Pediatric Astrocytoma

Updated: Aug 18, 2017
  • Author: Lauren R Weintraub; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Overview

Background

Brain tumors comprise approximately 20% of all childhood malignancies, second only to acute lymphoblastic leukemia in frequency. Astrocytoma is the most common brain tumor (see image shown below), accounting for more than half of all primary CNS malignancies.

This MRI shows a pilocytic astrocytoma of the cere This MRI shows a pilocytic astrocytoma of the cerebellum.

 

Astrocytomas comprise a wide range of neoplasms that differ in their extent of invasiveness, morphological features, tendency for progression, and clinical course. The most widely accepted grading schema for astrocytomas is the World Health Organization [WHO] that assigns a grade from I to IV based on the degree of anaplasia of tumor cells, proliferation index values and genetic alterations. WHO grade I tumors include pilocytic astrocytomas and subependymal giant cell astrocytomas. WHO grade II tumors include diffuse astrocytomas, oligodendrogliomas and pleomorphic xanthoastrocytomas. WHO grade III tumors include anaplastic astrocytomas and anaplastic pleomorphic xanthoastrocytomas. WHO grade IV tumors include glioblastoma multiforme and diffuse midline gliomas. [1]

Most astrocytomas are indolent low-grade (ie, WHO grade I-II) tumors for which surgical resection alone is sufficient to cure.  The prognosis decreases for low-grade tumors in unresectable locations and remains very poor for high-grade astrocytomas in spite of the addition of radiotherapy and chemotherapy.

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Pathophysiology

Pilocytic astrocytomas (ie, WHO grade I) arise throughout the neuraxis, but preferred sites include the optic nerve, optic chiasm/hypothalamus, thalamus and basal ganglia, cerebral hemispheres, cerebellum, and brain stem. These tumors show low cellularity, low proliferative and mitotic activity, and rarely metastasize or undergo malignant transformation. In general, they do not aggressively infiltrate surrounding tissue and regressive changes in long-standing lesions are common. These tumors are the principle CNS neoplasm of neurofibromatosis type 1 (NF1).  

Pilomyxoid astrocytoma (PMA) is a recently defined variant of pediatric low-grade astrocytoma. PMAs have been classified with pilocytic astrocytomas but have been found to have different histologic features and to behave more aggressively than pilocytic astrocytomas. PMAs have a tendency to disseminate and, in some reports, have a worse prognosis compared with pilocytic astrocytomas.

Diffuse astrocytomas (ie, WHO grade II) may arise in any area of the CNS but most commonly develop in the cerebrum, particularly the frontal and temporal lobes. The brain stem and spinal cord are the next most frequently affected sites, whereas the cerebellum is a distinctly uncommon site. These tumors are moderately cellular, infiltrative, and often enlarging, which distorts but does not destroy neighboring anatomical structures. Mitotic activity is generally absent. 

Anaplastic astrocytoma (ie, WHO grade III) arises in the same locations as diffuse astrocytomas, with a preference for the cerebral hemispheres. These tumors show increased cellularity, distinct nuclear atypia, marked mitotic activity, and a tendency to infiltrate through neighboring tissue. 

Glioblastoma multiforme (ie, WHO grade IV) tumors occur most often in the subcortical white matter of the cerebral hemispheres. Combined frontotemporal location with infiltration into the adjacent cortex, basal ganglia, and contralateral hemisphere is typical. Glioblastoma is the most frequent tumor of the brain stem in children, while the cerebellum and spinal cord are rare sites. These tumors are highly cellular, with high proliferative and mitotic activity. Although rapid and extensive invasion of surrounding tissue is common, distant metastasis within or outside the CNS is rare. Refer to the image below.

This section displays a typical field of a gliobla This section displays a typical field of a glioblastoma multiforme (grade IV) with pseudopalisading neovascularity, nuclear atypia, numerous mitoses, and areas of hemorrhage.

Increasing evidence indicates that the differences between the clinicopathologic entities of astrocytomas (ie, WHO grades I-IV) reflect specific genetic alterations. [2, 3]  Recent studies show that the majority of pilocytic astrocytomas possess a characteristic BRAF–KIAA1549 gene fusion. [4, 5]   Additional mutations found in low-grade gliomas include BRAFV600E and NF1. Mutations in TP53, EGFR, H3K27M, PDGFRA and PTEN are found in high-grade astrocytomas (WHO grade III and IV).  

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Epidemiology

Frequency

United States

Astrocytoma is the most common brain tumor of childhood. Researchers report that the annual incidence is approximately 14 new cases per million children younger than 15 years.

Mortality/Morbidity

In low-grade astrocytomas, complete surgical resection is associated with 5-year survival rates as high as 95-100% without further treatment. Patients with subtotal resections may have only a 60-80% survival rate over similar periods; however, after partial resection, long-term progression-free intervals may ensue. Current operative mortality rates are less than 1%. Morbidity depends largely on tumor location and is highest in diencephalic tumors, in which the incidence of hemiparesis or visual field deficits may be 10-20%. Cortical-based tumors may be associated with seizures.

In high-grade astrocytomas, the most recent 5-year survival rate is 15-30% for supratentorial lesions and less than 10% for pontine tumors. Neurologic morbidity, such as neurocognitive impairment, neuroendocrinologic deficiency, motor and coordination impairment, and cranial nerve dysfunction may occur from tumor invasion, surgical resection, and/or treatment with radiation and chemotherapy. Seizure disorders may develop depending on the tumor location.

Race

No specific racial predisposition is observed.

Sex

The male-to-female ratio is approximately 1:1, except for supratentorial low-grade gliomas, in which it is approximately 2:1.

Age

Most cases occur in the first decade of life, with the peak incidence occurring in children aged 5-9 years. High-grade supratentorial tumors occur slightly later, with a median age at diagnosis of 9-10 years.

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