Discussion:
Astroblastoma is a rare entity with limited reports in existing literature. Ahmed et al. reported a median overall survival (OS) of 55 months, with the 1-, 5-, and 10-year OS reported 71.1%, 48.5%, and 38.3% respectively in the largest report of astroblastoma patients [11]. Currently, no standard of care exists for astroblastoma as the clinical behavior and prognostic criteria for the disease entity remains unpredictable, largely owing to its molecular heterogeneity. Current treatment of choice for astroblastoma consists of gross total resection with adjuvant radiotherapy frequently performed in cases of high-grade tumors but with variable response [10]. The use of adjuvant chemotherapy such as temozolomide has been described but remains controversial [10].
In the current case, the patient was diagnosed with high-gradeMN1 altered astroblastoma based on histopathological findings and methylation profile. Initial consideration was given regarding the possible administration of adjuvant radiotherapy given the high proliferation index (a Ki-67 labeling index of approximately 80%). However, given the germline ATM gene heterozygous stop-gain variant, radiation therapy was deferred since the ATM gene product is implicated in the DNA damage recognition pathway, signaling in response to DNA double-strand breaks and oxidative stress, as well as activating cell cycle checkpoints [12]. Whereas ataxia-telangiectasia is a well-known autosomal recessive condition of the ATM gene predisposing affected individuals to higher risks of developing childhood leukemia and lymphoma, carriers of the gene are also said to have increased propensity for developing breast cancer, as well as possible radiosensitivity [12, 13]. To the best of our knowledge, this is the first case of MN1 -altered astroblastoma with concomitant ATM germline mutation to be reported and the implication of adjuvant radiotherapy remains unknown. Our case adds to molecular heterogeneity of MN1 -altered astroblastoma, highlighting the importance of DNA methylation and germline sequencing in the diagnosis and management of this rare pediatric tumor type.
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