• No specific causative agents are known, but there is an increased risk associated with radiation, chemical exposure, other malignancies, familial diseases.

• Glioma
  • Arise from astrocytes (supportive tissue)
  • 50% of childhood CNS tumors
  • Range from benign or low grade, often in the cerebellum or optic pathway, to malignant or grade III to IV, in the cerebrum or brainstem.
  • Locally recurrent and invasive when malignant
• Primitive neuroectodermal tumor (PNET)
  • Malignant embryonal tumor arising from poorly differentiated neuroepithelial cells
  • Comprise about 30% of childhood CNS tumors
  • Occur more frequently in the midline of the cerebellum (referred to as medulloblastoma)
  • Predisposition for leptomeningeal dissemination
• Ependymoma
  • Arise from ependymal cells that line the ventricular system
  • Comprise about 5% to 10% of childhood CNS tumors
  • Most commonly occur in the fourth ventricle; adults have a higher incidence in the spinal cord
  • Locally recurrent and invasive; prone to spinal metastases late in the course of the disease
• Rhabdoid or atypical teratoid tumor
  • Rare embryonal tumor arising from unknown cell type
  • Comprise less than 3% of childhood CNS tumors
  • Occur most often in infants less than 2 years of age
  • Propensity to arise in the posterior fossa with aggressive clinical pattern; reported in association with malignant rhabdoid tumors of the kidney
• Tumors of the choroid plexus and pineal gland
• Neuronal tumors
  • Ganglioglioma
  • Neuroblastoma
• Meningioma and hemangioblastoma, rare in children

• Not a heritable condition
• Primary CNS tumors are associated with several familial syndromes:
  • Neurofibromatosis with optic pathway tumors and meningiomas
  • Tuberous sclerosis with gliomas and rarely ependymomas
  • Li-Fraumeni syndrome with astrocytomas

• Most common solid neoplasm of childhood (second to leukemia in overall incidence)
• Incidence rising (about 1,700 new cases/yr)
• Peak age between 3 to 9 years old
• Slight male predominance
  • Majority arise infratentorially (within cerebellum or brainstem) in children older than 1 year of age

• Increased intracranial pressure (ICP)
  • Obstruction of cerebrospinal fluid (CSF) flow
  • Requires immediate neurosurgical evaluation
• Diencephalic syndrome
  • May be seen in infants with tumors involving the hypothalamus
  • Results in failure to thrive and emaciation in a euphoric child with increased appetite
• Cognitive and neuroendocrine deficits
  • Dependent on location of tumor, age, and therapy used
• Additional therapy-related complications:
  • Chemotherapy
    • Risks associated with bone marrow suppression (infection, bleeding, anemia)
    • Hearing loss
    • Risk of secondary leukemia
  • Radiation
    • Risk of second malignancies (meningioma, osteosarcoma, glioma, other sarcomas)
    • Neuropyschological damage is age and dose-related

• Glioma
  • Low grade: 90% survival
  • High grade: 25% survival
  • Brainstem: 10% survival
• PNET or medulloblastoma
  • 80% survival at 3 years if localized
  • Less than 50% survival if disseminated (improving with autologous “bone marrow transplantation”)
• Ependymoma
  • 60% to 70% survival at 5 years with total resection
  • Less than 30% survival with subtotal resection.
• Infants overall have a worse prognosis, possibly due to the limitations of therapy versus the aggressiveness of the tumor.

• Cerebral abscess

• Metastatic tumor to brain uncommon in childhood solid tumors

• Hemorrhage unlikely to be confused with tumor

• Arteriovenous malformation
• Hamartoma

• Some patients with nausea, vomiting, or behavior changes are first diagnosed with psychiatric disorders (anorexia nervosa) prior to discovery of a brain tumor.

Question: Headache frequency, intensity and vomiting?
Significance: Associated with increased intracranial pressure (ICP).

Question: New onset of neurological symptoms, difficulty chewing or swallowing.
Significance: Brainstem tumor.

Question: Diplopia
Significance: Cranial nerves or nodei affected.

Question: Visual field cuts (“bumps into things”)
Significance: Optic tract lesion

Question: Weakness
Significance: Pyramidal tract lesion

Question: Ataxia
Significance: Cerebellar lesion

Question: Changes in behavior or school performance, new onset seizures.
Significance: Supratentorial lesion

Finding: Head circumference/macrocephaly or bulging fontanelle and/or papilledema
Significance: Increased ICP

Finding: Focal deficit on neurological examination
Significance: Localizes mass lesion

Finding: Cranial nerves, palsies, parreflexia
Significance: Brainstem tumor

Finding: Coordinations; gait disturbances; head tilt
Significance: Cerebellar mass

Finding: Eye movements; nystagmus
Significance: Optic tract tumor

Finding: Changes in mental status
Significance: Supratentorial lesion

Finding: Signs of neurocutaneous disease (e.g., café au lait spots, Lisch nodules)
Significance: Syndrome like fibromatosis

Test: MRI with and without gadolinium enhancement
Significance: Gold standard image for identification, localization, and characterization of tumor

Test: CT
Significance: Can be used as a screen, but if negative with a high index of suspicion, follow with MRI

FALSE POSITIVES

Abscess, dysplastic brain, hamartoma

STAGING OF TUMOR

Test: Post-op head MRI within 48 to 72 hours
Significance: To determine residual disease

Test: Spine MRI; CSF cytology
Significance: Neuraxial staging for tumors with high risk of leptomeningeal dissemination

Test: Alpha-fetoprotein (AFP), B-HCG
Significance: Serum and CSF markers for germ cell tumors

• Both for histology and to attempt maximal tumor debulking, should be performed by experienced pediatric neurosurgeon
• Contraindicated in pontine (brainstem) glioma
• Ventriculoperitoneal (VP) shunt when needed for obstructive hydrocephalus (risk of peritoneal seeding minimal)

• Dexamethasone to control increased intracranial pressure (0.5 mg/kg divided q6h)
• Chemotherapy
  • Drugs are most often used in combination
• New protocols currently under development
  • CCNU, vincristine, procarbazine for high-grade glioma
  • Cisplatin, CCNU, vincristine for medulloblastoma or PNET
  • Carboplatin, vincristine, ± etoposide for low-grade glioma

• XRT to the tumor bed is used for most patients with brain tumors.
• Medulloblastoma/PNET patients need craniospinal XRT. The one exception is in infants and young children (<3 years of age) in whom cognitive deficits from XRT can be devastating.

• Radiation therapy: 6 weeks
• Chemotherapy: 1 to 2 years

• XRT (limited to structures in XRT field)
  • Hair loss
  • Otitis externa

• Neurological deficits can take months to improve or stabilize with permanent deficit.
• Any relapse or worsening of symptoms must be evaluated for tumor recurrence.
• MRI imaging every 3 months the first year, every 6 months for the next 4 years, and annually thereafter. Benefit of routine surveillance imaging is controversial.

• New onset of psychoses should prompt imaging to rule out tumor.
• Not referring the patient to a pediatric brain tumor/oncology center at diagnosis (preoperatively). This requires an experienced (pediatric) neurosurgeon.

Q: Are my other children at risk for getting a brain tumor?
A: No.

Q: Did something I do cause this?
A: No. In addition, the claims made about high-power lines and cellular phones causing brain tumors or cancer are unproven.

Q: Is this inherited?
A: No, except tumors associated with neurofibromatosis.

Cohen ME, Duffner PK. Brain tumors in children, 2nd ed. New York: Raven Press, 1994.

Gilles FH. Classifications of childhood brain tumors. Cancer 1985;56:1850–1857.

Gurney JG, Severson RK, Davis S, Robison LL. Incidence of cancer in children in the United States. Cancer 1995;75:2186–2195.

Heideman RL, Packer RJ, Albright LA. Tumors of the central nervous system. In: Pizzo PA, Poplack DG, eds. Principles and practice of pediatric oncology, 3rd ed. Philadelphia: JB Lippincott, 1997, 633–697.

Packer RJ. Childhood tumors. Curr Opin Pediatr 1997;9(6):551–557.

Reddy AT. Packer RJ. Pediatric central nervous system tumors. Curr Opin Oncol 1998;10(3):186–193.