Supratentorial Intracranial Tumors In Children

Introduction And Epidemiology

• Supratentorial tumors account for approximately 40.9% of primary pediatric central nervous system (CNS) tumors.
• Exhibit distinct age-related predilection.
• Predominate during first year of life (choroid plexus tumors, germ cell tumors).
• Predominate again after 10 years of age (diffuse astrocytomas, pituitary/craniopharyngeal tumors).

Classification By Anatomic Location

Cerebral Hemisphere

• Low-grade and high-grade gliomas.
• Ependymoma.
• Meningioma.
• Primitive neuroectodermal tumor (PNET).

Sella Or Chiasm

• Craniopharyngioma.
• Optic nerve glioma.
• Pituitary adenoma.
• Germ cell tumors (GCTs).

Pineal Region

• Pineoblastoma and pineocytoma.
• Germ cell tumors.
• Astrocytoma.

Ventricular System

• Choroid plexus papilloma.
• Choroid plexus carcinoma.

Specific Tumor Types And Pathologic Nuances

Astrocytomas

• Optic Pathway Gliomas: Constitute 5% of pediatric CNS tumors. Account for 15% of tumors in patients with neurofibromatosis type 1 (NF-1). Histologically, 90% are low-grade astrocytomas.
• Pilomyxoid Astrocytoma: Occurs primarily in hypothalamic/optic chiasmic region in infants. Carries high risk of cerebrospinal spread.
• Diffuse Astrocytomas: Predilect supratentorial locations. Evolution to malignant astrocytoma linked to cumulative molecular abnormalities (p53 mutation, platelet-derived growth factor receptor-alpha overexpression).
• High-Grade Gliomas: Include anaplastic astrocytoma and glioblastoma multiforme. Harbor characteristic genetic alterations: mutations in histone H3.3, H3.1, p53, BRAF, and amplification of oncogenes (PDGFRA).

Craniopharyngioma

• Arise in suprasellar region; account for 6-9% of pediatric CNS tumors.
• Adamantinomatous subtype common in children; exclusively harbors CTNNB1 mutations.
• Slow-growing, benign lesions engulfing vital anatomic structures.
• Neuroimaging demonstrates solid and cystic components with calcifications.

Germ Cell Tumors

• Arise predominantly in midline structures (pineal and suprasellar regions).
• Account for 3-5% of pediatric CNS tumors; peak incidence 10-12 years.
• Include pure germinomas (highly curable, >90% survival) and nongerminomatous GCTs (70-80% survival).
• Characterized by secretion of tumor markers: alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (b-hCG).

Ependymoma (Supratentorial)

• Arise from ependymal lining.
• Supratentorial molecular subgroups include EPN-YAP-1 and EPN-RELA.
• EPN-RELA confers dismal outcome (10-year survival ~50%).
• EPN-YAP-1 demonstrates significantly better outcomes.

Choroid Plexus Tumors

• Most common CNS tumor in infants <1 year.
• Predominantly occur supratentorially in lateral ventricles.
• Choroid plexus papilloma (WHO grade I) curable with complete resection.
• Choroid plexus carcinoma (WHO grade III) malignant, seeds cerebrospinal fluid (CSF).
• Strongly associated with Li-Fraumeni syndrome (p53 mutation).

Embryonal Tumors

• Supratentorial PNET: Composed of undifferentiated neuroepithelial cells; requires highly dose-intense therapy.
• Atypical Teratoid/Rhabdoid Tumor (AT/RT): Aggressive malignancy of infancy. Characterized by loss of chromosome 22q11.2 and INI1/SMARCB1 mutation.

Clinical Manifestations

Hemispheric Lesions

• Focal motor weakness or hemiparesis.
• Premature hand preference in infants.
• Focal seizures.
• Frontal lobe tumors induce personality changes and headaches.
• Temporal lobe tumors cause speech changes.

Suprasellar And Third Ventricle Lesions

• Visual Disturbances: Decreased visual acuity, visual field defects, Marcus Gunn pupil, nystagmus.
• Neuroendocrine Deficits: Precede neuroophthalmologic dysfunction by average 1.9 years. Include diabetes insipidus, delayed/precocious puberty, hypothyroidism, galactorrhea, abnormal linear growth.

Diencephalic Syndrome

• Caused by low-grade hypothalamic or thalamic gliomas in infants.
• Features severe emaciation despite normal caloric intake.
• Accompanied by inappropriately euphoric affect.

Pineal Region Lesions

• Parinaud Syndrome: Paresis of upward gaze, pseudo-Argyll Robertson pupil (reactive to accommodation, not light), convergence/retraction nystagmus, eyelid retraction.

Diagnostic Evaluation

Neuroimaging

• Magnetic resonance imaging (MRI) with and without gadolinium remains diagnostic standard.
• Delineates complex cystic/solid structures and blood-brain barrier breakdown.
• Computed tomography (CT) identifies focal calcifications typical of craniopharyngiomas or oligodendrogliomas.

Laboratory And Adjunctive Studies

• Formal ophthalmologic evaluation maps visual field deficits and acuity.
• Comprehensive endocrine panel required for midline/suprasellar tumors.
• Serum and CSF tumor markers (AFP, b-hCG) diagnostic for secreting germ cell tumors.
• Lumbar puncture for CSF cytology contraindicated with obstructive hydrocephalus or supratentorial midline shift (herniation risk).

Management Strategies

Surgical Intervention

• Primary goal remains gross total resection with preservation of neurologic function.
• Completely resected low-grade supratentorial astrocytomas yield 76-100% 5-year survival.
• Endoscopic third ventriculostomy useful for reducing intracranial pressure prior to definitive resection.

Radiotherapy

• Delayed or avoided in children <3 years due to severe late effects (microcephaly, cognitive impairment, panhypopituitarism).
• Proton-beam radiotherapy increasingly utilized to conform radiation volume and spare adjacent normal tissue.

Chemotherapy And Targeted Therapy

• Adjuvant chemotherapy utilized to shrink residual tumor or avoid radiation in infants.
• BRAF Inhibitors: Trametinib or dabrafenib effectively stabilize/shrink BRAF-mutated low-grade gliomas.
• mTOR Inhibitors: Everolimus utilized for tuberous sclerosis-associated subependymal giant cell astrocytomas.