Abstract
Space-occupying lesions—including brain tumors, vein of Galen malformations, and arachnoid cysts—represent important intracranial mass lesions and share certain clinical features. Improvements in management in recent years have made the prognosis of these serious disorders considerably more favorable than in the past in selected cases. Still, very few children survive without unfavorable consequences, including hydrocephalus, intractable seizures, or significant developmental delay. Risks of interventions, such as anesthesia and blood loss, are tolerated better by infants older than 3 months, and definitive treatment may be deferred until later in infancy. Arachnoid cysts are an exception and can often be treated immediately with minimally invasive techniques.
Keywords
brain tumor, intracranial teratoma, astrocytoma, medulloblastoma, craniopharyngioma, choroid plexus papilloma, gliosarcoma, glioma, glioneuronal tumor, vein of Galen malformation, arteriovenous malformation, arachnoid cyst
In this chapter, space-occupying lesions—including brain tumors, vein of Galen malformations, and arachnoid cysts—are discussed. These disorders are considered in the same chapter because they represent important intracranial mass lesions and share certain clinical features. We do not review management in detail; this is considered in depth in standard neurosurgical writings. Improvements in management in recent years have made the prognosis of these serious disorders considerably more favorable than in the past. But although the prognosis has improved, very few children with neonatal mass lesions will survive without unfavorable consequences, which can include hydrocephalus, intractable seizures, or significant developmental delay. Because the risks of interventions, such as anesthesia and blood loss, are tolerated better by infants older than 3 months, definitive treatment may be deferred until later in infancy. Arachnoid cysts are an exception, since they are now often treated with minimally invasive techniques.
Brain Tumors
Brain tumors manifesting either at birth or in utero or within the first 2 months of life account for approximately 1% to 2% of all brain tumors encountered in the pediatric age group, or 1 to 3 cases per million live births. Although in most major reviews neonatal brain tumors are grouped with tumors manifesting in the first 1 to 2 years of life, brain tumors appearing at birth or in utero or in the first 2 postnatal months are sufficiently distinctive in histological and clinical characteristics to be considered separately. In this chapter, we discuss only tumors manifesting at birth or in utero and in the first 2 postnatal months.
The diagnosis, treatment, and prognosis of neonatal brain tumors have progressed markedly since Raskind and Beigel attributed congenital brain tumors to cell rests in 1964. Genetic and molecular subtyping of pediatric brain tumors then began to transform the field. Derangements in the control of cell proliferation and differentiation are central to etiology, and abnormalities of genes encoding proteins that function as growth factors (e.g., platelet-derived growth factor), as stimulators of cell proliferation (e.g., oncogenes) or as suppressors of cell proliferation (e.g., tumor suppressor genes) have been identified in various tumors. Additionally, abnormal genetic material inserted into the human genome by certain viruses may induce tumor formation; polymerase chain reaction technology has been used to show the presence of DNA sequences of simian virus 40, one member of a family of viruses (polyomaviruses) that induces tumors in laboratory animals. These sequences were observed in 10 of 20 choroid plexus tumors and in 10 of 11 ependymomas in children; both of these tumors are relatively common in the neonatal period (see laterdiscussion). Molecular classification of ependymal tumors and atypical teratoid rhabdoid tumors (ATRTs) were recently proposed.For example, a tumor suppressor protein that regulates chromatin remodeling is missing in some ATRTs. Additional mutationsin the chromatin remodeling complex gene SMARCB1/HSNF5/INI1 ( SWI/SNF -related matrix-associated actin-dependentregulator of chromatin subfamily B member 1 gene, alsoknown as INI1 ) are present in 23% to 35% of infants with ATRT. Similarly, tumor suppressor p53 mutations have been found in 50% of choroid plexus tumors. Although in many instances progress is still limited to case reports, drugs targeting specific mutations can be effective in situations in which traditional chemotherapy has failed. The pace of genetic discoveries is accelerating with technical advances, and it is anticipated that the field will change markedly over the next decade.
Neuropathology
Histological Types
The histological types of neonatal brain tumors differ considerably according to the time of clinical presentation ( Table 37.1 ). Thus teratomas are the predominant tumors in infants who present clinically in fetal life or at birth, whereas tumors of neuroepithelial origin predominate in the first 2 postnatal months. The high proportion of teratomas shown in Table 37.1 is based on two large series (cumulative total, 425). These lesions are usually very large ( Fig. 37.1 ). Indeed, approximately 35% to 60% are so large that the site of origin in the supratentorial compartment cannot be determined. Nearly 20% of neonatal teratomas originate from the region of the lateral ventricle, and another approximately 10% to 20% originate from the region of the third ventricle. Only uncommonly do neonatal teratomas originate from the pineal region, the site of most intracranial teratomas that manifest clinically after the neonatal period.
| PERCENTAGE OF TUMORS WITH PRESENTATION AT BIRTH OR IN UTERO | PERCENTAGE OF TUMORS WITH PRESENTATION IN FIRST 2 MONTHS | |
|---|---|---|
| Teratoma | 47 | 26 |
| Neuroepithelial tumor | 40 | 65 |
| Other | 13 | 9 |
The major types of nonteratomatous tumors (i.e., neuroepithelial and mesenchymal tumors) are shown in Table 37.2 . Astrocytoma is the most common single category. Medulloblastoma, ATRT, choroid plexus papilloma (and carcinoma), and ependymoma are also relatively common. The remaining tumors encountered include other primitive neuroectodermal tumors (not medulloblastoma) and desmoplastic infantile ganglioglioma. Desmoplastic infantile gangliogliomas (DIGs) account for approximately 16% of infantile tumors and must be distinguished from glioblastomas (GBMs) owing to the marked difference in prognosis ( Fig. 37.2 ). Both occur supratentorially, have cystic and solid components, and have similar features on magnetic resonance imaging (MRI). The prognosis for DIG is generally favorable, although a few more aggressive cases have been reported. Of the neuroepithelial tumors, choroid plexus papilloma has the most consistent site of origin (i.e., the lateral ventricle in most cases). Among other tumors, craniopharyngioma is the most common single type, although sarcoma, fibroma, hemangioblastoma, hemangioma, and meningioma have all been documented. a
a References .
| A. Classification of nonteratomatous brain tumors a | |
| |
| B. Relative location of nonteratomatous neonatal brain tumors in modern series b | |
| Supratentorial | 66% |
| Infratentorial | 34% |
| C. Relative frequency of nonteratomatous neonatal brain tumors in modern case series c | |
| Astrocytoma (WHO grades I–IV) | 27% |
| Atypical teratoid/rhabdoid tumor | 18% |
| Choroid plexus papilloma/carcinoma | 16% |
| Ependymoma (WHO grades I–III) | 13% |
| Desmoplastic infantile ganglioglioma | 9% |
| Medulloblastoma/PNET | 8% |
| Glioneuronal tumor | 4% |
| Poorly differentiated carcinoma | 4% |
| Craniopharyngioma | 1% |
Particularly unusual, additional examples of neonatal brain tumors include intracranial chordoma, derived from midline remnants of notochord, gliomatosis cerebri, mixed neural tissue masses extending into the oropharynx, hypothalamic hamartoma, lipoma of corpus callosum, multiple lipomata, and subependymal giant cell astrocytoma associated with tuberous sclerosis. a
a References .
The astrocytomas associated with tuberous sclerosis are usually accompanied in the newborn by cardiac rhabdomyoma, and, indeed, this may be the principal clue to the diagnosis of tuberous sclerosis in the neonatal period in such patients. The cardiac tumor may lead to cardiac complications (e.g., arrhythmia) that can be life-threatening at the time of surgery for the subependymal astrocytoma. The mTOR inhibitor everolimus has shown benefit in a few infants with TSC tumors.Location
The location of neonatal brain tumors is distinctly different from that observed in pediatric patients in late infancy and childhood ( Table 37.3 ). Thus, supratentorial predominance is apparent, with 60% to 70% being supratentorial. This predominance is marked for teratomas, which are nearly always supratentorial in location. In contrast, medulloblastoma is the one type of neonatal brain tumor with consistent predominance in the infratentorial compartment. If only neuroepithelial tumors are considered, the ratio of supratentorial to infratentorial lesions is 1.7 : 1 for tumors manifesting at birth and 2.4 : 1 for those appearing in the first 2 postnatal months. If all neonatal brain tumors are considered (i.e., teratomas and mesenchymal tumors as well as neuroepithelial tumors), the supratentorial predominance is even more marked (see Table 37.3 ).
| PRESENTATION AT BIRTH | PRESENTATION IN FIRST 2 MONTHS | |||
|---|---|---|---|---|
| SUPRATENTORIAL | INFRATENTORIAL | SUPRATENTORIAL | INFRATENTORIAL | |
| Teratoma | 44 | 0 | 18 | 1 |
| Neuroepithelial tumor | ||||
| Medulloblastoma | 2 | 7 | 1 | 8 |
| Astrocytoma | 5 | 3 | 9 | 2 |
| Choroid plexus papilloma | 6 | 0 | 9 | 0 |
| Ependymoma, ependymoblastoma | 4 | 0 | 7 | 2 |
| Other neuroepithelial tumors | 10 | 6 | 8 | 2 |
| Total of all neuroepithelial tumors | 27 | 16 | 34 | 14 |
| Supratentorial-to-infratentorial ratio for neuroepithelial tumors | 1.7 : 1 | 2.4 : 1 | ||
| Supratentorial-to-infratentorial ratio for all tumors (teratoma, neuroepithelial, mesenchymal) | 5.2 : 1 | 3.4 : 1 | ||
Clinical Features
The clinical features of neonatal brain tumors can be divided essentially into four major syndromes ( Table 37.4 ). a
a References .
The first syndrome is characterized by a mass lesion that is so large in fetal life that severe macrocrania results in cranial-pelvic disproportion, dystocia, stillbirth, or premature labor. This obstetrical syndrome is characteristic of teratomas ( Fig. 37.3 ), but it may also be observed with large neuroepithelial tumors (see Table 37.4 ). Commonly, other features related to displacement of intracranial tissue by tumor (e.g., local skull swelling, proptosis, or epignathus) may be present in this syndrome. The second syndrome is characterized predominantly by macrocrania and bulging fontanelle, often secondary to hydrocephalus, and is observed in approximately 50% of newborns with CNS tumors. Seizures and progressive macrocephaly are observed with DIG tumors. This syndrome also may accompany the features just described for teratomas and may occur for tumors that manifest at birth or in the first 2 postnatal months (see Table 37.4 ). The third syndrome consists of specific neurological features related to the particular type and location of the tumor and is particularly characteristic of tumors manifesting after birth, in the first 2 postnatal months. These neurological features include seizures, present in 15% to 25% of patients with neonatal brain tumors; hemiparesis or quadriparesis; cranial nerve abnormalities; and signs of increased intracranial pressure, often secondary to hydrocephalus. The last of these characteristics is a consistent feature of choroid plexus papilloma. Specific neurological features of spinal cord tumors include torticollis with high cervical spinal cord lesions, usually astrocytoma, and weakness of lower extremities with disturbance of sphincter function in lumbosacral-coccygeal lesions, usually teratoma. The spinal cord lesions are particularly important to identify promptly, because abrupt neurological deterioration may occur spontaneously or after mild trauma (e.g., neck manipulation). The fourth clinical syndrome associated with neonatal brain tumors is abrupt onset of intracranial hemorrhage ( Figs. 37.4 and 37.5 ). aa References .
Hemorrhage with brain tumor is more common in neonatal lesions than in tumors at later ages and develops in approximately 8% to 18% of cases, more commonly in patients with neuroepithelial lesions or vascular tumors (e.g., cavernous hemangioma) than in patients with teratomas ( Table 37.5 ). More often, the hemorrhage is an incidental finding at the time of diagnostic brain imaging, surgery, or autopsy, but occasionally it is large enough to be the presenting clinical feature. Indeed, any infant with an intraparenchymal hemorrhage with no readily identifiable cause (see Chapter 22 ) should be evaluated for the presence of brain tumor.| SIGNS AND SYMPTOMS | PRESENTATION AT BIRTH (%) | PRESENTATION IN FIRST 2 MONTHS (%) | |
|---|---|---|---|
| TERATOMA | OTHERS | ||
| Dystocia | 45 | 20 | – |
| Stillborn | 40 | 15 | – |
| Prematurity | 30 | 20 | – |
| Large head and/or bulging fontanelle | 70 | 55 | 70 |
| Epignathus | 10 | – | – |
| Local skull swelling | 10 | 5 | 2 |
| Proptosis | 8 | 1 | – |
| Seizure | – | 2 | 15 |
| Vomiting | – | 1 | 30 |
a n = 200 in reference , n = 250 in reference , and n = 534 in reference . Numbers are rounded off.
| HISTOLOGICAL TYPE | INCIDENCE OF HEMORRHAGE (%) |
|---|---|
| Teratoma | 8 |
| Neuroepithelial and other | 18 |
| All tumors | 14 |
Diagnosis
The diagnosis is based on a high index of clinical suspicion. Notably, only 18% of neonatal brain tumors reported are identified by prenatal ultrasound. The majority of congenital tumors undergo rapid growth during the third trimester. The need for evaluation for brain tumor is straightforward in the infant with macrocrania, bulging anterior fontanelle, hydrocephalus of unknown cause, or focal neurological deficit. Sometimes overlooked is the need to consider tumor in the infant with unexplained intracranial hemorrhage (see earlier discussion), seizures, irritability, or persistent vomiting. The diagnostic approach should begin with a brain imaging procedure, and cranial ultrasonography is the best initial choice. This noninvasive modality demonstrates tumors in and near the lateral and third ventricles especially well ( Figs. 37.6 and 37.7 ). The addition of Doppler evaluation of blood flow within the tumor is useful in the identification of choroid plexus papilloma, a strikingly hypervascular tumor ( Fig. 37.8 ). In general, however, MRI is the mainstay of the diagnostic evaluation (see Fig. 37.4 ; Figs. 37.9 to 37.13 ). MRI is preferred for all lesions, especially for those in the posterior fossa and spinal cord (see Fig. 37.13 ). Computed tomography (CT) is currently reserved for use in neonates when emergent neurosurgical intervention is indicated and a timely MRI is not available.
Prognosis
The outcome of patients with neonatal brain tumors depends on the size and location of the lesion, the time of diagnosis, and particularly the histological type of the tumor. General conclusions concerning prognosis of the most common neonatal brain tumors are summarized in Table 37.6 . a
a References .
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