You are in: eMedicine Specialties > Radiology > BRAIN/SPINE Astrocytoma, BrainArticle Last Updated: Jun 27, 2006AUTHOR AND EDITOR INFORMATIONAuthor: Felice J Esposito, DO, Staff Physician, Department of Radiology, Mercy Catholic Medical Center Felice J Esposito is a member of the following medical societies: American College of Radiology, American Medical Association, American Osteopathic Association, American Roentgen Ray Society, and Pennsylvania Medical Society 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 Editors: Chi-Shing Zee, MD, Chief of Neuroradiology, Professor, Departments of Radiology and Neurosurgery, University of Southern California School of Medicine; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Val Runge, MD, Robert and Alma Moreton Centennial Chair in Radiology, Professor, Editor-in-Chief of Investigative Radiology, Department of Radiology, Scott and White Clinic and Hospital; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; L Gill Naul, MD, Professor and Head, Department of Radiology, Texas A&M University College of Medicine; Chair, Department of Radiology, Chief, Section of Magnetic Resonance Imaging, Scott and White Memorial Hospital and Clinic Author and Editor Disclosure Synonyms and related keywords: primary intra-axial brain tumors, primary intraaxial brain tumors, gliomas, supratentorial tumors, grade I astrocytomas, pilocytic astrocytoma, subependymal giant cell astrocytoma, giant-cell astrocytoma, pleomorphic xanthoastrocytoma, grade II astrocytomas, protoplasmic astrocytomas, gemistocytic astrocytomas, fibrillary astrocytomas, grade III astrocytomas, anaplastic astrocytomas, grade IV astrocytomas, glioblastoma multiforme, GBM, giant cell glioblastomas, giant-cell glioblastomas, gliosarcoma variants, low-grade astrocytomas, PTEN/MMAC1, DMBT1, EGFR, p53, TP53, p16, PDGFR, retinoblastoma cell-cycle regulatory genes INTRODUCTIONBackgroundPrimary 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
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. PathophysiologyTo 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. FrequencyUnited StatesAstrocytomas 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/MorbidityThe Table below shows mortality rates, as described in the Surveillance, Epidemiology, and End Results report of data collected in 1973-1999.
*ND is no data. SexSupratentorial 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. AgeIncidences 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. AnatomySupratentorial 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. Clinical DetailsBecause 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 ExaminationThe 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 TechniquesMRI 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. DIFFERENTIALS
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| Media file 1: Normal pattern on single-voxel magnetic resonance spectroscopy (MRS) of 4 key molecules show relative heights and typical values. N-acetylaspartate (NAA) peaks at 2.0 ppm (tallest peak). Creatine (Cr) peaks at 3.0 ppm. Choline (Cho) peaks at 3.2 ppm. Myo-inositol (MI) peaks at 3.6 ppm. | |
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| Media file 2: Pilocytic astrocytoma in a 20-year-old man. Top row (left to right), Sagittal, coronal, and axial contrast-enhanced T1-weighted MRIs. Bottom row: Axial fluid-attenuated inversion recovery (FLAIR), diffusion, and apparent diffusion coefficient (ADC) images. Note the cystic mass with an intensely enhancing mural nodule in the inferior cerebellar vermis, as well as the mass effect on the brainstem, upper cervical cord, cerebellum, and fourth ventricle. | |
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| Media file 3: Grade II astrocytoma in a 27-year-old woman. Nonenhanced CT scan shows a heterogeneous, ill-defined, hypoattenuating area in the right temporal lobe. | |
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| Media file 4: Grade II astrocytoma in a 30-year-old man. Nonenhanced T2-weighted MRI shows a well-circumscribed area of increased signal intensity in the left temporal lobe. | |
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| Media file 5: Low-grade astrocytoma in a 52-year-old woman. Top row (left to right), Nonenhanced CT scan, fluid-attenuated inversion recovery (FLAIR) MRI, and diffusion-weighted MRI. Bottom row (left to right), Single-voxel spectroscopic image showing with region of interest, spectrum, and perfusion image. Images show an ill-defined, hypoattenuating lesion in the right centrum semiovale extending to the left side through the body of the corpus callosum. The lesion has increased signal intensity on the FLAIR image. The true nature of the lesion cannot be easily established on anatomic imaging. Magnetic resonance spectroscopy (MRS) shows mild elevation of the choline (Cho) peak in relation to the N-acetylaspartate (NAA) peak with an inverted lactate peak. The findings are compatible with a low-grade neoplasm. | |
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| Media file 6: Grade II astrocytoma. Left, Fluid-attenuated inversion recovery (FLAIR) image demonstrates an area of increased signal intensity in the parietooccipital region. Right, Perfusion MRI demonstrates decreased relative cerebral blood volume (rCBV), consistent with a low-grade neoplasm. The final pathologic diagnosis was a grade II astrocytoma. | |
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| Media file 7: Grade III astrocytoma in a 33-year-old woman. Nonenhanced studies (right) show a mixed-attenuation lesion (solid and cystic areas) in the right parietal lobe with adjacent vasogenic edema. After contrast enhancement (left), the solid component is enhancing. | |
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| Media file 8: Grade III astrocytoma in a 33-year-old woman. Top row (left to right), Axial nonenhanced and contrast-enhanced T1-weighted, proton densityweighted, and fluid-attenuated inversion recovery (FLAIR) MRIs. Bottom row (left to right), Sagittal nonenhanced and contrast-enhanced T1-weighted MRIs, axial diffusion-weighted images, and axial apparent diffusion coefficient (ADC) map. T1-weighted images demonstrate a well-defined area of mixed signal intensity in the right parietal lobe extending to the corpus callosum with adjacent vasogenic edema. Mixed areas represent hemorrhage. Contrast-enhanced images show minimal enhancement of the lesion. Also appreciated is dural enhancement secondary to previous intervention. | |
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| Media file 9: Grade III astrocytoma in a 71-year-old man. Contrast-enhanced (left) and nonenhanced (right) images show a cystic lesion with thick walls in the left parietal lobe, with thick rim enhancement on the enhanced image. Moderate surrounding vasogenic edema causes mass effect on the atrium of the left lateral ventricle. | |
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| Media file 10: Grade III astrocytoma in a 71-year-old man. Top row (left to right), Axial nonenhanced and contrast-enhanced T1-weighted, proton densityweighted, and fluid-attenuated inversion recovery (FLAIR) MRIs. Bottom row (left to right), Sagittal nonenhanced and contrast-enhanced T1-weighted MRIs, axial diffusion-weighted images, and axial apparent diffusion coefficient (ADC) map. Images show a cystic, well-defined lesion in the left parietal region with surrounding vasogenic edema and a thick rim enhancement on enhanced images. Diffusion and ADC images shows no evidence of acute restriction. | |
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| Media file 11: Image show no evidence of recurrence in a 37-year-old woman with a history of grade 3 astrocytoma who underwent resection 7 years ago. Coronal contrast-enhanced T1-weighted, diffusion-weighted, and apparent diffusion coefficient (ADC) imaging were initially performed, followed by multivoxel magnetic resonance spectroscopy (MRS) and perfusion imaging. Because findings on cross-sectional imaging were not conclusive, additional studies were performed. MRS shows low levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in an area of encephalomalacia, with a normal spectrum in the rest of the brain. Perfusion imaging shows no increased activity in the area of concern. These findings are compatible with gliosis. | |
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| Media file 12: Grade IV astrocytoma in a 73-year-old man. Top row (left to right), Nonenhanced CT images and fluid-attenuated inversion recovery (FLAIR) MRI. Bottom row, Axial nonenhanced and enhanced and coronal enhanced T1-weighted MRIs. CT demonstrates an inhomogeneous area of abnormal attenuation in the right temporal lobe that extends to the parietal region, with surrounding edema and mass effect. Enhanced MRI demonstrates heterogeneous enhancement, extensive vasogenic edema, and mass effect. Note the ependymal and subependymal enhancement involving the adjacent lateral ventricle and enhancement of the adjacent dura; this finding is consistent with spread. | |
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| Media file 13: Recurrent grade IV astrocytoma in the region of the right caudate and putamen in a 76-year-old man. Top row (left to right), Nonenhanced CT scan, nonenhanced T1-weighted MRI, T2-weighted MRI, and fluid-attenuated inversion recovery (FLAIR) MRI. Second row from top (left to right): Diffusion-weighted MRI, apparent diffusion coefficient (ADC) map, and axial and coronal contrast-enhanced T1-weighted MRIs. Third row from top: Perfusion-weighted MRIs show increased flow in the caudate and putamen but not in the other areas of abnormal signal intensity. Bottom row: Axial spectroscopic image shows the 2 regions of interest in the right caudate corresponding to the multivoxel spectra. Note the large, infiltrating mass centered in the right basal ganglia and extending to the right frontal lobe, temporal lobe, and insula. Image shows thick peripheral enhancement and central necrosis. Multivoxel spectroscopy demonstrates decreased N-acetylaspartate (NAA), elevated choline, and elevated lactate values in thecaudate. | |
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| Media file 14: A, Image in a patient after resection of a left frontoparietal, high-grade astrocytoma. Positron emission tomography (PET) demonstrates increased activity in this region, consistent with recurrence. B, Image in another patient being evaluated for recurrence of a high-grade astrocytoma. Image shows no abnormally increased activity to suggest recurrence. | |
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Article Last Updated: Jun 27, 2006