Comparative molecular profiles of distinct tumor components in recurrent tentorial meningioma after stereotactic radiosurgery: a case report implicating acquired aggressive alterations associated with WHO grade progression

Meningiomas, the most common primary benign intracranial tumors, may recur and, in some cases, undergo WHO grade progression, acquiring more aggressive clinical behavior. The molecular mechanisms underlying such progression, particularly following stereotactic radiosurgery (SRS), remain poorly understood. We report a 70-year-old woman with a gradually enlarging tentorial meningioma treated with SRS as primary therapy. The irradiated lesion remained stable on serial MRI for 30 months following treatment. Subsequently, a rapidly enlarging marginal progression was detected posterior to the original tumor site. Surgical resection revealed two distinct pathological components: the anterior, irradiated lesion was a fibrous meningioma whereas the posterior, marginally progressed lesion was diagnosed as an anaplastic meningioma (WHO grade 3). Whole-exome sequencing identified shared NF2 mutations and losses at 1p and 18p in both components, while the marginally progressed lesion harbored additional high-risk alterations, including homozygous CDKN2A/B deletion and loss of the X chromosome. Despite re-irradiation and further surgical resections, the patient succumbed to tumor progression and disseminated disease 8 months after the marginal progression. These findings suggest that a subset of tumor cells may have acquired genetic alterations driving WHO grade progression, ultimately leading to marginal progression after SRS.