eMedicine Specialties > Radiology > Brain/Spine

Astrocytoma, Brain

Author: Felice J Esposito, DO, Staff Physician, Department of Radiology, Mercy Catholic Medical Center
Coauthor(s): Stephen Pirrone, ; Rajesh Mithalal, MD, Staff Physician, Department of Radiology, Mercy Catholic Medical Center; Michele Papa, MD, Professor, Department of Neuroanatomy, Second University of Naples, Italy; Mimi Huynh Pinto, DO, Staff Physician, Department of Radiology, Mercy Catholic Medical Center; Djamil Fertikh, MD, ATTENDING, Radiology Division, Association of Alexandria Radiologists; Michael L Brooks, MD, Director of Neuroradiology, Mercy Diagnostic Imaging; Medical Director, Department of Radiology, Mercy Catholic Medical Center
Contributor Information and Disclosures

Updated: Jun 27, 2006

Introduction

Background

Primary intra-axial brain tumors account for approximately two thirds of all brain neoplasms, whereas the remaining one third is made up of metastases. As a group, gliomas are the most common brain tumors and include astrocytomas, oligodendrogliomas, ependymomas, and choroid plexus tumors. Astrocytomas account for approximately 80% of all gliomas and are the most common supratentorial tumor in all age groups.

The classification of astrocytomas is currently histologic, and the new World Health Organization (WHO) classification of brain tumors is the most widely accepted system. This system has essentially replaced the Kernohan classification because its grades most closely correspond with the prognosis. The first edition was published in 1979 and was the result of nearly a decade of work. In 1993, a second edition incorporated immunohistochemical findings. A working group of experts who convened in July 1999 in Lyon, France, created the current system. Instead of dividing tumors into glial or nonglial categories, tumors are divided by their tissue of origin. Astrocytomas fall into the largest category of tumors of neuroepithelial tissue. The other categories are tumors of peripheral nerves, tumors of the meninges, lymphomas and hematopoietic neoplasms, germ-cell tumors, tumors of the sellar region, and metastatic tumors.

WHO classification of astrocytic tumors

• WHO grade II astrocytoma - Diffuse astrocytoma
  • Fibrillary astrocytomas
  • Protoplasmic astrocytomas
  • Gemistocytic astrocytoma
• WHO grade III astrocytoma - Anaplastic astrocytomas
• WHO grade IV astrocytoma - Glioblastoma
  • Giant-cell glioblastoma
  • Gliosarcoma
• WHO grade II astrocytoma - Pleomorphic xanthoastrocytoma
• WHO grade II astrocytoma - Choroid glioma
• Pilocytic astrocytomas
• Subependymal giant-cell astrocytomas

Pilocytic astrocytomas and subependymal giant-cell astrocytomas are in category 1 of the Systemized Nomenclature of Medicine (SNOMED) classification scheme. This category is defined as tumors of low or uncertain malignant potential or borderline malignancy. The remaining astrocytic tumors are category 3, or malignant. SNOMED category 2 denotes an in situ lesion, and category 0 denotes a benign lesion.

Gliomatosis cerebri is defined as an infiltrative neoplasm involving at least 2 lobes of the brain. Although it is currently defined as an epithelial neoplasm of uncertain origin, many authors believe it to be of glial origin.

Astrocytomas are often divided into circumscribed or infiltrating tumors. Pilocytic astrocytomas and subependymal giant-cell astrocytomas are circumscribed group because they tend to respect anatomic boundaries and because they do not invade. Grade II, III, and IV astrocytomas are infiltrating because of their tendency to insinuate and invade. Tumor cells are often found distant from the imaged mass. Pleomorphic xanthoastrocytomas occupy an intermediate position; although they are well circumscribed and slow growing, malignant progression may occur.

Diffuse astrocytomas (WHO grade II astrocytomas) demonstrate slow growth, moderate hypercellularity, occasional nuclear atypia, and diffuse infiltration of neighboring brain structures. These lesions have a tendency for malignant transformation, possibly dedifferentiating all the way to glioblastoma. Included in this group are protoplasmic, gemistocytic, fibrillary, and mixed variants.

Anaplastic astrocytomas (WHO grade III astrocytomas) demonstrate hypercellularity, moderate nuclear atypia, prominent mitotic activity, and diffuse infiltration. These tumors are most often the result of dedifferentiation of a grade II astrocytoma.

Glioblastomas (WHO grade IV astrocytomas) are the most malignant astrocytic tumors. They demonstrate marked nuclear atypia, high mitotic activity, microvascular proliferation, and areas of coagulative necrosis. This group includes glioblastoma multiforme (GBM) and 2 variants: giant-cell glioblastoma and gliosarcoma. Although a glioblastoma may represent a dedifferentiated grade II or III astrocytoma, most are primary glioblastomas and do not derive from a less malignant precursor.

Pleomorphic xanthoastrocytoma (WHO grade II astrocytomas) are histologically characterized by pleomorphic and lipid laden cells. When high mitotic activity or areas of necrosis are present, the term anaplastic pleomorphic xanthoastrocytoma is used.

The 2000 WHO revision added a new entity, namely, chordoid glioma. This tumor is low grade and typically involves the third ventricle of middle-aged women. Although the tumor histologically resembles a chordoma, immunohistochemical staining revealed glial-type qualities.

Pilocytic astrocytomas are generally well circumscribed and often cystic. Subependymal giant-cell astrocytomas are also well circumscribed; they are seen in patients with tuberous sclerosis.

Brain-tumor imaging has dramatically progressed over the past few decades with the development and refinement of CT, MRI, positron emission tomography (PET), and, most recently, advanced magnetic resonance (MR) sequences.

Pathophysiology

To date, the pathophysiology of astrocytoma remains is not clearly understood, though continuing research is being conducted to evaluate possible molecular pathways. Specific genes believed to play a role in astrocytoma pathogenesis include PTEN/MMAC1, DMBT1 (deleted in malignant brain tumor-1), EGFR, TP53, P16, PDGFR, and retinoblastoma cell-cycle regulatory genes. Research is also directed against disease syndromes with increased rates of astrocytomas, including neurofibromatosis 1 and 2, tuberous sclerosis, and Li-Fraumeni cancer syndrome.

Frequency

United States

Astrocytomas are the most common supratentorial intra-axial tumor in all age groups and the most common brain tumor in children. Among children, astrocytoma is second only to leukemia in cancer prevalence.

The incidence of astrocytoma is 1.22 cases per 100,000 person-years for individuals aged 0-19 years and 1.29 cases per 100,000 person-years for those aged 0-14 years. In general, the incidence of grade I or II tumors decreases with age, whereas that of grade III or IV tumors increases with age. In the 1995-1999 study involving the Central Brain Tumor Registry, the incidence of pilocytic astrocytoma peaked at ages 0-14 years, and the incidence of grade III or IV astrocytoma peaked at ages 65-74 years.

The prevalence of pediatric malignant brain tumors is estimated to be 7.9 cases per 100,000 population, affecting approximately 21,000 children in the United States. The prevalence for adults is 29.5 per 100,000 persons; therefore, more than 81,000 adults in the United States are living with a malignant brain tumor. The most common malignant brain tumor in adults is GBM.

Mortality/Morbidity

The Table below shows mortality rates, as described in the Surveillance, Epidemiology, and End Results report of data collected in 1973-1999.

Open table in new window

*ND is no data.

Sex

Supratentorial low-grade astrocytomas are more common in male individuals than in female individuals, with a male-to-female ratio of 2:1. Choroid glioma is most frequent in women. No sex predilection is observed in the other types of astrocytomas.

Age

Incidences of the types of astrocytomas depend on the patient's age. Pilocytic astrocytomas are most common in children and adolescents aged 5-15 years. Low-grade astrocytomas are most common in adults aged 25-40 years. The incidence of anaplastic astrocytomas peaks at 40-50 years. The peak incidence of GBM is in those aged 45-70 years.

Anatomy

Supratentorial astrocytomas are most common in adults. The most common locations are the cerebral hemispheres, but the hypothalamus, optic chiasma, and corpus callosum are also commonly affected.

Infratentorial astrocytomas are most common in children. These tumors most often involve the cerebellum, followed by the brainstem.

Diffuse astrocytomas preferentially involve the cerebral hemispheres. Two thirds of diffuse astrocytomas involve the frontal or temporal lobes. Glioblastomas most often involve the subcortical white matter of the cerebral hemispheres. About 98% of pleomorphic xanthoastrocytomas are supratentorial (most often in the temporal lobes) and typically superficial (in the cerebrum and meninges). Choroid glioma most often involves the third ventricle. Pilocytic astrocytomas occur throughout the CNS. The most common locations include the cerebellum, optic nerve and/or chiasm, hypothalamus, thalamus, basal ganglia, cerebral hemispheres, brainstem, and (uncommonly) spinal cord. Subependymal giant-cell astrocytomas most often originate from the walls of the lateral ventricles in patients with tuberous sclerosis.

Presentation

Because of its occupation of a confined space and its relatively soft parenchyma, the brain is especially vulnerable to the mass effect and edema a neoplastic process causes. The effects of a tumor on the brain depend on the characteristics of the occupied brain and the nature of the tumor. Mass effect is less deleterious in atrophic brain than in normal brain because the vault increases the space for displacement of the brain parenchyma. Of course, an aggressive tumor causes more mass effect and edema than does a benign tumor.

Furthermore, the location of the tumor is of fundamental importance. For example, tumor involving a frontal lobe may simply cause personality changes, whereas one that affects the medulla or obstructs the third ventricle most likely results in a poor outcome. Increased intracranial pressure associated with an intracranial mass is an important cause of brain herniation and associated morbidity and mortality.

Increased intracranial pressure, which is observed in 50-75% of patients, causes the most common initial presentations of patients with brain tumors. These presentations include seizures, headache, vomiting, changes in behavior, and changes in mental status. These same changes can also be the result of direct tumoral invasion. Seizures occur in 25-50% of patients. Focal neurologic changes can occur when certain anatomic areas are affected. Children often present with behavioral changes and bulging fontanels.

Preferred Examination

The diagnosis of astrocytoma ultimately requires a tissue sample.

At present, contrast-enhanced MRI is the imaging modality of choice. The large amount of streak artifact in the posterior fossa that can be encountered with CT does not affect MRI. The sensitivity of MR studies is 82-100%, and the specificity is 81-100%. The excellent intrinsic contrast of conventional MRI makes it a sensitive study. The addition of contrast material and additional sequences can substantially improve the specificity. Additional techniques include MR spectroscopy (MRS), which allows clinicians to characterize the chemical composition of the mass by determining the presence and/or alteration of components such as lactate, N -acetylaspartate (NAA), choline (Cho), and myo-inositol (Ins).

Two investigational sequences are often helpful in difficult cases, though the resultant images should be interpreted with caution. The first is perfusion-weighted imaging improves characterization of the tumor and aids in equivocal cases when other causes of signal abnormality are suggested, such as with demyelinating lesions, infarcts, and abscesses. The second is diffusion-tensor imaging, which can demonstrate the relationship of the tumor to white matter tracts.

Although MRI has distinct advantages over CT, contrast-enhanced CT is still used at many centers as the imaging modality for the evaluation of intra-axial mass lesions. The sensitivity of contrast-enhanced CT is 65-100%, and the specificity is 72-100%. Positive aspects of CT include relatively short scanning times, decreased cost, and an open environment for patients with claustrophobia.

Limitations of Techniques

MRI and CT can depict the gross morphologic characteristics of the tumor, its relationship with adjacent tissue, and certain aspects of the chemical composition of the tumor (with MRS). Perfusion-weighted and diffusion-tensor images must be interpreted with caution.

Tumor margins are often difficult to determine with accuracy. Studies have demonstrated that the extent of tumoral involvement in grades I-III astrocytomas is underestimated when current conventional imaging is used. Although MRS has been useful, it also causes underestimation of the tumor burden. Tumor cells have been demonstrated well beyond the margin of any imaging abnormality.

Although imaging is instrumental in diagnosing the tumor and in evaluating the extent of disease or recurrence, only biopsy helps in determining the grade of tumor.

Differential Diagnoses

Other Problems to Be Considered

Supratentorial mass in an adult

Astrocytoma
Oligodendroglioma
Ependymoma
Metastasis
Meningioma
Lymphoma
Pineal gland tumors
Infarct

Supratentorial mass in a child

Astrocytoma
Ganglioglioma
Primitive neuroectodermal tumors
Dysembryoplastic neuroectodermal tumors
Ependymoma
Pleomorphic xanthoastrocytomas

Infratentorial mass in an adult

Astrocytoma
Metastasis
Hemangioblastoma
Medulloblastoma
Ependymoma
Meningioma
Cerebellar-pontine angle schwannoma
Infarct

Infratentorial mass in a child

Astrocytoma (usually pilocytic)
Medulloblastoma
Ependymoma
Epidermoid inclusion cyst
Craniopharyngioma

Astrocytomas can occur in the white mater of the spinal cord (mostly in children).

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