Astrocytomas

Astrocytomas are a heterogeneous group of pediatric CNS tumors that account for approximately 40% of cases. These tumors occur throughout the CNS.

Low-grade astrocytomas (LGAs), the predominant group of astrocytomas in childhood, are characterized by an indolent clinical course. PA is the most common astrocytoma in children, accounting for about 20% of all brain tumors (Fig. 491-3). On the basis of clinicopathologic features using the WHO Classification System, PA is classified as a WHO grade I tumor. Although PA can occur anywhere in the CNS, the classic site is the cerebellum. Other common sites include the hypothalamic/third ventricular region and the optic nerve and chiasmal region. The classic but not exclusive neuroradiologic finding in PA is the presence of a contrast medium–enhancing nodule within the wall of a cystic mass (see Fig. 491-3). The microscopic findings include the biphasic appearance of bundles of compact fibrillary tissue interspersed with loose microcystic, spongy areas. The presence of Rosenthal fibers, which are condensed masses of glial filaments occurring in the compact areas, helps establish the diagnosis. PA has a low metastatic potential and is rarely invasive. A small proportion of these tumors can progress and develop leptomeningeal spread, particularly when they occur in the optic path region. A PA very rarely undergoes malignant transformation to a more aggressive tumor. A PA of the optic nerve and chiasmal region is a relatively common finding in patients with neurofibromatosis type 1 (15% incidence). Unlike in diffuse fibrillary astrocytomas, there are no characteristic cytogenetic abnormalities in PA nor are there any known molecular abnormalities. Other tumors occurring in the pediatric age group with clinicopathologic characteristics similar to those of PA include pleomorphic xanthoastrocytoma, desmoplastic cerebral astrocytoma of infancy, and subependymal giant cell astrocytoma.

Figure 491-3 A, Axial T1-weighted MR image of a patient with cerebellar pilocytic astrocytoma, demonstrating predominantly cystic (hypointense) component (arrows) involving the left cerebellar hemisphere and vermis. B, Gadolinium-enhanced axial T1-weighted MR image in the same child demonstrates enhancement of the solid component (large arrow), enhancement of the capsule (small black arrows), and layering of contrast material (white arrow) at the bottom of the cyst.

(From Kuhn JP, Slovis TL, Haller JO: Caffey’s pediatric diagnostic imaging, ed 10, Philadelphia, 2004, Mosby, p 576.)

The second most common astrocytoma is fibrillary infiltrating astrocytoma, which consists of a group of tumors characterized by a pattern of diffuse infiltration of tumor cells among normal neural tissue and potential for anaplastic progression. On the basis of their clinicopathologic characteristics, they are grouped as low-grade astrocytomas (WHO grade II), malignant astrocytomas (anaplastic astrocytoma; WHO grade III), and glioblastoma multiforme (GBM; WHO grade IV). Of this group, the fibrillary LGA is the second most common astrocytoma in children, accounting for 15% of brain tumors. Histologically, these low-grade tumors demonstrate greater cellularity than normal brain parenchyma, with few mitotic figures, nuclear pleomorphism, and microcysts. The characteristic MRI finding is a lack of enhancement after contrast agent infusion (Fig. 491-4). Molecular genetic abnormalities found among low-grade diffuse infiltrating astrocytomas include mutations of p53 and overexpression of platelet-derived growth factor α-chain and platelet-derived growth factor receptor-α. Fibrillary infiltrating astrocytoma has the potential to evolve into malignant astrocytoma, a development that is associated with cumulative acquisition of multiple molecular abnormalities.

Figure 491-4 A, Gadolinium-enhanced axial T1-weighted MR image of grade III astrocytoma of the right thalamus demonstrating diffuse enhancement (arrow). B, Gadolinium-enhanced sagittal T1-weighted MR image showing enhancement of grade III astrocytoma of the thalamus with extension into the midbrain (black arrow) and hypothalamus (white arrow).

(From Kuhn JP, Slovis TL, Haller JO: Caffey’s pediatric diagnostic imaging, ed 10, Philadelphia, 2004, Mosby, p 595.)

Pilomyxoid astrocytoma occurs most commonly in the hypothalamic/optic chiasmic region and carries a high risk of local as well as cerebrospinal spread. This astrocytoma affects young children and infants. It is classified as a WHO grade II tumor.

The clinical management of LGAs focuses on a multimodal approach incorporating surgery as the primary treatment as well as radiation therapy and chemotherapy. The outcome of PA is better than with fibrillary LGAs. With complete surgical resection the overall survival approaches 80-100%. In patients with partial resection (<80% resection), overall survival varies from 50% to 95%, depending on the anatomic location of the tumor. In the patient who has undergone partial tumor resection and has stable neurologic status, the current approach is to follow the patient closely by examination and imaging. With evidence of progression, and second surgical resection should be considered. In patients in whom a second procedure was less than complete or is not feasible, radiation therapy is beneficial. Radiation therapy is delivered to the tumor bed at a total cumulative dose ranging from 50 to 55 Gy given on a daily schedule over 6 wk. Historically, patients with deep midline tumors were treated empirically, with radiation therapy and without surgery or biopsy, with variable survival rates from 33% to 75%. Modern surgical techniques and innovative radiation therapy methodology may have a positive impact on the survival and clinical outcome of these patients. The role of chemotherapy in the management of LGAs is evolving. Because of concerns regarding morbidity from radiation therapy in young children, several chemotherapy approaches have been evaluated, especially in children <5 yr of age. Complete response to chemotherapy is uncommon; however, these approaches have yielded durable control of disease in 70-100% of patients. Patients with midline tumors in the hypothalamic/optic chiasmatic region have tended to do less well. Taken together, the chemotherapy approaches have permitted delay and, potentially, avoidance of radiation therapy. Chemotherapy agents given singly or in combination in LGA include carboplatin, vincristine, temozolomide, vinblastine, lomustine, and procarbazine. Observation is the primary approach in clinical management of selected patients with LGAs that are biologically indolent. One such group includes patients with neurofibromatosis type 1, in whom an LGA of the optic chiasm/optic pathway or brainstem may develop; it is found incidentally. Another group includes patients with midbrain astrocytomas who have resolution of clinical symptoms after ventricular shunting and do not require further intervention.

Malignant astrocytomas are much less common in children and adolescents than in adults, accounting for 7-10% of all childhood tumors. Among this group, anaplastic astrocytoma (WHO grade III) is more common than GBM (WHO grade IV). The histopathology of anaplastic astrocytomas demonstrates greater cellularity than that of low-grade diffuse astrocytomas, cellular and nuclear atypia, presence of mitoses, and, variably, microvascular proliferation. Characteristic histopathologic findings in GBM include dense cellularity, high mitotic index, microvascular proliferation, and foci of tumor necrosis. Limited information is available regarding the molecular abnormalities in malignant astrocytomas in children. Overexpression of p53 in malignant astrocytoma in a child is an adverse prognostic factor. The frequency of mutations in p53 as well as loss of heterozygosity at 19q and 22q in childhood malignant astrocytomas is similar to that noted in adults, although the frequency of such mutations in malignant astrocytomas of children <3 yr of age is lower. This finding suggests differing mechanisms of oncogenesis in younger and older children. Optimal therapeutic approaches for malignant astrocytomas have yet to be defined. Standard therapy continues to be surgical resection followed by involved-field radiation therapy. A study of adult glioblastoma showed significantly better survival with temozolomide during and after irradiation than with irradiation alone. Current therapeutic approaches incorporate novel therapeutic agents with radiation therapy.

Oligodendrogliomas are uncommon tumors of childhood. These infiltrating tumors occur predominantly in the cerebral cortex and originate in the white matter. Histologically, oligodendrogliomas consist of rounded cells with little cytoplasm and microcalcifications. Observation of a calcified cortical mass on CT in a patient presenting with a seizure is suggestive of oligodendroglioma. Treatment approaches are similar to those for infiltrating astrocytomas.

Ependymal Tumors

Ependymal tumors are derived from the ependymal lining of the ventricular system. Ependymoma (WHO grade II) is the most common of these neoplasms, occurring predominantly in childhood and accounting for 10% of childhood tumors. Approximately 70% of ependymomas in childhood occur in the posterior fossa. The mean age of patients is 6 yr, with approximately 40% of cases occurring in children <4 yr of age. The incidence of leptomeningeal spread approaches 10% overall. Clinical presentation can be insidious and often depends on the anatomic location of the tumor. MRI demonstrates a well-circumscribed tumor with variable and complex patterns of gadolinium enhancement, with or without cystic structures (Fig. 491-5). These tumors usually are noninvasive, extending into the ventricular lumen and/or displacing normal structures, sometimes leading to significant obstructive hydrocephalus. Histologic characteristics include perivascular pseudorosettes, ependymal rosettes, monomorphic nuclear morphology, and occasional nonpalisading foci of necrosis. Other histologic subtypes include anaplastic ependymoma (WHO grade III), which is much less common in childhood and is characterized by a high mitotic index and histologic features of microvascular proliferation and pseudopalisading necrosis. Myxopapillary ependymoma (WHO grade I) is a slow-growing tumor arising from the filum terminale and conus medullaris and appears to be a biologically different subtype. There are no well-defined characteristic cytogenetic or molecular genetic alterations in ependymoma, largely owing to their heterogenous nature, although various pathways have been implicated. Preliminary studies suggest that there are genetically distinct subtypes, exemplified by an association between alterations in the NF2 gene and spinal ependymoma. Surgery is the primary treatment modality, with extent of surgical resection a major prognostic factor. Two other major prognostic factors are age, with younger children having poorer outcomes, and tumor location, with localization in the posterior fossa, which often is seen in young children, associated with poorer outcomes. Surgery alone is rarely curative. Multimodal therapy incorporating irradiation with surgery has resulted in long-term survival in approximately 40% of patients with ependymoma undergoing gross total resection. Recurrence is predominantly local. Ependymoma is sensitive to a spectrum of chemotherapeutic agents; the role of chemotherapy in multimodal therapy of ependymoma is still unclear. Current investigations are directed toward identification of optimal radiation dose, surgical questions addressing the use of second-look procedures after chemotherapy, and further evaluation of classic as well as novel chemotherapeutic agents.

Figure 491-5 A, Sagittal T1-weighted MR image of a patient with ependymoma, demonstrating a hypointense mass (arrows) within the fourth ventricle. B, Axial T2-weighted image of an ependymoma showing a hyperintense mass (open arrows) and a hypointense central area of calcification (closed arrow) within the fourth ventricle. C, Gadolinium-enhanced sagittal T1-weighted image demonstrating an ependymoma (arrows).

(From Kuhn JP, Slovis TL, Haller JO: Caffey’s pediatric diagnostic imaging, ed 10, Philadelphia, 2004, Mosby, p 579.)

Choroid Plexus Tumors

Choroid plexus tumors account for 2-4% of childhood CNS tumors. They are the most common CNS tumor in children <1 yr of age and account for 10-20% of CNS tumors in infants. These tumors are intraventricular epithelial neoplasms arising from the choroid plexus. Children present with signs and symptoms of increased ICP. Infants may present with macrocephaly and focal neurologic deficits. In children, these tumors predominantly occur supratentorially in the lateral ventricles. Choroid plexus papilloma (WHO grade I), the most common of this group, is a well-circumscribed lesion on neuroimaging and closely resembles normal choroid plexus histologically. Choroid plexus carcinoma (WHO grade III) is a malignant tumor with metastatic potential to seed into the CSF pathways. This malignancy has the following histologic characteristics: nuclear pleomorphism, high mitotic index, and increased cell density. Immunopositivity for transthyretin (prealbumin) is useful in confirming the diagnosis of choroid plexus tumors. The tumors are associated with the Li-Fraumeni syndrome. Simian virus 40 (SV40) may play an etiologic role in choroid plexus tumors. After complete surgical resection, the frequency of cure for choroid plexus papilloma approaches 100%, whereas the frequency of cure for choroid plexus carcinoma approaches 20-40%. Reports suggest that radiation therapy and/or chemotherapy may lead to better disease control for choroid plexus carcinoma.

Embryonal Tumors

Embryonal tumors or primitive neuroectodermal tumors (PNETs) are the most common group of malignant CNS tumors of childhood, accounting for ≈20 % of pediatric CNS tumors. They have the potential to metastasize to the neuraxis and beyond. The group includes medulloblastoma, supratentorial PNET, ependymoblastoma, medulloepithelioblastoma, and atypical teratoid/rhabdoid tumor (ATRT), all of which are histologically classified as WHO grade IV tumors.

Medulloblastoma, which accounts for 90% of embryonal tumors, is a cerebellar tumor occurring predominantly in males and at a median age of 5-7 yr. Most of these tumors occur in the midline cerebellar vermis; however, older patients may present with tumors in the cerebellar hemisphere. CT and MRI demonstrate a solid, homogeneous, contrast medium–enhancing mass in the posterior fossa causing 4th ventricular obstruction and hydrocephalus. Up to 30% of patients with medulloblastoma present with neuroimaging evidence of leptomeningeal spread. Among a variety of diverse histologic patterns of this tumor, the most common is a monomorphic sheet of undifferentiated cells classically noted as small, blue, round cells. Neuronal differentiation is more common among these tumors and is characterized histologically by the presence of Homer Wright rosettes and by immunopositivity for synaptophysin. An anaplastic variant is often more aggressive and may be associated with worse prognosis. Patients present with signs and symptoms of increased ICP (i.e., headache, nausea, vomiting, mental status changes, and hypertension) and cerebellar dysfunction (i.e., ataxia, poor balance, dysmetria). Standard clinical staging evaluation includes MRI of the brain and spine, both preoperatively and postoperatively, as well as lumbar puncture after the increased ICP has resolved (Fig. 491-6). The Chang staging system, originally based on surgical information, has been modified to incorporate information from neuroimaging to identify risk categories. Clinical features that have consistently demonstrated prognostic significance include age at diagnosis, extent of disease, and extent of surgical resection. Patients <4 yr of age have a poor outcome, partly as the result of a higher incidence of disseminated disease on presentation and past therapeutic approaches that have used less intense therapies. Patients with disseminated disease at diagnosis (M >0), including positive CSF cytologic result alone (M1), have a markedly worse outcome than those patients with no dissemination (M0). Similarly, patients with gross residual disease after surgery have worse outcomes than those in whom surgery achieved gross total resection of disease.

Figure 491-6 MRI of medulloblastoma. A, Sagittal T1-weighted image shows hypointense mass involving the vermis (arrows). B, Axial T2-weighted image shows hyperintense mass (arrows) with areas of hypointensity representing acute hemorrhagic infarction within the medulloblastoma involving the vermis.

(From Kuhn JP, Slovis TL, Haller JO: Caffey’s pediatric diagnostic imaging, ed 10, Philadelphia, 2004, Mosby, p 574.)

Cytogenetic and molecular genetic studies have demonstrated multiple abnormalities in medulloblastoma. The most common abnormality involves chromosome 17p deletions, which occur in 30-40% of all cases. These deletions are not associated with p53 mutations. Several signaling pathways have been shown to be active in medulloblastomas, including Sonic Hedgehog pathway, predominately associated with the desmoplastic variants, and the WNT pathway, which can occur in up to 15% of cases and has been associated with improved survival. Amplification of the MYCC oncogene as well as increased expression of the tyrosine kinase receptor ERBB2 have been associated with poorer outcomes, whereas improved survival is demonstrated in patients with overexpression of the neurotrophin-3 receptor (TRKC). Two risk stratification systems for medulloblastoma combining molecular markers with clinical factors have been proposed. One system is based on retrospective analysis of information about histologic variants (classic, nodular desmoplastic, anaplastic large cell); TRKC, MYCC, and ERBB2 expression; and clinical characteristics in children with medulloblastoma. One study found that the combination of clinical characteristics and ERBB2 expression provided a highly accurate means of discriminating disease risk. Another study found that gene expression profiling predicted medulloblastoma outcome independent of clinical variables. Both approaches still must be validated in larger prospective studies. With the evolution of gene array technology, preliminary studies have identified clusters of genes/gene expression that appear to be associated with metastatic medulloblastoma and outcome.

A multimodal treatment approach is pursued in medulloblastoma, with surgery the starting point of treatment. Medulloblastoma is sensitive to both chemotherapy and radiation therapy. Historically, surgery alone was ineffective. In the 1940s radiation therapy was found to be effective, improving overall outcome to a 30% survival rate. With technologic advances in neurosurgery, neuroradiology, and radiation therapy, as well as identification of chemotherapy as an effective modality, overall outcome among all patients approaches 60-70%. Standard radiation treatment in medulloblastoma incorporates craniospinal radiation at a total cumulative dose of 24 Gy, with a cumulative dose of 50-55 Gy to the tumor bed. Craniospinal radiation at this dose in children <3 yr of age results in severe late neurologic sequelae, including microcephaly, learning disabilities, mental retardation, neuroendocrine dysfunction (growth failure, hypothyroidism, hypogonadism, and absence/delay of puberty), and/or second malignancies. Similarly, in older children, late sequelae, such as learning disabilities, neuroendocrine dysfunction, and/or second malignancies, can occur. These observations have resulted in stratification of treatment approaches into the following three strata: (1) patients <3 yr of age; (2) standard-risk patients >3 yr of age with surgical total resection and no disease dissemination (M0); and (3) high-risk patients >3 yr of age with disease dissemination (M >0) and/or bulky residual disease after surgery. With the risk-based approach to treatment, children with high-risk medulloblastoma receive high-dose cranial-spinal radiation (36 Gy) with chemotherapy during and after radiation therapy, and those with standard-risk (nonmetastatic) disease receive lower dose craniospinal radiation (24 Gy) with chemotherapy during and after radiation therapy. Approaches in young children (<4 yr of age) incorporate high-dose chemotherapy with peripheral stem cell re-infusion and exclude radiation therapy. Overall survival in children with nonmetastatic medulloblastoma and gross total tumor resection approaches 85%. The presence of bulky residual tumor (56% survival) or metastases (38%) confers a poor prognosis.

Supratentorial primitive neuroectodermal tumors (SPNETs) account for 2-3% of childhood brain tumors, primarily in children within the first decade of life. These tumors are similar histologically to medulloblastoma and are composed of undifferentiated or poorly differentiated neuroepithelial cells. Historically, patients with SPNETs have had poorer outcomes than those with medulloblastoma after combined-modality therapy. In current clinical trials, children with SPNETs are considered among the high-risk group and receive dose-intense chemotherapy with craniospinal radiation therapy.

Atypical teratoid/rhabdoid tumor is a very aggressive embryonal malignancy that occurs predominantly in children <5 yr of age and can occur at any location in the neuraxis. The histology demonstrates a heterogeneous pattern of cells, including rhabdoid cells that express epithelial membrane antigen and neurofilament antigen. The characteristic cytogenetic pattern is partial or complete deletion of chromosome 22q11.2 that has been associated with mutation in the INI1 gene. The relation between this mutation and tumorigenesis is unclear. Outcome after combined-modality therapy with intensive chemotherapy is very poor, but long-term survival has been reported in some children.

Pineal Parenchymal Tumors

The pineal parenchymal tumors are the most common malignancies after germ cell tumors that occur in the pineal region. These include pineoblastoma, occurring predominantly in childhood, pineocytoma, and the mixed pineal parenchymal tumors. The therapeutic approach in this group of diseases is multimodal. There was significant concern regarding the location of these masses and the potential complications of surgical intervention. With developments in neurosurgical technique and surgical technology, the morbidity and mortality associated with these approaches have markedly decreased. Stereotactic biopsy of these tumors may be adequate to establish diagnosis; however, consideration should be pursued for total resection of the lesion before institution of additional therapy. Pineoblastoma, the more malignant variant, is considered a subgroup of childhood PNETs. Chemotherapy regimens incorporate cisplatin, cyclophosphamide (Cytoxan), etoposide (VP-16), and vincristine and/or lomustine. Data have shown that survival outcome of combined modality therapy of chemotherapy and radiation in pineal region PNETs approaches 70% at 5 yr, similar to that noted for medulloblastoma. Pineocytoma usually is approached with surgical resection.

Craniopharyngioma

Craniopharyngioma (WHO grade I) is a common tumor of childhood, accounting for 7-10% of all childhood tumors. The adamantinomatous variant of craniopharyngioma predominates in childhood. Children with craniopharyngioma often present with endocrinologic abnormalities such as growth failure and delayed sexual maturation. Visual changes can occur and may include decrease acuity or visual field deficits. These tumors are often quite large and heterogenous, displaying both solid and cystic components, and occur within the suprasellar region. They are minimally invasive, adhere to adjacent brain parenchyma, and engulf normal brain structures. MRI demonstrates the solid tumor with cystic structures containing fluid of intermediate density. CT may show calcifications associated with the solid and cystic wall components. Surgery is the primary treatment modality, with gross total resection curative in small lesions. Controversy exists regarding the relative roles of surgery and radiation therapy in large, complex tumors. Significant morbidity (panhypopituitarism, growth failure, visual loss) is associated with these tumors and their therapy, owing to the anatomic location. There is no role for chemotherapy in craniopharyngioma.

Germ Cell Tumors

Germ cell tumors of the CNS are a heterogeneous group of tumors that are primarily tumors of childhood, arising predominantly in midline structures of the pineal and suprasellar regions. They account for 3-5% of pediatric brain tumors. The peak incidence of these tumors is in children 10-12 yr of age. Overall, there is a male preponderance, although there is a female preponderance for suprasellar tumors. Germ cell tumors occur multifocally in 5-10% of cases. This group of tumors is much more prevalent in Asian populations than European populations. Delays in diagnosis can occur because these tumors have a particularly insidious course; the initial presenting symptoms may be subtle, including poor school performance and behavior problems. As in peripheral germ cell tumors, the analysis of protein markers, α-fetoprotein, and β-human chorionic gonadotropin may be useful in establishing the diagnosis and monitoring treatment response. Surgical biopsy is recommended to establish the diagnosis; however, nongerminomatous germ cell tumors may be diagnosed on the basis of protein marker elevations. Therapeutic approaches to germinomas and mixed germ cell tumors are different. The survival proportion among patients with pure germinoma exceeds 90%. The postsurgical treatment of pure germinomas is somewhat controversial in defining the relative roles of chemotherapy and radiation therapy. Clinical trials have investigated the use of chemotherapy and reduced-dose radiation after surgery in pure germinomas. The therapeutic approach to nongerminomatous germ cell tumors is more aggressive, combining more intense chemotherapy regimens with craniospinal radiation therapy. Survival rates among patients with these tumors are markedly less than those noted in patients with germinoma, ranging from 40% to 70% at 5 yr. Trials have shown benefit of the use of high doses of chemotherapy with blood stem cell rescue.

Tumors of the Brainstem

Tumors of the brainstem are a heterogeneous group of tumors that account for 10-15% of childhood primary CNS tumors. Outcome depends on tumor location, imaging characteristics, and the patient’s clinical status. Patients with these tumors may present with motor weakness, cranial nerve deficits, cerebellar deficits, and/or signs of increased ICP. On the basis of MRI evaluation and clinical findings, tumors of the brainstem can be classified into four types: focal (5-10% of patients); dorsally exophytic (5-10%); cervicomedullary (5-10%); and diffuse intrinsic (70-85%) (Fig. 491-7). Surgical resection is the primary treatment approach for focal and dorsally exophytic tumors and leads to a favorable outcome. Histologically, these two groups usually are low-grade gliomas. Cervicomedullary tumors, owing to their location, may not be amenable to surgical resection but are sensitive to radiation therapy. Diffuse intrinsic tumors, characterized by the diffuse infiltrating pontine glioma, are associated with very poor outcome independent of histologic diagnosis. These tumors are not amenable to surgical resection. Biopsy in children in whom MRI shows a diffuse intrinsic tumor is controversial and is not recommended unless there is suspicion of another diagnosis, such as infection, demyelination, vascular malformation, multiple sclerosis, or metastatic tumor. These diagnoses are much more common in adults. The standard approach for treatment of diffuse infiltrating pontine gliomas has been radiation therapy, and median survival with this treatment is 12 mo, at best. Use of chemotherapy, including high-dose chemotherapy with blood stem cell rescue, has not yet been of survival benefit in this group of patients. Current approaches include evaluation of investigational agents alone or in combination with radiation therapy, similar to approaches being pursued in patients with malignant gliomas.

Figure 491-7 T1-weighted sequence post-gadolinium sagittal MR image of a pontine diffuse infiltrating glioma in a 10 yr old girl presenting with headache, cranial nerve palsies, and left-sided weakness.

Metastatic Tumors

Metastatic spread of other childhood malignancies to the brain is uncommon. Childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma can spread to the leptomeninges, causing symptoms of communicating hydrocephalus. Chloromas, which are collections of myeloid leukemia cells, can occur throughout the neuraxis. Rarely, brain parenchymal metastases occur from lymphoma, neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and clear cell sarcoma of the kidney. Therapeutic approaches are based on the specific histologic diagnosis and may incorporate radiation therapy, intrathecal administration of chemotherapy, and/or systemic administration of chemotherapy. Medulloblastoma is the childhood brain tumor that most commonly metastasizes extraneuronally. Less commonly, extraneuronal metastases from malignant glioma, PNET, and ependymoma can occur. Ventriculoperitoneal shunts have been known to allow extraneural metastases, primarily within the peritoneal cavity but also systemically.