Metastatic grade 1 meningioma lacking genetic abnormalities commonly associated with bad prognosis.

Aims: Meningioma metastasis is a rare event, observed primarily in World Health Organization (WHO) grade 3 tumors, although it has also been reported in WHO grade 1 meningiomas. This study aims at clarifying whether the metastasis of a WHO grade 1 meningioma was associated with genetic abnormalities commonly found in cases that are more aggressive.

Methods: Using next generation sequencing of a panel of 174 genes, we analyzed the genetic alterations of a WHO grade 1 skull-base meningioma and its paired lung metastases detected 22 years after craniotomy.

Results: Similar to the primary tumor, lung metastases did not show mitoses or histological signs of malignancy. Consistent with their origin from intracranial tumor, they harbored the same genetic alterations as this one. These consisted of the pathogenic mutation p. E17K of AKT1 and variants of unknown significance in NOTCH1 (p. P2133T), SERPINB8 (p. H359Y) and SMARCA4 (p. P277S).

Conclusions: The E17K AKT1 mutation is frequently found in skull base meningiomas and without prognostic significance. Our findings suggest that metastasis of grade 1 meningiomas is independent of genetic alterations (CDKN2A homozygous deletion, pTERT mutation, or 1p, 9p, 14q and 18q loss of heterozygosity) commonly found in more aggressive tumors.