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

Abstract

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. This mini-review revisits historical perspectives and critically evaluates the limitations of the traditional arachnoid-based 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. 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 a broader spectrum of progenitors whose characteristics vary according to anatomical location and embryological lineage. 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 arachnoid-cap-cell model.