PRIMITIVE NEUROECTODERMAL TUMORS

Incidence

• More common in children• Posterior fossa/ medulloblastomas- most

common malignant brain tumors in children

• Constitute approx 20% of childhood brain tumors and 30% of all posterior fossa tumors

• 1% of adult tumors

• Median age of diagnosis- 9y.o.• 1.4-1.8 times more common in males than

females• Syndromes with increased familial incidence

of PNET:• 1.turcot’s syndrome• 2. Gorlin’ s syndrome

• Supratentorial PNET-may be seen with retinoblastoma termed as pinealoblastoma

• Pathology• Approx 50% of medulloblastoma has neuronal

or glial differentiation• Homer wright peudorosettes found in 40% of

medulloblastoma

Homer wright pseudorosettesHighly cellular medulloblastoma with scanty cytoplasm

Pathology

• Astrocytic differentiation is seen in >50% of tumors, (+) GFAP

• Gross: soft, friable, purplish tumors located in proximity to the 4th ventricle

• An isochromosome of the long arm of 17q is seen in up to 66% of medulloblastoma—related to tumor progression

CLINICAL EVALUATION

• Children with medulloblastoma present with s/sx of increased ICP

• Other symptoms: unsteady gait, ataxia, decreased coordination

• In very children: macrocephaly, loss of milestones, irritability & vomiting

• Many have evidence of hydrocephalus

• Diplopia is secondary to CN VI palsy• Severity of hydrocephalus may result to loss of

VA & blindness • Radiographic evaluation:• CT- hyperdense & homogenously enhancing,

with smaller areas of calcification• MRI- isointense or hypointense ion T1-weighted

images.hyperintense in T2. intensely enhancing in gad

• 10-15% of medulloblastoma do not enhance with contrast in MRI

• Treatment• Hydrocephalus- placement of EVD or

ventriculostomy at the time of surgery• Dexamethasone given preop• Preoperative shunting before removal of the

tumor is discouraged to avoid upward herniation

• In the postoperative period the level of EVD is gradually increased to allow normal CSF pathways to resume absorption

• not to wean from EVD when: s/sx increased ICP; CSF leakage from the wound; development of pseudomeningocele

• The need for postoperative shunting has been correlated with: younger patients, large ventricles, longstanding ventriculostomy & large tumors

• Tumor removal:• 24-48 hrs.Preop corticosteroid decrease

peritumoral edema• AED are not needed for PNET

• Preop EVD placement is generally reserved for moribund state & hydrocephalus is so severe

• Adequate venous access & arterial pressure monitoring are important

• Angulated concorde position for tumors in posterior fossa

• Dura is usually opened in Y-shaped fashion.

• Special attention to the circulator sinus & occipital sinus

• Medulloblastoma of 4th ventricle generally involve the vermis & occasionally invade bainstem

• Protecting the floor of 4th ventricle before splitting the tonsils & resecting a portion of inferior 4th ventricle

• Dissection between the vermis & tonsils may adequate exposure

• Debulking of the tumor can allow the surgeon to bring the edges of the tumor

• Gross total resection of the tumor is the goal

Complications

• 15-40% of medulloblastomas invade the floor of the 4th ventricle or brainstem—may limit the total resection of the tumor

• Sever deficits preoperativele have greatest introp risk

• Postop morbidity-50% of patients: transient or permanent deficits, hemiparesis, nausea & vomiting

• Posterior fossa syndrome AKA cerebellar mutism in 15%-20%—a post op complication of resection of medulloblastoma

• Characterized by: mutism, abulia, high-pitched cry, oral motor apraxia, drooling & ataxia

• Associated with edema of the dentorubrothalamic tract, splitting of the inferior vermis

OUTCOME:

• With residual tumor of <1.5cc correlated with improved outcome

• Gross total resection without adjuvant therapy, tumors tend to recur locally & disseminate through CSF

• Doubling in survival rates in patients who received radiation treatment 50%-70% with 5400 to 5800cGy

• Cognitive deficits are associated with craniospinal irradiation esp in patients younger than 3 y.o

• Children younger than 3y.o with malignant are treated with cyclophosphamide +vincristine followed by cisplatin +etoposide----40% progression free survival

• Supratentorial PNET are staged and treated the same as posterior fossa PNET & medulloblastoma

• 2 factors correlating survival in medulloblastoma: 1. age at diagnosis 2. evidence of spread

• Recurrence of medulloblastoma after initial treatment is usually incurable

PINEAL TUMORS

• Most pineal masses originate infratentorially & expand into the posterior 3rd ventricle

• Malignant tumors of glial origin can inavde into midbrain & thalamus

Pathology

• 4 main categories of pineal tumors:• 1.germ cell tumors• 2. pineal parenchymal cell tumors• 3. glial cell tumors• 4. cysts/miscellaneous tumors

• Miscellaneous tumors: meningioma, hemangioblastoma, choroid plexus papiplloma, metastatic tumor, chemotectoma, adenocarcinoma, lymphoma

• Vascular lesions: cavernous malformation, arteriovenous malformation, vein of galen malformation

Clinical features

• Symptoms:• 1. s/sx of increase ICP from obstructive

hydrocephalus• 2. direct brainstem & cerebellar compression • 3. endocrine dysfunction• Headache- most common symptom

associated with increase ICP

• Direct compression of the midbrain at the superior colliculus can cause disorders of EOM-Parinaud’s syndrome(upward gaze palsy, convergence or retraction nystagmus, light-near pupillary dissociation)

• Sylvian aqueduct syndrome-paresis in downward gaze or horizontal gaze

• Collier’s sign- lid retraction (due to dorsal midbrain compression or infiltration) diplopia and head tilt

• Ataxia & dysmetria-- Interference with cerebellar efferent pathways of the superior cerebellar peduncles

• DI- occurs with germinoma spreading along the floor of 3rd ventricle

• Precocious pseudopuberty- hypothalamic-gonadal axis is not mature—limited in males with chorioCA or germinoma producing beta HCG

diagnostic

• MRI with gad- principal diagnostic test for pineal tumors

• Reveals the degree of hydrocephalus, tumor size, vascularity, homogeneity and anatomic relationships with surrounding structures

• Tumor markers- CSF alpha feto protein and beta human chorionic gonadrotropin

• Tumor markers are useful for monitoring response to adjuvant therapy or early signs of recurrence

• CSF cytology ocassionally reveals malignant cells but is rarely diagnostic

• Presence of malignant cell markers tissue tissue diagnosis is unnecessary—chemotherapy and RT should proceed

• Stereotactic biopsy-for patients with known primary systemic tumors, multiple lesions or medical conditions that make open resection dangerous and radiographic evidence of brainstem invasion

treatment

• Management of hydrocephalus:• Mildly symptomatic patients—ventricular

drain placed at the time of surgical resection

• More advance symptoms– ct-guided stereotactic ETV to allow gradual reduction of ICP

• Open resection- ability to obtain larger amounts of tissue & extensive tissue sampling---esp for tumors where heterogeneity and mixed cell population are common

• Tumor burden is reduced• 1/3 of tumors that are benign resection

is usually complete & curative

Surgery

• Stereotactic procedure• 2 possible approaches:1. Precoronal entry point– reaching the

tumor throught the anterolaterosuperior approach

2. Posterolaterosuperior approach near the parieto-occipital junction

• Patient positioning1. Sitting position-preferred for the

infratentorial-supracerebellar approach2. Lateral position—for the occipital-

transtentorial approach the head should be positioned with the patient’s nose rotated 30 deg toward the floor

• More desirable variation of lateral position is the three-quarter prone position—suitable for more posterior approaches such as the occipital-transtentorial

• Operative approachesI.Supratentorial approaches- transcallosal-

interhemispheric, occipital-transtentorial, transcortical-transventricular

II. Infratentorial-supracerebellar approach

• Location of most pineal tumors infratentorially and midline gives the infratentorial-supracerebellar approach several advantage

• The approach is less favorable if the tumor has a significant supratentorial or lateral extension

Complication

• Immediate postop- impairment of extraocular movements particularly limited up-gaze and convergence

• More sever morbidity can be a sequela of overzealous brainstem manipulation

• Most devastating complications is hemorrhage into an incompletely resected tumor bed

Surgical outcome

• The impact of surgery on long-term outcome depends on the tumor’s histology and responsiveness to adjuvant therapy

• Benign tumors with complete surgical removal, excellent long-term follow-up--- probable cure

Postoperative work-up

• postopMRI with Gad should be done within 72hours of the surgery

• Tumor markers should be measured postop for detecting early recurrence or for monitoring treatment response

Adjuvant therapy

• Radiation therapyMalignant germ cell or pineal cell tumors-

recommended dose 5500cGy given in 180 cGy daily fractions with 4000cGy to the ventricular system & additional 1500cGy to the tumor bed

• RT may be withheld for the rare histologically benign pineocytoma or ependymoma that has been completely resected

• Chemotherapy• Beneficial for patients with

nongerminomatous malignant germ cell tumors

• Regimen of cisplatin or carboplatin with etoposide is among the most widely used

EPENDYMOMA

• Neoplasms arising from ependymal cells lining the ventricles and central canal of the spinal cord

• 4 most prevalent locations: 1.supratentorial

2.infratentorial 3.spinal 4. conus-cauda-filum

• Behavior:1.Resistance to drugs and radiotherapy2. Propensity to recur 10-20 years after the

initial resection3.Marked inconsistencies between their

histology and prognosis4. Infants & children are affected without

obviuos risk factors

Epidemiology

• Incidence rate for children-3/100,000 children younger than 15 yrs

• Male-to-female ratio in children is about 14:1

• The rate of new cases peaks at about age 4 years

Diagnosis

• S/sx of increased ICP: frequent HA that are worst in the morning (assoc with nausea, vomittng, ataxia, lethargy, irritability & decline in school or wok performance)

• Papilledema; nystagmus; changes in vision

GRADE NAME COMMON LOCATION1 Myxopapillary Spine, 4th ventricle, lateral

ventricleSubependymoma

2 Papillary CP anglecellular 4th ventricle and midline areaClear cell 4th ventrice and midline area

3 anaplastic Cerebral hemisphere4 Ependymoblastoma several

Diagnostic surgical pathology

• Characteristic features: rosette pattern of cells formed by a ring of polygonal cells surrounding a central cavity

• Malignant cells are generally characterized by significant mitotic activity, nuclear polymorphism & variation in the shape of the membrane

• Parameters for prognosis:1.Number of mitosis2. Labeling indexes of proliferation markers3. Cell density

• ImagingCT non-contrast- lesionis isodense to cerebral

cortex. Low density necrotic areas are also seen

Highly suggestive of ependymoma-presence of desmoplastic development & a tumor-vermis cleavage plane in a posterior fossa that isodense

• MRI- T1 weighted images- hypointense to isointense with gray matter.

• T2 weighted images-isointense to hyperintense

TReatment

• Surgical resection offers long-term remission in about half of the newly diagnosed patients

• Radical surgery alone may be sufficient for infants and adults with low-grade tumors

• Second look surgery may be useful in dealing with residual tumors

• Aggressive efforts at local control and surgery in eloquent areas such as the brainstem can lead to significant morbidity

• In addition to preoperative deficits new or increased postsurgical cranial nerve palsies worsening ataxia and bulbar dysfunction occurred in 10-19 children

• Postoperative deficits arising from aggressive surgery in 11 infants with CP angle tumors resolved at a median follow-up of 37 months

HEMNGIOBLASTOMAS OF THE CNS

EPIDEMIOLOGY AND GENETICS

• Account for 2% of intracranial tumors• 10% of posterior fossa tumors• Constitute 2%-3% of all intramedullary

spinal cord tumors• 25% are associated with VHL disease• Sporadic hemangioblastomas typically

present at 40-50 years of age

• Patients with VHL present in their 20s to 30s• Absolute ratio of men to women varies from

1.3:1 to 2:1

CLINICAL PRESENTATION

• sporadic hemangioblastomas predominantly occur in the cerebellum but VHL associated hemangioblastomas occur in the cerebellum brainstem or spinal cord with multiple hemngiomas in various sites.

• Slowly growing masses associated with cysts in the cerebellum or a syrinx in the brainstem or spinal cord

• In the posterior fossa cause impaired cerebrospinal flow because of compression of the 4th ventricle

• S/SX:• Headache-subocciptal region worse in the

morning• Lhermitte’s sign neck stiffness due to

compression of the brainstem as ot passes through the foramen magnum

• Vomiting is common due to obstructive hydrocephalus

• Vertigo-for tumors located in the brainstem or middle cerebellar peduncle adjacent to the vestibular nuclei

• Unstable gait-tumors in the cerebellum or pons

• Cerebellar hemispheric lesions cause limb ataxia, dysmetria and intention tremor

• Spinal pain and spasticity, weakness, sensory changes, hyperactive reflexes, impaired urination

DIAGNOSTIC STUDIES

• MRI with contrast is the dx of choice• T1 weighted images appears as contrast

enhancing nodule with an associated sharply demarcated non-enhancing smooth cyst

• Without contrast in T1-weighted images nodule is hypointense to isointense

• On T2 its hyperinstense

Conventional angiography

• Can demonstrate the location of dominant feeding arteries.

• It shows the highly vascular tumor nodule with an avascular cyst

TREATMENT

• Surgery with complete excision• Tumors in the cerebellum are best approach with

the patient in the prone position through a suboccipital craniotomy or craniectomy

• Brainstem hemangiblastoma resection is not recommeded

• Tumors located dorsally in the spinal cordwide laminectomy with resection of the medial portion of the facets provides adequate exposure

• Ventrally located tumors are best approached using a posterolateral trajectory with laminectomy facetectomy, resection of the pedicle & gentle rolling of the spinal cord

RADIATION THERAPY

• External beam radiation can be used to control incompletely resected solid lesions or multiple lesion in the patients VHL disease

• SRS provide greater benefit for VHL disease with recurrent disease or multiple tumors in the brainstem and spinal cord