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  • Updated 12.29.2023
  • Released 10.14.1996
  • Expires For CME 12.29.2026

Hemispheric low-grade gliomas and neuronal and glioneuronal tumors of childhood



Supratentorial low-grade gliomas and neuronal mixed neuronal-glial tumors are comprised of a variety of different histological subtypes. In the revised “2021 WHO Classification of CNS Tumors,” the glial tumors will be either pediatric-type diffuse low-grade gliomas or circumscribed astrocytic tumors, predominantly pilocytic astrocytomas. Fourteen distinct subvarieties of glioneural and neuronal tumors are recognized (85). Outcome is excellent after gross total resection, but some tumors may arise from infiltration of critical areas of brain structure where aggressive surgery is relatively contraindicated. For these lesions, radiation therapy and, in some cases, chemotherapy may be indicated. In addition, biologically based therapy utilizing molecular-targeted agents is becoming an increasing reality. The author summarizes these new approaches and the clinical implications of new biological insights. New molecular information has been added and its clinical implications discussed.

Key points

• The most common presentation of supratentorial low-grade gliomas and neuronal mixed neuronal-glial tumors of childhood is a seizure.

• Supratentorial, pilocytic astrocytomas of childhood and some and neuronal and mixed neuronal-glial tumors can be cured after total resection without any additional chemotherapy.

• Differential diagnosis may be difficult in infancy, as congenital astrocytomas may be difficult to classify.

Historical note and terminology

Supratentorial low-grade gliomas of childhood are a subset of primary central nervous system tumors, comprising a variety of different histological types. These low-grade tumors have an extremely variable growth rate, which, although somewhat related to the histological subtype of the tumor, may be relatively unpredictable even within a single glial subtype. These tumors have been subdivided primarily on the basis of their cytologic architecture. In the 1920s, Bailey and Cushing separated childhood low-grade supratentorial low-grade glial tumors into predominantly protoplasmic or fibrillary types (04). As time has gone on, many other classification schemas have been used. The terms "diffuse," "protoplasmic," and "gemistocytic" have been used by some authors. Russell and Rubinstein used the descriptive terms "fibrillary," "protoplasmic," "pilocytic," and "gemistocytic" to classify the majority of low-grade cerebral gliomas (114). The Kernohan grading system separated low-grade gliomas into either grade 1 or grade 2 astrocytomas, using grades 3 and 4 to designate malignant tumors (64). In the World Health Organization histological typing of central nervous system tumors, low-grade gliomas were classified primarily under the nomenclature of “astrocytoma” and then subdivided into fibrillary, protoplasmic, or gemistocytic astrocytomas (68; 83). The pilocytic astrocytoma has been given its own separate subgroup. Other tumor types believed to be of glial lineage, such as the pleomorphic xanthoastrocytoma and subependymal giant astrocytoma, have also been placed within the astrocytoma grouping.

By convention, other tumor types are often included in the general category of low-grade glial tumors. Oligodendroglial tumors and mixed gliomas do not have frank areas of histological anaplasia, and are often included in series reviewing childhood low-grade cortical tumors. Astroblastoma is a distinctive tumor that some authors have considered to have a poor prognosis but other authors have considered to be a relatively benign form of childhood glioma. In the 2016 World Health Organization classification of central nervous system tumors, pilocytic astrocytoma, subependymal giant cell astrocytoma, and angiocentric glioma are considered grade 1 tumors. Diffuse astrocytoma is considered a grade 2 lesion, with the IDH mutant being a distinct entity, which infrequently arises in pediatric-aged patients until adolescents or the teenage years. Pleomorphic xanthoastrocytoma is also a grade 2 lesion (84).

Low-grade astrocytomas may also be intermixed with cells that are apparently neuronally derived. These neuronal and mixed neuronal-glial tumors are also often included in series reviewing childhood low-grade glial tumors. In the World Health Organization categorization, tumors composed predominantly of mature ganglion cells with a minor component of supportive non-neoplastic glial cells have been termed "gangliocytomas." The term "ganglioglioma" has been used predominantly to designate a tumor where there seems to be neoplastic neuronal cells intermixed with predominantly glial neoplastic cells. Two more tumor types, the desmoplastic infantile ganglioglioma and the dysembryoplastic neuroepithelial tumor, have also been included in reviews of low-grade cortical tumors (125; 127; 27). Other rare forms of mixed neuronal tumors are also included in the 2017 WHO classification schema (84). In very low-grade diffuse tumors, separation of the leading edge of the low-grade tumor from normal surrounding brain is often microscopically impossible. Arbitrary decisions are often made concerning whether a lesion is a true low-grade glioma or an area of reactive gliosis. Molecular understandings have dramatically affected classification and insights into tumor pathogenesis.

The 2021 revised WHO classification of central nervous system tumors increasingly includes molecular subclassification (85). This is discussed in detail in the biological basis section (102; 25; 24; 116; 82; 59; 98; 115; 30). Combined molecular and epigenetic (including methylation data) are changing how these tumors are classified, but more conventional histologic features need to be incorporated cannot be for the most impactful understanding of an individual tumor (36). Some diffuse low-grade gliomas and glioneuronal tumors are diagnosed on the basis of molecular finding, including methylation clustering (36).

Table 1. WHO Classification of Low-Grade Glial and Glioneuronal Tumor

Pediatric-type diffuse low-grade gliomas

• Diffuse astrocytoma, MYB- or MYBL1-altered
• Angiocentric glioma
• Polymorphous low-grade neuroepithelial tumor of the young
• Diffuse low-grade glioma, MAPK pathway-altered

Circumscribed astrocytic gliomas

• Pilocytic astrocytoma

• High-grade astrocytoma with piloid features
• Pleomorphic xanthoastrocytoma
• Subependymal giant cell astrocytoma
• Choroid glioma
• Astroblastoma, MN1-altered

Glioneuronal and neuronal tumors

• Ganglioglioma
• Desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytoma
• Dysembryoplastic neuroepithelial tumor

• Diffuse glioneuronal tumor with oligodendroglioma like features and nuclear clusters
• Papillary glioneuronal tumor
• Rosette-forming glioneuronal tumor
• Myxoid glioneuronal tumor
• Diffuse leptomeningeal glioneuronal tumor
• Gangliocytoma
• Multinodular and vacuolating neuronal tumor
• Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)
• Central neurocytoma
• Extraventricular neurocytoma
• Cerebellar liponeurocytoma

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