Medulloblastoma

Medulloblastoma is a cancerous brain tumor that begins in the cerebellum, the part of the brain responsible for balance and coordination. Though it can occur at any age, it is the most common malignant brain tumor in children, with most cases diagnosed between ages 5 and 9.

Table of contents

• What is medulloblastoma?
• Where does medulloblastoma form?
• Signs and symptoms
• Causes and risk factors
• How is medulloblastoma diagnosed?
• Types and classification
• Treatment approaches
• Survival and outlook

What is medulloblastoma?

Medulloblastoma is a cancerous brain tumor that starts in the lower back part of the brain called the cerebellum. The cerebellum is the area of the brain involved in muscle coordination, balance, and movement^[1]. This type of tumor begins as a growth of cells that multiply quickly and can spread to other parts of the brain and spinal cord^[1].

While leukemias are the most common type of cancer affecting children, brain tumors are the most common solid tumors in this age group. Medulloblastoma is the most common malignant brain tumor in children, making up nearly 20% of all pediatric brain tumors^[3]. About 500 new cases of pediatric medulloblastoma are diagnosed every year in the United States^[15].

Although medulloblastoma can happen at any age, it most often occurs in young children. Most cases are diagnosed between the ages of 5 and 9^[2]. The condition is more common in boys than girls^[4]. Though rarer in older individuals, medulloblastoma can occur in adults as well, usually diagnosed between the ages of 20 and 45^[2].

• Cerebellum
• Posterior fossa
• Brain
• Spinal cord

Where does medulloblastoma form?

Medulloblastomas most commonly form in the cerebellum, the bottom part of the brain located at the back of the skull, between the larger upper part of the brain (called the cerebrum) and the brainstem^[5]. The cerebellum is situated in an area called the posterior fossa, which is the space at the back of the head^[15].

The tumor usually appears as a solid mass in the cerebellum^[5]. Medulloblastomas are known as embryonal neuroepithelial tumors because they form in fetal cells that remain after birth^[5]. They often grow in the central part of the cerebellum, though they can also develop in the outer parts^[6].

Signs and symptoms

Medulloblastoma symptoms happen when the cancer grows or causes pressure to build up in the brain. The tumor can block the flow of cerebrospinal fluid, which is the clear liquid that surrounds and protects the brain and spinal cord. This blockage can cause an abnormal build-up of fluid, increasing pressure inside the skull, a condition known as hydrocephalus^[5].

Because of the tumor’s typical location in the posterior fossa, many symptoms are related to increased pressure inside the skull and problems with the cerebellum’s functions. Symptoms may appear over a few weeks or months before diagnosis^[4]. Signs and symptoms may include^[1][2]:

• Headaches, especially in the morning
• Nausea and vomiting (being sick often makes the headaches feel better)
• Dizziness
• Double vision or changes in vision
• Poor coordination and balance issues
• Difficulty walking or unsteady walk
• Frequent falls, especially falling backward
• Tiredness or extreme sleepiness
• Back pain
• Problems with handwriting or fine motor skills
• Changes in behavior or personality
• In young children: being more irritable or taking longer to settle

In young infants, symptoms picked up during routine development check-ups might include an increasing head size or a swollen soft spot on top of the skull^[4]. If the medulloblastoma has spread to the spine, symptoms may include loss of strength in the lower body, difficulty walking, or problems controlling bowel and bladder function^[2].

Causes and risk factors

It is not clear what causes most cases of medulloblastoma. The cause of most medulloblastomas is not known^[5]. Like other cancers, medulloblastoma is a genetic disease, meaning it is caused by certain changes to genes that control the way cells function. However, these gene changes usually happen during a person’s lifetime rather than being inherited^[5].

There is an increased risk of medulloblastoma with some inherited family cancer syndromes. However, less than 5 out of every 100 cases of medulloblastoma (less than 5%) are linked with these inherited conditions^[4]. Genetic disorders that could increase the risk for developing medulloblastoma include^[2][3]:

• Nevoid basal cell carcinoma syndrome (NBCCS), also called Gorlin syndrome: This hereditary condition often occurs alongside skin cancers. People with NBCCS have about a 5% chance of developing medulloblastoma
• Turcot syndrome: People with this syndrome have colon cancer along with a tumor in their central nervous system
• Li-Fraumeni syndrome: This condition increases the risk of many types of cancer, including brain tumors
• BRCA1 and BRCA2 gene mutations: These genes make proteins to help repair damaged DNA. People who inherit certain variants have increased risks for many types of cancer
• Familial adenomatous polyposis (FAP)
• Fanconi anemia

Some studies have found possible links between medulloblastoma and factors during pregnancy, such as maternal diet and blood or immune disorders. Others report associations with viral infections, such as early John Cunningham (JC) viral infections or human cytomegalovirus (CMV) infections in childhood^[3]. However, these connections are not definitively established.

How is medulloblastoma diagnosed?

The process of diagnosing medulloblastoma usually starts with a medical history review and discussion of signs and symptoms. Your healthcare provider will perform a thorough clinical and neurological examination^[11]. Several tests and procedures are used to diagnose medulloblastoma.

Neurological exam: During this exam, the doctor checks vision, hearing, balance, coordination, and reflexes. This helps determine which part of the brain might be affected by the tumor^[8].

Imaging tests: Imaging tests capture pictures of the brain and can show the size and location of the tumor. Magnetic resonance imaging (MRI) is the best test to assess and follow up medulloblastoma^[11]. Medulloblastomas usually appear as a solid mass in the cerebellum. The tumor often brightens with contrast material^[5]. It can also block the cerebrospinal fluid pathways, causing hydrocephalus. CT scans (computed tomography scans) may also be used in certain situations^[8].

Spinal imaging: Because medulloblastomas can spread to other areas of the brain and spinal cord, a magnetic resonance imaging (MRI) scan of the spinal cord is performed to check if the tumor has spread^[5].

Tissue sample testing: To get an accurate diagnosis, a piece of tumor tissue is usually removed during surgery. A specialist called a neuropathologist then reviews the tumor tissue under a microscope^[5]. Biopsies for medulloblastoma are uncommon but might be used in certain situations. In a biopsy, part of the skull is removed and a needle is used to take a sample of the tumor^[8].

Spinal tap (lumbar puncture): This test involves inserting a needle between two bones in the lower spine to draw out cerebrospinal fluid from around the spinal cord. The fluid is tested in a lab to look for tumor cells^[8]. A surgeon takes a sample of cerebrospinal fluid to test it for cancer cells. This test is only done after managing the pressure in the brain or removing the tumor^[2].

Types and classification

Medulloblastomas are all classified as grade 4 (also written as grade IV) tumors. This means they are malignant (cancerous) and fast-growing^[5]. However, researchers have learned that medulloblastoma is not a single disease, but rather several different diseases that look similar under the microscope.

Histological types: Based on what the cells look like under the microscope, there are four main histological types^[4]:

• Classical medulloblastoma: Around 8 out of 10 children (around 80%) have classical medulloblastoma
• Anaplastic or large cell medulloblastoma
• Nodular or desmoplastic medulloblastoma: This type is most common in infants
• Medulloblastoma with extensive nodularity (MBEN)

Molecular subgroups: Advances in molecular profiling have shown that medulloblastomas can be divided into at least four molecular subgroups based on their genetic features. These subgroups have been identified in children and adults, although their frequency and genetic features vary depending on the age of the patient^[5]:

• WNT-activated
• SHH-activated
• Group 3 (non-WNT / non-SHH)
• Group 4 (non-WNT / non-SHH)

Each subgroup has a distinct survival rate, ranging from 20 to 90 percent^[6]. These molecular discoveries are important for risk stratification and treatment planning.

Risk stratification: Using the stage of the cancer, the patient’s age, and whether the tumor remains after surgery, a healthcare team can estimate the risk of the tumor coming back. This process is called risk stratification, and medulloblastomas are classified into two risk groups: standard risk (or average risk) and high risk^[5].

Treatment approaches

Treatment for medulloblastoma usually includes surgery followed by radiation therapy or chemotherapy, or both^[1]. Surgical resection followed by radiation and chemotherapy are the mainstay of therapy^[3]. The healthcare team considers many factors when creating a treatment plan, including the tumor’s location, how fast it’s growing, whether it has spread, the patient’s age, and the molecular subtype of the tumor^[8].

Surgery: Doctors usually begin treatment with surgery to safely remove as much of the tumor as they can^[6]. After they remove as much of the tumor as possible, doctors can use chemotherapy medicines and radiation therapy to prevent the tumor from coming back or spreading^[17].

Radiation therapy: Radiation therapy uses X-rays (photon therapy) or proton beam therapy to kill cancer cells and shrink tumors. It is often used to destroy cancer cells still in the brain after surgery and cancer cells in the spinal cord^[17]. Because the tumor can spread through the cerebrospinal fluid, craniospinal radiation therapy (radiation to the brain and spine) is often part of treatment^[16]. In children younger than 3 years old, radiation therapy is avoided when possible because it can affect brain growth and development^[17].

Chemotherapy: Chemotherapy uses medicines to kill cancer cells. Medicines often used include cisplatin, vincristine, and cyclophosphamide^[17]. For young children, high-dose chemotherapy followed by stem cell rescue may be used to avoid or delay radiation treatment^[18].

Targeted therapies: New information about genetic changes in medulloblastoma tumors has led to many new treatments that specifically target these changes. These subgroup-specific therapies are being used with standard treatments or are being studied in clinical trials^[17].

Survival and outlook

The outcomes for children with medulloblastoma have improved dramatically over the past several decades^[6]. Treatment has improved in recent years, and more children are making a full recovery^[17]. Five-year survival rates range between 50% to 90%, depending on multiple factors^[3]. The cumulative relative survival rate for all age groups was 60%, 52%, and 47% at 5 years, 10 years, and 20 years, respectively, with children doing better than adults^[7].

This wide range in survival is multifactorial, owing in part to age at diagnosis, the presence of spread at diagnosis, the molecular subgroup of medulloblastoma, and how much of the tumor could be removed with surgery^[3]. The highest chance of medulloblastoma relapse is within the first two years after treatment^[18].

Despite significant progress in treatment, long-term side effects from treatment remain a concern. Treatment-related cognitive, neurologic, and endocrinologic effects can be debilitating^[3]. Long-term complications can include neurocognitive impairments, endocrine dysfunction, hearing loss, growth problems, and a small risk of secondary cancers^[16][18].

Survivors of medulloblastoma require long-term follow-up care. Imaging with MRI is done yearly for at least 10 years to check for tumor recurrence^[18]. Specialized clinics for cancer survivors help monitor for late effects of treatment and provide support as patients transition to life after cancer^[18].