Low-Grade Astrocytoma

Updated: Oct 27, 2014
  • Author: George I Jallo, MD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Overview

Background

Low-grade astrocytomas are a heterogeneous group of intrinsic central nervous system (CNS) neoplasms that share certain similarities in their clinical presentation, radiologic appearance, prognosis, and treatment. The most common intrinsic brain tumor, glioblastoma multiforme, is high grade and malignant. This contrasts with low-grade astrocytomas, which are less common and therefore less familiar to practitioners.

Improvements in neuroimaging permit the diagnosis of many low-grade astrocytomas that would not have been recognized previously. Low-grade astrocytomas are, by definition, slow growing, and patients survive much longer than those with high-grade gliomas. Proper management involves recognition, treatment of symptoms (eg, seizures), and surgery, with or without adjunctive therapy. Low-grade astrocytomas are found in both the brain and the spinal cord.

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Pathophysiology

Low-grade astrocytomas are primary tumors (rather than extraaxial or metastatic tumors) of the brain. Astrocytomas are one type of glioma, a tumor that forms from neoplastic transformation of the so-called supporting cells of the brain, the glia or neuroglia. Gliomas arise from the glial cell lineage from which astrocytes, oligodendrocytes, and ependymal cells originate. The corresponding tumors are astrocytomas, oligodendrogliomas, and ependymomas. Grading of a glioma is based on the histopathologic evaluation of surgical specimens. Several classification schemes have been proposed.

The World Health Organization (WHO) scheme is based on the appearance of certain characteristics: atypia, mitoses, endothelial proliferation, and necrosis. These features reflect the malignant potential of the tumor in terms of invasion and growth rate. Tumors without any of these features are classified as grade I. Tumors with cytological atypia alone are considered grade II (diffuse astrocytoma). Those that show anaplasia and mitotic activity in addition to cytological atypia are considered grade III (anaplastic astrocytoma) and those who exhibit all of the previous features as well as microvascular proliferation and/or necrosis are considered grade IV. [1] Thus, the low-grade group of astrocytomas are grades I and II.

A subset of low-grade astrocytomas may have features of high-grade lesions including endothelial proliferation and necrosis although they remain slow growing and well circumscribed. This subset comprises juvenile pilocytic astrocytoma (JPA) pilomyxoid astrocytoma, pleomorphic xanthoastrocytoma (PXA), and subependymal giant-cell astrocytoma (SEGA).

Low-grade astrocytomas generally cause symptoms by perturbing cerebral function (e.g seizures), elevating intracranial pressure (ICP) by either mass effect or obstruction of cerebrospinal fluid (CSF) pathways (i.e hydrocephalus), or causing neurologic (e.g paralysis, sensory deficits, aberrant behavior, headaches) and endocrine abnormalities.

Most low-grade astrocytomas tend to occur in the lobes of the cerebral hemispheres. Although pilocytic astrocytomas occur supratentorially, the cerebellum is their most common location especially in children. Pleomorphic xanthoastrocytomas are more common in the supratentorial space in a characteristic superficial location which involves both the cerebrum as well as the overlying meninges. Subependymal giant-cell astrocytomas (SEGA) are found most commonly in the wall of the lateral ventricles and are frequently associated with patients with Tuberous Sclerosis, a group of autosomal dominant disorders.

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Epidemiology

Frequency

United States

The overall incidence of primary brain and central nervous system tumors in the United States is 21.03 per 100,000. In children the rate is 5.26 per 100,000. Of all glioma subtypes, diffuse astrocytomas represent 9.1% and pilocytic astrocytomas 5.1%. [2] Although these numbers represent an approximate estimation of the epidemiology of low-grade astrocytomas, there are no studies that have addressed this group specifically. This is in part due to the fact that low-grade astrocytomas are generally categorized as part of a broader group collectively known as low-grade gliomas which include tumors derived from oligodendrocytes as well as mixed glial-neuronal tumors.

Gliomas are associated with certain phakomatoses, especially neurofibromatosis type 1 (NF-1). Low-grade astrocytomas occur more commonly in these patients, particularly in the optic nerve and chiasm. As mentioned before, subependymal giant-cell astrocytomas are found almost exclusively in patients with tuberous sclerosis.

International

The incidence of low-grade astrocytoma has not been shown to vary significantly with nationality. However, studies examining the incidence of malignant CNS tumors have shown some variation with national origin. Since some of these high-grade lesions arise from low-grade tumors, these trends are worth mentioning. Specifically, the incidence of CNS tumors in the United States, Israel, and the Nordic countries is relatively high, while Japan and Asian countries have a lower incidence. These differences probably reflect some biological differences as well as differences in pathologic diagnosis and reporting.

A study of the incidence of brain tumors in Europe concluded that of all glial tumors the astrocytic subtype is the most common with a reported incidence of 4.8 cases/100.000/year. This number represents all astrocytic tumors without a specific mention of low-grade cases. [3]

Mortality/Morbidity

Due to the inherent differences in biology and natural history of this heterogeneous patient population it is hard to determine an exact mortality rate for low-grade astrocytomas. Pylocitic tumors can potentially be cured with surgical resection while diffuse pontine gliomas constitute a very different category regarding treatment options and prognosis but nonetheless they are both classified as low-grade astrocytomas.

Pilocytic astrocytomas have a 25 year survival rate of 95% when they are cystic and well circumscribed. For cerebellar tumors that are completely resected, the 10-year survival rate is almost 100%. [4]

Race

No clear evidence has been published in the literature that low-grade astrocytomas are more common in any racial or ethnic group. In the United States, malignant CNS tumors are slightly more common in whites than in blacks. Whether this applies to low-grade tumors as well remains to be shown.

Sex

There is a slight male predominance in the incidence of primary brain and central nervous system tumors according to the latest report of the Central Brain Tumor Registry of the United States (CBTRUS). This applies both for low-grade lesions, as well as grade III and IV tumors. [2]

Age

The median age of patients diagnosed with a low-grade astrocytoma, approximately 35 years, is younger than that of patients with more malignant gliomas. Juvenile pilocytic astrocytomas have a median age at diagnosis about a decade younger than other low-grade astrocytomas. This may account for the positive influence on survival duration in some series in which the pilocytic phenotype is associated with an improved outcome. The incidence of primary brain tumors, malignant astrocytomas in particular, is increasing in elderly patients. [5] Whether this is a true increase in incidence or simply the result of higher rates of detection due to increased imaging or reporting is unknown.

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