Doctor123.org

Brain Tumor, Pediatric

Basics

Description

- 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

- 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

- 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

- 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

- Secondary to disease - Increased intracranial pressure - Obstruction of CSF flow - Requires immediate neurosurgical evaluation

- Secondary to chemotherapy - Risks associated with bone marrow suppression (infection, bleeding, anemia) - Hearing loss - Risk of secondary leukemia

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 ependymomasLi-Fraumeni syndrome with astrocytomasVon Hippel-Lindau with cerebellar hemangioblastomaTurcot syndrome with primitive neuroectodermal tumor

Pathophysiology

The majority of tumors are classified based on their histology. The most common are the following:

  • GliomaArises from glial cells (e.g., astrocytes most common)>50% of childhood CNS tumorsRanges 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/medulloblastomaMalignant embryonal tumor arising from unknown cell typeComprises ~20% of childhood CNS tumorsMost common malignant brain tumor in childrenMajority arise in the midline of the cerebellum (referred to as medulloblastoma).Predisposition for leptomeningeal dissemination
  • EpendymomaArises from ependymal cells that line the ventricular system8-10% of childhood CNS tumorsMost commonly occurs in the 4th ventricle; may arise in the spinal cordLocally recurrent and invasive; spinal metastases rare at initial diagnosis
  • Germ cell tumorDerived from totipotent germ cells3-5% of childhood CNS tumorsMajority are located in the pineal or suprasellar region.
  • Atypical teratoid/rhabdoid tumorRare embryonal tumor arising from unknown cell type; often misdiagnosed as primitive neuroectodermal tumor<3% of childhood CNS tumorsMajority 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
  • CongenitalArteriovenous malformationHamartomaDysplastic 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)
  • ChemotherapyDrugs are most often used in combination:Carboplatin, vincristine, or 6-thioguanine, procarbazine, CCNU, vincristine for low-grade gliomaCisplatin, CCNU, vincristine, etoposide, and cyclophosphamide are active agents for primitive neuroectodermal tumor/medulloblastoma.Temozolomide for high-grade gliomaNew protocols currently being evaluated:High-dose chemotherapy with autologous stem cell rescue for high-risk primitive neuroectodermal tumor/medulloblastomaTargeted therapies, angiogenesis inhibitorsDuration 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
  • GliomaLow-grade: ≥90% 5-year progression-free survival (PFS) following gross total resection; 45-65% for subtotal resectionHigh-grade: median survival 8-31 months; depends on grade and extent of resectionIntrinsic pontine: median overall survival of 9-13 months from diagnosis
  • Medulloblastoma79-83% PFS at 5 years if localized, gross total resection achieved, and >3 years old at diagnosis<50% PFS if disseminated
  • Ependymoma50-70% 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 diseaseIncreased intracranial pressureObstruction of CSF flowRequires immediate neurosurgical evaluation
  • Secondary to radiotherapyNeurocognitive 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 chemotherapyRisks associated with bone marrow suppression (infection, bleeding, anemia)Hearing lossRisk 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.