Chapter 4

Facts About Brain Tumors

In the following pages there may be words that are new to you. There is a glossary of definitions available to assist you.

What Is A Tumor?

A tumor is any abnormal mass which results from the increased multiplication (division) of cells. A tumor may also be called a neoplasm or growth (mass).

Why Do Tumors Occur?

The reason why brain tumors occur remains a mystery. Researchers have considered environmental and genetic factors, but in brain tumors, there are no clear-cut associations. Research is progressing into a number of new areas such as oncogenes (the presence of special genes in our cells that may be associated with cancer) and the abnormal production of specialized growth factors. At the present time, there is no way to prevent or predict who will get a brain tumor.

How Do Brain Tumors Become Evident?

Symptoms may have developed in your child because of one or both of the following:

The tumor may block the cerebrospinal fluid pathways or because of its ize cause pressure to build up inside the child's head. Symptoms of increased pressure due to hydrocephalus or tumor size include headaches (often in the morning or during sleep), often associated with nausea and vomiting. After vomiting, the child may feel some relief of his/her headache.
The tumor has pressed on the surrounding brain, affecting its ability to function properly.

Symptoms that commonly occur in children, depending on the area of the brain affected, include:

unsteady walking
changes in eye movements
blurred or double vision
weakness of arm and leg on one side
seizures
fatigue or changes in energy level or sleep patterns
personality change
growth and development patterns may be disturbed (rarely)

If your child is a baby, the only symptom may be a head that is growing too fast. Because an infant skull can grow to accommodate the extra volume (tumor), a baby may present with an enlarged head. Other symptoms may be delayed, in their onset, in infants.

How is a Brain Tumor Diagnosed?

Most parents take their child to see their family doctor because something unusual has happened or changed in his/her daily health pattern. If the ymptoms that have brought your child to the physician cannot be attributed to other illnesses, the child will be sent to a neurosurgeon or neurologist who will, after a thorough neurological assessment, order such tests as EEG, CT Scan or MRI Scan to make a definite diagnosis. Once a brain tumor has been diagnosed, a decision will be made as to the best method(s) of treatment.

What Is Meant By Primary And Secondary Brain Tumors?

Primary brain tumors are those that start in the specialized cells that make up the brain and its coverings. Secondary brain tumors (metastatic brain tumors) tart in some other body organ such as the lung, breast, kidney or skin and then pread to the brain. Most brain tumors in children are primary. Rarely may cancers elsewhere in the body spread to the brain and its coverings. These include leukemia, bone cancers and neuroblastomas.

What Is Meant By Benign And Malignant Brain Tumors?

Benign brain tumors are made up of cells which are slow growing (the tumor grows very slowly) and do not invade important structures, although they may urround them. If a benign tumor can be completely removed surgically, it usually does not regrow. If a benign tumor is incompletely removed, it may regrow (recur).

Malignant tumors are fast growing since the cells that are found in them divide quickly. These tumors may invade and damage important structures and it is uncommon for primary malignant tumors to be completely removed surgically. Malignant primary brain tumors seldom travel (metastasize) to any other part of the body though they may spread to other parts of the brain or spinal cord.

How Common Are Brain Tumors?

Fortunately, brain tumors in children are rare. They are, however, the most common cause of solid cancer (forming a mass) in children, and the second most common cause of cancer in children with leukemia being the most common.

Over 10,000 cases of brain tumors (primary and secondary) occur in Canada every year. At least one third of these cases are primary brain tumors.

Different types of tumors in childhood appear to be related to certain ages. The majority of tumors occur between the ages of 4 and 8.

What Types Of Brain Tumors Are Common In Children?

The World Health Organization's designation system organizes tumors on the basis of their histologic (cellular) features. These categories, along with the position in which these tumors arise are used to explain the tumor types.

On occasion, the cells in the tumors may change and the diagnosis may change from one category to another.

This classification system may again change in the future as pathologists, geneticists and biochemists look at things such as glial proteins present in cells, genetics and other markers in making their diagnosis.

The following contains a description of some brain tumors common in children. For more detailed information consult your physician.

Gliomas

This is a name given to a family of brain tumors that are formed from the supporting cells of the nervous system. They do not arise from the neurons (nerves). These tumors account for over half of all brain tumors. Gliomas are subclassified into categories according to their cell type.

Gliomas may be given different names from centre to centre and over the past few years, patients have become increasingly confused when they read literature or speak to someone beyond their primary physician.

Generally, gliomas are classified according to whether they are slow or fast growing.

Astrocytomas

One third of all pediatric brain tumors are astrocytomas.

Grading Systems for Astrocytic Tumors

A number of different brain tumor classification systems have been proposed and continue to be used to group brain tumors into subtypes which help predict specific tumor growth characteristics.

An accurate and reliable classification system used by physicians world-wide would be especially useful in the evaluation of different brain tumor treatments. The use of different classification systems for the same tumor has led to some confusion and it is recommended that you be aware of the type of tumor classification system used in the centre where your child is receiving treatment. The major classification systems used are outlined in the table below. The classification system used in this book is that of the World Health Organization's revised 1993 classification. Pilocytic astrocytoma is clearly differentiated from Astrocytoma (low grade) and the designation anaplastic astrocytoma and glioblastoma multiforme (GBM) are used to denote malignant astrocytic tumors. Please refer to the table at the end of this chapter for a complete schedule of classifications.

World Health Organization Designation	Kernohan Grading	St. Anne / Mayo Clinic
Comparison of a number of commonly used grading systems for astrocytomas *
World Health Organization Designation	Kernohan Grading	Designation	Histological Criteria
Pilocytic Astrocytoma		Astrocytoma Grade 1	Zero criteria
Astrocytoma (low grade)	Astrocytoma Grade 1 Astrocytoma Grade 2	Astrocytoma Grade 2	One criteria usually nuclear atypia
Anaplastic Astrocytoma	Astrocytoma Grade 3	Astrocytoma Grade 3	Two criteria usually nuclear atypia and mitotic activity
Glioblastoma Multiforme (GBM)	Astrocytoma Grade 4	Astrocytoma Grade 4	Three criteria, usually nuclear atypia, mitoses, endotherial proliferation and/or necrosis
* Adapted from Kleihues et al Brain Pathology 3. 255-268 (1993)

Cerebellar Pilocytic Astrocytomas

These tumors are considered benign. First symptoms of these tumors are usually headache, vomiting or an unsteady gait. They occur equally between the sexes and at all ages in children, although they are unusual in infants. Approximately two-thirds of these tumors are cystic (have a fluid cyst associated with a solid mass) in nature.

Management of the child with an astrocytoma usually involves also treating the problem of hydrocephalus. This is usually accomplished pre-operatively with steroids (dexamethasone, or the more common trade name of Decadron) which frequently relieve symptoms in 24-48 hours. A second approach to hydrocephalus infrequently requires the placement of a shunt in the days before surgery. See the section on shunts in Chapter 11.

The goal of treatment of a cerebellar astrocytoma is complete surgical removal. This is achieved in a large majority of cases, and no further treatment is necessary. If total removal is not possible (for example it may have grown into the brain stem) radiation therapy may be necessary. Chemotherapy has not been found to be useful in the treatment of cerebellar astrocytomas. Pilocytic astrocytomas can occur in other parts of the brain and their treatment is usually urgery and radiation therapy if necessary.

Hemispheric Astrocytoma (low grade)

These are astrocytomas that are located in the hemispheres of the brain. They are most common in children between the ages of 8 and 12 years. First symptoms of these tumors usually include nausea, vomiting, headache and difficulties with vision.

Surgical removal is the method of treatment for these astrocytomas. Radiation may also be necessary if the tumor is in an area of the brain responsible for uch functions as speech, understanding or movement and it cannot be easily urgically removed.

Anaplastic Astrocytoma

The cells of these tumors are moderately fast growing and less well defined than an astrocytoma (low grade). Treatment involves removal of as much tumor as safely possible plus radiation and chemotherapy.

Glioblastoma Multiforme (GBM)

These tumors may contain various cell types, hence the name "multiforme". These tumors are more common in the elderly.

New data suggests that these tumors may be on the increase in the adult population. Surgery may be performed to remove as much tumor as possible. Radiation and chemotherapy are used to control growth of the tumor. Most of these tumors occur in the front portion of the brain (cerebral hemispheres).

The cells of these tumors grow quickly, are not well defined, and they may frequently spread throughout the brain.

Brain Stem Gliomas

Brain stem gliomas are astrocytomas that usually start in the pons. Ten to twenty-five percent (10%-25%) of pediatric brain tumors will be brain stem gliomas. These tumors occur equally between sexes and most often occur between the ages of 5-10 years. Brain tem gliomas are located in an area of the brain and spinal cord that is responsible for many vital body functions. These include vision, balance, trength, gagging, coughing and swallowing.

Because of the location of these tumors, surgery is rarely an option (except for biopsy and draining of cyst). Radiation to the mass is the usual method of treatment. Some centres may add chemotherapy before or after radiation treatment.

Optic Nerve Gliomas

Optic nerve gliomas represent four to six percent (46%) of all pediatric brain tumors. They are located along the optic nerves, the optic chiasm and the hypothalamus. See the section on Eye Signs and Symptoms in Chapter 11.

These tumors are usually slow growing (astrocytomas). Symptoms will vary depending on location but may include decreased vision, double vision and papilledema (swelling of the optic nerve). If vision has been lost, surgery may be considered. If visual function remains, there will be careful follow-up with imaging studies done at regular intervals. Radiation therapy may be an option. For tumors that involve the hypothalamus and the third ventricle, there may be igns of hydrocephalus as well as hormone imbalance. Surgical treatment of hydrocephalus may be considered. Some tumors located here respond well to chemotherapy and it may be considered.

Oligodendrogliomas

These tumors are not common in children and are slow growing. The mass usually appears calcified (calcium deposits) on imaging (CT scan or MRI scan) showing that it has been there for many years. These tumors arise from the oligodendroglial cells which make up the myelin that insulates nerve fibres. Symptoms of these tumors may include seizures, headache and vision problems. Treatment usually involves surgical removal along with a course of radiation and/or chemotherapy if sub-totally removed.

Ependymomas

These tumors arise from the cells lining the ventricles (hollow channels) of the brain (most commonly the fourth ventricle). As these tumors grow and fill the ventricle, they obstruct the flow of cerebrospinal fluid (CSF) through the brain. These tumors appear more commonly among younger children. Symptoms of this tumor include headache, nausea, vomiting, balance problems and visual disturbances.

Hydrocephalus, caused by the blocking of the flow of cerebrospinal fluid, may make shunting necessary. Total surgical removal is not always possible, and treatment often involves radiation therapy and/or chemotherapy.

Gangliogliomas

Gangliogliomas are generally slow growing tumors and may occur anywhere in the brain although the temporal lobe is the most common ite. The average age at the time of diagnosis is 12 years. Many children are diagnosed after a long history of seizures that have been difficult to treat. Intellectual and behavioral difficulties may be present. Treatment is usually total removal by surgery.

Mixed Gliomas

You may hear this term used. A tumor may be composed of two or more cell types (as seen under the microscope). The tumor is generally named for the type of glioma cells which grow the fastest.

Primitive Neuroectodermal Tumors (PNET)

Medulloblastoma

Twenty percent (20%) of all pediatric brain tumors are PNETs. They are most commonly found in the cerebellum and are called medulloblastomas when they occur here. They are most commonly found in the cerebellum. These tumors are twice as common in boys, with diagnosis frequently between the ages of 4 and 8. These tumors are fast growing and symptoms include a short, progressive history of headaches, vomiting, loss of appetite and coordination difficulties. Spread outside of the brain and spinal cord is rare although it may occur. Very often, these tumors have spread within the central nervous system before diagnosis. Spread through the CSF is common (carcinomatous meningitis). The extent of the tumor is often classified according to a staging system. This system is outlined below and is an important consideration when planning appropriate treatment:

Stage	Description
Staging System for Medulloblastomas *
T1	Tumor is less than 3cm. in diameter and does not go beyond the midline of the brain, the roof of the fourth ventricle or the cerebellar hemispheres.
T2	Tumor is greater than 3 cm. in diameter and grows into neighboring brain or spinal cord, or partly fills the fourth ventricle.
T3a	Tumor grows into two neighboring parts of the brain or spinal cord or completely fills in the fourth ventricle, producing signs of hydrocephalus.
T3b	Tumor grows from the floor of the fourth ventricle or brain stem and fills the fourth ventricle, producing signs of hydrocephalus.
T4	Tumor spreads to involve the third ventricle or midbrain or upper cervical cord.
M0	No evidence of spread around the brain or to any other part of the body.
M1	Microscopic tumor cells found in cerebrospinal fluid.
M2	Tumor seeding (separate from primary tumor) found in cerebellum, subarachnoid space or in the third or lateral (on either side) ventricles.
M3	Tumor seeding (separate from primary tumor) found in spinal subarachnoid space.
M4	Tumor spread outside the cerebrospinal system.
* Chang CH, Housepian EM, Herbert C Jr.: An operative staging system and a megavoltage radiotherapeutic technique for cerebellar medulloblastomas, Radiology 93: 1351-1359, 1969

It is important to be aware of the above stages as they may be discussed with you in terms of treating your child's tumor.

Treatment almost always involves surgery with the goal of removing all (gross total) or as much as possible (subtotal) of the tumor. Radiation is very effective against this tumor and is generally done to the entire head and spinal cord because of the high possibility of seeding malignant cells by way of the cerebrospinal fluid. Chemotherapy has been shown to be effective.

After your child has had his/her tumor staged, the treatment best fitted for his/her tumor will be used. An effective chemotherapy protocol has been developed and although we do not yet know the long-term results of its use, the outlook for this type of tumor has improved dramatically over the last ten years. Shunting may be necessary to treat hydrocephalus caused by the tumor interrupting the pathways of the cerebrospinal fluid.

Other Primitive Neuroectodermal Tumors

cerebral neuroblastoma (located in hemispheres)
ependymoblastoma (arises from ventricles)
pineoblastoma (occurs in area of pineal gland)

The cells of these tumors are generally not alike and they are fast growing. They are found throughout the brain and tend to seed (spread in the spinal fluid). They make up less than five percent (5%) of all pediatric brain tumors. They are treated with complete surgical removal if possible and are followed by radiation and chemotherapy.

Pineal Region Tumors

The pineal gland is located centrally in the brain and is an outpouching of the third ventricle. Hydrocephalus is usually a presenting symptom as the cerebrospinal fluid pathway may be blocked. The optic (vision) pathways may also be involved and there may be some double vision. Surgery is sometimes possible or a biopsy may be performed to obtain a diagnosis. Some of these tumors are sensitive to radiation. A shunt may be necessary to treat the hydrocephalus, although hydrocephalus may be initially controlled by the use of steroids. Some germ cell tumors may be treated with chemotherapy.

There are four categories of pineal region tumors:

Germ cell tumors:

fast growing:

choriocarcinoma
embryonal carcinoma
endodermal sinus tumor

not as fast growing:

germinomas

slow growing:

dermoid cysts
epidermoid cysts
teratomas

Dermoid and Epidermoid Cysts

Teratomas

Pineal cell tumors:

fast growing: pinealoblastomas
slow growing: Pinealocytomas

Treatment is usually biopsy, or if small, surgical removal. Radiation therapy follows and some centres are using chemotherapy.

Glial cell tumors:

Any glial tumor, both slow and fast growing, can be found in the pineal region. These are discussed earlier in this chapter (e.g. astrocytomas).

Miscellaneous tumors:

These tumors are almost all slow growing:

cysts: accumulation of abnormal fluid enclosed in a lining.
meningiomas: a tumor with distinct borders usually causing symptoms by pressure on the neighboring area of the brain (discussed later in this chapter).

Craniopharyngiomas

These slow growing tumors account for approximately nine percent (9%) of all pediatric brain tumors and usually occur in children between 5 and 10 years of age. These tumors arise from cells along the pituitary stalk and may grow up and involve the hypothalamus, optic nerve pathways and the third ventricle. These tumors are cystic in nature and slow growing. At diagnosis, children may have igns of increased pressure in the brain (third ventricle blocked), visual loss (either decreased vision or visual field problems) and hormone difficulties (growth delay, thyroid deficiency, sexual delay). Complete removal of this tumor is possible if it is in a favorable location. Otherwise, radiation therapy may be used. All of these children will require long term follow-up by an endocrinologist (a physician who studies the hormone systems of the body) and a neuroopthalmologist. Some of these children will require neuropsychological follow-up. Usually, lifelong hormone replacement is necessary.

Choroid Plexus Papillomas

The choroid plexus is an infolding of the lining of the ventricular surface. This surface has many blood vessels. The choroid plexus is involved in the production of most of the cerebrospinal fluid. A child with a choroid plexus papilloma usually has marked hydrocephalus due to obstruction of flow and sometimes an overproduction of cerebrospinal fluid.

The most common location for this tumor is in the lateral ventricles (the ventricles on either side of the brain). These tumors account for one to three percent (1%-3%) of pediatric brain tumors and are most common in children under the age of 2 years. They make up eight percent (8%) of brain tumors diagnosed in newborn babies.

These tumors are separated into 2 categories as follows:

Papillomas: slow growing (vast majority)
Carcinomas: fast growing (rare)

Treatment for these tumors involves complete surgical resection (removal) for papillomas, whereas carcinomas require surgery, radiation and chemotherapy. On rare occasions, carcinomas may spread to other areas.

Meningiomas

This is a rare tumor of childhood. It is usually a benign tumor that grows within the skull but on the outside of the brain. On rare occasions it may grow within the ventricles. Surgical removal may be curative. Radiation may be used if complete removal is impossible, or the tumor is fast growing. Meningiomas are more common in adults, especially in old age.

Colloid Cysts

These cysts usually occur in the third ventricle and can cause hydrocephalus. They contain embryonic tissue (tissue formed before birth). Treatment includes surgery and sometimes shunting.

Chordomas

These tumors develop from remnants of embryonic tissue. They are slow growing and usually do not produce symptoms until middle age. These tumors can arise in the skull bones at the base of the brain, or in the vertebral bones in the neck or sacrum. Treatment is surgery and radiation therapy.

Lymphomas

Lymphomas arise from specialized cells of the lymphatic ystem and occur both in the brain and spinal cord. The incidence is increased in patients after organ transplantation and patients whose immune system is depressed (e.g. AIDS). These tumors are frequently responsive to steroid medication. Surgery and radiation may be indicated along with chemotherapy.

Primary brain lymphomas are rare in children, but lymphomas starting elsewhere in the body may spread to the brain or spinal fluid.

Pituitary Adenomas

These are tumors of the pituitary gland and can be divided into two groups. The first group shows signs of a space-occupying lesion where the other shows signs of abnormal activity of the gland.

Space-occupying lesions (nonfunctioning tumor) - Symptoms of these tumors result from pressure on neighboring structures. They may produce visual disturbances if they compress the visual pathways. Hormone secretion by the pituitary gland can be decreased by compression caused by the growing tumor. This can result in signs of hypopituitarism such as a lack of menstrual periods, reduction of body hair, increased sensitivity to the cold and decreased function of glands stimulated by the pituitary. Treatment is surgical removal and radiation is sometimes used, either alone or in conjunction with surgery.

Secreting Pituitary Tumors (functioning tumors) - Pituitary tumors that contain hormone-secreting cells often produce clinical symptoms before tests can actually show enlargement of the pituitary gland.

Prolactin Secreting Adenomas - These tumors alter hormones resulting in lack of menstrual periods and infertility in women and impotence in men. Galactorrhea (milk coming from the breasts) can also occur.

Growth Hormone Secreting Adenomas - This tumor secretes excessive amounts of growth hormone. In children, giantism results and in adults, acromegaly results. Common features of giantism include rapid growth, joint and muscle tenderness, exercise intolerance and fatigue. In the adult, changes can occur slowly over years. Other conditions that may occur include diabetes mellitus, kidney problems, increased metabolic rate and hypertension (high blood pressure).

In young children, hypopituitary function (lack of) can result in decreased overall growth and the child doesn't grow at a normal rate.

ACTH (Adrenocorticotropic) Secreting Adenomas - These tumors produce ACTH which stimulates the production of cortisol from the adrenal gland. This overproduction of cortisol impairs the body's response to injury and infection. It can deplete the body's potassium while retaining sodium and water. This tumor may result in a change in the body's fat distribution (Cushingoid appearance).

Treatment for hormone secreting tumors may consist of surgery, radiation or drug therapy. Drug therapy consists of using a medication that decreases the compound released by a specific tumor (e.g. growth hormone, prolactin, ACTH). Hormone replacement may be required after surgery. For further information on this subject, see the chapter on neuroendocrine function.

Familial Diseases Associated with Brain Tumors

Genetic counselling is advised in all of the following conditions. Ask for a referral if one is not offered.

Neurofibromatosis

Type 1 - This is a genetically dominant disorder that is passed from one generation to the next. Neurofibromas are slow growing tumors located on or beneath the skin. They may also occur in deeper layers as well as in internal organs. Neurofibromas are composed of tissues from the nervous system, (neuro) and fibrous tissue(fibroma), which form the support structure of the nerve. The skin, bones, endocrine glands and nervous system are sites of congenital abnormality.

Many types of brain tumors can be associated with neurofibromatosis. Most commonly, these are optic nerve tumors, gliomas in other areas, meningiomas and neurofibromas, especially along the spinal cord. These tumors are usually benign. Surgery and/or radiation therapy is sometimes indicated, when the tumor occurs within the central nervous system (brain and spinal cord).

Type 2 - This is different from Type 1 but is also a genetically dominant disorder. It is usually diagnosed by the presence of acoustic neuromas (Schwannomas) on the vestibulo-cochlear nerves on one or both sides of the brain. It usually presents as deafness. Other gliomas may be present. Surgery is often indicated.

The Neurofibromatosis Society of Ontario,

Neurofibromatosis, Inc.

Hippel-Lindau Disease

Tuberous Sclerosis

Tuberous Sclerosis Association of Canada,

National Tuberous Sclerosis Foundation

Spinal Cord Tumors

Tumors which occur in the brain can also occur in the pinal cord, the most common ones being in the glioma family (astrocytomas, ependymomas).

Intrinsic - These occur in the substance of the spinal cord and may be invasive. Treatment is surgery and/or radiation.
Extrinsic - These occur outside the spinal cord and exert pressure on the cord as they grow. The symptoms of these tumors are related to pressure. These tumors can arise from:

dura (meningiomas) or nerves (neurofibromas and Schwannomas) surrounding the spinal cord. These tumors indent the spinal cord like a marble.
metastatic deposits from tumors elsewhere in the body. These tumors start in the bone surrounding the spinal cord and may compress the spinal cord from a number of sides.

Spinal cord tumors frequently present with pain. The pain is usually worse at night and may disturb sleep. At times, the pain may radiate around the chest wall and feel like a grip. Any patient who has had a tumor elsewhere in the body and develops frequent back pain should see his/her doctor.

Treatment is surgery and/or radiation.

See also the graphic on Spinal Cord and Coverings.

Other Tumors

Neuroblastoma

Rhabdomyosarcoma

The extent and location of this disease will determine the required treatment. Radiation and chemotherapy are the usual treatment. Surgery may be an option.

Arachnoid Cysts

Benign Intracranial Hypertension

(Sometimes referred to as Pseudotumor Cerebri)

This entity may often initially be confused with a brain tumor and/or hydrocephalus. The reasons for this confusion are twofold:

The child may complain of headache, blurred or double vision, slight numbness of the face, or dizziness.
When the physician looks into the child's eyes, he/she finds evidence of increased pressure or papilledema.

Together, these findings make one suspicious of a brain tumor or build up of CSF. However, when a CT scan is done, no tumor in the brain is found but the ventricles may be small.

The reasons for this problem are not entirely clear. It is known to occur most often in overweight adolescent girls. The diagnosis is made when a lumbar puncture is performed and the pressure measured (it will be increased ignificantly). It is very important to treat promptly because the increased pressure can lead to permanent visual loss.

Treatment consists mainly of medication (Diamox) which decreases CSF production and may be supplemented by lumbar punctures to remove CSF until normal pressure is maintained. Lastly, it may be necessary to place a permanent shunt in some children.

Leukemia

Leukemia is a cancer of the blood cells. Acute Lymphoblastic Leukemia (ALL) involves the blood forming cells called the lymphocytes. Acute Nonlymphoblastic Leukemia (ANLL) refers to fast dividing blood cells arising from any blood cells other than the lymphocytes.

The survival rate of children with leukemia is high. Children are treated with a combination of chemotherapy drugs with or without radiation treatment. It will continue for 2 to 3 years depending on age, sex, white blood cell count at diagnosis as well as other variables.

Occasionally, a child at high risk with leukemia may require radiation to the head and spinal cord. Radiation is used because drugs commonly used for chemotherapy cannot get through the blood-brain barrier into the brain and kill tumor cells in this location. Very rarely do some leukemia cells make it into the brain and it is expected that they will be killed by the radiation therapy. Alternately, instead of radiation therapy, sometimes chemotherapy drugs are injected directly into the cerebrospinal fluid, either by lumbar puncture or through an Ommaya reservoir into the lateral ventricle, to help prevent the pread of leukemia into the brain or spinal fluid.

It is possible that the child may form a tumor in the brain from the leukemia cells, or much more commonly, that the cells will grow in the cerebrospinal fluid that circulates in the ventricles and around the brain. This is called carcinomatous meningitis. If a child has previously received radiation therapy, he/she cannot receive it again without significant risk of harming healthy cells. In this case, it is possible that an Ommaya reservoir will be put in place by a neurosurgeon. (See Ommaya Reservoir.). Through this reservoir, chemotherapy can be administered directly into the CSF around and in the brain (and thereby bypassing the blood-brain barrier).

Occasionally, children with leukemia or other solid tumors may develop peculiar lesions involving the brain. An example of this would be an infection with bacteria, fungus or virus. A neurosurgeon may be asked to biopsy such a lesion to help in its diagnosis and treatment.

Type of Tumor	Description	Location	Signs & Symptoms	Treatment
Comparison of Common Pediatric Brain Tumors
GLIOMAS:
Astrocytoma, Cerebellar Astrocytoma	May be cystic, usually slow growing	Cerebellum	Headache, vomiting, double vision, incoordination, balance problems	Surgery Radiation if not completely removed Shunting may be necessary for hydrocephalus Chemotherapy may be used for Grades 3 and 4.
Hemispheric Astrocytoma	Usually slow growing	Hemispheres of brain	Headache, nausea, vomiting, visual changes, others depending on specific location of tumor	Surgery Radiation if not completely removed Chemotherapy may be used for Grades 3 and 4
Optic Nerve Glioma	Slow growing; puts pressure on surrounding important areas	Along optic nerves, optic chiasm and hypothalamus	Depends on area along nerves. Maybe dim vision, loss of half of vision, hormone imbalance	Surgery Radiation if incomplete removal or removal not possible
Brain Stem Glioma	May be slow or fast growing	Brain stem (pons)	Double vision, facial weakness, balance problems, vomiting	Surgery usually not possible due to location Radiation Chemotherapy
Oligodendroglioma	Slow growing;frequently calcified. Arise from cells which make the myelin that insulates nerve fibres	Hemispheres of the brain, especially frontal and temporal lobes. More common in the thalamus of children	Seizures, headache, vision problems	Surgery Radiation if not completely removed Chemotherapy may be used
Ependymoma	Usually slow growing; arise from the cells that line the ventricles	Ventricles, especially the fourth ventricle	Signs of hydrocephalus including headache, nausea, vomiting, visual disturbances	Surgery: removal if location allowed Radiation: may be used if child over 4 years (growth and development may be affected under this age) Chemotherapy may be used Shunting, if necessary
Gangliogliomas	Usually slow growing	Anywhere in brain; most common site is temporal lobe	Seizures. There may be intellectual and behavioral difficulties	Surgery is curative Radiation if entire tumor not removed
PRIMITIVE NEUROECTODERMAL TUMORS (PNET):
Medulloblastoma	Fast growing	Cerebellum; may involve fourth ventricle, 3rd and neighbouring ventricles, mid-brain, spinal cord; may involve seeding to other parts of brain, spinal cord and other parts of body outside the brain and spinal cord	Short, progressive history of headache, vomiting,loss of appetite and there may be coordination problems	Surgery Radiation of brain and spinal cord Chemotherapy may be used Shunting, if necessary
Cerebral neuroblastomas, Ependymoblastomas, Pineoblastomas	Fast growing	Throughout the brain and spinal cord; tendency to seed	Depends on location	Surgery, total removal if possible Radiation Chemotherapy
PINEAL REGION TUMORS:
GERM CELL TUMORS:		Pineal region	Hydrocephalus, visual difficulties. Choriocarcinoma, embryonal carcinoma and endodermal sinus tumors can be diagnosed by a blood test or cerebrospinal fluid test	Biopsy Surgery if possible Radiation Steroids Shunting may be necessary Chemotherapy may be used for germ cell tumors and pineal cell tumors
Choriocarcinoma	Fast growing
Embryonal carcinoma	Fast growing
Endo-dermal sinus tumor	Fast growing
Germinomas	Less fast growing
Dermoid cysts	Slow growing	Pineal region and skull
Epidermoid cysts	Slow growing	Pineal region and skull
PINEAL CELL TUMORS:		Pineal region
Pineoblastomas	Fast growing (Actually a PNET of the pineal gland)
Pinealomas (Pinealocytoma)	Slow growing
GLIAL CELL TUMORS:
Discussed under glial tumors	Pineal region and other
MISCELLANEOUS TUMORS:
Cysts	Slow growing	pineal region and other	Hydrocephalus, visual difficulties Choriocarcinoma, embryonal carcinoma and endodermal sinus tumors can be diagnosed by a blood test or cerebrospinal fluid test	Biopsy Surgery if possible Radiation Steroids Shunting if necessary Chemotherapy may be used for germ cell tumors and pineal cell tumors
Meningiomas	Slow growing	Pineal region and other	Discussed below under meningiomas
Craniopharyngiomas	Slow growing, may be cystic in nature	Along the pituitary stalk; may involve the hypothalamus, optic nerve pathways and the third ventricle	Hydrocephalus; hormonal difficulties (e.g. growth delay, diabetes); visual loss including decreased vision and visual field difficulties	Surgery, complete removal if possible Radiation if incomplete removal
CHOROID PLEXUS PAPILLOMAS:
Papillomas	Slow growing	Lining of ventricular surface	Hydrocephalus and its associated symptoms	Surgery
Carcinomas	Fast growing	Lining of ventricular surface	Hydrocephalus and its associated symptoms	Surgery Radiation Chemotherapy
PITUITARY ADENOMAS:
Space occupying or non-secreting tumors	Slow growing; do not invade structures	Optic pathways; pituitary gland	Symptoms related to pressure on neighbouring structures; usually hormone imbalance and visual problems	Surgery Radiation if incomplete removal
SECRETING PITUITARY TUMORS:
Prolactin secreting adenomas	Tumors contain hormone secreting cells and may enlarge glands	Pituitary gland	Delay in expected onset of menstruation; lack of menstruation; alterations in menstruation after it has started (amenorrhea)	Surgery Radiation Drug therapy to reduce the amount of hormone released by the tumor Hormone replacement may be required after surgery
Growth hormone secreting adenomas			Giantism, diabetes millitus
ACTH (adrenocorticotropic) secreting adenomas			Overproduction of cortisol can impair response to injury and infection; decreased potassium
MENINGIOMAS:
Meningiomas	Very slow growing and rare in children	Within the skull but on the outside of the brain	Symptoms related to pressure on neighboring structures	Surgery Radiation, if incomplete removal

WHO Histological Typing of CNS Tumors *
1	Tumors of Neuroepithelial Tissue
	1.1	Astrocytic Tumors
		1.1.1	Astrocytoma
			1.1.1.1	Variants: Fibrillary
			1.1.1.2	Protoplasmic
			1.1.1.3	Gemistocytic
		1.1.2	Anaplastic (malignant) astrocytoma
		1.1.3	Glioblastoma
			1.1.3.1	Variants: Giant cell glioblastoma
			1.1.3.2	Gliosarcoma
		1.1.4	Pilocytic astrocytoma
		1.1.5	Pleomorphic xanthoastrocytoma
		1.1.6	Subependymal giant cell astrocytoma (Tuberous Sclerosis)
	1.2	Oligodendroglial tumors
		1.2.1	Oligodendroglioma
		1.2.2	Anaplastic (malignant) oligodendroglioma
	1.3	Ependymal tumors
		1.3.1	Ependymoma
			1.3.1.1	Variants: Cellular
			1.3.1.2	Papillary
			1.3.1.3	Clear cell
		1.3.2	Anaplastic (malignant) ependymoma
		1.3.3	Myxopapillary ependymoma
		1.3.4	Subependymoma
	1.4	Mixed Gliomas
		1.4.1	Oligo-astrocytoma
		1.4.2	Anaplastic (malignant) oligo-astrocytoma
		1.4.3	Others
	1.5	Choroid plexus tumors
		1.5.1	Choroid plexus papilloma
		1.5.2	Choroid plexus carcinoma
	1.6	Neuroepithelial tumors of uncertain origin
		1.6.1	Astroblastoma
		1.6.2	Polar spongioblastoma
		1.6.3	Gliomatosis cerebri
	1.7	Neuronal and mixed neuronal-glial tumors
		1.7.1	Gangliocytoma
		1.7.2	Dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos)
		1.7.3	Desmoplastic infantile ganglioglioma
		1.7.4	Dysembryoplastic neuroepithelial tumor
		1.7.5	Ganglioglioma
		1.7.6	Anaplastic (malignant) ganglioglioma
		1.7.7	Central neurocytoma
		1.7.8	Paraganglioma of the filum terminale
		1.7.9	Olfactory neuroblastoma (Aesthesioneuroblastoma)
			1.7.9.1	Variant: Olfactory neuroepithelioma
	1.8	Pineal parenchymal tumors
		1.8.1	Pineocytoma
		1.8.2	Pineoblastoma
		1.8.3	Mixed / transitional pineal tumors
	1.9	Embryonal tumors
		1.9.1	Medulloepithelioma
		1.9.2	Neuroblastoma
			1.9.2.1	Variant: Ganglioneuroblastoma
		1.9.3	Ependymoblastoma
		1.9.4	Primitive neuroectodermal tumors (PNETS)
			1.9.4.1	Medulloblastoma
				1.9.4.1.1	Variants: Desmoplastic medulloblastoma
				1.9.4.1.2	Medullomyoblastoma
				1.9.4.1.3	Melanotic medulloblastoma
2	Tumors of Cranial and Spinal Nerves
	2.1	Schwannoma (Neurilemmoma, Neurinoma)
		2.1.1	Variants: Cellular
		2.1.2	Plexiform
		2.1.3	Melanotic
	2.2	Neurofibroma
		2.2.1	Circumscribed (solitary)
		2.2.2	Plexiform
	2.3	Malignant peripheral nerve sheath tumor (MPNST) (Neurogenic sarcoma, Anaplastic neurofibroma, "Malignant schwannoma")
		2.3.1	Variants: Epithelioid
		2.3.2	MPNST with divergent mesenchymal and / or epithelial differentiation
		2.3.3	Melanotic
3	Tumors of the Meninges
	3.1	Tumors of the meningothelial cells
		3.1.1	Meningioma
			3.1.1.1	Variants: Meningothelial
			3.1.1.2	Fibrous (fibroblastic)
			3.1.1.3	Transitional (mixed)
			3.1.1.4	Psammomatous
			3.1.1.5	Angiomatous
			3.1.1.6	Microcystic
			3.1.1.7	Secretory
			3.1.1.8	Clear cell
			3.1.1.9	Chordoid
			3.1.1.10	Lymphoplasmacyte-rich
			3.1.1.11	Metaplastic
		3.1.2	Attypical meningioma
		3.1.3	Papillary meningioma
		3.1.4	Anaplastic (malignant) meningioma
	3.2	Mesenchymal, non-meningothelial tumors
	3.3	Benign neoplasms
		3.3.1	Osteocartilaginous tumors
		3.3.2	Lipoma
		3.3.3	Fibrous histiocytoma
		3.3.4	Others
	3.4	Malignant neoplasms
		3.4.1	Hemangiopericytoma
		3.4.2	Chondrosarcoma
			3.4.2.1	Variant: Mesenchymal chondrosarcoma
		3.4.3	Malignant fibrous histiocytoma
		3.4.4	Rhabdomyosarcoma
		3.4.5	Meningeal sarcomatosis
		3.4.6	Others
	3.5	Primary melanocytic lesions
		3.5.1	Diffuse melanosis
		3.5.2	Melanocytoma
		3.5.3	Malignant melanoma
			3.5.3.1	Variant: Meningeal melanomatosis
	3.6	Tumors of uncertain histogenesis
		3.6.1	Hemangioblastoma (Capillary hemangioblastoma)
4	Lymphomas and Hemopoietic Neoplasms
	4.1	Malignant lymphomas
	4.2	Plasmacytoma
	4.3	Granulocytic sarcoma
	4.4	Others
5	Germ Cell Tumors
	5.1	Germinoma
	5.2	Embryonal carcinoma
	5.3	Yolk sac tumor (endodermal sinus tumor)
	5.4	Choriocarcinoma
	5.5	Teratoma
		5.5.1	Immature
		5.5.2	Mature
		5.5.3	Teratoma with malignant transformation
	5.6	Mixed germ cell tumors
6	Cysts and Tumor-like Lesions
	6.1	Rathke cleft cyst
	6.2	Epidermoid cyst
	6.3	Dermoid cyst
	6.4	Colloid cyst of the third ventricle
	6.5	Enterogenous cyst
	6.6	Neuroglial cyst
	6.7	Granular cell tumor (Choristoma, Pituicytoma)
	6.8	Hypothalamic neuronal hamartoma
	6.9	Nasal glial heterotopia
	6.10	Plasma cell granuloma
7	Tumors of the Sellar Region
	7.1	Pituitary adenoma
	7.2	Pituitary carcinoma
	7.3	Craniopharyngioma
	7.3.1	Variants: Adamantinomatous
	7.3.2	Papillary
8	Local Extensions from Regional Tumors
	8.1	Paraganglioma (Chemodectoma)
	8.2	Chordoma
	8.3	Chondroma
	8.4	Chondrosarcoma
	8.5	Carcinoma
9	Metastatic Tumors
10	Unclassified Tumors
* Reproduced from: P. Kleihues, P.C. Burger, B.W. Scheithauer (1993) Histological Typing of Tumours of the Central Nervous System, World Health Organization, International Histological Classification of Tumours, Springer-Verlag: Berlin, Heidelberg

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