Overview of Medulloblastoma

Medulloblastoma is an aggressive type of brain tumor most commonly found in children, though it can also occur in adults. Originating in the cerebellum—the region of the brain that controls coordination, balance, and movement—medulloblastoma is an aggressive form of cancer that demands prompt and specialized care.

A comprehensive understanding of medulloblastoma, including its subtypes, potential causes, symptoms, and treatment approaches, is essential for patients and caregivers. Gaining insight into these aspects can empower those affected to navigate the complexities of diagnosis and treatment effectively.

This article provides an in-depth overview of medulloblastoma, detailing its classification, typical symptoms, diagnostic processes, and available treatment options to support informed decision-making and optimize care.

Medulloblastoma is not a uniform disease; it can be classified into several subtypes based on molecular and genetic features. These classifications help guide treatment and predict outcomes, as each subtype has unique characteristics.

• WNT-Activated: These tumors are linked to the WNT pathway and generally have a very favorable outlook, with over 90% survival in children. They are typically localized and less likely to spread, which contributes to better outcomes. WNT-activated tumors represent about 10% of medulloblastomas.
• SHH-Activated: Associated with the Sonic Hedgehog pathway, SHH-activated tumors occur across all ages but are more common in infants and adults. Prognosis varies depending on age and specific genetic factors. They range from aggressive in older children to more manageable in infants.
• Group 3: Among the most aggressive, Group 3 tumors grow and spread quickly, often requiring intensive treatment. Early diagnosis and comprehensive care are essential for improving outcomes. These account for about 25% of medulloblastomas.
• Group 4: The most common subtype, Group 4 tumors grow moderately and may spread, though generally slower than Group 3. Treatment success varies, but research advancements are improving outcomes through targeted therapy. They make up around 35% of medulloblastomas.

Apart from molecular characteristics, medulloblastomas are also classified histologically, which refers to how the tumor cells look under a microscope. The four main histological types are:

• Classic Medulloblastoma: The most common type, found in patients of all ages. These tumors have a typical structure and are often used as a reference for comparison in diagnosis.
• Desmoplastic/Nodular: Often seen in infants, this type has a better prognosis than other forms. The nodular regions within the tumor create a distinct appearance, which can be linked to a less aggressive behavior, especially in younger children.
• Medulloblastoma with Extensive Nodularity (MBEN): Typically found in very young children and associated with a more favorable outcome. The extensive nodularity resembles desmoplastic tumors, and this structure often indicates a less aggressive cancer.
• Large Cell/Anaplastic: These tumors are more aggressive, have a higher tendency to spread, and require intensive treatment. They present with larger, abnormal cells and are usually associated with poorer outcomes. Recognizing this type early is crucial for planning aggressive therapies.

The exact causes of medulloblastoma are not fully understood, but researchers have identified certain genetic and environmental factors that may increase the risk.

Some inherited genetic conditions can raise the likelihood of developing medulloblastoma, including:

• Li-Fraumeni Syndrome: Associated with mutations in the TP53 gene, leading to an increased risk of various cancers, including brain tumors. This genetic mutation disrupts the normal function of tumor-suppressing proteins, leading to uncontrolled cell growth.
• Gorlin Syndrome: Linked to mutations in the PTCH1 gene and primarily related to SHH-activated tumors. Patients with this syndrome are more likely to develop medulloblastoma, as well as other cancers like basal cell carcinoma.
• Turcot Syndrome: Increases the risk of colon and brain tumors, including medulloblastoma. This syndrome is tied to mutations in genes responsible for DNA repair, which means cells can accumulate more mutations over time, leading to tumor development.

In addition to inherited conditions, spontaneous genetic mutations during development can lead to medulloblastoma. Ongoing research into the genetic and molecular features of these tumors aims to develop more targeted therapies that can effectively treat different subtypes.

While no definitive environmental causes have been linked to medulloblastoma, researchers are exploring possible influences, such as:

• Radiation Exposure: Previous exposure to radiation, especially cranial radiation for other conditions, may increase the risk of developing medulloblastoma. This is particularly concerning for children who have undergone radiation therapy for other cancers.
• Parental Exposure to Toxins: Limited evidence suggests a possible link between parental exposure to certain chemicals or toxins and childhood brain tumors, though more research is needed. Studies are exploring the effects of pesticides, industrial chemicals, and even certain lifestyle factors during pregnancy.

Recognizing the symptoms of medulloblastoma early can lead to prompt diagnosis and treatment, improving the chances of a favorable outcome. Symptoms often arise from increased pressure in the brain or the tumor's effect on nearby brain structures. Common symptoms of medulloblastoma include: 

• Persistent Headaches: Often worse in the morning or when lying down, caused by increased pressure in the brain due to fluid buildup.
• Nausea and Vomiting: Commonly linked to increased brain pressure, often occurring with headaches and may improve temporarily after vomiting.
• Balance and Coordination Issues: Tumors in the cerebellum can lead to clumsiness, unsteady walking, and frequent falls.
• Vision Changes: Blurred or double vision and eye movement issues may occur if the tumor affects areas controlling vision.
• Behavioral and Cognitive Changes: Difficulty concentrating, mood swings, memory issues, or social withdrawal are possible signs, especially noticeable in children.

Diagnosis typically involves a combination of symptom evaluation, imaging, and laboratory tests. Accurate and timely diagnosis is crucial for planning effective treatment.

Imaging is the first step in diagnosing medulloblastoma. Common techniques include:

• Magnetic Resonance Imaging (MRI): The preferred method, offering detailed images of the brain to determine the size, location, and extent of the tumor. MRI scans can reveal any associated swelling and help guide the treatment plan.
• Computed Tomography (CT) Scan: May be used in emergencies or to detect calcifications within the tumor. Although less detailed than MRI, CT scans can be quicker and useful in initial evaluations.
• Spinal Imaging: Conducted if there is concern that the tumor has spread, as medulloblastomas can metastasize to the spinal cord. This helps determine the extent of the disease.

A biopsy is often performed to confirm the diagnosis. During the procedure, a sample of the tumor is taken and analyzed under a microscope to identify the type of tumor cells present.

Molecular testing can further classify the tumor based on genetic markers, guiding treatment decisions and helping predict outcomes.

To check if the tumor has spread, a lumbar puncture may be done to analyze the cerebrospinal fluid for cancer cells. This helps determine the extent of the disease and plan appropriate treatment. The presence of tumor cells in the spinal fluid may indicate the need for more aggressive therapy.

Treatment for medulloblastoma typically involves a combination of therapies, each addressing different aspects of the tumor. The main approaches include:

Surgery is often the initial step, aimed at removing as much of the tumor as possible. Complete resection is ideal, but if the tumor is in a sensitive area, partial removal may be necessary.

As with any brain surgery, there are risks, including potential neurological complications. Recovery may include rehabilitation to help regain motor skills or address speech difficulties.

Radiation is used after surgery to target any remaining cancer cells and prevent the tumor from returning. Since medulloblastomas can spread through the cerebrospinal fluid, radiation is often applied to the entire brain and spinal cord.

More advanced techniques, like proton therapy, minimize damage to surrounding healthy tissue, especially in children.

Chemotherapy is used alongside surgery and radiation, particularly for aggressive tumors or when the cancer has spread beyond the original site. In some cases, doctors may recommend high-dose chemotherapy followed by a stem cell rescue.

This treatment allows for higher doses of chemotherapy drugs, which can effectively kill cancer cells that may not respond to standard chemotherapy. The stem cell rescue procedure helps replenish the body’s ability to produce blood cells, which can be damaged by intensive chemotherapy.

This approach is particularly beneficial for younger children, who may not tolerate traditional radiation therapy well.

Advances in understanding the genetics of medulloblastoma have led to targeted therapies that focus on specific pathways cancer cells use to grow. These drugs are designed to interfere with specific molecular processes that are essential for tumor growth.

For instance, medications that block the SHH (Sonic Hedgehog) pathway have shown promise in treating SHH-activated tumors. This personalized approach can minimize damage to normal cells, reducing side effects and potentially improving outcomes.

Patients, especially those whose tumors are resistant to traditional treatments, may have the opportunity to participate in clinical trials. These trials offer access to experimental drugs and novel therapeutic approaches that could improve the treatment of medulloblastoma.

Families are encouraged to discuss the possibility of clinical trials with their healthcare team to explore all available options. More information about clinical trials can be found here.

Surviving medulloblastoma is a significant milestone, but recovery extends beyond initial treatment. Patients require long-term care and monitoring to address any lingering effects of the tumor and therapies.

Many patients need rehabilitation to help regain motor skills, speech, and cognitive functions. Physical therapy, occupational therapy, and speech therapy are common facets of rehabilitation, and they play a crucial role in the patient’s recovery.

Supportive care can also involve managing treatment side effects, including fatigue, hormonal imbalances, and cognitive challenges.

The journey through diagnosis and treatment can be mentally and emotionally taxing for patients and their families. Access to mental health resources, including counseling and support groups, can provide a space to navigate these challenges.

Programs tailored for children and young adults can offer age-appropriate support. These support programs are effective tools in helping patients cope with the psychological effects of cancer and treatment.

Even after successful treatment, regular follow-up care is critical to detect any signs of recurrence early. Follow-ups typically include periodic imaging, physical exams, and blood tests to monitor for the return of cancer. Patients may also have ongoing assessments to address any long-term side effects, ensuring they receive comprehensive care as they continue their recovery.

• Medulloblastoma is a complex and aggressive brain tumor that can be classified into different types, each influencing treatment and prognosis.
• Genetic factors, including certain inherited conditions, may increase the risk, but spontaneous mutations are also common causes.
• Early recognition of symptoms such as persistent headaches, nausea, and coordination problems is vital for timely diagnosis.
• Treatment usually involves a combination of surgery, radiation, and chemotherapy, with newer targeted therapies offering hope for better outcomes.
• Long-term care is essential to manage life after treatment, including rehabilitation, emotional support, and regular follow-ups.

• National Cancer Institute - Medulloblastoma
• The Brain Tumour Charity - Medulloblastoma
• Brain Tumour Research - Types of Brain Tumours: Medulloblastoma
• American Brain Tumor Association - Medulloblastoma
• Medulloblastoma.org