12Z","timestamp":1775807712000},"page":"1206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Histo-Molecular Intratumoral Heterogeneity in Meningiomas: A Narrative Review"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4277-9767","authenticated-orcid":false,"given":"Nourou Dine Adeniran","family":"Bankole","sequence":"first","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"},{"name":"INSERM, Imaging Brain & Neuropsychiatry iBrain U1253, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan","family":"Le Van","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Kerherve","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard","family":"Morlaix","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Bellus","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerima","family":"Belhajali","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Lopez","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"De Buck","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia Sayda","family":"Houidi","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Farah","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Lleu","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Baland","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Cao","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"El Cadhi","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Beaurain","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6494-6725","authenticated-orcid":false,"given":"Thiebaud","family":"Picart","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Hospices Cilvils de Lyon-Pierre Wertheimer Hospital, 69500 Bron, France"},{"name":"INSERM 1052 UMR 5286, Research Cancerology Center of Lyon, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moncef","family":"Berhouma","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Dijon University Hospital Center, 21000 Dijon, France"},{"name":"Functional and Molecular Imaging Team, Centre National de la Recherche Scientifique 6302, Molecular Chemistry Institute (ICMUB), University of Bourgogne, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bi, W.L., Zhang, M., Wu, W.W., Mei, Y., and Dunn, I.F. 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