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Cerebellar neoplasms in children
Cerebellar Neoplasms in Children By Debra A. Gusnard
EOPLASIA in children is uncommon; yet, the most common site for the occurrence of solid neoplasmsin children is the central nervous system.’ The present incidence is approximately 2.5 central nervous system tumors per 100,000 children per year. Pediatric brain tumors, in fact, constitute 15% to 20% of all primary brain tumors. However, unlike the situation in the adult population, the posterior fossais a common location for primary brain tumors to occur.2*3 Approximately one half of the childhood cases are discovered in the posterior fossa. The vast majority of these arise in either the parenchyma of the cerebellum (hemispheres or vermis), or the linings of the fourth ventricle (eg, the primitive neuroectodermal tumor/medulloblastoma, cerebellar astrocytoma, ependymoma). A small, though not insignificant, proportion of posterior fossa neoplasms in children arise within the brainstem (These are discussed in the article by Richard Smith in this issue). Metastases, as well as the extraaxial neoplasms that are frequently seenin the posterior fossaeof adults (eg, acoustic neuroma, meningioma), are rare in children. The goals of the radiologic assessmentof a child who presents with signs suspicious for an underlying posterior fossa mass are twofold; to determine whether a massis present and, if one is present, to suggest a likely histologic (differential) diagnosis, which will aid the neurosurgeon and radiation therapist in their treatment planning. In those caseswhere a neoplasm has been discovered, follow-up after the institution of treatment is imperative in order to assessthe response of the tumor as well as to identify possible complications of the treatment. Over the past decade,the cornerstone of radiologic assessmentof these patients has been computed tomography (CT). More recently, magnetic resonance imaging (MR) has played an important role for four reasons: (1) its greater contrast resolution than CT, (2) its multiplanar capability, (3) its lack of artifacts arising from cortical bone that with CT can obscure adjacent soft tissue detail (eg, posterior fossa images on CT), and (4) the introduction of a paramagnetic contrast agent (gadolinium-DTPA) that, like the
From the Department of Radiology, The Children’s Hospital of Philadelphia, Philadelphia, PA. Address reprint requests to Debra A. Gusnard. MD. Department of Radiology. The Children’s Hospital of Philadelphia, 34th and Civic Center Blvd. Philadelphia, PA 19104. o 1990 by W.B. Saunders Company. 0037-198X/90/2503-0005$5.00/0
Seminars in Roenfgenology, Vol XXV, No 3 (July), 1990: pp 263-276
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iodinated agents used in CT, demonstrates sites of breakdown in the blood-brain barrier.2y4m7 In this article, an approach to the imaging evaluation of childhood posterior fossa neoplasms (excluding brainstem gliomas) is presented. This includes a detailed discussion of the more common neoplasms-their clinical presentations, pathologic characteristics, radiologic manifestations, and differential diagnoses. TECHNIQUE
The nature of the clinical presentation of a child who has a posterior fossa neoplasm frequently determines the direction and extent of the preoperative radiologic evaluation (Fig 1). For example, a child in extremis, who has signs of increased intracranial pressure,should undergo a CT scan with and without contrast enhancement, which includes thin (3mm to 5mm) sections through the posterior fossa. This can be performed expeditiously and provides information necessary for emergent intervention, such as when severe hydrocephalus is present. In these cases,when the patient is clinically unstable, an MR scan is usually not obtained initially because of logistical difficulties, but may be obtained later when the patient is more stable. More often, the patient’s condition is not unstable, his symptoms having developed subacutely, so that an MR scan is the initial examination obtained. Though calcification is less accurately detected and tissue characterization is essentially no better than with CT, MR does have the advantage of being able to better define tumor extent because of its greater contrast resolution and multiplanar capability (Fig 2 A through C). As in the case of the CT exam, contrast (gadolinium-DTPA) should be administered routinely as a part of the MR examination in these patients. Not only do the enhancement
DEBRA A. GUSNARD
264 Unstable patient with signs of posterior fossa mass
CT with and without
Stable patient with signs of posterior fossa mass
contrast
CT with and without
(-
(+ tumor)
tumor)
contrast
(+ tumor)
MR with and without contrast
t
i
w
(+ tumor)
(Surgery)
CT with and without
contrast baseline postoperative
/
\
Patients with medulloblastoma-PNET, ependymoma
Patients with cerebellar astro, other
I Myelogram and/or MR with contrast to evaluate for spinal drop metastases \ Follow-up MR with and without contrast (interval determined tumor type, stage of disease and results of previous study) Fig 1.
Radiologic
evaluation
of pediatric
posterior
by
fossa.
characteristics of tumors aid in differential diagnostic considerations, but contrast-enhanced MR is notably more sensitive in the detection of subarachnoid spread of tumor than is contrastenhanced CT.’ Thus, a properly performed MR scan (Tl- and T2-weighted images and postgadolinium Tl -weighted images) can contribute significantly to planning the surgical approach, the radiation portal, and the patient’s tumor staging. Once the posterior fossa neoplasm has been defined and surgical debulking/resection has taken place, in certain cases another CT or MR with and without contrast should be obtained within 48 hours of the surgical procedure. It is theorized that obtaining the scan within the first 48 hours of the immediate postoperative period optimizes the distinction between residual tumor and granulation tissue that has not yet had the opportunity to develop within the surgical bed. For some tumors (eg, medulloblastoma, ependymoma), it is known that the amount of tumor left
at surgery correlates inversely with the prognosis. A baseline post-op CT, therefore, provides information pertinent to immediate clinical decision making as well as a reference for further follow-up studies. It should be recognized that residual tumor that enhanced preoperatively may not enhance postoperatively when the patient is on large doses of steroids. For those tumors that have a significant likelihood of metastasizing along the subarachnoid space (ie, medulloblastoma, “malignant” ependymoma), another important step in radiologic staging is the evaluation of the spinal canal. The traditional method has been myelography (*post myelogram CT)9~10performed approximately 10 days to 2 weeks after surgery (the delay being necessary since interpretation of the myelogram performed in the early postoperative period may be compromised due to filling defects caused by blood clots within the subarachnoid space). However, the role of the contrast-enhanced MR in this setting is controversial and presently under investigation. Tl-weighted images of the spine after gadolinium-DTPA administration can show drop metastases in the form of enhancing nodular deposits within the thecal sac along the nerve roots and cord or as fine linear enhancement along same (Fig 3A and 13).s*“*‘z MR is clearly advantageous because it is noninvasive, and it appears to be more sensitive than myelography in the demonstration of fine metastatic coating of the spinal cord. However, it has been suggested that MR is less sensitive in the detection of nerve root involvement. This may be due to the fact that the evaluation of nerve roots on MR is best performed in the axial plane, though determination of the levels at which to perform axial images generally depends on information acquired from sagittal images. Other reasons suggested for potential falsely negative MR studies include the small size of many metastatic nodules, CSF flow that can shift the position of (involved) nerve roots as well as induce artifacts that can obscure them, and technical difficulties that can mar interpretation.‘* Also, it has been observed that drop metastases occasionally do not demonstrate contrast enhancement, which obviously compromises their visualization. Whether and how often nerve root involvement is
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Tumor characterization and definition (ependyFig 2. momaj. (A-B) Axial unenhanced and enhanced CT images through the posterior fossa of this 14-year-old male demonstrate an inhomogeneous, partially calcified (arrow), and enhancing midline soft tissue mass (arrowheads). The fourth ventricle is not discernible and beam-hardening artifacts compromise definition of tumor margins. Obstructive hydrocephalus is present. (Cj Coronal long TR/short TE spin-echo image more clearly depicts the lobulated mass (arrowheads) filling the fourth ventricle and insinuating just above the tentorial notch. Note the multiple serpiginous flow voids of vessels around the margins of, as well as within. the mass suggesting its relative hypervascularity. Note, also, the high-signal intensity due to transependymal resorption of cerebrospinal fluid around the dilated bodies of the lateral ventricles.
missed by MR (in the absence of seeding of the cord) has yet to be determined. For now, although either a positive myelogram or positive MR is sufficient for confirmation of metastatic spread, neither a negative myelogram or negative MR would appear to be sufficient alone. From a clinical standpoint, it is useful to be aware that cytological analysis of cerebrospinal fluid is com-
plementary to the results of radiologic evaluation. Cerebrospinal fluid obtained at the time of myelography is negative in up to one half of patients who have radiographically documented leptomeningeal spread of the disease.” When only cerebrospinal fluid cytology is positive, the analysis is repeated (generally about 21 days after surgery) in order to confirm dissemination.
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Fig 3. MR evaluation for drop metaatasas. (A and B) Bagittal short TR/TE images of cervical/upper thoracic and lumboaacral spines after Gd-DTPA. Multiple fine linear and other nodular foci of abnormal enhancement (arrows) representing metastatic deposits are seen studding the spinal cord and cauda equina in this patient who has PNET/medulloblestoma.
DISCUSSION
Primitive Neuroectodermal Tumor/Medulloblastoma The primitive neuroectodermal tumor of the posterior fossa/medulloblastoma (PNET-MB) is the most common malignant primary central nervous system tumor in the pediatric population, constituting 13% to 20% of all pediatric brain tumors and 33% of those arising in the posterior fossa in childhood.13 Like other CNS neoplasms in childhood, the biology of the PNETMB remains poorly understood. Even the classification of the PNET-MB is controversial. A popular concept’4 has been that the tumor arises from the primitive neuroepithelial cells in the inferior medullary velum, which normally migrate upward and laterally to form the external granular layer of the cerebellum, a conception that has been regarded as useful for explaining the fact that tumors of this type in childhood are generally in the midline along the roof of the fourth ventricle, whereas those in adults are nearly always located more laterally in the cerebellar hemispheres. I5 However, in 1983, Rorke16
proposed a classification wherein all embryonic small-cell neuroepithelial tumors of the CNS would be regarded as primitive neuroectodermal tumors and then subdivided on the basis of light microscopy evidence for differentiation along various cell lines (such as medulloblastoma, pineoblastoma). Rubenstein14 strongly disagrees with this classification and argues for retaining the term “medulloblastoma” for the primitive neuroectodermal tumor in the posterior fossa, his argument being that the histogenesis of this portion of the central neuraxis (specifically, the cerebellum) is unique and that the clinical course of patients who have tumors in this location is much better delineated than that for primitive neuroectodermal tumors arising elsewhere in the CNS. While resolution of this controversy awaits the results of further study, other features of the tumor are well defined. Approximately 7.5% of patients who have PNET-MB present within the first decade of life. These rapidly growing tumors generally present with symptoms of short duration (less than 1 month prior to diagnosis). The
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signs are usually nonspecific ones,consistent with a posterior fossa mass and increased intracranial pressure, such as headache, nausea, and vomiting. In children less than 1 year of age, rapidly increasing head size is frequent, whereas the more specific sign of truncal ataxia is more frequent in the older child. The vast majority of childhood casesare situated midline along the cerebellar vermis, encroaching upon or completely occluding the fourth ventricle. Most extend posteriorly into the cisterna magna, frequently down to the level of the cervical cord. Grossly, the tumors in children have been described as rather friable and moderately demarcated from the cerebellar tissues, in contrast to those laterally located tumors in the older population, which tend to be more “woody” or fibrous in consistency and more clearly demarcated from surrounding tissues.14 Histologically, the tumors are extremely cellular, often with no signs of differentiation or definite architectural arrangement of the cells. In other cases,however, evidence for differentiation along neuroblastic, neuronal, spongioblastic, or oligodendroglia-like cell lines is apparent.‘4916 PNET-MB’s may metastasize through the ventricular system or subarachnoid space. Me-
PNET-ME. (A and B) Axial unenhanced Fig 4. classic appearance of a PNET-MB. Mild obstructive
and enhanced hydrocephalus.
tastases to extracranial sites (eg, bone, lymph nodes) occasionally occur via vesselsor shunts. At present, patients are treated with surgery and total craniospinal irradiation at the time of diagnosis. This has resulted in more than half of the patients being free of disease 5 years after diagnosis. Prognostic criteria for stratifying patients into risk groups have been developed.” Poor risk patients who have a significantly worse prognosis contrast with those who are average risk by satisfying one or more of the following criteria at the time of diagnosis: (1) being less than 4 years of age, (2) having evidence for tumor dissemination, (3) having a tumor greater than 3 cm in size, and (4) having a tumor with features of histologic differentiation. The radiographic manifestations of the PNETMB are frequently diagnostic.17918 Typically, the tumor appears on CT as a well-defined homogeneously hyperdense midline vermian mass that enhances uniformly with contrast (Fig 4 A and B). Less frequently, the tumor is isodenseprecontrast and/or demonstrates patchy enhancement. Calcification may occur in approximately 15%. Though cystic or necrotic areas have been described as occurring rarely, one clinical series reported this finding in 47% of its cases.l’ Mild to
CT images
through
the posterior
fossa
demonstrate
the
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DEBRA A. GUSNARD
moderate edema surrounds the tumor in most patients. Hydrocephalus is associated in approximately 95% of cases. Intratumoral hemorrhage is unusual. On MR, the appearance of the PNET-MB is less specific. The tumor may be seen to originate from the inferior medullary velum and may demonstrate relative hypointensity on long TR/ TE images (presumed to be due to its being a densely cellular mass having a high nuclear to cytoplasmic ratio and, consequently, less free water content). However, the tumor’s appearance on MR is often less specific than this. That is, the tumor appears as a midline mass that is hypointense on short TR/TE images and isointense or hyperintense to brain parenchyma on long TR/TE images (Fig 5 A and B). The pattern of enhancement after injection of gadolinium-DTPA is similar to that after injection of iodinated contrast with CT (Fig 6 A through D). Though it is not unique, given this tumor’s relative predilection for dissemination, when there is evidence for subarachnoid seeding it is a helpful feature for distinguishing this tumor type from others occurring in the posterior fossa. Precontrast, this appears as blurring of the folia and gyral surfaces and, after contrast, as regions of dense linear or nodular extra-axial enhancement (Fig 7 A and B). Cerebellar Astrocytoma Cerebellar astrocytoma is the second most common posterior fossa tumor in children in most series, being just slightly less common than the PNET-MB. On the basis of a series of 132 patients, a pathological classification was proposed by Winston, Gilles, et alI9 that distinguished two types of childhood cerebellar glioma on the basis of clustering of histologic features and differences in survival (which accounted for 90% of the tumors in their series). Type A, with features of microcysts, leptomeningeal deposits, Rosenthal fibers, or foci of oligodendroglia was associated with a 94% IO-year survival rate in children with a median age of 5 years. Type B, with features of perivascular rosettes, high cell density, necrosis, mitoses, and calcification, was associated with a 29% lo-year survival rate in children with a median age of 3 years. A more commonly used classification method at present is one that distinguishes the generally
Fig 5. PNET-MB. (A) Bagittal short TR/TE image demonstrates midline mass the epicenter of which is in the vicinity of the inferior medullary velum (arrow). Mass occupies inferior portion of fourth ventricle, involves vermis. and compresses medulla and upper cervical cord. 1B1 Axial long TR/TE image demonstrates the moderately well-demarcated nearly isointense mass.
benign juvenile pilocytic astrocytoma (JPA) or “typical” form of cerebellar astrocytoma from the diffuse fibrillary type that is more frequently associated with anaplastic change.20m22 The JPA constitutes 75% to 85% of all cerebellar astrocytomas. It has a peak incidence in the first decade of life and is associated with a nearly 90%
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Fig 6. PNET-MB enhancement on MR. (A and B) Axial long TR/short TE and long TR/long TE images demonstrate an unusually laterally-located tumor mass that proved at surgery to be a PNET-MB in this B-year-old female who has neurofibromatosis and a history of two other malignancies (AML and Wilm’s Tumor). (C and D) Axial and sagittel short TR/TE images after Gd-DTPA show marked diffuse contrast enhancement of the mass.
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25year survival rate. The rarer, diffuse, fibrillary type is more common in adolescents and young adults and is associated with an approximately 40% 25-year survival rate. The sharply marginated JPA also contrasts in its ease of resectability with the more infiltrative diffuse type.21 Cerebellar astrocytomasgenerally present with signs of increased intracranial pressure, such as headache,nausea,and vomiting. Symptoms may be present from several weeks to up to 3 years prior to diagnosis. Localizing signs such as (truncal) ataxia may be present. Because of their generally benign character and slow growth, these tumors tend to be large at the time of diagnosis, frequently five centimeters or more in size. Nearly 85% of the tumors in children arise from the vermis; extension into cerebellar hemispheres is seen in approximately one third of these cases. Nearly half of these tumors may be grossly cystic; these generally have a tumor nodule within the cyst wall. The wall in thesecasesconsistsof compressednonneoplastic cerebellar tissue.2’*23 Approximately 40% however, are actually solid tumors with a cystlike necrotic center. Less than 10% are completely solid tumors. When cystic, the cerebellar astocytomas are, in general, easily diagnosed radiographically. Typically, the tumor appears as a large midline cystic mass with an enhancing nodule along a portion of its wall (Fig 8 B).20,24Occasionally, the mural nodule fails to enhance or it enhances
DEBRA A. GUSNARD
Fig 8. Cystic astrocytoma. Axial contrast-enhanced CT image demonstrates a large, well-demarcated, cystic varmisn mass with en enhancing nodule along its anterolateral margin. Note the lack of enhancement of the remainder of the wall, compressed nonneoplastic cerebellar tissue. Hydrocephalus.
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inhomogeneously. This nodule may be round or plaque-like. The compressed cerebellar tissue constituting the remainder of the wall does not enhance. Though often somewhat similar in appearance prior to contrast administration, the appearance of the cystic tumors is unlike that of necrotic tumors after contrast administration, since the nonnecrotic walls and septations of the latter demonstrate marked enhancement. The distinction is important, particularly for the surgeon who needs to resect the neoplastic (solid) components of these tumors (ie, the mural nodule alone in the case of the cystic tumors in contrast to the entire mass in the case of the necrotic tumors). On CT, the solid tumors are generally hypo- to isodense before contrast and demonstrate enhancement that may be patchy or homogeneous after contrast. Occasionally, these tumors fail to enhance. Calcification is seen in approximately 20% (Fig 9). On MR, these tumors have a variable appearance depending upon their cystic or solid features.20 Also, most of them will appear as hypointense on short TR/TE and hyperintense on long TR/TE images, so that distinction between the components is not always clear-cut.
Cystic astrocytoma. (A and 6) Sagittal short Fig 10. TR/TE and coronal long TR/TE images demonstrate a very large, predominantly cystic mass. Note higher signal intensity of proteinaceous contents of cyst relative to that of CSF within the ventricles. Solid component of tumor mass is seen extending into left cerebellar hemisphere on long TR image (arrows).
Fig 9. Cystic astrocytoma. Nonenhenced CT shows this somewhat unusual appearing cystic astrocytoma with nodular calcifications along a saptation end portions of its wall.
Frequently, however, cystic areas will appear of even higher signal intensity than CSF on long TR/TE images (Fig 10 A and B) due to their highly proteinaceous fluid contents. Flow-related artifacts within a cyst can also be useful for distinguishing its fluid nature. Distinction of the solid componentsof these tumors is facilitated by administration of gadolinium-DTPA, the effect of which is equivalent to the iodinated contrast used for CT (Fig 11 A and B).
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Fig 11. Solid astrocytoma. (A and B) Axial short TR/TE images precontrast and postcontrast. Before contrast, a poorly-defined region of low-signal intensity associated with mass effect is seen in the vermis and right cerebellar hemisphere; the fourth ventricle is compressed and displaced. After contrast, the entire margin of this solid tumor enhances, distinguishing it from surrounding edema.
Ependymoma
Ependymomas comprise 9% to 16% of all primary central nervous system tumors in children and, although they may occur at any level of the central neuraxis, the majority (60% to 70%) are infratentorial in location.25-27There are approximately two age peaksfor this posterior fossa neoplasm,one in young children (over 50% occur in children less than 5 years of age) and one in adults (30 to 40 years of age).26,28 These tumors are believed to arise from the ependymal lining of the fourth ventricle (the floor more commonly than the roof) or from cell rests that, in the posterior fossa, can be located adjacent to the foraminae of Luschka, near the ventricular outlets or along the tela choroidea.*’ A rare embryonal variant, the ependymoblastoma occurs in children and has a marked predilection for subarachnoid dissemination.*’ However, ependymomasare also classified into benign or differentiated and malignant or anaplastic types.25-32 Calcification, mitoses, endothelial proliferation, and hypervascularity are histologic
features that have been negatively associated with prognosis. There is somecontradictory data regarding histologic variation and survival in children who have these tumors. Kricheff et al found no correlation between histology and prognosis.3oOthers have noted a striking difference in survival between differentiated and anaplastic ependymomas,60% to 70% versus 10%to 30%, respectively.33 In his series of 360 cases, Gilles3* observeda paradoxically worse prognosis in children who had a more benign histology. This was considered likely to be attributable to these tumors’ pattern of growth. That is, it is known that the degree of surgical resection of thesetumors correlates with survival. Despite the fact that it appears that the majority of the infratentorial neoplasms are histologically benign (in contrast to the supratentorial neoplasms), tumors in this location frequently have extensive extramedullary growth that compromises their resectability. Macroscopically, the tumors, which may be soft and papillary or firm with gritty areas of
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calcification, typically project into the fourth ventricle, occluding its lumen.25~27They may protrude into the foramen of Luschka, out into the cerebellopontine angle, or into the cisterna magna and insinuate through the foramen magnum to surround the medulla and upper cervical cord. Commonly, they infiltrate along the floor of the fourth ventricle into the brainstem. Becauseof the exophytic and infiltrative growth patterns of these tumors, symptoms are usually less than a few months in duration at the time of diagnosis. As in the casesof the PNET-MB and cerebellar astrocytoma, nonspecific signs related to increased intracranial pressure, as well as more specific signs related to cerebellar dysfunction, are common. Other signs referable to tumor extension around the brainstem and through the foramen magnum, such as cranial nerve palsies, torticollis, and nuchal rigidity, may also be present.26*29 All patients undergo surgical resection/debulking and radiation therapy. Controversy exists regarding the appropriate radiation treatment volume. This relates to the issue of the difference in frequency of tumor dissemination at the time of diagnosis between the benign and malignant casesof infratentorial ependymoma. Thus, while craniospinal irradiation is indicated for all malignant ependymomas, it is variably provided in benign cases.26’33 The CT appearance of this posterior fossa neoplasm is the least distinctive of the three that have been described. That is, the tumor may appear isodense, hyperdense, hypodense, or of After contrast injection, it mixed density.26V28*29 may patchily or homogeneously enhance or fail to enhance at all. Ependymomas may occasionally mimic the classic appearance of the PNETMB-a hyperdense, well-marginated midline masswith homogeneousenhancement. However, in the series of posterior fossa ependymomas of Swartz et a129and that of Zee et a1,2812 out of 15 and sevenout of 10 cases,respectively, appeared as (predominantly) isodense masseson precontrast CT scans, unlike the usual PNET-MB or astrocytoma, so that this appearsto be a diagnostically useful appearance, when present. Ependymomas may exhibit regions of cyst formation, though this appears to occur more commonly in those tumors in a supratentorial location. Though not common (- lo%), intratumoral hemorrhage
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is a more likely occurrence in these tumors than in the PNET-MB or astrocytoma. Approximately 50% Contain foci of calcification, generally in the form of small nodular deposits. This has been suggested28to be the single most significant finding for diagnosing an ependymoma. Calcification in the PNET-MB is statistically less common (-15%), but the incidence of this tumor is appreciably greater than the ependymoma, so that the presence of calcification may be a useful sign but should be weighed in the context of the overall appearance of the mass (Fig 2 A and B). Of note, however, is the fact that the tendency of the ependymomasto calcify may actually be problematic in the posttreatment evaluation of patients being followed for tumor recurrence, since tumoral calcification and dystrophic calcification in adjacent tissues may be indistinguishable.29 The inability of MR to specifically detect calcification limits the diagnostic usefulness of MR regarding this histologic feature. By signal intensity characteristics, this tumor is somewhat nondistinctive. It is usually heterogeneousdue to the presenceof foci of hemorrhage, calcification, small cystic areas, and blood vessels (Fig 12). The greater contrast resolution and the multiplanar capability of MR define the extent of the tumor clearly, and it is the tumor’s morphology that appears most useful for diagnosis. That is, the “melted wax” appearanceof a massinsinuating along the margins of the fourth ventricle, extending into and expanding adjacent cerebrospinal fluid spaces, and enveloping the brainstem with only moderate mass effect is characteristic of ependymoma (Fig 13 A and B). PNET-MB can mimic this appearance, but uncommonly. DIFFERENTIAL DIAGNOSTIC CONSIDERATIONS
When a mass lesion is identified in the posterior fossa of a child, the three aforementioned neoplasms are primary considerations. Tumors of less common histology can arise and enter into the differential diagnosis. For example, another glial tumor, the oligodendroglioma, may arise in the cerebellum. Though oligodendrogliomas (anywhere in the CNS) are generally regarded as unusual in childhood, in one small series,34a biphasic age distribution
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Fig 12. Epandymoma. Long TR/short TE image shows heterogeneous signal intensity arising from amorphous mass (arrowheads), expanding fourth ventricle and left foraman of Luschka. Note multiple prominent flow voids (arrows) in this hyparvascular mass.
with a small peak between 6 and 12 years and a large peak between 25 and 50 years was noted. Little information is present in the literature regarding the natural history of these tumors in childhood. Four casesof oligodendrogliomas (all
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histologically malignant) of the cerebellar region were observed at the Children’s Hospital of Philadelphia between 1975 and 1982.35Radiographically, they appeared as large, solid, homogeneousmassesof variable density (hypodenseto hyperdense) and demonstrated variable contrast enhancement, which involved either cerebellar hemisphere or vermis. Three had appearances indistinguishable from the solid form of the cerebellar astrocytoma. These tumors may be superficially located, as in the case of a 3-yearold patient reported by Rubenstein in whom the tumor was seen to infiltrate the leptomeninges and erode the overlying bone.36 Anatomic relationships can influence the differential diagnosis. Because of the close proximity of structures at the tentorial hiatus, the epicenter of a mass lesion crossing the hiatus is frequently difficult to discern. For example, a superior vermian mass, such as a PNET-MB extending upward, may in some casesbe difficult to distinguish from a pineal mass, such as a pineoblastoma extending downward. Contrast enhancement is an important part of the cross-sectional imaging evaluation of cystic (mass) lesions in the posterior fossa, since it will aid in confirming distinction between the cystic astrocytoma and other cystic lesions with no enhancing components, such as arachnoid cysts and the trapped fourth ventricle.
Fig 13. Epandymoma. (A) Sagittal short TR/TE image. Lobulated mass (arrowheads) occupies fourth ventricle. hugs posterior aspect of brain stem, and insinuates inferiorly and posteriorly into upper cervical spinal canal and cisterna magna. (6) Coronal long TR/short TE image in another patient. Lobulatad mass envelopes left side of brain stem. Note the more “plastic” extension and lesser mass effect associated with this neoplasm as compared with the more discrete and bulky mass in Fig 4.
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In the differential of enhancing lesions along the margins of the fourth ventricle are vascular malformations and the choroid plexus papilloma (CPP) (Fig 14). The latter most frequently occur in the bodies of the lateral ventricles in neonates; rarely, they may be discovered in the fourth ventricle in older children and adolescents.37 Inflammatory lesions, such as abscesses,may occur in the cerebellum and occasionally mimic a cystic/necrotic neoplasm, though the amount of associated vasogenic edema is generally greater than that seen with cerebellar astrocytomas. Mass effect may be present in the absence of a true mass lesion, as in casesof basilar meningitis associated with marked extraaxial enhancement (similar to that seen with subarachnoid dissemination of tumor), effacement of CSF spaces,and hydrocephalus. In the context of patients who have known posterior fossa neoplasms, a particularly vexing and crucial diagnostic dilemma may arise in the follow-up of those patients who have undergone radiation therapy. Not infrequently, nonenhancing abnormalities consequent to radiation vasculitis are noted to develop within the white matter
Fig 14. Choroid plexus pspilloma. (A and 6) Sagittal male demonstrate a small wall-defined homogeneously ventricle in the expected location of the choroid plexus.
included in the radiation portal, Of more concern, however, is the occasional development of enhancing lesions with masseffect that represent the effects of radiation necrosis. These typically arise more than a year after radiation treatment and may be indistinguishable from a recurrent tumor.38-40Biopsy may be required for distinction. Unlike the situation in adults, extraaxial neoplasms in the posterior fossa of children are relatively rare. Two of those that occur more frequently, however, are the epidermoid and dermoid tumors. These are believed to represent cell rests consequent to incomplete disjunction of neuroectoderm from cutaneous ectoderm (epidermoid) or from cutaneous ectoderm and mesoderm (dermoid) at the time of neural tube closure. Epidermoids of the posterior fossa are most commonly located in the cerebellopontine angle; generally, they appear as lobulated lowdensity masseson CT that do not enhance after contrast. On MB, they typically follow the signal intensity of CSF and, as a consequence, may actually be difficult to perceive except by the fact of their interface with and mass effect upon
short TR/TE images pracontrast and postcontrast in this g-year-old enhancing soft tissue mass (arrow) along the roof of the fourth
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Dermoid. Axial short TR/TE image shows a Fig 15. midline mass of high signal intensity compatible with fatty tissue in the region of the cerebellar vermis.
adjacent brainstem and/or cerebellar hemisphere. Occasionally, they manifest high-signal intensity on short TR/TE images, making the distinction between them and dermoids more difficult. Dermoids are generally midline lesions, either in the fourth ventricle or along the vermis (Fig 15), which have density and signal intensity characteristics of fat on CT and MR. Neuroblastoma, a relatively common malignancy of childhood, frequently metastasizes to Table
1. Differential
Diagnosis
of Pediatric
Posterior
Astrocytoma Density (CT), TSI (MR T2WI) Density (CT), TSO to lSl (Ml3 T2WI) Calcification No enhancement Homogeneous enhancement Inhomogeneous enhancement Peritumoral edema Solid Cystic Midline (vermis fourth ventricle) Midline (extraaxial) Lateral (hemisphere) Extension thru outlets of fourth ventricle, foramen magnum
+++ + Occas ++ ++ + ++ +++ ++
++ -
Fig 16. Metaatatic nauroblastoma. Axial long TR/short TE image demonstrates soft tissue mass (arrows) in the expected location of the torcula. Mass is clearly separate from adjacent inferior vermis (arrowhead) and cerebellar hemispheres.
the calvarium. Bony destruction is often associated with an epidural soft tissue mass.One of the more common locations for this to occur is in the region of the torcula Herophili (Fig 16), where involvement can be associatedwith impedance of venousoutflow and the development of communicating hydrocephalus. In conclusion, for the radiographic differential diagnosis of posterior fossaneoplasmsin children Fossa Neoplasms-Radiographic MB-PNET
Ependymona
+ ++ + Rare
++ + +++ + + +++ occas ++ ++ +++ -
+++ + ++ +++ Rare +++ + Rare
++
Characteristics Other Teratoma CPP, vast malf Dermoid, neuroblastoma -
NOTE. Plus and minus signs refer to the degree of the tumor, minus meaning that it does not have that characteristic. Abbreviations: CPP, choroid plexus papilloma; vast malf, vascular malformation.
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(Table I), there are a number of considerations when a masslesion is evident involving either the fourth ventricle or cerebellum. Attention to imaging details and an awareness of the diverse
manifestations and clinical characteristics of the pathologic processesthat can occur there, however, permits significant diagnostic accuracy and communication of clinically useful information.
REFERENCES 1. Farwell JR, Dohrmann GH, Flannary JT: Central nervous system tumors in children. Cancer 40:3123-3132, 1977 2. Segall HD, Batnitzky S, Zee C, et al: Computed tomography in the diagnosis of intracranial neoplasms in children. Cancer 56:1748-1755, 1985 3. Zimmerman RA, Bilaniuk LT, Schut L, et al: Medical imaging of pediatric brain tumors. Prog Exp Tumor Res 30:61-80, 1987 4. Bird CR, Drayer BP, Medina M, et al: Gd-DTPAenhanced MR imaging in pediatric patients after brain tumor resection. Radiology 169:123-126, 1988 5. Cohen BH, Bury E, Packer RJ, et al: GadoliniumDTPA-enhanced magnetic resonance imaging in childhood brain tumors. Neurology 39:1178-l 183, 1989 6. Felix R, Schorner W, Laniado M, et al: Brain tumors: MR imaging with gadolinium-DTPA. Radiology 156:681688,1985 7. Kucharczyk W, Bran&Zawadski M, Sobel D, et al: Central nervous system tumors in children: Detection by magnetic resonanceimaging. Radiology 155:131- 136, 1985 8. Sze G, Soletsky S, Bronen R, et al: MR imaging of the cranial meninges with emphasis on contrast enhancement and meningeal carcinomatosis. AJNR 10:965-975, 1989 9. George RE, Laurent JP, McCluggage CW, et al: Spinal metastasisin primative neuroectodermaltumors (medulloblastoma) of the posterior fossa: Evaluation with CT myelography and correlation with patient age and tumor differentiation. Pediatr Neurosci 12:157-160, 1985-1986 10. Packer RJ, Sutton LN, D’Angio G, et al: Management of children with primitive neuroectodermal tumors of the posterior fossa/medulloblastoma. Pediatr Neurosci 12: 272-282, 1985-1986 11. Parizel PM, Baleriaux D, RodeschG, et al: Gd-DTPA enhanced MR imaging of spinal tumors. AJNR 10:249-258, 1989 12. Sze G, Abramson A, Krol G, et al: Gadolinium-DTPA in the evaluation of intradural extramedullary spinal disease. AJNR 9:153-163, 1988 13. Arseni C, Ciurza AV: Statistical survey of 276 casesof medulloblastomas (1935-1978). Acta Neurochir 57:159-162, 1982 14. Russell DS, Rubenstein LJ: Pathology of Tumors of the Nervous System (ed 5). Baltimore, MD, Williams & Wilkins 1989, pp 251-279 15. Raaf J, Kernahan JW: Relation of abnormal collections of cells in posterior medullary velum of the cerebellum to origin of medulloblastoma. Arch Neurol and Psych 52:163175,1944 16. Rorke LB: The cerebellar medulloblastoma and its relationship to primitive neuroectodermal tumors. J Neuropath01Exp Neurol42:1-151983
17. Sandhu A, Kendall B: Computed tomography in management of medulloblastomas. Neuroradiology 29:444452,1987 18. Zimmerman RA, Bilaniuk LT, Pahlajani H: Spectrum of medulloblastomas demonstrated by computed tomography. Radiology 126:137-141,1978 19. Winston K, Gilles FH, Leviton A, et al: Cerebellar gliomas in children. J Nat1 Cancer Inst 58:833-838, 1977 20. Lee Y, Van Tassel P, Bruner JM, et al: Juvenile pilocytic astrocytomas: CT and MR characteristics. AJNR 10:363-370, 1989 21. Russell DS, Rubenstein LJ: Pathology of Tumors of the Nervous System (ed 5). Baltimore, MD, Williams & Wilkins 1989, pp 95-111 22. Steinberg GK, Shuer LM, Conley FK, et al: Evolution and outcome in malignant astroglial neoplasmsof the cerebellum. J Neurosurg 62:9-17,1985 23. Go1A, McKissack W: The cerebellar astrocytomas: A report on 98 verified cases.J Neurosurg 16:287-296,1959 24. Zimmerman RA, Bilaniuk LT, Bruno L, et al: Computed tomography of cerebellar astrocytoma. AJR 130:929933,1978 25. Rorke LB: Relationship of morphology of ependymoma in children to prognosis. Prog Exp Tumor Res 30:170174,1987 26. Kun LE, Kovner EH, Sanford RA: Ependymomas in children. Pediatr Neurosci 14:57-63, 1988 27. Russell DS, Rubenstein LJ: Pathology of Tumors of the Nervous System. (ed 5). Baltimore, MD, Williams & Wilkins 1989,pp 192-219 28. Zee C, Segal HD, Ahmadi J, et al: Computed tomography of posterior fossa ependymomas in childhood. Surg Neurol20:221-226,1983 29. Swartz JD, Zimmerman RA, Bilaniuk LT: Computed tomography of intracranial ependymomas.Radiology 143:97101.1982 30. Kricheff II, Becker M, Schneck SA, et al: Intracranial ependymomas: Factors influencing prognosis. J Neurosurg 21:7-14, 1964 31. Liu HM, Boggs J, Kidd J: Ependymomas of childhood. I. Histological survey and clinicopathological correlation. Childs Brain 2:92-l 10, 1976 32. Gilles FH, Leviton A, Hedley-White ET, et al: Childhood brain tumor update. Human Path0114:834-845, 1983 33. Salazar OM, Castro-Vita H, VanHoutte P, et al: Improved survival in casesof intracranial ependymoma after radiation therapy. Late report and recommendations. J Neurosurg 59:652-659,1983 34. Chin HW, Hazel1 JJ, Kim TH, et al: Oligcdendrogliomas. I. A clinical study of cerebral oligodendrogliomas. Cancer 45:1458-1466,198O
278 35. Packer RJ, Sutton LN, Rorke LB, et al: Oligodendroglioma of the posterior fossa in childhood. Cancer 56:195199,1985 36. Russell DS, Rubenstein LJ: Pathology of Tumors of the Nervous System. (ed 5). Baltimore, MD, Williams & Wilkins 1989, p 177 37. Tomita T, McLone DG, Flannery AM: Choroid plexus papillomas of neonates, infants and children. Pediatr Neurosci 14:23-30, 1988
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38. Curnes JT, Laster DW, Ball MR, et al: Magnetic resonance imaging of radiation injury to the brain. AJNR 7:389-394, 1986 39. Dooms GC, Hecht S, Brant-Zawadski M, et al: Brain radiation lesions: MR imaging. Radiology 158:149-155, 1986 40. Tsuruda JS, Kortman KE, Bradley WG, et al: Radiation effects on cerebral white matter: MR evaluation. AJNR 8:431-437, 1987
EOPLASIA in children is uncommon; yet, the most common site for the occurrence of solid neoplasmsin children is the central nervous system.’ The present incidence is approximately 2.5 central nervous system tumors per 100,000 children per year. Pediatric brain tumors, in fact, constitute 15% to 20% of all primary brain tumors. However, unlike the situation in the adult population, the posterior fossais a common location for primary brain tumors to occur.2*3 Approximately one half of the childhood cases are discovered in the posterior fossa. The vast majority of these arise in either the parenchyma of the cerebellum (hemispheres or vermis), or the linings of the fourth ventricle (eg, the primitive neuroectodermal tumor/medulloblastoma, cerebellar astrocytoma, ependymoma). A small, though not insignificant, proportion of posterior fossa neoplasms in children arise within the brainstem (These are discussed in the article by Richard Smith in this issue). Metastases, as well as the extraaxial neoplasms that are frequently seenin the posterior fossaeof adults (eg, acoustic neuroma, meningioma), are rare in children. The goals of the radiologic assessmentof a child who presents with signs suspicious for an underlying posterior fossa mass are twofold; to determine whether a massis present and, if one is present, to suggest a likely histologic (differential) diagnosis, which will aid the neurosurgeon and radiation therapist in their treatment planning. In those caseswhere a neoplasm has been discovered, follow-up after the institution of treatment is imperative in order to assessthe response of the tumor as well as to identify possible complications of the treatment. Over the past decade,the cornerstone of radiologic assessmentof these patients has been computed tomography (CT). More recently, magnetic resonance imaging (MR) has played an important role for four reasons: (1) its greater contrast resolution than CT, (2) its multiplanar capability, (3) its lack of artifacts arising from cortical bone that with CT can obscure adjacent soft tissue detail (eg, posterior fossa images on CT), and (4) the introduction of a paramagnetic contrast agent (gadolinium-DTPA) that, like the
From the Department of Radiology, The Children’s Hospital of Philadelphia, Philadelphia, PA. Address reprint requests to Debra A. Gusnard. MD. Department of Radiology. The Children’s Hospital of Philadelphia, 34th and Civic Center Blvd. Philadelphia, PA 19104. o 1990 by W.B. Saunders Company. 0037-198X/90/2503-0005$5.00/0
Seminars in Roenfgenology, Vol XXV, No 3 (July), 1990: pp 263-276
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iodinated agents used in CT, demonstrates sites of breakdown in the blood-brain barrier.2y4m7 In this article, an approach to the imaging evaluation of childhood posterior fossa neoplasms (excluding brainstem gliomas) is presented. This includes a detailed discussion of the more common neoplasms-their clinical presentations, pathologic characteristics, radiologic manifestations, and differential diagnoses. TECHNIQUE
The nature of the clinical presentation of a child who has a posterior fossa neoplasm frequently determines the direction and extent of the preoperative radiologic evaluation (Fig 1). For example, a child in extremis, who has signs of increased intracranial pressure,should undergo a CT scan with and without contrast enhancement, which includes thin (3mm to 5mm) sections through the posterior fossa. This can be performed expeditiously and provides information necessary for emergent intervention, such as when severe hydrocephalus is present. In these cases,when the patient is clinically unstable, an MR scan is usually not obtained initially because of logistical difficulties, but may be obtained later when the patient is more stable. More often, the patient’s condition is not unstable, his symptoms having developed subacutely, so that an MR scan is the initial examination obtained. Though calcification is less accurately detected and tissue characterization is essentially no better than with CT, MR does have the advantage of being able to better define tumor extent because of its greater contrast resolution and multiplanar capability (Fig 2 A through C). As in the case of the CT exam, contrast (gadolinium-DTPA) should be administered routinely as a part of the MR examination in these patients. Not only do the enhancement
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264 Unstable patient with signs of posterior fossa mass
CT with and without
Stable patient with signs of posterior fossa mass
contrast
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(-
(+ tumor)
tumor)
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t
i
w
(+ tumor)
(Surgery)
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contrast baseline postoperative
/
\
Patients with medulloblastoma-PNET, ependymoma
Patients with cerebellar astro, other
I Myelogram and/or MR with contrast to evaluate for spinal drop metastases \ Follow-up MR with and without contrast (interval determined tumor type, stage of disease and results of previous study) Fig 1.
Radiologic
evaluation
of pediatric
posterior
by
fossa.
characteristics of tumors aid in differential diagnostic considerations, but contrast-enhanced MR is notably more sensitive in the detection of subarachnoid spread of tumor than is contrastenhanced CT.’ Thus, a properly performed MR scan (Tl- and T2-weighted images and postgadolinium Tl -weighted images) can contribute significantly to planning the surgical approach, the radiation portal, and the patient’s tumor staging. Once the posterior fossa neoplasm has been defined and surgical debulking/resection has taken place, in certain cases another CT or MR with and without contrast should be obtained within 48 hours of the surgical procedure. It is theorized that obtaining the scan within the first 48 hours of the immediate postoperative period optimizes the distinction between residual tumor and granulation tissue that has not yet had the opportunity to develop within the surgical bed. For some tumors (eg, medulloblastoma, ependymoma), it is known that the amount of tumor left
at surgery correlates inversely with the prognosis. A baseline post-op CT, therefore, provides information pertinent to immediate clinical decision making as well as a reference for further follow-up studies. It should be recognized that residual tumor that enhanced preoperatively may not enhance postoperatively when the patient is on large doses of steroids. For those tumors that have a significant likelihood of metastasizing along the subarachnoid space (ie, medulloblastoma, “malignant” ependymoma), another important step in radiologic staging is the evaluation of the spinal canal. The traditional method has been myelography (*post myelogram CT)9~10performed approximately 10 days to 2 weeks after surgery (the delay being necessary since interpretation of the myelogram performed in the early postoperative period may be compromised due to filling defects caused by blood clots within the subarachnoid space). However, the role of the contrast-enhanced MR in this setting is controversial and presently under investigation. Tl-weighted images of the spine after gadolinium-DTPA administration can show drop metastases in the form of enhancing nodular deposits within the thecal sac along the nerve roots and cord or as fine linear enhancement along same (Fig 3A and 13).s*“*‘z MR is clearly advantageous because it is noninvasive, and it appears to be more sensitive than myelography in the demonstration of fine metastatic coating of the spinal cord. However, it has been suggested that MR is less sensitive in the detection of nerve root involvement. This may be due to the fact that the evaluation of nerve roots on MR is best performed in the axial plane, though determination of the levels at which to perform axial images generally depends on information acquired from sagittal images. Other reasons suggested for potential falsely negative MR studies include the small size of many metastatic nodules, CSF flow that can shift the position of (involved) nerve roots as well as induce artifacts that can obscure them, and technical difficulties that can mar interpretation.‘* Also, it has been observed that drop metastases occasionally do not demonstrate contrast enhancement, which obviously compromises their visualization. Whether and how often nerve root involvement is
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Tumor characterization and definition (ependyFig 2. momaj. (A-B) Axial unenhanced and enhanced CT images through the posterior fossa of this 14-year-old male demonstrate an inhomogeneous, partially calcified (arrow), and enhancing midline soft tissue mass (arrowheads). The fourth ventricle is not discernible and beam-hardening artifacts compromise definition of tumor margins. Obstructive hydrocephalus is present. (Cj Coronal long TR/short TE spin-echo image more clearly depicts the lobulated mass (arrowheads) filling the fourth ventricle and insinuating just above the tentorial notch. Note the multiple serpiginous flow voids of vessels around the margins of, as well as within. the mass suggesting its relative hypervascularity. Note, also, the high-signal intensity due to transependymal resorption of cerebrospinal fluid around the dilated bodies of the lateral ventricles.
missed by MR (in the absence of seeding of the cord) has yet to be determined. For now, although either a positive myelogram or positive MR is sufficient for confirmation of metastatic spread, neither a negative myelogram or negative MR would appear to be sufficient alone. From a clinical standpoint, it is useful to be aware that cytological analysis of cerebrospinal fluid is com-
plementary to the results of radiologic evaluation. Cerebrospinal fluid obtained at the time of myelography is negative in up to one half of patients who have radiographically documented leptomeningeal spread of the disease.” When only cerebrospinal fluid cytology is positive, the analysis is repeated (generally about 21 days after surgery) in order to confirm dissemination.
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Fig 3. MR evaluation for drop metaatasas. (A and B) Bagittal short TR/TE images of cervical/upper thoracic and lumboaacral spines after Gd-DTPA. Multiple fine linear and other nodular foci of abnormal enhancement (arrows) representing metastatic deposits are seen studding the spinal cord and cauda equina in this patient who has PNET/medulloblestoma.
DISCUSSION
Primitive Neuroectodermal Tumor/Medulloblastoma The primitive neuroectodermal tumor of the posterior fossa/medulloblastoma (PNET-MB) is the most common malignant primary central nervous system tumor in the pediatric population, constituting 13% to 20% of all pediatric brain tumors and 33% of those arising in the posterior fossa in childhood.13 Like other CNS neoplasms in childhood, the biology of the PNETMB remains poorly understood. Even the classification of the PNET-MB is controversial. A popular concept’4 has been that the tumor arises from the primitive neuroepithelial cells in the inferior medullary velum, which normally migrate upward and laterally to form the external granular layer of the cerebellum, a conception that has been regarded as useful for explaining the fact that tumors of this type in childhood are generally in the midline along the roof of the fourth ventricle, whereas those in adults are nearly always located more laterally in the cerebellar hemispheres. I5 However, in 1983, Rorke16
proposed a classification wherein all embryonic small-cell neuroepithelial tumors of the CNS would be regarded as primitive neuroectodermal tumors and then subdivided on the basis of light microscopy evidence for differentiation along various cell lines (such as medulloblastoma, pineoblastoma). Rubenstein14 strongly disagrees with this classification and argues for retaining the term “medulloblastoma” for the primitive neuroectodermal tumor in the posterior fossa, his argument being that the histogenesis of this portion of the central neuraxis (specifically, the cerebellum) is unique and that the clinical course of patients who have tumors in this location is much better delineated than that for primitive neuroectodermal tumors arising elsewhere in the CNS. While resolution of this controversy awaits the results of further study, other features of the tumor are well defined. Approximately 7.5% of patients who have PNET-MB present within the first decade of life. These rapidly growing tumors generally present with symptoms of short duration (less than 1 month prior to diagnosis). The
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signs are usually nonspecific ones,consistent with a posterior fossa mass and increased intracranial pressure, such as headache, nausea, and vomiting. In children less than 1 year of age, rapidly increasing head size is frequent, whereas the more specific sign of truncal ataxia is more frequent in the older child. The vast majority of childhood casesare situated midline along the cerebellar vermis, encroaching upon or completely occluding the fourth ventricle. Most extend posteriorly into the cisterna magna, frequently down to the level of the cervical cord. Grossly, the tumors in children have been described as rather friable and moderately demarcated from the cerebellar tissues, in contrast to those laterally located tumors in the older population, which tend to be more “woody” or fibrous in consistency and more clearly demarcated from surrounding tissues.14 Histologically, the tumors are extremely cellular, often with no signs of differentiation or definite architectural arrangement of the cells. In other cases,however, evidence for differentiation along neuroblastic, neuronal, spongioblastic, or oligodendroglia-like cell lines is apparent.‘4916 PNET-MB’s may metastasize through the ventricular system or subarachnoid space. Me-
PNET-ME. (A and B) Axial unenhanced Fig 4. classic appearance of a PNET-MB. Mild obstructive
and enhanced hydrocephalus.
tastases to extracranial sites (eg, bone, lymph nodes) occasionally occur via vesselsor shunts. At present, patients are treated with surgery and total craniospinal irradiation at the time of diagnosis. This has resulted in more than half of the patients being free of disease 5 years after diagnosis. Prognostic criteria for stratifying patients into risk groups have been developed.” Poor risk patients who have a significantly worse prognosis contrast with those who are average risk by satisfying one or more of the following criteria at the time of diagnosis: (1) being less than 4 years of age, (2) having evidence for tumor dissemination, (3) having a tumor greater than 3 cm in size, and (4) having a tumor with features of histologic differentiation. The radiographic manifestations of the PNETMB are frequently diagnostic.17918 Typically, the tumor appears on CT as a well-defined homogeneously hyperdense midline vermian mass that enhances uniformly with contrast (Fig 4 A and B). Less frequently, the tumor is isodenseprecontrast and/or demonstrates patchy enhancement. Calcification may occur in approximately 15%. Though cystic or necrotic areas have been described as occurring rarely, one clinical series reported this finding in 47% of its cases.l’ Mild to
CT images
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DEBRA A. GUSNARD
moderate edema surrounds the tumor in most patients. Hydrocephalus is associated in approximately 95% of cases. Intratumoral hemorrhage is unusual. On MR, the appearance of the PNET-MB is less specific. The tumor may be seen to originate from the inferior medullary velum and may demonstrate relative hypointensity on long TR/ TE images (presumed to be due to its being a densely cellular mass having a high nuclear to cytoplasmic ratio and, consequently, less free water content). However, the tumor’s appearance on MR is often less specific than this. That is, the tumor appears as a midline mass that is hypointense on short TR/TE images and isointense or hyperintense to brain parenchyma on long TR/TE images (Fig 5 A and B). The pattern of enhancement after injection of gadolinium-DTPA is similar to that after injection of iodinated contrast with CT (Fig 6 A through D). Though it is not unique, given this tumor’s relative predilection for dissemination, when there is evidence for subarachnoid seeding it is a helpful feature for distinguishing this tumor type from others occurring in the posterior fossa. Precontrast, this appears as blurring of the folia and gyral surfaces and, after contrast, as regions of dense linear or nodular extra-axial enhancement (Fig 7 A and B). Cerebellar Astrocytoma Cerebellar astrocytoma is the second most common posterior fossa tumor in children in most series, being just slightly less common than the PNET-MB. On the basis of a series of 132 patients, a pathological classification was proposed by Winston, Gilles, et alI9 that distinguished two types of childhood cerebellar glioma on the basis of clustering of histologic features and differences in survival (which accounted for 90% of the tumors in their series). Type A, with features of microcysts, leptomeningeal deposits, Rosenthal fibers, or foci of oligodendroglia was associated with a 94% IO-year survival rate in children with a median age of 5 years. Type B, with features of perivascular rosettes, high cell density, necrosis, mitoses, and calcification, was associated with a 29% lo-year survival rate in children with a median age of 3 years. A more commonly used classification method at present is one that distinguishes the generally
Fig 5. PNET-MB. (A) Bagittal short TR/TE image demonstrates midline mass the epicenter of which is in the vicinity of the inferior medullary velum (arrow). Mass occupies inferior portion of fourth ventricle, involves vermis. and compresses medulla and upper cervical cord. 1B1 Axial long TR/TE image demonstrates the moderately well-demarcated nearly isointense mass.
benign juvenile pilocytic astrocytoma (JPA) or “typical” form of cerebellar astrocytoma from the diffuse fibrillary type that is more frequently associated with anaplastic change.20m22 The JPA constitutes 75% to 85% of all cerebellar astrocytomas. It has a peak incidence in the first decade of life and is associated with a nearly 90%
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Fig 6. PNET-MB enhancement on MR. (A and B) Axial long TR/short TE and long TR/long TE images demonstrate an unusually laterally-located tumor mass that proved at surgery to be a PNET-MB in this B-year-old female who has neurofibromatosis and a history of two other malignancies (AML and Wilm’s Tumor). (C and D) Axial and sagittel short TR/TE images after Gd-DTPA show marked diffuse contrast enhancement of the mass.
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25year survival rate. The rarer, diffuse, fibrillary type is more common in adolescents and young adults and is associated with an approximately 40% 25-year survival rate. The sharply marginated JPA also contrasts in its ease of resectability with the more infiltrative diffuse type.21 Cerebellar astrocytomasgenerally present with signs of increased intracranial pressure, such as headache,nausea,and vomiting. Symptoms may be present from several weeks to up to 3 years prior to diagnosis. Localizing signs such as (truncal) ataxia may be present. Because of their generally benign character and slow growth, these tumors tend to be large at the time of diagnosis, frequently five centimeters or more in size. Nearly 85% of the tumors in children arise from the vermis; extension into cerebellar hemispheres is seen in approximately one third of these cases. Nearly half of these tumors may be grossly cystic; these generally have a tumor nodule within the cyst wall. The wall in thesecasesconsistsof compressednonneoplastic cerebellar tissue.2’*23 Approximately 40% however, are actually solid tumors with a cystlike necrotic center. Less than 10% are completely solid tumors. When cystic, the cerebellar astocytomas are, in general, easily diagnosed radiographically. Typically, the tumor appears as a large midline cystic mass with an enhancing nodule along a portion of its wall (Fig 8 B).20,24Occasionally, the mural nodule fails to enhance or it enhances
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Fig 8. Cystic astrocytoma. Axial contrast-enhanced CT image demonstrates a large, well-demarcated, cystic varmisn mass with en enhancing nodule along its anterolateral margin. Note the lack of enhancement of the remainder of the wall, compressed nonneoplastic cerebellar tissue. Hydrocephalus.
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inhomogeneously. This nodule may be round or plaque-like. The compressed cerebellar tissue constituting the remainder of the wall does not enhance. Though often somewhat similar in appearance prior to contrast administration, the appearance of the cystic tumors is unlike that of necrotic tumors after contrast administration, since the nonnecrotic walls and septations of the latter demonstrate marked enhancement. The distinction is important, particularly for the surgeon who needs to resect the neoplastic (solid) components of these tumors (ie, the mural nodule alone in the case of the cystic tumors in contrast to the entire mass in the case of the necrotic tumors). On CT, the solid tumors are generally hypo- to isodense before contrast and demonstrate enhancement that may be patchy or homogeneous after contrast. Occasionally, these tumors fail to enhance. Calcification is seen in approximately 20% (Fig 9). On MR, these tumors have a variable appearance depending upon their cystic or solid features.20 Also, most of them will appear as hypointense on short TR/TE and hyperintense on long TR/TE images, so that distinction between the components is not always clear-cut.
Cystic astrocytoma. (A and 6) Sagittal short Fig 10. TR/TE and coronal long TR/TE images demonstrate a very large, predominantly cystic mass. Note higher signal intensity of proteinaceous contents of cyst relative to that of CSF within the ventricles. Solid component of tumor mass is seen extending into left cerebellar hemisphere on long TR image (arrows).
Fig 9. Cystic astrocytoma. Nonenhenced CT shows this somewhat unusual appearing cystic astrocytoma with nodular calcifications along a saptation end portions of its wall.
Frequently, however, cystic areas will appear of even higher signal intensity than CSF on long TR/TE images (Fig 10 A and B) due to their highly proteinaceous fluid contents. Flow-related artifacts within a cyst can also be useful for distinguishing its fluid nature. Distinction of the solid componentsof these tumors is facilitated by administration of gadolinium-DTPA, the effect of which is equivalent to the iodinated contrast used for CT (Fig 11 A and B).
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Fig 11. Solid astrocytoma. (A and B) Axial short TR/TE images precontrast and postcontrast. Before contrast, a poorly-defined region of low-signal intensity associated with mass effect is seen in the vermis and right cerebellar hemisphere; the fourth ventricle is compressed and displaced. After contrast, the entire margin of this solid tumor enhances, distinguishing it from surrounding edema.
Ependymoma
Ependymomas comprise 9% to 16% of all primary central nervous system tumors in children and, although they may occur at any level of the central neuraxis, the majority (60% to 70%) are infratentorial in location.25-27There are approximately two age peaksfor this posterior fossa neoplasm,one in young children (over 50% occur in children less than 5 years of age) and one in adults (30 to 40 years of age).26,28 These tumors are believed to arise from the ependymal lining of the fourth ventricle (the floor more commonly than the roof) or from cell rests that, in the posterior fossa, can be located adjacent to the foraminae of Luschka, near the ventricular outlets or along the tela choroidea.*’ A rare embryonal variant, the ependymoblastoma occurs in children and has a marked predilection for subarachnoid dissemination.*’ However, ependymomasare also classified into benign or differentiated and malignant or anaplastic types.25-32 Calcification, mitoses, endothelial proliferation, and hypervascularity are histologic
features that have been negatively associated with prognosis. There is somecontradictory data regarding histologic variation and survival in children who have these tumors. Kricheff et al found no correlation between histology and prognosis.3oOthers have noted a striking difference in survival between differentiated and anaplastic ependymomas,60% to 70% versus 10%to 30%, respectively.33 In his series of 360 cases, Gilles3* observeda paradoxically worse prognosis in children who had a more benign histology. This was considered likely to be attributable to these tumors’ pattern of growth. That is, it is known that the degree of surgical resection of thesetumors correlates with survival. Despite the fact that it appears that the majority of the infratentorial neoplasms are histologically benign (in contrast to the supratentorial neoplasms), tumors in this location frequently have extensive extramedullary growth that compromises their resectability. Macroscopically, the tumors, which may be soft and papillary or firm with gritty areas of
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calcification, typically project into the fourth ventricle, occluding its lumen.25~27They may protrude into the foramen of Luschka, out into the cerebellopontine angle, or into the cisterna magna and insinuate through the foramen magnum to surround the medulla and upper cervical cord. Commonly, they infiltrate along the floor of the fourth ventricle into the brainstem. Becauseof the exophytic and infiltrative growth patterns of these tumors, symptoms are usually less than a few months in duration at the time of diagnosis. As in the casesof the PNET-MB and cerebellar astrocytoma, nonspecific signs related to increased intracranial pressure, as well as more specific signs related to cerebellar dysfunction, are common. Other signs referable to tumor extension around the brainstem and through the foramen magnum, such as cranial nerve palsies, torticollis, and nuchal rigidity, may also be present.26*29 All patients undergo surgical resection/debulking and radiation therapy. Controversy exists regarding the appropriate radiation treatment volume. This relates to the issue of the difference in frequency of tumor dissemination at the time of diagnosis between the benign and malignant casesof infratentorial ependymoma. Thus, while craniospinal irradiation is indicated for all malignant ependymomas, it is variably provided in benign cases.26’33 The CT appearance of this posterior fossa neoplasm is the least distinctive of the three that have been described. That is, the tumor may appear isodense, hyperdense, hypodense, or of After contrast injection, it mixed density.26V28*29 may patchily or homogeneously enhance or fail to enhance at all. Ependymomas may occasionally mimic the classic appearance of the PNETMB-a hyperdense, well-marginated midline masswith homogeneousenhancement. However, in the series of posterior fossa ependymomas of Swartz et a129and that of Zee et a1,2812 out of 15 and sevenout of 10 cases,respectively, appeared as (predominantly) isodense masseson precontrast CT scans, unlike the usual PNET-MB or astrocytoma, so that this appearsto be a diagnostically useful appearance, when present. Ependymomas may exhibit regions of cyst formation, though this appears to occur more commonly in those tumors in a supratentorial location. Though not common (- lo%), intratumoral hemorrhage
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is a more likely occurrence in these tumors than in the PNET-MB or astrocytoma. Approximately 50% Contain foci of calcification, generally in the form of small nodular deposits. This has been suggested28to be the single most significant finding for diagnosing an ependymoma. Calcification in the PNET-MB is statistically less common (-15%), but the incidence of this tumor is appreciably greater than the ependymoma, so that the presence of calcification may be a useful sign but should be weighed in the context of the overall appearance of the mass (Fig 2 A and B). Of note, however, is the fact that the tendency of the ependymomasto calcify may actually be problematic in the posttreatment evaluation of patients being followed for tumor recurrence, since tumoral calcification and dystrophic calcification in adjacent tissues may be indistinguishable.29 The inability of MR to specifically detect calcification limits the diagnostic usefulness of MR regarding this histologic feature. By signal intensity characteristics, this tumor is somewhat nondistinctive. It is usually heterogeneousdue to the presenceof foci of hemorrhage, calcification, small cystic areas, and blood vessels (Fig 12). The greater contrast resolution and the multiplanar capability of MR define the extent of the tumor clearly, and it is the tumor’s morphology that appears most useful for diagnosis. That is, the “melted wax” appearanceof a massinsinuating along the margins of the fourth ventricle, extending into and expanding adjacent cerebrospinal fluid spaces, and enveloping the brainstem with only moderate mass effect is characteristic of ependymoma (Fig 13 A and B). PNET-MB can mimic this appearance, but uncommonly. DIFFERENTIAL DIAGNOSTIC CONSIDERATIONS
When a mass lesion is identified in the posterior fossa of a child, the three aforementioned neoplasms are primary considerations. Tumors of less common histology can arise and enter into the differential diagnosis. For example, another glial tumor, the oligodendroglioma, may arise in the cerebellum. Though oligodendrogliomas (anywhere in the CNS) are generally regarded as unusual in childhood, in one small series,34a biphasic age distribution
274
Fig 12. Epandymoma. Long TR/short TE image shows heterogeneous signal intensity arising from amorphous mass (arrowheads), expanding fourth ventricle and left foraman of Luschka. Note multiple prominent flow voids (arrows) in this hyparvascular mass.
with a small peak between 6 and 12 years and a large peak between 25 and 50 years was noted. Little information is present in the literature regarding the natural history of these tumors in childhood. Four casesof oligodendrogliomas (all
DEBRA A. GUSNARD
histologically malignant) of the cerebellar region were observed at the Children’s Hospital of Philadelphia between 1975 and 1982.35Radiographically, they appeared as large, solid, homogeneousmassesof variable density (hypodenseto hyperdense) and demonstrated variable contrast enhancement, which involved either cerebellar hemisphere or vermis. Three had appearances indistinguishable from the solid form of the cerebellar astrocytoma. These tumors may be superficially located, as in the case of a 3-yearold patient reported by Rubenstein in whom the tumor was seen to infiltrate the leptomeninges and erode the overlying bone.36 Anatomic relationships can influence the differential diagnosis. Because of the close proximity of structures at the tentorial hiatus, the epicenter of a mass lesion crossing the hiatus is frequently difficult to discern. For example, a superior vermian mass, such as a PNET-MB extending upward, may in some casesbe difficult to distinguish from a pineal mass, such as a pineoblastoma extending downward. Contrast enhancement is an important part of the cross-sectional imaging evaluation of cystic (mass) lesions in the posterior fossa, since it will aid in confirming distinction between the cystic astrocytoma and other cystic lesions with no enhancing components, such as arachnoid cysts and the trapped fourth ventricle.
Fig 13. Epandymoma. (A) Sagittal short TR/TE image. Lobulated mass (arrowheads) occupies fourth ventricle. hugs posterior aspect of brain stem, and insinuates inferiorly and posteriorly into upper cervical spinal canal and cisterna magna. (6) Coronal long TR/short TE image in another patient. Lobulatad mass envelopes left side of brain stem. Note the more “plastic” extension and lesser mass effect associated with this neoplasm as compared with the more discrete and bulky mass in Fig 4.
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275
In the differential of enhancing lesions along the margins of the fourth ventricle are vascular malformations and the choroid plexus papilloma (CPP) (Fig 14). The latter most frequently occur in the bodies of the lateral ventricles in neonates; rarely, they may be discovered in the fourth ventricle in older children and adolescents.37 Inflammatory lesions, such as abscesses,may occur in the cerebellum and occasionally mimic a cystic/necrotic neoplasm, though the amount of associated vasogenic edema is generally greater than that seen with cerebellar astrocytomas. Mass effect may be present in the absence of a true mass lesion, as in casesof basilar meningitis associated with marked extraaxial enhancement (similar to that seen with subarachnoid dissemination of tumor), effacement of CSF spaces,and hydrocephalus. In the context of patients who have known posterior fossa neoplasms, a particularly vexing and crucial diagnostic dilemma may arise in the follow-up of those patients who have undergone radiation therapy. Not infrequently, nonenhancing abnormalities consequent to radiation vasculitis are noted to develop within the white matter
Fig 14. Choroid plexus pspilloma. (A and 6) Sagittal male demonstrate a small wall-defined homogeneously ventricle in the expected location of the choroid plexus.
included in the radiation portal, Of more concern, however, is the occasional development of enhancing lesions with masseffect that represent the effects of radiation necrosis. These typically arise more than a year after radiation treatment and may be indistinguishable from a recurrent tumor.38-40Biopsy may be required for distinction. Unlike the situation in adults, extraaxial neoplasms in the posterior fossa of children are relatively rare. Two of those that occur more frequently, however, are the epidermoid and dermoid tumors. These are believed to represent cell rests consequent to incomplete disjunction of neuroectoderm from cutaneous ectoderm (epidermoid) or from cutaneous ectoderm and mesoderm (dermoid) at the time of neural tube closure. Epidermoids of the posterior fossa are most commonly located in the cerebellopontine angle; generally, they appear as lobulated lowdensity masseson CT that do not enhance after contrast. On MB, they typically follow the signal intensity of CSF and, as a consequence, may actually be difficult to perceive except by the fact of their interface with and mass effect upon
short TR/TE images pracontrast and postcontrast in this g-year-old enhancing soft tissue mass (arrow) along the roof of the fourth
276
Dermoid. Axial short TR/TE image shows a Fig 15. midline mass of high signal intensity compatible with fatty tissue in the region of the cerebellar vermis.
adjacent brainstem and/or cerebellar hemisphere. Occasionally, they manifest high-signal intensity on short TR/TE images, making the distinction between them and dermoids more difficult. Dermoids are generally midline lesions, either in the fourth ventricle or along the vermis (Fig 15), which have density and signal intensity characteristics of fat on CT and MR. Neuroblastoma, a relatively common malignancy of childhood, frequently metastasizes to Table
1. Differential
Diagnosis
of Pediatric
Posterior
Astrocytoma Density (CT), TSI (MR T2WI) Density (CT), TSO to lSl (Ml3 T2WI) Calcification No enhancement Homogeneous enhancement Inhomogeneous enhancement Peritumoral edema Solid Cystic Midline (vermis fourth ventricle) Midline (extraaxial) Lateral (hemisphere) Extension thru outlets of fourth ventricle, foramen magnum
+++ + Occas ++ ++ + ++ +++ ++
++ -
Fig 16. Metaatatic nauroblastoma. Axial long TR/short TE image demonstrates soft tissue mass (arrows) in the expected location of the torcula. Mass is clearly separate from adjacent inferior vermis (arrowhead) and cerebellar hemispheres.
the calvarium. Bony destruction is often associated with an epidural soft tissue mass.One of the more common locations for this to occur is in the region of the torcula Herophili (Fig 16), where involvement can be associatedwith impedance of venousoutflow and the development of communicating hydrocephalus. In conclusion, for the radiographic differential diagnosis of posterior fossaneoplasmsin children Fossa Neoplasms-Radiographic MB-PNET
Ependymona
+ ++ + Rare
++ + +++ + + +++ occas ++ ++ +++ -
+++ + ++ +++ Rare +++ + Rare
++
Characteristics Other Teratoma CPP, vast malf Dermoid, neuroblastoma -
NOTE. Plus and minus signs refer to the degree of the tumor, minus meaning that it does not have that characteristic. Abbreviations: CPP, choroid plexus papilloma; vast malf, vascular malformation.
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277
IN CHILDREN
(Table I), there are a number of considerations when a masslesion is evident involving either the fourth ventricle or cerebellum. Attention to imaging details and an awareness of the diverse
manifestations and clinical characteristics of the pathologic processesthat can occur there, however, permits significant diagnostic accuracy and communication of clinically useful information.
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