- Author: George I Jallo, MD; Chief Editor: Amy Kao, MD more...
No specific biochemical test exists for the presence of medulloblastoma, although several molecular studies have revealed that histologically identical medulloblastomas are composed of distinct subgroups with different prognosis. The expression of ErbB2 has been shown to be a negative predictor of outcome. Conversely, expression of TrkC or neurotophin-3 receptor is associated with a favorable outcome. However, these markers are not standard testing at this time.
Molecular markers such as chromosome 10q and chromosome 17 statuses can be used for molecular risk stratification of adult medulloblastoma, but only in a subgroup-specific context
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- Computed tomographic scan
- Because most patients present with headache, a noncontrast head CT scan usually is performed because of its easy availability. These tumors typically are located midline in the cerebellum and extend into and fill the fourth ventricle.
- Prior to administration of intravenous (IV) contrast, the tumor is hyperdense to the brain as a result of its high cellularity as shown below. Preoperatively, high density on CT scan can help distinguish medulloblastoma from the hypodense appearance of a cerebellar astrocytoma. Medulloblastoma shows marked contrast enhancement. Surrounding hypodensity is indicative of vasogenic edema. Owing to compression of the fourth ventricle and outflow of CSF, marked hydrocephalus is the rule.
- Ependymoma is another hyperdense tumor that affects the posterior fossa of children. Unlike medulloblastoma, however, it often contains calcifications that can be recognized easily on CT scan. Choroid plexus papilloma usually arises in the trigone of the lateral ventricle in children; however, in adults it is most common in the fourth ventricle. Similar to ependymoma, choroid plexus papilloma commonly contains calcifications.
- Magnetic resonance imaging
- MRI with the administration of gadolinium DTPA is the diagnostic test of choice for medulloblastoma. Unlike CT scan, MRI can obtain multiplanar views without significant bony artifact in the posterior fossa.
- Nevertheless, with any increased intracranial pressure, MRI of children must be considered carefully. Younger children usually require sedation for this study. Without careful monitoring, cerebral carbon dioxide levels may increase, further aggravating intracranial hypertension.
- Tumor appears hypointense on pre-gadolinium T1-weighted images, usually seen expanding the fourth ventricle from its origin in the cerebellar vermis as depicted in the following images. Brain stem is compressed and shifted ventrally. T1-weighted sagittal MRI of an 8-year-old boy who presented with nausea and vomiting reveals an enhancing tumor within the fourth ventricle. The child underwent a suboccipital craniotomy and resection of his medulloblastoma.T1-weighted sagittal MRI of 4-year-old boy who presented with gait ataxia and precocious puberty. MRI shows a heterogenous enhancing tumor located within the fourth ventricle with marked hydrocephalus.T1-weighted axial MRI shows heterogeneous enhancement of the medulloblastoma in a 4-year-old boy who presented with gait ataxia and precocious puberty.
- Upon administration of gadolinium in children, homogeneous enhancement commonly occurs, whereas in adults, a more heterogeneous pattern usually is seen. Proton density and T2-weighted imaging displays a hyperintense mass with a surrounding area of edema.
- If the tumor extends upward into the cerebral aqueduct and third ventricle, marked hydrocephalus with transependymal reabsorption of CSF may occur. Extension also can be inferior into the cervical canal.
- Occasional areas of hemorrhage or cyst can be distinguished. Because calcifications are very rare, any area of signal loss must be considered a vascular flow void.
- MRI can help differentiate medulloblastoma from ependymoma: the latter extends further into the lateral recess of the fourth ventricle or even further into the cerebellopontine angle.
- MRI also can help distinguish between medulloblastoma and exophytic brainstem glioma (the latter having a broader attachment to the floor of the fourth ventricle).
- Adults, more frequently than children, can have the desmoplastic variant of medulloblastoma. This form of the tumor is situated laterally in the hemisphere with indistinct borders and small cystic or necrotic areas.
- Besides identifying the primary lesion, MRI is beneficial in detecting metastatic lesions. To rule out drop metastases, MRI of the spine is obligatory when medulloblastoma is either considered or diagnosed.
- Imaging of the spine is best performed prior to surgery in order to avoid postoperative artifacts, which may be interpreted as tumor metastasis. Metastases can occur in the basal cisterns. Both recurrent lesions and metastases show sparse enhancement.
- In the past, myelography was the standard diagnostic test for medulloblastoma metastases to the spine.
- Today, when MRI is contraindicated, myelography is utilized, accompanied by CT scan.
- Skeletal imaging
- Metastasis to the bone must be considered in any child with medulloblastoma and bone pain.
- A skeletal survey helps elucidate lytic or sclerotic lesions.
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- Cerebrospinal fluid
- Cytology of CSF is important for the staging of medulloblastoma; however, no standardized method has been agreed upon for how and when to obtain CSF.
- Lumbar puncture is the most common method for obtaining CSF; however, this can precipitate cerebellar tonsillar herniation (coning) in a patient with increased intracranial pressure.
- Although safer, lumbar puncture performed shortly after surgery can have misleading results; the fluid may contain clinically insignificant cells that have been disturbed during surgery. This may be performed 2 weeks following surgery.
- If a ventricular drain is placed, it can be used to obtain CSF for cytologic testing; however, ventricular samples of CSF will contain malignant cells less commonly than a sample obtained from the thecal sac.
- Some authors suggest obtaining CSF at the time of surgery from the cisterna magna for cytologic analysis.
- Tumor genetics
- To date, use of cytogenetic studies has been controversial.
- Some original reports found a correlation between aneuploid DNA content and a better prognosis. Interestingly, DNA content of most medulloblastoma cells is diploid, signifying a poorer outcome. More recent studies, however, have failed to reproduce this relationship between ploidy and outcome.
- The most common genetic abnormality found in medulloblastoma, 17qi, is an isochromosome on the long arm of chromosome 17. Found in one third to two thirds of medulloblastomas, it is common in other tumors, including leukemias.
- Accompanying the isochromosome 17qi is the loss of genetic material from the short arm of chromosome 17, where the tumor-suppressor gene p53 is located.
- Studies have shown that loss or damage to the p53 site is rare in medulloblastoma. Theories now implicate another focus on the short arm of chromosome 17, which is either a tumor-suppressor gene in itself or a modulator for the function of p53.
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- Lumbar puncture: To obtain CSF, a lumbar puncture may be necessary. Consider this very carefully since obstructive hydrocephalus, common in medulloblastoma, is an absolute contraindication.
- Ventriculostomy: If the patient is symptomatic from obstructive hydrocephalus, placement of an external ventricular drain may be a lifesaving procedure. Some centers also advocate an endoscopic third ventriculostomy to bypass the obstruction. This may also obviate the need for a shunt in the future following surgical removal of the tumor.
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- Upon gross examination, medulloblastoma appears as a pinkish-gray mass usually arising from the cerebellar vermis in children. Cysts, areas of necrosis, or calcification are rare.
- On microscopic examination, cells are small and poorly differentiated, with scant cytoplasm and little stroma (see the image below). A high mitotic index is common. Classic Homer-Wright rosettes can be seen in one fifth of cases. Elongated cells surrounding eosinophilic circular zones devoid of lamina and blood vessels form these pseudorosettes. Differentiation can be seen along astrocytic, neuronal, ependymal, or even mesenchymal lines.
- Rorke classified this tumor with other primitive neuroectodermal tumors, which include pineoblastoma, ependymoblastoma, retinoblastoma, central neuroblastoma, and peripheral neuroblastoma. This classification system is not accepted universally.
- Desmoplastic medulloblastoma is a variant more often seen in adults and more common in the cerebellar hemisphere. In addition to containing all microscopic characteristics of childhood medulloblastoma, the desmoplastic type contains a dense reticulin network; cells are arranged in a biphasic pattern with areas of high and low cellularity. Cells in this variant may assemble along reticulin fibers.
- Histologic subtypes
- Three other histologic subtypes exist: Medullomyoblastoma, melanotic medulloblastoma, and large cell medulloblastoma.
- Medullomyoblastoma: Striated and smooth muscle cells are the hallmark of medullomyoblastoma. The tumor can contain cells that show elements of neuronal and glial differentiation. If the presumptive medullomyoblastoma contains elements of ectodermal, mesodermal, and endodermal differentiation, the tumor must be considered a teratoma.
- Melanotic medulloblastoma: Small, undifferentiated cells containing melanin are characteristic of the very rare melanotic medulloblastoma.
- Large-cell medulloblastoma: This subtype has large vesicular nuclei with prominent nucleoli. Cells of the large-cell medulloblastoma are remarkable in their immunoreactivity for synaptophysin. This particular tumor is associated with a poorer clinical outcome.
- Although large-cell medulloblastoma is associated with a more aggressive course, medullomyoblastoma has a clinical course similar to that of ordinary medulloblastoma. However, the desmoplastic variant has a more favorable outcome.
- Three other histologic subtypes exist: Medullomyoblastoma, melanotic medulloblastoma, and large cell medulloblastoma.
- Aside from these findings, associating histologic findings with outcome has been very difficult. As in other tumors, vascularity and endothelial hyperplasia do not seem to influence recurrence rates. In some studies, however, the presence of necrosis (or a high mitotic index) has been associated with a shorter relapse-free interval.
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