NFS-13. Unusual Neurofibromatosis Type 1-Associated Pilocytic Astrocytomawith Malignant Transformation in a 7-Year-Old Girl

Abstract INTRODUCTION Neurofibromatosis type 1(NF1) is a tumor predisposition syndrome with germline NF 1 gene aberrations with overactivation of the RAS–MAPK signaling pathway. NF1-associated gliomas in children are usually low-grade Glioma with indolent course. Malignant transformation in NF1 associated LGG is predominated in adults is scarce in children METHOD A 7-year-old girl diagnosed as NF1-based on diagnostic criteria and germline NF1 gene mutation, presented with progressive RT side hemiplegia, Brain MRI showed a large left thalamic cystic and solid mass and obstructive hydrocephalus she had VPS insertion and stereotactic biopsy.pathological examination revealed aggressive High-grade Glioma HGG features diffuse brain infiltration, endothelial hyperplasia, increased mitotic activity necrosis, and High Ki67. Immunohistochemically and molecular analysis showed NF1 mutation in addition to TP53 mutation, retained ATRX, negative CDKN2A/B, and high tumor mutational burden (6 Muts/Mb). Tumor methylation profiling (DKFZ CNS v12.5) classified as Supratentorial midline pilocytic astrocytoma (score 0.6878). debulking of the tumor and ommaya reservoir insertion was done with recurrent aspiration of the cystic component. The second biopsy demonstrated low-grade pilocytic astrocytoma, confirmed by methylation profiling (score 0.9377). Immunohistochemically and molecular analysis showed NF1 mutation, negative TP53, and Retained ATRX RESULT She was treated with low-grade glioma chemotherapy carboplatin/ vincristine, with improved clinical and neurological condition and stable MRI evaluation. One year after diagnosis while on maintenance LGG chemotherapy MRI imaging showed tumor progression Subtotal resection of the mass was performed, morphology and molecular studies confirmed HGG, and she received focal radiation therapy. Up till now, the patient is currently stable clinically and by imaging surveillance. CONCLUSION Our case characterized a transformed glioma in a child with NF1 illustrating the intratumoral heterogeneity and presence of transformed/anaplastic clone within NF1-associated pilocytic astrocytoma and demonstrate the complexity of molecular genetics of gliomas in children with NF1.