PMC9639353_01
Meningioma and treatment. (A) Preoperative magnetic resonance imaging (MRI). (B) Postoperative magnetic resonance imaging. (C) H&E histology. Scale bar, 100 microm. (D) Ki-67 immunohistochemistry (IHC). Scale bar, 100 microm. (E) Single-cell RNA sequencing UMAP showing cell types distinguished by marker gene expression in accordance with the cellular architecture of human meningiomas. (F) Single-cell RNA sequencing feature plots showing meningioma marker genes (PTDGS) or Hedgehog target genes (GLI1, PTCH1). (G) SF13398 immunofluorescence and quantification of ciliary SMO intensity after 24 hours of treatment with recombinant Sonic Hedgehog (SHH, 1 microg/mL) compared to vehicle control. Cilia are marked by Arl13b immunofluorescence. Lines show means and error bars show standard error of the mean. NS, nonsignificant (Student's t-test). Scale bar, 10 microm. (H) SF13398 cell proliferation after 5 days of treatment with vismodegib or abemaciclib. Points show means and error bars show standard error of the mean. (I) Intensity modulated radiotherapy (IMRT) isodose lines overlaid on postoperative MRI.
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We present the case of a 45-year-old female patient who underwent MRI for subacute left eye vision changes, revealing a dural based, homogenously enhancing lesion arising from the sphenoid wing (Figure 1A). Frontotemporal orbitozygomatic craniotomy was performed for tumor resection, and a postoperative MRI demonstrated residual tumor along the left anterior clinoid, left cavernous sinus, and prepontine cistern (Figure 1B). Histologic examination showed a solid, moderately to highly cellular neoplasm comprised of spindled to epithelioid cells growing in nests and fascicles (Figure 1C). There were up to 2 mitotic figures per 2 mm2 (Figure 1D). Cell clusters were defined in accordance with the reported cellular architecture of human meningiomas (Figure 1E), and no evidence of Hedgehog target gene expression was identified (Figure 1F), suggesting the SMO L412F mutation was not associated with Hedgehog pathway misactivation. Immunofluorescence of a primary meningioma cell line derived from the resection specimen (SF13398) showed SMO accumulation in primary cilia did not increase in response to recombinant Sonic Hedgehog stimulation (Figure 1G). Treatment of SF13398 cells with vismodegib or the cell cycle inhibitor abemaciclib, which blocks the growth of Immune-enriched or Hypermitotic meningiomas, did not block Merlin-intact SF13398 cell proliferation (Figure 1H). In the absence of therapeutic alternatives, she was treated with intensity modulated radiotherapy (Figure 1I), which is associated with high rates of local control but can also cause toxicity.