Overview Flashcards
Estimate the annual incidence of medulloblastoma (MB) in the United States. What is its frequency relative to other CNS tumors in children?
∼500 cases/yr of MB in the United States. It is the 2nd most common pediatric CNS tumor (20% of cases; #1 is low-grade glioma at 35%–50%). It is the most common malignant brain tumor in the PF in children and adolescents, comprising 40% of all PF tumors.
What is the median age of MB at Dx?
MB has a bimodal age distribution, with a median age of 7 yrs in children (peak incidence b/t 5 and 9 yrs) and 25 yrs in adults.
Is there a sex predilection 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 tumor (along with PNET and atypical teratoid rhabdoid tumor [ATRT]).
Mutation of which gene distinguishes ATRT from MB?
Loss of INI1 distinguishes ATRT from MB. INI1 is found on chromosome 22 and functions as a tumor suppressor gene.
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 NSE, synaptophysin, and nestin.
What are some other types of small round blue cell tumors?
Small round blue cell tumors of childhood:
Lymphoma
EWS
Acute lymphoblastic leukemia
RMS
NB
Neuroepithelioma
MB
Retinoblastoma
(Mnemonic: LEARN NMR)
What are the 3 histologic variants of MB?
Histologic variants of MB:
- Classic
- Nodular/Desmoplastic (better prognosis)
- Large cell/Anaplastic (worse prognosis)
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?
2%–5% of MBs are familial. Associated genetic syndromes include Gorlin syndrome (PTCH1 mutation, associated with nevoid basal cell carcinoma syndrome) and Turcot syndrome (APC mutation, associated with FAP).
What are the common cytogenetic abnormalities in MB?
Common cytogenetic abnormalities in MB include:
- Deletion of 17p (40%–50%)
- Isochromosome 17q
- Deletion of 16q
- LOH 9q (desmoplastic variant)
Where does MB most commonly arise?
Midline cerebellar vermis (75%), with the rest in cerebellar hemispheres.
What is the DDx for a PF mass?
DDx for a PF mass includes:
- MB
- Ependymoma
- ATRT
- Astrocytoma
- Brainstem glioma
- Juvenile pilocytic astrocytoma
- Hemangioblastoma
- Mets
What are the 4 genetic MB subgroups and what mutations tend to occur in each subgroup?
- Wingless homolog (WNT) group: CTNNB1 mutation. Associated with Turcot syndrome. Least common (10%) subgroup.
- Sonic hedgehog (SHH) group: PTCH1, GLI3, MYCN. 30% of MB, often desmoplastic. Overrepresented in infants and adults (bimodal).
- Group 3: MYC amplification, GABAergic expression. Enrich for large cell histology and are frequent mets at Dx. Worst prognosis.
- Group 4: MYCN, CDK6 amplification
(Northcott PA et al., JCO 2011)
Describe the prognosis for each subgroup.
Good prognosis: WNT group and infants in SHH group
Intermediate prognosis: Group 4 and SHH group
Poor prognosis: Group 3
What percentage of pediatric CNS tumors do medulloblastomas comprise?
What genetic syndromes are associated with this diagnosis?
20%. This makes it the second most common pediatric CNS tumor behind low-grade glioma (35%–50%). The United States incidence is 500 cases per year. Gorlin syndrome (nevoid basal cell carcinoma syndrome) and desmoplastic medulloblastoma are associated through the Sonic Hedgehog Pathway. Turcot syndrome, which is associated with the APC gene, is associated with medulloblastoma that develop via the WNT pathway. Li-Fraumeni syndrome, which results from p53 mutations, accounts for a small percentage of medulloblastoma.
What are poor prognostic factors for medulloblastoma?
Male gender, age less than 5 years, less than GTR, and M+ disease
