PMC8506147_01
Histopathology. Case 1 shows atypical ganglion cells immersed in disorganized glia (A. H&E, original magnification x200) with positive immunohistochemistry for mutant BRAF V600 E (B. x200). Case 2 has been published in greater detail previously.

 Case 4 shows mitotically active atypical epithelioid cells (C. H&E x400) which strongly express mutant BRAF V600 E (D. x200). Case 3 not shown.
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She underwent a right parietal craniotomy and pathology confirmed an epithelioid GBM, WHO grade IV (Figure 1), negative for IDH1 R132H by IHC and confirmed IDH1/2 wild-type by NGS, ATRX-retained, MGMT promoter-methylated, negative for 1p/19q co-deletion, and positive for BRAF V600 E mutation by FoundationOne  assay (see supplementary Table 1 for complete NGS results from FoundationOne ).
Magnetic Resonance Imaging of the brain of case #1 at initial diagnosis and before and after treatment with BRAF/MEK inhibitors. On 05/2017, initial MRI brain showed interval tumor growth of the ganglioglioma involving brainstem and upper cervical spinal cord as seen with increased enhancing tumor and T2 signal (A, D, G, J.). The enhancing part of the upper largest brainstem lesions measures 1.17 cm on axial view (A.) and 1.06 x 0.83 cm on sagittal view (G.). On 05/2018, MRIs showed disease progression with increase in the size of the lesions, with the enhancing part of the upper brainstem lesion now measuring 1.48 cm in axial view (B.) and 1.42 x 1.43 cm in sagittal view (H.) (B, E, H, K.). BRAF/MEK inhibitors were added. Most current MRIs as of 10/2020 show overall smaller in the size of the lesions, with the enhancing part of the upper brainstem lesion now measuring 1.32 cm in axial view (C.) and 1.10 x 0.80 cm in sagittal view (L.) (C, E, I, L.). A-C and G-L = T1 Post-Gadolinium. D-F and J-L = T2 FLAIR sequences.
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However, 12 months after initial diagnosis, a repeat MRI scan showed increase in tumor growth both in the enhancing and the non-enhancing regions involving both the brainstem and the upper cervical cord (Figure 2). The enhancing part of the upper largest diameter of the brainstem lesion increased to 1.48 cm (compared to prior measuring 1.17 cm) on axial view (Figures 2A and 2B) and to 1.42 42 x 1.43 cm (compared to prior measuring 1.06 x06 x .83 cm) on sagittal view (Figures 2G and 2H). Since the treatment was held, she has remained with clinical and radiographic SD ongoing at 29 months after initial start of BRAF/MEKi and 18 months after addition of chloroquine to BRAF/MEKi therapy (Figure 2).
PMC8506147_02
PMC8506147_03
PMC8506147_04
Histopathology. Case 1 shows atypical ganglion cells immersed in disorganized glia (A. H&E, original magnification x200) with positive immunohistochemistry for mutant BRAF V600 E (B. x200). Case 2 has been published in greater detail previously.

 Case 4 shows mitotically active atypical epithelioid cells (C. H&E x400) which strongly express mutant BRAF V600 E (D. x200). Case 3 not shown.
10.1177_10732748211040013-fig1.jpg
PMC8506147_04_10.1177_10732748211040013-fig1.jpg
fig1-10732748211040013
She underwent a right parietal craniotomy and pathology confirmed an epithelioid GBM, WHO grade IV (Figure 1), negative for IDH1 R132H by IHC and confirmed IDH1/2 wild-type by NGS, ATRX-retained, MGMT promoter-methylated, negative for 1p/19q co-deletion, and positive for BRAF V600 E mutation by FoundationOne  assay (see supplementary Table 1 for complete NGS results from FoundationOne ).
Magnetic Resonance Imaging of the brain of case #4 pre- and post-cystic drainage, and before and after treatment with BRAF/MEK inhibitors. On 01/2016, MRI brain performed pre- (A. and E.) and post-surgical drainage of the cystic component of the lesion and before starting treatment with maintenance temozolomide (B. and F.). On 02/2016, MRI with rapid refilling of the cystic component of the lesion and before starting treatment with BRAF/MEK inhibitors (C. and G.). Most current MRIs as of 10/2020 show stable disease since started on BRAF/MEK inhibitors, without requiring further surgical drainage (D. and H.). A-D = T1 Post-Gadolinium. E-H = T2 FLAIR sequences.
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Shortly thereafter, she developed a symptomatic increase in the size of the cystic region of the lesion and was taken back to the operating room for drainage, with quick refilling requiring a second drainage in the operating room a month later (Figure 3).