Medulloblastoma

FACTS

#1 most common pediatric brain malignancy

WHO grade IV

embryonal tumor

typical location: cerebellum (in vermis near apex of roof of 4th ventricle) + dorsal brainstem

BOARDS: sonic hedgehog gene (SHH) mutations cause medulloblastoma (along with holoprosencephaly). Other frequently associated mutations are in the genes MYCN, CDK6, CTNNB1, and WNT.

CONSULT

HPI

usual presenting sx: HA, n/v, ataxia

infants: irritability, lethargy, macrocrania

Drop mets ROS: back pain, urinary retention, leg weakness

Associated with Fanconi Anemia

FOCUSED EXAM

truncal and appendicular ataxia

nystagmus

EOM palsies

head size (infants)

IMG

MRI Brain w/wo = enhancing midline in children (lateral in adults more likely), T2 = heterogenous (cysts, vessels, Ca2+)

MR spectrography: high Chol, low NAA

ependymomas vs. medulloblastomas

ependymoma = floor

medulloblastomas = roof

A/P
At the time of consult

MRI pan neuro axis w/wo to evaluate for drop mets

Optho c/s for papilledema

Neuro-oncology c/s

3 Pronged Approach to Treatment

Surgical debulking: better to reave last remnant in the brainstem

Radiation: exact fractions will vary based on risk stratification (molecular diagnosis)

Chemotherapy: options include cisplatin, lomustine, vincristine, cyclophosphamide, cyclophosphamide, etoposide, high dose IV MTX/intrathecal MTX Of mafosfamide or intraventricular methotrexate

LP post-op for CSF cytology

Counsel: this is a life changing diagnosis, careful and appropriate delivery to family is important.

post-op cerebellar mutism is a common complication in cerebellar tumors for children (up to 53% in medulloblastomas). Risk factors include midline location, brainstem involvement (Greenberg)

30-40% will require permanent VP shunt

there is a risk of tumor spread with surgery

long-term survivors have high risk of endocrine/cognitive sequalae from treatments

poor predictors of prognosis: younger age (<3 years), disseminated disease, inability to perform GTR, poor KPS

Classification

Histologic criteria

1. classic

2. desmoplastic / nodular (Nevoid Basal Cell Carcinoma, Gorlin Syndrome)

3. extensive nodularity

Molecular criteria

WNT-activated

SHH-activated (TP53 WT vs. mutant)

Pathology

Figure 1: Homer Wright rosettes (neuroblastoma, medulloblastomas, PNETs) = halos of cells surrounding a neuropil containing central region

Rosette	Description	Pathology
Homer-Wright	halo of tumor cells surrounding centril neuropoil	medullo, neuroblastoma, PNET
Flexner-Wintersteiner	tumor cells surrounding central lumen of cytoplasmic extensions	retinoblastoma
True Ependymal rosette	tumors surrounding empty lumen	Ependymoma (not seen in every case)
Perivascular pseudorosette	tumor cells around blood vessels	Ependymoma > medulloblastoma, PNET, neuroblastoma

Associations

Figure 1: Holoprosencephaly and medulloblastoma share a connection: both involve mutations in SHH gene