CNS Tumors

Epidemiology And Anatomic Distribution

Most common solid malignancy in pediatrics; represents 20-25% of childhood cancers. Leading cause of cancer-related mortality in patients 0-14 years.

Infants (<1 year): Supratentorial tumors predominate (choroid plexus tumors, germ cell tumors).
Children (1-10 years): Infratentorial tumors predominate (pilocytic astrocytoma, medulloblastoma).
Adolescents (>10 years): Supratentorial tumors predominate (diffuse astrocytomas, pituitary/craniopharyngioma).

Majority occur sporadically. Approximately 5% associated with familial syndromes or prior cranial ionizing radiation.

Syndrome	Gene / Locus	Associated Central Nervous System Tumors
Neurofibromatosis Type 1	NF1 (17q11.2)	Optic pathway gliomas, astrocytomas, malignant peripheral nerve sheath tumors.
Neurofibromatosis Type 2	NF2 (22q12)	Vestibular schwannomas, meningiomas, ependymomas.
Tuberous Sclerosis	TSC1 (9q34), TSC2 (16p13)	Subependymal giant cell astrocytoma (SEGA), cortical tubers.
Li-Fraumeni Syndrome	TP53 (17p13.1)	Astrocytomas, primitive neuroectodermal tumors (PNET), choroid plexus carcinoma.
Von Hippel-Lindau	VHL (3p25)	Hemangioblastomas.
Turcot Syndrome	APC (5q21), hMLH1	Medulloblastoma, glioblastoma.
Gorlin Syndrome	PTCH1 (9q22)	Medulloblastoma.

Presentation depends on tumor location, growth rate, and patient age.

Results from cerebrospinal fluid (CSF) pathway obstruction.

Infants: Emesis, lethargy, irritability, macrocephaly, open cranial sutures.
Children/Adolescents: Morning headache, emesis, diplopia, papilledema.
Severe: Cushing triad (hypertension, bradycardia, altered respiration); indicates impending herniation.

Anatomic Region	Characteristic Clinical Signs
Infratentorial / Cerebellar	Ataxia, equilibrium disorders, dysmetria, nystagmus, torticollis (tonsillar herniation).
Brainstem	Gaze palsy, multiple cranial nerve palsies, hemiparesis, hyperreflexia, clonus.
Supratentorial / Hemispheric	Focal motor/sensory deficits, seizures, premature hand preference.
Optic Pathway	Decreased visual acuity, visual field defects, Marcus Gunn pupil (afferent defect).
Suprasellar / Hypothalamic	Neuroendocrine deficits (diabetes insipidus, precocious/delayed puberty, hypothyroidism, growth failure).
Diencephalic	Diencephalic syndrome: failure to thrive, emaciation, euphoric affect.
Pineal Region	Parinaud syndrome: upward gaze paresis, pseudo-Argyll Robertson pupils, eyelid retraction.

Immediate neurologic assessment and neuroimaging required.

Magnetic Resonance Imaging (MRI): Gold standard; performed with and without gadolinium contrast. Detects leptomeningeal spread via spinal MRI.
Computed Tomography (CT): Utilized acutely; detects calcifications, hemorrhage, bony lesions.

Lumbar Puncture: Cytologic evaluation for dissemination. Contraindicated in newly diagnosed hydrocephalus, supratentorial midline shift, or large infratentorial masses due to herniation risk.
Tumor Markers: Serum and CSF alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin ( $β$ -hCG) diagnostic for specific germ cell tumors.

Account for ~40% of pediatric central nervous system malignancies.

Low-Grade (WHO Grade I-II): Pilocytic astrocytoma (PA) most common. Often infratentorial (cerebellum) or optic pathway. BRAF fusions or BRAF V600E mutations common. Biphasic histology, Rosenthal fibers. >90% survival with total resection.
High-Grade (WHO Grade III-IV): Anaplastic astrocytoma, Glioblastoma Multiforme. Less common. Associated with TP53, BRAF, and histone H3.3/H3.1 mutations. Poor prognosis; requires maximal resection, local radiation, alkylator chemotherapy.

Represent ~9% of tumors; highly malignant (WHO Grade IV) with neuraxis dissemination potential.

Medulloblastoma: Cerebellar origin. Classic presentation: morning headache, emesis, truncal ataxia. Four molecular subgroups determine prognosis: WNT (excellent), SHH (intermediate), Group 3 (MYC amplified, poor), Group 4 (intermediate). Management requires maximal safe resection, craniospinal irradiation (CSI), and multiagent chemotherapy.
Atypical Teratoid/Rhabdoid Tumor (AT/RT): Aggressive, predominantly <5 years age. Characterized by 22q11.2 deletion (INI1 loss). Extremely poor prognosis; requires intensive multimodal therapy.

Arise from ependymal lining; fourth ventricle most common (70%).

Presentation: Emesis, ataxia, obstructive hydrocephalus.
Molecular Subgroups: Posterior fossa EPN-A (young children, dismal outcome); EPN-B (adolescents, better outcome).
Management: Gross total surgical resection crucial. Followed by focal radiation (54-60 Gy).

Diffuse Intrinsic Pontine Glioma (DIPG): 70-85% of brainstem tumors. Cranial nerve deficits, long tract signs. H3K27M mutation prevalent. Unresectable; uniformly fatal. Palliative radiation yields median survival <12 months.
Focal / Dorsally Exophytic: 15-20% of brainstem tumors. Typically low-grade; resectable with favorable outcomes.

Arise in suprasellar region (WHO Grade I).

Subtypes: Adamantinomatous (CTNNB1 mutation, children); Papillary (BRAF V600E, adults).
Presentation: Bitemporal hemianopsia, profound endocrine dysfunction.
Management: Gross total resection curative but carries high morbidity. Subtotal resection plus radiation alternative.

Midline structures (pineal, suprasellar).

Germinoma: Highly radiosensitive, >90% survival.
Non-germinomatous: Elevated AFP or $β$ -hCG. Requires intensive chemotherapy and craniospinal radiation.

Multimodal approach dictates overall survival approaching 60-70%.

Surgery: Essential for tissue diagnosis, relieving obstruction, and maximal safe debulking.
Radiation Therapy: Utilized post-operatively for high-grade or residual disease. Craniospinal irradiation required for embryonal tumors. Avoided or delayed in infants (<3 years) due to devastating neurocognitive sequelae.
Chemotherapy: Efficacy depends on tumor histology. Utilized to delay radiation in infants, or concomitantly for synergistic effect.

Affect >50% of long-term survivors.

Neurocognitive: Learning disabilities, decreased processing speed, memory deficits (secondary to leukoencephalopathy, mineralizing microangiopathy).
Neuroendocrine: Growth hormone deficiency, central hypothyroidism, precocious/delayed puberty.
Secondary Neoplasms: High-grade gliomas, meningiomas within prior radiation fields.