Pediatric Brain Tumors: From Modern Classification System to Current Principles of Management

Abstract

Central nervous system (CNS) malignancies contribute significantly to the global burden of cancer. Brain tumors constitute the most common solid organ tumors in children and the second most common malignancies of childhood overall. Accounting for nearly 20% of all pediatric malignancies, these are the foremost cause of cancer-related deaths in children 0–14 years of age. This book chapter provides a state-of-the-art overview of pediatric brain tumors. It discusses their morbidity and mortality and introduces the WHO 2021 classification of CNS tumors, which is critical to therapeutic decision-making. It then describes the modern understanding of tumor grading and its clinical implications, followed by the general principles of diagnosis and management. The chapter then discusses, in detail, those brain tumors which have the highest disease burden in children, including medulloblastoma, astrocytoma, ependymoma, schwannoma, meningioma, amongst others. The landscape of treatment of pediatric brain tumors has been rapidly evolving, with several effective therapies on the horizon.

DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets

“…The most recent, fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) took this one step further by incorporating the recommen-dations from the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) [14,[19][20][21][22], along with the landmark DNA methylation-based classification of CNS tumors published in Nature [12]. The WHO CNS5 uses an integrated histo-molecular assessment, prioritizing genetic and molecular alterations, which were emphasized for several tumor types [5].…”

Pioneering models of pediatric brain tumors

“…Xenograft models are generally established in immunocompromised rodents, with various strains used. BALB/c mice and severe combined immunodeficient mice [9] , as well as Rag1-deficient mice are the commonly used strains. These models, however, have different susceptibilities based on their genetic background.…”

“…The genes associated with these familial brain tumor predisposition syndromes include NF1 for neurofibromatosis type 1, NF2 for neurofibromatosis type 2, TP53 for Li-Fraumeni syndrome, PTCH1 for Gorlin syndrome, and SMARCB1 for rhabdoid tumor predisposition syndrome [8] . The genetic backgrounds of sporadic pediatric brain tumors have been extensively studied, in addition to these familial tumor predisposition syndromes [9] . For example, medulloblastomas are molecularly subclassified into four groups driven by different mutations of genes, including CTNNB1, PTCH1, MYC , and MYCN [10] .…”

Spontaneous Regression of Glioma–Mimicking Brainstem Lesion in a Child: A Case Report

“…Brainstem gliomas, which make up 10%–20% of pediatric central nervous system tumors, are classified into two different types—focal brainstem gliomas and diffuse intrinsic pontine gliomas (DIPGs)—largely based on MRI findings [ 1 ]. Focal brainstem gliomas are usually benign tumors of World Health Organization (WHO) grade I–II, whereas DIPGs are almost always highly malignant and fatal [ 1 2 3 ]. The prototypical features of focal brainstem gliomas on brain MRI are well-defined borders, lack of surrounding edema, iso- or hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and homogeneous contrast enhancement.…”

“…Most sporadic brainstem gliomas exhibit neurological symptoms and signs, such as isolated cranial nerve deficits, neck stiffness, pain, and contralateral hemiparesis [ 3 ]. However, some of them occur asymptomatically, especially among neurofibromatosis type I patients [ 8 ].…”