Pediatric Neuro-oncology Flashcards
- Which one of the following lists of primary brain tumors in children is from most common to LEAST common (all age groups combined)?
a. Astrocytoma, craniopharyngioma, medulloblastoma, ependymoma, germ cell tumors
b. Astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, germ cell tumors
c. Ependymoma, astrocytoma, medulloblastoma, craniopharyngioma, germ cell tumors
d. Medulloblastoma, astrocytoma, craniopharyngioma, ependymoma, germ cell tumors
e. Medulloblastoma, craniopharyngioma,
ependymoma, astrocytoma, germ cell
tumors
b. Astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, germ cell tumors
Overall incidence approximately 5 per 100,000
persons per year (compared to 20-30 per
100,000 in adults). Incidence rates of tumor
types vary by age, hence although posterior
fossa tumors are much more common in children
than adults, in children infratentorial tumors
may only be commoner than supratentorial
tumors within certain age groups (e.g. 4-10 years
of age). Roughly 60-70% are gliomas; specific
frequency of tumor types is astrocytomas 30%,
medulloblastoma (15-20%), craniopharyngioma
(10-15%), ependymomas (5-10%), germ cell
tumors (5-10%). Commonest tumors vary by
age (see below). Incidence in 19 years or younger
in the Central Brain Tumor Registry of the
United States:
Which one of the following is associated with the highest incidence of brain metastases in children?
a. Neuroblastoma
b. Sarcoma
c. Wilms tumor
d. Leukemia
e. Lymphoma
b. Sarcoma
The commonest primary neoplasms in children
uncommonly demonstrate hematogenous seeding resulting in brain metastasis—the overall rate
approximates 4% in patient followed up
>10 years. In a pooled analysis of multiple studies
in over 2000 children, cerebral hematogenous
metastases were reported in 4.4% of 429 patients
with neuroblastoma, 1.9% of 574 rhabdomyosarcoma patients, 6.5% of 386 patients with osteosarcoma, 3.3% of 487 Ewing sarcoma patients,
3.6% of 44 melanoma patients, 13.5% of 37
patients with germ cell tumors, and 1.3% of the
78 patients with Wilms tumor.
Which one of the following statements regarding posterior fossa tumors in children is LEAST accurate?
a. Pilocytic astrocytomas account for 35% of posterior fossa tumors in children
b. Medulloblastoma account for 30% of posterior fossa tumors in children
c. Ependymomas account for 20-30% of
posterior fossa tumors in children
d. Brainstem gliomas account for 10-20% of posterior fossa tumors in children
e. Hemangioblastomas account for 10% of posterior fossa tumors in children
e. Hemangioblastomas account for 10% of posterior fossa tumors in children
A 17-year-old boy patient presents with left arm clumsiness. MRI is shown. Which one of the following is most likely?
a. Hemangioblastoma
b. Medulloblastoma
c. Neuroblastoma metastasis
d. Pilocytic astrocytoma
e. Vestibular schwannoma
d. Pilocytic astrocytoma
Pilocytic astrocytomas are the most frequent posterior fossa tumors in children (approximately
35%). Peak age is 5-13 years; approximately half
arise in the midline vermis and half from the cerebellar hemispheres. They are circumscribed, discrete, slow-growing lesions, often associated
with cysts within and around the tumor. On CT
they are large cystic lesions with a hypodense
solid component which enhances avidly on
contrast administration. On T1WI, the solid component tends to be iso- to hypointense and on
T2WI it is hyperintense, with heterogeneity is due to microcystic and necrotic areas. The solid
and mural components enhance prominently.
Enhancement of the cyst wall suggests tumor infiltration of the capsule. They maintain their WHO
grade I status for years; they only rarely show
malignant transformation (anaplastic pilocytic
astrocytomas). A large percentage of pilocytic
astrocytomas, particularly those arising within
the cerebellar hemisphere, have demonstrated
alterations in the BRAF gene but this is not prognostically significant. Resection is the treatment of choice for well-circumscribed lesions and extent
of resection most strongly associated with outcome. Gross total resection leads to over 90%
long-term survival. Cerebellar lesions are generally completely resectable hence adjuvant therapy
is not indicated, whereas. Those arising from the
brainstem are often not and require adjuvant chemotherapy, usually including carboplatin and vincristine, and consideration of radiotherapy at
progression. Trials of BRAF and MAPK pathway
inhibitors, and antiangiogenic agents bevacizumab and linalidomide are ongoing. The main differential diagnosis is hemangioblastoma, which
usually presents in young adults but may present
in children with VHL but these may be multiple,
show greater vascularity/abnormal vessels associated with enhancing portion/nodule, are usually abutting a pial surface, and have a considerably higher rCBV than pilocytic astrocytomas on
perfusion imaging.
A 5-year-old with features of NF-1 presents with visual disturbance. T1 postcontrast MRI is shown. Which one of the following statements regarding management of these lesions is most accurate?
a. Surgical decompression is prophylactic to save bilateral vision
b. Chemotherapy is second line management in children under 9 years old
c. Biopsy should only be performed if there are features of NF-1
d. Somatostatin has been shown to improve outcome
e. Cranial irradiation is contraindicated in this case
e. Cranial irradiation is contraindicated in this case
Optic pathway gliomas are congenitalWHO grade
I astrocytoma of optic nerves or chiasm, and may
be associated with NF-1 (50-60%) or be sporadic.
Sporadic tumors typically arise within the
chiasmatic-hypothalamic region or in other brain
structures adjacent to, or involving the optic tract,
and do not typically involve the optic nerves. In
contrast, OPG associated with neurofibromatosis
type 1 characteristically involve optic nerve, chiasm
and optic radiation, including the geniculate
ganglion. Tumors involving optic chiasm and
hypothalamus are of a higher histologic grade
(grade 2) than tumors confined to optic nerve and
may cause considerable morbidity and even death.
Usually discovered during first decade due to visual
impairment, endocrine deficit, focal neurological deficit, hypothalamic behavioral disturbance
(appetite, rage, obesity), stationary or progressive
visual loss in one eye or both. Examination may
show iris hamartomas (Lisch nodules) and/or eyelid plexiform neurofibromas, visual acuity and/or
visual field loss, afferent pupil defect, pendular
(monocular or seesaw) nystagmus, optic disc
abnormality, proptosis if large intraorbital component. MRI shows intrinsic mass of optic nerves,
optic chiasm, optic tracts, or hypothalamus and
may also show hamartomas elsewhere that are typical of neurofibromatosis type 1. By definition, due to their location, surgery will inevitably damage the optic nerve or pathway (plus risk vascular supply to hypothalamus and pituitary) and biopsy cannot usually be justified if imaging is diagnostic (it is done only if imaging is non-diagnostic/atypical),
and where useful vision is maintained ipsilateral
to tumor debulking or resective surgery seems
unnecessary. However, when there is unilateral
failing or useless vision debulking, resective surgery
may be appropriate to protect vision on the good
side, potentially controlling hydrocephalus and
delaying radiotherapy in what is often a young
patient group. Surgical treatment may also be
offered for optic nerve gliomas causing disfiguring
proptosis in a blind eye (excision of optic nerve
only). Chemotherapy is used for patients under
age 9 with glioma involving the chiasm and/or
hypothalamus and who have severe or worsening
visual or hypothalamic dysfunction or signs of
tumor growth (to delay radiotherapy and neurocognitive side effects, or in NF-1 for additional risk of secondary moyamoya disease and intracranial
tumors). Cranial radiation is contraindicated in
NF-1 but may have a vision sparing effect in sporadic tumors in older children and adults. Visual
function often stable in untreated patients, but
visual decline may result from tumor progression.
A 16-year-old male patient who previously underwent excision of a right temporooccipital lesion 7 years previously, with good control of seizures since, presents with increased frequency of tonic-clonic seizures and headaches. Neurological examination was unremarkable. MRI is shown. Which one of the following is most likely?
a. Diffuse astrocytoma
b. DNET
c. GBM
d. Pilocytic astrocytoma
e. Pleomorphic xanthoastrocytoma
e. Pleomorphic xanthoastrocytoma
Pleomorphic xanthoastrocytoma is a very rare
brain tumor accounting for only 1% of all brain
neoplasms. It is however important to be familiar
with the radiological findings of this tumor
because it has a characteristic imaging appearance
and is highly amenable to surgical resection with a
good prognosis. PXAs predominantly occur in
children and young adults and there is no gender
predilection. PXA predominately affects the cerebral hemispheres, showing mainly involvement of
the temporal and parietal lobes. The most common clinical presentation of this tumor is seizures, whilst increased intracranial pressure appears to be a less frequent finding. On CT,
PXAs are usually seen as well-defined, partially
cystic masses of various sizes, which show
enhancement after contrast administration. The
solid component of the neoplasm tends to be heterogeneous and isodense to gray matter, and calcification may be present. MRI reveals that most
of these tumors are predominately superficial,
cortical, partially cystic masses which are hypoto isointense to gray matter on unenhanced
T1-weighted images while mildly hyperintense
on T2-weighted images. Gadolinium-enhanced
T1-weighted images typically show marked
enhancement of the solid component. The most
consistent findings are peripheral location of
the tumor, leptomeningeal contact of the tumor
and marked enhancement of the solid tumor
component. The radiologic differential diagnosis
of PXAs includes mainly other astrocytomas,
ganglioglioma, meningioma, meningiosarcoma
and fibrous xanthoma. The treatment of choice
for pleomorphic xanthoastrocytomas is complete
surgical excision which is favored by the superficial location, relative circumscription, and cyst/
mural nodule architecture of the tumor.
A 2-year-old presents after his mother noted an abnormal white reflection in his right eye. MRI is shown. Which one of the following
would you look for?
a. AT/RT
b. Hypothalamic hamartoma
c. Optic glioma
d. Pineoblastoma
e. Pontine glioma
d. Pineoblastoma
The T2-weighted MRI shows left sided retinoblastoma. Retinoblastomas are bilateral in 30-
40% of cases, and may be associated with pineoblastoma (“trilateral retinoblastoma” as the pineal
gland has been historically labeled as the “inner/
third eye”) in 15% of cases.
A 4-year-old presents with torticollis, facial asymmetry and ophthalmoparesis. Which one of the following is appropriate next management?
a. Biopsy
b. Radiotherapy
c. Chemotherapy
d. Midline suboccipital resection
e. Transoral resection
b. Radiotherapy
Brainstem gliomas account for 10-20% of all
CNS tumors in children. They are broadly
classified into diffuse or focal. Diffuse intrinsic
pontine gliomas are high-grade fibrillary astrocytomas with median overall and progression-free survival of up to eleven and nine months respectively. They present with a short history, often characterized by cranial nerve palsies and ataxia.
They are diagnosed radiologically and when typical, do not require biopsy. They are hyperintense on T2- and hypointense on T1-weighted images,
with ill-defined boundaries and diffuse enlargement of the brain stem. They generally do not
enhance with contrast. Surgical resection has no
role in these tumors. Radiation is indicated to
the tumor with a margin to a dose of approximately 54 Gy. Symptoms generally resolve with
treatment. Unfortunately, duration of symptom
relief is usually short lived, on the order of
6 months. This disease is uniformly fatal, and
the median survival for these children is 1 year.
Despite several clinical trials over the last fifteen
years, based on various chemotherapeutic agents
and radiotherapy delivery techniques, there has
been no improvement in clinical outcome. Focal
brainstem tumors are well-circumscribed masses
that may be intrinsic, exophytic or cervicomedullary, solid or cystic, under 2 cm in diameter, and
are commonly low grade astrocytomas. In one
retrospective study of focal brainstem gliomas,
following 52 children over a mean of ten years,
the survival rate was 98% at five years and 90%
at ten years; 36. 5% underwent gross or near total
resection. If there is clinical or MRI progression,
options include resection (for accessible tumors
where the patient and family understand the high
risk of new neurological deficit) or stereotactic
biopsy followed by radiation.
Which one of the following conditions is most likely?
a. NF-1
b. NF-2
c. Tuberous sclerosis
d. Li-Fraumeni syndrome
e. Cowden syndrome
c. Tuberous sclerosis
Tuberous sclerosis complex (TSC) is a genetic,
multi-organ condition characterized by the development of benign tumors in the brain, heart, kidneys, liver, and lungs. Subependymal giant cell
astrocytomas (SEGAs), develop in 10-15% of individuals with TSC. SEGAs can be unilateral or
bilateral, developing from those benign subependymal nodules (hamartomas) located near the foramen of Monro. SEGA development is a gradual process that generally occurs within the first 2 decades of life. These are slow-growing, glial neuronal tumors, usually developing over 1-3 years.
SEGAs are usually asymptomatic until they block
circulation of cerebrospinal fluid (CSF), leading to
increased intracranial pressure and hydrocephalus.
Typically, serial neuroimaging is performed every
1-3 years in pediatric TSC patients and until the mid-20s, even in the absence of SEGA symptoms.
Options include surgery or pharmacotherapy. Surgical tumor resection has traditionally been the
standard therapy for SEGA and earlier intervention has been proposed to avoid sequelae of hydrocephalus. Indications for surgery include:
asymptomatic SEGAs with documented tumor
growth or enlargement of the ventricles is
observed; symptomatic SEGA (e.g. behavioral
changes, worsening of seizures, symptoms of
raised ICP). Prognosis is good, particularly in cases
where surgery is performed early for small lesions;
in most cases resection is curative if tumor removal
is complete. The goal of pharmacotherapy with
mTOR pathway inhibitor (everolimus) is to shrink
or stabilize the tumor in adults and children 3 years
or older with SEGA associated with TSC who
require therapeutic intervention but are not amenable to surgery (e.g. contraindications exist for
anesthesia or surgery in general, total resection
unlikely to be possible, or in rare cases of bilateral
fornix lesions with high risk of morbidity). Treatment reduces tumor size, and the effect is sustained in EXIST-1 trial. The role of stereotactic radiosurgery has not yet been fully elucidated
A 5-year-old child presents with gait ataxia. MRI is shown. Which one of the following management strategies is appropriate in this case?
a. Complete resection followed by surveillance
b. Complete resection followed by focal radiotherapy boost
c. Neoadjuvant chemotherapy followed by resection and postoperative adjuvant chemotherapy
d. Debulking surgery followed by craniospinal irradiation
e. Stereotactic radiosurgery
b. Complete resection followed by focal radiotherapy boost
Ependymoma is the third most common pediatric
brain tumor; over 50% of cases arise in children
under 5 years of age. Chromosomal abnormalities
include 22q; chromosome 1q gain has been found
in up to 22% of childhood ependymomas, and is
associated with posterior fossa location, anaplastic
features and a poor prognosis. Infratentorial
ependymomas in children are classified as
WHO grade 2 or 3 (grade 1 being reserved only
for subependymoma and myxopapillary ependymoma). Infratentorial ependymomas arise from the floor or roof of the fourth ventricle and grow into the ventricular lumen. They have a propensity to extend through the foramen of Luschka into the cerebellopontine cistern and around the brainstem, as well as down through the foramen magnum. They are well-delineated, soft,
heterogeneous tumors, often with cystic, necrotic
and hemorrhagic elements. On CT, ependymomas are iso- or hyperdense lesions, up to 50% have punctate calcification, and they enhance heterogeneously on contrast administration. On
MRI, they are iso- to hypointense on T1-
weighted sequences and hypointense on T2 but
calcification, cysts, areas of necrosis and hemorrhage cause heterogeneity within the tumor mass on enhanced and non-enhanced sequences. Leptomeningeal dissemination at presentation is less common than in medulloblastoma; full spinal
MRI at diagnosis is imperative as part of the staging process. The extent of surgical resection is a
major determinant of outcome. In historical
series, five-year overall survival for ependymoma
has ranged from 50 to 64%. Despite several
multi-institutional studies, mostly including
platinum-based agents, no single chemotherapeutic regimen has demonstrated significant
survival benefit for ependymoma. The role of
chemotherapy alongside postoperative radiotherapy remains unclear. In a recent single-institution
study, conformal radiotherapy, administered
immediately after surgery, led to better overall
survival rates, up to 85% at five years, compared
to earlier studies with up to 73% at five years.
This may be partly attributable to the high rate
of gross total resection (82%) and use of radiotherapy for the first time in children under
three years.
A 9-year-old girl presents with headache and vomiting. On examination there is bilateral papilledema but she is otherwise neurologically stable. MRI is performed. Which one of the following is the next appropriate step?
a. ICP monitoring
b. Lumbar puncture
c. Serum AFP and HCG
d. External ventricular drain
e. Endoscopic third ventriculostomy and biopsy of lesion
c. Serum AFP and HCG
Pineal region masses have a wide differential
diagnosis, and considering she is neurologically
stable, the priority is to narrow the differential
diagnosis ideally before any surgical intervention
is required. In general germ cell tumors account
for 60%, pineal parenchymal tumors for 30%,
supporting cells/meninges for 10%, and cysts,
vascular lesions and metastases. Approximately
60-70% of germ cell tumors are highly radiosensitive germinomas, while the rest are classed as non-germinomatous germ cell tumors
(NGGCT: teratoma, choriocarcinoma, embryonal carcinoma, yolk sac tumors). The main question is whether the lesion is likely to be a
germinoma (requiring non-surgical treatment
with craniospinal irradiation), a NGGCT
(requiring neoadjuvant chemotherapy, followed by surgery and radiotherapy), or another pineal
region tumor (e.g. pineoblastoma requiring
surgery followed by radiotherapy). The tumor
markers alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), placental alkaline
phosphatase, and lactic dehydrogenase isoenzymes are useful in the diagnosis and treatment
monitoring of germ cell tumors. Elevations in
levels of AFP alone in cerebrospinal fluid (CSF)
and serum are found in pure endodermal sinus
tumor, and may or may not be seen in mature teratomas. Elevated levels of both HCG and AFP
are found in embryonal carcinoma, and high
levels of HCG alone are found in choriocarcinoma. The serum and CSF levels in cells of
AFP may be 10-100 times baseline. Serum
HCG levels may be 100 times baseline, and there
may be a CSF/serum gradient, especially when
lumbar CSF is assayed. Normal levels are generally thought to be less than 1.5 IU/l or 1 IU/l for
β-hCG, however, and less than 1.5 ng/ml for
AFP. Modest elevations of HCG may be found
in germinoma (CSF more likely), usually in the
presence of elevated placental alkaline phosphatase and/or lactic dehydrogenase isoenzymes,
whereas a serum or CSF HCG >50 IU/l and/
or an AFP >25 ng/ml in the presence of a midline
CNS tumor is supportive of a diagnosis of
NGGCT. Germinomas may secrete low levels
of B-HCG if it contains some syncytiotrophoblasts (unlike the very high levels secreted by choriocarcinomas >2000 IU/l) but pure germinomas
do not, although they may secrete placental alkaline phosphatase. In this situation, biopsy of the
tumor is required to distinguish between
germinoma/non-secreting germ cell tumor and
a pineal parenchymal tumor. This is ideally done
at the same time as endoscopic third ventriculostomy. Additionally, endodermal sinus tumors secrete alpha fetoprotein, and embryonal carcinomas secrete a mixture of beta human chorionic gonadotropin and alpha fetoprotein. Pineal germinomas most often occur in male patients, pineal parenchymal neoplasms occur with equal frequency in male and female patients. Both
tumors can arise at any age, but pineoblastomas
peak during the first decade of life, whereas pineocytomas peak during the second and third
decades. On CT imaging, pineal parenchymal
tumors classically demonstrate a rim of
“exploded” calcification that can be helpful in distinguishing them from germ cell tumors which
have a central calcified pineal gland. Teratomas
possess unique imaging characteristics because
of fat and calcium, and choriocarcinomas may
hemorrhage; these characteristics help identify
these entities. The remainder of the NGGCTs
have no unique characteristics that can be used
to confidently distinguish them.
A 13-year-old presents with polydipsia and polyuria. Clinical examination is unremarkable. Serum blood tests show a Na 149 mEq/l and serum osmolality is 315 mOsm/kg H2O, with urine osmolality f 115 mOsm/l. MRI is shown. Subsequent serum AFP and BHCG are within normal limits. Which one of the following is most likely?
a. Craniopharyngioma
b. Germinoma
c. Langerhans cell histiocytosis
d. NGGCT
e. Pineoblastoma
b. Germinoma
This child is presenting with features of diabetes
insipidus, withMRI evidence of enhancing lesions
in the hypothalamus-sellar area and the pineal
region consistent with bifocal (synchronous) germinoma. Typical neuroimaging findings of CDI
include absence of the posterior pituitary hyperintensity and normal or thickened infundibulum but they are nonspecific as they may progress to develop germinoma, Langerhans cell histiocytosis, or lymphocytic hypophysitis. Less common causes include lymphoma and granulomatous diseases (such as tuberculosis and sarcoidosis). Germ cell tumors are the most common neoplasm arising from the pineal region, accounting for roughly two thirds of pineal region neoplasms. They are much more common in people of Asian descent within the second and third decades of life, with men affected 10 times more frequently than women. The majority arise in the pineal region, and the rest are suprasellar or in the basal ganglia.
On imaging, they classically engulf calcification,
enhance avidly, and demonstrate intrinsic hyperdensity on CT and isointensity to gray matter on most MRI sequences. Because they are histologically unencapsulated, they sometimes invade the adjacent thalamus or tectum and disseminate via the CSF. For this reason, imaging of the entire neural axis for detection of metastases is vital during the initial workup. Pure germinomas are very radiosensitive, and patients typically have an excellent prognosis.
A 12-year-old boy presents with precocious puberty and headache. CT head demonstrates obstructive hydrocephalus and pineal
region mass on CT. Serum HCG is 8178 IU/l, AFP is 5 ng/ml. What would be the most appropriate next step in management?
a. Stereotactic biopsy
b. Endoscopic biopsy
c. Endoscopic third ventriculostomy without biopsy
d. Tumor debulking
e. Ventriculoperitoneal shunt
c. Endoscopic third ventriculostomy without biopsy
The history is suggestive of a non-germinomatous
germ cell tumor, given the precocious puberty and
raised serum HCG (e.g. choriocarcinoma). As
such, tumor biopsy is not necessary in the initial
management of this patient (but may be required
later if there is no response to therapy). Instead,
initially endoscopic third ventriculostomy can be
performed and CSF samples taken for cytology
and tumor markers to further stratify treatment.
Beyond this, NGGCT treatment requires neoadjuvant chemotherapy followed by resective surgery and postoperative radiation to the tumor
bed with or without craniospinal irradiation.
An 8-year-old girl presents with symptoms of raised intracranial pressure over the last 2 weeks. T1 +GAD MRI is shown. Which one of the following is most likely?
a. Arachnoid cyst
b. AT/RT
c. Choroid plexus papilloma
d. DNET
e. Medulloblastom
c. Choroid plexus papilloma
Choroid plexus papillomas and carcinomas represent 0.4-0.6% of all intracranial tumors. They are more common in the pediatric population and
account for approximately 3% of childhood brain
tumors. More commonly, the lesions are seen in
the lateral and third ventricle, but 30% are seen in
the fourth ventricle, and less than 5% occur in the
cerebellopontine angle. The lesions usually present with obstruction of the CSF pathways as well
as overproduction of CSF with resultant hydrocephalus. These lobulated intraventricular masses may have internal small flow voids and possibly calcifications. Choroid plexus carcinomas are more heterogeneous in appearance than are choroid plexus papillomas and usually extend beyond the margins of the ventricle. CT shows an iso- to hyperdense mass with punctate calcification and homogeneous enhancement. On MRI the papillomas appear as lobulated, intraventricular masses of heterogeneous, predominantly intermediate signal intensity on both T1 and T2 images, with intense contrast enhancement. Choroid plexus carcinomas are rare, highly malignant tumors that invade the adjacent brain parenchyma to a greater degree than papillomas. On MR spectroscopy, choroid plexus papillomas tend to have an elevated myoinositol peak, whereas choroid plexus carcinomas are more often associated with an elevated choline peak.
A 6-year-old child presents with clumsiness and slurred speech. On examination and papilledema. CT head is abnormal therefore MRI of the craniospinal axis is performed showing the lesion above. Spinal MRI is normal. Which one of the following best describes conventional treatment?
a. Neoadjuvant chemotherapy, surgical
resection, postoperative focal radiotherapy
b. Surgical resection followed by focal radiotherapy plus craniospinal irradiation
c. Surgical resection followed by focal radiotherapy plus adjuvant chemotherapy
d. Surgical resection followed by
chemotherapy
e. Surgical resection followed by craniospinal irradiation and focal radiotherapy with concurrent chemotherapy
e. Surgical resection followed by craniospinal irradiation and focal radiotherapy with concurrent chemotherapy
Medulloblastoma is a primitive neuroectodermal tumor (PNET) arising from aberrant proliferation of granule neuron precursor cells that go
on to constitute the external granular layer of the
cerebellum. It represents 30% of posterior fossa
tumors and is the commonest malignant brain
tumor in children with an incidence of 6.5 per
1,000,000 children per year. It is a WHO grade
4 tumor and has a propensity to leptomeningeal
dissemination. Associations include familial cancer syndromes such as Gorlin syndrome, LiFraumeni syndrome, Turcot syndrome, Gardner syndrome, and Cowden syndrome. It is a
midline lesion in 75%—a cerebellar location is
associated with older age and desmoplastic histology. The mass is hypointense on T1- and
T2-weighted images; it enhances heterogeneously on gadolinium administration, may have cysts, and is diffusion restricting on DWI (due to
hypercellularity). Leptomeningeal disease is
identified as enhancing nodules on the surface
of the brain and spinal cord (“sugar coating”).
Histologically, medulloblastoma is composed
of small blue round cells with a high nuclear to
cytoplasmic ratio in four distinct pathological
subgroups: classical (65-80%), desmoplastic/
nodular (15-25%), medulloblastoma with extensive nodularity (15-25%), and an anaplastic/
large cell variant (4-5%). The desmoplastic variant is commoner in older children and is associated with a better prognosis. The large cell and
anaplastic variants are associated with a poor
prognosis. Molecular classification is based on
Wnt and SHH signaling abnormalities, which
confer a very good and intermediate prognosis
respectively. Treatment is maximal safe resection (including via transvermian, transcortical,
or telovelar-cerebellar) followed by further adjuvant treatment depending on whether they are
classified/staged as standard or high-risk cases
based on preoperative craniospinal axis MRI
(macroscopic metastases) and lumbar CSF cytology two weeks postoperatively to avoid false positives early after resection (microscopic metastases).
High-risk patients include all children <3 years,
those with positive CSF, macrometastases on
MRI, and >1.5 cm of residual tumor visible on
postoperative MRI (done within 24-72 h).
Children older than three with anaplastic histology
or c-myc amplification are also considered
high risk. Children >3 years old classified as standard risk undergo craniospinal irradiation
(23.4 Gy), commenced within 40 days of surgery
with a posterior fossa boost to a total dose of
54-55.8 Gy and concurrent chemotherapy once
weekly (“PACKER” regime, consisting of cisplatin, vincristine, CCNU) which yields a 5-year
event-free survival of up to 80%. In children with
high-risk disease, 5-year progression-free survival
has historically been approximately 40% but in
recent studies using a higher dose to the craniospinal axis, hyperfractionated radiotherapy with higher posterior fossa boosts, and myoablative
myeloablative courses of chemotherapy followed
by peripheral blood stem cell rescue, 5-year progression-free survival of up to 73% has been seen.
Furthermore, as the neurocognitive sequelae of
radiotherapy are more severe in young children
repeated cycles of chemotherapy have been used
after surgery in those <3 years in an attempt to
prevent progression until they become eligible
for radiotherapy.
