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Based on data collected from several central cancer registries during the years 2007-2011, the Central Brain Tumor Registry of the United States (CBTRUS) estimates that 67,900 new cases of primary brain and central nervous system (CNS) tumors will be reported in 2014—one third of which will be malignant. The brain and CNS are also common sites of secondary tumor implantation; metastases may occur up to 10 times more frequently than primary brain tumors.
The 2014 CBTRUS statistical report found that brain and CNS tumors are the most common neoplasm among those aged 0 to 19 years, with an average age-adjusted incidence rate slightly higher than leukemia. Children and young adults generally have better survival outcomes for most histologies; survival estimates have a large variation depending on tumor histology, ranging from a 5-year survival rate of 94% for pilocytic astrocytoma to 5% for glioblastoma.
The fourth edition of the World Health Organization (WHO) classification of tumors of the CNS was published in 2007 and continues to improve and expand histologic and clinical diagnostic criteria that enable the possibility of worldwide communication, clinical trials, and epidemiologic studies. In 2007 several new entities and histologic variants were added and genetic profiles were updated and discussed in a review article. The WHO-edited book publication includes concise commentary on the clinicopathologic characteristics of each tumor type. Box 9-1 is a list of tumors discussed in this chapter, which have been organized into clinically and imaging-relevant histology groups and reflect the 2007 WHO classification.
Circumscribed
Pilocytic astrocytoma
Pleomorphic xanthoastrocytoma
Subependymal giant cell astrocytoma
Diffuse
Low-grade astrocytoma
Optic pathway glioma
Brainstem glioma
Anaplastic astrocytoma
Glioblastoma
Gliomatosis cerebri
Gliosarcoma
Low-grade oligodendroglioma
Anaplastic oligodendroglioma
Ependymoma
Anaplastic ependymoma
Subependymoma
Choroid plexus papilloma
Choroid plexus carcinoma
Ganglioglioma
Gangliocytoma
Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos)
Desmoplastic infantile ganglioglioma
Dysembryoplastic neuroepithelial tumor
Central neurocytoma
Pineoblastoma
Pineocytoma
Medulloblastoma
CNS primitive neuroectodermal tumor
Schwannoma
Neurofibroma
Malignant peripheral nerve sheath tumors
Meningioma
Melanocytic tumors (melanocytoma, malignant melanoma, meningeal melanomatosis, diffuse melanocytosis)
Hemangioblastoma
Mesenchymal tumors
Lipoma
Chondrosarcoma
Rhabdomyosarcoma
Hemangiopericytoma
Primary CNS lymphoma
Secondary CNS lymphoma
Granulocytic sarcoma (chloroma)
Germinoma
Teratoma
Other germ cell tumors (embryonal carcinoma, yolk sac tumor, and choriocarcinoma)
Pituitary adenoma
Microadenoma
Macroadenoma
Craniopharyngioma
Rathke's cleft cyst
Tumors of the neurohypophysis (granular cell tumor, Langerhans cell histiocytosis)
Chordoma
Metastases to the brain
Metastases to the skull and intracranial dura
Leptomeningeal metastasis (leptomeningeal carcinomatosis)
Although many brain and CNS tumors are not histologically confirmed, particularly those with benign behavior, the most frequently reported histology overall in the United States from 2014 CBTRUS data was meningioma (36%) followed by glioblastoma (15%). Tumors of the pituitary gland and nerve sheath tumors combined account for about one fourth of all tumors, the vast majority of which are nonmalignant.
The presenting symptoms in most patients with intracranial neoplasms are often nonspecific. Headache has been shown to occur in a majority of patients with primary brain tumors; indeed, headache is a common initial presentation for patients with high-grade gliomas. The headache is frequently described as diffuse and more severe in the morning and often dissipates in a few hours even without treatment. When unilateral, it can accurately indicate the hemisphere involved by tumor. Episodes of confusion or change in behavior also commonly bring the patient to the physician but can be confused with depression and result in delay of diagnosis. It is the persistent and progressive nature of the symptoms, often with development of visual disturbances or protracted nausea and vomiting, that eventually leads to consideration of brain tumor as a diagnostic possibility. Less common but more declarative presentations are focal neurologic symptoms (e.g., unilateral weakness, aphasia) and onset of seizures, the type and associated symptoms of which vary by tumor location. Seizures occur more frequently in low-grade gliomas and meningiomas than in higher-grade gliomas and lymphomas.
Intracranial neoplasms produce symptoms by three mechanisms: (1) infiltration and destruction of normal tissues (e.g., by a glioblastoma), (2) localized cortical irritation or depression (e.g., by a convexity meningioma), or (3) expansion within the rigid and unyielding cranial vault. Edema of the white matter adjacent to the tumor is often extensive and may account for much of the patient's symptomatology and neurologic deficit, an impression that is verified by the striking improvement, both clinically and on imaging, exhibited by many patients after systemic administration of corticosteroids. An increase in intracranial pressure above the normal level of 180 mm H 2 O commonly accompanies an expanding intracranial mass. Headache, nausea, vomiting, and sixth cranial nerve palsy may reflect increased intracranial pressure. Prolonged or significantly elevated intracranial pressure manifests clinically as loss of attentiveness, apathy, and drowsiness. These signs of depressed cerebral function are most likely caused by diminished cerebral blood flow secondary to distention of the intracranial contents. This distention also produces traction on the overlying meninges, probably accounting for the headache, nausea, and vomiting that occur with chronic intracranial hypertension.
Brain imaging is routinely performed using computed tomography (CT) or magnetic resonance imaging (MRI), typically after intravenous (IV) administration of iodinated contrast media (CT) or gadolinium contrast (MRI). The goals of diagnostic imaging in the patient with suspected intracranial tumor include detection of the presence of a neoplasm, localization of the extent of the tumor (including definition of involvement of key structures and assessment of the presence and severity of secondary changes [e.g., edema, herniation, hemorrhage]), and characterization of the nature of the process.
Imaging (usually MRI) is also extensively used in treatment planning before surgery or radiation to define the gross tumor margins and permit selection of the safest approach to the lesion. Increasingly, various functional/physiologic applications of MRI are employed preoperatively to determine the location of functionally eloquent cortex and critical white matter tracts, which can then be avoided during surgery. Interactive computerized neuronavigational devices use these data (1) to allow administration of very high doses of precisely focused radiation to small (up to 3 cm) intracranial tumors while sparing the adjacent normal brain and (2) to accurately register the previously acquired image data set onto intraoperative space, thus enabling precise intraoperative localization of surgical instrumentation relative to tumor margins, key vascular structures, and other critical anatomy. A continually evolving application is image-guided surgery, in which the entire surgical resection is guided by direct real-time MRI in the operating room environment.
IV administration of iodinated contrast medium causes a transient increase in the attenuation coefficient of normal gray matter and accentuates the difference in radiographic density on CT images between white matter and gray matter in the normal brain. Similarly, IV administration of paramagnetic contrast agent (e.g., gadolinium chelates) transiently induces shortening of both the T1 and T2 relaxation times of normal gray matter and accentuates the difference in MR signal intensity between normal cerebral gray matter and white matter. Most WHO grade IV and, to a slightly lesser extent, WHO grade III primary intracranial neoplasms and certain lower-grade primary brain tumors exhibit “contrast enhancement” in all or part of the tumor. The presence, extent, and pattern of tumor contrast enhancement have proved to be of significant value in improving detection, localization, and characterization of intracranial neoplasms by CT and MRI. Although the passage of intravascular contrast agent through brain parenchyma causes brief transient enhancement of the normal cerebral cortex, leakage of contrast material into the extravascular extracellular space accounts for the more pronounced and somewhat longer lasting contrast enhancement seen in many tumors and other structural abnormalities of the brain on both CT and MRI. The mechanisms involved in contrast enhancement of intracranial neoplasms on CT and MRI and in the uptake of radionuclide by such tumors appear to be identical.
In the normal brain, tight intercellular junctions between capillary endothelial cells create a blood-brain barrier that prevents escape of radionuclide or contrast agent from the intravascular space. In gliomas, electron microscopy studies have demonstrated that the endothelial junctions are frequently patent and the level of junctional patency is proportional to the degree of tumor malignancy. It therefore seems reasonable to postulate that the intensity of contrast enhancement in gliomas and other intracranial tumors reflects the degree of blood-brain barrier breakdown. Experimental data support this hypothesis by demonstrating that the peak intensity of tumor contrast enhancement in malignant gliomas occurs 20 to 60 minutes later than the peak serum concentration of contrast agent. Furthermore, glucocorticoids, which are known to diminish defects in the blood-brain barrier, also significantly reduce the extent of contrast enhancement in primary and secondary brain tumors.
Factors involved in maximizing contrast enhancement of intracranial neoplasms on CT or MRI include the quantity of injected contrast agent and the timing of the images. The standard dose of paramagnetic contrast agent (typically a chelate of gadolinium) administered IV for MRI is 0.1 millimoles per kilogram of body weight and is usually assessed on T1-weighted images. Application of a strong radiofrequency pulse that is slightly offset from the resonance frequency of water protons before initiation of the standard T1-weighted spin echo pulsing sequence produces saturation of protons in macromolecules, which is then transferred to the adjacent free water protons, thus diminishing their signal intensity. Because this maneuver, known as magnetization transfer (MT), does not affect the T1 shortening caused by IV administration of gadolinium, the intensity and conspicuity of resultant contrast enhancement are increased. However, because of greater suppression of white matter signal, MT alters tissue contrast relationships such that certain structures (basal ganglia, pulvinar, substantia nigra) become more conspicuous on noncontrast MT images, whereas other structures that normally enhance (choroid plexus, cerebral veins and dural venous sinuses, body of caudate nucleus, pituitary gland) do so more conspicuously on MT images acquired after contrast administration. The reader must therefore exercise caution in interpreting areas of apparent contrast enhancement as possibly signifying disease.
Edema or swelling of the brain is a common accompaniment of many brain tumors and other structural abnormalities of the brain. When sufficiently severe, edema may be responsible for both focal and generalized signs of brain dysfunction. Edema is not a single pathologic response to a variety of insults but rather occurs in at least three different forms: vasogenic (secondary to tumor, inflammation, hemorrhage, extensive infarction, or contusion), cytotoxic (in response to hypoxia, early infarction, or water intoxication), and interstitial (resulting from acute obstruction to the flow or absorption of cerebrospinal fluid [CSF]).
Vasogenic edema is the form of brain swelling most typically associated with intracranial neoplasms. It is caused by a breakdown in the blood-brain barrier with seepage of a plasma filtrate containing plasma proteins through patent junctions between capillary endothelial cells. Gray matter is relatively resistant to the development of edema, and the extracellular plasma filtrate mainly accumulates in the white matter, extending along the major white matter fiber tracts. The subcortical arcuate (U) fibers between adjacent gyri offer greater resistance to the spread of edema than the long white matter tracts and are therefore involved relatively later and in more severe cases.
The severity of edema associated with various brain tumors varies widely even between lesions of identical histology. In general, white matter swelling is greatest in association with carcinomatous metastases, and it is not unusual for a small metastasis to provoke a disproportionately large amount of edema. In order of declining severity, edema is associated with metastases, glioblastomas, meningiomas, and low-grade gliomas, but exceptions to this order are common. Rarely a low-grade glioma may be surrounded by extensive edema, whereas occasional metastases or meningiomas may have little associated white matter swelling.
On CT, vasogenic edema appears as widening and diminished density of the major white matter tracts with fingerlike extensions into the arcuate fibers in each gyrus. The overlying cortical gray matter is compressed and thinned by the expanded pseudopods of edematous white matter (see Figs. 9-14 and 9-17 ).
On noncontrast MRI, the high water content in the edematous peritumoral white matter causes prolonged T1 and T2 relaxation in the involved white matter; these findings manifest as an increase in signal intensity on T2-weighted images and as a less conspicuous decrease in signal intensity on T1-weighted images (see Figs. 9-1A, 9-15, and 9-20B ). It is often difficult to delineate the boundary between tumor and edema on these noncontrast images; IV administration of paramagnetic contrast agent permits gross demarcation on T1-weighted (see Fig. 9-20C ) and fluid-attenuated inversion recovery (FLAIR) images in many tumors (e.g., metastases) but not in malignant gliomas.
Systemic administration of glucocorticoids minimizes the blood-brain barrier defect inherent in most higher-grade brain tumors, with resultant reduction in fluid and protein extravasation. Diminution in peritumoral white matter swelling as well as in the volume and intensity of tumor contrast enhancement is often evident on follow-up imaging studies within a few days after institution of steroid therapy.
Interstitial edema secondary to obstruction of CSF pathways appears on CT as poorly circumscribed periventricular hypodensity and on T2-weighted MRI as bandlike periventricular hyperintensity of varying thickness and margination. These findings are often symmetric and are most evident surrounding the anterosuperior margins of the dilated frontal horns of the lateral ventricles (see Fig. 9-2D ) and the posterior margins of the occipital horns. Fluid accumulates in the periventricular white matter as a result of transependymal seepage of ventricular fluid across microscopic breaks in the ependymal lining of the ventricles. Systemic glucocorticoids do not affect this type of edema, but surgical insertion of a ventriculostomy shunt catheter above the level of obstruction usually results in prompt decompression of the ventricles and disappearance of the periventricular hypodensity/hyperintensity.
An expanding mass within the rigid cranial vault, whether due to tumor, edema, or a combination of both processes, compresses and distorts the adjacent normal brain, producing internal herniation of the brain under the relatively rigid falx or through the tentorial incisura.
Laterally placed masses in the cerebral hemispheres, particularly those located in the superior temporal, midfrontal, or frontoparietal regions, displace the deep central structures (basal ganglia, thalamus, third ventricle, lateral ventricles, septum pellucidum) medially. The ipsilateral cingulate gyrus is compressed and displaced across the midline under the free edge of the falx (subfalcine herniation). Medially located high frontoparietal (parasagittal) masses depress and displace the cingulate gyrus contralaterally but without significantly affecting the deep central structures. Subfalcine herniation is most clearly depicted on coronal images, which also demonstrate depression and contralateral displacement of the corpus callosum and the underlying body of the ipsilateral ventricle ( Fig. 9-1 ; see Fig. 9-11 ). The septum pellucidum and third ventricle are bowed away from the side of the mass. On axial CTs and MRIs, the ipsilateral ventricle appears compressed and displaced contralaterally.
Tumors of the temporal lobe and middle cranial fossa displace the uncus and parahippocampal gyrus on the medial aspect of the temporal lobe toward the midline, with resultant encroachment on the lateral aspect of the suprasellar and ambient (circummesencephalic) cisterns and the tentorial incisura (descending transtentorial herniation) (see Figs. 9-7 and 9-18A ). The ipsilateral margin of the midbrain is compressed, displaced contralaterally, and rotated by the impinging temporal lobe. Noncontrast MRI, postcontrast CT, or both may demonstrate medial displacement of the posterior communicating and posterior cerebral arteries, narrowing of the contralateral crural and circummesencephalic cisterns, and widening of their ipsilateral counterparts behind the impinging temporal lobe. Late secondary signs include hemorrhages in the compressed midbrain and unilateral or bilateral medial occipital infarctions (due to occlusion of one or both posterior cerebral arteries). Large centrally located cerebral masses for which the primary vector of force is directly downward may cause bilateral transtentorial herniation.
Ascending transtentorial herniation with upward displacement of the superior cerebellar vermis and hemisphere through the posterior aspect of the tentorial incisura is caused by expanding masses in the superior portion of the posterior compartment of the posterior cranial fossa, including the upper half of the cerebellum. As the superior cerebellar vermis is forced anteriorly and superiorly into the incisura, it protrudes into and compresses the superior cerebellar cistern from below and flattens the normal posterior convexity of the quadrigeminal cistern from behind. Increasing severity of herniation leads to reversal of that convexity and eventually to obliteration of the quadrigeminal and superior cerebellar cisterns ( Fig. 9-2A and B ) with flattening of the posterior margin of the third ventricle.
Tumors of the lower half of the cerebellum and other masses in the inferior portion of the posterior compartment of the posterior fossa may produce downward displacement of the cerebellar tonsils through the foramen magnum (tonsillar herniation). This situation can be visualized directly on T1-weighted MRI in the sagittal and coronal planes (see Fig. 9-2A and C ) and can be suggested on axial CT or MRI if the cisterna magna and upper cervical posterior subarachnoid spaces are encroached on and partially or completely obliterated by soft tissue density.
Hemorrhage is not a common accompaniment of most intracranial neoplasms at initial presentation. In a series of 973 intracranial tumors, CT demonstrated acute intratumoral bleeding in 28 patients (3%) at the time of initial diagnosis and in 7 additional patients (0.7%) who experienced clinical deterioration during their subsequent course. In Cushing and Eisenhardt's meticulously reported experience, hemorrhage was found in association with intracranial gliomas in 31 of 832 cases (3.7%) (see Fig. 9-14 ). Acute hemorrhage was demonstrated on CT in 6 of a series of 131 meningiomas (4.6%).
Intratumoral bleeding is more common in certain tumors, notably metastases from choriocarcinoma, melanoma (see Fig. 9-63 ), carcinomas of the lung and thyroid, and renal cell carcinoma, as well as in neuroblastoma, lymphoma, and medulloblastoma. In metastatic melanoma and choriocarcinoma, the typically hyperdense appearance of the metastatic nodules on CT has been attributed to the presence of acute hemorrhage or hemosiderin within the tumor.
Because many of the breakdown products of blood have paramagnetic properties, MRI provides a unique and highly sensitive method for detection of subacute or chronic intracranial bleeding. Hemorrhage associated with intracranial tumors may occur centrally within a necrotic tumor cavity (in glioblastoma [see Fig. 9-14 ] and some metastases) or peripherally around the tumor (seen in other metastases and meningiomas). Signal intensity (MRI) or density (CT) is typically more heterogeneous in intratumoral hemorrhage than in benign intracranial hemorrhage. On occasion, hemorrhage may completely mask the presence of the underlying neoplasm, but images obtained after injection of contrast medium may demonstrate contrast enhancement of tumor along a margin of the hematoma or in other locations within the brain. Hemorrhage into a pituitary adenoma is a common cause of “pituitary apoplexy” and may obliterate not only the entire tumor but also the normal pituitary (see Figs. 9-56 and 9-57 ).
Gliomas include all primary brain tumors of astrocytic, oligodendroglial, or ependymal origin—astrocytomas, oligodendrogliomas, and ependymomas—as well as choroid plexus papillomas and carcinomas.
Astrocytomas (tumors derived from astrocytes) are the most common of all primary intracranial neoplasms. In the 1993 revision of the WHO classification of brain neoplasms, astrocytomas were subdivided into four histologic grades. This histologic grading system has demonstrated a high positive correlation with the biological potential and behavior of tumors. Tumors of lower histologic grades (I and II) demonstrate few mitoses, little cellular structural variation (pleomorphism), and no vascular proliferation or necrosis. Tumors in grades III (anaplastic astrocytoma) and IV (glioblastoma multiforme) are characterized by more frequent mitoses, higher degrees of cellular dedifferentiation, and increasing angioneogenesis at the tumor periphery and by necrosis within the more central portion of the tumor.
Astrocytomas are characterized on both gross dissection and diagnostic imaging into two groups: circumscribed and diffuse. In general, the diffuse astrocytomas are more common, tend to occur more in adulthood, and are more infiltrative or aggressive with spread along the white matter tracts.
Three histologic types of astrocytoma are assigned to the circumscribed group. They are pilocytic astrocytoma (PA), pleomorphic xanthoastrocytoma (PXA), and subependymal giant cell astrocytoma (SCGA). All three types occur mainly in younger individuals, are more localized, and have a less aggressive biological potential than the diffuse astrocytomas.
The most common type of circumscribed astrocytoma, PA, occurs in the cerebellum (60% of cases) in children ( Fig. 9-3 ; see Fig. 9-2 ), with a peak age distribution between 5 and 15 years. PA also frequently (30% of cases) originates in the optic pathways and the adjacent hypothalami ( Fig. 9-4 ), usually in slightly younger children (2-3 years), often in association with neurofibromatosis type 1 (NF1).
PA is the classic well-circumscribed brain neoplasm, but it lacks a true tumor capsule. It grows mainly by expansion rather than by infiltration. It is widely considered to be a benign (biologically stable) neoplasm and is classified histologically as grade I. It may be densely cellular or more loosely arranged with intervening microcysts, and both patterns may coexist in different portions of the same tumor. Histologic characteristics include the frequent presence of eosinophilic Rosenthal fibers in tumor cell cytoplasm, although these can also be seen in reactive gliosis. Mitoses are rare in this lesion, and necrosis is not seen. Most often the tumor represents a mural nodule in the wall of a well-circumscribed cyst. The origin and nature of the cyst are not well understood, but the cyst fluid is proteinaceous and likely secreted from coiled capillaries found in the midst of the nodular tumor. With the exception of the mural tumor nodule, the wall of the cyst consists of compacted normal brain or nonneoplastic gliotic tissue. Intratumoral calcification is occasionally identified (5%-25% of cases), but hemorrhage into or adjacent to the tumor is rare.
The clinical presentation of children with PA depends on the tumor site. The cerebellar tumors typically manifest with headache, nausea, and vomiting because of hydrocephalus secondary to obstruction of the fourth ventricle. Weakness and loss of equilibrium are not uncommon. The optic tumors typically cause difficulties with vision, but signs of hydrocephalus may appear if the tumor has extended into the hypothalamus and is obstructing the third ventricle.
On CT the typical cerebellar PA appears as a smoothly marginated hypodense cystlike mass with a well-defined less hypodense tumor nodule on one wall (see Fig. 9-3A ). The nodule may contain one or more areas of dense calcification. The cyst fluid is less hypodense than the CSF (15-25 Hounsfield units [HU]) because of its high protein concentration. Typically after IV administration of a contrast agent, dense homogeneous contrast enhancement of the mural nodule but not of the other walls of the cyst is seen (see Fig. 9-3B and C ). More extensive enhancement of the cyst walls suggests a more aggressive (higher histologic grade) tumor.
On MRI the mural nodule appears homogeneously hyperintense to gray matter on T2-weighted images and hypointense to isointense on T1-weighted images. Intratumoral calcification may cause a more heterogeneous appearance. The associated cyst is even more hyperintense on T2-weighted images and even more hypointense on T1-weighted images (see Fig. 9-2A ). Edema of the adjacent white matter is usually minimal. Homogeneous contrast enhancement of the tumor nodule is characteristic (see Figs. 9-2C and 9-3B and C ), although a calcific focus (if present) does not demonstrate enhancement.
The clinical prognosis of cerebellar PA is guardedly optimistic. The cerebellar tumor nodule can often be totally excised, and long-term survival rates exceeding 75% are commonly reported. The location and extent of the optic-chiasmatic-hypothalamic tumors typically preclude total excision, but irradiation and chemotherapy often achieve long-term tumor control.
Optic pathway PA manifests on both CT and MRI with enlargement of the optic nerve as an intraconal mass, with characteristic kinking or buckling of the nerve secondary to the neoplasm itself and vascular congestion. Isointensity on T1-weighted MRI and heterogeneous hyperintensity on T2-weighted MRI are typical, with variable enhancement following IV contrast material administration.
PXA was newly designated in the 1993 WHO revised classification. The number of cases documented in the literature is still small. PXA is presumed to arise from subpial astrocytes near the surface of the cerebral hemispheres. Rare tumors have also been described in the posterior cranial fossa and in the spinal cord. The gross morphology resembles the mural nodule and cystic appearance of cerebellar PA. The nodule is often based on the pial surface of the brain.
On CT and on MRI the appearance is similar to that of PA but in a different location: well circumscribed, hypodense to isodense on CT, hypointense on T1- and hyperintense on T2-weighted MRI, often with a cystic component that is isointense to CSF ( Fig. 9-5A ). However, the location is supratentorial (in order of descending frequency: temporal, frontal, parietal) and superficial, with little or no mass effect. Although the tumor presents a circumscribed appearance, it usually grows slowly and may infiltrate the adjacent brain and the overlying pia, even causing focal thickening of the meninges (dural tail). Intense homogeneous contrast enhancement of the solid portion of the tumor and the overlying meninges is the rule (see Fig. 9-5B and C ).
Histologically, as the name implies, the tumor nodule is pleomorphic, but cells with a foamy myxoid cytoplasm are common. PXA is usually classified as grade II, but later dedifferentiation into higher-grade neoplasm may occur. The clinical presentation most commonly consists of seizures that may be intractable. Most reported cases have been in adolescents or young adults; the median age at diagnosis is 26 years. Treatment is usually surgical. Malignant transformation has been described in 10% to 25% of cases, but the 10-year survival is reported as 70%.
This low-grade (WHO grade I) tumor occurs almost exclusively in patients with tuberous sclerosis. It is estimated that 10% to 15% of patients with tuberous sclerosis develop this neoplasm, usually in the late first or second decade of life. These tumors arise from subependymal nodules located on the lateral wall of the lateral ventricle overlying the head of the caudate nucleus. By convention, subependymal nodules that are more than 1 cm in diameter or become symptomatic are considered giant cell astrocytomas. The tumor does not invade into the underlying caudate head but rather grows exophytically into the ventricular lumen near the foramen of Monro, which may be obstructed either unilaterally or bilaterally. Despite this tendency for intraventricular growth, the overlying ependyma remains intact and dissemination via CSF is rare. Intratumoral calcification is common and may be heavy.
Histologically the tumor is seen to contain large multinucleated giant cells of uncertain origin. On cytochemical analysis, some of these cells display GFAP (glial fibrillary acidic protein) reactivity, a feature consistent with an astrocytic origin, whereas others contain neuron-specific enolase, a finding consistent with neuronal origin.
Subependymal giant cell astrocytomas present a characteristic appearance on CT. They appear as large, hypodense, polypoid, sharply marginated intraventricular masses at the level of the foramen of Monro ( Fig. 9-6A ). The tumor may be heavily calcified and may obstruct the foramen unilaterally or bilaterally, causing gross enlargement of one or both lateral ventricles. Other manifestations of tuberous sclerosis are usually evident, including cortical tubers and subependymal hamartomatous nodules. On MRI, subependymal giant cell astrocytoma appears as a heterogeneous sharply demarcated intraventricular mass that is mildly hyperintense on T2-weighted images and hypointense or isointense on T1-weighted images. It is located within the frontal horn of the left ventricle, without evidence for deep invasion or spread within the basal ganglia. On both CT and MRI, intense but heterogeneous contrast enhancement is often demonstrated (see Fig. 9-6B ). The heterogeneous signal on MRI both without and with contrast enhancement reflects the presence of dense calcification in these tumors. Differentiation of this tumor from the subependymal hamartomatous nodules that are so ubiquitous in patients with tuberous sclerosis is sometimes problematic, but the factors usually considered are the characteristic tumor location, its larger size, and the presence of contrast enhancement; contrast enhancement is not seen in the nontumorous nodules. Clinically these patients present with signs of increased intracranial pressure (headache, nausea, vomiting, and obtundation) due to obstruction of the foramen of Monro. Treatment is surgical, and the recurrence rate is low if the resection is complete.
Poorly marginated diffuse astrocytomas demonstrate much more aggressive infiltrative behavior than circumscribed astrocytomas. Progression from lower histologic grade (astrocytoma, WHO grade II) to higher grades (anaplastic astrocytoma, WHO grade III; glioblastoma, WHO grade IV) is common; it is estimated that 50% of low-grade astrocytomas undergo subsequent dedifferentiation into higher-grade tumors (anaplastic astrocytoma or glioblastoma).
Diffuse astrocytomas are characterized genetically by inactivation of the TP53 gene, which is located on the short arm of chromosome 17. The TP53 gene encodes a protein that is involved in regulation of the cell cycle and DNA formation. Inactivation of this gene by mutation may lead to formation of abnormal DNA as well as other changes that can contribute to malignant transformation of the cells. It is interesting to note that primary glioblastomas that arise de novo and not from preexisting lower-grade astrocytoma do not exhibit loss of the TP53 gene.
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