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Pediatric central nervous system tumors are the most common solid tumors in children and the leading cause of cancer-related morbidity and mortality.
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The World Health Organization brain tumor classification is in flux and now includes some molecular parameters.
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Recent understandings of tumor biology and genomic aberrations have led to better prediction of outcome and alteration of treatment approaches for children with brain tumors.
Pediatric Brain Tumors
Section snippets
Key points
Presentation
The clinical presentation primarily depends on location of tumor and age of the patient. Infants tend to exhibit relatively nonspecific symptoms, such as macrocephaly, irritability, failure to thrive, loss of developmental milestones, and vomiting.4 Older children most commonly present with localizing neurologic deficits and symptoms related to increased intracranial pressure secondary to obstruction of the normal flow of cerebral spinal fluid (CSF) leading to hydrocephalus. Nonlocalizing
Classification
Brain tumor classification is difficult given that many pediatric CNS tumors may have multiple cell types. Previous classifications tried to identify morphologic appearance on histology and stages of development within the nervous system. As a result, the 2007 World Health Organization (WHO) classification of CNS tumors was based primarily on histologic appearance. However, with recent advancements in tumor biology, in 2016, this classification was changed to incorporate some molecular
Medulloblastoma
Medulloblastoma is, by definition, an embryonal tumor of the posterior fossa and is thought to be the most common malignant brain tumor in children. It comprises up to 20% of all pediatric brain tumors.1 Primarily a tumor of childhood, medulloblastoma is most commonly diagnosed before 15 years of age and has a male predominance.6 There is a biphasic incidence with peaks at 3 to 4 years of age and again at 8 to 9 years of age.7 Previously, in the 2007 WHO classification, medulloblastoma was
Supratentorial embryonal tumors
Non–posterior fossa embryonal tumors, formally known as CNS-primitive neuroectodermal tumors (PNETs), are a group of rare pediatric brain tumors comprising fewer than 3% of pediatric brain tumors and carry a poor prognosis.40, 41 The 2016 WHO classification system incorporates the presence or absence of amplification of the C19MC region on chromosome 19 in defining several subgroups.5 All CNS embryonal tumors are highly malignant and are considered WHO grade IV tumors. Molecular studies have
Atypical teratoid/rhabdoid tumors
ATRTs are rare malignant intracranial neoplasms most commonly occurring in infants and young children. They account for only 1% to 2% of all pediatric brain tumors but approximately 10% to 20% of CNS tumors in patients younger than 3 years.47, 48 ATRTs were previously misclassified until being described as a discrete clinical entity in the 1980s. The genetic hallmark of ATRTs are mutations in SMARCB1.49 In addition to the somatic mutation detected in tumor tissue, approximately a third of the
High-Grade Gliomas
In children, high-grade gliomas (HGGs) occur at an incidence of 0.8 per 100,000 children per year.30 Approximately 20% of all childhood gliomas are HGGs, and include anaplastic astrocytoma (AA), diffuse intrinsic pontine glioma (DIPG), and glioblastoma multiforme (GBM).57 Children with HGGs have an overall poor prognosis despite intensive therapy. Patients may present with headaches, weakness, behavioral changes, or seizures.58 The extent of surgical resection remains one of the most important
Ependymomas
Ependymomas are the third most common brain tumor in children and account for approximately 8% to 10% of all childhood CNS tumors.94 They are neuroepithelial malignancies that occur in the supratentorial brain, posterior fossa, and spinal cord and can affect both children and adults. In children, most occur intracranially with two-thirds located in the posterior fossa.8, 95 There is an increased risk for intramedullary spinal cord ependymomas in patients with NF-2.96 The clinical presentation
Craniopharyngioma
Craniopharygiomas are slow-growing benign epithelial tumors that arise from embryonic remnants of the Rathke pouch in the suprasellar region adjacent to the optic chiasm. They account for approximately 5% to 10% of pediatric brain tumors.103, 104 Symptoms occur as a result of compression of nearby neural structures and can include visual deficits, endocrinopathies, panhypopituitarism from compression of the pituitary gland or stalk, and symptoms of increased intracranial pressure from
Choroid plexus tumors
Choroid plexus tumors are very rare and account for fewer than 1% of all brain tumors and 3% to 4% of pediatric intracranial tumors.115 Patients often present with symptoms of hydrocephalus due to overproduction of CSF by the tumor and less commonly obstruction.116, 117 They are intraventricular papillary neoplasms derived from the choroid plexus epithelium. Histologically they can range from benign well-differentiated choroid plexus papillomas (CPPs) (WHO grade I), atypical CPPs (WHO grade II)
Germ cell tumors
Intracranial germ cell tumors (GCTs) represent approximately 3% of pediatric brain tumors and most commonly arise in midline locations, such as the pineal or suprasellar region of the brain.126 The incidence can vary according to geography, with CNS GCTs accounting for up to 11% of all pediatric brain tumors in Asian countries such as Japan.126, 127, 128 The WHO classification system divides intracranial GCTs into germinomas and non-germinomatous GCTs (NGGCTs). NGGCTs comprise a heterogeneous
Spinal cord tumors
Primary spinal cord tumors are rare CNS tumors in childhood with an annual incidence of less than 1 per 100,000 children per year141 and account for fewer than 6% of all childhood CNS tumors.142 They are difficult to diagnose due to the vague nature of symptoms that can be difficult to characterize. Spinal cord tumors are unique in that they can cause both local and distal symptoms due to tumors interrupting ascending and descending spinal cord pathways. Symptoms typically have a gradual onset
References (150)
- et al.
Presentation of childhood CNS tumours: a systematic review and meta-analysis
Lancet Oncol
(2007) - et al.
Medulloblastoma in childhood: new biological advances
Lancet Neurol
(2007) - et al.
Central nervous system tumors
Hematol Oncol Clin North Am
(2010) - et al.
Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial
Lancet Oncol
(2006) - et al.
FISH and chips: the recipe for improved prognostication and outcomes for children with medulloblastoma
Cancer Genet
(2011) - et al.
Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition
Cancer Cell
(2014) - et al.
BET bromodomain inhibition as a therapeutic strategy to target c-Myc
Cell
(2011) - et al.
HDAC and PI3K antagonists cooperate to inhibit growth of MYC-driven medulloblastoma
Cancer Cell
(2016) - et al.
Atypical teratoid/rhabdoid tumors are comprised of three epigenetic subgroups with distinct enhancer landscapes
Cancer Cell
(2016) - et al.
Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma
Cancer Cell
(2012)
Pediatric brain stem gliomas: a review
Int J Radiat Oncol Biol Phys
A detrimental effect of a combined chemotherapy-radiotherapy approach in children with diffuse intrinsic brain stem gliomas?
Int J Radiat Oncol Biol Phys
Diffuse brainstem glioma in children: critical review of clinical trials
Lancet Oncol
There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy
Int J Radiat Oncol Biol Phys
Natural history of optic pathway tumors in children with neurofibromatosis type 1: a longitudinal study
J Pediatr
Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas
Am J Pathol
Clinicopathologic study of 61 patients with ependymoma including MIB-1 immunohistochemistry
Ann Diagn Pathol
The role of prophylactic spinal irradiation in localized intracranial ependymoma
Int J Radiat Oncol Biol Phys
Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups
Cancer Cell
Defining the molecular landscape of ependymomas
Cancer Cell
CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009-2013
Neuro Oncol
Germline mutations in predisposition genes in pediatric cancer
N Engl J Med
Tumors of the brain and nervous system after radiotherapy in childhood
N Engl J Med
WHO classification of tumours of the central nervous system, revised. 4th edition
Medulloblastoma: clinical and biologic aspects
Neuro Oncol
The 2007 WHO classification of tumours of the central nervous system
Acta Neuropathol
Molecular subgroups of medulloblastoma: the current consensus
Acta Neuropathol
Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features
PLoS One
The whole-genome landscape of medulloblastoma subtypes
Nature
Correlation of neurosurgical subspecialization with outcomes in children with malignant brain tumors
Neurosurgery
Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children's Oncology Group
J Neurosurg
Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma
J Clin Oncol
Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy
J Neurosurg
Long-term neurologic and neurosensory sequelae in adult survivors of a childhood brain tumor: childhood cancer survivor study
J Clin Oncol
New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study
J Natl Cancer Inst
Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas
Acta Neuropathol
Subtypes of medulloblastoma have distinct developmental origins
Nature
The molecular basis of Turcot's syndrome
N Engl J Med
Wnt/Wingless pathway activation and chromosome 6 loss characterize a distinct molecular sub-group of medulloblastomas associated with a favorable prognosis
Cell Cycle
Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics
J Pathol
Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma
Development
Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem
Acta Neuropathol
Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations
J Clin Oncol
Molecular mechanisms and therapeutic targets in pediatric brain tumors
Sci Signal
Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma
J Clin Oncol
MYC family amplification and clinical risk-factors interact to predict an extremely poor prognosis in childhood medulloblastoma
Acta Neuropathol
Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449
N Engl J Med
Phase I study of vismodegib in children with recurrent or refractory medulloblastoma: a pediatric brain tumor consortium study
Clin Cancer Res
Pediatric brain tumors: current knowledge and therapeutic opportunities
J Pediatr Hematol Oncol
Subgroup-specific structural variation across 1,000 medulloblastoma genomes
Nature
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Disclosures: None.