Progestin-related WHO grade II meningiomas behavior-a single-institution comparative case series.

WHO grade II progestin-related meningiomas have been reported in recent series but we found no previous study describing their long-term outcome. Our study aimed to evaluate patients operated on for high-grade intracranial meningioma and who underwent long-term exposure to high dose of cyproterone acetate, nomegestrol acetate, and chlormadinone acetate. Our study retrospectively included 9 patients with high-grade progestin-related intracranial meningioma between December 2006 and September 2021. In each patient, clinico-radiological follow-up was performed every 6 months after diagnosis and treatment withdrawal recommendation. The mean progestative exposure was 11.4 years. Edema existence or absence of cleft sign on MRI were the key factors for surgical indication. All patients underwent surgery. Adjuvant radiotherapy was indicated in 1 patient, and Gamma Knife radiosurgery was proposed in 2 other patients for a second location of meningioma. Six patients harbored a grade II chordoid meningioma subtype with 100% PR expression and 3 patients a grade II atypical meningioma subtype with lower PR expression. The mean follow-up was 8.1 years and none of the 9 patients presented with a recurrence. Patients with grade II progestin-related meningiomas have less tumor recurrence after surgery than patients with sporadic grade II meningiomas, especially after progestin withdrawal. The presence/appearance of peri-meningioma edema and the absence of cleft sign before volumetric change should suggest the existence of an underlying WHO grade II meningiomas. In these cases, surgical resection may immediately be considered and adjuvant radiotherapy should be reserved for proven recurrence cases.

Atypical evolution of meningiomatosis after discontinuation of cyproterone acetate: clinical cases and histomolecular characterization.

PURPOSE: The long-term use of cyproterone acetate (CPA) is associated with an increased risk of developing intracranial meningiomas. CPA discontinuation most often induces a stabilization or regression of the tumor. The underlying biological mechanisms as well as the reasons why some meningiomas still grow after CPA discontinuation remain unknown. We reported a series of patients presenting CPA-induced meningiomatosis with opposed tumor evolutions following CPA discontinuation, highlighting the underlying histological and genetic features. METHODS: Patients presenting several meningiomas with opposite tumor evolution (coexistence of growing and shrinking tumors) following CPA discontinuation were identified. Clinical and radiological data were reviewed. A retrospective volumetric analysis of the meningiomas was performed. All the growing meningiomas were operated. Each operated tumor was characterized by histological and genetic analyses. RESULTS: Four women with multiple meningiomas and opposite tumor volume evolutions after CPA discontinuation were identified. Histopathological analysis characterized the convexity and tentorial tumors which continued to grow after CPA discontinuation as fibroblastic meningiomas. The decreasing skull base tumor was characterized as a fibroblastic meningioma with increased fibrosis and a widespread collagen formation. The two growing skull base meningiomas were identified as meningothelial and transitional meningiomas. The molecular characterization found two NF2 mutations among the growing meningiomas and a PIK3CA mutation in the skull base tumor which decreased. CONCLUSION: To our knowledge, this is the first report describing an atypical tumor evolution of CPA-associated meningiomas after CPA discontinuation. The underlying biological mechanisms explaining this observation and especially the close relationship between mutational landscapes and embryologic origins of the meninges in CPA-related meningiomas as well as their clonal origin require further research.