Pediatric-Type Diffuse Low-Grade Gliomas: A Subgroup Defined by Peculiar Molecular Features and Distinct Prognostic...

Despite their biological and molecular heterogeneity, pediatric-type diffuse low-grade gliomas exhibit significantly different prognostic outcomes compared to their adult-type counterparts. Accurate diagnosis is essential to avoid aggressive overtreatment and to enable exploration of relevant molecular targets for personalized therapy. This review provides a comprehensive overview of the epidemiology, clinical presentation, radiologic findings, histopathologic features, and key molecular events characterizing the newly defined WHO subgroup "pediatric-type diffuse low-grade gliomas." The review also outlines the conventional treatment modalities, including surgery, chemotherapy, and radiotherapy, while discussing their limitations and adverse effects. In addition, emerging therapeutic strategies based on molecular targets are briefly highlighted, offering a glimpse into current clinical trials and FDA-approved targeted therapies. Data were retrieved from credible scientific sources including PubMed, Google Scholar, and the 2021 WHO Classification of Central Nervous System Tumors. The newly established molecular subgroup comprises four distinct entities: 1) Diffuse astrocytoma, MYB or MYBL1-altered; 2) Angiocentric glioma; 3) Polymorphous low-grade neuroepithelial tumor of the young; and 4) Diffuse low-grade glioma, MAPK pathway-altered. Unlike circumscribed astrocytic gliomas, these tumors exhibit partial infiltrative behavior. However, they tend to have a more favorable prognosis than adult-type diffuse gliomas, IDH-mutant. Circumscribed gliomas are typically managed with gross total resection and show a lower recurrence rate in comparison to this newly recognized subgroup. While surgical resection remains curative for small, superficial tumors, deeper or more infiltrative variants may recur following subtotal resection. A thorough understanding of the clinicopathological and molecular features of these gliomas is imperative for accurate classification and appropriate therapeutic intervention.