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Imaging of Congenital Brain Tumors
Imaging of Congenital Brain Tumors Hemant A. Parmar, MD,* Sumit Pruthi, MD,† Mohannad Ibrahim, MD,* and Dheeraj Gandhi, MD‡ Brain tumors of the fetus and neonate are uncommon entities, compared with those of the older child and adolescents. They differ from those occurring in the older child and adolescent in several ways, including the tumor histology, tumor location, and overall prognosis. In this article, we review the most common intracranial tumors encountered in very young children, with emphasis on their imaging features. Semin Ultrasound CT MRI 32:578-589 © 2011 Elsevier Inc. All rights reserved.
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ongenital tumors are defined as those presenting within 60 days of birth according to the definition proposed by Arnstein et al.1 According to Solitare and Krigman,2 there are 3 categories of intracranial tumors in newborns: definitely congenital (present at birth), probably congenital (detected within the first week of life), and possibly congenital (detected within the first 2 months of life). Some authors extend the time frame of congenital tumors to first 6 months after birth.3 These divisions are arbitrary and defining the true congenital nature may be complex, as some true in-utero tumor may not manifest in the early period of life. Brain tumors of the fetus and neonate are uncommon compared with those of the older child and adolescent.4 They account for only 10% of all antenatal tumors, ranking behind extracranial teratomas, neuroblastomas, and soft-tissue tumors.4 Intracranial teratoma, a relatively uncommon central nervous system (CNS) tumor in children, is the most common fetal brain tumor, accounting for approximately one-half of all reported cases.4 They are followed in frequency by astrocytomas of various grades, lipomas, choroid plexus papillomas (CPP), craniopharyngiomas, and primitive neuroectodermal tumors (PNET).4,5 These tumors differ from those occurring in the older child and adolescent in several ways. First, the location is not entirely the same. Primary intracranial tumors in the older child are mostly infratentorial in contrast to the fetus and neonate in whom most tumors are found in the supratentorial compartment.4 The clinical presentation and frequency of the various histologic types are
*Department of Radiology, University of Michigan, Ann Arbor, MI. †Department of Radiology, Vanderbilt University Medical Center, Nashville, TN. ‡Department of Radiology, Johns Hopkins Hospital, Baltimore, MD. Address reprint requests to Hemant A. Parmar, MD, Department of Radiology, University of Michigan Health System, Taubman Center/B1/132 F, 1500 East Medical Center, Ann Arbor, MI 48109-0302. E-mail: [email protected]
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dissimilar. In general, the prognosis is poor because of the large tumor size and the limitations of adjuvant chemotherapy and radiotherapy at such a young age.6,7 Brain immaturity and the expansile capacity of the infant’s skull delay the diagnosis, and surgical resection may be impossible when it is finally detected. The 2 notable exceptions are fetuses with lipomas and fetuses with CPP, both of which fare far better than fetuses with other congenital brain tumors.4,5
Incidence Congenital tumors account for 18% of brain tumors presenting during the first year of life and approximately 0.5%-1.5% of those in childhood.8 Overall, CNS tumors are the cause of 5%-20% of deaths in the fetal and neonatal period.9 Intracranial teratoma is the most common fetal brain tumor, accounting for approximately one-half of all reported cases. Teratoma is followed in frequency by astrocytomas of various grades, lipomas, CPP, craniopharyngiomas, and PNET.9 A cooperative study by the International Society of Pediatric Neurosurgery revealed more frequent supratentorial tumor location for these tumors.10 A total of 41% of patients presented with intracranial hypertension and only 12% with seizures. High mortality (40%) was observed, along with mild and severe psychomotor retardation in 95 and 143 of the 473 surviving patients. Congenital tumors are often detected incidentally on routine prenatal ultrasound (US) studies. The next imaging method used is fetal magnetic resonance imaging (MRI), which now uses ultrafast sequences that provide high-resolution imaging and eliminate motion artifacts without fetal sedation.11
Clinical Features An abnormally large head circumference is the most common finding observed in the fetus or newborn with a brain tumor regardless of the histologic type. Macrocephaly may be the
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Figure 1 Coronal T2- (A, B), axial T2- (C), T1- (D), and postcontrast-enhanced T1-weighted MRI in a 4-week-old infant shows a large heterogeneous mass in the supratentorial compartment. The mass shows multilobulated margins with peripheral areas of necrosis and multiple foci of T2 hypointensity (arrows) suggestive for calcification. There is heterogeneous and predominantly central pattern of enhancement (E).
result of hydrocephalus or the size of the tumor itself or both.4,12 Hydrocephalus, the second-most common finding, is caused by compression of the ventricular system or by hemorrhage from the tumor obstructing the ventricles. Choroid plexus tumors cause hydrocephalus by overproduction of cerebrospinal fluid (CSF). Some brain tumors grow enormously in utero causing dystocia or stillbirth.8,13 There is a high incidence of stillbirth associated with perinatal brain tumors, especially intracranial teratomas, glioblastomas, and PNETs.8,13 Large tumors cause fetal hydrops or require aspiration or decompression of the skull to permit vaginal delivery. Polyhydramnios, secondary to depressed swallowing from hypothalamic dysfunction, is also a common complication antenatally.9 Neonates with a rapidly growing neoplasm exhibit signs of increased intracranial pressure, such as vomiting, lethargy, macrocephaly, separation of cranial sutures, and bulging fontanels. According to Volpe,14 the clinical findings in neonates with brain tumors can be categorized into the following 4 main groups: (1) gigantic tumors producing severe macrocrania leading to cephalopelvic disproportion, dystocia, stillbirth, or premature labor; (2) infants presenting with a large head and bulging fontanel because of hydrocephalus; (3) specific neurologic findings related to the type and site of the lesion (eg, seizures, hemiparesis, or quadriparesis, cranial nerve abnormalities, and signs of in-
creased intracranial pressure); and (4) when sudden onset of intracranial hemorrhage (noted in 8%-18% of affected newborns) is the initial finding.
Tumor Types Teratoma Teratoma is not only the main intracranial germ cell tumor occurring in the first year of life but also is the most common neonatal brain tumor.4,15 Several forms of congenital intracranial teratoma are described, including massive tumors replacing the intracranial contents, smaller tumors causing hydrocephalus, large intracranial teratomas with extension into the orbit or neck, and teratomas presenting as an incidental postmortem finding in a stillborn fetus.15 Teratomas arise from several locations within the central nervous system: the pineal region, the hypothalamic area, the suprasellar region, and the cerebral hemispheres.4,8,16 Because of large size of some tumors, the standard anatomic landmarks are lost and it is therefore practically impossible to determine the exact site of origin of these tumors.5 In patients in whom the locus of origin can be demonstrated, the cerebral hemispheres are the most common primary site, followed by the third ventricle and pineal region. Large tumors erode through the skull
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and extend into the orbit, oral cavity, or into the neck.4,16 Spontaneous rupture of the macrocephalic fetal head during delivery is not an uncommon event.17 Intracranial teratomas typically are large cystic tumors with solid areas replacing much of the brain16 (Fig. 1). Histologically, they consist of both mature components from all 3 germ layers and immature neuroglial elements, which are the usual tissues found in teratomas arising from other locations in this age group. Intracranial teratomas with malignant germ cell tumor components are reported in newborns.18 Mature teratomas are generally large, heterogeneous cystic/ solid masses with foci of calcification and fatty tissue.19 Computed tomography (CT) shows mixed-density lesions with markedly hypodense fatty components and also clearly depicts calcified portions, which are often multiple and may sometimes reflect the presence of bone and teeth. The association of fat, calcification, and solid tissue is strongly suggestive of a teratoma. Fat-suppression MRI techniques and CT may be useful in differentiating fat from hemorrhage. Contrast enhancement usually is heterogeneous either limited to the solid components or involving cyst walls. Immature or highly malignant teratomas show less defined margins, fewer cysts, and calcifications, and cannot be differentiated from other congenital CNS tumors based on neuroimaging alone (Fig. 1).3 Perifocal edema and CSF metastases may be observed, contrary to mature teratomas.3
Astrocytoma/Glioma Astrocytomas are the foremost neuroglial tumors occurring throughout infancy and childhood and are derived from and composed of astrocytes exhibiting various degrees of differentiation. They follow teratomas in frequency in the fetus and neonate. Generally, astrocytomas of the fetus and neonate are found outside the posterior cranial fossa and above the tentorium. The cerebral hemisphere, optic nerve, thalamus-hypothalamus, mesencephalon, and pons are common primary sites.4 Those astrocytomas arising from the cerebral hemisphere are often large, involve more than one lobe, and displace the lateral ventricle.4,8,20,21 Typically astrocytomas present in the perinatal period with macrocephaly or with an intracranial mass detected on routine prenatal sonography may be the initial finding. Intracerebral hemorrhage is another important sign. Histologically, they range from benign (low-grade) to malignant (high-grade) tumors. The low grade 1 pilocytic astrocytoma is on the benign end of the spectrum and consists of small bipolar- and stellate-shaped cells with scanty processes forming loose and compact areas. They arise throughout the neuraxis, but the cerebellum (Fig. 2), optic nerve, and hypothalamic/chiasmatic region are the most common sites in infants.4 The inherent benign nature of the optic astrocytoma associated with long periods of dormancy and spontaneous regression indicate that treatment should be conservative and that a surprisingly favorable outcome often can be anticipated.22 Anaplastic astrocytomas occur in the fetus and newborn.23 The term anaplastic astrocytoma refers to astrocytomas of intermediate-grade malignancy roughly corresponding to the
Figure 2 Pilocytic astrocytoma. Sagittal T1-weighted MRI before (A) and after (B) contrast administration in a 2-month-old infant shows a large mass arising from the superior aspect of the cerebellar vermis with marked mass effect on the brainstem. The tumor shows predominantly peripheral pattern of contrast enhancement. This was a WHO grade I pilocytic astrocytoma at surgery.
World Health Organization (WHO) classification grades 2 and 3.4 Microscopically, they manifest cytoplasmic and nuclear pleomorphism, hypercellularity, mitotic activity, and, to a degree, the anaplasia of glioblastoma but lack pallisading necrosis, hemorrhage, and vascular proliferation evident in the latter.23 Children with anaplastic astrocytomas have a better outcome than those with glioblastoma. Some longterm survivors are reported.23 Glioblastoma multiforme (GBM; malignant astrocytomas) arises from the cerebral hemisphere and basal nuclei of fetuses, stillborns, and infants.4,24 It comprises approximately one-third of the astrocytomas reported in the young. The
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Figure 3 GBM. Axial T2-weighted MRI of the fetus at 29 weeks’ gestation (A) shows a large intra-axial lesion in the left frontal lobe. The differential diagnosis was a complex hematoma, possibly a hemorrhagic tumor. Axial T2 (B) and postcontrast enhanced T1-weighted MRI (C) obtained immediately after birth shows a heterogeneous T2 signal, with both T2 hypointensity anteriorly and T2 iso to hyperintensity posteriorly, involving the left frontal lobe with peripheral enhancement. There is hemorrhage within the ventricles. Because of large size and mass effect, the patient was taken for surgery and this lesion was found to be GBM.
tumor is detected by prenatal sonography. Characteristic sonographic findings of glioblastoma consist of a unilateral echogenic mass occupying most of one hemisphere, sometimes with a shift of midline structures and obstructive hydrocephalus.25 Hemorrhage (within the tumor) may be the initial imaging finding in the perinatal period. The presenting findings are macrocephaly (most common), hydrocephalus, bulging fontanel, seizures, hydrops, and vomiting. Grossly the tumors are large bulky soft pale-gray, and necrotic with variable hemorrhage.25 Microscopically, they are densely cellular tumors, demonstrating marked pleomorphism, microvascular proliferation, and neoplastic spindle-shaped cells forming pallisades around central necrotic foci.4,25 Glial fibrillary acidic protein and vimentin immunoreactivity are characteristic features. P53 staining is variable. On both fetal
and postnatal MRI, congenital GBMs appear isointense to the brain or slightly hyperintense on T1-weighted images and isointense on T2-weighted images. Tumors may appear to almost completely replace cerebral lobes.26 Restricted diffusion is typical and correlates with high tumor grade.3 Tumors with hemorrhage will appear very heterogeneous and may not show contrast enhancement (Fig. 3). It is extremely important to obtain follow up imaging in cases with complex hemorrhages to differentiate such hemorrhagic tumors from more bland intracranial hemorrhages.9
Ependymoma Ependymomas comprise 10% of all CNS tumors in young children.27 Most ependymomas of the fetus and neonate
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Figure 4 Ependymoma-posterior fossa. Axial T2- (A) and axial postcontrast enhanced T1-weighted MRI in axial (B) and sagittal (C) planes show a large heterogeneous mass involving the posterior fossa. The mass arises from the fourth ventricle and extends out through the left foramen of Luschka (white arrows). There is also some extension into the cervical canal (black arrow).
arise from the region of the fourth ventricle, with few cases occurring in the supratentorial compartment, believed to arise from embryonic rests of ependymal tissue trapped in the developing cerebral hemispheres.27 Extension into the subarachnoid space occurs frequently, sometimes with encasement of the medulla and upper cervical cord.6 Neonates with ependymomas present with macrocephaly, hydrocephalus, and signs of increased intracranial pressure. Some tumors cause dystocia, stillbirth, and spontaneous intracerebral hemorrhage.27 CNS metastases may be present at the time of diagnosis.27 Ependymomas are tumors derived from ependymal cells and consist of ependymal cells originating from within or near the ependymal lining of the ventricles or central canal of the spinal cord.27 Classically presenting as papillary intraventricular tumors, on imaging they show heterogeneous features, including calcification, cystic/necrotic area, hemorrhage and/or tumor vascularity with irregular margins with associated moderate intense heterogeneous contrast enhancement. Extension through the foramen of Luschka (Fig. 4) and Ma-
gendie may be seen, giving rise to additional component of the mass in the cerebellopontine angle cistern or within the upper cervical spinal canal. As other malignant intracranial tumors in young children, spread via CSF can occur and imaging of entire neuraxis is important (Fig. 5).
Embryonal Tumors Primitive Neuroectodermal Tumor The term PNET is applied to a group of small-cell malignant tumors of the central and peripheral nervous systems and soft tissues.4,28 The neural crest is proposed as the site of origin of these highly malignant neoplasms. PNETs occur primarily in the pediatric age group and are characterized by the capacity for differentiation along neuronal, astrocytic, ependymal, muscular, and melanotic cell lines.4 Moreover, they share a similar biological behavior in the CNS regardless of their primary site. Although they comprise approximately 25% of primary CNS tumors in children, perinatal PNETs are not as common.29 Generally, PNETs have a poor prognosis because
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Figure 5 Ependymoma-supratentorial. Axial CT (A), axial fluid-attenuated inversion recovery, FLAIR (B), and sagittal postcontrast-enhanced T1-weighted MRI (C) in a 4-month-old show a large intraventricular mass causing obstructive hydrocephalus. The mass is isodense on CT with few areas of calcifications. The mass is mildly hyperintense on FLAIR-weighted images. The mass does not show significant enhancement but there are multiple nodular areas along the ependymal surface of lateral ventricle (arrows), suggesting CSF dissemination.
they are highly aggressive, metastasizing widely throughout the CSF pathways and invading the meninges of the brain and spinal cord. PNETs occur in several locations, including, most commonly, the cerebellum (where they are called medulloblastoma), the cerebral hemispheres (cerebral neuroblastoma, ganglioneuroblastoma), pineal (pineoblastoma), brainstem, spinal cord, olfactory nerve, and retina (retinoblastoma).20,30 Some metastasize not only locally to extracranial tissues but also to distant sites, such as the lungs, liver, lymph nodes, and bone marrow.31 Cerebral PNET is an uncommon highly malignant small blue cell tumor occurring primarily in young children and is characterized by early recurrence, metastasis, and high mortality.32 One-fourth of all cerebral PNETs occur before 2 years of age.33 Cerebral PNETs tend to be large bulky masses with extensive cystic necrosis and hemorrhage occupying much of a cerebral hemisphere. MRI (Fig. 6) shows large heterogeneous masses that are hypointense on T2-weighted images and give re-
stricted diffusion consistent with high cellularity. Perifocal edema may be remarkably scant despite the huge size of the mass.31 Medulloblastoma Medulloblastomas (MBs; cerebellar PNET) follow in frequency teratomas and astrocytomas and choroid plexus tumors in several perinatal series.4 Congenital anomalies in patients with medulloblastoma have been described, (eg, imperforate anus, omphalocele, cleft palate, myelomeningocele, cerebellar agenesis, dural arteriovenous malformations, and acrania).8,34 Of all brain tumors in the young, familial occurrence has been documented most often with medulloblastoma.4,8 The incidence of medulloblastoma in Gorlin’s syndrome, an autosomal-dominant condition with multiple basal cell carcinomas, jaw cysts, and vertebral abnormalities, is 3.6%.34 Medulloblastomas originate from the vermis of the cerebellum and grow into the fourth ventricle and adja-
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Figure 6 PNET. Sagittal T2- (A), T1- (B), and postcontrast-enhanced T1-weighted MRI (C) in a 3-week-old infant shows a large heterogeneous mass in the supratentorial compartment. The lesion infiltrates all the structures at the sella and suprasellar region and also the brainstem (but preserved the normal pituitary signal). Predicting exact site of origin in such tumor if often difficult. The tumor is iso to mildly hyperintense on T2, isointense on T1 and show heterogeneous pattern of contrast enhancement. Axial diffusion-weighted images (D) with ADC mapping (E) shows the mass to have high diffusion signal, which can be seen in round blue cell tumors with a high nucleus-to-cytoplasmic ratio.
cent cerebellar hemispheres. Subsequently, obstructive hydrocephalus and leptomeningeal seeding occur along the cerebrospinal axis.35 With vascular invasion the tumor enters the bloodstream and metastasizes, in 5%-18% of the time, to organs outside the CNS, primarily to the liver, lungs, and bone marrow, and sometimes to the lymph nodes.35 Therefore, bone marrow examination and CSF cytology should be an integral part of the initial metastatic evaluation before beginning therapy.4 On MRI, MBs are characterized by a macroscopic multinodular structure, which allows their confident recognition among other posterior fossa tumors of children .36 The tumor is usually predominantly solid, although intratumoral cysts may be found in individual cases. The solid components have a similar appearance as in other embryonal tumors, with restricted diffusion and low T2 signal, consistent with their hypercellular nature. Contrast enhancement may be variable, although there is a tendency for a more marked enhancement than in other MB variants where enhancement may be heterogeneous or also thoroughly absent. Atypical Teratoid/Rhabdoid Tumor Malignant rhabdoid tumors are rare childhood neoplasms predominantly of renal origin, originally described by Beckwith and Palmer37 in 1978. Biggs et al38 first described the
intracranial malignant rhabdoid tumor, and Rorke et al named the primary CNS-malignant rhabdoid tumor as “atypical teratoid/rhabdoid tumor” (AT/RT) because it showed the unique combination of neuroepithelial, peripheral epithelial, and mesenchymal elements.39 Statistically, the most common biologically malignant CNS tumor occurring during the first decade of life is the PNET, more familiarly known as MB (PNET-MB), which usually arises in the cerebellum.39 During the last decade it has become apparent that AT/RT has been often misdiagnosed as PNET-MB because 70% of AT/RT contains histologic fields indistinguishable from classic PNET-MB and AT/RT is still a rather unfamiliar entity.39,40 Nonetheless, differentiation between these 2 entities is important because AT/RT has a grave prognosis and requires radical and aggressive treatment with surgery and adjuvant therapies such as radiotherapy and high-dose chemotherapy with autologous bone marrow transplant.39 More than 100 cases of AT/RT have been reported in literature since its first description.39,40 Imaging features of intracranial AT/RT are nonspecific, but these tumors have greater tendency towards large size, tumoral calcification, hemorrhage, necrosis and CSF dissemination (Fig. 7).40 These tumors should be considered in the differential diagnosis for any pediatric supratentorial tumors with CSF spread and for any tumor in the posterior fossa, especially in children ap-
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Figure 7 AT/RT. Sagittal T1- (A), T2- (B), axial T2- (C), and postcontrast-enhanced T1-weighted MRI (D) in a 2-monthold infant shows a large mass in the posterior fossa with mass effect on the brainstem and secondary tonsillar herniation. The tumor is isointense on T1- and T2-weighted images with few foci of T1 hyperintense hemorrhagic foci (arrows). There is no contrast enhancement within the mass.
proximately 3 years of age. Contrast-enhanced MRI of the entire neuroaxis should be included at initial assessment and during follow-up of AT/RT because of the high incidence of tumor relapse and their propensity to spread via CSF pathway.40 A correct diagnosis of AT/RT is important because intensive therapy could potentially alter the natural progression of these tumors.
Choroid Plexus Tumors Choroid plexus tumors constitute a small fraction of all pediatric CNS tumors. Although their overall incidence in the pediatric group is 2%-4%, they represent up to 15% of tumors occurring in the first year of life.41 These tumors are most often associated with significant hydrocephalus. CPP are highly vascular tumors composed of mature epithelial cells, histologically closely resembling a nonneoplastic choroid plexus and corresponding to WHO grade I classification.3 CPP may arise wherever choroid plexus is found within the ventricular system, but there is a strong age–location correlation, with ⬎80% of infantile CPP arising in the lateral ventricle.3 CPP in adults are often found within the fourth ventricle and the cerebellopontine angle cisterns.3 Imaging of
CPP show a large intraventricular frond-like or cauliflowerlike mass (Fig. 8). The mass is usually isointense to hypointense on T1-weighted imaging, and isointense to hyperintense to gray matter on T2-weighted imaging.42 Intense and homogeneous contrast enhancement is caused by its rich vascularity. Enlarged feeding arteries may be identified on both MRI and MR angiography.42 Choroid plexus carcinoma are malignant forms of choroid plexus tumors with features of high mitoses, increased cellular density, nuclear pleomorphism, blurring of papillary pattern, and brain invasion on histopathology.43 It is important to realize that routine imaging cannot differentiate between CPP and more malignant choroid plexus carcinoma because both tend to have with overlapping imaging features. MR spectroscopy usually shows absence of creatine and the neuronal/axonal marker N-acetylaspartate, and may help to distinguish between CPP and choroid plexus carcinoma; carcinoma shows levels of choline and lactate higher than those in CPP, whereas myoinositol level is significantly higher in CPP.42 Because choroid plexus tumors can spread via the CSF; imaging of the neuraxis is warranted for correct staging.
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Figure 8 Choroid plexus papilloma. Axial T2- (A) and axial postcontrast enhanced T1-weighted MRI (B) in a 1-monthold infant show a “frond-like” intraventricular mass at the midline. The mass shows avid postcontrast enhancement. Also notice hydrocephalus, which is often seen in these tumors because of overproduction of CSF.
Desmoplastic Infantile Tumors Desmoplastic infantile gangliogliomas and desmoplastic astrocytomas of infancy are very similar tumors primarily seen in young children and infants. They are characterized by presence of both astrocytic and ganglionic cells with predominant desmoplastic stroma.44 They are exclusively supratentorial tumors. They are often massive tumors, involving multiple lobes and can mimic a malignant neoplasm on imaging. Most patients present with a history of increased head circumference with or without accompanying symptoms of increased intracranial pressure. On gross pathology the tumor
is firm, with multiple cystic components. Microscopically, the tumor is characterized by presence of abundant desmoplastic stroma. Some tumors may exhibit focally aggressive features, such as areas of necrosis or high mitotic activity. On imaging desmoplastic infantile gangliogliomas are seen as large hypodense cystic masses with a solid isodense to hyperdense nodular component that show contrast enhancement (Fig. 9). On MRI the cystic component is hypointense on T1-weighted image, hyperintense on T2-weighted image, the solid component is isointense and enhances with contrast. The solid component is T2 hypointense, a feature that helps
Figure 9 Desmoplastic infantile ganglioglioma. Axial CT of the head before (A) and after (B) contrast in a 3-month-old infant show a large solid and cystic mass in the left frontal region with surrounding mass effect and vasogenic edema. The solid component of the mass showed some calcification and avid post contrast enhancement.
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Figure 10 Central neurocytoma. Axial T2- (A) and sagittal T1-weighted MRI before (B) and after (C) contrast administration in a 3-month-old infant shows a solid and cystic mass in the hypothalamic region. The lesion is isointense on T1- and T2-weighted images and does not show any contrast enhancement. This mass was found to be extraventricular neurocytoma at surgery.
Figure 11 Neonatal hemorrhage masquerading as a malignant mass. Axial T2- (A) and postcontrast-enhanced T1- (B) weighted MRI in a 5-day-old neonate shows a large heterogeneous but T2 hypointense intraaxial lesion in the right occipital region with intraventricular hemorrhage (arrows). As in Fig. 3, the differential diagnosis was complex hematoma, possibly a hemorrhagic tumor. The patient had surgical removal of this complex lesion and was found negative for any neoplasm or any vascular malformation.
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Other Tumors/ Tumor-Like Conditions The primary differential diagnosis for an intracranial tumor is hemorrhage, which may manifest as a disorganized intracranial mass and hydrocephalus (Fig. 11). Hemorrhage is often triggered by hematological conditions, including vitamin K deficiency and thrombophilia.48 Hemorrhage can simulate aggressive hemorrhagic tumors, such as AT/RT, PNET, or GBM. In survivors, follow-up imaging will show a dramatic reduction in the size of the hemorrhagic lesion because of clot retraction. Doppler sonography (showing no flow within a hemorrhage) and MRI may be helpful in distinguishing between the two. It is important to remember, however, that congenital brain tumors also have a propensity to bleed, and an underlying neoplasm should always be considered in the setting of spontaneous intracranial hemorrhage.4,8
Lipoma Lipoma, a benign fatty tumor, has the best prognosis of all the intracranial tumors. The prevalence of intracranial lipomas is underestimated in pathologic series because they are often asymptomatic and not generally resected. In 2 reviews that specifically analyzed brain tumors diagnosed with prenatal US, lipomas represented approximately 10% of cases.5,9 Lipomas in the midline are frequently associated with agenesis of the corpus callosum (Fig. 12). MRI is particularly helpful in these cases to confirm fat within the mass and to look for agenesis of the corpus callosum, which can be difficult to diagnose with US.49
Giant Subcortical Heterotopia Figure 12 Lipoma with corpus callosum dysgenesis. Sagittal (A) and axial (B) T1-weighted MRI in a 4-month-old infant with developmental delay and seizures shows dysplasia of the corpus callosum. There is also a bulky T1 hyperintense lesion along the superior aspect of the corpus callosum (arrows) with extension into the lateral ventricles (B), which is suggestive for a tubulonodular form of corpus callosal lipoma.
Giant subcortical heterotopia is an uncommonly reported50 mass-like nodular conglomerate of dysplastic gray matter that may replace a cerebral lobe or even the greater part of a hemisphere. Affected patients complain of contralateral hemiparesis, drug-resistant epilepsy, and psychomotor retardation.
Conclusions to differentiate this tumor from cystic astrocytoma.45 Surrounding edema is usually absent or moderate.46
Central Neurocytoma Central neurocytoma are tumors composed of uniform round cells with neuronal differentiation, typically located in the lateral ventricles in the region of foramen of Monro. Attachment of the septum pellucidum seems to be a feature of this tumor. These tumors are grayish with varying calcification and hemorrhage. On imaging they are isodense or slightly hyperdense with variable contrast enhancement. Calcification and cystic changes are seen. Extraventricular location of neurocytoma are seen, in which case they show cystic and solid components (Fig. 10). The extraventricular location can occur throughout the CNS.47
Congenital CNS tumors are rare and differ in their signs and symptoms, histologic characteristics, predominant location, neuroradiological features, and prognosis from tumors occurring later in childhood. Their outcome is usually poor, even with the notable advances in therapy that have occurred in the recent past. A thorough understanding of all these features is necessary to assemble the appropriate multidisciplinary team and to improve the therapeutic possibilities for these young children. Fetal MRI has greatly improved the prenatal diagnosis of these conditions, allowing for better management planning, including pregnancy and delivery management, and postnatal surgery and adjuvant therapy.
References 1. Arnstein LH, Boldrey E, Naffziger HC: A case report and survey of brain tumors during the neonatal period. J Neurosurg 8:315-319, 1951
Imaging of congenital brain tumors 2. Solitare GB, Krigman MR: Congenital intracranial neoplasm. A case report and review of the literature. J Neuropathol Exp Neurol 23:280292, 1964 3. Severino M, Schwartz ES, Thurnher MM, et al: Congenital tumors of the central nervous system. Neuroradiology 52:531-548, 2010 4. Isaacs H Jr: I. Perinatal brain tumors: A review of 250 cases. Pediatr Neurol 27:249-261, 2002 5. Rickert CH: Neuropathology and prognosis of foetal brain tumors. Acta Neuropathol 98:567-576, 1999 6. Vazquez E, Castellote A, Mayolas N, et al: Congenital tumours involving the head, neck and central nervous system. Pediatr Radiol 39:11581172, 2009 7. Chung SK, Wang KC, Nam DH, et al: Brain tumor in the first year of life: A single institute study. J Korean Med Sci 13:65-70, 1998 8. Wakai S, Arai T, Nagai M: Congenital brain tumors. Surg Neurol 21: 597-609, 1984 9. Woodward PJ, Sohaey R, Kennedy A, et al: From the archives of the AFIP: A comprehensive review of fetal tumors with pathologic correlation. RadioGraphics 25:215-242, 2005 10. Di Rocco C, Iannelli A, Ceddia A: Intracranial tumors of the first year of life. A cooperative survey of the 1986-1987 education committee of the ISPN. Childs Nerv Syst 7:150-153, 1991 11. Levine D, Barnes PD, Robertson RR, et al: Fast MR imaging of fetal central nervous system abnormalities. Radiology 229:51-61, 2003 12. Buetow PC, Smirniotopoulos JG, Done S: Congenital brain tumors: A review of 45 cases. AJR Am J Roentgenol 155:587-593, 1990 13. Doren M, Tercanli S, Gullotta F, et al: Prenatal diagnosis of a highly undifferentiated brain tumor—A case report and review of the literature. Prenat Diagn 10:967-971, 1997 14. Volpe JJ: Brain tumors and vein malformations, in Volpe JJ (ed): Neurology of the Newborn (ed 3). Philadelphia, W. B. Saunders, 1995, pp 795-807 15. Nanda A, Schut L, Sutton LN: Congenital forms of intracranial teratoma. Childs Nerv Syst 7:112-114, 1991 16. Alagappan A, Shattuck KE, Rowe T, et al: Massive intracranial immature teratoma with extracranial extension into oral cavity, nose, and neck. Fetal Diagn Ther 13:321-324, 1998 17. DiGiovanni LM, Sheikh Z: Prenatal diagnosis, clinical significance and management of fetal intracranial teratoma: A case report and literature review. Am J Perinatol 6:420-422, 1994 18. Ferreira J, Eviatar L, Schneider S, et al: Prenatal diagnosis of intracranial teratoma. Prolonged survival after resection of a malignant teratoma diagnosed prenatally by ultrasound: A case report and literature review. Pediatr Neurosurg 19:84-88, 1993 19. Fort DW, Rushing EJ: Congenital central nervous system tumors. J Child Neurol 12:157-164, 1997 20. Campbell AN, Chan HS, O’Brien A, et al: Malignant tumours in the neonate. Arch Dis Child 62:19-23, 1987 21. Geraghty AV, Knott PD, Hanna HM: Prenatal diagnosis of fetal glioblastoma multiforme. Prenat Diagn 9:613-616, 1989 22. Borit A, Richardson EP Jr: The biological and clinical behaviour of pilocytic astrocytomas of the optic pathways. Brain 105:161-167, 1982 23. Connolly B, Blaser SI, Humphreys RP, et al: Long-term survival of an infant with anaplastic astrocytoma. Pediatr Neurosurg 26:97-102, 1997 24. Winters JL, Wilson D, Davis DG: Congenital Glioblastoma multiforme: A report of three cases and a review of the literature. J Neurol Sci 188:13-19, 2001 25. Lee DY, Kim YM, Yoo SJ, et al: Congenital glioblastoma diagnosed by fetal sonography. Childs Nerv Syst 15:197-201, 1999 26. Hou LC, Bababeygy SR, Sarkissian V, et al: Congenital glioblastoma multiforme: Case report and review of the literature. Pediatr Neurosurg 44:304-312, 2008
589 27. Comi AM, Backstrom JW, Burger PC, et al: Clinical and neuroradiologic findings in infants with intracranial ependymomas. Pediatric Oncology Group. Pediatr Neurol 18:23-29, 1998 28. Mitchell D, Rojiani AM, Richards D, et al: Congenital CNS primitive neuroectodermal tumor: Case report and review of the literature. Pediatr Pathol Lab Med 15:949-956, 1995 29. Girschick HJ, Klein R, Scheurlen WG, et al: Cytogenetic and histopathologic studies of congenital supratentorial primitive neuroectodermal tumors: A case report. Pathol Oncol Res 7:67-71, 2001 30. Kayama T, Yoshimoto T, Shimizu H, et al: Neonatal medulloblastoma. J Neuro Oncol 15:157-163, 1993 31. Mitchell CS, Wood BP, Shimada H: Neonatal disseminated primitive neuroectodermal tumor. AJR Am J Roentgenol 162:1160, 1994 32. Horten BC, Rubinstein LJ: Primary cerebral neuroblastoma. A clinicopathological study of 35 cases. Brain 99:735-756, 1976 33. Becker LE, Hinton D: Primitive neuroectodermal tumors of the central nervous system. Hum Pathol 14:538-550, 1983 34. Evans DG, Farndon PA, Burnell LD, et al: The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br J Cancer 64:959-961, 1991 35. McComb JG, Davis RL, Isaacs H Jr: Extraneural metastatic medulloblastoma during childhood. Neurosurgery 9:548-551, 1981 36. Garrè ML, Cama A, Bagnasco F, et al: Medulloblastoma variants: Agedependent occurrence and relation to Gorlin syndrome—A new clinical perspective. Clin Cancer Res 15:2463-2471, 2009 37. Beckwith JB, Palmer NF: Histopathology and prognosis of Wilms’ tumour. Results from the first National Wilms’ tumor Study. Cancer 41:1937-1948, 1978 38. Biggs PJ, Garen PD, Powers JM, et al: Malignant rhabdoid tumor of the central nervous system. Hum Pathol 18:332-337, 1987 39. Ho DM, Hsu CY, Wong TT, et al: Atypical teratoid/rhabdoid tumor of the central nervous system: A comparative study with primitive neuroectodermal tumor/medulloblastoma. Acta Neuropathol 99:482-488, 2000 40. Parmar H, Hawkins C, Bouffet E, et al: Imaging findings in primary intracranial atypical teratoid/rhabdoid tumors. Pediatr Radiol 36:126132, 2006 41. Larouche V, Huang A, Bartels U, et al: Tumors of the central nervous system in the first year of life. Pediatr Blood Cancer 49:1074-1082, 2007 42. Wagle V, Melanson D, Ethier R, et al: Choroid plexus papilloma: Magnetic resonance, computed tomography, and angiographic observations. Surg Neurol 27:466-468, 1987 43. Jeibmann A, Hasselblatt M, Gerss J, et al: Prognostic implications of atypical histologic features in choroid plexus papilloma. J Neuropathol Exp Neurol 65:1069-1073, 2006 44. Tamburrini G, Colosimo C Jr, Giangaspero F, et al: Desmoplastic infantile ganglioglioma. Childs Nerv Syst 19:292-297, 2003 45. Barkovich AJ: Pediatric Neuroradiology (ed 4). Philadelphia, Lippincott Williams and Wilkins, 2005, pp 560-562 46. Trehan G, Bruge H, Vinchon M, et al: MR imaging in the diagnosis of desmoplastic infantile tumor: Retrospective study of six cases. AJNR Am J Neuroradiol 25:1028-1033, 2004 47. Zhang D, Wen L, Henning TD, et al: Central neurocytoma: Clinical, pathological and neuroradiological findings. Clin Radiol 61:348-357, 2006 48. Crespin M, Alhenc-Gelas M, Grangé G, et al: Fetal intracerebral hemorrhage in familial thrombophilia. Pediatr Neurol 41:291-293, 2009 49. Sonigo PC, Rypens FF, Carteret M, et al: MR imaging of fetal cerebral anomalies. Pediatr Radiol 28:212-222, 1998 50. Novegno F, Battaglia D, Chieffo D, et al: Giant subcortical heterotopia involving the temporo-parieto-occipital region: A challenging cause of drug-resistant epilepsy. Epilepsy Res 87:88-94, 2009
C
ongenital tumors are defined as those presenting within 60 days of birth according to the definition proposed by Arnstein et al.1 According to Solitare and Krigman,2 there are 3 categories of intracranial tumors in newborns: definitely congenital (present at birth), probably congenital (detected within the first week of life), and possibly congenital (detected within the first 2 months of life). Some authors extend the time frame of congenital tumors to first 6 months after birth.3 These divisions are arbitrary and defining the true congenital nature may be complex, as some true in-utero tumor may not manifest in the early period of life. Brain tumors of the fetus and neonate are uncommon compared with those of the older child and adolescent.4 They account for only 10% of all antenatal tumors, ranking behind extracranial teratomas, neuroblastomas, and soft-tissue tumors.4 Intracranial teratoma, a relatively uncommon central nervous system (CNS) tumor in children, is the most common fetal brain tumor, accounting for approximately one-half of all reported cases.4 They are followed in frequency by astrocytomas of various grades, lipomas, choroid plexus papillomas (CPP), craniopharyngiomas, and primitive neuroectodermal tumors (PNET).4,5 These tumors differ from those occurring in the older child and adolescent in several ways. First, the location is not entirely the same. Primary intracranial tumors in the older child are mostly infratentorial in contrast to the fetus and neonate in whom most tumors are found in the supratentorial compartment.4 The clinical presentation and frequency of the various histologic types are
*Department of Radiology, University of Michigan, Ann Arbor, MI. †Department of Radiology, Vanderbilt University Medical Center, Nashville, TN. ‡Department of Radiology, Johns Hopkins Hospital, Baltimore, MD. Address reprint requests to Hemant A. Parmar, MD, Department of Radiology, University of Michigan Health System, Taubman Center/B1/132 F, 1500 East Medical Center, Ann Arbor, MI 48109-0302. E-mail: [email protected]
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dissimilar. In general, the prognosis is poor because of the large tumor size and the limitations of adjuvant chemotherapy and radiotherapy at such a young age.6,7 Brain immaturity and the expansile capacity of the infant’s skull delay the diagnosis, and surgical resection may be impossible when it is finally detected. The 2 notable exceptions are fetuses with lipomas and fetuses with CPP, both of which fare far better than fetuses with other congenital brain tumors.4,5
Incidence Congenital tumors account for 18% of brain tumors presenting during the first year of life and approximately 0.5%-1.5% of those in childhood.8 Overall, CNS tumors are the cause of 5%-20% of deaths in the fetal and neonatal period.9 Intracranial teratoma is the most common fetal brain tumor, accounting for approximately one-half of all reported cases. Teratoma is followed in frequency by astrocytomas of various grades, lipomas, CPP, craniopharyngiomas, and PNET.9 A cooperative study by the International Society of Pediatric Neurosurgery revealed more frequent supratentorial tumor location for these tumors.10 A total of 41% of patients presented with intracranial hypertension and only 12% with seizures. High mortality (40%) was observed, along with mild and severe psychomotor retardation in 95 and 143 of the 473 surviving patients. Congenital tumors are often detected incidentally on routine prenatal ultrasound (US) studies. The next imaging method used is fetal magnetic resonance imaging (MRI), which now uses ultrafast sequences that provide high-resolution imaging and eliminate motion artifacts without fetal sedation.11
Clinical Features An abnormally large head circumference is the most common finding observed in the fetus or newborn with a brain tumor regardless of the histologic type. Macrocephaly may be the
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Figure 1 Coronal T2- (A, B), axial T2- (C), T1- (D), and postcontrast-enhanced T1-weighted MRI in a 4-week-old infant shows a large heterogeneous mass in the supratentorial compartment. The mass shows multilobulated margins with peripheral areas of necrosis and multiple foci of T2 hypointensity (arrows) suggestive for calcification. There is heterogeneous and predominantly central pattern of enhancement (E).
result of hydrocephalus or the size of the tumor itself or both.4,12 Hydrocephalus, the second-most common finding, is caused by compression of the ventricular system or by hemorrhage from the tumor obstructing the ventricles. Choroid plexus tumors cause hydrocephalus by overproduction of cerebrospinal fluid (CSF). Some brain tumors grow enormously in utero causing dystocia or stillbirth.8,13 There is a high incidence of stillbirth associated with perinatal brain tumors, especially intracranial teratomas, glioblastomas, and PNETs.8,13 Large tumors cause fetal hydrops or require aspiration or decompression of the skull to permit vaginal delivery. Polyhydramnios, secondary to depressed swallowing from hypothalamic dysfunction, is also a common complication antenatally.9 Neonates with a rapidly growing neoplasm exhibit signs of increased intracranial pressure, such as vomiting, lethargy, macrocephaly, separation of cranial sutures, and bulging fontanels. According to Volpe,14 the clinical findings in neonates with brain tumors can be categorized into the following 4 main groups: (1) gigantic tumors producing severe macrocrania leading to cephalopelvic disproportion, dystocia, stillbirth, or premature labor; (2) infants presenting with a large head and bulging fontanel because of hydrocephalus; (3) specific neurologic findings related to the type and site of the lesion (eg, seizures, hemiparesis, or quadriparesis, cranial nerve abnormalities, and signs of in-
creased intracranial pressure); and (4) when sudden onset of intracranial hemorrhage (noted in 8%-18% of affected newborns) is the initial finding.
Tumor Types Teratoma Teratoma is not only the main intracranial germ cell tumor occurring in the first year of life but also is the most common neonatal brain tumor.4,15 Several forms of congenital intracranial teratoma are described, including massive tumors replacing the intracranial contents, smaller tumors causing hydrocephalus, large intracranial teratomas with extension into the orbit or neck, and teratomas presenting as an incidental postmortem finding in a stillborn fetus.15 Teratomas arise from several locations within the central nervous system: the pineal region, the hypothalamic area, the suprasellar region, and the cerebral hemispheres.4,8,16 Because of large size of some tumors, the standard anatomic landmarks are lost and it is therefore practically impossible to determine the exact site of origin of these tumors.5 In patients in whom the locus of origin can be demonstrated, the cerebral hemispheres are the most common primary site, followed by the third ventricle and pineal region. Large tumors erode through the skull
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and extend into the orbit, oral cavity, or into the neck.4,16 Spontaneous rupture of the macrocephalic fetal head during delivery is not an uncommon event.17 Intracranial teratomas typically are large cystic tumors with solid areas replacing much of the brain16 (Fig. 1). Histologically, they consist of both mature components from all 3 germ layers and immature neuroglial elements, which are the usual tissues found in teratomas arising from other locations in this age group. Intracranial teratomas with malignant germ cell tumor components are reported in newborns.18 Mature teratomas are generally large, heterogeneous cystic/ solid masses with foci of calcification and fatty tissue.19 Computed tomography (CT) shows mixed-density lesions with markedly hypodense fatty components and also clearly depicts calcified portions, which are often multiple and may sometimes reflect the presence of bone and teeth. The association of fat, calcification, and solid tissue is strongly suggestive of a teratoma. Fat-suppression MRI techniques and CT may be useful in differentiating fat from hemorrhage. Contrast enhancement usually is heterogeneous either limited to the solid components or involving cyst walls. Immature or highly malignant teratomas show less defined margins, fewer cysts, and calcifications, and cannot be differentiated from other congenital CNS tumors based on neuroimaging alone (Fig. 1).3 Perifocal edema and CSF metastases may be observed, contrary to mature teratomas.3
Astrocytoma/Glioma Astrocytomas are the foremost neuroglial tumors occurring throughout infancy and childhood and are derived from and composed of astrocytes exhibiting various degrees of differentiation. They follow teratomas in frequency in the fetus and neonate. Generally, astrocytomas of the fetus and neonate are found outside the posterior cranial fossa and above the tentorium. The cerebral hemisphere, optic nerve, thalamus-hypothalamus, mesencephalon, and pons are common primary sites.4 Those astrocytomas arising from the cerebral hemisphere are often large, involve more than one lobe, and displace the lateral ventricle.4,8,20,21 Typically astrocytomas present in the perinatal period with macrocephaly or with an intracranial mass detected on routine prenatal sonography may be the initial finding. Intracerebral hemorrhage is another important sign. Histologically, they range from benign (low-grade) to malignant (high-grade) tumors. The low grade 1 pilocytic astrocytoma is on the benign end of the spectrum and consists of small bipolar- and stellate-shaped cells with scanty processes forming loose and compact areas. They arise throughout the neuraxis, but the cerebellum (Fig. 2), optic nerve, and hypothalamic/chiasmatic region are the most common sites in infants.4 The inherent benign nature of the optic astrocytoma associated with long periods of dormancy and spontaneous regression indicate that treatment should be conservative and that a surprisingly favorable outcome often can be anticipated.22 Anaplastic astrocytomas occur in the fetus and newborn.23 The term anaplastic astrocytoma refers to astrocytomas of intermediate-grade malignancy roughly corresponding to the
Figure 2 Pilocytic astrocytoma. Sagittal T1-weighted MRI before (A) and after (B) contrast administration in a 2-month-old infant shows a large mass arising from the superior aspect of the cerebellar vermis with marked mass effect on the brainstem. The tumor shows predominantly peripheral pattern of contrast enhancement. This was a WHO grade I pilocytic astrocytoma at surgery.
World Health Organization (WHO) classification grades 2 and 3.4 Microscopically, they manifest cytoplasmic and nuclear pleomorphism, hypercellularity, mitotic activity, and, to a degree, the anaplasia of glioblastoma but lack pallisading necrosis, hemorrhage, and vascular proliferation evident in the latter.23 Children with anaplastic astrocytomas have a better outcome than those with glioblastoma. Some longterm survivors are reported.23 Glioblastoma multiforme (GBM; malignant astrocytomas) arises from the cerebral hemisphere and basal nuclei of fetuses, stillborns, and infants.4,24 It comprises approximately one-third of the astrocytomas reported in the young. The
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Figure 3 GBM. Axial T2-weighted MRI of the fetus at 29 weeks’ gestation (A) shows a large intra-axial lesion in the left frontal lobe. The differential diagnosis was a complex hematoma, possibly a hemorrhagic tumor. Axial T2 (B) and postcontrast enhanced T1-weighted MRI (C) obtained immediately after birth shows a heterogeneous T2 signal, with both T2 hypointensity anteriorly and T2 iso to hyperintensity posteriorly, involving the left frontal lobe with peripheral enhancement. There is hemorrhage within the ventricles. Because of large size and mass effect, the patient was taken for surgery and this lesion was found to be GBM.
tumor is detected by prenatal sonography. Characteristic sonographic findings of glioblastoma consist of a unilateral echogenic mass occupying most of one hemisphere, sometimes with a shift of midline structures and obstructive hydrocephalus.25 Hemorrhage (within the tumor) may be the initial imaging finding in the perinatal period. The presenting findings are macrocephaly (most common), hydrocephalus, bulging fontanel, seizures, hydrops, and vomiting. Grossly the tumors are large bulky soft pale-gray, and necrotic with variable hemorrhage.25 Microscopically, they are densely cellular tumors, demonstrating marked pleomorphism, microvascular proliferation, and neoplastic spindle-shaped cells forming pallisades around central necrotic foci.4,25 Glial fibrillary acidic protein and vimentin immunoreactivity are characteristic features. P53 staining is variable. On both fetal
and postnatal MRI, congenital GBMs appear isointense to the brain or slightly hyperintense on T1-weighted images and isointense on T2-weighted images. Tumors may appear to almost completely replace cerebral lobes.26 Restricted diffusion is typical and correlates with high tumor grade.3 Tumors with hemorrhage will appear very heterogeneous and may not show contrast enhancement (Fig. 3). It is extremely important to obtain follow up imaging in cases with complex hemorrhages to differentiate such hemorrhagic tumors from more bland intracranial hemorrhages.9
Ependymoma Ependymomas comprise 10% of all CNS tumors in young children.27 Most ependymomas of the fetus and neonate
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Figure 4 Ependymoma-posterior fossa. Axial T2- (A) and axial postcontrast enhanced T1-weighted MRI in axial (B) and sagittal (C) planes show a large heterogeneous mass involving the posterior fossa. The mass arises from the fourth ventricle and extends out through the left foramen of Luschka (white arrows). There is also some extension into the cervical canal (black arrow).
arise from the region of the fourth ventricle, with few cases occurring in the supratentorial compartment, believed to arise from embryonic rests of ependymal tissue trapped in the developing cerebral hemispheres.27 Extension into the subarachnoid space occurs frequently, sometimes with encasement of the medulla and upper cervical cord.6 Neonates with ependymomas present with macrocephaly, hydrocephalus, and signs of increased intracranial pressure. Some tumors cause dystocia, stillbirth, and spontaneous intracerebral hemorrhage.27 CNS metastases may be present at the time of diagnosis.27 Ependymomas are tumors derived from ependymal cells and consist of ependymal cells originating from within or near the ependymal lining of the ventricles or central canal of the spinal cord.27 Classically presenting as papillary intraventricular tumors, on imaging they show heterogeneous features, including calcification, cystic/necrotic area, hemorrhage and/or tumor vascularity with irregular margins with associated moderate intense heterogeneous contrast enhancement. Extension through the foramen of Luschka (Fig. 4) and Ma-
gendie may be seen, giving rise to additional component of the mass in the cerebellopontine angle cistern or within the upper cervical spinal canal. As other malignant intracranial tumors in young children, spread via CSF can occur and imaging of entire neuraxis is important (Fig. 5).
Embryonal Tumors Primitive Neuroectodermal Tumor The term PNET is applied to a group of small-cell malignant tumors of the central and peripheral nervous systems and soft tissues.4,28 The neural crest is proposed as the site of origin of these highly malignant neoplasms. PNETs occur primarily in the pediatric age group and are characterized by the capacity for differentiation along neuronal, astrocytic, ependymal, muscular, and melanotic cell lines.4 Moreover, they share a similar biological behavior in the CNS regardless of their primary site. Although they comprise approximately 25% of primary CNS tumors in children, perinatal PNETs are not as common.29 Generally, PNETs have a poor prognosis because
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Figure 5 Ependymoma-supratentorial. Axial CT (A), axial fluid-attenuated inversion recovery, FLAIR (B), and sagittal postcontrast-enhanced T1-weighted MRI (C) in a 4-month-old show a large intraventricular mass causing obstructive hydrocephalus. The mass is isodense on CT with few areas of calcifications. The mass is mildly hyperintense on FLAIR-weighted images. The mass does not show significant enhancement but there are multiple nodular areas along the ependymal surface of lateral ventricle (arrows), suggesting CSF dissemination.
they are highly aggressive, metastasizing widely throughout the CSF pathways and invading the meninges of the brain and spinal cord. PNETs occur in several locations, including, most commonly, the cerebellum (where they are called medulloblastoma), the cerebral hemispheres (cerebral neuroblastoma, ganglioneuroblastoma), pineal (pineoblastoma), brainstem, spinal cord, olfactory nerve, and retina (retinoblastoma).20,30 Some metastasize not only locally to extracranial tissues but also to distant sites, such as the lungs, liver, lymph nodes, and bone marrow.31 Cerebral PNET is an uncommon highly malignant small blue cell tumor occurring primarily in young children and is characterized by early recurrence, metastasis, and high mortality.32 One-fourth of all cerebral PNETs occur before 2 years of age.33 Cerebral PNETs tend to be large bulky masses with extensive cystic necrosis and hemorrhage occupying much of a cerebral hemisphere. MRI (Fig. 6) shows large heterogeneous masses that are hypointense on T2-weighted images and give re-
stricted diffusion consistent with high cellularity. Perifocal edema may be remarkably scant despite the huge size of the mass.31 Medulloblastoma Medulloblastomas (MBs; cerebellar PNET) follow in frequency teratomas and astrocytomas and choroid plexus tumors in several perinatal series.4 Congenital anomalies in patients with medulloblastoma have been described, (eg, imperforate anus, omphalocele, cleft palate, myelomeningocele, cerebellar agenesis, dural arteriovenous malformations, and acrania).8,34 Of all brain tumors in the young, familial occurrence has been documented most often with medulloblastoma.4,8 The incidence of medulloblastoma in Gorlin’s syndrome, an autosomal-dominant condition with multiple basal cell carcinomas, jaw cysts, and vertebral abnormalities, is 3.6%.34 Medulloblastomas originate from the vermis of the cerebellum and grow into the fourth ventricle and adja-
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Figure 6 PNET. Sagittal T2- (A), T1- (B), and postcontrast-enhanced T1-weighted MRI (C) in a 3-week-old infant shows a large heterogeneous mass in the supratentorial compartment. The lesion infiltrates all the structures at the sella and suprasellar region and also the brainstem (but preserved the normal pituitary signal). Predicting exact site of origin in such tumor if often difficult. The tumor is iso to mildly hyperintense on T2, isointense on T1 and show heterogeneous pattern of contrast enhancement. Axial diffusion-weighted images (D) with ADC mapping (E) shows the mass to have high diffusion signal, which can be seen in round blue cell tumors with a high nucleus-to-cytoplasmic ratio.
cent cerebellar hemispheres. Subsequently, obstructive hydrocephalus and leptomeningeal seeding occur along the cerebrospinal axis.35 With vascular invasion the tumor enters the bloodstream and metastasizes, in 5%-18% of the time, to organs outside the CNS, primarily to the liver, lungs, and bone marrow, and sometimes to the lymph nodes.35 Therefore, bone marrow examination and CSF cytology should be an integral part of the initial metastatic evaluation before beginning therapy.4 On MRI, MBs are characterized by a macroscopic multinodular structure, which allows their confident recognition among other posterior fossa tumors of children .36 The tumor is usually predominantly solid, although intratumoral cysts may be found in individual cases. The solid components have a similar appearance as in other embryonal tumors, with restricted diffusion and low T2 signal, consistent with their hypercellular nature. Contrast enhancement may be variable, although there is a tendency for a more marked enhancement than in other MB variants where enhancement may be heterogeneous or also thoroughly absent. Atypical Teratoid/Rhabdoid Tumor Malignant rhabdoid tumors are rare childhood neoplasms predominantly of renal origin, originally described by Beckwith and Palmer37 in 1978. Biggs et al38 first described the
intracranial malignant rhabdoid tumor, and Rorke et al named the primary CNS-malignant rhabdoid tumor as “atypical teratoid/rhabdoid tumor” (AT/RT) because it showed the unique combination of neuroepithelial, peripheral epithelial, and mesenchymal elements.39 Statistically, the most common biologically malignant CNS tumor occurring during the first decade of life is the PNET, more familiarly known as MB (PNET-MB), which usually arises in the cerebellum.39 During the last decade it has become apparent that AT/RT has been often misdiagnosed as PNET-MB because 70% of AT/RT contains histologic fields indistinguishable from classic PNET-MB and AT/RT is still a rather unfamiliar entity.39,40 Nonetheless, differentiation between these 2 entities is important because AT/RT has a grave prognosis and requires radical and aggressive treatment with surgery and adjuvant therapies such as radiotherapy and high-dose chemotherapy with autologous bone marrow transplant.39 More than 100 cases of AT/RT have been reported in literature since its first description.39,40 Imaging features of intracranial AT/RT are nonspecific, but these tumors have greater tendency towards large size, tumoral calcification, hemorrhage, necrosis and CSF dissemination (Fig. 7).40 These tumors should be considered in the differential diagnosis for any pediatric supratentorial tumors with CSF spread and for any tumor in the posterior fossa, especially in children ap-
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Figure 7 AT/RT. Sagittal T1- (A), T2- (B), axial T2- (C), and postcontrast-enhanced T1-weighted MRI (D) in a 2-monthold infant shows a large mass in the posterior fossa with mass effect on the brainstem and secondary tonsillar herniation. The tumor is isointense on T1- and T2-weighted images with few foci of T1 hyperintense hemorrhagic foci (arrows). There is no contrast enhancement within the mass.
proximately 3 years of age. Contrast-enhanced MRI of the entire neuroaxis should be included at initial assessment and during follow-up of AT/RT because of the high incidence of tumor relapse and their propensity to spread via CSF pathway.40 A correct diagnosis of AT/RT is important because intensive therapy could potentially alter the natural progression of these tumors.
Choroid Plexus Tumors Choroid plexus tumors constitute a small fraction of all pediatric CNS tumors. Although their overall incidence in the pediatric group is 2%-4%, they represent up to 15% of tumors occurring in the first year of life.41 These tumors are most often associated with significant hydrocephalus. CPP are highly vascular tumors composed of mature epithelial cells, histologically closely resembling a nonneoplastic choroid plexus and corresponding to WHO grade I classification.3 CPP may arise wherever choroid plexus is found within the ventricular system, but there is a strong age–location correlation, with ⬎80% of infantile CPP arising in the lateral ventricle.3 CPP in adults are often found within the fourth ventricle and the cerebellopontine angle cisterns.3 Imaging of
CPP show a large intraventricular frond-like or cauliflowerlike mass (Fig. 8). The mass is usually isointense to hypointense on T1-weighted imaging, and isointense to hyperintense to gray matter on T2-weighted imaging.42 Intense and homogeneous contrast enhancement is caused by its rich vascularity. Enlarged feeding arteries may be identified on both MRI and MR angiography.42 Choroid plexus carcinoma are malignant forms of choroid plexus tumors with features of high mitoses, increased cellular density, nuclear pleomorphism, blurring of papillary pattern, and brain invasion on histopathology.43 It is important to realize that routine imaging cannot differentiate between CPP and more malignant choroid plexus carcinoma because both tend to have with overlapping imaging features. MR spectroscopy usually shows absence of creatine and the neuronal/axonal marker N-acetylaspartate, and may help to distinguish between CPP and choroid plexus carcinoma; carcinoma shows levels of choline and lactate higher than those in CPP, whereas myoinositol level is significantly higher in CPP.42 Because choroid plexus tumors can spread via the CSF; imaging of the neuraxis is warranted for correct staging.
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Figure 8 Choroid plexus papilloma. Axial T2- (A) and axial postcontrast enhanced T1-weighted MRI (B) in a 1-monthold infant show a “frond-like” intraventricular mass at the midline. The mass shows avid postcontrast enhancement. Also notice hydrocephalus, which is often seen in these tumors because of overproduction of CSF.
Desmoplastic Infantile Tumors Desmoplastic infantile gangliogliomas and desmoplastic astrocytomas of infancy are very similar tumors primarily seen in young children and infants. They are characterized by presence of both astrocytic and ganglionic cells with predominant desmoplastic stroma.44 They are exclusively supratentorial tumors. They are often massive tumors, involving multiple lobes and can mimic a malignant neoplasm on imaging. Most patients present with a history of increased head circumference with or without accompanying symptoms of increased intracranial pressure. On gross pathology the tumor
is firm, with multiple cystic components. Microscopically, the tumor is characterized by presence of abundant desmoplastic stroma. Some tumors may exhibit focally aggressive features, such as areas of necrosis or high mitotic activity. On imaging desmoplastic infantile gangliogliomas are seen as large hypodense cystic masses with a solid isodense to hyperdense nodular component that show contrast enhancement (Fig. 9). On MRI the cystic component is hypointense on T1-weighted image, hyperintense on T2-weighted image, the solid component is isointense and enhances with contrast. The solid component is T2 hypointense, a feature that helps
Figure 9 Desmoplastic infantile ganglioglioma. Axial CT of the head before (A) and after (B) contrast in a 3-month-old infant show a large solid and cystic mass in the left frontal region with surrounding mass effect and vasogenic edema. The solid component of the mass showed some calcification and avid post contrast enhancement.
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Figure 10 Central neurocytoma. Axial T2- (A) and sagittal T1-weighted MRI before (B) and after (C) contrast administration in a 3-month-old infant shows a solid and cystic mass in the hypothalamic region. The lesion is isointense on T1- and T2-weighted images and does not show any contrast enhancement. This mass was found to be extraventricular neurocytoma at surgery.
Figure 11 Neonatal hemorrhage masquerading as a malignant mass. Axial T2- (A) and postcontrast-enhanced T1- (B) weighted MRI in a 5-day-old neonate shows a large heterogeneous but T2 hypointense intraaxial lesion in the right occipital region with intraventricular hemorrhage (arrows). As in Fig. 3, the differential diagnosis was complex hematoma, possibly a hemorrhagic tumor. The patient had surgical removal of this complex lesion and was found negative for any neoplasm or any vascular malformation.
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Other Tumors/ Tumor-Like Conditions The primary differential diagnosis for an intracranial tumor is hemorrhage, which may manifest as a disorganized intracranial mass and hydrocephalus (Fig. 11). Hemorrhage is often triggered by hematological conditions, including vitamin K deficiency and thrombophilia.48 Hemorrhage can simulate aggressive hemorrhagic tumors, such as AT/RT, PNET, or GBM. In survivors, follow-up imaging will show a dramatic reduction in the size of the hemorrhagic lesion because of clot retraction. Doppler sonography (showing no flow within a hemorrhage) and MRI may be helpful in distinguishing between the two. It is important to remember, however, that congenital brain tumors also have a propensity to bleed, and an underlying neoplasm should always be considered in the setting of spontaneous intracranial hemorrhage.4,8
Lipoma Lipoma, a benign fatty tumor, has the best prognosis of all the intracranial tumors. The prevalence of intracranial lipomas is underestimated in pathologic series because they are often asymptomatic and not generally resected. In 2 reviews that specifically analyzed brain tumors diagnosed with prenatal US, lipomas represented approximately 10% of cases.5,9 Lipomas in the midline are frequently associated with agenesis of the corpus callosum (Fig. 12). MRI is particularly helpful in these cases to confirm fat within the mass and to look for agenesis of the corpus callosum, which can be difficult to diagnose with US.49
Giant Subcortical Heterotopia Figure 12 Lipoma with corpus callosum dysgenesis. Sagittal (A) and axial (B) T1-weighted MRI in a 4-month-old infant with developmental delay and seizures shows dysplasia of the corpus callosum. There is also a bulky T1 hyperintense lesion along the superior aspect of the corpus callosum (arrows) with extension into the lateral ventricles (B), which is suggestive for a tubulonodular form of corpus callosal lipoma.
Giant subcortical heterotopia is an uncommonly reported50 mass-like nodular conglomerate of dysplastic gray matter that may replace a cerebral lobe or even the greater part of a hemisphere. Affected patients complain of contralateral hemiparesis, drug-resistant epilepsy, and psychomotor retardation.
Conclusions to differentiate this tumor from cystic astrocytoma.45 Surrounding edema is usually absent or moderate.46
Central Neurocytoma Central neurocytoma are tumors composed of uniform round cells with neuronal differentiation, typically located in the lateral ventricles in the region of foramen of Monro. Attachment of the septum pellucidum seems to be a feature of this tumor. These tumors are grayish with varying calcification and hemorrhage. On imaging they are isodense or slightly hyperdense with variable contrast enhancement. Calcification and cystic changes are seen. Extraventricular location of neurocytoma are seen, in which case they show cystic and solid components (Fig. 10). The extraventricular location can occur throughout the CNS.47
Congenital CNS tumors are rare and differ in their signs and symptoms, histologic characteristics, predominant location, neuroradiological features, and prognosis from tumors occurring later in childhood. Their outcome is usually poor, even with the notable advances in therapy that have occurred in the recent past. A thorough understanding of all these features is necessary to assemble the appropriate multidisciplinary team and to improve the therapeutic possibilities for these young children. Fetal MRI has greatly improved the prenatal diagnosis of these conditions, allowing for better management planning, including pregnancy and delivery management, and postnatal surgery and adjuvant therapy.
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