Current evidence on the cell of origin of meningiomas disputes the arachnoid cap cell dogma

Sep 22, 2026

Uploaded by Adam

This mini-review analyzes the traditional view that meningiomas arise exclusively from arachnoid cap cells. It synthesizes historical perspectives with modern single-cell transcriptomics, spatial sequencing, developmental biology, and transgenic animal evidence, highlighting major limitations of the classical arachnoid-based paradigm. Multi-omic and developmental data indicate meningioma origin is likely driven by a broader spectrum of progenitors. The paper argues for redefining meningioma ontogeny and aligning future classification and therapeutic strategies with cellular diversity and anatomical context.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Introduction

The evolution of meningioma nomenclature

Origin of the "arachnoid cap cell origin theory"

How the evidence on meningioma ontogeny developed

Acta Neurochirurgica (2026) 168:114 [https://doi.org/10.1007/s00701-026-06908-1](https://doi.org/10.1007/s00701-026-06908-1) Current evidence on the cell of origin of meningiomas disputes the arachnoid cap cell dogma M. Necmettin Pamir1 · Ayça Erşen‑Danyeli2 · Koray Özduman1 Received: 29 April 2026 / Accepted: 6 May 2026 © The Author(s) 2026 Abstract Background For over a century, the dominant hypothesis has maintained that meningiomas arise exclusively from arachnoid cap cells. However, emerging evidence from single-cell transcriptomics, spatial sequencing, developmental biology, and transgenic animal models suggests a significantly more complex and heterogeneous cellular origin. Methods This mini-review revisits historical perspectives and critically evaluates the limitations of the traditional arachnoidbased paradigm. By synthesizing classical histological insights with contemporary molecular and proteomic data, the study explores alternative hypotheses, particularly those implicating fibroblast-like or regionally distinct meningeal progenitors. Results The synthesis of multi-omic and developmental data indicates that a singular cellular source is insufficient to account for the clinical and biological diversity of meningiomas. Findings suggest that meningioma ontogeny is likely driven by abroader spectrum of progenitors whose characteristics vary according to anatomical location and embryological lineage. Conclusions A redefinition of meningioma ontogeny is necessary. Future classification and therapeutic strategies should reflect the inherent diversity of their cellular sources and anatomical environments, moving beyond the classical arachnoidcap-cell model. Keywords Meningioma · Arachnoid cap cell · Ontogeny Introduction The ontogeny of a tumor, in other words “the cell of origin”, provides the scaffold that is necessary for diagnosis, risk stratification, prognostication, therapeutic targeting and experimental modelling for a tumor. It provides information on the etiology as it points to the specific vulnerability allowing the initial oncogenic change to occur, and very importantly its timing. Therefore, it has been in the focus of meningioma research for over a century. In almost all textbooks,“arachnoid cap cells” are cited as the “cell of origin” for meningiomas. Having originated from early reports of John Cleland and Martin Schmidt and subsequent support from Harvey Cushing, this hypothesis * M. Necmettin Pamir [npamir@acibadem.com](npamir@acibadem.com) 1 Departments of Neurosurgery, Acıbadem University, School of Medicine, Altunizade, Yurtcan Sokağı No : 1, 34662 Üsküdar, İstanbul, Turkey 2 Pathology, Acıbadem University, School of Medicine,İstanbul, Turkey has dominated the literature, despite very limited scientific evidence [13] . Novel findings and experimental evidence is slowly challenging this dogma and changing our understanding. The current evidence points to a more diverse set of cells rather than one single cell of origin. The current literature also supports the notion that such cells or origin are likely early progenitors that exist early during development of the meninges, secondarily shaped by the tumor microenvironment. The evolution of meningioma nomenclature The precise cellular and locational origins of meningiomas have consistently been questioned for almost three centuries. In 1774, Antoine Louis in France referred to dural-based tumors as “fungating tumors of the dura mater”, offering one of the earliest tumor descriptions linked to meninges [31] . This perspective was reinforced by Jean Cruveilhierin 1835, who differentiated between “bloody tumors- “ and“cancerous tumours-of the meninges” [12] . Cruveilhier’s description indicated to a histologically defined localization. Hermann Lebert published 21 of his cases and 80 others that he collected from the literature and published the first large study on this tumour type [27] . Lebert called the tumour“Tumeur

FAQs

What is the classical hypothesis about the cell of origin of meningiomas?

For over a century, meningiomas have been widely attributed to exclusive origin from arachnoid cap cells. The review states this view dominates textbooks and the literature historically.

Which modern evidence challenges the arachnoid cap cell dogma?

The review highlights emerging findings from single-cell transcriptomics, spatial sequencing, developmental biology, and transgenic animal models. It emphasizes that these data point to a more complex and heterogeneous origin.

What conclusion does the mini-review draw about meningioma ontogeny?

It concludes that a single cellular source is insufficient to explain clinical and biological diversity. Meningioma development is likely driven by a broader spectrum of progenitors shaped by anatomical location and embryological lineage.

Sep 22, 2026

Uploaded by Adam