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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