PMC9772816_01
Brain magnetic resonance imaging (MRI) at the time of epilepsy diagnosis. No lesion was identified (axial T2 and coronal T2-A and B). Brain MRI 20 months later with a large right temporal lobe lesion with mass effect and vasogenic edema (axial T2 and axial T1 with gadolinium-C and D). Post-surgery brain MRI showing near total resection (axial T2 and axial T1 with gadolinium-E and F). Brain MRI demonstrating local recurrence after 32 months of treatment (arrows) (axial T2 and axial T1 with gadolinium-G and H). Brain MRI demonstrating the second local recurrence after 47 months of treatment (arrows) (axial T2 Flair and axial T1 with gadolinium-I and J). Post-surgery brain MRI showing a gross total resection (axial T2 Flair and axial T1 with gadolinium-K and L).
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F1
Magnetic resonance imaging (MRI) at diagnosis of epilepsy was normal (Figure 1A and B). Brain MRI showed a large 5 cm heterogenous lesion localized in the right temporal lobe with mass effect and vasogenic oedema (Figure 1C and D). A high-grade tumor was suspected, and she underwent a near total resection (with a residue of less than 1 cm2) including a right-side amygdalohippocampectomy (Figure 1E and F). A follow-up MRI 3 months later demonstrated further tumor growth and the patient underwent a second surgery (Figure 1G and H). The patient continued her treatment but 15 months later a surveillance MRI demonstrated a new asymptomatic local progression (Figure 1I and J). The patient underwent a gross total resection of this recurrence 2 months later (Figure 1K and L).
Pathology of primary tumor and recurrences. (A, B) Primary tumor showing glioblastoma-like areas with loosely arranged astrocytic tumor cells in a myxoid or microcystic background, palisading necrosis (asterisk), and microvascular proliferation (open arrow) (A, HES), and areas more typical of PXA (grade 3) with streaming fascicules of spindle cells with glassy eosinophilic cytoplasm, frequent mitoses (circled), tumor necrosis (asterisk), and xanthomatous change and eosinophilic granular bodies (inset) (B, HES). (C, E) First tumor recurrence showing PXA-like (grade 3) areas with pleomorphic astrocytic tumor cells, abundant glassy or xanthomatous cytoplasm, frequent nuclear pseudo-inclusions, and brisk mitotic activity (circled) (C, HES), and areas more typical of low-grade glioma with monomorphic tumor cells in a background of fibrillary processes, hyalinized vessel walls, and no mitoses (D, HES); immunopositivity for BRAF V600E was weaker in areas of low-grade glioma histology (black asterisk) compared to areas with features of PXA (grade 3) (white asterisk) (E). (F) Second tumor recurrence showing typical PXA (grade 3) pathology with streaming pleomorphic tumor cells, abundant glassy or xanthomatous cytoplasm, nuclear pseudo-inclusions, lymphocytic aggregates, and frequent mitoses (circled) (hematoxylin and eosin). Bar in A-B, 250 microm, inset in B, 25 microm, C, D, F, 100 microm, E, 1 mm. HES, hematoxylin-eosin-saffron.
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The pathology was initially interpreted as GBM based on astrocytic morphology, necrosis, and microvascular proliferation (Figure 2A). Pathology was interpreted as recurrent GBM but with prominent areas of lower-grade glioma histology (Figure 2D). Reexamination of primary tumor pathology revealed areas compatible with PXA including scattered eosinophilic granular bodies and xanthomatous change (Figure 2B) and grade 3 was assigned based on brisk mitotic activity (9 per 10 high power fields); Ki67 proliferation index was 12.8%. Reexamination of the recurrent tumor revealed similar findings (Figure 2C). The areas of LGG histology, however, had a proliferation index <1%, did not show features of PXA (Figure 2D), and showed weaker BRAF V600E immunopositivity (Figure 2E). Pathology of the second recurrence revealed classic grade 3 PXA features (Figure 2F) with up to 12 mitoses per 10 high power fields, a KI67 proliferation index of 43%, and strong BRAF V600E immunopositivity.