Paradoxical evolution of spheno-orbital meningioma after cessation of progestin treatment

Abstract

Background: Meningioma is the most frequent primary benign intracranial tumor, with a higher incidence in women. Treatment with progesterone acetates, including cyproterone, nomegestrol, chlormadinone, promegestone, medrogestone, and medroxyprogesterone acetate, has been identified as a risk factor of meningioma, particularly in the anterior and middle cranial fossae. Discontinuation of these treatments often leads to volume stabilization or regression of the tumor.

Case description: A 42-year-old woman undergoing treatment with nomegestrol acetate (NA) presented with headaches and visual loss in her right eye. She was diagnosed with a large spheno-orbital meningioma invading the sphenoid and ethmoid sinuses, associated with hyperostosis of the sphenoid wing. An initial resection was performed using an extended endonasal approach. Immunohistochemistry confirmed a chondroid meningioma, Grade II, with progestin receptor in 100% of the tumor cell nuclei and a Ki-67 proliferation index of 3-5%. NA was immediately stopped on diagnosis. Despite the cessation of the NA, the intraosseous sphenoidal part of the tumor continued to grow, leading to optic nerve compression. A second surgery was performed using a right fronto-temporo-orbito-zygomatic approach. Examination of the dura of the middle fossa showed subtle tumoral infiltration, while the Ki-67% index was estimated at 1%. Examination of the sphenoid bone demonstrated reactive hyperostosis with minimal to no tumor infiltration.

Conclusion: This case illustrates that the proliferative activity of the progestin-associated meningioma does not account for intraosseous progression within the sphenoid bone following cessation of progestin therapy. Our observations suggest an upregulation of osteogenesis in infiltrated bone, even as the dural part of the meningioma regresses.

Keywords: Histopathological correlation; Hyperostosis; Meningioma; Paradoxical evolution; Progestin; Skull base.

Figure 1:

Visual field examination before and after surgical treatment. This figure shows the visual field examination of the right eye. Diffuse alteration of the visual field before the first resection (first line). One month after the endonasal resection, recovery of the visual field (second line). One year later, a novel decline in the visual acuity and visual field (third line). After fronto-temporo-orbito-zygomatic approach, iatrogenic altitudinal defect (fourth line). This defect improves over time (fifth line).

Figure 2:

Radiological evaluation of the intra-osseous meningioma progression. (a and b) Bone computed tomography (CT) scan at presentation and 3 months after the first surgery. (c and d) T1 post gadolinium magnetic resonance imaging (MRI) at presentation and 3 months after the first surgery. (e and f) T2 MRI at presentation and 3 months after the first surgery. The blue areas correspond to the volumetry of the osseous part of the lesion before the first surgery (a) and 3 months after this treatment and cessation of Nomegestrol Acetate therapy (c). We realized the volumetry analysis by comparison between the CT scan at the MRI sequences. We demonstrated the bony progression with a growth from 8.88 cm³ to 17.53 cm³.

Figure 3:

Histological examination of the various parts of the meningioma (a and b): Intranasal part of the meningioma (hematoxylin and eosin [H&E] and Ki67 [Dako 1:200], Magnification = 200× respectively) (c and d) Sphenoid wing dura (H&E and Ki67 [Dako 1:200] Magnification = 400× respectively) The high proliferative rate of the tumor with Ki67 between 3 and 5% before cessation of Nomegestrol in b drops to lower than 1% after cessation of Nomegestrol in d. (e) Sphenoid hyperostosis with a low tumor infiltration (H&E) Magnification = 100×.