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Medulloblastoma

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Medulloblastoma is a common type of primary brain cancer that affects children. It originates in the cerebellum, which is located at the back and bottom of the brain. This area sits within the posterior fossa, a space at the floor of the skull. The brain is divided into two main parts by a membrane called the tentorium. The larger cerebrum sits on top of this membrane. The smaller cerebellum sits below it. Because these tumors grow in the region below the tentorium, they are called infratentorial tumors.

This cancer is characterized by being invasive and growing very rapidly. Unlike many other brain tumors, medulloblastomas spread through the cerebrospinal fluid. This fluid flows around the brain and down the spinal cord. Because of this, the cancer frequently metastasizes to different surfaces of the central nervous system. When the cancer spreads all the way down to the cauda equina at the base of the spinal cord, it is called "drop metastasis." This ability to travel through the fluid makes the disease difficult to manage.

Scientists believe these tumors arise from cerebellar stem cells. These are cells that were prevented from dividing or differentiating into normal cell types. The specific cell of origin depends on the molecular subgroup of the tumor. For example, WNT tumors originate from the lower rhombic lip of the brainstem. SHH tumors originate from the external granular layer. In the past, doctors classified these tumors using histology, which is the study of tissue under a microscope. Now, integrated genomic studies show that medulloblastoma is composed of four distinct molecular variants.

These four molecular subgroups are WNT/β-catenin, Sonic Hedgehog (SHH), Group 3, and Group 4. Each group has different clinical characteristics and outcomes. The WNT subgroup has an excellent prognosis, meaning patients often recover well. The SHH subgroup is the best characterized, with 25% of human tumors having mutations in genes like Patched, Sufu, or Smoothened. Group 3 patients generally have a poor prognosis. Group 4 is considered to have an intermediate prognosis.

Diagnosis often involves using T1- and T2-weighted MRI scans. These scans show the tumor as having heterogeneous enhancement near the fourth ventricle. Under a microscope, the tumor appears solid and pink-gray in color. It is very cellular and shows high mitotic activity, which means the cells are dividing quickly. Doctors may also use DNA methylation profiling to help classify the specific subgroup. This helps them predict how the disease will behave. The Chang staging system is also used during the diagnostic process.

Treatment usually begins with maximal surgical removal of the tumor. Doctors may then add radiation to the entire neuraxis, which includes the brain and spinal cord. Chemotherapy is also a common part of the treatment plan. Using a combination of surgery, radiation, and chemotherapy can increase disease-free survival. In some cases, this combination allows for a 5-year survival rate of more than 80%. Some evidence suggests that proton beam irradiation may reduce damage to the heart or hearing. However, these treatments can cause long-term side effects like cognitive impairment or endocrine disruption.

Statistics show that medulloblastoma affects just under two people per million every year. It affects children ten times more often than adults. It is the most common malignant brain tumor in children, making up 14.5% of new pediatric brain tumor diagnoses. Historically, the cumulative relative survival rate was 60% at five years. It dropped to 52% at ten years and 47% at twenty years. However, children often do better than adults. In the HIT-SIOP PNET 4 study, standard-risk children had a 5-year survival rate between 85% and 87%.

Researchers use various models to study this cancer and find new treatments. Scientists have used rat models to identify genes like p53 that are involved in cancer. They have also used mouse models to study the SHH type of medulloblastoma. In these mice, the down regulation of a protein called Cxcl3 caused frequent tumors. Interestingly, treating these mice with Cxcl3 prevented the growth of the lesions. This makes Cxcl3 a potential target for future human therapies. Modern research is also exploring liquid biopsies to monitor how a patient responds to treatment.

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