What is a Medulloblastoma?

Medulloblastoma (also referred to as primitive neuroectodermal tumor or PNET) arises from the primitive or embryonal cells of the cerebellum. Medulloblastoma is a tumor that arises within the cerebellum and often grows into the fourth ventricle. These tumors have the capacity to spread (metastasize) through the spinal fluid (leptomeningeal spread), occurring in approximately 30% of cases, and they rarely spread to bone and bone marrow.

Medulloblastomas are categorized by their microscopic appearance, as defined by the World Health Organization (WHO) Classification System. All medulloblastomas are WHO IV tumors and are considered malignant (cancer). The WHO classification further subdivides medulloblastoma into classic medulloblastoma, desmoplastic/nodular medulloblastoma, medulloblastoma with extensive nodularity, and large-cell/anaplastic medulloblastoma. Patients with large cell/anaplastic medulloblastoma have the worst prognosis. Recent data suggests that medulloblastoma can be further classified into molecular subgroups, which have prognostic significance. These subgroups include tumors which have activation of the Wnt or SHH (sonic hedgehog) pathway and tumors which have amplification of MYC. Wnt pathway tumors appear to have the best prognosis, SHH pathway tumors have intermediate prognosis, and MYC tumors have a poor prognosis.

Medulloblastoma is the second most common pediatric brain tumor, following pilocytic astrocytoma (WHO I astrocytoma), and it is the most common malignant brain tumor in children.   Medulloblastoma accounts for 20% of childhood brain tumors. Approximately 500 cases of childhood medulloblastoma are diagnosed in the United States each year. The peak incidence of medulloblastoma is 4 years of age, although 20% occur in individuals over 15 years of age. Typically there is no obvious reason why an individual develops a medulloblastoma, but there are rare inherited causes including Gorlin’s Syndrome (Nevoid Basal Cell Carcinoma Syndrome), Turcot’s Syndrome, Li-Fraumeni Syndrome, or Ataxia Telangiectasia.

What are the symptoms of a Medulloblastoma?
The symptoms of medulloblastoma are related to its location within the cerebellum, with frequent growth into the 4th ventricle and pressure on the nearby brainstem.  The most common early symptoms of medulloblastoma are increased intracranial pressure due to obstruction of the fourth ventricle resulting in headaches, vomiting (especially morning vomiting), lethargy, papilledema (swelling of the optic nerve seen on ophthalmology exam), and poor balance.  These symptoms are present in up to 90% of patients by the time of diagnosis.  Poor balance, known as ataxia, and poor hand coordination, known as dysmetria are usually present due to cerebellar dysfunction.  Double vision and head tilt are often seen due to pressure on the brainstem.  Symptoms in babies are more nonspecific and frequently include increasing head size (macrocephaly), failure to thrive, and increased irritability.

How is a Medulloblastoma diagnosed?
All patients with symptoms concerning for a brain tumor will undergo an MRI of the brain and spine to further define the location of the tumor and to assess if there is any metastatic (spread) disease.  A biopsy of the tumor is required to make the final diagnosis of medulloblastoma and categorize it into the appropriate WHO subgroup and molecular subgroup.  All patients require a spinal tap (lumbar puncture)to assess for microscopic spread of the tumor in the spinal fluid.

How is a Medulloblastoma treated?
Risk statification
Medulloblastoma is treated according to prognostic or “risk” features.  Important prognostic features include: the age of the child, the extent of surgical resection, the presence or absence of metastatic disease and the presence or absence of large cell/anaplastic histology.
Average-risk Medulloblastoma includes children with less than 1.5 cm2 of residual tumor following surgery, no metastatic disease, and no large cell/anaplastic histology.
High-risk Medulloblastoma is defined by more than 1.5 cm2 of residual disease following surgery, and/or metastatic disease, and/or anaplastic/large cell histology.  Patients less than 3 years of age are also of higher risk because they cannot tolerate the necessary dosages of radiation to the craniospinal axis needed to control medulloblastoma.
Currently using molecular subtyping to determine risk and treatment is still considered experimental, but it will probably be an important prognostic factor in the near future, with Wnt pathway tumors falling into a low risk group, SHH pathway tumors falling into an average risk group, and MYC tumor falling into a high risk group.

Treatment
Surgery: The initial treatment for medulloblastoma involves surgery to remove as much of the tumor as possible.  Typically a complete removal is accomplished, but sometimes residual tumor is left behind because it is growing too intimately with normal brain structures.  Surgery alone will not cure medulloblastoma; therefore further treatment with chemotherapy and usually radiation therapy is indicated.

Radiation:  Following surgery, a course of radiation is typically given to kill any remaining tumor cells.  Radiation is given to the originating site of the tumor (“tumor bed”).  Radiation is also given to the entire brain and spine (“craniospinal radiation”), because medulloblastoma cells have a high likelihood of spread through the spinal fluid even if there were no signs of spread noted on the MRI of the spine and spinal tap.  The timing of radiation, the exact dose of radiation, and the specific area (“field”) of the brain and spine delivered radiation are dependent on if the child has average risk or high risk medulloblastoma.  Patients with high risk medulloblastoma need higher doses of craniospinal radiation than patients with average risk medulloblastoma.  Of note, radiation can cause significant long term toxicity in young children.  The toxicities include cognitive impairment, vascular changes, pituitary hormonal impairment and secondary cancers.  These to toxicities are worse in the youngest children and those who get the highest amount of radiation to the whole brain.  In children less than 3 years of age with medulloblastoma, due to the potential for long term toxicity, whole brain radiation is often eliminated or deferred until the child is older. Ongoing studies are looking at lowering the dose of radiation therapy in young children and in children with favorable risk factors.

Chemotherapy:  Chemotherapy is also used to treat all children with medulloblastoma.  The timing of radiation and the specific chemotherapy drugs used are dependent on which risk subgroup the patient falls into.  In children less than 3 years of age, chemotherapy is often used initially to delay radiation.

About treatment for Medulloblastoma at Children’s Hospitals and Clinics of Minnesota

Our cancer and blood disorders program consistently achieves excellent results ranking it in the top ten programs in the United States. Children’s Hospitals and Clinics of Minnesota treats the majority of children with cancer and blood disorders in Minnesota and provides patients access to a variety of clinical trials using ground-breaking new treatments. Through our renowned program, patients experience unparalleled family support, a nationally recognized pain management team, and compassionate, coordinated care.

If you are a family member looking for a Children’s neuro-oncologist, please call our clinic at 612-813-5940.

If you are a health professional looking for consultation or referral information, please call Children’s Physician Access at 1-866-755-2121 (toll-free) and ask for the on-call hematologist/oncologist.

Additional information on Medulloblastoma

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