Medulloblastoma Workup

Updated: Jan 10, 2018
  • Author: George I Jallo, MD; Chief Editor: Amy Kao, MD  more...
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Laboratory Studies

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.

Table. (Open Table in a new window)


Age group

Molecular characteristics

Genetic mutations


Prognosis (10-year overall survival)

WNT activation

Found in children and adults (not infants)

WNT pathway activation


DDX3X Chromatin-remodeling genes


Least common



SHH activation

5–18 years old

SHH pathway activation


About 25% of the cases



All age groups

SHH pathway activation

Non TP53 (wild type):


(mainly adults)

(mainly infants)

TERT promoter Chromatin-remodeling genes

If no MYCN amplification and no metastatic disease – favorable

Group 3

Infants and children (more common in boys than in girls)

Elevated expression of MYC



SMARCA4 Chromatin-remodeling genes

Genes of TGF-β pathway

About 25% of the cases

If MYC amplification present – very poor prognosis

Metastatic disease – very poor prognosis

Group 4

More common in children (not infants) than in adults

Lmx1A expression

Chromatin-remodeling genes

Most common

If no metastatic disease and chromosome 11 loss – favorable


Imaging Studies

Computed tomographic (CT) scan

Because most patients present with headache, a noncontrast head CT scan usually is performed because of its 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 can be present.

CT scan demonstrates a hyperdense lesion within th CT scan demonstrates a hyperdense lesion within the posterior fossa of an 8-year-old boy who presented with nausea and vomiting.

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 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 pre 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 enhancem T1-weighted axial MRI shows heterogeneous enhancement of the medulloblastoma in a 4-year-old boy who presented with gait ataxia and precocious puberty.
Coronal MRI confirms the presence of the tumor wit Coronal MRI confirms the presence of the tumor within the fourth ventricle of 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 superiorly into the cerebral aqueduct and third ventricle, or inferiorly into the aqueduct of Sylvius or cisterna magna through the foramen of Magendie, marked hydrocephalus with transependymal reabsorption of CSF may occur. 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 with diffusion tensor imaging provides white matter tractography and can help distinguish between medulloblastoma and exophytic brainstem glioma. Studies have suggested tumor location and enhancement patterns can serve as a surrogate for genetic testing of the different medulloblastoma subtypes. [11] Others tried to look at the enhancement pattern by subgroups. Perreault et al. summarized in 2014 that tumor location and enhancement pattern were predictive of molecular subgroups of pediatric medulloblastoma and may potentially serve as a surrogate for genomic testing. [11] Some works suggested the utility of apparent diffusion coefficient in order to differentiate medulloblastoma from other posterior fossa tumors and the different subgroups. [12, 13] Yet, we still don’t have a reliable tool to differentiate preoperatively the different subtypes of medulloblastoma. 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 neuroaxis 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. Yet, if for any reason MRI is contraindicated, the surgeon usually will prepare for surgery by using CT scan with contrast without obtaining myelography.

Skeletal imaging

Metastasis to the bone must be considered in any child with medulloblastoma and bone pain. This is not a routine test. A skeletal survey helps elucidate lytic or sclerotic lesions.


This is a fairly new entity in neuroradiology, trying to diagnose specific tumors by special radiology features. Several studies have been published regarding the possible use of multiple MRI features that will lead to pre-surgical diagnosis of medulloblastoma and the different subtypes. Historically, several attempts have been made to define the different histological subtypes by their anatomical location (medial, cerebellopontine, and hemispheric lesions). However, attempts to use location criteria as biomarkers for differentiation of genetic medulloblastoma entities have yielded only inconsistent results. [14]  There were some groups trying to define certain imaging features that can assist in pre-operative diagnosis of medulloblastoma subtypes. For example, Kelli et al. [14] found that hemorrhage was related to group 4 medulloblastomas, yet other groups found hemorrhage to be related to WNT-activated medulloblastomas as well. [15]  


Other Tests

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

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.

In recent years, with the finding of the main 4 subtypes, different studies described the genetic mutations relating to each group [16] :

  • WNT activation: These tumors almost uniformly have oncogenic mutations of catenin beta-1 ( CTNNB1), the protooncogene that encodes β-catenin. Their expression shows adherence to multipotential progenitor cells of the lower rhombic lip. [17] CTNNB1 mutations are found in approximately 90% of WNT medulloblastomas, and nuclear accumulation of β-catenin is a biomarker for WNT pathway activation. Other important mutations in this group include SMARCA4, Monosomy 6, which can be found in 80–85% of WNT medulloblastomas (without harboring telomerase reverse transcriptase [TERT] mutations), DEAD-box helicase 3 (DDX3X) mutations are found in 50% of WNT tumors, TERT mutations are found in 31% of WNT tumors. [18] Although tumor suppressor protein p53 (TP53) mutations can be found in 15% of the tunors in these group, it has no relevance in terms of prognosis. [19]
  • SHH activation: This subgroup is further subdivided by presence of TP53 mutation and by age groups. For infants (0–4 years) the SUFU mutations are more common than other age groups, and 42% of the infant samples have PTCH1 alterations. For children (4–17 years), there is a higher incidence of MYCN and GLI2 amplifcations that usually predict less favorable prognosis. In this subgroup, 36% pf the patients have PTCH1 alterations. [20, 21] For the adult population, the SMO mutations are more common (which allow for possible treatment options), and 54% of the adult samples have PTCH1 alterations. As a group, as long there are no PTEN or GNAS alteration, the prognosis tend to be good. [22] For the patients that harbor TP53 mutation (13% of SHH medulloblastomas), there is a need to search for germline mutations (like Li-Fraumeni syndrome). [23, 20] The prognosis in this group (SHH TP53 mutation positive) is very poor across all age groups.  
  • Non-WNT/non-SHH ( group 3): This group is known to generally have poor prognosis. Either the presence of MYC over-expression (~17% of cases), or the presence of Isochromosome 17q are a bad prognostic factors. [24] Other genes that have mutation in this subgroup are related chromatin remodeling and appear in almost 30% of the cases. [25] An important overexpression in this group includes GABRA5, which serves now as a potential treatment aim in this group. [26, 27]
  • Non-WNT/non-SHH: group 4: This is the most common group with relatively good prognosis. The homeobox transcription factor Lmx1A has been identifed as an very important regulator transcription factor of group 4 medulloblastomas. [28] Lmx1A is important in the normal development of cells in the upper rhombic lip and cerebellum, and it is also critical for the development of midbrain dopaminergic neurons, [28, 27]  which are thought to be where group 4 tumors originate. [16] The most common chromosomal aberration found in this sub-group of medulloblastoma is isochromosome 17q. Bad prognostic factors, such as chromosome 11 loss and chromosome 17 gain can be also found in this subgroup. [24] In addition, copy number changes in target genes that are important in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ) signaling pathway are found in this subgroup. [16]  


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.

CSF diversion

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 (ETV) with or without choroid plexus cauterization to bypass the obstruction. This may also obviate the need for a shunt in the future following surgical removal of the tumor. Yet, the incidence of urgent CSF diversion is not high. Schneider et al., published in 2015 that the overall rate of CSF diversion surgery for SHH, Group 3, and Group 4 medulloblastomas was around 30% in their series, but no patients with a WNT medulloblastoma required shunting. The low incidence of hydrocephalus in patients with WNT medulloblastoma likely reflects both host factors (age) and disease factors (lack of metastases). They speculated that the absence of hydrocephalus in patients with WNT medulloblastomas likely contributes to their excellent rate of survival and may also contribute to a higher quality of life than for patients in other subgroups. [29] Most neurosurgeons try not to do a definite CSF diversion (i.e., ETV or VP shunt), and advocate temporary diversion like external drain if needed and resection of the tumor that will alleviate the obstruction.


Histologic Findings

Upon gross pathology, medulloblastoma appears as a poorly demarcated pink-purple-gray friable mass usually arising from the cerebellar vermis in children. Areas of necrosis may be seen, however, cysts or calcifications are rare.

Desmoplastic variants may be more firm. 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.

High-power magnification hematoxylin and eosin (H& High-power magnification hematoxylin and eosin (H&E) section of a typical medulloblastoma

Rorke classified this tumor with other primitive neuroectodermal tumors, which include pineoblastoma, ependymoblastoma, retinoblastoma, central neuroblastoma, and peripheral neuroblastoma [30] . 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 this 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. 

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.