Medulloblastoma is a common primary malignant central nervous system (CNS) tumor that occurs in childhood which leads to pediatric morbidity and death. This disorder begins in the brain or spinal cord. It originates in the part of the brain that is mainly towards the back and the bottom, on the skull floor, in the cerebellum, or on the posterior fossa. Medulloblastoma tends to spread through cerebrospinal fluid (CSF) – the fluid that surrounds and protects your brain and spinal cord – to other areas around the brain and spinal cord. Medulloblastoma is a frequently occurring brain tumor in children that accounts for more than 15% of pediatric cases. Most of the intracranial tumors spread either through the direct extension of the formation or leptomeningeal seeding, whereas medulloblastoma is significantly different for its ability to metastasize outside the nervous system. Medulloblastoma is an embryonal neuroepithelial tumor – a tumor that initiates in the fetal or embryonic cells in the brain and remains after birth.

Grades of Medulloblastoma

Central Nervous System primary tumors can be graded based on the patient’s age, tumor type, tumor location, the extent of malignancy, genetic findings, and tumor remaining after surgery (if possible). Medulloblastomas are classified as Grade IV tumors i.e.; they are malignant/cancerous and fast-growing. Different grades have been identified in children with medulloblastoma that includes:
• WNT-activated
• SHH-activated
• Group 3 (non-WNT / non-SHH)
• Group 4 (non-WNT / non-SHH)

While metastatic dissemination is the predominant cause of morbidity and mortality for patients with this disease, most research efforts and clinical trials to date have focused on the primary tumor. Most current insights into the molecular drivers of metastasis have been derived from comparative molecular studies of metastatic and non-metastatic primary tumors.

Causes

The exact cause of medulloblastoma is unknown. Most cases have been found to originate randomly for no apparent reason. Several cases of medulloblastoma are linked with chromosomal abnormalities. These abnormalities are not inherited but occur at some unknown stage during a child’s development. Though the cause is unknown, research suggests that abnormalities of DNA (deoxyribonucleic acid) – the carrier of the body’s genetic code, are mainly basis of cellular malignant transformation. Depending upon the form of cancer and various other factors, abnormal genetic changes may occur spontaneously for some sporadic reasons.

Evidence suggests that approximately 1/3^rd to 1/2 of individuals with the disorder of medulloblastoma may possess a chromosomal abnormality – isochromosome 17q, with associated inactivation/loss of certain genetic information. Though the role of chromosomes leads to medulloblastoma is not clearly understood, but additional chromosomal abnormalities on chromosomes 1, 7, 8, 9, 10q, 11, and 16 have been identified among individuals with medulloblastoma. Extensive further research is required to determine the complex mechanisms responsible for the development of the tumor. In rare cases, individuals have an increased risk of developing medulloblastomas if they possess inherited disorders such as Gorlin syndrome (nevoid basal cell carcinoma), Li Fraumeni syndrome, Turcot syndrome, Rubinstein-Taybi syndrome, Nijmegen breakage syndrome, neurofibromatosis, and ataxia-telangiectasia.

Several subtypes of medulloblastoma are as follows: i) anaplastic medulloblastoma; classic medulloblastoma; ii) desmoplastic nodular medulloblastoma; iii) medulloblastoma with extensive nodularity (MBEN); iv) medullomyoblastoma; and v) melanotic medulloblastoma. The various subtypes of medulloblastoma show differences on cellular levels. However, such distinctions in the future may be beneficial to develop novel and targeted therapies based on a particular subtype.

Underlying Signs and Symptoms

The specific symptoms associated with a medulloblastoma vary from person to person, the exact location, size of medulloblastoma and whether the tumor has spread to other areas from its place of origin. The symptoms of medulloblastoma mainly result from the increased pressure within the skull region (an intracranial pressure). Medulloblastomas generally arise in or around the base of the skull – the posterior fossa. The posterior fossa, in turn, contains the cerebellum and the brainstem. Children with medulloblastoma are often found to have evidence of cerebellar dysfunction. Symptoms include poor coordination, difficulty in walking, and clumsiness (ataxia). Affected children tend to fall frequently and develop unsteady, clumsy walking. Children may also tend to stand with their feet widely separated, sway or stagger when walking and may easily lose their balance. As a tumor starts spreading from one region to another, additional symptoms like double vision/diplopia, rapid, jerky movements of the eyes/nystagmus, ringing in the ears/tinnitus, facial weakness, hearing loss and a stiff neck may develop.

Treatment

Treatment for medulloblastoma is usually corrected through surgery followed by radiation or chemotherapy, or sometimes both. The type of treatment depends upon the factors such as the age of the patient, tumor subtype, location, grade, and extent of a tumor. A medulloblastoma may grow to the extent that it can block the flow of cerebrospinal fluid (CSF), resulting in a buildup of fluid that can cause pressure on the brain, also known as hydrocephalus. Surgery is performed at that stage is to create a pathway (external ventricular drain or ventriculoperitoneal shunt) for the fluid to flow out of the brain. Sometimes, this procedure is combined with surgery to eliminate the tumor. All patients with medulloblastoma must receive additional treatments and care after surgery to target any remaining cells.

Due to the significant increased rate of the treatment failure in the metastatic compartment among the majority of patients with medulloblastoma, it is important to understand the pattern of metastatic dissemination during diagnosis. The research found that the pattern of metastatic dissemination during diagnosis is highly subgroup-specific.