The central nervous system (CNS) is the site of origin for approximately 20% of pediatric cancers. CNS neoplasms are the second most common type of childhood tumors, after leukemia. The overall 5-year survival rate for pediatric CNS malignancies is 70%. The prevalence of brain tumors in children younger than 15 years of age is approximately 2.4 per 100,000. High-grade (World Health Organization [WHO] grade ≥3) CNS neoplasms in children include primitive neuroectodermal tumor (PNET), malignant germ cell tumors, grade III/IV astrocytoma, leukemia/lymphoma, esthesioneuroblastoma, and metastatic disease. Low-grade (WHO grade ≤2) tumors include juvenile pilocytic astrocytoma, grade II astrocytoma, germinoma, craniopharyngioma, meningioma, ganglioglioma, nonanaplastic ependymoma, acoustic neuroma, low-grade oligodendroglioma, and dysembryoplastic neuroepithelial tumor (DNET).¹

In infants and toddlers, supratentorial tumors are more common than those of the posterior fossa. The most common supratentorial lesions in this age group are astrocytoma, ependymoma, and PNET. Neonatal brain tumors are rare; the most common types are teratoma, PNET, astrocytoma, and choroid plexus papilloma. Infratentorial tumors predominate in children between the ages of 4 and 11 years. The frequency of supratentorial and posterior fossa neoplasms is approximately equal in children older than 11 years of age.

Potential clinical manifestations of an intracranial neoplasm in a young child include progressive macrocephaly, nausea, vomiting, and lethargy. Nausea and vomiting in these children sometimes lead to a mistaken diagnosis of GI tract pathology. Common findings in older children include headache, nausea and vomiting, dizziness, visual impairment, and focal neurological signs such as cranial nerve palsy, ataxia, and hemiparesis. Seizures occur in 40% to 75% of pediatric patients with cerebral hemispheric tumors. Endocrine dysfunction can occur in association with a hypothalamic or pituitary lesion; potential sequelae include diabetes insipidus, growth failure, and precocious puberty.

Imaging Evaluation

MR is the imaging modality of choice for the detection and characterization of most brain neoplasms. CT is a lower cost alternative screening technique for children with nonspecific symptoms. CT is also occasionally useful to demonstrate calcifications in tumors or to evaluate calvarial destruction. The MR evaluation of brain neoplasms should include diffusion-weighted and contrast-enhanced images. MR angiography and MR spectroscopy are important for selected patients. In general, high-grade brain neoplasms tend to exhibit restricted diffusion on diffusion-weighted and apparent diffusion coefficient (ADC) map images, whereas low grade tumors are often isointense on these sequences.²

After surgical resection of a brain tumor, a baseline MR within 72 hours of the procedure is often helpful to detect residual neoplasm. A thin enhancing rim at the margin of the resection cavity is common, particularly during the first 24 hours. This postsurgical breakdown of the blood-brain barrier usually does not represent residual neoplasm. Nodular enhancement at this time is suspicious for residual neoplasm. Imaging at 1 to 2 weeks after surgery is suboptimal, as reactive nodular enhancement often has developed at this point. This nonneoplastic nodular enhancement usually decreases after approximately 6 weeks, but can persist for 12 months or longer. Areas of restricted diffusion adjacent to the resection margin in the immediate postoperative period usually represent surgical alterations rather than residual tumor. These areas often undergo contrast enhancement on intermediate-term follow up studies, and progress to encephalomalacia on long-term follow up.³

Hydrogen (proton) MR spectroscopy is useful for selected patients to assess the biological aggressiveness of a brain tumor and to differentiate recurrent/residual neoplasm from scaring or necrosis (Table 19-1), (Figure 19-1). The choline (Cho) peak of the MR spectra provides information about cell membrane synthesis and degradation. There is elevated Cho in malignant lesions, due to high cell turnover and elevated cell density. Synthesis of N-acetyl-Laspartate (NAA) occurs in the mitochondria of neurons and is a neuronal marker on the MR spectra. Neuronal destruction in malignant tumors causes diminished NAA levels. The NAA peak is usually normal or mildly diminished in benign lesions. The creatine (Cr) peak represents creatine and phosphocreatine. This peak indicates the status of cellular energy metabolism. In viable tissue, the Cr peak is relatively stable and serves as an internal reference for other metabolites. There is diminished or absent creatine in necrotic tissue, however. Lactate is the end product of the anaerobic energy pathway; the lactate peak is elevated in areas of ischemia or hypoxia. Myo-inositol is a glial marker that is a product of myelin degradation; this peak is diminished in most tumors.⁴

Radiation necrosis can mimic residual tumor on MRI. The enhancement intensity of areas of radiation necrosis may not peak until 4 to 6 months after the therapy. MR spectroscopy can be helpful in differentiating radiation necrosis or reactive nodular enhancement from recurrent or residual neoplasm. Neoplastic tissue usually causes an elevated Cho peak, diminished NAA peak, and high Cho/NAA ratio. Radiation necrosis typically results in reduced Cho and elevated lipid and lactate levels.⁵

Astrocytoma

Astrocytoma accounts for about one-third of cerebral hemispheric tumors in children. The peak prevalence is between the ages of 8 and 12 years; however, this neoplasm occurs in children of all ages. There is a slight male predominance. There is a spectrum of biological aggressiveness and histological types of astrocytoma (Table 19-2).

The most common histological types of supratentorial astrocytoma in children are pilocytic astrocytoma and diffuse or fibrillary astrocytoma. Pilocytic astrocytomas (WHO grade I) consist of “loosely knit” tissue with alternating areas of high and low cellularity, as well as microcysts. Pilomyxoid astrocytoma has a more aggressive clinical course than the pilocytic variety. About 60% of these tumors arise in the suprasellar region or medial aspect of the temporal lobe, usually in an infant or young child. Leptomeningeal metastasis is common. Diffuse astrocytomas are WHO grade II lesions that typically arise within the cerebral white matter. These are histologically hypercellular. Tumoral cysts are common. These usually undergo slow growth and diffusely infiltrate adjacent brain; there is a tendency for malignant transformation. Anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV) constitute “high-grade” astrocytomas. Anaplastic astrocytoma contains large numbers of pleomorphic cells. Glioblastoma multiforme has a similar histological appearance, but more prominent vascular proliferation and areas of necrosis. Astrocytoma accounts for approximately 80% of intracranial gliomas; other gliomas include oligodendroglioma, ependymoma, and choroid plexus tumors.

Supratentorial high-grade astrocytomas account for 6% to 12% of primary pediatric brain tumors and 20% of hemispheric astrocytomas. These lesions are most common in the adolescent age group; the incidence in patients between the ages of 15 and 19 years is approximately 0.2 per 100,000 person-years. Long-term survival is less than 20%. The signs and symptoms of a supratentorial high-grade astrocytoma relate to the region of the brain that is involved. Common features include seizures and signs of elevated intracranial pressure. The completeness of surgical resection is the most important clinical prognostic factor for supratentorial high-grade astrocytoma. Although a locally invasive neoplasm, leptomeningeal spread at the time of diagnosis occurs in less than 10% of patients. Approximately 90% of recurrences include disease at the original site. Leptomeningeal spread, usually in combination with local failure, is present in about one-third of recurrences.⁶

The clinical manifestations of a low-grade supratentorial astrocytoma vary with the location and size. A lesion of the cerebral hemisphere can cause headache, seizures, nausea, vomiting, hemiparesis, papilledema, and ataxia. Patients with an astrocytoma of the hypothalamus sometimes have hypothalamic-pituitary dysfunction (e.g., diabetes insipidus or obesity). A tumor at this location can also lead to diencephalic syndrome: emaciation, hyperkinesis, irritability, an alert appearance, and normal or accelerated body height. An astrocytoma of the thalamus frequently causes hemiparesis by way of corticospinal tract compression; hydrocephalus is also common. The most common location of a cerebral pilocytic astrocytoma is the temporal lobe.

There is considerable overlap in the neuroimaging appearances of the different types of supratentorial astrocytoma. In comparison to lower grade lesions, high-grade astrocytomas usually have more prominent necrosis and hemorrhage, are larger, and result in more extensive peritumoral vasogenic edema (Figure 19-2). Low-grade astrocytomas other than the pilocytic variety are usually solid homogeneous lesions, with relatively well-defined margins and limited perilesional edema. The enhancement characteristics of low-grade lesions are variable; some of these tumors undergo no appreciable contrast enhancement. A homogeneous solid nonenhancing astrocytoma sometimes mimics the imaging appearance of a debris-containing cyst. Supratentorial pilocytic astrocytoma is typically a cystic mass with a discrete mural nodule; the margins are well circumscribed (Figure 19-3). The solid components of a pilocytic astrocytoma usually enhance markedly and uniformly on CT and MR (Figure 19-4). Pilomyxoid astrocytoma usually has well-defined margins and undergoes intense contrast enhancement. Enhancement is often heterogeneous due to hemorrhage or necrosis. Restricted diffusion is lacking on MR. Diffuse astrocytoma is relatively hypoattenuating on unenhanced CT. The lesion is usually hypointense to brain on T1-weighted MR images and hyperintense on T2-weighted images (Figure 19-5). There are poorly defined margins. Contrast enhancement is variable, but tends to have a patchy character (Figure 19-6).

High-grade supratentorial astrocytoma usually has a heterogeneous character on CT and MR, due to the necrosis and hemorrhage (Figure 19-7). In some instances, the lesion is predominantly cystic, mimicking the appearance of a pilocytic astrocytoma. The solid components of viable tumor usually enhance with contrast (Figure 19-2). Defining the exact margins of infiltrative tumors such as glioblastoma multiforme is often imprecise with neuroimaging studies. In particular, the differentiation between active tumor and peritumoral vasogenic edema is difficult. In addition, tumor infiltration of white matter can occur without identifiable alterations on standard T2-weighted images. Because of these limitations, diffusion-weighted and diffusion-tensor MR images are sometimes useful to achieve more accurate depiction of the margins of active brain tumors.⁷

The MR spectroscopy findings of supratentorial astrocytomas vary according to the histology and grade of malignancy. Low-grade astrocytomas sometimes have near-normal spectral patterns. As with most brain tumors, astrocytomas (particularly high-grade lesions) have reduction of NAA and low NAA/Cr ratios. With high-grade astrocytomas, there is elevation of Cho within viable tumor (Figure 19-8). There is elevation of Cho/Cr and Cho/NAA ratios. Areas of necrosis have diminished levels of Cho, Cr, and NAA, and prominent lipid and lactate peaks.

Pleomorphic Xanthoastrocytoma

Pleomorphic xanthoastrocytoma is a rare developmental brain tumor of children and young adults that has aggressive histological features but a benign clinical course. This neoplasm is predominantly glial, but contains neuronal elements. In some patients, there is an association with cortical dysplasia. Pleomorphic xanthoastrocytoma most often arises in the peripheral aspect of a cerebral hemisphere. At least 90% are supratentorial and about half involve the temporal lobe. These lesions can occur, however, in any portion of the brain or spinal cord. The most common age at presentation is in adolescence or young adulthood. Seizures are common in these patients (>70%), particularly when the tumor arises in the temporal lobe.

Imaging studies of pleomorphic xanthoastrocytoma most often show a well-circumscribed peripheral cerebral mass. Pathological examination frequently demonstrates extension into the leptomeninges, usually without dural invasion. Adjacent calvarial erosion is occasionally present. About half of these lesions contain 1 or more macroscopic cysts. Cystic tumors may have an avidly enhancing mural nodule (Figure 19-9). The solid components of a pleomorphic xanthoastrocytoma usually appear similar to normal gray matter on CT and T1-weighted MR sequences. Fluid-attenuated inversion recovery (FLAIR) and spin echo T2-weighted images usually show only minimal tumor hyperintensity relative to normal brain. Typically, there is only minimal perilesional edema. Prominent contrast enhancement occurs within the solid portions (Figure 19-10).^8,9

Subependymal Giant Cell Astrocytoma

Subependymal giant cell astrocytoma (giant cell tumor) is a mixed glioneuronal neoplasm that occurs in children with tuberous sclerosis. This is the most common cerebral neoplasm in tuberous sclerosis patients, with a prevalence of 5% to 15%. It accounts for approximately 1.4% of brain tumors in all pediatric patients.¹⁰ It is presumed to arise from a subependymal hamartoma and is nearly always located adjacent to the foramen of Monro. Subependymal giant cell astrocytoma rarely occurs in patients without clinical manifestations of tuberous sclerosis; in most or all of these instances, the apparent absence of tuberous sclerosis is due to an insufficient period of time having elapsed before the clinical signs become manifest or is related to variable gene expression.^11,12

Although subependymal giant cell astrocytoma sometimes occurs in adults, the mean age at presentation is 11 years. Symptoms specifically related to the presence of the lesion are frequently lacking, and the mass is typically found during routine brain imaging for known tuberous sclerosis. In occasional patients, ventricular obstruction by the lesion leads to signs and symptoms of hydrocephalus (headache). Hemiparesis is an uncommon manifestation of this tumor. There appears to be an increased prevalence of cardiac rhabdomyoma in tuberous sclerosis patients with subependymal giant cell astrocytoma in comparison to those with subependymoma nodules only.^10–14

The histogenesis of subependymal giant cell astrocytoma is unclear, with evidence supporting both neuronal and astrocytic lineage. This tumor has a mixed glioneuronal pattern histologically. There is a low proliferative index; malignant histological features are rare. It is classified as a WHO grade I neoplasm. The mass grows slowly and exhibits benign biological behavior. Occasionally, there is degeneration into a higher grade infiltrating neoplasm.¹²

Neuroimaging studies show a subependymal giant cell astrocytoma as a nodular intraventricular mass. Although nearly always located near the foramen of Monro, it can develop anywhere along the ependymal surface. The lesion typically has slightly lower attenuation than normal brain on unenhanced CT.¹⁵ Calcification within the lesion is common. Increased attenuation due to recent hemorrhage is occasionally present. With MRI, subependymal giant cell astrocytoma is slightly hypointense to brain on T1-weighted images and hyperintense on T2-weighted images. The presence of calcification or hemorrhage may alter this appearance. In addition, the relative intensities with respect to normal brain are often different in neonates because of the high water content of the brain at this age; the lesion may appear slightly hyperintense on T1-weighted images and slightly hypointense on T2-weighted images. Intense contrast enhancement is visible on both CT and MRI of subependymal giant cell astrocytomas (Figure 19-11).^10,16–19

The hallmark neuroimaging appearance of a subependymal giant cell astrocytoma is that of an intensely enhancing subependymal mass in the region of the foramen of Monro in a child with tuberous sclerosis, with progressive enlargement on sequential studies. Accurate differentiation of this lesion from a benign subependymal hamartoma is not always possible. A giant cell tumor typically has a greater degree of contrast enhancement, but a subependymal hamartoma may also undergo some enhancement, particularly on MRI. A subependymal astrocytoma is usually a larger lesion than a hamartoma; lesions greater than or equal to 10 mm in diameter are usually astrocytomas. Hamartomas typically are stable in size on sequential neuroimaging studies. Although astrocytomas progressively enlarge, the rate of growth varies considerably between patients.²⁰

There is controversy about the optimal management of children with subependymoma giant cell astrocytoma. A rapidly growing or infiltrative lesion, or a tumor that causes a new focal neurological deficit, is usually treated surgically. If there is hydrocephalus due to a stable or slowly growing lesion, either surgical resection of the mass or simple diversionary ventricular shunting represent reasonable treatment options. Radiation therapy is not effective for the treatment of this lesion.^10,21,22

Oligodendroglioma

Oligodendroglioma is a glial neoplasm that is uncommon in the pediatric age group. This lesion accounts for approximately 1% of pediatric brain tumors. About six percent of oligodendrogliomas occur in children, with a peak age of 6 to 12 years. There is a male predilection. More than half of these lesions arise in the frontal lobes. Other supratentorial sites, in decreasing order of frequency, are the temporal, parietal, and occipital lobes. Additional potential sites for primary oligodendroglioma include the cerebellum, brainstem, spinal cord, ventricular system, leptomeninges, retina, and optic nerves.²³

Most oligodendrogliomas are low-grade neoplasms; that is, well-differentiated. This slowly growing neoplasm typically is associated with a protracted symptomatic period prior to diagnosis. The less common anaplastic variety usually has a much shorter clinical course. The most common presenting symptom is a seizure disorder, likely related to the propensity for the neoplasm to involve the cortical gray matter. Other potential findings include headache, visual alterations, mental status change, nausea, ataxia, and weakness.

Oligodendrogliomas presumably arise from oligodendrocytes, which are neuroglial cells that are predominantly located in the white matter of the CNS. Oligodendroglioma is usually a soft, fleshy mass. Histologically, there are sheets of uniformly dense cells. Calcifications, either microscopic or macroscopic, are present in approximately 90% of these lesions. Mucoid degeneration and leptomeningeal infiltration can occur. A well-differentiated oligodendroglioma is a WHO grade II lesion; the anaplastic variety is WHO grade III.

Neuroimaging studies typically show an oligodendroglioma as an oval cortical or subcortical mass. Most often, the margins are well defined and lobulated; occasionally, the mass blends imperceptibly with the adjacent brain parenchyma. Calcification is visible on CT in at least half of these lesions; this is the most common neoplasm of the cerebral hemisphere in children to calcify. The calcification may be nodular, shell-like, or linear. In some instances, the calcification has a gyriform pattern. The soft tissue components of the mass are most often hypoattenuating to normal brain, but an isoattenuating or hyperattenuating character occurs in 20% to 30% of these lesions. Rarely, a small isoattenuating oligodendroglioma is occult on CT. This slowly growing neoplasm sometimes causes erosion of the inner table of the calvaria (Figure 19-12). Contrast enhancement on CT is absent or minimal, and is more common with higher-grade tumors (Figure 19-13).²⁴

MRI of oligodendroglioma shows a mass that is predominantly hypointense on T1-weighted images and hyperintense on T2-weighted images (Figure 19-14). Heterogeneity is a characteristic feature of this tumor (Figure 19-15). Large calcifications, when present, are hypointense on both sequences. Microscopic calcifications may lead to regions of T1 hyperintensity or nonspecific heterogeneity. Cysts can occur with this tumor. Peritumoral vasogenic edema is usually absent or minimal, particularly with a low-grade lesion. Some oligodendrogliomas are infiltrative and have ill-defined margins. Contrast enhancement on MR ranges from none to moderate in intensity. As with CT, prominent MR contrast enhancement suggests aggressive biological behavior (Figure 19-16). The enhancement pattern often has a lacy or heterogeneous character. Most oligodendrogliomas are hypermetabolic to normal brain on positron emission tomographic (PET) imaging.²⁵

Primitive Neuroectodermal Tumor

PNET is a malignant embryonal tumor that accounts for less than 5% of supratentorial neoplasms in children. The most common CNS location of this lesion is the cerebellum (medulloblastoma). Other potential sites of origin include the pineal gland (pineoblastoma), cerebrum, spinal cord, and retina (retinoblastoma); the brainstem is a rare site. Histologically, PNET consists of primitive neuroepithelial cells. There is considerable variation between patients with regard to the cellular composition of PNETs; ependymal, melanocytic, mesenchymal, oligodendroglial, and photoreceptor differentiation can occur. These highly proliferative neoplasms tend to metastasize along the leptomeninges. Neuroblastoma, medulloblastoma, and pineoblastoma arise from similar primitive cells and represent additional members of this family of embryonal neoplasms (Table 19-3). PNET has also been termed “primary cerebral neuroblastoma.”²⁶

Supratentorial PNET most often occurs as a large hemispheric mass of heterogeneous composition. Most of these lesions arise in children under the age of 10 years. The most common presenting clinical manifestations are macrocephaly, seizures, and neurological signs of elevated intracranial pressure. The recurrence rate of this highly malignant neoplasm following surgical resection is approximately 40%. Potential pathways of metastasis include subarachnoid seeding and hematogenous spread to the lungs, liver, or bone marrow.

PNET is a highly cellular tumor. At least 90% of the lesion consists of undifferentiated cells. The neuroimaging features of PNET are quite variable. These tumors are usually large at the time of diagnosis (Figure 19-17). The tumor margins are well defined in many patients, but others have a lesion with an infiltrative character. Perilesional edema is variable. The cerebral white matter is usually the region of greatest involvement. Intraventricular extension can occur.

Most PNETs are heterogeneous, due to the presence of calcification, cysts, necrosis, or hemorrhage (Figure 19-18). Nonnecrotic portions undergo moderate contrast enhancement. The signal intensity of the solid components of the mass on T2-weighted MR images tends to be lower than in most other brain tumors, due to the high nuclear-to-cytoplasmic ratio of the primitive cells that make up the neoplasm (Figure 19-19). Some of these tumors are isointense to gray matter. Likewise, the lesion may be somewhat hyperattenuating to normal white matter on unenhanced CT. MR shows the solid components to have reduced diffusion, whereas cystic areas have increased diffusion. Necrosis and hemorrhage produce high signal intensity on FLAIR sequences, whereas clear cysts are hypointense. MR spectroscopy typically demonstrates high Cho/Cr and Cho/NAA ratios and elevation of glycine-ml (3.56 ppm).^27,28

Medulloepithelioma

Medulloepithelioma is a rare highly malignant embryonal tumor composed of epithelial elements. Most of these lesions arise in the supratentorial compartment, in either the suprasellar region or the cerebral hemispheres. Origin within the brainstem or cerebellum is also possible. Presentation usually occurs during infancy; nearly all of these lesions occur in children under the age of 5 years. Most patients have manifestations of intracranial hypertension and suffer severe neurological deficits. The prognosis is poor in the absence of complete resection.

Medulloepithelioma usually is isoattenuating or hypoattenuating to normal brain on unenhanced CT. The lesion is hypointense or isointense to brain on T1-weighted MR images. There is homogeneous hyperintensity on T2-weighted images; intratumoral hemorrhage results in heterogeneity in some patients. There are usually well-defined tumor margins. The contrast enhancement characteristics on CT and MR are variable; many of these tumors lack substantial enhancement.^29,30

Atypical Teratoid/Rhabdoid Tumor

Atypical teratoid/rhabdoid tumor is a rare embryonal tumor that is pathologically and clinically similar to PNET. Approximately 30% of atypical teratoid/rhabdoid tumors are supratentorial, with most of these in the cerebral hemispheres or pineal region. Three-quarters of these lesions present in children younger than 3 years of age. There is a male predominance. The clinical presentation usually relates to intracranial hypertension. Common findings include cranial nerve signs, nausea and vomiting, headache, and seizures. This is a highly aggressive neoplasm; most patients succumb within 1 year of the diagnosis.^31,32

Neuroimaging studies of supratentorial atypical teratoid/rhabdoid tumor demonstrate a predominantly solid mass that contains regions of necrosis (Figure 19-20). The solid components are isoattenuating-to-hyperattenuating relative to gray matter on CT and approximately isointense to gray matter on MR. Foci of necrosis and calcification produce a heterogeneous appearance in most of these tumors. Cysts are sometimes present. There is prominent contrast enhancement of the solid components (Figure 19-21). Metastatic disease at the time of diagnosis is common.^33,34

Ganglioglioma

Ganglioglioma is a rare lesion that accounts for less than 3% of pediatric CNS tumors. This neuronal-glial (glioneural) neoplasm contains varying amounts of atypical ganglion cells and neoplastic glial cells. There is histological overlap with gangliocytoma. Pediatric glioneural neoplasms comprise a spectrum of CNS lesions (Table 19-4). The histological grade and the clinical behavior of gangliogliomas vary between patients, although most are low grade.

Ganglioglioma can arise anywhere within the CNS; most are within the brain. The temporal lobe is the overall most common location, followed by the parietal and frontal lobes. Posterior fossa locations can also occur. Approximately 95% of patients with ganglioglioma have seizures; most common are temporomesial and temporolateral locations. Ganglioglioma accounts for approximately 40% of epilepsy-associated tumors. Removal of the lesion usually leads to improved seizure control. Although ganglioglioma usually follows a benign pattern of growth, there is a propensity for hemorrhage that can produce acute catastrophic symptoms.^35,36

The most characteristic imaging appearance of a ganglioglioma is that of a cystic mass with a mural nodule, although a completely solid composition can also occur (Figure 19-22). A cystic component is visible with imaging in approximately 80% of gangliomas in children under the age of 10 years (Figure 19-23). There can be a single cyst or multiple small cysts. There is evidence of calcification of the solid portion on CT evaluation in approximately 30%. The solid component often appears heterogeneous on MRI (Figure 19-24). Most often, the solid portion predominantly has relatively low signal intensity on T1-weighted MR images and high signal on T2-weighted images (Figure 19-25). Although most gangliogliomas enhance with IV contrast, the enhancement pattern is not consistent between lesions. Because this is a slow growing tumor, a peripheral ganglioglioma sometimes causes scalloped erosion of the adjacent portion of the inner table of the skull. There is a high Cho peak relative to the Cr and NAA peaks on MR spectroscopy. PET imaging (¹⁸F-fluorodeoxyglucose positron emission tomography) of ganglioglioma shows heterogeneous metabolic activity, including areas of hypermetabolism. Gangliogliomas have intense uptake on ²⁰¹TI scintigraphy.^37–39

Gangliocytoma

Gangliocytoma (ganglioneuroma) includes a spectrum of CNS tumors in which neuronal cells are the sole neoplastic constituents, although there is an accompanying network of nonneoplastic glial cells. The presence of anaplastic glial cells in ganglioglioma serves as the histopathological differentiating feature from gangliocytoma. Gangliocytomas most often arise in the cerebrum; other potential sites include the cerebellum, hypothalamus, pineal region, and pituitary. Fewer than 10% arise in the spinal cord.

Gangliocytoma is a rare lesion, accounting for fewer than 3% of pediatric brain tumors. The location of the mass determines the clinical manifestations. Most patients suffer seizures. Hydrocephalus can occur. The biological behavior is usually benign, with slow growth. Gangliocytoma of the cerebellum in patients with Lhermitte-Duclos disease is a slowly growing hamartomatous lesion.³⁶

The imaging features of gangliocytoma are varied, and often nonspecific. Differentiation from ganglioglioma is not possible. Gangliocytoma is an encapsulated tumor that contains varying proportions of Schwann cells, collagen fibers, and myxoid stroma. MR most often shows low signal intensity on T1-weighted images and high signal on T2-weighted images. Those lesions with a prominent fibrous composition and minimal myxoid stroma produce intermediate or low signal intensity on T2-weighted images. Cystic areas are common. Typically, there is mild contrast enhancement; enhancement may be lacking on early images and gradually increases on subsequent images. CT may show calcification. Some lesions are hyperattenuating on unenhanced CT images.^40–42

Desmoplastic Infantile Ganglioglioma

Desmoplastic infantile ganglioglioma is a rare mixed neuronal-glial tumor that has aggressive histological features, but a benign clinical course. Desmoplastic astrocytoma of infancy is a variant lesion. Desmoplastic infantile ganglioglioma is typically very large at the time of diagnosis, and is predominantly cystic. In the desmoplastic solid component, histological examination demonstrates fibroblasts, astrocytic cells, and ganglionic cells. There are spindle-shaped neoplastic cells that contain elongated pleomorphic nuclei. The presence of ganglionic cells may lead to histological features that overlap those of a classic ganglioglioma.^43,44

Desmoplastic infantile ganglioglioma is a supratentorial lesion. The usual sites of origin, in decreasing order of frequency, are parietal, frontal, and temporal. There is usually a short duration of symptoms prior to diagnosis. Physical examination shows macrocephaly and tense bulging fontanelles. Partial complex seizures may occur. Most patients present during the first several months of life. The treatment of desmoplastic infantile ganglioglioma is surgical excision. In many patients, the lesion is amenable to complete removal, which is associated with a favorable prognosis.^40,45

Neuroimaging studies show desmoplastic infantile ganglioglioma as a large, cystic, peripheral cerebral hemispheric mass. The cystic composition is readily apparent with sonography. The fluid component does not enhance on CT examination, and has attenuation values that are similar to those of cerebrospinal fluid (CSF). The superficial solid component is of equal or slightly greater attenuation as normal gray matter on CT and is isointense on standard T1-weighted and T2-weighted MR sequences; these features are helpful in the differentiation from a cystic astrocytoma. The solid component is often heterogeneous on T2-weighted MR images, whereas the cystic component is typically homogeneous and has the characteristics of clear fluid. The solid portion of the mass enhances intensely with IV contrast on MR. The solid component is peripherally located, and the tumor enhancement has characteristic extension to the leptomeninges.^46,47

Dysembryoplastic Neuroepithelial Tumor

DNET is a benign mixed neuronal-glial tumor of the CNS that is an important cause of medically refractory partial seizures in children and young adults. Typically, there is no neurological deficit. Most affected pediatric patients present during adolescence. The histopathological features raise the possibility that this lesion is a malformation rather than a true neoplasm. DNET is composed of heterogeneous cellular components that are located in a myxoid or mucinous interstitial matrix. There is frequently a background of cortical dysplasia adjacent to the lesion.

Most DNETs arise in the cerebral cortex, with the temporal lobes accounting for approximately 60% and the frontal lobes 30%. Although uncommon, posterior fossa and deep cerebral origins can occur. Imaging studies typically demonstrate a well-demarcated cortical lesion that extends into the subcortical white matter. The mesial cortex is a common site of origin.

The myxoid matrix and multinodular architecture of DNET cause a multicystic appearance on MR images in most patients. There is only minimal mass effect. The mass has low attenuation on CT. Calcifications are present in about one-third of these lesions. Bone remodeling of the adjacent portion of the skull is common. The mass is hypointense to normal gray matter on T1-weighted MR images and markedly hyperintense on T2-weighted images. Adjacent vasogenic edema is typically lacking. The mass may have a multilobulated or gyriform character. Contrast enhancement is either absent or of mild intensity. PET imaging shows similar metabolic activity within the tumor as in normal brain. The multicystic character of DNET helps in the differentiation from ganglioglioma and glioneuronal malformations.^40,48,49

Papillary Glioneuronal Tumor

Papillary glioneuronal tumor is a rare glioneural tumor of the brain that occurs in individuals of all ages. The lesion is usually asymptomatic or associated with mild clinical manifestations such as headache. The tumor usually arises adjacent to the lateral ventricle; the temporal lobe is the most common location. Histologically, there is a mixed neuronal-glial cell composition. CT or MRI of papillary glioneuronal tumor typically demonstrates a cystic cerebral mass with well-defined borders. The margins enhance with contrast. Septations are sometimes present. Occasionally, there is an enhancing mural nodule. Individuals with this low-grade lesion typically have an excellent prognosis.^50–52

Ependymoma

Ependymoma is a relatively common glial neoplasm of the CNS. This lesion accounts for 6% to 12% of brain tumors in children. Approximately 30% of intracranial ependymomas arise in a supratentorial location. In decreasing order frequency, the sites of origin of a cerebral ependymoma are the frontal, parietal, and temporal lobes. As is common with posterior fossa ependymomas, some of those in the supratentorial region arise within the ependyma of the lateral or third ventricles and produce an intraventricular mass. More often, however, the mass is completely extraventricular, arising from embryonic rests of ependymal tissue trapped within the developing cerebral hemispheres. Supratentorial ependymoma and infratentorial ependymoma are histologically identical.^53,54

The clinical presentation of a supratentorial ependymoma is often nonspecific. Headaches, seizures, and focal neurological signs are common. Manifestations of hydrocephalus may occur, particularly with an interventricular tumor. Clinical examination may demonstrate hemiparesis, hyperreflexia, and visual field abnormalities. The peak age range is between 1 and 5 years. The overall 5-year progression-free rate for children with ependymoma is approximately 50%. The prognosis is slightly better for supratentorial lesions than for those of the posterior fossa. Cerebrospinal fluid dissemination is also less common with supratentorial ependymomas, as most arise in an extraventricular location.⁵⁵

The typical neuroimaging appearance of supratentorial ependymoma is that of a heterogeneous, calcified, periventricular, off-midline mass (Figure 19-26). Supratentorial ependymomas tend to contain large cystic components (Figure 19-27); cysts are more common in supratentorial ependymomas than in those of the posterior fossa. (Supratentorial ependymomas without substantial cystic components or calcification are often indistinguishable on imaging studies from astrocytoma.) The mass is usually located in the cerebral parenchyma, most often in the cerebral white matter. An intraventricular ependymoma typically is a well-circumscribed mass that fills the ventricular lumen and sometimes extends into the adjacent brain parenchyma.⁵⁶

The soft tissue component of an ependymoma is usually isoattenuating or slightly hyperattenuating to brain on unenhanced CT. Calcifications, when present, are often multiple; the pattern of calcification ranges from small round densities to large confluent foci. There is a variable degree of enhancement of the solid components of the lesion. The character of a supratentorial ependymoma is frequently heterogeneous on MR, due to the presence of cysts, calcification, and hemorrhage (Figure 19-28). The solid components are hypointense or isointense to normal gray matter on T1-weighted images and isointense or mildly hyperintense on T2-weighted images. The viable soft-tissue components enhance with IV contrast.^57,58

Germinoma

Germinoma occasionally arises in the deep cerebral gray matter structures. This is the third most common intracranial location of this tumor, after the pineal and suprasellar regions. Germinoma at this location occurs with a strong male predilection and most commonly arises in older children and teenagers. Other types of germ cell tumor can also arise in the thalami and basal ganglia, but are much less common than germinoma.

A small germinoma of the basal ganglia or thalamus may have a subtle appearance on unenhanced neuroimaging studies. The solid component is isoattenuating or slightly hyperattenuating to normal tissue on CT, and isointense to slightly hyperintense to normal gray matter on T1-weighted and T2-weighted MR sequences. Larger germinomas frequently are heterogeneous, due to necrosis and cysts. There is prominent contrast enhancement of the solid components of a germinoma.⁵⁹

Intraventricular Tumors: Differential Diagnosis

The tissues in and around the ventricular system that can give rise to intraventricular neoplasms include the ependyma, subependymal plate, septum pellucidum, and choroid plexus. The ependyma and subependymal plate are composed of glial cells that can lead to formation of ependymoma, subependymoma, subependymal giant cell astrocytoma, and central neurocytoma. The choroid plexus can be the site of origin of choroid plexus papilloma, choroid plexus carcinoma, and metastatic disease. Neoplasms that on rare occasions are located within the ventricular system include oligodendroglioma, pilocytic astrocytoma, glioblastoma multiforme, lymphoma, medulloblastoma, PNET, meningioma, and teratoma. An accurate diagnosis of the common neoplastic and nonneoplastic intraventricular masses in children is usually possible by correlating the clinical and imaging findings. Table 19-5 shows the major differentiating features between these lesions; the neoplasms are listed in decreasing order of frequency.^11,60,61

Some intraventricular tumors achieve a relatively large size before the onset of symptoms. The clinical manifestations may relate to compression/invasion of an adjacent structure or to sequelae of elevated intracranial pressure. A lesion in the third ventricle can also result in findings of hypothalamic compression, such as diabetes insipidus, weight gain, or hypersomnia. Compression of the tectum by a tumor in the posterior aspect of the third ventricle may lead to Parinaud syndrome. Neoplasms of the trigone can cause posterior temporal lobe seizures. Hydrocephalus due to foraminal obstruction by an intraventricular mass can lead to macrocrania or other manifestations of elevated intracranial pressure.⁶²

Colloid Cyst

Colloid cyst (paraphyseal cyst) is a congenital mucin-containing epithelial-lined intraventricular cyst. More than 90% arise in the anterosuperior aspect of the third ventricle and bulge into the foramen of Monro. Other potential sites include the lateral ventricles, cerebellum, and extraaxial spaces. This lesion accounts for 15% to 20% of intraventricular masses. Despite the developmental origin of colloid cyst, the typical age at detection is early or middle adulthood; children account for less than 10% of cases. There is no substantial gender predilection.

Some colloid cysts are asymptomatic and discovered incidentally on imaging studies performed for an unrelated indication. Symptoms usually relate to obstructive hydrocephalus (e.g., headache). In some patients, headaches are positional. Rarely, acute obstruction causes a precipitous presentation. In addition to headache, patients with colloid cyst may have nausea, visual changes, memory loss, or gait disturbance. Surgical excision is the usual treatment for a symptomatic lesion.⁶³

Colloid cyst derives from embryonic endoderm. Mucinous secretions and desquamated epithelial cells fill the lumen. The outer wall is a thin fibrous capsule and the inner lining is a single layer of columnar cells. On unenhanced CT, the lesion is slightly hyperattenuating to brain in about two-thirds of patients and is isoattenuating in one-third. Calcification and manifestations of hemorrhage are rare. The CT finding of a hyperattenuating round or oval third ventricular mass is essentially pathognomonic. Findings of obstructive hydrocephalus are common. Contrast enhanced images occasionally show slight capsular enhancement; the cyst contents do not enhance.⁶⁴

The cholesterol concentration within a colloid cyst is the major determinant of the MR signal characteristics. About two-thirds of colloid cysts are hyperintense to brain on T1-weighted images and about one-third are isointense (Figure 19-29). Most are isointense to CSF on T2-weighted images, but there is considerable variation between patients. There is a heterogeneous character in about one-quarter of these lesions. Occasionally, a fluid–fluid level is present. There is no restricted diffusion. As with CT, MR shows no enhancement of the lesion or minimal enhancement confined to the capsule (Figure 19-30). Spectroscopy demonstrates a prominent peak in the region of 2.0 ppm due to the mucinous material; there is also a small lactate peak.^65,66

Choroid Plexus Tumors

Choroid plexus papilloma and carcinoma arise from the neuroepithelial tissue of the choroid plexus. Approximately 80% of choroid plexus tumors are papillomas. The papilloma is a benign, slow-growing neoplasm that carries a WHO grade I designation. The less common choroid plexus carcinoma is a WHO grade III neoplasm. Choroid plexus tumors account for 1% to 4% of pediatric brain tumors and 10% to 20% of brain tumors in children during the first year of life.^11,36,61

Choroid plexus tumors can arise anywhere that choroid plexus tissue exists, including the lateral ventricles, third ventricle, and fourth ventricle. There is no choroid plexus within the cerebral aqueduct or the temporal horns. The greatest volume of choroid plexus tissue is within the atria of the lateral ventricles. Approximately 50% of choroid plexus tumors arise within the lateral ventricles, 40% in the fourth ventricle, and 5% in the third ventricle. Up to 5% of these lesions are multicentric. Rarely, this tumor arises from choroid plexus tissue in the cerebellopontine angle. There are rare instances of choroid plexus tumors in other extraventricular locations, presumably arising from an embryonic rest of choroid plexus tissue. Choroid plexus tumors of the lateral ventricles most often present during the first decade of life, whereas those in the fourth ventricle have similar diagnostic incidences in children and adults. Choroid plexus tumors of the fourth ventricle are more common in males, but this gender predilection is absent for those that arise in the lateral ventricles.

The predominant clinical manifestations of choroid plexus tumors are due to hydrocephalus. Increased production of cerebrospinal fluid by the tumor is the typical cause of hydrocephalus in these patients. Additional potential factors are ventricular obstruction by the mass and impairment of arachnoid granulation CSF absorption due to the release of blood or proteinaceous material from the tumor.^67,68 A variety of other, less common, clinical findings can occur, including focal neurological deficits, cranial nerve palsies, and seizures.⁶⁹ A lateral ventricular choroid plexus tumor that has a pedicle may move within the ventricle, leading to clinical manifestations of intermittent ventricular obstruction (e.g., bobble-head doll syndrome).^67,70 Choroid plexus tumors can occur in patients with Li-Fraumeni syndrome and Aicardi syndrome.^71,72

The gross pathological appearance of a choroid plexus tumor is that of a soft, well-circumscribed cauliflower-like mass, with prominent peripheral lobulations. A vascular pedicle connects the mass to the choroid plexus. Both papillomas and carcinomas may contain cysts or areas of hemorrhage. Necrosis and parenchymal invasion are characteristics of carcinoma. On histological examination, choroid plexus papilloma usually appears similar to normal choroid plexus tissue. Findings with a choroid plexus carcinoma include invasion of adjacent normal tissue, hypercellularity, and prominent mitotic activity. Rarely, a choroid plexus tumor has histological features that do not allow definitive characterization as a papilloma or carcinoma; this is termed an atypical choroid plexus papilloma. Both choroid plexus papillomas and carcinomas can seed cells into the cerebrospinal fluid, but growth of metastatic deposits is much more common with carcinoma.¹¹

The diagnosis of a choroid plexus tumor with neuroimaging studies is usually straightforward. There are imaging features that help to distinguish between papillomas and carcinomas, but the imaging findings alone are not pathognomonic.^67,68 A papilloma usually appears on CT as a lobulated intraventricular mass that is of similar or slightly greater attenuation than normal brain. Calcification is present in about one-fourth of these lesions. Prominent, homogeneous contrast enhancement occurs.^67,73

The lobulated character of a papilloma is easily visualized on MRI. On T1-weighted images, a papilloma is usually homogeneous and isointense-to-hypointense relative to gray matter. The central aspect of a papilloma is often hypointense compared to gray matter on T2-weighted images; this hypointensity often has a branching pattern (Figure 19-31). Foci of hemorrhage or calcification within the lesion may produce some heterogeneity. Flow voids from prominent vessels are commonly visible. Choroidal artery enlargement may be demonstrable. Contrast enhancement is intense and uniform (Figure 19-32). Choroid plexus tumors that arise in the region of the trigone sometimes appear to engulf rather than invade the choroid plexus glomus.⁷⁴ Extension may occur from 1 ventricle to another, and a papilloma arising within the fourth ventricle can grow through the foramen of Luschka.⁷⁵

Sonography of a choroid plexus papilloma in an infant shows a lobulated echogenic intraventricular mass. Doppler evaluation may demonstrate bidirectional vascular flow within the lesion.^76,77

Choroid plexus carcinoma typically has imaging features of a more aggressive lesion than does papilloma, although there are unusual instances in which a papilloma grows through the ependyma and incites edema in the adjacent white matter (Figure 19-33). Features that favor the diagnosis of a carcinoma include extraventricular extension into the brain parenchyma, a heterogeneous composition, vasogenic edema in adjacent cerebral white matter, and relatively mild hydrocephalus (hydrocephalus tends to be more pronounced with papilloma) (Figure 19-34). Occasionally, a large choroid plexus carcinoma invades the brain parenchyma to an extent that the ventricular origin of the tumor cannot be determined with certainty on imaging studies.

On both CT and MRI, choroid plexus carcinoma typically has an irregular contour and prominent, but somewhat heterogeneous, contrast enhancement. Cysts, hemorrhage, and necrosis are common, producing a mixture of regions of high and low signal intensity on both T1-weighted and T2-weighted MR images.^{67 18}F-FDG PET imaging of choroid plexus carcinoma demonstrates prominent metabolic activity consistent with increased glycolysis. MR spectroscopy of choroid plexus tumors shows a prominent Cho peak and suppression of the NAA and Cr peaks (Figure 19-35). Elevation of lactate is sometimes present, particularly with carcinoma.⁷⁸

Surgical resection is the treatment for both choroid plexus papilloma and carcinoma. Imaging definition of the major vascular supply is sometimes helpful for presurgical planning in children with choroid plexus tumors. This is usually accomplished with MR angiography. The anterior, lateral-posterior, and medial-posterior choroidal arteries usually supply those tumors located in the lateral ventricle. Choroidal branches of the posterior inferior cerebellar artery usually supply choroid plexus tumors arising in the fourth ventricle. Preoperative embolization with transcatheter or stereotactic techniques has been utilized at some centers to facilitate the safety and efficacy of surgical resection. The prognosis for children following successful resection of a choroid plexus papilloma is excellent. The 5-year survival rate for children with a diagnosis of choroid plexus carcinoma is 26% to 50%.^68,69,79

Congenital choroid plexus cysts are nonneoplastic developmental lesions that result from invagination of neuroepithelium into the choroid plexus stroma. In the fetus, choroid plexus cysts often spontaneously disappear later in gestation. There is an association of large or multiple fetal choroid plexus cysts with chromosomal abnormalities such as trisomy 18 and trisomy 21. A choroid plexus cyst is an occasional, usually incidental, finding on neuroimaging studies of infants and children. Rarely, the lesion is large enough to cause intraventricular obstructive hydrocephalus. The cyst contents are anechoic on sonography and have similar characteristics as clear fluid on CT and MR. The fluid sometimes has restricted diffusion.⁶¹

Diffuse villous hyperplasia is a rare developmental lesion in which there is generalized choroid plexus enlargement without a localized mass. There is overproduction of cerebrospinal fluid that leads to ventriculomegaly.⁸⁰

Subependymoma

Subependymoma is a glial tumor that usually arises from the subependymal glial layer that surrounds the ventricles. This lesion nearly always grows into the adjacent ventricle; there are rare instances of location within the brain parenchyma, cerebellopontine angle, or spinal cord. Most occur in the fourth ventricle, with the lateral ventricle being the next most common site. Subependymoma is an uncommon lesion in adults, and is rare in children; approximately 80% occur in patients older than 15 years. This tumor is more common in males.^11,58,81,82

Symptoms in patients with subependymoma depend on the location and size of the tumor. The clinical findings are often nonspecific. Most subependymomas are small (<2 cm in diameter) and slow growing. Some patients are asymptomatic. The onset of symptoms is most often related to ventricular obstruction; other potential findings include focal neurological deficits, seizures, and subarachnoid hemorrhage. The treatment is surgical resection; post-surgical recurrence is rare.

Subependymoma is usually a well-circumscribed, hypovascular mass that attaches to the ventricular wall by a narrow pedicle. The histological appearance is that of a dense fibrillary matrix interrupted by numerous small cysts and nests of isomorphic nuclei that resemble subependymal glia. Mitotic activity is usually low or absent, and this lesion is classified as a WHO grade I tumor.⁸³ Approximately 10% to 15% of subependymomas have histological evidence of an admixture with an ependymoma; this finding indicates a more guarded prognosis than the excellent outcome that is typical of the pure form.⁸²

The neuroimaging findings of subependymoma are similar to, and frequently indistinguishable from, those of ependymoma, particularly when located in the fourth ventricle. Although ependymoma often has somewhat ill-defined margins, subependymoma usually appears on CT and MR as a well-circumscribed, lobulated intraventricular mass. Extension of a subependymoma beyond the ventricular margins is uncommon. On unenhanced CT, the mass usually is slightly hypoattenuating to normal brain parenchyma. The lesion has nonspecific hypointensity on T1-weighted images and hyperintensity on T2-weighted images. Calcification (usually amorphous) or cystic degeneration may be present. MR often shows a heterogeneous appearance due to tiny cysts. Manifestations of hemorrhage are sometimes visible on CT and MR. The enhancement characteristics vary considerable between patients, although those lesions that do enhance typically have a heterogeneous pattern, especially on MR. Hydrocephalus is common.^{11,15,57,58,81,84,85}

Central Neurocytoma

Central neurocytoma is a rare neuroepithelial brain tumor that occurs in individuals of all ages, although early adulthood is the peak age at presentation. There are 2 basic forms of this lesion: central neurocytoma occurs in the lateral and third ventricles, whereas extraventricular central neurocytoma refers to a lesion that arises elsewhere (cerebrum, cerebellum, or spinal cord). Central neurocytomas typically arise from the septum pellucidum or the ventricular wall. Nearly all involve the lateral ventricles. Uncommonly, there are bilateral ventricular lesions or extension of a lateral ventricular mass into the third ventricle. The most common location in the lateral ventricle is near the foramen of Monro. There is only a single case report of a central neurocytoma arising in the fourth ventricle. The clinical presentation of central neurocytoma is often related to hydrocephalus. Other potential findings include mental status changes, visual deficits (due to papilledema), and manifestations of intracranial hemorrhage. A lesion involving the third ventricle can lead to endocrine abnormalities.^11,86,87

The histological features of central neurocytoma are similar to those of oligodendroglioma: uniform round cells with round or oval nuclei. Calcification is common, and hemorrhage is sometimes present. This is a WHO grade II tumor. Central neurocytomas usually express immunoreactivity for synaptophysin and neuron-specific enolase (markers for neuronal differentiation), which aids in the differentiation from oligodendroglioma. Electron microscopy allows a definitive diagnosis, showing finely speckled chromatin, a small distinct nucleolus, and cell processes that have characteristic neuritic features.

Neuroimaging studies of central neurocytoma show a well-circumscribed, lobulated, intraventricular mass, most commonly located in the lateral ventricle near the foramen of Monro. Obstructive hydrocephalus is common. A broad attachment to either the lateral ventricle wall or the septum pellucidum is typically visible. The mass is of equal or higher attenuation than normal brain on unenhanced CT (subependymal giant cell astrocytomas and subependymomas are usually hypoattenuating). About half of these lesions contain calcifications, which are usually punctate. Cysts are present in two-thirds of cases. Moderate contrast enhancement usually occurs on both CT and MR. The lesion is heterogeneous on MR, and prominent flow voids may be present (Figure 19-36).^15,88,89

PET imaging of central neurocytoma shows hypermetabolic activity, increased blood flow, and increased blood volume.⁹⁰ MR spectroscopy is reported to demonstrate prominent glycine (Gly) and Cho and low NAA compared to normal brain.⁹¹ Kim et al also observed a characteristic signal peak at 3.55 ppm, likely produced by inositol or glycine.⁹²

Xanthogranuloma

Xanthogranuloma is a benign tumor that can arise in the ventricular wall. The histological features include xanthoma cells (macrophages), cholesterol clefts, hemosiderin, and manifestations of chronic inflammation. These lesions most often occur in the lateral ventricles and are typically asymptomatic. A third ventricle xanthogranuloma can cause obstructive hydrocephalus. Imaging studies show an oval, well-circumscribed lesion along the ventricular wall. The mass is hyperintense on T2-weighted MR images. There can be an isointense or hyperintense appearance on T1-weighted sequences, depending on the lipid content.⁶¹

Normal Pituitary Gland

The normal pituitary gland appears as a small oval structure in the inferior aspect of the sella turcica. In neonates, the anterior lobe of the pituitary gland (the adenohypophysis) is somewhat hyperintense relative to the brain on T1-weighted MR images (Figure 19-37). During the first few months of life, the gland becomes isointense to normal gray matter. In young children, the upper surface of the pituitary is usually flat or slightly concave. The normal gland usually measures no more than 6 mm in height. At around the time of puberty, there is a temporary increase in the size of the anterior lobe, particularly in girls. Superior convexity of the upper surface is typical in children of this age (Figure 19-38). The normal upper limits of pituitary gland height are 10 mm in teenage girls and 8 mm in boys. In postpartum females, the height can be up to 12 mm.⁹³

The neurohypophysis in individuals of all ages is hyperintense on T1-weighted images due to the presence of neurosecretory granules. Lack of this hyperintense appearance in children is often associated with diabetes insipidus. The normal posterior pituitary of the young infant often is isointense to the anterior pituitary on T1-weighted MR images. Differential signal intensity between the adenohypophysis and the neurohypophysis is also less pronounced in adults than in children.

With IV contrast, there is moderately intense homogeneous enhancement of the pituitary gland and infundibulum. A small nonenhancing cystic remnant of the Rathke pouch is occasionally present between the anterior and posterior lobes (Figure 19-39). The normal infundibulum tapers smoothly from the tuber cinereum to the neurohypophysis. The maximum thickness of the normal infundibulum is approximately 2.5 mm.

Clinical Presentations: Central Diabetes Insipidus

The major clinical features of diabetes insipidus are polyuria and polydipsia. There are 2 major forms of this abnormality. Central diabetes insipidus is due to lack of appropriate synthesis or secretion of arginine vasopressin (AVP; antidiuretic hormone [ADH]). Nephrogenic diabetes insipidus is a lack of an appropriate response by epithelial cells of the renal collecting ducts to circulating AVP. The major action of AVP is the stimulation of increased water permeability in the collecting ducts and distal convoluted tubules, thereby promoting reabsorption of water into the bloodstream and increased concentration of urine. In patients with diabetes insipidus, urinalysis demonstrates dilute urine with a low specific gravity; glycosuria is lacking. Patients who fail to consume sufficient compensatory fluids develop hypernatremia.

AVP is synthesized in the hypothalamus and transported through axons to the posterior pituitary, where it is stored and eventually released. Any lesion (traumatic, inflammatory, or neoplastic) that damages the hypothalamus or posterior pituitary can cause central diabetes insipidus. Sellar region tumors that can lead to central diabetes insipidus include craniopharyngioma, optic glioma, germinoma, metastasis, leukemic infiltration, lymphoma, teratoma, pituitary adenoma, and hypothalamic glioma. Trauma, neurosurgical procedures, encephalitis, meningitis, Langerhans cell histiocytosis, sarcoidosis, Wegener granulomatosis, leukemia, arachnoid cyst, and Rathke cleft cyst can also cause diabetes insipidus. Diabetes insipidus in neonates can occur in association with intracranial hemorrhage, asphyxia, meningitis, and Listeria monocytogenes sepsis. Central diabetes insipidus is clinically masked in dialysis patients, and rapid dehydration and hypernatremia can occur in these patients after successful kidney transplantation.^94–98

There are primary inherited forms of central diabetes insipidus that are quite rare. The AVP-neurophysin II gene is located on chromosome 20p13, and encodes for the precursor protein of AVP. Familial diabetes insipidus is most often inherited as an autosomal dominant or X-linked recessive trait, with variable severity and age of onset. Central diabetes insipidus can occur as part of septo-optic dysplasia. It is also associated with Wolfram syndrome, which is an autosomal recessive mitochondrial disorder.

Between 20% and 50% of children with central diabetes insipidus have an idiopathic form; that is, neuroimaging studies and clinical evaluations fail to identify a cause. However, some patients with diabetes insipidus and normal neuroimaging studies subsequently develop a suprasellar mass (Figure 19-40). The delay in appearance of a detectable mass may be up to a few years after the onset of diabetes insipidus; therefore, periodic reevaluation with MRI is indicated for those patients with apparent idiopathic central diabetes insipidus. The development of neurological signs or symptoms in a patient with idiopathic central diabetes insipidus should prompt immediate reevaluation with cranial MRI.⁹⁹

High signal intensity on T1-weighted MR images in the normal posterior lobe of the pituitary represents neurosecretory granules that consist of an ADH–neurophysin (carrier protein) complex packaged within a phospholipid membrane. Patients with central diabetes insipidus lack this high signal intensity. Any process (e.g., pituitary macroadenoma or hypothalamic germ cell tumor) that disturbs the transport of ADH from the hypothalamus to the posterior lobe can lead to the accumulation of high signal intensity material in the median eminence or the pituitary stalk proximal to the obstruction.

MRI of children with diabetes insipidus nearly always demonstrates lack of the normal hyperintense appearance of the posterior pituitary on T1-weighted images (Figure 19-41). Occasionally, this sign is not present at the time of the initial diagnosis, but becomes apparent on follow up imaging. The second most common MRI finding in patients with diabetes insipidus is thickening of the pituitary stalk. This may involve the entire stalk or be limited to the upper portion. Rarely, CT imaging demonstrates symmetrical calcifications in the basal ganglia and gray-white matter junctional regions of the cerebrum.

The appearance of the pituitary stalk on sequential MR examinations varies considerably between patients with central diabetes insipidus. Most often, the appearance of the stalk remains normal if it was normal on the initial examination. Some patients have increase in size of the stalk on subsequent studies, and occasionally an initially thickened stalk normalizes on subsequent examinations. Although the identification of progressive thickening of the pituitary stalk on sequential neuroimaging studies is nonspecific, it should be considered as a possible early indicator of a germinoma. In those patients suffering disruption of the stalk due to trauma or surgery, the defect is usually demonstrable on MRI.¹⁰⁰

Anterior pituitary hormone deficits can occur in patients with both the idiopathic and secondary forms of diabetes insipidus. The development of anterior pituitary hormone deficits may lag the onset of diabetes insipidus, however. Growth hormone deficiency tends to be the first manifestation of anterior pituitary dysfunction. The demonstration of progressive reduction in size of the anterior pituitary on sequential MR examinations indicates a heightened risk for the development of anterior pituitary hormone deficits. In contradistinction, if sequential MRI shows increase in size of the anterior pituitary in combination with thickening of the stalk, the presence of a germinoma is likely.¹⁰¹

Optic Chiasm Glioma

Optic pathway glioma (optic pathway astrocytoma; visual pathway glioma) encompasses astrocytomas that arise in the optic nerves, chiasm, or optic radiations. In general, the term optic nerve glioma refers to prechiasmatic lesions. Chiasmatic glioma (chiasmatic/hypothalamic astrocytoma) refers to a lesion that arises in the chiasm or chiasmatic/hypothalamic region; this accounts for 10% to 15% of supratentorial neoplasms. The term diffuse optic pathway glioma refers to involvement of multiple components of the optic pathway. The presence of bilateral optic nerve gliomas is nearly pathognomonic for neurofibromatosis type 1. Optic pathway gliomas are usually pilocytic astrocytomas. Most often, they are histologically benign and slow-growing. Astrocytomas of the optic chiasm and hypothalamus, however, tend to be more aggressive than those of the optic nerves. Aggressive biological behavior is particularly common when these tumors present in infants and young children.^102,103

Approximately 65% of optic pathway gliomas present within the first 5 years of life. There is an approximately equal gender incidence. The prevalence of optic pathway glioma in individuals with neurofibromatosis type 1 is approximately 15%. Infants with a chiasmatic glioma may present with failure to thrive, macrocephaly, nystagmus, and profound visual loss. The diencephalic syndrome (due to hypothalamic disturbance) is common in these patients. Potential clinical manifestations of chiasmatic glioma in older children include precocious puberty, growth failure, and visual loss. Diffuse optic pathway glioma may cause visual loss. In some instances, however, detection of the lesion is by screening of an otherwise asymptomatic patient with neurofibromatosis type 1.

CT and MR show a chiasmatic glioma as an enhancing suprasellar mass. With a large lesion, it is usually impossible to differentiate a chiasmatic versus hypothalamic origin (Figure 19-42). As with other pilocytic astrocytomas, the mass is hypointense or isointense to normal brain on T1-weighted images and hyperintense on T2-weighted images. Some degree of heterogeneity due to calcification or prior hemorrhage may be present. More extensive calcification is uncommon, however. A cystic component (uncommon in NF1 patients) sometimes extends laterally into the temporal fossa or superiorly to the base of the third ventricle. The appearance of diffuse optic pathway glioma on MR is that of T2 hyperintensity and diffuse enlargement of the optic nerves, chiasm, optic tracts, and optic radiations. In patients with associated neurofibromatosis type 1, additional manifestations of the genetic disease are sometimes present, such as multiple small foci of T2 hyperintensity within the brain.¹⁰⁴

Hypothalamic Astrocytoma

An astrocytoma of the hypothalamus sometimes causes hypothalamic-pituitary dysfunction (e.g., diabetes insipidus or obesity). A tumor at this location can also lead to diencephalic syndrome: emaciation, hyperkinesis, irritability, an alert appearance, and normal or accelerated body height despite failure to thrive. Hypothalamic astrocytoma is often indistinguishable from a chiasmatic glioma on neuroimaging evaluations. MR demonstrates a suprasellar mass that is hypointense on T1-weighted images and hyperintense on T2-weighted and FLAIR sequences. Cystic components are sometimes present in large astrocytomas (Figure 19-43). Prominent contrast enhancement is typical (Figure 19-44). The hypothalamus is a common location for pilomyxoid astrocytoma. This is a more aggressive lesion than pilocytic astrocytoma. Cysts, calcification, and perilesional edema are common with this form of astrocytoma.^105–107

Craniopharyngioma

Craniopharyngioma is a rare, benign, dysontogenetic tumor/malformation that arises from ectoblastic remnants of the Rathke pouch. Craniopharyngioma is the most common intracranial tumor of nonglial origin in the pediatric population, constituting 6% to 9% of pediatric brain tumors. This lesion accounts for about half of all suprasellar masses in children. The incidence is approximately 0.5 to 2 new cases/million population per year. This tumor presents in patients of all ages; 30% to 50% of newly diagnosed lesions are in children and adolescents. The peak prevalence is between the ages of 5 and 10 years.

Potential clinical manifestations of craniopharyngioma include visual changes, endocrine abnormalities (60% to 90% of patients), motor deficits, and macrocephaly (hydrocephalus). The most common presenting symptoms of craniopharyngioma are headache, nausea and vomiting, and growth failure. Mass effect on adjacent structures may cause visual compromise or hydrocephalus. Growth hormone deficiency is the most common pituitary hormone abnormality (approximately 80% of patients); growth failure or delayed puberty is present in about one-third of children with craniopharyngioma at the time of diagnosis. Following resection, most children with craniopharyngioma develop diabetes insipidus. Multiple pituitary hormonal deficiencies are more frequently observed in children treated with radical surgery than in those treated with conservative surgery and radiotherapy.¹⁰⁸

Craniopharyngiomas arise from embryonic rests of the Rathke pouch; this tumor may be located anywhere along the developmental path of this structure. The pituitary stalk is the most common site of origin. Other potential sites include the pituitary gland, the third ventricle, and the sphenoid sinus. Craniopharyngiomas have variable compositions. The typical pathological finding is adamantinomatous epithelium and various amounts of keratin and keratohyaline granules. Coexistent regions of squamous epithelium are present in some craniopharyngiomas. Other common histological components include cysts, cholesterol clefts, and calcification. The epithelial tissue character determines the histological type of craniopharyngioma: adamantinomatous (the most common variety in children), squamous, papillary, or mixed. Craniopharyngiomas, particularly the adamantinomatous subtype, tend to locally invade the hypothalamus. This is a potential site of recurrence following gross resection.^109,110