Childhood medulloblastomas, which form primarily in the cerebellum, are the most common type of malignant brain tumor among children. The standard treatment for children with medulloblastoma usually involves a combination of craniotomy, tumor removal, radiation therapy and/or chemotherapy. For children who also have hydrocephalus, treatment can also include ventriculostomy or shunt placement.
The World Health Organization grades tumors on a scale of one to four, with Grade 1 being the least aggressive and Grade 4 the most. Childhood medulloblastomas, known for growing quickly and having the potential to metastasize to other areas, are Grade 4.
Childhood medulloblastomas are located in the cerebellum, and as they grow, they can expand into one of the ventricles. There, circulating cerebrospinal fluid can pick up malignant tumor cells from the medulloblastoma and transport them to other areas in the brain and spinal cord. Medulloblastomas rarely metastasize to parts of the body other than the brain or spinal cord, but if they do, bone is the most likely destination.
Childhood medulloblastomas develop from embryonal cells that accidentally remained in the brain beyond early development. Normally, embryonal cells mature into specialized cells and tissue, but rarely, they can become trapped in a certain part of the body—for instance, the brain—and develop into a tumor. Researchers continue to investigate the exact type, or types, of embryonal cells from which medulloblastomas arise.
Originally believed to be one disease, childhood medulloblastomas are now known to be a complex set of diseases composed of several subtypes. This knowledge has refined the treatment approaches and improved prognosis for children with medulloblastomas.
Childhood medulloblastomas were initially categorized according to histology characteristics, which can be identified in tissue samples under a microscope. There are seven histologic types:
- Classic medulloblastoma
- Desmoplastic nodular medulloblastoma
- Medulloblastoma with extensive nodularity
- Large-cell medulloblastoma
- Anaplastic medulloblastoma
- Melanotic medulloblastoma
The latest research has gone one step past histologic types to identify four genetic subgroups: WNT, SHH, Group 3, and Group 4. WNT and SHH are named after cell pathways WNT and SHH, in which the respective mutations occur. Groups 3 and 4 have not been named according to which genes are mutated; research is still establishing the full genetic basis of these subtypes. Group 3 and Group 4 differ by the aggressiveness of the disease and age of occurrence. Research continues into these four subgroups and how the genetic characteristics of each overlap with the histologic types.
Symptoms of childhood medulloblastomas can vary and depend on a child’s age. Most children and infants with medulloblastomas experience hydrocephalus. The growing tumor and hydrocephalus can raise intracranial pressure, leading to classic signs such as headache upon waking, nausea and vomiting, and lethargy.
Infants may have the following additional symptoms:
- Macrocephaly—The buildup of fluid can cause the soft head to expand and the fontanel on the top of the head to bulge
- Failure to thrive
- Sun setting sign
Children may have the following additional symptoms:
- Worsening handwriting and other motor skills
- Staggered gait
- Neck stiffness and torticollis
- Visual problems such as diplopia, esotropia and nystagmus
Childhood medulloblastomas that have metastasized to the spinal cord may produce the following symptoms:
- Problems walking
- Reduced ability to control bowel and bladder function
- Back pain
A physical examination is performed to identify a child’s symptoms, followed by a neurological examination to detect other symptoms relating to brain function. This exam consists of evaluating sense of smell, motor function, swallowing, hearing, sensation, eye movements, balance, and coordination.
If a brain tumor is suspected, then imaging tests are ordered to provide a diagnosis.
The preferred imaging test is usually magnetic resonance imaging (MRI), particularly because the test visualizes the spinal cord, an area to which childhood medulloblastomas can metastasize. Children must be carefully monitored because the sedatives administered may further increase already elevated pressure inside the head.
Although imaging tests may strongly suggest a brain tumor, a biopsy must be performed during surgery to confirm the tumor is indeed medulloblastoma. Also, genetic testing is conducted on the tumor tissue sample to identify whether the tumor is WNT, SHH, Group 3, or Group 4.
To determine whether the childhood medulloblastoma has spread through the cerebrospinal fluid, a lumbar puncture can be performed. However, for children with increased pressure inside the skull, this procedure may be unsafe. A lumbar puncture is usually reserved until after the medulloblastoma has been resected and the pressure is normal.
To identify bone metastasis, a bone scan is often conducted for children who have bone pain in addition to medulloblastoma.
The cause of medulloblastomas among children is not yet clear. The majority of medulloblastomas during childhood occur spontaneously.
Most medulloblastomas affect children—about half of all medulloblastomas occur before the age of 6. Each year in the United States, about 250 children are diagnosed with medulloblastoma.
Childhood medulloblastomas tend to occur more often in boys than girls.
Children who have certain genetic conditions, such as Gorlin, Turcot, and Li-Fraumeni syndromes, have an increased risk of developing childhood medulloblastomas.
Nearly half of childhood medulloblastomas have a genetic abnormality on chromosome 17. Research has also identified abnormalities in some tumors on chromosomes 1, 7, 8, 9, 10q, 11, and 16. How these genetic abnormalities relate to the four subtypes is currently being studied.
At Columbia, our neurosurgeons customize a treatment plan for each child and use the most sophisticated surgical techniques to treat childhood medulloblastomas, providing the best possible outcomes for our patients.
For most children, treatment consists of a combination of open surgery, radiation therapy, and chemotherapy.
Surgical resection is often the first step in treatment, the aim of which is to debulk the tumor while maintaining overall brain function. To gain access to the brain tumor, the neurosurgeon performs a craniotomy, a procedure in which a piece of the skull bone is removed. The neurosurgeon then resects as much tumor as is safely possible. The more tumor that can be resected, in general, the better the prognosis. Removing the tumor also allows the CSF to flow normally, resolving any hydrocephalus.
Tumors located in a region that cannot be safely accessed surgically are termed inoperable, and treatment involves radiation therapy and/or chemotherapy. If hydrocephalus accompanies an inoperable tumor, a ventriculostomy is usually performed. A ventriculostomy entails making a small hole in the skull and then inserting a catheter through the hole, into one of the ventricles. Then the fluid from the ventricle can drain through the catheter, relieving pressure.
Sometimes neither surgery alone nor ventriculostomy successfully treats hydrocephalus. To treat hydrocephalus long-term, a neurosurgeon can surgically insert a shunt to reroute the fluid and control the pressure.
Once the medulloblastoma is surgically resected, a neurosurgeon can categorize a child’s medulloblastoma as average risk or high risk, which can guide the next treatment decisions. The categorization depends on the amount of tumor remaining and whether it has metastasized.
- Average risk—The amount of tumor left is less than 1.5 cm2 and the tumor has not metastasized outside of the brain.
- High risk—The amount of tumor left is more than 1.5 cm2 or the tumor has metastasized outside of the brain.
Depending on a child’s age and other factors, a combination of radiation therapy and chemotherapy is used to eliminate residual tumor after surgery. In infants and young children, radiation therapy is often avoided because it can hinder brain development, producing severe long-term effects. Instead, chemotherapy alone is used.
If a child is old enough to receive radiation therapy, radiation is administered to the spinal cord as well as the brain in order to prevent metastasis to the spinal cord.