Medulloblastoma in

children 201
18/10/59
Paul N. Kongkham
Cynthia Hawkins
James T. Rutka
Outlin
e
• Epidemiology
• Genetics
• Pathology
• Clinical finding
• Diagnostic imaging
• Staging and prognostic factors
• Treatment
• Surveillance imaging and disease recurrence
Epidemiolog
y
• The most common malignant pediatric posterior fossa tumor
• Median age 6 to 9 years(during first decade)
• Can occur in adulthood
• Midline cerebellum, in the region of the mid and inferior vermis
• May spread along the cerebellar peduncles and extend upward
through the tentorial hiatus or downward into the cervical spinal
canal
• All patient must be evaluated for “drop mets”
Genetics
• Granule cell precursor (GCP) cell
Familial cancer
syndromes
Gorlin’s syndrome Turcot’s syndrome
• AD • heritable disorder
• PTCH1 gene • adenomatous polyposis coli (APC)
• multiple cutaneous basal cell gene
carcinomas • multiple colorectal neoplasm
• 5% • central nervous system tumors(GBM,
AA, MB, pineoblastoma,
ganglioglioma, ependymoma)
Familial cancer
syndromes
• Li-Fraumeni syndrome
• mutations of the p53 tumor suppressor gene
• Rubenstein-Taybi
• Aicardi’s syndrome
Molecular
biology
•Non-random chromosomal abnormalities
• consistent deletion of 17p markers

• Information from gene profiling

• ZIC and NSCL1

• Abnormalities in signal transduction pathways

• neurotrophin signaling pathway (important in cerebellar development) or
Sonic hedgehog (Shh)
Patholog
y
• All MB are WHO grade IV

• Gross
• pinkish gray to purple mass, commonly arising from the medullary velum
• most of its blood supply from the posterior inferior cerebellar artery
• firm, discrete
• “sugar-coated” appearance of the cerebellar surface
Patholog
y
• 1.classic (90%)
• small, densely packed undifferentiated cells with hyperchromatic nuclei,
scant cytoplasm
• inconstant cell clusters in Homer-Wright rosettes
• sometimes called “blue tumor” (monotonous appearance)

• 2. Desmoplastic (6%)
• similar to classic type with “glomeruli” AKA pale islands (collagen bundles
and scattered, less cellular areas)
• Marked tendency for neuronal differentiation
• More common in adults
• Prognosis controversi11al: may be the same or less aggressive than
Patholog
y
• 3. large cell (4%)
• large, round, and/or pleomorphic nucleoli, higher mitotic activity
• In the few case reports, all were male
• More aggressive than classic
• Resembles atypical teratoid/rhabdoid tumors of cerebellum , but has
different phenotype and cytogenic features
 H&E : 200x H&E : 100x
Desmoplastic MB

Desmoplastic MB
Reticulin stain

H&E : 400x H&E : 400x

Anaplastic MB Large-cell MB
nuclear pleomorphism, large nuclei with
nuclear molding, prominent nucleoli
cell-cell wrapping nuclear molding
high mitotic index abundant
cytoplasm
Clinical
finding
• Most common triad : headache, lethargy, and vomiting
• Short clinical history : 1.5 Mo, 3 Mo
• Infants and young children
• irritability, loss of appetite, weight loss, and failure to thrive
• increased intracranial pressure, including lethargy, drowsiness, vomiting,
sunsetting, a full fontanelle, or an increasing head circumference
• Older children
• headache, neck stiffness, dizziness, or diplopia
Clinical
finding
• Neurological examination
• truncal or appendicular ataxia, dysmetria, nystagmus, or cranial nerve palsies
• A head tilt, signifying descent of the cerebellar tonsils into the foramen
magnum with compression of the C1 or C2 nerve roots
• Not specific
• Ddx : other posterior fossa lesions such as astrocytoma, ependymoma, or
cystic mass lesions
Diagnostic
imaging
• CT
• Non-contrast : homogeneous hyperdense midline mass within the posterior
fossa
• Contrast : homogeneous enhancement
• Peritumoral edema and hydrocephalus
• Minimal : Calcification, necrosis, cystic degeneration, and hemorrhage
Diagnostic
imaging
• MRI
• Brain and spine
• Early post operative MRI : residual tumor
• T1 : hypointense to isointense
• T2 : isointense to hyperintense
• T1 c Gd : typically robust but may appear homogeneous or slightly
heterogeneous
• DWI : restricted diffusion
Chang
Classification
 Prognosi
• Average-risk patients s
• Children 3 years and older
• Without evidence of gross or microscopic metastatic disease at diagnosis
• And with less than 1.5 cm2 of residual tumor after surgical resection
• High-risk patients
• younger than 3 years or any patient
• With evidence of metastatic tumor spread
• Or significant residual tumor (>1.5 cm2) after surgery
Treatment
• Surgery
• Radiation
• Chemotherapy
Surger
y
• Goal
• obtaining a tissue diagnosis
• achieving maximal safe tumor resection
• relieving critical structures from mass effect
• addressing any associated hydrocephalus
Symptomatic hydrocephalus
• Decision must be made whether to treat the hydrocephalus
beforehand or at the time of tumor resection
• Temporary CSF diversion : external ventricular drain (EVD), diversion
through a ventriculoperitoneal shunt (VPS), diversion via endoscopic
third ventriculostomy (ETV)
• 10-40% require permanent CSF diversion after resection of the
tumor
• Factor
• more severe hydrocephalus at diagnosis
• younger patient age
• larger preoperative tumor size
Surger
y
• Midline suboccipital approach
• Inferior telovelar approach
• If an EVD was placed : gradual weaning
• MRI is performed within 48 hours postoperatively : Significant
residual tumor (>1.5 cm2) should prompt consideration of early
repeat resection
• Unless the procedure was stopped early because of problems with
hemostasis or invasion of tumor into critical structures
Postoperative complications
• Cranial nerve palsies, ataxia, dysmetria, or bulbar symptoms : If
potential for recovery, it typically occurs within 6 months after
surgery
• Infection, aseptic meningitis, CSF leak, pseudomeningocele, and
persistent hydrocephalus.
• Cerebellar mutism
Cerebellar mutism
• unique postoperative complication seen in children after resection of a
posterior fossa mass lesion
• result from splitting of the vermis and exertion of pressure on the medial
cerebellum
• 10% to 25%
• 1 to 2 days after surgery
• Mutism and ataxia are typically the most significant symptoms
• Emotional lability, hypotonia
• Resolving week to month
• Improvements in affect and oral intake ability occur before resolution of
the speech difficulties
Radiatio
n
• Craniospinal irradiation (CSI)
• Average-risk patient and High-risk patients
• Highly radiosensitive
• Short-term side effects
• hair loss, fatigue, weakness, nausea, and vomiting
• Long-term adverse effects
• Neurologic, cognitive, and endocrine abnormalities
• Hypothalamic-pituitary axis dysfunction secondary to CSI may result in
obesity, hypothyroidism, precocious puberty, and growth retardation
• Short stature or scoliosis (or both)
Chemotherapy
• Adjuvant chemotherapy
• Average-risk patient and High-risk patients
• Moderate chemosensitive
• No standard regimen
• Lomustine(CCNU), Cisplatin, Vincristine(VCR)
Chemotherapy
• Platinum based agent : SNHL
• Alkylating agent : acute myelogenous leukemia
• Complication
• Myelocompression
• Fatigue,nausea,vomiting,loss of apetite,stomatitis, infection
• Nephrotoxicity,hepatotoxicity,cardiomyopathy,urinary bladder and pulmonary
fibrosis
Surveillance imaging and disease recurrence
• After resection,postopeararive MRI within 48 hr
• accurately assess the degree of residual disease
• baseline for assessing response to subsequent adjuvant therapy
• disease recurrence on follow-up imaging studies
• Long-term follow-up imaging
• repeat MRI every 3 to 6 months for the first 2 years after treatment
• Surveillance imaging has not been shown to detect a significant proportion of
asymptomatic disease recurrence in some studies
Surveillance imaging and disease
recurrence
•Recurrence at the primary site is most common
• Metastasis outside the nervous system is uncommon
• Despite adjuvant treatment, up to 60% of patients will display evidence of
disseminated disease at relapse
• Patients with recurrent disease who were initially treated with adjuvant
radiation therapy and chemotherapy : salvage therapy with either repeat
chemotherapy or focal stereotactic radiotherapy (or both)
• Patients treated initially with surgery and chemotherapy alone, long-term
disease control after local recurrence: salvage high-dose chemotherapy
followed by autologous stem cell rescue combined with radiotherapy
Surveillance imaging and disease
recurrence
• Collins’ law
• Period of risk of recurrence(PRR)
• Age at diagnosis plus 9 month
• Patients that remain free of recurrence beyond the PRR have a much lower
risk of recurrence