Basics
Description
A primary neoplasm arising in the CNS
Epidemiology
- Most common solid neoplasm of childhood (2nd to leukemia in overall incidence)
- Slight male predominance
- Majority arise infratentorially (within cerebellum or brainstem) in children 1-11 years of age.
- Majority arise supratentorially in children <1 year of age.
Incidence
- Incidence rising (>3,000 new cases/year)
- 4.5 cases/100,000 children/year
- Peak incidence in children ≤7 years of age
Risk Factors
Genetics
- Not a heritable condition
- Primary CNS tumors are associated with several familial syndromes:
- Neurofibromatosis with optic pathway gliomas (NF1) and meningiomas (NF2)
- Tuberous sclerosis with gliomas and rarely ependymomas
- Li-Fraumeni syndrome with astrocytomas
- Von Hippel-Lindau with cerebellar hemangioblastoma
- Turcot syndrome with primitive neuroectodermal tumor
Pathophysiology
The majority of tumors are classified based on their histology. The most common are the following:
- Glioma
- Arises from glial cells (e.g., astrocytes most common)
- >50% of childhood CNS tumors
- Ranges from low-grade (often in the cerebellum or optic pathway) to high-grade (grade III-IV; in the cerebrum or brainstem)
- Locally recurrent and invasive when high-grade
- Primitive neuroectodermal tumor/medulloblastoma
- Malignant embryonal tumor arising from unknown cell type
- Comprises ~20% of childhood CNS tumors
- Most common malignant brain tumor in children
- Majority arise in the midline of the cerebellum (referred to as medulloblastoma).
- Predisposition for leptomeningeal dissemination
- Ependymoma
- Arises from ependymal cells that line the ventricular system
- 8-10% of childhood CNS tumors
- Most commonly occurs in the 4th ventricle; may arise in the spinal cord
- Locally recurrent and invasive; spinal metastases rare at initial diagnosis
- Germ cell tumor
- Derived from totipotent germ cells
- 3-5% of childhood CNS tumors
- Majority are located in the pineal or suprasellar region.
- Atypical teratoid/rhabdoid tumor
- Rare embryonal tumor arising from unknown cell type; often misdiagnosed as primitive neuroectodermal tumor
- <3% of childhood CNS tumors
- Majority arise in children <5 years of age.
- Propensity to arise in the posterior fossa with frequent leptomeningeal dissemination; reported in association with malignant rhabdoid tumors of the kidney
- Craniopharyngioma: 6-9% of childhood CNS tumors
- Choroid plexus tumors (papilloma and carcinoma)
- Ganglioglioma
- Meningioma and hemangioblastoma, rare in children
Etiology
- No specific causative agents are known, but there is an association with radiation, chemical exposure, other malignancies, familial/heritable diseases, immunosuppression/immunodeficiency (CNS lymphoma).
- Molecular markers and variants of individual tumor types are being identified.
Diagnosis
Tumor location dictates symptoms and signs.
History
- Headache and vomiting (particularly in the morning), irritability, and lethargy are associated with increased intracranial pressure.
- Difficulty swallowing, slurred speech, and diplopia may indicate brainstem tumor.
- Visual field deficits (bumps into things) could indicate optic pathway lesion.
- Focal weakness hints at pyramidal tract lesion.
- Ataxia may be a sign of cerebellar lesion.
- Changes in behavior or school performance, new-onset seizures, and weakness could be signs of supratentorial lesion.
- Polyuria/polydipsia may indicate hypothalamic/pituitary lesion.
- Failure to thrive, emaciation, euphoria, and increased appetite in an infant may indicate hypothalamic lesion (diencephalic syndrome).
- Back pain, extremity weakness, and bowel/bladder dysfunction could signify spinal cord metastases (often seen with primitive neuroectodermal tumor/medulloblastoma and germ cell tumors).
Physical Exam
- Papilledema, impaired upgaze and/or lateral gaze, macrocephaly (infants), and bulging fontanelle are signs of increased intracranial pressure.
- Focal deficit on neurologic exam helps localize the mass lesion:
- Isolated cranial nerve VI and VII palsies may indicate brainstem tumor.
- Ataxia and dysmetria could indicate cerebellar mass.
- Decreased visual acuity, visual field deficit, absent pupillary light response, and strabismus may all be signs of optic pathway tumor.
- Changes in cognitive function, mood, and affect could indicate supratentorial lesion.
- Impaired upgaze, convergence nystagmus, and pupils responding to accommodation but poorly to light are signs of pineal lesion (Parinaud or dorsal midbrain syndrome).
- Signs of neurocutaneous disease (e.g., caf © au lait spots, Lisch nodules) may indicate a syndrome such as neurofibromatosis type 1.
Diagnostic Tests & Interpretation
Imaging
- MRI with and without gadolinium enhancement is the "gold standard"ť for identification, localization, and characterization of tumors.
- CT can be used as an initial study, but if negative and a high index of suspicion, follow with MRI. Useful to evaluate for hydrocephalus and hemorrhage
Diagnostic Procedures/Other
Staging of tumor
- Postoperative head MRI within 24-48 hours to determine residual disease before postoperative inflammatory changes are prominent
- Spine MRI and CSF cytology required for neuraxis staging of tumors with high risk of leptomeningeal dissemination
- Elevated α-fetoprotein and quantitative β-human chorionic gonadotropin in CSF and serum are markers for germ cell tumors.
Differential Diagnosis
- Infection: cerebral abscess
- Tumors: metastatic tumor to brain, uncommon with childhood cancers
- Trauma: hemorrhage unlikely to be confused with tumor
- Congenital
- Arteriovenous malformation
- Hamartoma
- Dysplastic brain
- Psychosocial: Some patients with nausea, vomiting, or behavior changes are first diagnosed with psychiatric disorders, GI disorders, failure to thrive, or anorexia nervosa prior to discovery of a brain tumor.
Alert
New onset of psychoses should prompt imaging to rule out tumor.
Treatment
Surgery/Other Procedures
- Both for histology and to attempt maximal tumor debulking; should be performed by experienced pediatric neurosurgeon
- Rarely indicated in intrinsic pontine (brainstem) glioma; although biopsy for molecular profiling increasingly in use
- Ventriculoperitoneal shunt or endoscopic 3rd ventriculostomy when needed for obstructive hydrocephalus (risk of peritoneal seeding minimal)
Alert
Patient should be referred to a pediatric brain tumor/oncology center at diagnosis (preoperatively).
Radiotherapy
- Volume and dose vary depending on histology.
- Radiation therapy to the tumor bed is used for most patients with brain tumors.
- Medulloblastoma/primitive neuroectodermal tumor patients need craniospinal radiation therapy. The one exception is infants and young children (<3 years of age) in whom cognitive deficits from radiation therapy are devastating.
- Duration of radiation therapy: usually 6 weeks
- Newer approaches to limit exposure of normal brain include intensity-modulated and proton radiotherapy.
Medication
- Dexamethasone to control increased intracranial pressure (0.5 mg/kg/24 h IV/PO divided q6h)
- Chemotherapy
- Drugs are most often used in combination:
- Carboplatin, vincristine, or 6-thioguanine, procarbazine, CCNU, vincristine for low-grade glioma
- Cisplatin, CCNU, vincristine, etoposide, and cyclophosphamide are active agents for primitive neuroectodermal tumor/medulloblastoma.
- Temozolomide for high-grade glioma
- New protocols currently being evaluated:
- High-dose chemotherapy with autologous stem cell rescue for high-risk primitive neuroectodermal tumor/medulloblastoma
- Targeted therapies, angiogenesis inhibitors
- Duration of chemotherapy: 6 months to 2 years
Alert
Possible conflict with other treatments: Chemotherapy can alter anticonvulsant levels.
Ongoing Care
- Neurologic deficits can take months to improve or stabilize with permanent deficit.
- Any worsening or relapse of symptoms must be evaluated for tumor recurrence.
- MRI every 3 months the 1st year, every 6 months for the next 2 years, and annually thereafter. Benefit of routine surveillance imaging is controversial.
Prognosis
- Dependent on histology of tumor, location, and extent of initial resection
- Glioma
- Low-grade: ≥90% 5-year progression-free survival (PFS) following gross total resection; 45-65% for subtotal resection
- High-grade: median survival 8-31 months; depends on grade and extent of resection
- Intrinsic pontine: median overall survival of 9-13 months from diagnosis
- Medulloblastoma
- 79-83% PFS at 5 years if localized, gross total resection achieved, and >3 years old at diagnosis
- <50% PFS if disseminated
- Ependymoma
- 50-70% survival at 5 years with total resection
- <30% survival with subtotal resection
- Infants overall have a worse prognosis, possibly due to the limitations of therapy and/or the aggressiveness of the tumor.
Alert
Even benign tumors may be life threatening if their location precludes resection.
Complications
- Secondary to disease
- Increased intracranial pressure
- Obstruction of CSF flow
- Requires immediate neurosurgical evaluation
- Secondary to radiotherapy
- Neurocognitive sequelae (age- and dose-related)
- Endocrinopathy (growth hormone deficiency, hypothyroidism, gonadal dysfunction)
- Risk of second malignancies (meningioma, glioma, sarcoma)
- Increased risk of stroke
- Secondary to chemotherapy
- Risks associated with bone marrow suppression (infection, bleeding, anemia)
- Hearing loss
- Risk of secondary leukemia
Additional Reading
- Abdullah S, Qaddoumi I, Bouffet E. Advances in the management of pediatric central nervous system tumors. Ann N Y Acad Sci. 2008;1138:22-31. [View Abstract]
- Blaney SM, Haas-Kogan D, Poussaint TY, et al. Gliomas, ependymomas, and other nonembryonal tumors. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2010:717-824.
- Ostrom QT, Gittleman H, Liao P, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol. 2014;16(Suppl 4):iv1-iv63. [View Abstract]
- Packer RJ. Brain tumors in children. Arch Neurol. 1999;56(4):421-425. [View Abstract]
- Phillips PC, Grotzer MA. Brain tumors in children. In: Asbury AK, McKhann GM, McDonald WI, et al, eds. Diseases of the Nervous System: Clinical Neuroscience and Therapeutic Principles. 3rd ed. Cambridge, United Kingdom: Cambridge University Press; 2002:1448-1461.
- Sievert AJ, Fisher MJ. Pediatric low-grade gliomas. J Child Neurol. 2009;24(11):1397-1408. [View Abstract]
Codes
ICD09
- 239.6 Neoplasm of unspecified nature of brain
- 191.9 Malignant neoplasm of brain, unspecified
- 225.0 Benign neoplasm of brain
- 225.2 Benign neoplasm of cerebral meninges
ICD10
- D49.6 Neoplasm of unspecified behavior of brain
- C71.9 Malignant neoplasm of brain, unspecified
- D33.2 Benign neoplasm of brain, unspecified
- D32.9 Benign neoplasm of meninges, unspecified
SNOMED
- 126952004 Neoplasm of brain (disorder)
- 428061005 malignant neoplasm of brain (disorder)
- 92030004 benign neoplasm of brain (disorder)
- 126960003 Neoplasm of cerebellum (disorder)
- 302820008 Intracranial meningioma
- 126961004 Neoplasm of brain stem (disorder)
FAQ
- Q: Are my other children at risk for getting a brain tumor?
- A: No (except in rare cases of certain familial syndromes).
- Q: Did something I do caused this?
- A: No. In addition, the claims made about high-power lines and cellular phones causing brain tumors or cancer are unproven.