Pediatric low-grade gliomas

Abstract

Pediatric low-grade gliomas encompass a heterogeneous set of tumors of different histologies. Cerebellar pilocytic astrocytomas occur most frequently followed by supratentorial diffuse fibrillary astrocytomas. Recent research has implicated activation of the RAS/RAF/MEK pathway in tumorigenesis of these tumors. Surgery is the mainstay of therapy. Overall survival rates for patients whose tumors are completely resected are 90% or greater, 10 years from diagnosis. Conversely, most optic pathway/hypothalamic, deep midline, and brain stem gliomas have minimal potential for resection; these tumors can be difficult to treat and deserve special attention. Combination chemotherapy is currently recommended as front-line adjuvant treatment for progressive or recurrent tumors. Second-line radiotherapy can also improve overall survival but is associated with more frequent and significant neurocognitive, endocrine, and other long-term toxicities.

Conflict of interest statement

The authors have no conflicts of interest to disclose with regard to this article.

Figures

Figure 1

Distribution by location of pediatric low-grade gliomas. Shown are the approximate frequencies of low-grade gliomas compared with all pediatric central nervous system tumors.

Figure 2

Postgadolinium magnetic resonance (MR) images of (A) optic nerve glioma (axial), (B) optic chiasm/hypothalamic glioma (coronal), and (C) optic tract/radiation tumor (axial).

Figure 3

Sagittal postgadolinium magnetic resonance image of a pilocytic astrocytoma of the cerebellum.

Figure 4

Axial magnetic resonance images of a right thalamic fibrillary astrocytoma status postbiopsy. A, Heterogeneous and hyperintense on T2-weighted images. B, Minimal enhancement on postgadolinium imaging. The patient had left hemiparesis. Because of its location, the tumor was treated with chemotherapy.

Figure 5

Pediatric low-grade glioma tumorigenesis. BRAF, an oncogene implicated in malignant melanoma and other carcinomas, may be involved in the tumorigenesis of sporadic low-grade gliomas. A BRAF fusion gene with increased kinase activity upregulates the downstream MEK/ERK pathway and results in increased transcriptional activity and cellular proliferation. Low-grade gliomas in children with susceptibility syndromes also reveal some of the pathways leading to tumorigenesis; inactivation of the tumor suppressor neurofibromin in neurofibromatosis type 1 results in RAS activation and upregulation of the RAS/RAF/MEK pathway; in tuberous sclerosis, mutation in 1 of 2 tumor suppressor genes, TSC1 or TSC2, can lead to direct activation of the mammalian target of rapamycin pathway. Neurofibromatosis type 1 tumors also reveal increased mammalian target of rapamycin expression, albeit by different mechanisms.

Figure 6

Magnetic resonance (MR) images of low-grade gliomas of the brain stem. A, Postgadolinium sagittal image of a dorsally exophytic glioma. B, Postgadolinium sagittal image of a cervicomedullary glioma. C, T2-weighted sagittal image of a tectal glioma.