Clinical and genomic differences in supratentorial versus infratentorial NF2 mutant meningiomas

Abstract

OBJECTIVE Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities—however, they can also be found in the posterior fossa. The authors investigated whether NF2 mutant meningiomas differ in clinical and genomic features based on their location relative to the tentorium. METHODS Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic NF2 mutant meningiomas were reviewed and analyzed. RESULTS A total of 191 NF2 mutant meningiomas were included (165 supratentorial, 26 infratentorial). Supratentorial NF2 mutant meningiomas were significantly associated with edema (64.0% vs 28.0%, p < 0.001); higher grade—i.e., WHO grade II or III (41.8% vs 3.9%, p < 0.001); elevated Ki-67 (55.0% vs 13.6%, p < 0.001); and larger volume (mean 45.5 cm3 vs 14.9 cm3, p < 0.001). Furthermore, supratentorial tumors were more likely to harbor the higher-risk feature of chromosome 1p deletion (p = 0.038) and had a larger fraction of the genome altered with loss of heterozygosity (p < 0.001). Infratentorial meningiomas were more likely to undergo subtotal resection than supratentorial tumors (37.5% vs 15.8%, p = 0.021); however, there was no significant difference in overall (p = 0.2) or progression-free (p = 0.4) survival. CONCLUSIONS Supratentorial NF2 mutant meningiomas are associated with more aggressive clinical and genomic features as compared with their infratentorial counterparts. Although infratentorial tumors have higher rates of subtotal resection, there is no associated difference in survival or recurrence. These findings help to better inform surgical decision-making in the management of NF2 mutant meningiomas based on location, and may guide postoperative management of these tumors.

Multiple ossified intracranial and spinal meningiomas: a rare case report and literature review

“…Thus, SSTR2a immunohistochemistry can be useful in establishing the diagnosis of meningiomas, including high-grade meningiomas with poor differentiation. Additionally, Ki-67 ( 35 ) is frequently utilized for the evaluation of meningiomas proliferation trend. The expression level of Ki67 demonstrates a positive correlation with the pathological grade, growth rate, peritumoral edema, and recurrence rate of meningiomas.…”

The Evolving Classification of Meningiomas: Integration of Molecular Discoveries to Inform Patient Care

“…Non-NF2 meningiomas are found along the skull base [9,101,102], with those harboring Hedgehog activating events located in the ventral midline [66,96,103]. By contrast, NF2-mutated meningiomas are located along the convexity and falx and are often the transitional/fibroblastic subtype [104,105]. Secretory meningiomas, a rare subtype associated with peritumoral edema, uniformly harbor co-mutation of TRAF7/KLF4 [66,106,107].…”