Astrocytomas.

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.

Circumscribed astrocytomas.

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.

Pilocytic astrocytoma.

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).

Juvenile pilocytic astrocytoma of the cerebellum. A, Axial CT image without IV contrast. A large well-circumscribed hypodense mass is noted in the left cerebellar hemisphere. A flat nodular density is seen on the posteromedial wall of this cystic hypodensity (arrow). Axial ( B ) and parasagittal ( C ) T1-weighted MRIs following IV gadolinium demonstrate intense homogeneous contrast enhancement of the mural nodule (arrows) within the cystic hypointense mass.

Juvenile pilocytic astrocytoma of the optic chiasm and hypothalamus with spread along visual pathways in a patient with NF1. Axial T1-weighted MRIs obtained with fat saturation following IV gadolinium. A, At the level of the mid-orbits, arrows indicate contrast enhancement in and marked widening of the intraorbital optic nerves bilaterally due to tumor spread. B, At the level of the optic chiasm, note widening of the chiasm and extension of the contrast-enhancing tumor into the left optic tract (arrow). C, At the level of the mid–third ventricle, intense homogeneous contrast enhancement indicates tumor extension into the basal ganglia bilaterally (arrows).

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.

Pleomorphic xanthoastrocytoma.

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 ).

Pleomorphic xanthoastrocytoma of the left frontal convexity. A, Coronal turbo FLAIR MRI displays a semilunar hyperintense bandlike lesion indenting the left frontal convexity (arrow). More superficially the mass appears hypointense and mushrooms outward, eroding the calvarium and bulging into the overlying scalp. T1-weighted coronal ( B ) and parasagittal ( C ) images following IV gadolinium demonstrate contrast enhancement of the mural nodule (arrows). The findings suggest a superficial cystic tumor with mural nodule of long standing.

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%.

Subependymal giant cell astrocytoma.

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.

Subependymal giant cell astrocytoma in a patient with tuberous sclerosis. Axial CT images prior to ( A ) and following ( B ) IV administration of iodinated contrast medium. A partially calcified ( arrow in A ) multilobulated mass arising on the medial surface of the head of the right caudate nucleus fills and obscures the frontal horn of the right lateral ventricle. On the left, a calcified tuber (not neoplastic) obstructs the foramen of Monro; the dilated left frontal horn is compressed and displaced by a cyst, which is likely secondary to previous ventriculostomy complication. The noncalcified portion of the right frontal intraventricular tumor demonstrates homogeneous contrast enhancement ( arrow in B ).

Diffuse astrocytomas.

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.

Low-grade astrocytoma.

Low-grade (WHO grade II) supratentorial astrocytomas are hypercellular tumors that consist of well-differentiated fibrillary or gemistocytic astrocytes and demonstrate few mitoses and moderate pleomorphism but no vascular proliferation or necrosis. On immunohistochemistry studies, they demonstrate strong affinity for GFAP. They arise in white matter and grow by infiltration predominantly along white matter tracts, extending between and separating anatomic landmarks. The involved area of the brain eventually appears larger than its contralateral counterpart. Cerebral astrocytomas are usually solid masses that, because of their infiltrative characteristics, are poorly circumscribed and blend imperceptibly with the adjacent cerebral parenchyma. Small and large cysts are occasionally found within these tumors, but hemorrhage is rare.

Approximately two thirds of low-grade astrocytomas are supratentorial; these arise mainly in the frontal, parietal, and temporal lobes ( Figs. 9-7 and 9-8 ). They typically provoke little or no edema in the surrounding tissues. Because such a tumor begins in the white matter without affecting the more eloquent cortical centers, symptoms are usually vague and nonlocalizing until the lesion gains sufficient size, extends into eloquent cortex, or undergoes dedifferentiation into a grade III or IV tumor. The peak age range for occurrence of low-grade astrocytoma is the third through fifth decades of life.

Low-grade astrocytoma of the temporal lobe. Axial T1-weighted MRIs prior to ( A ) and following ( B ) IV gadolinium. A mostly ill-defined homogeneously hypointense mass expands the left anterior temporal lobe (arrow). There is no contrast enhancement and no surrounding edema. Note medial displacement of the medial margin (uncus and parahippocampal gyrus) of the left temporal lobe indicating early transtentorial herniation with compression of the left ambient cistern and the anterolateral aspect of the left cerebral peduncle.

Low-grade astrocytoma of the frontal lobe. Axial ( A ) and coronal ( B ) turbo FLAIR images without contrast and coronal T1-weighted postgadolinium ( C ) image in a 30-year-old man complaining of headache following a questionable seizure. A large well-demarcated homogeneously T2 hyperintense mass is centered in the right frontal opercular subcortical white matter on the FLAIR images ( A and B ). Following IV gadolinium, the T1-weighted image ( C ) demonstrates no intrinsic contrast enhancement of this large homogeneously hypointense tumor. The margins of this mass appear less well defined on the T1-weighted images. Although the overlying sulci are effaced, there is no gross surrounding edema or midline shift.

Some diffuse (initially low-grade) astrocytomas occur in childhood, notably involving the optic nerves and chiasm, optic tracts, and visual pathways as well as the hypothalamus and thalamus. More than half of the optic pathway gliomas of early childhood involve the optic chiasm and hypothalamus, and 40% of these are diffuse fibrillary astrocytomas. In contradistinction to the young child with NF1 in whom more circumscribed PAs develop along the visual pathways, the more diffuse fibrillary astrocytomas arise without any identifiable genetic predilection, although in a similar age group (peak age, 2-3 years); these are termed sporadic optic pathway astrocytomas. However, the diffuse fibrillary tumors share with their adult counterparts a poorer prognosis and thus merit a more aggressive course of management.

Another relatively common location of diffuse low-grade astrocytoma in childhood is in the brainstem. Brainstem gliomas constitute 10% to 20% of all pediatric brain tumors. The peak age of occurrence is 5 to 10 years. These tumors arise mainly in the pons but commonly involve the midbrain and medulla and may extend into the upper cervical spinal cord. Despite their proximity to the aqueduct and fourth ventricle, considerable tumor growth may take place without causing obstruction of the ventricular system. Multiple cranial nerve deficits, long tract signs, and ataxia are the most common presenting findings. Although these tumors are often regarded as low-grade lesions, histologic heterogeneity with intermixed areas of higher-grade neoplastic change is common. Approximately 60% of brainstem gliomas demonstrate foci of glioblastomatous change with central necrosis. Five-year survival rates range from 15% to 30%.

On CT, low-grade diffuse cerebral astrocytomas appear most commonly as poorly marginated areas of decreased attenuation involving the white matter of one or more lobes of the brain with mild to moderate mass effect. A more heterogeneous appearance with patchy areas of normal or slightly higher tissue density intermixed with hypodensity is seen in a small number of cases. Contrast enhancement is usually absent, reflecting a lack of tumor vascularity, blood-brain barrier breakdown, or both.

Because low-grade astrocytomas are predominantly hypodense (15-30 HU) and usually do not exhibit contrast enhancement, it is often not possible with CT to differentiate the margin of the tumor from the adjacent white matter. However, because the blood-brain barrier is intact, extensive peritumoral edema is unusual in low-grade astrocytomas. Grossly identifiable areas of intratumoral hemorrhage or necrosis are also not typically seen on CT or MRI studies in these lesions. Calcification is identified in 20% of low-grade diffuse astrocytomas, and cysts are occasionally demonstrated. The presence of hemorrhage, necrosis, edema, and/or contrast enhancement suggests progression to a higher tumor grade.

Optic pathway diffuse astrocytomas appear on CT and MR as rounded or lobulated thickening of the more posterior optic pathway, typically involving the optic chiasm and retrochiasmal segment of the optic pathway. This typically appears homogeneously hypodense on CT, T1 isointense to brain, and variably hyperintense on T2-weighted images. The tumor may encase the arteries of the circle of Willis and invade the floor of the third ventricle, causing obstructive hydrocephalus. Necrosis and hemorrhage are uncommon. In contrast to optic pathway PAs, cystic foci may be seen. Contrast enhancement is highly variable and typically does not signify malignant progression, a rare occurrence in sporadic diffuse optic pathway astrocytoma in childhood.

Brainstem glioma typically appears on CT as ill-defined diffuse heterogeneously hypodense and isodense asymmetric expansion of the pons and medulla, with dorsal displacement of the floor of the fourth ventricle and aqueduct and ventral encroachment on the pontine cistern ( Fig. 9-9A and B ). Despite the impression of the tumor on the aqueduct and the floor of the fourth ventricle, hydrocephalus is a relatively late finding. Approximately 50% of brainstem gliomas exhibit varying degrees of contrast enhancement on CT and MRI after IV administration of contrast medium (see Fig. 9-9C ). Contrast enhancement at presentation suggests higher grade and is usually patchy and heterogeneous. However, new enhancement after treatment does not necessarily suggest disease progression but may actually represent treatment response.

Brainstem glioma. Axial T2-weighted ( A ) and T1-weighted ( B ) noncontrast MRIs through the mid-pons demonstrate a poorly circumscribed mass with heterogeneous signal intensity involving the pons, which is larger on the left than on the right (arrows). This expansile and invasive tumor causes thinning of the prepontine cistern and flattening and posterior displacement of the floor of the fourth ventricle. C, On this midsagittal T1-weighted image following IV gadolinium, note extension of the tumor (arrow) superiorly into the midbrain, with posterior bowing of the aqueduct and floor of the fourth ventricle and patchy intratumoral contrast enhancement.

On MRI, diffuse low-grade astrocytomas appear relatively homogeneous and demonstrate varying degrees of prolonged T1 and T2 relaxation. They therefore appear homogeneously hypointense on T1-weighted images and hyperintense on T2-weighted images in comparison with normal brain (see Figs. 9-7A and 9-8A and B ). Because of the inherently higher contrast resolution of MRI, astrocytomas are often better demarcated from adjacent normal white matter on MRI than on CT, reflecting their higher water content. Nevertheless, as on CT, the apparent margins of the lesion on MRI (without or with contrast enhancement) do not closely correlate with histopathologic evidence of tumor extent. As on CT, there is no grossly evident contrast enhancement on MRI in diffuse low-grade cerebral astrocytomas (see Figs. 9-7B and 9-8C ); the demonstration of contrast enhancement should raise the strong suspicion of a higher tumor grade.

The differential imaging diagnosis of low-grade diffuse astrocytoma on CT and MRI is ubiquitous. Principal considerations are cerebral infarction, cerebritis, and higher-grade glioma (e.g., anaplastic astrocytoma). Infarctions tend to involve overlying cortical gray matter more extensively and are often more sharply delineated from the adjacent cerebral parenchyma. Inflammatory processes and higher-grade gliomas are often associated with blood-brain barrier breakdown and exhibit contrast enhancement and surrounding edema.

The prognosis in low-grade astrocytoma is guarded. Many of these tumors in young adults progress to a higher grade. Median survival has been reported as 5 to 8 years.

Anaplastic astrocytoma.

As the name implies, anaplastic astrocytomas (WHO grade III) exhibit considerable variation in cellular morphology, with high cellularity, frequent mitoses, and foci of vascular proliferation, findings that are not present in low-grade (grade II) astrocytomas. However, no necrosis is present in anaplastic astrocytomas on either gross inspection or microscopic evaluation. These tumors tend to occur in a slightly older age group (peak age, mid-40s) than the grade II lesions and often represent a progressive dedifferentiation of a previously low-grade tumor.

Reflecting the increased histologic variation, the imaging findings are also less homogeneous than in the lower-grade tumors ( Figs. 9-10A and 9-11A ). On T2-weighted MRI, anaplastic astrocytomas are most often heterogeneously hyperintense, frequently involve the overlying cortex, and are associated with a greater degree of vasogenic edema and overall mass effect (see Fig. 9-11A ). Restricted diffusion is often identified within these tumors, likely reflecting foci of increased cellularity. Contrast enhancement is common on both CT and T1-weighted MRI (see Figs. 9-10B and 9-11B and C ); compared with glioblastoma (grade IV) the enhancement pattern is often not ringlike but rather patchier. Although the region of contrast enhancement may appear discrete, infiltration of tumor cells beyond the margin of enhancement into the edematous surrounding white matter is nearly always present, often referred to as infiltrative edema.

Anaplastic astrocytoma, left frontotemporal. Axial CT images prior to ( A ) and following ( B ) IV administration of iodinated contrast medium. On the noncontrast image ( A ), patchy areas of hyperdensity (arrows) are noted on both sides of the left sylvian fissure, involving the medial (insular) and lateral (temporal) aspects. There is mild mass effect on the lateral margin of the atrium of the left lateral ventricle by the posterior extension of this tumor (posterior arrow). Note the ill-defined diffuse hypodensity extending between and surrounding the hyperdense regions; this likely represents a mixture of infiltrating tumor cells and reactive edema. B, On the postcontrast image, there is diffuse contrast enhancement of the previously hyperdense regions (arrows). Note that the enhancement reaches the ependymal surface of the left atrium. There is no evidence of intratumoral necrosis.

Anaplastic astrocytoma in the deep frontal lobe. Axial noncontrast turbo FLAIR ( A ) and T1-weighted axial ( B ) and coronal ( C ) postgadolinium images in a 31-year-old man who presented following a seizure. A, A large poorly demarcated heterogeneously T2 hyperintense mass is identified in the right deep frontal region involving the putamen, the head of the caudate nucleus, and the overlying insula and subinsular white matter. This mass displaces the sylvian fissure laterally, and the third ventricle and interhemispheric fissure are displaced to the left of the midline. B and C, Postgadolinium images demonstrate irregular contrast enhancement in the region of the anterior putamen.

Current estimates indicate that anaplastic astrocytomas represent about 25% of all primary gliomas of the brain. Median survival for patients with anaplastic astrocytoma is 2 to 3 years. Most tumors progress relatively rapidly to frank glioblastoma with intratumoral necrosis.

Glioblastoma.

Glioblastoma (WHO grade IV) is the most common primary malignant tumor of the CNS, accounting for more than half of all intracranial gliomas. It is biologically the most aggressive of the gliomas, with rapid progression of clinical signs and symptoms and a mean survival time in the range of 12 months. Like all other astrocytomas, glioblastoma characteristically involves the cerebral white matter, but this highly malignant process readily infiltrates and destroys the adjacent gray matter with loss of gray-white differentiation. As their name implies, these highly malignant tumors have a variegated histologic appearance with interspersed areas of hypercellularity, cellular pleomorphism, endothelial proliferation, and intratumoral necrosis.

It is probable that most glioblastomas arise by anaplastic change within preexisting low-grade cerebral astrocytomas, although some likely occur de novo. Although most commonly focal and singular in their presentation, glioblastomas may be multifocal or multicentric in origin. The peak age of incidence of glioblastoma is during the fifth and sixth decades of life, some 10 to 20 years later than the peak age for astrocytoma. However, glioblastoma is not rare in younger adults or even in children; of all glioblastomas, approximately 3% occur in childhood, mainly in the brainstem and cerebellum.

On gross inspection, glioblastomas appear more or less spherical when confined to one lobe of a cerebral hemisphere. However, these rapidly growing neoplasms invariably infiltrate into adjacent lobes, the corpus callosum (“butterfly gliomas”), and the contralateral hemisphere. Tumors that have extended widely tend to have more irregular configurations with lobulated margins of varying thickness. Infiltration of the ependyma of the lateral and third ventricles and penetration of the cerebral cortex with invasion of the overlying meninges occur commonly and may lead to seeding through the CSF pathways. Vascular endothelial proliferation with formation of large sinusoidal channels (angioneogenesis) is a typical finding in glioblastomas, and intratumoral hemorrhage is common. The central portions of these tumors frequently outgrow their blood supply and undergo ischemic coagulative necrosis, leaving only a peripheral rim of viable tumor of variable thickness. Cysts of varying size representing the residua of central necrosis may be found within the more solid periphery of many glioblastomas.

The gross pathologic findings described are accurately portrayed on CT and MRI. Although smaller tumors are generally rounded, more extensive lesions have irregular configurations indicating their spread along white matter pathways and penetration into and through cerebral cortex. These tumors typically appear on noncontrast CT as heterogeneous masses with irregular borders of normal or slightly increased density with central cavitation of diminished attenuation (see Fig. 9-14 ). The irregular hyperdense borders demonstrate avid contrast enhancement.

Findings on MRI parallel those on CT. Because of the greater inherent sensitivity of MRI for detecting subacute and chronic hemorrhage and for demonstrating tumor hypervascularity (curvilinear and racemose signal voids), the overall appearance of the lesion is even more heterogeneous on MRI than on CT. Areas of intratumoral central necrosis, which tend to dominate the appearance of the most aggressive of these tumors, appear notably hyperintense on T2-weighted images except where interrupted by more solid masses of cellular debris ( Fig. 9-12A ). Compared with this central necrotic T2 hyperintensity, the surrounding rim of viable and growing tumor appears significantly less hyperintense (owing to its hypercellularity) with unsharp margins and may blend with or be indistinguishable from the peritumoral infiltrative edema.

Glioblastoma multiforme involving the septum pellucidum. A, Axial T2-weighted MRI through the inferior aspect of the frontal horns of the lateral ventricles. An ovoid heterogeneously hyperintense mass (arrow) arising from the inferior aspect of the septum pellucidum indents and partially occludes the frontal horns bilaterally. Note the irregularly marginated intratumoral marked hyperintensity suggesting central necrosis. B, Following IV gadolinium, a coronal T1-weighted image demonstrates intense contrast enhancement (arrow) of the thick peripheral rind with nonenhancement of the central cavity.

Virtually all glioblastomas are associated with edema in the surrounding peritumoral white matter, usually graded as moderate or severe ( Figs. 9-13A ; see Fig. 9-15A ). The origin of this edema is uncertain; it may reflect production of a vascular permeability factor by the tumor cells. On CT and on T1-weighted MRI, grossly evident mildly hyperdense or slightly hyperintense tumor margins are typically unsharp, but after IV administration of a contrast agent, they stand out in contrast to the surrounding hypodense or hypointense edematous white matter (see Figs. 9-13B and 9-15B ).

Left deep frontoparietal glioblastoma with extension through corpus callosum. A, Axial T2-weighted MRI through the level of the upper third ventricle. A large area of diffuse hyperintensity involves the left posterior thalamus and basal ganglia and extends posteriorly to involve the subcortical white matter in the left parietooccipital convexity. It is not possible on this image to either define the tumor margins or separate gross tumor from surrounding edema. The third ventricle and the flow voids of the two parallel internal cerebral veins are bowed to the right of the midline secondary to the left-sided deep mass effect. Note that this hyperintensity also extends into and widens the splenium of the corpus callosum (arrow), crossing the midline into the contralateral hemisphere and creating a “butterfly glioma” pattern. B, Axial T1-weighted image following IV gadolinium demonstrates patchy heterogeneous contrast enhancement within the splenium (arrow) and surrounding the dilated and posteriorly displaced atrium of the left lateral ventricle; the tumor has blocked the posterior portion of the ventricle, and the marginal contrast enhancement of the atrium suggests subependymal tumor spread.

Hemorrhage within the tumor is common in these aggressive tumors with extensive angioneogenesis. The appearance of acute intratumoral hemorrhage in glioblastoma on both CT and MRI differs from acute nonneoplastic intracerebral hemorrhage in that the former is more sharply circumscribed and more heterogeneous in density/signal because of the surrounding and intermixed tumor and necrotic debris ( Fig. 9-14 ), whereas the latter is more irregularly marginated and homogeneous in density/signal because it dissects along otherwise normal white matter tracts. Also, evolution of intratumoral hemorrhage usually proceeds more slowly compared with hyper­tensive, posttraumatic, or other nonneoplastic types of parenchymal hematomas.

Intratumoral hemorrhage into large right posterior frontoparietal glioblastoma. Axial CT image without IV contrast. A large well-demarcated hypodense cystic cavity in the deep right frontoparietal white matter is surrounded by poorly defined hypodensity. On the posterior margin of this cavity there is a sharply defined scythelike hyperdense collection (arrow) representing intratumoral hemorrhage. Note the considerable mass effect secondary to diffuse edema in the right frontal lobe, with shift of the lateral and third ventricles and the septum pellucidum to the left of midline. The atrium of the left lateral ventricle is compressed and displaced anteromedially by this cavitated tumor.

Contrast enhancement of viable tumor, including the peripheral rim and the intratumoral solid portions, is nearly universal in glioblastomas (see Figs. 9-12B, 9-13B, and 9-15B ). The opacifying tumor ring is typically irregular and of varying thickness. The intensity of the enhancement correlates with the level of cellular anaplasia, but it does not accurately reflect the extent of microscopic tumor infiltration. Careful imaging-histopathologic correlation studies in patients with malignant gliomas have conclusively established the presence of viable tumor cells well beyond the margin of contrast enhancement, and the zone of edema in the surrounding white matter must be understood as including foci of microscopic tumor infiltration ; thus the term infiltrative edema.

Multicentric glioblastoma. Coronal MRIs through the posterior atrial region. A, T2-weighted image demonstrates a hyperintense rounded mass in and deep to the high right frontoparietal convexity (white arrow) and a second similar mass in the inferomedial right temporooccipital cortex and white matter (black arrow). Between these masses is a large area of greater hyperintensity, likely representing edema with probable microscopic tumor infiltration, which effaces the overlying convexity cortex and severely compresses and obscures the atrium of the right lateral ventricle. B, On a T1-weighted image following IV gadolinium administration, both lesions demonstrate inhomogeneous contrast enhancement (arrows) . The inferomedial tumor has invaded the splenium of the corpus callosum, extending across the midline into the left hemisphere. Note also extension of this tumor inferiorly, protruding into the tentorial notch and impinging on the right side of the superior cerebellar vermis (black arrow) .

Differentiation by CT or MRI between glioblastoma (or other grade IV glioma), carcinomatous metastasis, and lymphoma is often difficult. All three processes may appear as irregularly rounded, contrast-enhancing, ringlike masses with walls of varying thickness. In all, the viable tumor rim is typically irregular and nonuniform in thickness, and histologic examination is usually required for definitive diagnosis. Primary CNS lymphoma is typically more central in location and homogeneously solid (see Figs. 9-46 and 9-74 ), but central necrosis, infiltration into the corpus callosum and other major white matter pathways, and tumor extension into the meninges and along the ependyma (all common late manifestations in glioblastoma) are not rare occurrences with lymphoma.

Additionally, a large area of active demyelination with inflam­mation and edema secondary to previously undiagnosed multiple sclerosis may also simulate a glioblastoma on CT or MRI. Such tumefactive demyelinating lesions (e.g., in multiple sclerosis or in acute disseminated encephalomyelitis [ADEM]) often demonstrate arclike (open toward the adjacent cortex) contrast enhancement and increased or facilitated diffusion, findings that are much less common in glioblastomas.

When images demonstrate multiple nodular or ringlike masses, multicentric glioblastoma must be included in the differential diagnosis ( Fig. 9-15 ), along with metastases and pyogenic cerebral abscesses. The peripheral rim of an abscess is typically (but not always) thinner and more uniform than that of a glioblastoma or a metastasis. Diffusion-weighted imaging (DWI) demonstrates restriction of diffusion in the central cavity of an abscess but not in the coagulative necrosis of a primary or metastatic neoplasm. Besides DWI, other advanced neuroimaging techniques can be used to differentiate glioblastoma, solitary metastases, and abscesses, namely magnetic resonance spectroscopy (MRS), perfusion MRI, and positron emission tomography (PET) imaging, as discussed later in this chapter (see “Advanced Neuroimaging Techniques”).

A commonly encountered clinical problem is the need to differentiate radiation necrosis from recurrent glioblastoma in a patient who has undergone surgical resection and a complete course of radiation therapy and several months after the radiation therapy demonstrates a change in neurologic status. If the follow-up imaging study demonstrates interval increase in the size of the apparent tumor mass and the extent of contrast enhancement, differentiation of recurrent tumor from radiation necrosis in this lesion on the basis of CT or MRI is not possible. In such circumstances, advanced neuroimaging techniques are often employed with perfusion MRI, MRS, and PET imaging, using both ¹⁸ F FDG and non-FDG radiotracers, greatly improving sensitivity and specificity, as discussed later in this chapter (see “Advanced Neuroimaging Techniques”).

Gliomatosis cerebri.

A comparatively uncommon pattern of glial neoplasia, gliomatosis cerebri is characterized by widespread diffuse neoplastic infiltration in multiple lobes and both cerebral hemispheres without formation of an obvious tumor mass. The cell of origin is uncertain; the tumor is classified as WHO grade III. The extent of infiltration is out of proportion to the other histopathologic features, such as the level of anaplasia and the relative lack of destruction of normal tissues. Despite the extent of tumor infiltration, neural connections are preserved, and the clinical signs and symptoms are relatively mild. Nevertheless the clinical course is relentlessly progressive over periods varying from months to a few years.

The process tends to extend along the white matter tracts but also involves the adjacent gray matter with loss of clear gray-white distinction both on gross pathology and on imaging studies. The involved parenchyma is both expanded and distorted by the tumor infiltration. Microscopically the tumor cells are elongated and infiltrate between myelinated fibers without destroying them, much like in a low-grade astrocytoma, but there is greater cellular atypia and mitotic frequency, and foci of necrosis are occasionally seen.

Diagnostic imaging studies demonstrate extensive and scattered areas of parenchymal involvement with ill-defined areas of hyperintensity on T2-weighted MRI and subtle areas of hypodensity on CT scans ( Fig. 9-16A ). No well-demarcated or circumscribed tumor masses are identified on imaging in this disorder. Focal expansion and distortion are seen as areas of diffuse effacement of sulci and compression and displacement of the adjacent ventricles and cisterns. The incidence and level of contrast enhancement are often less than the extent of apparent tumor infiltration (see Fig. 9-16B ) because enhancement relates closely to the degree of cellular dedifferentiation. Clinically the principal differential diagnosis is with multiple sclerosis, but the imaging pattern of multiple widespread areas of expansion and distortion as well as the relatively rapid and consistent progressive clinical course favor a diagnosis of neoplasm.

Gliomatosis cerebri in the left cerebral hemisphere. A, On this axial T2-weighted MRI, there is evidence of diffuse enlargement of the left frontal, temporal, and parietal lobes, with extensive but ill-defined hyperintensity involving the temporoparietal convexity cortex and adjacent white matter (arrows). B, Axial T1-weighted MRI following IV gadolinium demonstrates widely separated patchy areas of faint contrast enhancement (arrows) that represent scattered foci of malignant gliomatous infiltration.

Gliosarcoma.

A rare tumor, gliosarcoma consists of both glial and mesenchymal elements. Most reported patients have been between 50 and 70 years old. The origin of the mesenchymal element remains uncertain and controversial; it presumably arises from spontaneous neoplastic transformation of vascular elements within the glial neoplasm, but prior radiation therapy has been implicated in a few case reports. The mesenchymal element is usually a fibrosarcoma, but other sarcomas have been reported. Immunohistochemistry studies demonstrate both GFAP reactivity, confirming the astrocytic nature of the glial component, and positive staining for collagen and reticulin, confirming the mesenchymal component.

The glial component of these mixed tumors is typically glioblastoma, and gross pathology as well as both CT and MRI demonstrate the variegated pattern of that tumor with areas of central necrosis and peripheral infiltration both along white matter tracts and into adjacent gray matter ( Fig. 9-17 ). Invasion into and involvement of the overlying meninges are often noted (see Fig. 9-17B ); invasion into bone and extracranial soft tissue likely reflects the sarcomatous element within the tumor, and systemic metastasis (a rare occurrence in glioblastoma) is well described for gliosarcoma.

Gliosarcoma. A, Axial CT image following IV contrast demonstrates a lobulated mass with variegated contrast enhancement in the high right frontal convexity, with multiple intratumoral calcifications (arrow) surrounding an area of central hypodensity that likely represents necrosis. The contrast enhancement crosses the midline into the high left frontal convexity. Extensive white matter hypodensity, likely representing edema, involves the surrounding frontal lobe white matter bilaterally. B, Coronal T1-weighted MRI after IV gadolinium confirms the presence of a lobulated high right frontal convexity contrast-enhancing tumor (arrow) and also clearly demonstrates the extensive spread of this tumor along the inner table of the skull bilaterally, with bandlike meningeal thickening over the convexities of both cerebral hemispheres.

Oligodendroglioma.

Oligodendrogliomas (tumors derived from oligodendrocytes) represent 15% to 20% of intracranial gliomas and 5% to 10% of all intracranial neoplasms. The diagnosis is made much more commonly in recent years than in the past, reflecting a reevaluation of the histologic and immunochemical criteria (oligodendrogliomas are GFAP negative) that define the distinction between oligodendroglioma and astrocytoma. These tumors occur principally in the supratentorial white matter. Like low-grade astrocytomas, they tend to infiltrate along white matter tracts in a nondestructive manner. However, more commonly than astrocytomas, oligodendrogliomas also involve the subcortical white matter and the overlying cortex, and involvement of deep structures is also common. Eighty-five percent occur in the cerebral hemispheres, more than half in the frontal lobes.

The peak age of incidence of oligodendrogliomas is in the fourth and fifth decades of life; these tumors are much less common in childhood or adolescence. The initial clinical presentation is most often a seizure, reflecting the predilection for cortical involvement. Tumor growth is generally slower than in astrocytomas of similar grade (WHO grade II) and the prognosis is better, but a more biologically aggressive category is now recognized in the revised WHO classification as anaplastic oligodendroglioma (WHO grade III). Cytogenetic studies have noted loss of the 1p and 19q chromosomes in approximately half of patients with oligodendroglioma; on imaging studies, patients with loss of 1p and 19q have demonstrated a significant association with positive response to multiagent nitrosourea-based chemotherapy.

Oligodendrogliomas are typically densely cellular and solid, contain multiple irregular masses of dystrophic calcification, and grow very slowly. Median survival is approximately 10 years. They can attain considerable size before they produce symptoms. They may contain a dense network of branching capillaries. Areas of cystic degeneration are found in 20% of cases, mainly in the larger tumors. Intratumoral hemorrhage is also a frequent finding. Treatment is primarily surgical resection with adjuvant chemotherapy and radiotherapy, but local recurrence is common.

Anaplastic oligodendrogliomas on histology demonstrate greater cellular atypia and mitotic activity, more extensive tumor vascularity, and necrosis. The prognosis is less favorable, with median survival of 4 years and 10-year survival of approximately 15%.

Foci of astrocytoma are frequently found in association with oligodendroglioma, and when these are prominent, the tumor is termed an oligoastrocytoma. Oligoastrocytomas are typically WHO grade II tumors and anaplastic oligoastrocytomas WHO grade III. When there is a clear preponderance of neoplastic oligodendrocytes (75%-90%), the tumor is classified as an oligodendroglioma.

On CT, oligodendrogliomas most often appear as masses of heterogeneous density (predominantly hypodense) in the frontal lobe, with irregular and poorly defined margins involving the more superficial white matter and frequently infiltrating into the overlying cortex and obscuring the gray-white interface. The characteristic feature in the great majority of cases is the presence of large nodular or clumplike calcifications within the tumor ( Fig. 9-18A ). The frequency of intratumoral calcification in oligodendrogliomas (70%-90%) is the highest of any cerebral neoplasm, but overall, intratumoral calcification is most common in astrocytomas (frequency, 25%) because of the much greater prevalence of that lesion. Intratumoral cyst formation is common in oligodendrogliomas (20%), but frank intratumoral necrosis is unusual and indicates a poor prognosis. Contrast enhancement is noted in approximately 50% of oligodendrogliomas (see Fig. 9-18C ), but the degree of enhancement is variable and appears to correlate with higher histologic grade and lower survival.

Oligodendroglioma. A, Axial noncontrast CT image demonstrates a large mass with poorly defined margins in the left midtemporal lobe (arrow). The mass is predominantly hypodense with a large amorphous central calcification and involves the convexity cortex as well as the underlying white matter. The expanded left temporal lobe herniates across the tentorial margin and compresses the lateral aspect of the left cerebral peduncle. B, On this axial T2-weighted image, the large intratemporal tumor appears heterogeneously hyperintense, with the calcified portion (arrow) exhibiting lesser intensity. C, Axial T1-weighted MRI following IV gadolinium. The tumor appears predominantly hypointense, has ill-defined margins, and involves mainly white matter but also extends into the convexity cortex and demonstrates faint heterogeneous contrast enhancement (arrow).

On MRI, oligodendrogliomas appear heterogeneous on both T1- and T2-weighted images because of the presence of intratumoral cysts and calcifications. On T1-weighted images, the tumors appear predominantly hypointense to gray matter, and on T2-weighted images they are most often hyperintense, with small intratumoral cysts and focal calcifications and hemorrhages contributing to the overall heterogeneity (see Fig. 9-18B ). Peritumoral edema is noted in about one third of cases. Enhancement is variable and typically heterogeneous, with anaplastic oligodendrogliomas (grade III) enhancing more commonly than low-grade oligodendroglioma (grade II). Also, as with other gliomas, new enhancement within a previously nonenhancing oligodendroglioma suggests anaplastic transformation.

Ependymoma.

The ependyma lining the floor of the fourth ventricle is the most common site of origin of intracranial ependymomas (65%). Nevertheless, approximately 30% of ependymomas occur above the tentorium, arising mainly from ependymal cell rests in the cerebral white matter adjacent to the lateral ventricles. Infratentorial ependymomas occur predominantly in children between 1 and 6 years of age; supratentorial ependymomas occur mainly in the second through the fourth decades of life.

Posterior fossa ependymomas make up approximately 10% to 15% of all primary CNS neoplasms of childhood and approximately 3% to 5% of all intracranial neoplasms. They are the third or fourth most common posterior fossa tumor of childhood, exceeded only by PA, medulloblastoma, and possibly brainstem glioma. Ependymomas are usually slow-growing tumors of moderate malignancy (WHO grade II), but the prognosis is guarded because of their notable tendency to recur locally and disseminate via the subarachnoid spaces. The incidence of seed metastases via the CSF is approximately 10% overall but is considerably higher in the infratentorial tumors of early childhood; tumor seeding into the subarachnoid spaces is found initially or on follow-up studies in approximately one third of fourth ventricle ependymomas.

Supratentorial ependymomas are commonly paraventricular, located most frequently within cerebral parenchyma near the atrium of the lateral ventricle or the foramen of Monro and presumably arising from ependymal cell rests. Infratentorial ependymomas are lobulated, well-circumscribed, soft exophytic masses that expand within the cavity of the fourth ventricle rather than infiltrate into the surrounding parenchyma. They often extend in a tonguelike fashion through the lateral recesses into the lateral medullary and cerebellopontine angle cisterns (15%) or through the foramen of Magendie into the vallecula (10%). Tumor growth within the fourth ventricle eventually leads to occlusion of the ventricle, with resultant obstructive hydrocephalus.

Ependymomas are highly cellular with small uniform cells that tend to form characteristic perivascular pseudorosettes. Although they do not invade through the ventricular walls, they are firmly attached to the ventricular floor, and complete resection of the tumor base is frequently not possible. The rate of local tumor recurrence after surgical resection is 90% to 95% within 3 years, and the 5-year survival is currently 45% to 70%. Furthermore, about 25% of ependymomas exhibit features of anaplasia, with a high mitotic rate, cellular pleomorphism, and intratumoral necrosis; these tumors are known as anaplastic ependymomas (WHO grade III).

Intratumoral calcification and cyst formation are common in ependymomas (20%-50% of reported cases). Peritumoral edema is a prominent and frequent finding in association with both cerebellar and cerebral ependymomas.

On noncontrast CT, fourth ventricle ependymomas appear as hypodense or isodense heterogeneous, well-circumscribed, rounded masses within the fourth ventricle that partially or completely obliterate the cavity of the ventricle. The tumor is typically well defined by a prominent surrounding hypodense halo of peritumoral edema. Aggregates of calcification, usually small and round but sometimes quite large, are found in up to half of these lesions, and focal lucencies resulting from cyst formation are nearly as common. In supratentorial tumors, the cysts are both larger and more frequent (up to 80%) than in fourth ventricle ependymomas (see Fig. 9-20A ). Intratumoral hemorrhage is relatively less common, with reported frequency of 20% or less. After IV administration of contrast agent, the solid portions and cyst walls of the tumor mass exhibit moderate but variable heterogeneous contrast enhancement.

The MRI appearance of ependymomas is heterogeneous, reflecting mixed signals from intratumoral calcification, cysts, and hemorrhage. Usually these tumors are isointense to hypointense relative to white matter on T1-weighted images and isointense to hyperintense to white matter on T2-weighted images ( Fig. 9-19A and B ; Fig. 9-20B ). Contrast enhancement is the rule, but it is variable in degree and typically not uniform, seen in both ependymoma and anaplastic ependymoma. (see Figs. 9-19C and 9-20C ). Although the MRI features of ependymoma are nonspecific, the multiplanar capabilities of this modality offer unique visualization of infratentorial tumor extent within the cranial vault and the region of the cervicocranial junction.

Ependymoma of the fourth ventricle. A, Axial T1-weighted MRI demonstrates a large predominantly hypointense mass filling and distending the fourth ventricle and compressing the pons from behind. Only a small more hypointense crevice at the right lateral margin of the tumor (arrow) indicates the presence of CSF in the markedly compressed lumen of the fourth ventricle. Small foci of hypointensity within the tumor likely represent areas of calcification. Note the marked dilatation of the temporal horns secondary to obstruction of the fourth ventricle. B, On this axial T2-weighted image, the intraventricular tumor appears heterogeneously mildly hyperintense, while the signal within the residual compressed fourth ventricle (arrow) is strongly hyperintense. Intratumoral calcification is strongly hypointense. C, Following IV gadolinium, an axial T1-weighted MRI demonstrates irregular heterogeneous intratumoral contrast enhancement (arrow).

Supratentorial ependymoma. A, Axial CT image after IV contrast demonstrates a cystic-appearing hypodense mass with irregular rimlike contrast enhancement (arrow) in the medial aspect of the left temporal lobe. B, On this axial T2-weighted MRI, the tumor (arrow) exhibits mixed signal intensity; it is predominantly isointense to gray matter and hypointense to CSF. A tiny ovoid hypointensity in its posteromedial surface likely represents calcification. There is extensive surrounding edema in the temporal lobe and in the lateral aspect of the left cerebral peduncle. C, Axial T1-weighted postgadolinium image demonstrates irregular rimlike and central contrast enhancement (arrow) with medial extension into the lateral margin of the midbrain.

On both CT and MRI as well as in the clinical setting, the presentation of ependymoma of the fourth ventricle may closely resemble that of medulloblastoma and PA. The incidence and extent of intratumoral calcification, heterogeneity of density or signal intensity, and propensity for tumor extension into the fourth ventricular recesses are greater in ependymomas than in medulloblastomas or astrocytomas. In general, medulloblastomas appear more dense on CT with a lower frequency of intratumoral calcification, and they exhibit more homogeneous contrast enhancement than ependymomas. Differentiation can be difficult but is aided by DWI, as discussed later in this chapter. Astrocytomas tend to occur in slightly older patients and are much less frequently centered in the midline.

Subependymoma.

A rare variant of ependymoma that actually consists of both highly differentiated ependymal cells and astrocytes, subependymoma is classified as a benign (WHO grade I) glial neoplasm. It is considered to arise from beneath the ventricular lining and projects into the ventricular cavity as a sharply outlined intraventricular mass but does not extend deeply from its base into the adjacent brain parenchyma ( Fig. 9-21 ). Subependymomas are typically solid and homogeneous, although larger tumors may contain calcifications, microcystic changes, and evidence of intratumoral hemorrhage.

Subependymoma of the fourth ventricle and vestibular schwannoma in the right cerebellopontine angle. Axial T1-weighted ( A ) and T2-weighted ( B ) MRIs demonstrate a small, sharply marginated, isointense (T1-weighted)/hyperintense (T2-weighted) nodular intraventricular mass in the central and left lateral aspects of the fourth ventricle (white arrows). The mass appears continuous with the left lateral wall of the ventricle. Also evident is a rounded heterogeneously hypointense (T1-weighted)/hyperintense (T2-weighted) mass in the right cerebellopontine angle and internal auditory canal that indents the lateral aspect of the pons and middle cerebellar peduncle and the anterior margin of the right cerebellar hemisphere (black arrows). C, Axial T1-weighted image after IV gadolinium administration demonstrates nearly homogeneous contrast enhancement of both lesions (arrows); the uptake of contrast in the intraventricular nodule is more subtle than in the cerebellopontine angle lesion.

Subependymomas occur most commonly (50%-60%) in the fourth ventricle but also arise in the lateral ventricles. Most present clinically in adults, but many of these lesions are asymptomatic and found incidentally at autopsy. Those that become symptomatic (causing obstructive hydrocephalus) occur mostly in the lateral ventricles ( Fig. 9-22 ) in relation to the septum pellucidum and foramen of Monro and much less commonly in the region of the aqueduct.

Large supratentorial subependymoma. A, Axial T1-weighted MRI demonstrates an intraventricular mass with slight signal heterogeneity in the body of the right lateral ventricle. This mass abuts both the septum pellucidum medially and the corona radiata laterally. Both lateral ventricles appear enlarged. B, On the axial T2-weighted image, the mass also appears mildly heterogeneous. There are small foci within the mass that follow CSF signal intensity on both the T1- and T2-weighted images. C, On the axial turbo FLAIR image, the mass demonstrates heterogeneous signal hyperintensity. The focal areas that followed CSF signal intensity on the T1- and T2-weighted images have their signal suppressed on this image and are consistent with cystic areas containing simple CSF-like fluid. There is no evidence for edema in the right corona radiata adjacent to the mass. There is abnormal signal hyperintensity in the subependymal regions of the brain adjacent to the anterior and posterior aspects of lateral ventricles bilaterally that, along with the lateral ventricular enlargement, suggests hydrocephalus with transependymal flow of CSF; this is secondary to obstruction of the foramen of Monro bilaterally. D, Axial T1-weighted MRI after administration of gadolinium demonstrates only a few scattered linear areas of enhancement within the mass that may represent small blood vessels. There is no significant enhancement of the mass itself.

On CT and MRI, symptomatic lesions in the fourth or lateral ventricles usually appear homogeneous in density and signal intensity. They appear homogeneously isodense or slightly hypodense on CT. On T2-weighted MRI the tumor appears homogeneously hyperintense to adjacent brain. There is variable contrast enhancement after IV administration of contrast medium. However, larger tumors may exhibit internal heterogeneity of density and signal owing to intratumoral calcification and hemorrhage.

The differential diagnosis includes central neurocytoma, ependymoma, and subependymal giant cell astrocytoma. Patient age, nature of the symptoms, presence of associated disease, tumor size, presence and extent of calcification, cystic change, evidence of hemorrhage, and contrast enhancement are the key factors in making the differentiation.

Choroid Plexus Papilloma and Carcinoma.

Papillomas arising in the choroid plexus are benign intraventricular neoplasms that locally expand the involved ventricle and cause hydrocephalus, which may be secondary to ventricular obstruction, overproduction of CSF, or impairment of CSF absorption. Choroid plexus papillomas represent less than 1% of all brain tumors but are more common in young children (3% of all pediatric brain tumors), particularly in the neonatal period; 85% occur in the first 5 years of life, and these tumors represent 40% of all brain tumors in the first 60 days of life.

The atria of the lateral ventricles and fourth ventricle are the most common sites of involvement. An age disparity exists with regard to tumor location, with lateral ventricle tumors occurring mainly in young children, and fourth ventricle papillomas appearing more commonly in adults. It is not uncommon for fourth ventricle tumors to extend through the lateral recesses and protrude into the cerebellopontine angle cisterns.

Histologically, choroid plexus papillomas consist of well-differentiated proliferation of both the surface epithelium of the choroid plexus and the underlying vascular connective tissue core and are usually classified as WHO grade I. They grow slowly and are noninvasive, tending to expand within the confines of the ventricle or its outlet foramina. Occasionally, however, the epithelium may exhibit malignant change, and in such cases the tumors are classified as carcinomas; they may extend into the adjacent brain parenchyma. The prognosis in these malignant choroid plexus tumors depends on the completeness of surgical resection, but overall the 5-year survival ranges from 26% to 40%.

Because of the friability and high vascularity of choroid plexus papillomas, intratumoral and intraventricular hemorrhage are common.

On CT, choroid plexus papillomas appear as large, rounded or lobulated, isodense or hyperdense intraventricular masses that engulf and separate the normal choroid plexus calcifications and exhibit intense homogeneous contrast enhancement. Small hypodense nonenhancing foci are occasionally identified within these tumors.

On MRI, choroid plexus papillomas are usually isointense or hypointense with respect to brain on T1-weighted images and heterogeneously hyperintense relative to brain on T2-weighted images ( Fig. 9-23A and B ) ; the heterogeneity of signal intensity within the tumor mass may be due to areas of vascularity, calcification, or previous hemorrhage (see Fig. 9-23A ). As noted previously the tumor typically expands the ventricle locally at the site of origin and may obstruct ventricular drainage, causing dilatation (entrapment) of the more proximal portion of the affected ventricle. On both CT and MRI, these tumors usually demonstrate intense contrast enhancement (see Fig. 9-23C ), which may be homogeneous or heterogeneous depending on the tumor contents.

Choroid plexus papilloma of the left lateral ventricle. A, Axial T1-weighted MRI demonstrates an intraventricular mass with heterogeneous signal intensity in the body of the left lateral ventricle (arrow). The lateral portion of this mass is hyperintense (likely indicating the presence of subacute hemorrhage), while the medial portion is mainly hypointense relative to the white matter. B, On this axial T2-weighted image, the tumor (arrow) appears slightly hyperintense to adjacent brain but hypointense to the fluid in the lateral ventricles. C, Axial T1-weighted postgadolinium image demonstrates heterogeneous contrast enhancement of the tumor mass (arrow).

The differential diagnosis of choroid plexus papilloma on imaging studies usually includes ependymoma in older children and adults and meningioma in adults. The lobulated tumor margins, lack of invasion of brain parenchyma despite the large tumor size, and heterogeneous signal pattern within the tumor all aid in distinguishing this lesion.

Neuronal and Mixed Neuronal and Glial Tumors.

In this group of tumors of neuroepithelial origin, neuronal and glial differentiation is present in varying degrees. This chapter will discuss the following recognized entities: ganglioglioma, gangliocytoma, dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), desmoplastic infantile ganglioglioma, dysembryoplastic neuroepithelial tumor, and central neurocytoma.

Ganglioglioma and gangliocytoma.

Gangliogliomas are un­common low-grade tumors consisting of a mixture of neoplastic astrocytes and dysplastic neurons. Slow-growing neoplasms with well-differentiated ganglion cells and a low-grade astrocytomatous stroma, these tumors are considered WHO grade I or II. Gangliocytomas (also known as ganglioneuromas ) are relatively less common and contain only neuronal elements; they are classified as WHO grade I. Together these tumors account for 1.3% of all primary brain tumors.

Gangliogliomas and gangliocytomas occur in young people (peak incidence in the second decade of life) and constitute approximately 3% to 4% of primary brain tumors in children. They are found most commonly in the temporal lobes but may occur anywhere in the cerebral hemispheres. The clinical presentation is usually with seizures of long duration, and gangliogliomas are considered the most common cause of chronic temporal lobe epilepsy. These tumors are usually well-circumscribed solid masses but may include one or more cysts. Gross total resection of a tumor is the treatment of choice. Overall, gangliogliomas and gangliocytomas have a 92% 3-year survival. In approximately 10% of cases, however, the tumor is more aggressive; in these cases, the malignant element is always glial.

Diagnostic imaging findings are relatively nonspecific and similar to those in other low-grade intracerebral neoplasms. Noncontrast CT scans demonstrate relatively well-circumscribed hypodense (occasionally isodense with adjacent brain) lesions typically located in the periphery of the hemisphere, with little associated mass effect or surrounding vasogenic edema. Foci of calcification are identified in 33% to 40% of cases, and cysts in 50% of cases. Calcification is less common in noncystic tumors. Rarely a peripherally located indolent tumor may erode the inner table of the overlying skull. Hemorrhage is rare in these tumors. Contrast enhancement is observed in about 50% of cases and may be homogeneous or heterogeneous depending on the presence and size of cystic and calcific changes.

On MRI, these tumors (like many other intracerebral neoplasms) are usually heterogeneous in appearance, predominantly hypointense to gray matter on T1-weighted images and hyperintense on T2 ( Fig. 9-24A ). Mild to moderate contrast enhancement of the solid noncystic portion of the tumor is found in the majority of cases on both CT and MRI (see Fig. 9-24B ).

Ganglioglioma of the right temporal lobe. A, Axial T2-weighted MRI demonstrates a well-circumscribed cystic mass (arrow) with a hypointense rim (secondary to calcification) in the region of the right parahippocampal gyrus and surrounding hyperintensity (due to edema). There is associated mass effect with effacement of the sulci of the right temporooccipital convexity, but there is no evidence of tentorial herniation. B, On this postgadolinium T1-weighted coronal image, peripheral rimlike contrast enhancement (arrow) outlines the margins of this cystic tumor, which is located immediately above the right leaf of the tentorium. The contents of the cyst are slightly hyperintense relative to CSF, reflecting a higher protein content.

Findings on CT and MRI in these ganglion cell tumors are not characteristic; oligodendroglioma is a common differential consideration. However, in a young patient with a protracted history of seizures and a relatively well-circumscribed cystic tumor containing calcification in the periphery of the temporal lobe with little or no associated mass effect, ganglioglioma should be strongly considered.

Dysplastic gangliocytoma of the cerebellum.

A rare lesion, dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease) is considered a complex hamartoma or malformation and is classified as WHO grade I. Dysplastic gangliocytoma may exist as an isolated entity or as part of Cowden’s disease, a rare syndrome with multiple mucosal hamartomas. The clinical presentation is usually ataxia and signs of increased intracranial pressure in a young adult. A large dysplastic mass occupies most or all of the cerebellar hemisphere, with thickening of the granular and molecular layers of the overlying cerebellar cortex ( Fig. 9-25A ). The enlarged mass causes displacement and compression of the fourth ventricle. On MRI the mass is poorly demarcated, hypointense on T1-weighted images and hyperintense on T2-weighted images, and the thickened folia present a distorted striate pattern (see Fig. 9-25B ). Contrast enhancement of either the tumor or the thickened cerebellar folia is unusual (see Fig. 9-25C ).

Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos). A, Axial CT image without IV contrast demonstrates a poorly marginated heterogeneous predominantly hypodense mass (arrow) occupying most of the right cerebellar hemisphere and displacing the fourth ventricle to the right of the midline. A striate pattern of calcification is noted within this process. B, On this T1-weighted axial noncontrast MRI the poorly marginated hypointense mass presents a distorted internal architecture (arrow) and compresses and displaces the pons anteriorly and to the left. C, Axial T1-weighted image post IV gadolinium; there is no evident contrast enhancement of this hamartomatous process (arrow).

Desmoplastic infantile ganglioglioma.

Desmoplastic infantile ganglioglioma (DIG) is an unusual lesion that occurs in young infants. It consists of immature neurons and astrocytes together with extensive fibrocollagenous (desmoplastic) thickening and cyst formation. The solid desmoplastic portion is often located adjacent to the meninges. Despite its variegated appearance, this tumor is classified as WHO grade I and has a favorable long-term prognosis after complete excision.

DIGs are large and superficial hemispheric tumors that occur mainly in the frontal and parietal lobes and present a markedly heterogeneous appearance on both gross inspection and MRI ( Fig. 9-26 ). The solid portions of this tumor are hypointense relative to normal brain on T2-weighted images and frequently demonstrate intense contrast enhancement. DIG differs from the usual ganglioglioma in that it presents in infancy, is predominantly frontoparietal in location, and has dense desmoplasia. On MRI, the intermixed collagenous and multicystic pattern of this lesion most resembles that of a primitive neuroectodermal tumor (PNET), which carries a much less favorable prognosis; however, PNET is also characterized by the common presence of intratumoral calcification, hemorrhage, and necrosis, findings that are uncommon in DIG.

Desmoplastic infantile ganglioglioma (DIG). A, Axial T2-weighted MRI demonstrates a well-circumscribed heterogeneous left high frontal convexity tumor that is predominantly hypointense to adjacent brain (arrow). On its posteromedial aspect, there are two small cysts and one large ovoid cyst on the left and a single large cyst on the right, all with hyperintense contents. There is extensive white matter edema bilaterally surrounding the large cysts and extending into the left frontoparietal convexity gyri. Following IV gadolinium, axial ( B ) and left parasagittal ( C ) T1-weighted images demonstrate intense contrast enhancement of the superficial solid area of this tumor (arrows), which consists of thick dense fibrocollagenous (desmoplastic) tissue. Contrast enhancement is also seen to a variable degree in the rims of the cystic elements of this lesion. On C, note the posteroinferior displacement and compression of the atrium and temporal horn of the left lateral ventricle by the large left cystic mass.

Dysembryoplastic neuroepithelial tumor.

Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon benign intracortical tumors that characteristically occur in young patients (<20 years) above the tentorium, mainly in the temporal lobe (60%-80%) or frontal lobe. They can be multifocal and rarely arise in the septum pellucidum. Patients typically present with intractable partial seizures. Partial or complete excision is the treatment of choice, and no recurrences have been reported. The tumor is termed dysembryoplastic because of its multinodularity, with areas of cortical dysplasia at the margins between the tumor nodules and adjacent brain.

DNETs are lesions of long standing that most frequently involve the convexity cortex and often protrude beyond the adjacent cortical margin, eroding the overlying inner table of the calvarium. The imaging findings, except for the superficial cortical location, are similar to those of other low-grade glial tumors (astrocytoma, oligodendroglioma). On CT, DNET typically appears as a well-circumscribed hypodense superficial mass, occasionally with intratumoral calcification or cystic change or both. MRI demonstrates a mass centered in the convexity cortex and bulging externally that is hypointense to adjacent brain on T1-weighted images ( Fig. 9-27B ) and hyperintense on T2-weighted images (see Fig. 9-27A ) with no surrounding edema. The protruding external margin may present a “soap bubble” appearance, reflecting internal cystic change. Contrast enhancement is seen in only a minority of these lesions (see Fig. 9-27C ).

Dysembryoplastic neuroepithelial tumor (DNET). A, Axial T2-weighted MRI demonstrates a well-circumscribed superficial cystic mass with heterogeneous signal hyperintensity in the right midfrontal convexity cortex with an outwardly bulging external surface. B, Axial turbo FLAIR image through the lesion demonstrates suppression of signal in the anterior aspect consistent with relatively simple fluid and persistence of mild signal hyperintensity in the posterior aspect consistent with either proteinaceous fluid or a soft tissue component. C, Axial T1-weighted image after IV gadolinium demonstrates no contrast enhancement within the cyst. The lesion is eroding the inner table of the overlying calvarium.

Central neurocytoma.

A relatively rare benign slow-growing (WHO grade II) intraventricular tumor, central neurocytoma has now been recognized as a separate entity. It occurs almost exclusively in the anterior portion of the lateral ventricle, arising from the superolateral ventricular wall and extending medially adjacent to the septum pellucidum and the foramen of Monro; extension through the foramen into the third ventricle is unusual. No such tumors have been reported arising in the third or fourth ventricles, and only a few hemispheric lesions have been found. Central neurocytomas are tumors of young adults and are rare in children and older adults. Patients typically present clinically with headache and signs of increased intracranial pressure secondary to ventricular obstruction. Partial or complete surgical excision is the treatment of choice, and no deaths from tumor growth or recurrence have been reported.

Histologically, central neurocytoma is identical to oligodendroglioma. It is characterized by nests of small well-differentiated cells separated by thin fibrovascular septa. Intratumoral calcification and multiple small cysts are common findings, but hemorrhage (either intratumoral or intraventricular) is unusual. It is only with electron microscopy and immunohistochemistry that its neuronal origin can be determined.

CT demonstrates a sharply marginated, inhomogeneous, isodense to slightly hyperdense intraventricular mass with a broad-based attachment to the wall of the frontal horn or anterior body of the lateral ventricle and abutting the septum pellucidum. Calcifications, either coarse or globular, and multiple small intratumoral hypodense cysts are found in 50% or more of central neurocytomas. Mild to moderate contrast enhancement of the isodense to hyperdense regions is common.

The findings on MRI are similar. The tumor demonstrates a heterogeneous pattern with intermixed foci of isointensity (compared with adjacent gray matter) and hypointensity (due to calcifications and cysts) on T1-weighted images and isointensity to hyperintensity on T2-weighted images ( Fig. 9-28A ). Inhomogeneous mild contrast enhancement is common (see Fig. 9-28B ).

Central neurocytoma in the anterior body and frontal horn of the left lateral ventricle. A, Axial T2-weighted MRI demonstrates a large multilobulated heterogeneous but predominantly isointense (to gray matter) intraventricular mass arising from the lateral wall of the left lateral ventricle (arrow) with multiple small hyperintense foci and one large intratumoral hyperintense cyst. The tumor expands the left lateral ventricle. Enlargement of both lateral ventricles is likely secondary to obstruction of the foramen of Monro by this mass. B, Coronal T1-weighted spoiled gradient echo image following IV gadolinium administration; the plane of section passes through the anterior portion of the tumor. The more solid portion of this tumor demonstrates faint contrast enhancement (arrow) . Note extension of the tumor inferiorly and medially at a level just anterior to the foramen of Monro.

The differential diagnosis is that of a well-circumscribed intraventricular mass at or near the foramen of Monro and includes subependymal giant cell astrocytoma and subependymoma. The absence of deep extension into adjacent brain parenchyma, associated nodular tubers and intratumoral hemorrhage, and the relatively young age of the patient favor the diagnosis of central neurocytoma.

Pineal Parenchymal Tumors.

Tumors arising within the parenchyma of the pineal gland constitute less than 1% of all primary brain tumors in adults. However, pineal tumors represent nearly 10% of all pediatric brain tumors. The most common tumors to involve the pineal gland are the germ cell tumors, which constitute 50% to 70% of pineal region tumors and are discussed elsewhere in this chapter.

Pineal parenchymal tumors represent only 15% to 30% of pineal region neoplasms. They include a range from primitive undifferentiated (pineoblastoma) through transitional forms (primary parenchymal tumor of intermediate differentiation) to well-differentiated (pineocytoma).

Pineoblastoma.

Pineoblastomas are pediatric tumors with a peak incidence in the first 2 decades of life and rare after age 30. These malignant highly cellular undifferentiated small cell tumors are histologically and histochemically identical to other primitive neuroectodermal tumors and exhibit similar biological behavior. They are locally invasive and may spread into the third ventricle, thalami, and quadrigeminal plate. Pineoblastomas frequently contain areas of hemorrhage and necrosis, and intratumoral calcification is common. Presenting symptoms include precocious puberty (possibly related to destruction of normal pineal tissue with loss of melatonin secretion), Parinaud’s syndrome and other cranial nerve deficits, and obstructive hydrocephalus. Dissemination via the CSF with leptomeningeal and ependymal metastases occurs in 10% of cases and may be found at the time of initial diagnosis. The 5-year survival rate is 58%.

On CT, pineoblastomas appear hyperdense with irregular intratumoral calcification, infiltration into neighboring structures, and mass effect on the posterior aspect of the third ventricle and the tectum of the midbrain. They demonstrate dense contrast enhancement. On MRI, pineoblastomas appear heterogeneous in signal, predominantly hypointense to gray matter on T1-weighted images and isointense to gray matter on T2-weighted images, with interspersed foci of hypointensity secondary to intratumoral necrosis and calcification ( Fig. 9-29A and B ). As on CT, contrast enhancement of the solid portion of the tumor is the rule (see Fig. 9-29C ). The chief differential consideration is germinoma, which may look identical on CT and MRI.

Pineoblastoma. A, Axial T2-weighted MRI demonstrates a small ovoid tumor mass (arrow) arising in the region of the pineal gland and protruding posteriorly into the quadrigeminal plate cistern. The tumor is heterogeneous in signal but predominantly hyperintense to gray matter. Axial T1-weighted images before ( B ) and after ( C ) IV gadolinium administration demonstrate intense homogeneous contrast enhancement of the entire tumor mass (arrows). Note the blunting of the posterior margin of the third ventricle by this pineal tumor.

A rare occurrence that is nevertheless important for recognition and management is the association of bilateral retinoblastomas with pineoblastoma, often termed trilateral retinoblastoma. This condition, an inherited disorder occurring in very young children (<2 years), is found in 3% of patients with bilateral retinoblastomas.

Pineocytoma.

Pineocytomas are tumors of adults, with a mean age of presentation of 36 years. Compared with pineoblastomas, these lesions are less densely cellular with well-differentiated cells that have more cytoplasm arranged in lobules in an architecture similar to that of the normal pineal gland. They tend to follow a slower and more benign clinical course, but transitional tumors intermediate in cellularity and mitotic activity also exist. Intratumoral calcification is present in more than 50%. Subarachnoid seeding is not seen in the more benign neoplasms. The 5-year survival for pineocytomas is 67%.

On CT, the typical appearance is of a rounded, well-circumscribed, homogeneously hyperdense lobulated expansile mass with intratumoral calcification situated at and often obstructing the posterior margin of the third ventricle ( Fig. 9-30A ). There is no evidence of invasion of neighboring structures. Multiplanar MRI demonstrates a rounded or ovoid mass compressing the posterior margin of the third ventricle and the superior aspect of the quadrigeminal plate. The mass is homogeneously hypointense to isointense on T1-weighted images and hyperintense relative to gray matter on T2-weighted images. The signal characteristics reflect the higher water content of these more mature tumors compared with pineoblastomas. Contrast enhancement of all or a major portion of a pineocytoma is the rule on both CT (see Fig. 9-30B ) and MRI.

Pineocytoma. Axial noncontrast ( A ) and postcontrast ( B ) CT images demonstrate a well-circumscribed markedly hyperdense mass in the midline ( arrow in A ) in the pineal region, with bilateral lobulated intense contrast enhancement impinging on the medial aspects of both thalami ( arrow in B ). The tumor is partially obstructing the posterior aspect of the third ventricle, accounting for the enlarged lateral and anterior third ventricles.

Embryonal Tumors.

The terminology regarding primitive or embryonal tumors of neuroepithelial origin has been a source of controversy for more than 2 decades. Gradually, however, a consensus appears to be emerging concomitant with advances in applied molecular biology. PNETs of the CNS appear to be one group of a larger category of embryonal tumors that occur throughout the body (e.g., neuroblastomas of the adrenal and sympathetic ganglia). These are the second most common intracranial tumors of childhood, representing approximately 15% to 20% of all childhood brain tumors and exceeded in frequency only by astrocytomas. They have a common histology consisting of densely packed undifferentiated round cells with a high nucleus-to-cytoplasm ratio and high mitotic activity but follow divergent patterns of differentiation.

The classic PNET is the medulloblastoma of the cerebellar vermis, which constitutes 85% of this group of tumors. The remaining 15%, almost all supratentorial, include pineoblastomas (see earlier), ependymoblastomas, and medulloepitheliomas. The histogenesis of PNETs is undetermined, but one hypothesis is that they arise from immature pluripotential precursor cells in the subependymal layers of the developing ventricular system and in the external granular layer of the cerebellum.

Medulloblastoma.

An invasive and highly malignant tumor (WHO grade IV), medulloblastoma is the second most common primary brain tumor of childhood and the most common pediatric posterior fossa neoplasm. Although medulloblastomas may occur at any age, 75% present clinically before age 15. There are two distinct age peaks, at 4 to 8 years and 15 to 35 years. In children, medulloblastomas are primarily tumors of the cerebellar vermis ( Fig. 9-31 ), but in adults they tend to be located more laterally in the cerebellar hemispheres (see Fig. 9-31 ). The typical clinical presentation consists of signs of obstructive hydrocephalus, cerebellar dysfunction, or both—headache, nausea, vomiting, and ataxia.

Medulloblastoma of the cerebellar vermis in an 11-year-old child. A, Axial noncontrast CT image demonstrates a large lobulated hyperdense round tumor (arrow) with an internal hypodense cavity to the right of the midline that compresses the fourth ventricle from behind. An ill-defined faintly hypodense band surrounding the hyperdense mass represents white matter edema. The intratumoral area of marked hypodensity to the right of the midline likely represents necrosis. A smaller focus of lesser hypodensity on the left posterolateral tumor margin suggests an intratumoral cyst. These findings are confirmed on noncontrast axial T1-weighted ( B ) and T2-weighted ( C ) MRIs; the solid portion of the tumor appears mildly hypointense on T1-weighting and mildly hyperintense on T2-weighting (arrow). Following IV gadolinium, an axial T1-weighted image ( D ) demonstrates irregular patchy contrast enhancement of the solid areas of the tumor (arrow).

These aggressive tumors grow rapidly with extension from the vermis into the fourth ventricle and spread inferiorly into its recesses and outlet foramina and superiorly into the aqueduct. More than 90% present clinically with hydrocephalus. They have a strong tendency to seed via the CSF, and approximately 40% demonstrate subarachnoid or retrograde ependymal metastases at the time of initial diagnosis. They are highly radiosensitive, and the standard treatment approach is gross total resection plus chemotherapy and total craniospinal axis irradiation. Ten-year survival rates are in the range of 50% to 70%, but the prognosis is poorer in children younger than 3 years. Recurrence after the initial treatment regimen is about equally distributed between local regrowth at the primary tumor site and distant metastasis. Systemic metastasis, a highly unusual occurrence with most CNS primary neoplasms, is identified in approximately 5% of patients, mainly to bone.

Compared with other highly aggressive brain tumors, medulloblastomas appear relatively discrete and solid with convex margins on gross inspection but may contain foci of necrosis and hemorrhage. Microscopically the tumor cells tend to be arranged in pseudorosettes, and areas of vascular proliferation, cellular pleomorphism, and calcification are occasionally identified. Electron microscopy and immunostaining usually confirm neuronal differentiation. Approximately 15% of medulloblastomas contain a significant amount of collagen and reticulin and may demonstrate a nodular pattern; designated desmoplastic medulloblastomas, these tumors are relatively more common in the cerebellar hemispheres in adolescents and young adults.

On noncontrast CT, medulloblastomas appear as rounded or oblong, mainly homogeneous, isodense to slightly hyperdense masses centrally located in the inferior vermis and cavity of the fourth ventricle (see Fig. 9-31A ). Differentiation of medulloblastoma from diffuse solid cerebellar astrocytoma is most reliably made on noncontrast CT. The solid hyperdense appearance of medulloblastoma reflects the dense cellular nature of this tumor, whereas astrocytomas are typically rather uniformly hypodense. Obstruction of the fourth ventricle, inferior aqueduct, or both with resulting enlargement of the third and lateral ventricles is commonly seen on CT at the time of clinical presentation. Punctate or nodular intratumoral calcifications are identified in 10% to 20% of cases. Hypodense intratumoral foci of necrosis and cysts are found in up to 50% of medulloblastomas (see Fig. 9-31A ). Many medulloblastomas are surrounded by a thick poorly marginated hypodense halo representing extensive peritumoral edema (see Fig. 9-31A and B ). The imaging findings in young adults are similar except for the more lateral (hemispheric) location of the tumor.

After IV administration of contrast medium, moderate to intense homogeneous enhancement of the solid tumor mass is the rule in medulloblastomas, although approximately 10% do not demonstrate contrast enhancement on CT. Areas of tumor seeding in the posterior fossa cisterns or in the third or lateral ventricles exhibit similar homogeneous contrast enhancement in a nodular or sheetlike configuration.

The appearance of medulloblastomas is less specific on MRI than on CT. The tumors are mildly hypointense to isointense relative to the adjacent cerebellar vermis on T1 and isointense to slightly hyperintense on T2-weighted images ( Fig. 9-32A ; see Fig. 9-31B and C ). Isointensity (or even hypointensity) of the tumor matrix on T2-weighted images is likely due to the hypercellularity and high nucleus-to-cytoplasm ratio of this tumor. However, heterogeneity of signal intensity is often seen on T2-weighted images (see Figs. 9-31C and 9-32B ) secondary to intratumoral cysts, necrosis, vascular flow voids, and hemorrhage. Contrast enhancement of the solid portions of the tumor, seen in more than 90% of patients, is typically intense and homogeneous (see Figs. 9-32B and 9-75A ) but may be irregular and patchy (see Fig. 9-31D ). MRI with contrast enhancement is very sensitive for detecting tumor spread and metastatic seeding in the cranial and spinal subarachnoid spaces.

Medulloblastoma of the anteroinferior right cerebellar hemisphere in a 26-year-old patient. A, Axial T2-weighted MRI demonstrates a poorly circumscribed mass with a heterogeneous signal pattern in the anteroinferior portion of the right cerebellar hemisphere. Irregular areas of pronounced hyperintensity (arrow) are interspersed in a mildly hyperintense background that likely represents surrounding edema. The tumor extends medially into the inferior vermis. B, After IV gadolinium the tumor demonstrates homogeneous contrast enhancement with well-circumscribed margins (arrow). Punctate intratumoral hypointensities represent enlarged vascular channels and/or focal calcifications.

CNS primitive neuroectodermal tumor.

Some 15% of all PNETs of the CNS occur above the tentorium. However, they represent less than 1% of all pediatric brain tumors. Like their infratentorial counterparts, they occur mainly in the very young (65% of patients < 5 years; 85% < 10 years). Patients may present clinically with seizures or with symptoms and signs of increased intracranial pressure. The distribution of these aggressive tumors within the cerebral hemispheres is, in diminishing order of frequency, frontal, parietal, temporal, and occipital. Approximately one third are pineoblastomas; the remainder are central neuroblastomas, ependymoblastomas, ganglioneuroblastomas, medulloepitheliomas, and other rare immature round cell tumors.

On CT, CNS PNETs appear heterogeneous and well circumscribed. The heterogeneity reflects cystic or necrotic changes and intratumoral hemorrhage. The solid elements are hyperdense because of their high cellularity and demonstrate contrast enhancement. Coarse calcifications are described in 50% to 70%, a much higher proportion than in cerebellar medulloblastomas. CNS PNETs share with their infratentorial counterparts a strong propensity for spread via CSF.

MRI also demonstrates heterogeneity of signal intensity on both T1- and T2-weighted images ( Fig. 9-33 ; see Fig. 9-73 ). These are often large tumors with relatively lesser degrees of surrounding edema. The differential diagnosis includes other large well-circumscribed supratentorial tumors such as ependymomas and oligodendrogliomas. As on CT, the solid portions of the tumor demonstrate strong contrast enhancement, a feature that may aid differentiation.

Primitive neuroectodermal tumor in the left parietooccipital region (postcraniotomy). A, Axial T2-weighted MRI demonstrates an ovoid heterogeneously hyperintense mass in the left parietooccipital white matter with extension into the overlying convexity cortex and a single large intratumoral sharply marginated central collection of marked hyperintensity, likely representing a combination of necrosis, surgical resection cavity, and/or cyst formation (arrow). The mass compresses and displaces the atrium of the left lateral ventricle from behind. B, Following IV gadolinium, an axial T1-weighted image demonstrates irregular contrast enhancement within the tumor interstices without enhancement of the central cavity (arrow).

Schwannoma.

Schwannoma is a benign (WHO grade I) encapsulated tumor that arises from Schwann cells of nerve sheaths of cranial and spinal nerves. It is estimated to account for between 5% and 10% of primary intracranial neoplasms and for nearly 30% of intraspinal tumors.

Intracranial schwannomas occur in all age groups, but the peak incidence is in the fourth through seventh decades of life. There is a distinct sex predilection, with a female-to-male ratio of 2 : 1, although no such predilection exists in regard to spinal schwannomas.

By far the most common site of intracranial involvement is the superior vestibular division of the eighth cranial nerve. Trigeminal nerve schwannomas are much less common, with facial, trochlear, and abducens nerve tumors only rarely reported. Only the first (olfactory) and second (optic) cranial nerves lack Schwann cell sheaths and are therefore not potential sites of origin. The clinical presentation varies according to the site of origin. Vestibular schwannoma (also called acoustic neuroma or neurinoma ) typically presents with symptoms of a mass in the cerebellopontine angle, including tinnitus, sensorineural hearing loss, and facial paresthesias. Despite the tumor’s origin from the vestibular nerve, symptoms and signs of vestibular dysfunction do not become manifest until relatively late. These tumors have a distinct propensity to involve the sensory nerve roots; motor symptoms are uncommon.

Multiplicity of intracranial schwannomas strongly suggests the presence of neurofibromatosis type 2 (NF2), a congenital inherited disorder associated with a mutation on the long arm of chromosome 22. The occurrence of bilateral vestibular schwannomas (see Fig. 9-35 ) is pathognomonic of this disorder, which has also been termed MISME (multiple inherited schwannomas, meningiomas, and ependymomas). In fact, labeling this disorder “neurofibromatosis” is a misnomer because neurofibromas are not a part of its constellation of abnormalities. Patients with this disorder typically present clinically in the second and third decades of life, much earlier than those with sporadic intracranial schwannoma.

On gross inspection, schwannomas appear as focal well-circumscribed globular or ovoid masses that do not infiltrate the nerve but rather arise and grow eccentrically, displacing the uninvolved portion of the cranial nerve of origin to the side. As the tumor grows and matures, it may undergo cystic degeneration or develop patchy areas of lipid accumulation. Vestibular schwannomas typically enlarge within the cerebellopontine angle cistern and may displace and compress the adjacent pons, medulla, and fourth ventricle (see Fig. 9-21 ). They can attain considerable size before becoming clinically evident. Obstruction of the ipsilateral cerebellopontine angle cistern may occur with formation of one or more extratumoral arachnoid cysts. Trigeminal schwannomas tend to occur more commonly in the parasellar region of the middle cranial fossa than in the posterior fossa, although approximately 25% extend through the tentorial notch, involving both fossae.

Microscopic evaluation of a schwannoma typically demonstrates a well-encapsulated tumor containing collections of spindle-shaped Schwann cells in both compact cellular (Antoni A) and less cellular and more loosely textured (Antoni B) arrangements. Histologic variations are commonly encountered in larger tumors, including intratumoral clusters of lipid-laden cells, confluent microcysts and larger cysts, and dilated vascular sinusoids surrounded by foci of hemorrhage.

The diagnosis of vestibular schwannoma on CT rests on demonstration of a well-circumscribed globular or ovoid, hypodense to isodense (with respect to the adjacent pons and cerebellum) extraaxial mass in the cerebellopontine angle cistern, with its base on the posterior aspect of the petrous temporal bone in the region of the internal auditory meatus. Images displayed in a bone window may demonstrate fusiform widening of the internal auditory canal with erosion of its bony margins. However, soft tissue detail within the cisternal portion of the tumor is often obscured by beam-hardening artifacts caused by the adjacent dense cortical bone and pneumatized air cells of the petrous pyramid. Tumors up to about 1 cm in diameter typically demonstrate homogeneous density and homogeneously strong contrast enhancement, but larger tumors often demonstrate heterogeneity of both density and contrast enhancement because of the presence of intratumoral cystic degeneration, xanthomatous change, or intermixed areas of hypercellularity and hypocellularity.

On MRI, smaller tumors can be more reliably detected, especially within the internal auditory canal, because of the lack of bone-induced artifact and the multidimensional capability of this modality. The transition zone between the central (oligodendroglial) and peripheral (Schwann cell) portions of the eighth (vestibulocochlear) nerve, the presumed site of origin of schwannomas of this nerve, occurs within the canal. Tumors less than 5 mm in diameter can be reliably identified on thin-section T1-weighted MRI, appearing as homogeneously mildly hypointense or isointense (to adjacent brain) ovoid or tubular intracanalicular masses with intense homogeneous contrast enhancement ( Fig. 9-34 ). On T2-weighted pulsing sequences, small vestibular schwannomas appear mildly to markedly hyperintense and may be obscured by the similarity in signal intensity to that of the surrounding CSF.

Vestibular schwannoma. Axial T1-weighted image of the posterior fossa and skull base following IV gadolinium. A small intensely enhancing intracanalicular ovoid mass protrudes slightly medially into the cerebellopontine angle cistern on the patient’s right (arrow).

As these tumors enlarge, the intratumoral degenerative changes previously described cause increasing heterogeneity of signal within the main tumor mass in the cerebellopontine angle cistern. On axial images the tumor often has a comma-like shape with a globular cisternal mass medially and a short tapered fusiform extension laterally into the internal auditory canal. Contrast enhancement is seen in nearly all schwannomas and may be homogeneous (two thirds of cases) or heterogeneous ( Fig. 9-35 ; see Figs. 9-21 and 9-34 ). Larger tumors compress and displace the adjacent anterolateral margin of the cerebellar hemisphere posteromedially; displace, compress, and rotate the pons and medulla; and narrow the fourth ventricle, elongating it in the anteroposterior direction (see Figs. 9-21 and 9-35 ). Peritumoral vasogenic edema is frequently observed, and (as noted previously) associated arachnoid cysts are visualized in 5% to 10% of cases.

Bilateral vestibular schwannomas and right trigeminal schwannoma in a patient with NF2. Coronal postgadolinium T1-weighted MRI demonstrates three intensely contrast-enhancing lesions in the posterior cranial fossa. The large left-sided lobulated vestibular schwannoma fills the left cerebellopontine angle cistern (white arrow); compresses, indents, and displaces the left lateral margin of the pons inward; and extends laterally into the widened left internal auditory canal. A tiny punctate focus of contrast enhancement in the right petrous temporal region (arrowhead) represents a small intracanalicular vestibular schwannoma. A third focus of contrast enhancement abuts and indents the right lateral margin of the pons (black arrow); this is a trigeminal (fifth cranial nerve) schwannoma.

Vestibular schwannomas represent 80% to 85% of cerebellopontine angle masses. The major differential diagnostic considerations include meningioma and epidermoid tumor. Meningioma involving the dura of the posterior margin of the petrous temporal bone can project posteriorly into the cerebellopontine angle and simulate a vestibular schwannoma ( Fig. 9-36 ). Such lesions represent about 10% of cerebellopontine angle masses. Although meningiomas are typically more dense on CT, these two neoplasms may have identical signal intensity characteristics on MRI. Intense homogeneous or slightly heterogeneous contrast enhancement is another shared characteristic (see Fig. 9-36B ). However, meningiomas are usually situated eccentric to the internal auditory canal and form a more obtuse angle with the petrous ridge than schwannomas. Extension of meningioma into the internal auditory canal is uncommon but not unknown, and rarely schwannoma may simulate the appearance of a dural tail on postcontrast images.

Meningioma arising from the posterior aspect of the left temporal bone. A, Axial T2-weighted MRI demonstrates a large rounded extraaxial tumor mass in the right side of the posterior fossa with its base on the posterior dura of the left temporal bone. The mass is slightly hyperintense relative to gray matter and compresses and displaces the right cerebellar hemisphere posteriorly and medially. A narrow cleft of CSF (arrow) separates the medial margin of the tumor from the adjacent compressed cerebellum and pons. Note that the internal auditory canals bilaterally are filled with CSF. B, Following IV gadolinium, an axial T1-weighted image demonstrates intense homogeneous contrast enhancement of this large dural-based tumor (arrow).

Epidermoid may resemble vestibular schwannoma on noncontrast CT but typically appears more lobulated and more hypodense and tends to insinuate more extensively into the subarachnoid spaces adjacent to the pons without causing major compression of the pons or fourth ventricle. On both CT and MRI, epidermoid does not demonstrate contrast enhancement. On MRI, larger epidermoids appear more homogeneous than schwannomas of similar size and may mimic CSF in intensity with high T2 signal and low T1 signal ; differentiation from arachnoid cyst is made by the demonstration on DWI of restricted diffusion in epidermoid.

Neurofibroma.

Neurofibromas are well-demarcated infiltrative intraneural or diffusely infiltrative extraneural benign tumors that consist of a mixture of neoplastic Schwann cells, perineurial cells, and fibroblasts in a collagenous and mucoid matrix. They are histologically benign and considered WHO grade I. With only extremely rare exceptions, neurofibromas do not arise within the intracranial portions of the cranial nerves. However, they can arise peripherally and extend retrogradely into the cranial vault, notably in the facial nerve (CN VII) and the ophthalmic division of the trigeminal nerve (CN V1).

The tumors exhibiting this retrograde intracranial extension are usually plexiform neurofibromas that involve multiple nerve fascicles or trunks with fusiform multinodular enlargement often described as ropelike. On noncontrast CT, they appear isodense to adjacent muscle, and on MRI they are isointense to adjacent muscle on T1-weighted images and hyperintense on T2-weighted images. Contrast enhancement is variable, with areas of moderate to strong enhancement after IV administration of gadolinium.

Multiple neurofibromas are typically associated with NF1 (von Recklinghausen’s disease), an autosomal dominant congenital disorder associated with a gene defect on the long arm of chromosome 17. Approximately 50% of patients report no family history and are presumed to have new spontaneous germline mutations. In addition to multiple neurofibromas of the spinal and peripheral nerves, NF1 also includes optic nerve and chiasm gliomas (see earlier); foci of “hamartomatous” change of uncertain etiology in the region of the basal ganglia and in the optic tracts and radiations, cerebral peduncles, and brainstem; astrocytomas of the spinal cord; multiple café au lait spots; axillary and inguinal freckling; malignant peripheral nerve sheath tumors; iris hamartomas (Lisch nodules); and dysplastic osseous lesions (sphenoid wing dysplasia, pencil-like hypoplasia of the metaphyses of long bones). Patients with NF1 usually present clinically very early in life, whereas those with sporadic solitary neurofibroma involving a cranial nerve may present in later youth and adult life.

On noncontrast CT, plexiform neurofibroma appears as a poorly circumscribed irregular widening of the involved nerve root, which is isodense with adjacent muscles. Erosion of adjacent bone with widening of bony foramina may be evident. MRI demonstrates the widened nerve, which is isointense to adjacent muscle on T1-weighted images and hyperintense on T2-weighted images. Contrast enhancement after IV administration of gadolinium is the rule, varying from moderate to intense.

Malignant Peripheral Nerve Sheath Tumors.

Malignant peripheral nerve sheath tumors are rare tumors that appear to arise de novo in the cranial nerves, the fifth cranial nerve being more frequently involved than any other. Elsewhere in the body, almost two thirds of reported cases of malignant peripheral nerve sheath tumors have arisen from preexisting neurofibromas, often in the setting of NF1. Approximately 50% occur in association with NF1. The incidence of malignant progression in patients with plexiform neurofibroma is approximately 5%. Imaging findings include irregularity and loss of clear tumor margins together with inhomogeneous contrast enhancement. Evidence of diffuse invasion of the skull base may also be present.

Meningioma.

Meningiomas are solid, well-circumscribed, highly cellular, slow-growing tumors that are usually benign histologically (WHO grade I). These sometimes spherical, sometimes lobulated, and sometimes flat and broad-based tumors are composed of neoplastic meningothelial cells originating from the arachnoid layer of the meninges, with a broad attachment to the adjacent dura. Most commonly they project inward from the dura, indenting and compressing the underlying brain, causing neurologic symptoms and signs through compression of the adjacent cortex.

Meningiomas are the most common primary extracerebral tumors of the CNS, accounting for approximately 20% of primary brain tumors. They occur mainly in middle and old age, with a peak incidence in the fifth through seventh decades of life; these tumors can, however, be found in all age groups. Meningiomas exhibit a strong sex predilection, occurring preponderantly in females, with a female-to-male ratio of at least 2 : 1. However, meningiomas associated with hereditary tumor syndromes such as NF2 generally occur in younger patients and do not demonstrate a gender predilection.

Common sites of origin are in the frontal and parietal convexities and the parasagittal region (in close association with the falx cerebri); tumors in these locations constitute about 50% of all intracranial meningiomas. Meningiomas arising in relation to the sphenoid wings, olfactory grooves, sylvian fissures, and parasellar regions represent about 35%. Less than 10% arise below the level of the tentorium, mainly from the meninges overlying the clivus and petrous pyramid and the leaves and free edge of the tentorium. Multiple meningiomas are reported in 6% to 9% of cases, occurring as a component of NF2 and less commonly sporadically.

Although most meningiomas are slow-growing and well-encapsulated globular masses, variations in shape and histology are not unusual. Invasion of the dura and encasement or invasion of the nearby dural venous sinuses are common. Tumors arising in relation to the sphenoid wing are frequently flat (en plaque) and tend to invade through both layers of the cranial dura into the adjacent bone, provoking a notable bony reaction with thickening and sclerosis (meningioma bone). Such bony changes are a source of considerable controversy; many clinical neuroscientists regard bony sclerosis and thickening as highly indicative of tumor infiltration into the haversian canals of the calvaria, whereas others state that such hyperostosis can also occur without histologic evidence of bone infiltration by tumor. Meningiomas arising adjacent to the cribriform plate and planum sphenoidale and those occurring over the high cerebral convexities are more typically rounded and invaginate the underlying brain; however, they can also show a propensity for stimulating adjacent bony thickening and sclerosis ( Fig. 9-37 ).

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related posts:

Imaging Principles in Computed Tomography Normal Anatomy Paranasal Sinuses Meningeal Processes Imaging of the Head and Neck in the Pediatric Patient Imaging Principles in Magnetic Resonance Angiography

Stay updated, free articles. Join our Telegram channel

Join