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).
Genetic Syndromes And Predisposition
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. |
Clinical Manifestations
Presentation depends on tumor location, growth rate, and patient age.
Signs Of Increased Intracranial Pressure
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.
Focal Neurologic Deficits By Location
| 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. |
Diagnostic Evaluation
Immediate neurologic assessment and neuroimaging required.
Neuroimaging
- 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.
Cerebrospinal Fluid And Tumor Markers
- 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 (-hCG) diagnostic for specific germ cell tumors.
Specific Tumor Profiles
Astrocytomas
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.
Embryonal Tumors
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.
Ependymomas
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).
Brainstem Gliomas
- 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.
Craniopharyngiomas
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.
Germ Cell Tumors
Midline structures (pineal, suprasellar).
- Germinoma: Highly radiosensitive, >90% survival.
- Non-germinomatous: Elevated AFP or -hCG. Requires intensive chemotherapy and craniospinal radiation.
Management Principles And Complications
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.
Chronic Late Effects
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.