Astrocytoma 

  • Author: Benjamin Kennedy; Chief Editor: Jules E Harris, MD   more...
 
Updated: Jan 17, 2012
 

Background

Astrocytomas are CNS neoplasms in which the predominant cell type is derived from an immortalized astrocyte.[1] Two classes of astrocytic tumors are recognized—those with narrow zones of infiltration (eg, pilocytic astrocytoma, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma) and those with diffuse zones of infiltration (eg, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma). Members of the latter group share various features, including the ability to arise at any site in the CNS, with a preference for the cerebral hemispheres; clinical presentation usually in adults; heterogeneous histopathological properties and biological behavior; diffuse infiltration of contiguous and distant CNS structures, regardless of histological stage; and an intrinsic tendency to progress to more advanced grades. See the image below.

Gross specimen of a low-grade astrocytoma. Gross specimen of a low-grade astrocytoma.

Numerous grading schemes based on histopathologic characteristics have been devised, including the Bailey and Cushing grading system, Kernohan grades I-IV, World Health Organization (WHO) grades I-IV, and St. Anne/Mayo grades 1-4. Regions of a tumor demonstrating the greatest degree of anaplasia are used to determine the histologic grade of the tumor. This practice is based on the assumption that the areas of greatest anaplasia determine disease progression.

This article focuses on the widely accepted WHO grading scheme that relies on assessments of nuclear atypia, mitotic activity, cellularity, vascular proliferation, and necrosis.[2] WHO grade I corresponds to pilocytic astrocytoma, WHO grade II corresponds to low-grade (diffuse) astrocytoma, WHO grade III corresponds to anaplastic astrocytoma, and WHO grade IV corresponds to glioblastoma multiforme (GBM). This article is confined to low-grade and anaplastic astrocytomas. GBM and pilocytic astrocytoma are not discussed in this article (for more information, see Glioblastoma Multiforme).

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Pathophysiology

Regional effects of astrocytomas include compression, invasion, and destruction of brain parenchyma. Arterial and venous hypoxia, competition for nutrients, release of metabolic end products (eg, free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (eg, cytokines) disrupt normal parenchymal function. Elevated intracranial pressure (ICP) attributable to direct mass effect, increased blood volume, or increased cerebrospinal fluid (CSF) volume may mediate secondary clinical sequelae. Neurological signs and symptoms attributable to astrocytomas result from perturbation of CNS function. Focal neurological deficits (eg, weakness, paralysis, sensory deficits, cranial nerve palsies) and seizures of various characteristics may permit localization of lesions.[3]

Infiltrating low-grade astrocytomas grow slowly compared to their malignant counterparts. Doubling time for low-grade astrocytomas is estimated at 4 times that of anaplastic astrocytomas. Several years often intervene between the initial symptoms and the establishment of a diagnosis of low-grade astrocytoma. One recent series estimated the interval to be approximately 3.5 years. The clinical course is marked by a gradual deterioration in half of cases, a stepwise decline in one third of cases, and a sudden deterioration in 15% of cases. Seizures, often generalized, are the initial presenting symptom in about half of patients with low-grade astrocytoma.

For patients with anaplastic astrocytomas,[4] the growth rate and interval between onset of symptoms and diagnosis is intermediate between low-grade astrocytomas and glioblastomas. Although highly variable, a mean interval of approximately 1.5-2 years between onset of symptoms and diagnosis is frequently reported. Compared to low-grade lesions, seizures are less common among patients with anaplastic astrocytomas. Initial presenting symptoms most commonly are headache, depressed mental status, and focal neurological deficits.

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Epidemiology

Frequency

United States

The annual incidence of glioma in the United States is 5.4 cases per 100,000 population.

International

Incidence differences are not significant between the United States and other countries.

Mortality/Morbidity

Morbidity and mortality, as defined by the length of a patient's history and the odds of recurrence-free survival, are correlated most highly with the intrinsic properties of the astrocytoma in question. Typical ranges of survival are approximately 10 years from the time of diagnosis for pilocytic astrocytomas (WHO grade I), more than 5 years for patients with low-grade diffuse astrocytomas (WHO grade II),[5] 2-5 years for those with anaplastic astrocytomas (WHO grade III), and less than 1 year for patients with glioblastoma (WHO grade IV).

Race

Although genetic determinants are recognized in astrocytoma development and progression, astrocytomas do not differ intrinsically in incidence or behavior among racial groups. Demographic and sociological factors, such as population, age, ethnic attitude toward disease, and access to care, have been reported to influence measured distributions.

Sex

No clear sex predominance has been identified in the development of pilocytic astrocytomas. A slight male predominance, with a male-to-female ratio of 1.18:1 for development of low-grade astrocytomas, has been reported. A more significant male predominance, with a male-to-female ratio of 1.87:1 for the development of anaplastic astrocytomas, has been identified.

Age

Most cases of pilocytic astrocytoma present in the first 2 decades of life. In contrast, the peak incidence of low-grade astrocytomas, representing 25% of all cases in adults, occurs in people aged 30-40 years. Ten percent of low-grade astrocytomas occur in people younger than 20 years; 60% of low-grade astrocytomas occur in people aged 20-45 years; and 30% of low-grade astrocytomas occur in people older than 45 years. The mean age of patients undergoing a biopsy of anaplastic astrocytoma is 41 years.

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Contributor Information and Disclosures
Author

Benjamin Kennedy  Columbia University College of Physicians and Surgeons

Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey N Bruce, MD  Edgar M Housepian Professor of Neurological Surgery Research, Vice-Chairman and Professor of Neurological Surgery, Director of Brain Tumor Tissue Bank, Director of Bartoli Brain Tumor Laboratory, Department of Neurosurgery, Columbia University College of Physicians and Surgeons

Jeffrey N Bruce, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Neurological Surgeons, American Society of Clinical Oncology, Congress of Neurological Surgeons, New York Academy of Sciences, North American Skull Base Society, Pituitary Society, Society for Neuro-Oncology, and Society of Neurological Surgeons

Disclosure: NIH Grant/research funds Other

Specialty Editor Board

Robert C Shepard, MD, FACP  Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International

Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

Additional Contributors

We wish to acknowledge previous contributions to this chapter from Patrick Senatus, MD, PhD and Allen Waziri, MD.

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Low-grade fibrillary astrocytoma and low cellularity with minimal nuclear atypia.
Fibrillary astrocytoma with microcyst formation.
Gemistocytic astrocytoma tumor cells have eosinophilic cytoplasm with nuclei displaced to the periphery.
Characteristic pilocytic astrocytoma, long bipolar tumor cells, and Rosenthal fibers.
Anaplastic astrocytoma with high cellularity with marked nuclear atypia.
Gross specimen of a low-grade astrocytoma.
Axial CT scan, precontrast and postcontrast, shows a low-grade astrocytoma of the left frontal lobe. The tumor is nonenhancing.
Coronal postcontrast T1-weighted MRI shows a low-grade astrocytoma in the right inferior frontal lobe just above the sylvian fissure. No enhancement is present post–gadolinium administration.
Axial T2-weighted MRI shows a low-grade astrocytoma of the inferior frontal lobe with mild mass effect and no surrounding edema.
 
 
 
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