Our findings confirm that larger meningiomas are generally associated with higher WHO grade [3, 11, 12]. Tumor volume correlated with histopathological markers of aggressive behavior, including Ki-67 index, mitotic activity, hypercellularity, necrosis, and brain invasion. These results support the hypothesis that meningiomas become more aggressive with successive cell divisions.

However, we also found that posterior parasagittal meningiomas exhibit more aggressive features even at smaller sizes. Specifically, NSB-POST-M tumors, which corresponds to the parasagittal/parafalcine meningiomas posterior to the coronal suture, exhibited more aggressive features irrespective of the tumor volume. This pattern, consistent across both independent cohorts, challenges the long-standing assumption that tumor size alone reliably predicts meningioma grade. Several biological mechanisms may underlie this phenomenon:

First, there is clear evidence of regional differences in driver mutations. Anterior parasagittal meningiomas are often driven by TRAF7, KLF4, or SMO mutations, while posterior ones are typically NF2-driven [8]. NF2-driven meningiomas have been associated with a more aggressive histology and earlier recurrence [4, 6,7,8,9].

Second, genetic instability inherent to posterior parasagittal meningiomas may result in tumors that are aggressive while still small. Prior comprehensive molecular genetic analyses have identified parasagittal meningiomas as genetically unstable [14,15,16,17]. Posterior parasagittal meningiomas had the highest incidence of chromosome 1p loss, which is currently considered the earliest finding in meningioma genetic instability and criteria for higher grade tumors [18] This molecular vulnerability could predispose even small tumors in this location to exhibit atypical or anaplastic features, without the need for a high number of cell divisions.

Third, the embryologic origin of the meninges may also influence tumor behavior. Posterior parasagittal meninges are believed to arise from mesenchymal progenitors, whereas anterior regions may be derived from neural crest cells [19]. This distinction may underlie spatial variations in tumor biology. Our previous finding of a ventro-caudal decreasing gradient of epithelial vs. mesenchymal markers reinforce the idea that parasagittal/falx meningiomas follow a spatial gradient rather than a categorical division [4, 6].

Lastly, we acknowledge that anatomical constraints can limit tumor expansion and influence the timing of clinical detection. To account for this, we used the volume index (Vi) to normalize for anatomical constraints on tumor size, allowing a more accurate comparison of tumor behavior across regions.

These findings carry clinical implications. Current surveillance protocols, which often consider size a primary risk factor, may underestimate the risk associated with posterior midline meningiomas [20, 21]. Recognizing high-risk behavior in a small meningioma has potential to influence decisions on surveillance, surgical timing, aggressivity of treatment and follow-up and can also guide patient counselling, especially when discussing treatment options for small but high-risk tumors. Surveillance strategies may need to be adjusted and even small incidental meningiomas in this location may warrant shorter imaging intervals and closer monitoring for subtle growth or early radiologic signs of aggressiveness (e.g., edema, invasion, heterogeneity). Similarly surgical timing may need reconsideration based on the location of the meningioma: The traditional “ watchful waiting” approach commonly applied to small, asymptomatic tumors may not be appropriate for posterior midline lesions. Early surgical or radiosurgical intervention could potentially prevent progression to a more aggressive phenotype. In addition, early resection might be pursued not only for symptomatic or radiographic growth, but to obtain early histopathological and molecular diagnosis. Finally, these findings may also influence treatment decisions. Knowledge of the location-specific risk can guide neurosurgeons and oncologists in discussions of extent of resection, the need for adjuvant radiotherapy, and more aggressive treatment plans—even for relatively small lesions. Taken together, our findings suggest that anatomical location—particularly NSB-POST-M positioning—should be incorporated into future clinical guidelines alongside tumor size and WHO grade.

While our study provides evidence that posterior parasagittal meningiomas exhibit aggressive behavior, a survival analysis was not in the scope of this analysis. Similarly, a comprehensive molecular analysis for a mechanistic explanation, why the posterior parasagittal region has more aggressive behavior is under study. Future studies should investigate whether early intervention in these tumors improves patient outcomes.