Supratentorial hemispheric low-grade gliomas of childhood

Roger J Packer MD (Dr. Packer of George Washington University; Senior Vice President, Center for Neuroscience and Behavioral Medicine; and Gilbert Endowed Distinguished Professor in Neurofibromatosis and Director, Gilbert Neurofibromatosis Institute and Brain Tumor Institute, Children’s National Health System, has no relevant financial relationships to disclose.)
Originally released October 14, 1996; last updated August 11, 2017; expires August 11, 2020

This article includes discussion of supratentorial hemispheric low-grade gliomas of childhood, cortical gliomas, and supratentorial astrocytomas. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Supratentorial low-grade gliomas are comprised of a variety of different histological subtypes. 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 of childhood is a seizure.

 

• Supratentorial, pilocytic astrocytomas of childhood 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 tumors into predominantly protoplasmic or fibrillary types (Bailey and Cushing 1926). 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 (Russell and Rubinstein 1989). 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 (Kernohan et al 1949). 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 (Kleihues et al 1993; Louis et al 2007). 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 (Louis et al 2016).

Molecular understandings may in time dramatically affect classification and insights into tumor pathogenesis. The 2016 revised WHO classification of central nervous system tumors does not include molecular subclassification (Louis et al 2016). BRAF point mutations have been found in pleomorphic xanthoastrocytomas (Dias-Santagata et al 2011). BRAF mutations, especially fusion protein abnormalities, are common in pilocytic astrocytomas and gangliomas (Pfister et al 2008; Dougherty et al 2010; Schindler et al 2011; Lin et al 2012; Packer et al 2017; Ryall et al 2017).

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 (Taratuto et al 1984; VandenBerg et al 1987; Dumas-Duport et al 1988). Other rare forms of mixed neuronal tumors are also included in the 2017 WHO classification schema (Louis et al 2016). 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.

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

Diffuse astrocytic and oligodendroglial tumors

• Diffuse astrocytoma, IDH-mutant

 

- Gemistocytic astrocytoma, IDH-mutant

• Diffuse astrocytoma, IDH-wildtype
• Diffuse astrocytoma, NOS

Other astrocytic tumors

• Pilocytic astrocytoma

 

- Pilomyxoid astrocytoma

• Subependymal giant cell astrocytoma
• Pleomorphic xanthoastrocytoma
• Anaplastic pleomorphic xanthoastrocytoma

Other gliomas

• Choroid glioma of the third ventricle
• Angiocentric glioma
• Astroblastoma

Neuronal and mixed neuronal-glial tumors

• Dysembryoplastic neuroepithelial tumour
Gangliocytoma
• Dysplastic cerebellar gangliocytoma

 

- (Lhermitte-Duclos disease)

• Desmoplastic infantile astrocytoma and ganglioglioma
• Papillary glioneuronal tumour
• Rosette-forming glioneuronal tumour
• Diffuse leptomeningeal glioneuronal tumour
Central neurocytoma
• Extraventricular neurocytoma
• Cerebellar liponeurocytoma
• Paraganglioma

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