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

Pineal Region

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.