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Research ArticleOriginal Article
Open Access

Unraveling morphology, methylation profiling, and diagnostic challenges in BRAF-Mutant pediatric glial and glioneuronal tumors

Murad Alturkustani
Neurosciences Journal July 2024, 29 (3) 168-176; DOI: https://doi.org/10.17712/nsj.2024.3.20230108
Murad Alturkustani
From the Department of Pathology, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, and from the Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada
MBBS, FRCPC
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  • For correspondence: [email protected]
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  • Figure 1
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    Figure 1

    - Tumors with modified diagnoses. A, B) Case 24: DLGNT. A) Biphasic tumor with piloid glial cells and numerous Rosenthal fibers. B) Glial component with round to oval nuclei. C–F) Case 25: PLNTY. C) Dysmorphic ganglion cell (arrow). D) Oligodendroglioma-like component. (E, F) Infiltrative component. Scale bars: 200 μm (A–F).

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    Figure 2

    - Tumors with debatable diagnoses. A–D) Case 29: temporal lobe mass in a three-year-old boy. A) Neoplastic cells with round and elongated nuclei and many EGBs. B, C) Many dysmorphic ganglion cells with binucleated form in (C). D) Diffusely positive GFAP in the background, but negative in dysmorphic ganglion cells. E–F) Case 31: cerebellar tumor in a 3-year-old boy. E) Infiltrative components consist of elongated neoplastic cells with entrapped neurons. F) Many dysmorphic ganglion cells. Scale bars: 200 μm (A–F).

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    Figure 3

    - Two cases with morphology of high-grade astrocytoma and MC of PXA. A–D) Case 34: parieto-temporal mass in a nine-year-old girl. A) Cellular component with round neoplastic cells infiltrative around entrapped nuclei. B) Two granular mitoses in the center of the field. (C) NeuN immunostain, an immunopositive subset of neoplastic nuclei, which raised the possibility of a neuronal component, but there was no clear neuronal differentiation. (D) GFAP immunostain shows a cytoplasmic rim in many neoplastic cells and the background. (E–F) Case 35: temporal lobe mass in a two-year-old boy. (E) High-cellular area with round-oval hyperchromic neoplastic cells and significant mitotic activity. (F) Many neoplastic cells with eccentric round eosinophilic cytoplasm resembling rhabdoid or epithelioid neoplastic cells. Scale bars: 200 μm (A, C, D); 100 μm (B, E, F).

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    Figure 4

    - Examples of cases in the non-contributary category. A–C) Case 46: parietal lobe mass in a thirteen-year-old woman. A) Spindled neoplastic cells infiltrate around entrapped neurons with scattered pleomorphic neoplastic cells. B) Scattered dysmorphic ganglion cells, but no EGBs present. C) CD34 immunostaining shows diffuse staining in the neoplastic cells. D–F) Case 47: occipital/temporal lobe mass in an eleven-year-old girl. D) Infiltrative glial component with round to slightly elongated nuclei. E) Area with many EGBs and scattered pleomorphic ganglion cells. (F) A rare example of a binucleated dysmorphic ganglion cell (arrow). Scale bars: 200 μm (A, B, C–F); 5 mm (C).

Tables

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    Table 1

    - Summary of clinical and molecular characteristics of studied cases.

    No.Age (Y)SexSitePDNGSAFMC V12.5MC V12.8Final diagnosis
    11.7MOPPABRAF V600E0.29PA-M (0.99)PA-M (0.99)PA
    27FCePABRAF A598_T599insV0.31PA-I (0.99)PA-I (0.99)PA
    317MTLPABRAF V600Dfs*470.08PA-H (0.89)PA-H (0.79)PA
    411MFL;PLPABRAF V600E0.19PA-H (0.93)PA-H (0.96)PA
    512FOPPABRAF V600E0.13PA-M (0.99)PA-M (0.99)PA
    615MCePABRAF L410Q0.22PA-I (0.99)PA-I (0.99)PA
    71.6MTLPABRAF V600E0.28PA-H (0.98)PA-H (0.81)PA
    815MOPPABRAF V600E0.15PA-M (0.99)PA-M (0.99)PA
    915MCePABRAF T599dup, Ad10.48PA-I (0.89)PA-M (0.59)PA
    101.2MOPPABRAF V600E0.2PA-M (0.99)PA-M (0.98)PA
    1114FBSPA-RBRAF T599dup0.59PA-I (0.98)PA-I (0.90)PA
    1216MTLPABRAF V600E0.26PA-H (0.94)PA-H (0.98)PA
    1314FTLGGBRAF V600E0.24GG (0.99)GG (0.99)GG
    140.75FTLGGBRAF V600E0.18GG (0.94)GG (0.98)GG
    152MTLGGBRAF V600E0.18GG (0.75)GG (0.85)GG
    163MTLGGBRAF V600E0.41GG (0.99)GG (0.99)GG
    1714FTLPXABRAF V600E0.36PXA (0.99)PXA (0.99)PXA
    1813MTLPXABRAF V600E0.48PXA (0.99)PXA (0.99)PXA
    199FFLPXABRAF V600E0.51PXA (0.99)PXA (0.99)PXA
    2014FFLPXABRAF V600E0.29PXA (0.99)PXA (0.99)PXA
    2114MTLPXABRAF V600E0.41PXA (0.99)PXA (0.99)PXA
    2210MPLPXABRAF V600E0.3PXA (0.99)PXA (0.99)PXA
    2312.3FTLAs- InfBRAF V600E0.3GG (0.50)GG (0.80)LG GNT vs As
    2316.3FHipPXABRAF V600E0.24PXA (0.99)PXA (0.99)PXA
    243.6FSCPABRAF V600E0.49DLGNT-1 (0.99)DLGNT-1 (0.99)DLGNT
    2513.9FTLGGBRAF V600E0.69PLNTY (0.73)PLNTY (0.48)PLNTY
    2618MTLGGBRAF V600E0.12PA-H (0.83)PA-H (0.97)GG
    2719FOL;TLGGBRAF V600E0.19PA-H (0.94)PA-H (0.81)GG
    2810MTLGGBRAF V600E0.14PA-H (0.82)GG (0.32)GG
    293MTLGGBRAF V600E0.38PA-H (0.99)PA-H (0.99)GG
    3015FTLGGBRAF V600E0.19PA-H (0.85)PA-H (0.99)GG
    313MCeGGBRAF V600E0.29PA-I (0.99)PA-I (0.95)GG
    320.25FOPDIABRAF V600E0.28PA-M (0.99)PA-M (0.99)DIA vs PA
    336MOPDIGBRAF V600E0.34PA-M (0.99)PA-M (0.99)PA vs DIG
    349FPL;TLHG AsBRAF V600E0.46PXA (0.99)PXA (0.99)pHGG, NEC
    352MTLHG AsBRAF V600E0.89PXA (0.99)PXA (0.98)pHGG, NEC
    3611FTLGGBRAF V600E0.07C-RM (0.56)C-IM (0.43)GG
    3714MFLGGBRAF T599dup IF ins0.24C-RM (0.64)C-RM (0.46)GG
    384MBSGGBRAF V600E0.15C-RM (0.38)C-RM (0.44)GG
    394FFLGGBRAF V600E, Ad20.09C-RM (0.74)C-RM (0.54)GG
    402MTLGGBRAF V600E0.18PA-H (0.45)PA-H (0.57)GG
    4116MTLGGBRAF V600E0.08C-RM (0.98)C-RM (0.86)GG
    4220FBSLG AsBRAF V600E0.11C-RM (0.98)C-RM (0.96)LG As
    4311FPL;TLPA/PMABRAF V600E0.16C-RM (0.99)C-RM (0.97)PA/PMA
    449MTLHG As, NECBRAF V600E, Ad30.53pHGG, RTK1 (0.38)DPHGG, RTK1 (0.47)pHGG, NEC
    4511FThDMG, K27MBRAF V600E, Ad40.16G-IDHw-M (0.43)C-IM (0.88)DMG, K27M
    4613FPLLG G/GNBRAF V600E0.33GG (0.52)PA-H (0.24)GG
    4711FOL;TLLG G/GNBRAF V600E0.26PXA (0.52)PXA (0.36)PXA

    Ad: additional mutations [Ad1: P53 X307_splice and CDH1 X177_splice; Ad2: NF1 C1792*; Ad3: TP53 R248L; Ad4: H3F3A K28M, TERT promotor mutation (not specified)]. AF: allelic frequency; BS: brainstem; C-IM: control tissue, inflammatory microenvironment; C-RM: control tissue, reactive tumor microenvironment; Ce: cerebellum; DLGNT-1: diffuse leptomeningeal glioneuronal tumor, subtype 1; F: female; FL: frontal lobe; G-IDHw-M: glioblastoma, IDH-wildtype, mesenchymal type; Hip: hippocampus; LV: lateral ventricle; M: male; ND: not done; NEC: not elsewhere classified; OL: occipital lobe; OP: optic pathway; PA-H: pilocytic astrocytoma, hemispheric; PA-I: pilocytic astrocytoma, infratentorial; PA-M: pilocytic astrocytoma, midline; pHGG: diffuse pediatric-type high-grade glioma; PL: parietal lobe; PLNTY: polymorphous low-grade neuroepithelial tumor of the young; PXA: pleomorphic xanthoastrocytoma; SC: spinal cord; Th: thalamus; TL: temporal lobe; Y: years

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    Unraveling morphology, methylation profiling, and diagnostic challenges in BRAF-Mutant pediatric glial and glioneuronal tumors
    Murad Alturkustani
    Neurosciences Journal Jul 2024, 29 (3) 168-176; DOI: 10.17712/nsj.2024.3.20230108

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    Unraveling morphology, methylation profiling, and diagnostic challenges in BRAF-Mutant pediatric glial and glioneuronal tumors
    Murad Alturkustani
    Neurosciences Journal Jul 2024, 29 (3) 168-176; DOI: 10.17712/nsj.2024.3.20230108
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