Medulloblastoma is a type of rapidly growing, cancerous brain tumor that develops in the cerebellum, the part of the brain that controls coordination, balance, and fine motor skills. It is among the most common malignant (cancerous) brain tumors in children, but it can also occur in adults. Common symptoms include headaches, nausea, vomiting, problems with balance or walking, clumsiness, double vision, and fatigue. The tumor can also cause changes in behavior, trouble with fine motor skills, or signs of increased pressure in the skull, such as early morning headaches or extreme sleepiness.

In the United States, medulloblastomas make up about 15% to 20% of all childhood central nervous system tumors, with an annual incidence of about five cases per one million children. This type of tumor is more common in males than females and is most often diagnosed in children between ages 3 and 10, though it can occur at any age. About 70% of cases occur in children, while 30% occur in adults.

Medulloblastoma is typically treated with a combination of surgery, radiation therapy, and chemotherapy.

Medulloblastoma is a malignant, fast-growing brain tumor that arises in the cerebellum, the part of the brain located at the back of the skull. The cerebellum is responsible for helping the body maintain balance, coordinate movement, and perform tasks that require precision. When a medulloblastoma develops, it can interfere with these functions. As the tumor grows, it may block the flow of cerebrospinal fluid, resulting in increased pressure inside the skull (hydrocephalus), which can cause headaches, nausea, vomiting, and changes in behavior or alertness.

Medulloblastoma is classified as a grade IV (or grade 4) tumor, which means it tends to grow and spread quickly. It most often spreads through the cerebrospinal fluid to other parts of the brain and spinal cord. In some cases, it may spread to other areas of the body such as bones or lymph nodes.

There are several types of medulloblastoma, which are classified based on their molecular and genetic features as well as their appearance under the microscope. The main types include:

• WNT-activated medulloblastoma
• SHH-activated (sonic hedgehog) medulloblastoma
• Group 3 medulloblastoma
• Group 4 medulloblastoma

Each type has different characteristics, including genetic origins, typical age of onset, and how it affects the body.

Medulloblastoma is a type of tumor that arises from brain cells from early development (embryonic cells) that remain after birth and then proliferate abnormally. In most cases, there is no clear reason why medulloblastoma develops in some people. Certain genetic changes and inherited conditions can increase the risk.

A small percentage of medulloblastomas are linked to disorders that run in some families, such as Gorlin syndrome, Turcot syndrome, familial adenomatous polyposis, Li-Fraumeni syndrome, Fanconi anemia, and Rubinstein-Taybi syndrome. These disorders increase the chance of changes (mutations) in specific genes that lead to the development of medulloblastoma. Researchers have also identified several genetic pathways that are often altered in medulloblastoma. Changes in these pathways can lead to uncontrolled cell growth in the developing brain.

Some studies have found a link with other factors, such as high birth weight, breathing in certain kinds of air pollution, or parental exposure to certain chemicals, but no definitive evidence connects these factors to medulloblastoma.

The following factors are linked to a higher risk of developing medulloblastoma:

• Male sex
• Age between 3 and 10 years
• Family history of syndromes that increase cancer risk, including:
• Gorlin syndrome (nevoid basal cell carcinoma syndrome)
• Turcot syndrome
• Familial adenomatous polyposis
• Li-Fraumeni syndrome
• Fanconi anemia
• Rubinstein-Taybi syndrome
• Certain genetic mutations
• High birth weight
• Exposure to diesel particulate matter air pollution
• Maternal smoking before or during pregnancy

Symptoms of medulloblastoma may include:

• Headaches, often worse in the morning
• Nausea and vomiting
• Loss of appetite
• Clumsiness or unsteady walking
• Trouble with balance or coordination
• Double vision or blurred vision
• Fatigue or extreme sleepiness
• Behavioral changes or irritability
• Difficulty with fine motor skills, such as handwriting
• Slurred speech
• Confusion or changes in alertness
• Seizures
• Hearing loss
• Facial weakness

In infants, symptoms may also include:

• Feeding difficulties
• Loss of developmental milestones
• Bulging fontanel (soft spot on the head)
• Abnormal eye movements, such as the "sun setting" sign (inability to raise the eyes upward)
• Macrocephaly (enlarged head)

To diagnose medulloblastoma, a doctor will review the patient’s medical history, conduct a physical exam, and order one or more diagnostic tests.

The doctor may ask about symptoms, such as headaches, nausea, vomiting, balance problems, or changes in behavior, as well as any family history of syndromes that increase the risk of cancer. During the physical exam, the doctor will look for signs of increased pressure in the skull, such as papilledema (swelling of the optic nerve), abnormal eye movements, unsteady walking, or other neurological changes.

Additional tests are necessary to make a diagnosis. They may include the following:

• Magnetic resonance imaging (MRI) of the brain and spine: This imaging test is used to identify the presence, size, and location of the tumor, as well as to check for spread to other areas of the brain or spinal cord. This test may be done with or without contrast, which is a dye that makes the tumor easier to see.
• Computed tomography (CT) scan: This imaging test may be used if MRI is unavailable to detect a mass in the brain and signs of fluid buildup.
• Lumbar puncture (spinal tap): This test collects cerebrospinal fluid to check for cancer cells and determine if the tumor has spread through the central nervous system.
• Fundoscopy (ophthalmoscopy): This exam allows visualization of the back of the eye, including the retina and optic nerve, to check for swelling or other changes.
• Biopsy of the tumor: A sample of tumor tissue is examined under a microscope to confirm the diagnosis and determine the tumor’s molecular and genetic features.
• Additional tests may include hearing tests (audiometry), blood tests, and baseline heart and lung function tests before starting certain treatments.

Doctors use the results of these tests to confirm the diagnosis, determine the type and risk level of the tumor, and guide treatment planning.

Medulloblastoma is treated with a combination of therapies aimed at removing the tumor, preventing its spread, and reducing the risk of recurrence. The main treatments include:

• Surgery: The first step in treatment is usually surgical removal of as much of the tumor as possible. Surgery also helps relieve pressure in the brain caused by the tumor, and allows the tissue to be further examined for additional treatment options.
• Radiation therapy: After surgery, most patients receive radiation therapy to the brain and spinal cord to target any remaining cancer cells and reduce the risk of the tumor spreading or returning. In young children, radiation may be delayed or avoided to reduce long-term side effects.
• Chemotherapy: Chemotherapy uses drugs to kill cancer cells or stop them from growing. It is often given after surgery and may be used in combination with radiation therapy, or on its own in very young children to delay or avoid radiation.
• Targeted therapy: For certain subtypes of medulloblastoma, targeted therapies that block specific molecular signals are being studied and may be used in clinical trials.
• Stem cell transplant: In some cases, stem cell transplant using the patient’s own cells may be considered along with chemotherapy and radiation.
• Supportive care: Additional treatments include medications and therapies to manage symptoms, prevent complications, and support recovery, such as physical, occupational, and speech therapy.

Treatment plans are tailored to each patient based on age, tumor type, risk level, and overall health.

People with medulloblastoma or who have had treatment for medulloblastoma may be at increased risk for certain complications, including:

• Neurological deficits: Ongoing problems with movement, balance, coordination, or speech
• Posterior fossa syndrome (cerebellar mutism syndrome): A condition that can occur after surgery, leading to reduced or absent speech, emotional changes, and problems with movement and coordination
• Endocrine dysfunction: Hormone problems such as growth hormone deficiency, thyroid problems, or early or delayed puberty, often due to radiation therapy
• Cognitive effects: Difficulties with memory, attention, learning, or processing speed, which may persist long-term
• Secondary tumors: The development of new cancers later in life, sometimes because of radiation or chemotherapy
• Infection: Increased risk of infections
• Infection or shunt malfunction: Problems associated with devices used to relieve fluid buildup in the brain
• Stroke or other blood vessel problems: Increased risk of stroke or other issues
• Somnolence syndrome: Episodes of excessive sleepiness
• Hearing loss: Damage to the inner ear, sometimes as a result of a tumor or chemotherapy
• Behavioral and psychological problems: Anxiety, depression, or other emotional challenges related to the disease or its treatment

Recent progress in understanding medulloblastoma has improved treatment options and therapies that can lead to good results for many children and adults. However, the outlook for people with medulloblastoma varies widely depending on several factors, including the person’s age, the type and molecular features of the tumor, whether the tumor has spread, how much of the tumor can be removed with surgery, and how the tumor responds to treatment.

Certain subtypes of medulloblastoma are linked to better or worse outcomes. For example, people with WNT-activated tumors generally have an excellent outlook, with five-year survival rates of 90% to 100%. Those with SHH-activated tumors have an intermediate outlook, with overall survival between 70 and 88%. People with Group 3 tumors tend to have the lowest survival rates, especially if the tumor has MYC gene amplification. Group 4 tumors have survival rates between those of SHH and Group 3 tumors.

Even after successful treatment, some people may experience long-term effects, such as learning difficulties, hormone problems, or other health challenges related to the tumor or its treatment.

“The Yale Pediatric Brain Tumor Clinic offers cutting edge modalities such as proton beam therapy and access to the latest targeted therapies through clinical trials to ensure our patients have the best chances of a full recovery if diagnosed with medulloblastoma,” says Yale Medicine hematologist and oncologist Asher Marks, MD, director of Pediatric Neuro-Oncology. “Our multidisciplinary team includes pediatric trained neuro-oncologists, neurologists, endocrinologists, and neuro-surgeons along with dedicated ancillary staff including nutritionists, physical therapists and a team of psycho-social staff to support our patients and families.”