Neuroscience Clerkship

 

 

Neurosurgery Lecture

Brain Tumors
Powerpoint Lecture On-Line
   (download file)
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.