Pediatric brain tumors represent the second most common form of pediatric cancer and the most common solid malignancy. The most recent statistics available report findings from 2004, and they show that the incidence of pediatric brain tumors is approximately 1100 per year, representing 20% of all childhood cancers. These neoplasms also represent the second leading cause of cancer death in US children, and the sixth leading cause of death in US children overall.1,2 Survival for children with central nervous system (CNS) neoplasms, however, has dramatically risen over the past 30 years, with 5-year survival rates of 74%, up from 57% in 1977. Most of these results are due to a combination of improved chemotherapeutic regimens, more accurately targeted and dosed radiation, and safer, more accurate surgical resection techniques.1,3

The location of childhood tumors differs from those in adults. Most pediatric tumors occur in the posterior fossa, with medulloblastoma, juvenile pilocytic astrocytoma (JPA), and ependymoma making up the majority of these lesions.1-4

The etiology of childhood tumors is poorly understood. Although certain genetic syndromes are responsible for an increased risk of tumorigenesis (Table 25-1), the majority of tumors arise de novo. Certain environmental exposures have also been implicated in the development of tumors, including toxic chemicals, cigarette smoke, radiation, medications, home microwave ovens, cellular telephones, and electromagnetic fields. Of these, the only exposure that has a proven link to tumorigenesis is ionizing therapeutic radiation.5

Brain tumors arise from multiple different cell lineages, and thus are a heterogeneous population of tumors. In this review, we will examine the following lesions: low-grade glioma, high-grade glioma, medulloblastoma, ependymoma, juvenile pilocytic astrocytoma, brainstem glioma, craniopharyngioma, and pineal region tumors (usually germ cell).

Pediatric brain tumors appear to arise from a different set of circumstances than do similar adult lesions. Craniopharyngiomas represent remains of embryonic cells that slowly differentiate over time, leading to growth of large lesions. Medulloblastomas are primitive neuroectodermal tumors (PNETs) that arise from similar but more aggressive embryonic rests. High- and low-grade gliomas are derived from newly differentiated glial cells that undergo multiple different genetic mutations, leading to malignant transformation.6

Presentation of pediatric brain tumors can differ depending on location and vary from subtle changes to fulminant coma with the need for emergent neurosurgical treatment (Table 25-2). The most common symptom of mass lesions is headache. This can be difficult to localize, and headache in the absence of other neurological signs is not an indication for neuroimaging. Other signs and symptoms include seizures, nausea/vomiting, ataxia/dysmetria, visual disturbances, macrocephaly/hydrocephalus, weakness (focal deficit), altered level of consciousness, and endocrine disturbances (including weight loss/gain, precocious puberty, amenorrhea, hypothyroidism, and diabetes insipidus).7

History and Physical Examinations

Diagnosis of pediatric brain tumors starts with a detailed clinical history and physical examinations. A combination of findings from the list of symptoms described in the earlier section will often lead to an imaging study.7 In the vast majority of cases, neuroimaging will lead to discovery and, often, diagnosis of a lesion. For emergency situations, computed tomography (CT) scanning is the study of choice. CT scanning, however, has low soft-tissue resolution, which can limit its ability to identify intrinsic brain lesions. CT also has the disadvantage of using ionizing radiation. Thus, if there is appropriate clinical suspicion, magnetic resonance imaging (MRI) is indicated. MRI allows for multiplanar imaging and much more sensitive and subtle differentiation of normal and abnormal tissues. MRI is especially suited for posterior fossa imaging, where beam hardening artifact from CT often makes accurate diagnosis of a lesion difficult or impossible. Enhanced MRI with the administration of gadolinium increases sensitivity and reveals areas of breakdown of the blood-brain barrier. This accurately depicts the tumor nidus, although this does not necessarily imply tumor grade.8

Postoperatively, enhanced MRI is the gold standard for evaluation of residual tumor. Other more specialized imaging techniques, including MR-spectroscopy and positron-emission tomography (PET) scanning, may give additional information regarding brain lesions. These technologies, however, are currently reserved for monitoring tumor response to therapy and differentiating tumor regrowth versus treatment effects such as radiation necrosis.9 The specific imaging characteristics of different types of tumors will be discussed with each separate lesion.

Medulloblastoma

Medulloblastoma is a highly aggressive form of childhood brain tumor and is the most common malignant central nervous system tumor in children. The term “medulloblastoma” is actually a misnomer, derived from the idea that these tumors arose from multipotential cells known as medulloblasts. These tumors have since been reclassified as PNETs and thus can be referred to interchangeably as PNET-MB, medulloblastoma, or infratentorial PNET. MB represents about 20% of all pediatric brain tumors and 30% of posterior fossa tumors. There is a 2 to 1 male predominance. These tumors present with a classic posterior fossa syndrome, including headache that is worse in the morning, nausea, vomiting, and a fairly rapid decline over 1 to 2 months. Occasionally presentation can be related to spinal pathology from drop metastases, including back pain, leg pain, or paraparesis. Physical examination findings include papilledema, sixth-nerve palsies, lethargy, or ataxia. The diagnostic evaluation of these lesions begins with imaging. CT can be used for emergent symptoms, but contrasted MRI is the study of choice. CT shows hyperdensity in the area of the vermis, often with speckled calcifications, ± cyst formation (Figure 25-1). MRI will show T1 iso- to hypodensity and T2 hyperintensity, as well as avid enhancement with contrast (Figures 25-2, 25-3, and 25-4). Diffusion-weighted imaging can also help differentiate these tumors from others, as it will often reveal restricted diffusion as a consequence of the lesions’ hypercellularity (Figures 25-5 and 25-6). Due to the propensity of these tumors to spread through the neural axis, MR imaging of the entire neuraxis to assess for drop metastases is also indicated (Figure 25-7).10,11

Initial treatment is aimed at stabilizing the patient, often with the administration of steroids. Occasionally, emergent cerebrospinal fluid diversion such as external ventricular drain placement or endoscopic third ventriculostomy is performed. This should be followed by surgical evaluation. Tumor resection is the treatment of choice and allows for relief of mass effect, cerebrospinal fluid (CSF) diversion/drainage, and tissue diagnosis. Due to the location of these tumors and their adherence to critical brain structures, morbidity is fairly high, on the order of 25% to 40%. Complications include cranial nerve deficits, swallowing/breathing difficulties, cerebellar mutism, gaze abnormalities, hydrocephalus, and infection.12

After surgical resection, the next step in treatment is adjuvant, in the form of chemotherapy and radiation. For children older than 3 years, radiation to the tumor bed and the craniospinal axis, followed by chemotherapy alone, is the current standard.13,14 For those considered to be high risk (age less than 3 years, >1.5 mL of residual tumor, tumor dissemination) are offered chemotherapy alone if younger than 3 years, and either concurrent chemotherapy/irradiation followed by chemotherapy, or induction chemotherapy with stem cell rescue if the patient is older than 3 years. Five-year survival for low-risk tumors is as high as 80%, and recent data for recurrent and progressive disease indicates 5-year survival of almost 70% with a stem cell rescue strategy.15 Overall, however, continued research is ongoing and is attempting to focus not only on survival, but also on the morbidity, especially neurocognitive, of these treatments.

Ependymoma

Ependymomas represent about 10% of pediatric brain tumors and 15% of posterior fossa tumors.2,16 They are the third most common pediatric brain tumor behind medulloblastoma and cerebellar astrocytoma. These tumors arise from ependymal cells that line the ventricular system. The presentation of posterior fossa ependymoma is similar to that of medulloblastoma, although rarely as rapid. Signs and symptoms of hydrocephalus, compression of the brainstem, and cranial neuropathies are the most common. Classically, it is not uncommon for these patients to have gastrointestinal (GI) problems including nausea, vomiting, and poor appetite that have gone on for a prolonged period, resulting in a prolonged gastrointestinal workup prior to eventual neuroimaging that reveals a brain tumor.16-20 The best diagnostic study is contrasted MRI. These tumors will be iso- to hypointense on T1 and T2 and show heterogeneous enhancement (Figures 25-8, 25-9, and 25-10). The tumor can often be seen arising from the floor of the fourth ventricle and also exiting through the foramina of the fourth ventricle, including Luschka and Magendie (Figures 25-10 and 25-11). The extrusion of ependymomas out of the fourth ventricle is often referred to as plastic ependymoma. Imaging of the entire spinal axis is also indicated due to the rare (<10 %) occurrence of drop metastases. This imaging preoperatively is also important to distinguishing between new tumor spread and expected postoperative changes.8,9

Surgical treatment of these tumors is the first option. This allows for pathologic diagnosis, tumor gross total resection if possible, and reestablishment of CSF flow channels. Following diagnosis, the current mainstay of adjuvant therapy is conformal local radiation therapy. This currently includes conformal radiotherapy to the tumor bed in a variety of fractions and total doses ranging from 54 to 59.4 Gy.21-24 Chemotherapy also has a role in this disease, and multiple different regimens have been used, with cisplatin appearing to be the most effective agent, with approximately a 40% response rate.25-28 Overall, 5-year survival for patients with ependymoma is approximately 55% in historical studies, with some improvement recently to as high as 70% with gross total resection followed by adjuvant local involved field radiation.

Juvenile Pilocytic Astrocytoma

Juvenile pilocytic astrocytoma (JPA) is another of the most common pediatric brain tumors and is most often located in the posterior fossa. It is the second most common posterior fossa tumor, representing approximately 20% to 35% of these lesions.1,2 These tumors can also be found in the hypothalamus (Figure 25-12), optic nerves (Figure 25-13), thalamus, and the cerebral hemispheres. Pilocytic tumors are also associated with neurofibromatosis type I, and the optic nerve and hypothalamic lesions are more common in this setting. Pathologically, the classic finding with JPA is fibrillar astrocytes against a microcystic background and the presence of eosinophilic intracytoplasmic inclusions called Rosenthal fibers. Signs and symptoms of these tumors are similar to other posterior fossa lesions, including headaches, ataxia, and hydrocephalus. Optic nerve lesions can lead to visual loss.29 The diagnostic workup for these tumors is contrasted MRI. Often, these tumors have a cystic appearance with an enhancing mural nodule. Solid lesions can also have varying degrees of contrast enhancement. In spite of this enhancement, however, these tumors are often benign in their course.8 Surgical removal, when possible, is the treatment of choice.29-31 For WHO grade I tumors, survival exceeds 90% at 10 years with gross total resection. Adjuvant therapy for JPA is usually reserved for subtotally resected lesions that show signs of continued growth or for recurrent lesions after gross total resection. Radiotherapy has not been shown to affect overall survival in the nonrecurrent setting, although it has shown some efficacy in preventing disease progression.32 Chemotherapy has also not been greatly effective for these lesions in the posterior fossa, although multiple trial regimens are available.29