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Childhood Brain Stem Glioma Treatment (PDQ®)

  • Last Modified: 05/19/2014

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General Information About Childhood Brain Stem Glioma

Incidence
Anatomy
Clinical Features
Diagnosis
Prognosis and Prognostic Factors
Follow-up After Treatment

Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis.

The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization (WHO) classification of nervous system tumors.[1,2] For a full description of the classification of nervous system tumors and a link to the corresponding treatment summary for each type of brain tumor, refer to the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview.

The term brain stem glioma is a generic description that refers to any tumor of glial origin arising in the brain stem, inclusive of the midbrain, pons, and medulla. The following two histologies predominate:

  • Diffuse (infiltrating) astrocytomas centered in the pons, also called diffuse intrinsic pontine glioma (DIPG).

  • Pilocytic astrocytomas, which occur throughout the brain stem.

Incidence

Approximately 300 to 400 pediatric brain stem tumors are diagnosed each year in the United States. DIPG accounts for approximately 75% to 80% of pediatric brain stem tumors.[3] Most children with DIPG are diagnosed between the ages of 5 and 10 years. Focal pilocytic astrocytomas in the brain stem occur less frequently.[4]

Anatomy

Enlarge
Drawing of the inside of the brain showing  the lateral ventricle, third ventricle, and fourth ventricle, cerebrum, choroid plexus, hypothalamus, pineal gland, pituitary gland, optic nerve, tentorium, cerebellum,  brain stem, pons, medulla, and spinal cord.
Anatomy of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in blue), and other parts of the brain. The posterior fossa is the region below the tentorium, which separates the cortex from the cerebellum and essentially denotes the region containing the brain stem, cerebellum, and fourth ventricle.


Clinical Features

In children with DIPG, a classic triad of symptoms (cranial neuropathies, long tract signs, and ataxia) is often described. However, children often present with only one or two of these findings. Obstructive hydrocephalus due to expansion of the pons can also be a presenting symptom. Nonspecific symptoms may also occur, including behavioral changes and decreased school performance.

Focal pilocytic astrocytomas in the brain stem present in multiple ways depending on tumor location. Common presenting symptoms include the following:[4]

  • Raised intracranial pressure with associated hydrocephalus.
  • Unilateral hemiparesis.
  • Unilateral cranial neuropathies.
  • Ataxia.
Diagnosis

Primary tumors of the brain stem are most often diagnosed based on clinical findings and on neuroimaging studies using magnetic resonance imaging (MRI).[5] Histologic confirmation of presumed DIPGs is usually unnecessary. However, histologic confirmation is currently performed for research studies and may be more routinely recommended in the future.[6] Biopsy or resection may be indicated for brain stem tumors that are not diffuse and intrinsic or when there is diagnostic uncertainty based on imaging findings. New approaches with stereotactic needle biopsy may make biopsy safer.[7,8]

Children with neurofibromatosis type 1 (NF1) are at an increased risk of developing a brain stem glioma. They may present with a long history of symptoms or be identified by screening tests.

Prognosis and Prognostic Factors

The median survival for children with DIPGs is less than 1 year.[9] In contrast, focal pilocytic astrocytomas have a markedly improved prognosis, with 5-year overall survival exceeding 90%.[4]

Prognostic factors include the following:

  • Histology/grade of the tumor: Astrocytic tumors predominate in the brain stem. Pilocytic astrocytomas (WHO grade 1) have a favorable prognosis and can arise throughout the brain stem, including the tectum of the midbrain, focally within the pons, or at the cervicomedullary junction where they are often exophytic. In contrast, DIPGs are diffuse astrocytomas which, when biopsied at diagnosis or at postmortem evaluation, are often anaplastic astrocytoma (WHO grade 3) or glioblastoma (WHO grade 4).[10-13] Low-grade fibrillary astrocytomas (WHO grade 2) can occur as focal tumors throughout the brain stem, with a good prognosis. Conversely, some children with imaging features supportive of a diagnosis of DIPG in whom tissue is eventually obtained may also show low-grade fibrillary histology.[14]

  • Age at diagnosis: Children younger than 3 years may have a more favorable prognosis, perhaps reflecting different biologic characteristics.[15]

  • NF1: Children with NF1 and brain stem gliomas may have a better prognosis than other patients who have intrinsic lesions.[16,17]

Follow-up After Treatment

For children with brain stem tumors and anticipated long-term survival, standard follow-up tends to include interval clinical assessments and periodic imaging with MRI. The required duration of follow-up with MRI varies; it largely depends on the presence or absence of residual imaging abnormalities and the original histology of the tumor after treatment.

References
  1. Louis DN, Ohgaki H, Wiestler OD, et al., eds.: WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon, France: IARC Press, 2007. 

  2. Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 (2): 97-109, 2007.  [PUBMED Abstract]

  3. Warren KE: Diffuse intrinsic pontine glioma: poised for progress. Front Oncol 2: 205, 2012.  [PUBMED Abstract]

  4. Klimo P Jr, Pai Panandiker AS, Thompson CJ, et al.: Management and outcome of focal low-grade brainstem tumors in pediatric patients: the St. Jude experience. J Neurosurg Pediatr 11 (3): 274-81, 2013.  [PUBMED Abstract]

  5. Liu AK, Brandon J, Foreman NK, et al.: Conventional MRI at presentation does not predict clinical response to radiation therapy in children with diffuse pontine glioma. Pediatr Radiol 39 (12): 1317-20, 2009.  [PUBMED Abstract]

  6. Walker DA, Liu J, Kieran M, et al.: A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method. Neuro Oncol 15 (4): 462-8, 2013.  [PUBMED Abstract]

  7. Cage TA, Samagh SP, Mueller S, et al.: Feasibility, safety, and indications for surgical biopsy of intrinsic brainstem tumors in children. Childs Nerv Syst 29 (8): 1313-9, 2013.  [PUBMED Abstract]

  8. Grill J, Puget S, Andreiuolo F, et al.: Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma. Pediatr Blood Cancer 58 (4): 489-91, 2012.  [PUBMED Abstract]

  9. Cohen KJ, Pollack IF, Zhou T, et al.: Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group. Neuro Oncol 13 (3): 317-23, 2011.  [PUBMED Abstract]

  10. Ballester LY, Wang Z, Shandilya S, et al.: Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas. Am J Surg Pathol 37 (9): 1357-64, 2013.  [PUBMED Abstract]

  11. Wu G, Diaz AK, Paugh BS, et al.: The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46 (5): 444-50, 2014.  [PUBMED Abstract]

  12. Taylor KR, Mackay A, Truffaux N, et al.: Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet 46 (5): 457-61, 2014.  [PUBMED Abstract]

  13. Buczkowicz P, Hoeman C, Rakopoulos P, et al.: Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet 46 (5): 451-6, 2014.  [PUBMED Abstract]

  14. Warren KE, Killian K, Suuriniemi M, et al.: Genomic aberrations in pediatric diffuse intrinsic pontine gliomas. Neuro Oncol 14 (3): 326-32, 2012.  [PUBMED Abstract]

  15. Broniscer A, Laningham FH, Sanders RP, et al.: Young age may predict a better outcome for children with diffuse pontine glioma. Cancer 113 (3): 566-72, 2008.  [PUBMED Abstract]

  16. Pascual-Castroviejo I, Pascual-Pascual SI, Viaño J, et al.: Posterior fossa tumors in children with neurofibromatosis type 1 (NF1). Childs Nerv Syst 26 (11): 1599-603, 2010.  [PUBMED Abstract]

  17. Albers AC, Gutmann DH: Gliomas in patients with neurofibromatosis type 1. Expert Rev Neurother 9 (4): 535-9, 2009.  [PUBMED Abstract]