Medulloblastoma

John P. Christodouleas and Ori Shokek

Background

Estimate the annual incidence of medulloblastoma (MB) in the U.S. What is its frequency relative to other CNS tumors in children?

~400 cases/yr of MB in the U.S. It is the 2^nd most common pediatric CNS tumor (20% of cases; #1 is low-grade glioma at 35%–50%).

What is the median age of MB at Dx?

MB has a bimodal age distribution, with a median age of ~7 yrs in children and 25 yrs in adults.

Is there a gender predilction to MB?

Yes. Males are more commonly affected than females (2:1).

What is the cell of origin?

Neuroectodermal cells from the sup medullary velum (germinal matrix of cerebellum) or cerebellar vermis

MB is a subtype of what class of tumors?

MB is a subtype of embryonal tumors (along with PNET and atypical teratoid rhabdoid tumor/ATRT).

What % of pts present with CSF spread at Dx?

30%–40% of MB cases present with CSF spread at Dx.

For what MB age group is CSF spread more common?

This is more common in younger pts.

Does extra-axial spread occur in MB? If so, where?

Extra-axial spread is rare, but when it does occur it is typically to bone.

What are the characteristic histologic features and markers for MB?

MB appears as small round blue cells. 40% have Homer-Wright rosettes, and most stain + for neuron-specific enolase, synaptophysin, and nestin.

What are some other types of small round blue cell tumors?

Other small round blue cell tumors:

Lymphoma
Ewing
Acute lymphoblastic leukemia
Rhabdomyosarcoma
Neuroblastoma
Neuroepithelioma
Medulloblastoma
Retinoblastoma

(Mnemonic: LEARN NMR)

What are the 3 histologic variants of MB?

Histologic variants of MB:

Classic
Nodular/Desmoplastic
Large cell/Anaplastic

The desmoplastic histologic variant of MB is associated with what clinical features?

The desmoplastic variant is associated with:

LOH 9q
Older age at Dx
Better prognosis

What is the most aggressive histologic variant that also has a particularly high rate of CSF dissemination?

Large cell/Anaplastic is the most aggressive MB variant.

What % of MBs are familial, and what are some associated genetic syndromes?

5% of MBs are familial. Associated genetic syndomes include Gorlin (PTCH mutation) and Turcot (APC mutation).

What are common cytogenetic abnormalities in MB?

Common cytogenetic abnormalities in MB:

Deletion of 17p (40%–50%)
Isochromosome 17q
Deletion of 16q

Where does MB most commonly arise?

Midline cerebellar vermis (75%), with the rest in cerebellar hemispheres

What is the DDx for a posterior fossa (PF) mass?

DDx for a PF mass:

MB
Ependymoma
Astrocytoma
Brainstem glioma
Juvenile pilocytic astrocytoma
Hemangioblastoma
Mets

Workup/Staging

What are some common presenting Sx for MB?

HA, n/v, altered mentation due to hydrocephalus, truncal ataxia, head bob, and diplopia (CN VI)

To what are common presenting Sx due in MB?

Obstructive hydrocephalus/↑ICP (HA and vomiting)

What is the “setting-sun” sign?

Downward deviation of gaze from ↑ICP (CNs III, IV, and VI)

List the general workup for a PF mass at presentation.

PF mass workup: H&P (funduscopic exam, CN exam), CBC/CMP, MRI brain/spine, CSF cytology (may not be possible due to herniation risk), and baseline ancillary tests

Is a tumor Bx necessary for Dx? Is a BM Bx necessary?

Per current COG MB protocol ACNS0331, a tumor Bx is unnecessary; pts often go straight to surgery. BM Bx is not part of the standard workup.

Is there any risk of CSF dissemination with shunt placement for MB?

No. There is no risk of CSF dissemination.

What are some important ancillary tests to obtain prior to starting Tx?

Baseline audiometry, IQ testing, TSH, and growth measures

What tests should be obtained on days 10–14 postop?

MRI spine, CSF cytology. (Delay to day 10 to avoid a false+ result from surgical debris.)

When is MRI of the brain done? Of the spine?

MRI brain: preop and 24–48 hrs postop
MRI spine: preop or 10–14 days postop

What can be done before Tx to reduce ICP?

Ventricular shunt/drain, steroids, acetazolamide (Diamox)

Is there a risk of CSF dissemination with shunt placement?

No. There is no risk of CSF dissemination with shunt placement.

List the T staging according to the modified Chang staging system for MB.

T1: ≤3 cm, confined
T2: >3 cm, partial fill of 4^th ventricle, invades 1 adjacent structure
T3a: invades 2 adjacent structures, complete fill of 4th ventricle
T3b: extends into brain stem, arises from floor of 4^th ventricle, complete fill of 4^th ventricle
T4: extends beyond aqueduct of Sylvius or foramen magnum to involve 3^rd ventricle/midbrain/upper cervical cord