Brain Tumors in Children/Pediatric Brain Tumors and Cancers

Dr Prem Pillay
Senior Consultant Pediatric Neurosurgeon and Expert in Pediatric Brain Tumors and Cancers
(Higher training in Pediatric Neurosurgery including brain tumors and cancers at the Childrens Center of the Cleveland Clinic,  Fellow at MD Anderson Cancer Center and The Hospital for Sick Children, Toronto).

What is a brain tumor?

Brain tumors are the most common solid tumors in children. Brain and Spinal cord tumors account for 1 in 4 childhood cancers. Approximately 4,000 children and adolescents in the U.S. are diagnosed with primary brain tumors each year. Primary brain tumors start in the brain and generally do not spread outside the brain tissue. Most central nervous system cancers are brain tumors. Brain tumors, either malignant or benign, are tumors that originate in the cells of the brain. A tumor is an abnormal growth of tissue.

A benign tumor does not contain cancer cells and usually, once removed, does not recur. Most benign brain tumors have clear borders, meaning they do not invade surrounding tissue. These tumors can, however, cause symptoms similar to cancerous tumors because of their size and location in the brain.

Malignant brain tumors contain cancer cells. Malignant brain tumors are usually fast growing and invade surrounding tissue. Malignant brain tumors very rarely spread to other areas of the body, but may recur after treatment. Sometimes, brain tumors that are not cancer are called malignant because of their size and location, and the damage they can do to vital functions of the brain.

Brain tumors can occur at any age. Brain tumors that occur in infants and children are very different from adult brain tumors, both in terms of the type of cells and the responsiveness to treatment.

The American Cancer Society states that no apparent reason can be found for the development of brain tumors in children. Brain tumors cannot be directly linked to something the parents or child did or did not do.

In addition, both the American Academy of Pediatrics and the National Cancer Institute recommend that children receive brain cancer diagnosis and treatment by Neurosurgeons that specialize in pediatric brain tumors and cancers. Research studies  show a 20% to 40% higher survival rates when children receive such care.

Anatomy of the brain

The central nervous system (CNS) consists of the brain and spinal cord. The brain is an important organ that controls thought, memory, emotion, touch, motor skills, vision, respirations, temperature, hunger, and every process that regulates our body.

The brain can be divided into the cerebrum, the brainstem, and the cerebellum:

Anatomy of the brain

  • Cerebrum (front of brain). The cerebrum is composed of the right and left hemispheres. Functions of the cerebrum include: initiation of movement, temperature sensation, touch, vision, hearing, judgment, reasoning, problem solving, emotions, and learning.
  • Brainstem (base of brain). This includes the midbrain, the pons, and the medulla. Functions of this area include: movement of the eyes and mouth, relaying sensory messages (for example, hot, pain, or loud), hunger, respirations, consciousness, cardiac function, body temperature, involuntary muscle movements, sneezing, coughing, vomiting, and swallowing.
  • Cerebellum (back of brain). Located at the back of the head, the cerebellum’s function is to coordinate voluntary muscle movements and to maintain posture, balance, and equilibrium.

What causes brain tumors?

The majority of brain tumors have abnormalities of genes involved in cell cycle control, causing uncontrolled cell growth. These abnormalities are caused by alterations directly in the genes, or by chromosome rearrangements that change the function of a gene.

Patients with certain genetic conditions (neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni syndrome, and retinoblastoma) also have an increased risk for developing tumors of the central nervous system. There have also been some reports of children in the same family developing brain tumors who do not have any of these genetic syndromes.

Some chemicals may change the structure of a gene that protects the body from diseases and cancer. Research has been investigating parents of children with brain tumors and their past exposure to certain chemicals, including pesticides and petroleum products.

Children who have received radiation therapy to the head as part of prior treatment for other malignancies are also at an increased risk for new brain tumors.

What are the symptoms of a brain tumor?

The following are the most common symptoms of a brain tumor. However, each child may experience symptoms differently. Symptoms vary depending on size and location of tumor. Many symptoms are related to an increase in pressure in or around the brain, except in very young children (whose skull bones have not yet fused together), as there is no spare space in the skull for anything except the delicate tissues of the brain and its fluid. Any tumor, extra tissue, or fluid can cause pressure on the brain and result in the following symptoms:

  • Increased intracranial pressure (ICP). ICP is caused by extra tissue or fluid in the brain. Pressure may increase because one or more of the ventricles that drain cerebrospinal fluid (CSF, the fluid that surrounds the brain and spinal cord) has been blocked, causing the fluid to be trapped in the brain. Increased ICP can cause the following:
    • Headache
    • Vomiting (usually in the morning)
    • Nausea
    • Personality changes
    • Irritability
    • Drowsiness
    • Depression
    • Decreased cardiac and respiratory function and eventually coma if not treated
  • Symptoms of brain tumors in the cerebrum (front of brain) may include:
    • Seizures
    • Visual changes
    • Slurred speech
    • Paralysis or weakness on half of the body or face
    • Increased intracranial pressure (ICP)
    • Drowsiness and/or confusion
    • Personality changes/impaired judgment
    • Short-term memory loss
    • Gait disturbances
    • Communication problems
  • Symptoms of brain tumors in the brainstem (base of brain) may include:
    • Seizures
    • Endocrine problems (diabetes and/or hormone regulation)
    • Visual changes or double vision
    • Headaches
    • Paralysis of nerves/muscles of the face, or half of the body
    • Respiratory changes
    • Increased intracranial pressure (ICP)
    • Clumsy, uncoordinated walk
    • Hearing loss
    • Personality changes
  • Symptoms of brain tumors in the cerebellum (back of brain) may include:
    • Increased intracranial pressure (ICP)
    • Vomiting (usually occurs in the morning without nausea)
    • Headache
    • Uncoordinated muscle movements
    • Problems walking (ataxia)

The symptoms of a brain tumor may resemble other conditions or medical problems. Some pituitary tumors may cause diabetes insipidus, with symptoms of abnormal electrolytes and changes in mental status. Some people with deep thalamic tumors have abnormal eating patterns. These tumors may be particularly difficult to diagnose in adolescents because of the symptoms. Always consult your child’s doctor for a diagnosis.

How is a brain tumor diagnosed?

In addition to a complete medical history and physical examination of your child, examination procedures for a brain tumor may include:

  • Neurological exam. Your child’s doctor tests reflexes, muscle strength, eye and mouth movement, coordination, and alertness.
  • Computed tomography scan (also called a CT or CAT scan). A diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce horizontal, or axial, images (often called slices) of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs, such as the brain. CT scans are more detailed than general X-rays.
  • Magnetic resonance imaging (MRI). A diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body. MRI is very helpful for looking at the brain and spinal cord.
  • X-ray. A diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.
  • Angiogram. A dye is used to visualize all the blood vessels in the brain with X-rays in order to detect certain types of tumors. (This test is used less often than in the past because special CT or MRI angiogram techniques can now be used to look at blood vessels in the brain.)
  • Myelogram. An X-ray of the spine, similar to an angiogram.
  • Lumbar puncture/spinal tap. A special needle is placed into the lower back, into the spinal canal. This is the area around the spinal cord. A small amount of cerebral spinal fluid (CSF) can be removed and sent for testing. CSF is the fluid which bathes the brain and spinal cord.
  • Positron emission tomography (PET). In nuclear medicine, a procedure that measures the metabolic activity of cells. A PET scan may show areas of cancer that may not be seen on a CT scan or an MRI scan.
  • Liquid Biopsy : this is done using fluid from a CSF tap (Cerebrospinal Fluid) or from a blood test. NGS(Next Gen Sequencing) can be used on cell fragments containing DNA or RNA from the tumor. Cell based cytology may also be possible.
  • Brain Biopsy: Needle biopsies can be done to obtain tissue for detailed study including microscopy and special staining for cell types. Computer Image-guided Neuro Navigation, Robotics and Endoscopy may be used depending on the circumstances of the tumor and patient.

Examination of a brain tumor depends mostly on the types of cells in which the tumor begins and the tumor location.

What are the different types of brain tumors?

location-of-brain tumors

The different types of brain tumors include the following:

  • The most common type of brain tumor is a glioma. Gliomas begin from glial cells, which are the supportive tissue of the brain. There are several types of gliomas, categorized by where they are found, and the type of cells that originated the tumor. The following are the different types of gliomas:
    • Astrocytomas. Astrocytomas are glial cell tumors that are derived from connective tissue cells called astrocytes. These cells can be found anywhere in the brain or spinal cord. Astrocytomas are the most common type of childhood brain tumor. Astrocytomas are generally subdivided into high-grade, medium-grade or low-grade tumors. High-grade astrocytomas are the most malignant of all brain tumors. Astrocytomas are further classified for presenting signs, symptoms, treatment, and prognosis, based on the location of the tumor. The most common location of these tumors is in the cerebellum where they are called cerebellar astrocytomas. These tumors usually cause symptoms of increased intracranial pressure, headache, and vomiting. There can also be problems with walking and coordination, as well as double vision.
    • Brain stem gliomas / DIPG (Diffuse Intrinsic Pontine Glioma). Brain stem gliomas / DIPG are tumors found in the brain stem; 80% in then pons and the remaining 20% in the medulla, mid-brain and cervico-medullary junction. Most brain stem tumors cannot be surgically removed because of the remote location and delicate and complex function this area controls. Brain stem gliomas occur almost exclusively in children; the group most often affected is the school-age child. The child usually does not have increased intracranial pressure, but may have problems with double vision, movement of the face or one side of the body, or difficulty with walking and coordination.Stereotactic Biopsy can be done to diagnose these tumors and obtain tissue for Molecular genetic markers that could aid treatment and diagnosis. This includes the lysine 27 to methionine (K27M) mutation on Histone 3 (H3K27M).
    • Ependymomas. Ependymomas are also glial cell tumors. They usually develop in the lining of the ventricles or in the spinal cord. The most common place they are found in children is near the cerebellum. The tumor often blocks the flow of the CSF (cerebral spinal fluid, which bathes the brain and spinal cord), causing increased intracranial pressure. Ependymomas can be slow growing, compared to other brain tumors, but may recur after treatment is completed. Recurrence of ependymomas results in a more invasive tumor with more resistance to treatment. About 5 to 10 percent of childhood brain tumors are ependymomas.
    • Optic nerve gliomas. Optic nerve gliomas are found in or around the nerves that send messages from the eyes to the brain. They are frequently found in persons who have neurofibromatosis, a condition a child is born with that makes him or her more likely to develop tumors in the brain. Persons usually experience loss of vision, as well as hormone problems, since these tumors are usually located at the base of the brain where hormonal control is located and arise (begin) from the optic nerve. These are typically difficult to treat due to the surrounding sensitive brain structures.

Primitive neuroectodermal tumors (PNET). PNET can occur anywhere in the brain of a child, although the most common place is in the back of the brain near the cerebellum. When they occur here, they are called medulloblastomas. The symptoms depend on their location in the brain, but typically the child experiences increased intracranial pressure. These tumors are fast growing and often malignant, with occasional spreading throughout the brain or spinal cord.

Medulloblastomas. Medulloblastomas are one type of PNET that are found near the midline of the cerebellum. This tumor is rapidly growing and often blocks drainage of the CSF (cerebral spinal fluid, which bathes the brain and spinal cord), causing symptoms associated with increased ICP. Medulloblastoma cells can spread (metastasize) to other areas of the central nervous system, especially around the spinal cord. A combination of surgery, radiation, and chemotherapy is usually needed to control these tumors.

Craniopharyngiomas. Craniopharyngiomas are benign tumors that occur at the base of the brain near the nerves from the eyes to the brain, and the hormone centers. Most occur in children and young adults, but can develop at any age. Symptoms include headaches, as well as problems with vision. Hormonal imbalances are common, including poor growth and short stature. Symptoms of increased intracranial pressure may also be seen. Although these tumors are benign, they are hard to remove due to the sensitive brain structures that surround them. They may need a combination of surgery using microsurgery followed by focussed radiation such as Radiosurgery including Gamma knife and Micro(MLC) Radiosurgery in order to achieve good tumor control and results.

Pineal region tumors. Many different tumors can arise near the pineal gland, a gland which helps control sleep and wake cycles. Gliomas are common in this region, as are PPID Pineal Parenchymal Tumors of Intermediate Diffrentiation, pinealcytomas and pineoblastomas (a type of PNET). In addition, germ cell tumors including Germinomas, another form of malignant tumor, can be found in this area. Benign pineal gland cysts are also seen in this location, which makes the diagnosis difficult between what is malignant and what is benign. Biopsy or removal of the tumor is frequently necessary to tell the different types of tumors apart. Persons with tumors in this region frequently experience headaches or symptoms of increased intracranial pressure. Treatment depends on the tumor type and size.

Treatment for brain tumors

If your child has been diagnosed with a brain tumor, you may want to consider getting a second opinion before beginning treatment.  According to the American Cancer Society, it is very rare that the time it will take to get a second opinion will have a negative impact on your treatment. The peace of mind a second opinion provides may be well worth the effort.

Specific treatment for brain tumors will be determined by your child’s doctor based on:

  • Your child’s age, overall health, and medical history
  • Type, location, and size of the tumor
  • Extent of the disease
  • Your child’s tolerance for specific medications, procedures or therapies
  • Expectations for the course of the disease
  • Your opinion or preference

Treatment may include (alone or in combination):

  • Surgery. Surgery is usually the first step in the treatment of brain tumors. The goal is to remove as much of the tumor as possible while maintaining neurological function. Surgery for a biopsy may also be done to examine the types of cells the tumor is made of for a diagnosis. This is frequently done if the tumor is in an area with sensitive structures around it that may be injured during removal. Modern forms of surgery including Computer Aided Image Guided Microsurgery with Neuro Monitoring where needed explains Dr Prem Pillay a Singapore Neurosurgeon who specializes in Pediatric or Childrens Brain Tumors (He trained at the Cleveland Clinic-USA, MD Anderson Cancer Center and the Hospital for Sick Children-Toronto).
  • Chemotherapy and Immunotherapy
  • Radiation therapy including more advanced forms such as Stereotactic Radiotherapy and Radiosurgery; and Proton Beam Therapy explains Dr Prem Pillay who is an expert in the treatment of Childrens Brain and Spinal cord tumors.
  • Steroids (to treat and prevent swelling especially in the brain)
  • Antiseizure medication (to treat and prevent seizures associated with intracranial pressure)
  • Ventriculoperitoneal shunt (also called a VP shunt). A VP shunt may be placed in the head to drain excess fluid from inside the brain to the abdomen. A VP shunt helps control the pressure inside the brain. Endoscopic Third Ventriculostomy is another option where a small opening is made in the floor of the third Ventricle.
    Ventriculoperitoneal-shunt
  • Bone marrow transplantation
  • Supportive care (for the side effects of the tumor or treatment)
  • Rehabilitation (to regain lost motor skills and muscle strength; speech, physical, and occupational therapists may be involved in the health care team)
  • Antibiotics (to treat and prevent infections)
  • Continuous follow-up care (to manage disease, detect recurrence of the tumor and to manage late effects of treatment)

Long-term outlook for a child with a brain tumor

Prognosis greatly depends on:

  • The type of tumor
  • The extent of the disease
  • Size and location of the tumor
  • Presence or absence of metastasis
  • The tumor’s response to therapy
  • The age and overall health of your child
  • Your child’s tolerance of specific medications, procedures, or therapies
  • New developments in treatment

As with any cancer, prognosis and long-term survival can vary greatly from individual to individual. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for a child diagnosed with a brain tumor. Side effects of radiation and chemotherapy, as well as second malignancies, can occur in survivors of brain tumors.

Rehabilitation for lost motor skill and muscle strength may be required for an extended amount of time. Speech therapists and physical and occupational therapists may be involved in some form of rehabilitation. More research is needed to improve treatment, decrease side effects of the treatment for this disease, and develop a cure. New methods are continually being discovered to improve treatment and to decrease side effects.

References and Acknowledgements

Columbia University Dept of Neurology Information and Protocols

Singapore Brain Spine Nerves Center Protocols