Shenandoah Robinson, M.D.
Department of Neurological Surgery
Rainbow Babies and Children’s Hospital B-501
Telephone: 216-844-5741
E-mail:
shenandoah.robinson@uhhs.com
Epidemiology
Adults:
50,000 cancer deaths/year involve the CNS (15% of total
cancer deaths)
8500 deaths/year due to primary brain tumors
Pediatrics:
Most common solid tumor in children
Prevention
1. Only known extrinsic cause is cranial radiation
(scalp tumors, leukemia)
2. Genetic causes (phakomatoses, cancer syndromes that
include CNS tumors)
Clinical Presentation
Brain tumors:
1. Signs of increased intracranial pressure –mass effect
or obstructive hydrocephalus
headache, emesis, papilledema
2. Seizures
3. Focal neurological symptoms and signs
speech and cognitive problems, visual or hearing loss,
weakness, numbness, poor coordination and gait
Spine and spinal cord tumors:
1. Back pain, particularly worse at night;
intraparenchymal tumors may have no pain
2. Focal neurological symptoms and signs
weakness or numbness, difficulty with walking, bowel and
bladder dysfunction
Pathology
Pathological diagnosis is based on the presumed cell of
origin. Morphology is supplemented by
immunohistochemistry. Frequently tumors are heterogenous
so sampling error can occur with needle biopsies.
Astrocytomas, oligodendrogliomas, or mixed
oligoastrocytomas can be grade II, III or IV. Grade III
and IV tumors can arise “de novo” or occur as
progression from a low-grade tumor.
Gliomas have 4 grades by
World Health Organization
(WHO)
Benign: Malignant:
I pilocytic III anaplastic
II low-grade IV glioblastoma
Pilocytic tumors are very benign histologically and
typically occur in children.
Low-grade tumors can be slow-growing and controlled by
treatment. If they recur, they usually are higher grade
tumors.
Anaplastic tumors are malignant tumors with mitoses and
nuclear atypia.
Glioblastoma multiforme are malignant tumors with
necrosis and microvascular proliferation.
The terms benign and malignant can be used to
describe the pathologic appearance of a brain tumor, but
the terms often do not convey appropriate information
about the overall prognosis from a tumor. A tumor can
have a benign histology but be unresectable and
difficult to control with radiation or chemotherapy, and
thus be a life-limiting problem. Examples of benign
tumors with a possible poor prognosis are
craniopharyngiomas, meningiomas, schwannomas, or
hypothalamic gliomas.
Treatment
1. Surgery
Biopsy – needle biopsy, often with frameless MRI
guidance
Subtotal Resection – debulking to decrease mass effect
and improve symptoms. May not change overall prognosis.
Gross Total Resection – for most tumors (except CNS
lymphoma, germinoma), the prognosis is significantly
improved by gross total tumor resection. Benefits of
resection for tumor control must be balanced against
minimizing neurologic deficits.
2. Radiation
Cranial – whole brain radiation often used for
metastatic disease. Delayed (>2yrs) cognitive decline in
about 10%
Focal – fractionated radiation to involved area of brain
or spine to limit microscopic growth while minimizing
damage to normal tissue and exposure of uninvolved areas
Stereotactic – linear accelerator or gamma knife used to
deliver ablative dose to small (<4 cc3) defined area
3. Chemotherapy
Highly effective for very few tumors:
Oligodendroglioma with specific genetic abnormalities (LOH
1p & 19 q)
Procarbazine, lomustine, vincristine (PCV)
Chemosensitive tumor survival from diagnosis >10 yrs
Used as adjunct for many tumors, but relatively
ineffective:
Most gliomas (nitrosureas
CNS lymphoma
Primitive neuroectodermal tumors (medulloblastoma)
Germ cell tumors
Common CNS Tumors in Adults (at diagnosis)
Metastatic tumors 30%
Primary CNS tumors 70%
Gliomas 65%
(2/3’s of primary brain tumors are gliomas, and 2/3’s
are malignant)
Meningiomas 15%
Schwannoma 6%
Primitive neuroectodermal tumors 6%
Pituitary tumors 5%
Craniopharyngiomas 3%
Adult Tumors
1. Metastatic tumors
One quarter of all patients with systemic cancer develop
CNS metastatic disease.
Single lesion (50%), multiple lesions (50%), or
carcinomatous meningitis.
Most common cause is lung carcinoma.
Other common causes are colon, renal, breast and
melanoma.
65% of melanomas metastasize to the brain. Often
hemorrhage.
Treat with surgery and radiation (cranial and
stereotactic)
2. Gliomas
Most common primary tumor in adults, two-thirds of which
are malignant.
Significant prognostic indicators:
Patient age
Tumor location and resectability
Neurologic function at diagnosis
Average survival with maximal therapy has remained about
1 year. Tumors recur locally and infiltrate extensively.
3. Meningiomas
Tumors occur along the skull base, the falx and
tentorium, and over the convexity. Although the
pathology is usually benign, the tumors can invade from
the dura into the bone, and entrap cranial nerves and
vessels. Meningiomas have a varied course. Some are
quiescent for many years without treatment, some are
cured by surgical resection, and others recur
extensively despite surgery and radiation.
4. Schwannomas
Nerve sheath tumors frequently occur on the vestibular
nerve (acoustic neuroma), but can occur on other cranial
nerves. Small tumors can be treated with observation,
surgery, or stereotactic radiosurgery, and larger tumors
require surgery.
5. Pituitary Tumors
Tumors are classified by size (microadenoma <1cm,
macroadenoma >1cm), and by hormone secretion.
Macroadenomas present with symptoms of pituitary
dysfunction or visual symptoms, while microadenomas
typically present with endocrine symptoms. Prolactinomas
are the most common tumor. Other hormone secreting
tumors include growth-hormone, ACTH, and mixed tumors.
Pituitary apoplexy (hemorrhage into a pituitary tumor)
can cause sudden visual loss and hypopituitarism that
can be life-threatening.
Common CNS Tumors in Children
Location by age Supratentorial Infratentorial
< 2 yrs 75% 25%
2-10 yrs 40% 60%
10-20 yrs 60% 40%
Adult 75% 25%
Pediatric CNS Tumor Histology by Age
Infants Children
Supratentorial gliomas 35% 30%
Primitive neuroectodermal tumor 25% 20%
Cerebellar juvenile pilocytic astrocytoma 15%
Brainstem gliomas 15%
Ependymoma 15% 5%
Choroid plexus papilloma 10%
Craniopharyngiomas 5%
Pineal region tumors 5%
Spinal canal 5%
Rhabdoid tumors 5%
Pediatric Tumors
1. Supratentorial gliomas
Two-thirds of tumors are low-grade. Half of the
low-grade tumors are astrocytomas; half have more exotic
pathology. If the tumors are resectable some can be
cured. Prognosis depends upon tumor histology, tumor
location, and extent of resection. Children with
malignant tumors and maximal therapy survive 1-3 years.
2. Primitive neuroectodermal tumors
Malignant tumors that occur throughout the CNS with
similar histology and prognosis, but that were given
different names in the past depending on location.
Medulloblastomas arise in the fourth ventricle, and
comprise 30% of posterior fossa tumors of childhood.
Medulloblastoma is the most common malignant brain tumor
of childhood. Medulloblastomas occur in adults
infrequently. The 5 year survival of pediatric
medulloblastoma has improved to about 70%, on the basis
of complete surgical resection and adjuvant therapy
which usually includes craniospinal radiation (because
of the strong tendency of medulloblastoma to seed the
subarachnoid space) and often chemotherapy.
3. Juvenile pilocytic astrocytomas
Tumors occur in the cerebellar hemispheres, frequently
with cysts. Gross total resection can cure >95% in the
posterior fossa. Pathology is WHO grade I, the same
pathology as optic and hypothalamic astrocytomas. In
contrast to cerebellar astrocytomas, astrocytomas of the
optic apparatus and hypothalamus are generally not
amenable to gross total resection.
4. Brainstem gliomas
Diffusely infiltrative unresectable tumors that show a
poor response to radiation and chemotherapy. Some
midbrain tectal gliomas remain dormant but may cause
obstructive hydrocephalus. Pontine tumors usually
present with long tract symptoms and signs and cranial
palsies, but not hydrocephalus. Pathology can vary from
WHO I to IV, but the prognosis is typically dismal
(almost all die by 18 months after diagnosis).
5. Ependymoma
Malignant tumor that often arises in the posterior fossa,
but is found throughout the CNS. Tumor tends to extrude
through the outlets of the fourth ventricle and encase
cranial nerves and vessels. Typically present with
symptoms of obstructive hydrocephalus, but frequently
have lower cranial nerve palsies after resection. The
prognosis is generally significantly worse than that for
medulloblastoma. With complete resection and radiation,
survival may reach 40% at 5 years. Chemotherapy is not
effective. Late recurrences occur.
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