Brain tumors in children

Brain tumors are the most common solid malignancies and the leading cause of death from cancer in children.

Tumors of the CNS account for 20% of childhood cancers I and are  second only to leukemia in frequency. 

Age adjusted incidence of brain tumors in children in the US is 5.65 cases per hundred thousand population with 0.72 deaths per hundred thousand among children who are newborn to 14 years of age.

Low-grade gliomas are the most frequent brain tumors of childhood and account for one third of all cases if mixed glioneoronal  and neuronal tumors are included.

Unlike low-grade gliomas in adults, low-grade gliomas in children rarely transform into higher brain tumors.

 I D H 2 or IDH 2 mutants in  low-grade gliomas in adults is much less common in childhood low grade gliomas.

Most low-grade tumors have one of more alterations in the MAPK pathway, including mutation or fusion of the BRAF oncogene, NF1 mutation, fibroblast growth factor receptor 1 mutation, and neirotrophic tyrosine receptive kinase (NTRK) family fusions.

BRAF mutations in children’s low-grade gliomas is associated with a poor prognosis to conventional chemo radiation.

Treatment for most low-grade gliomas in  children is surgery to establish the diagnosis and maximum resection.

In  children with low-grade gliomas the five year progressive free survival is about 69%, and the overall survival about 95%. 

Risk factors for progression are, young age, incomplete resection, fibrillary histologic features, and hypothalamic or chiasmatic location.

Gross  resection of low-grade gliomas may not be possible,  and since many of these tumors are indolent, observation with surveillance is sometimes an option. 

Radiotherapy is effective for recurrent or residual low-grade gliomas with a five-year progression  free  survival of 71% and overall survival of 93%.

Adjuvant chemotherapy in this setting is considered because of concern about neurotoxic effects of radiation on the developing brain and agents showing to be effective, either alone, or in combination, include: vincristine , carboplatinum,  inblastinr, 6-thioguanine, procarbaxine, , lomistine, cisplatinum, etoposide , and irinotecan.

The role of temozolomide is not clear in low-grade gliomas.

Pilocytic astrocytomas are the most common astrocytomas of childhood, counting for about 20% of brain tumors in children, adolescents, and young adults.

Pilocytic astrocytomas are generally slow growing and circumscribed. 

Pilocystic astrocytomas are associated with a 10 year survival exceeding 90%.

High grade gliomas account for 10% of brain tumors in children and have a poor prognosis.

Despite therapy 70 to 90% of affected children die within two years after diagnosis.

High grade gliomas have driver mutations of family of histone H3.

These tumors are associated with worth survival than wild type counter parts.

H3K27 alterations are specific for diffuse midline high-grade gliomas in children.


H3G 34 mutant arises in the cerebral hemispheres in older children and young adults.

Histone mutations are identified in more than 80% of midline high-grade gliomas any more than 40% of those in the central hemispheres, predominantly in children.

Diffuse intrinsic Pontine glioma (DIPG) is often associated mutations in histone protein H3 genes and is the leading cause of brain tumor related deaths in childhood.

Treatment options are limited because of the location, infiltrate of nature and the aggressive behavior of this tumor and despite transient benefit with standard radiotherapy there is progressive neurologic deterioration, with a median survival of less than one year and two year survival under 10%.

A third subtype is the diffuse pediatric type high grade  glioma, H3 wild type 

 IDH wild type: aggressive tumors usually found in the cerebral hemispheres with a poor prognosis. 

A fourth subtype a distinct neoplasm in newborns and infants often harbors receptor tyrosine kinase gene fusions including ALK, NTRK, ROS1 , and MET4.

: potentially targetable  with improved outcomes.

Treatment is standard adjuvant therapy with focal palliative irradiation, but long-term survival is poor with no appreciable improvement in outcomes in the past 50 years for pediatric high grade gliomas.

Three-year event free survival an overall survival rate for children with high-grade gliomas or 10% and 20%, respectively. 

The outcome for diffuse midline gliomas of the pons come with a median survival of four months in the absence of radiotherapy, and only 8 to 11 months with radiotherapy.

Chemotherapy and targeted therapy appear to have limited effectiveness in the treatment of high grade gliomas in children.

Temozolomide fails to improve outcome in children with high-grade gliomas.

Ependymomas is the third most common brain tumors of childhood, after gliomas and medulloblastomas, and account for 5 to 10% of CNS tumors in children. 

90% of ependymomas are intracranial with most arising in the posterior fossa, and the remainder in the spine.

There are at least nine molecular subtypes classified on histologic characteristics, molecular features and location.

Ependymomas are still classified as grade one, two, or three according to the degree of anaplasia.

Children with nonmetastatic Ependymomas are initially treated with maximum safe resection followed by conformal radiation, except for infants. 

Chemotherapy’s role has not been established. 

The long-term outcome of childhood ependymomas remains poor with ten year rates  of overall. And progressive free survival of 50% and 30%, respectively.

Embryonal tumors primarily affect young children and account for approximately 20% of childhood brain tumors.

Such tumors arising in the posterior fossa are called medulloblastomas, and those in the pineal region are called Pineoblastomas.

Medulloblastomas are the most common malignant brain tumors of childhood and usually arise in the cerebellum.

Patients  with medulloblastoma  present with signs of increased intracranial pressure or cerebeller dysfunction.

Medulloblastomas account for more than 60% of childhood embryonal tumors, 70% of occur children under the age of 10 years, affecting boys more than girls.

One third of cases are rising children under the age of three years.

The wingless/integrated (WNT) activated subtype accounts for 10% of all major medulloblastomas occurring in older children or adults.

WNT medulloblastomas are frequently associated with accumulation of beta-catenin, encoded by CTNNBI, which is present in 90% of cases and propels oncogenesis.

WNT medulloblastomas have a very good prognosis with a 10 year event free survival rate exceeding 95%.

Sonic hedgehog (SHH) activated medulloblastomas account for 30% ofmedulloblastomas,  and have an equal sex distribution.

Sonic hedgehog (SHH) activated medulloblastomas are usually located in the cerebellar hemispheres.

In contrast to  WNT medulloblastomas, hedgehog (SHH) medulloblastomas have more biologic and clinical relevant heterogeneity.

SHH activated medulloblastomas that have TP 53 mutations have a poor prognosis.

TERT promoted mutations that affect structural maintenance of the telomere occur in 40% of SHHmedulloblastomas and are present in almost all cases in adults.

Non-WNT and non-SHHmedulloblastomas affect males more than females, and are most likely to have metastasized at the time of presentation.

These lesions are located in the cerebellar midline, and usually have classic large cell anaplastic histologic features.

management of medulloblastomas consist of maximal safe resection, followed by radiation and chemotherapy.





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