Pathology and Molecular Biology of Medulloblastoma

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor in pediatric age group. It is an embryonal tumor which is assigned WHO grade IV. It is a tumor of posterior fossa which arises in the cerebellum and rarely from brain stem. Histologically, MB is characterized by small, blue, round or carrot shaped poorly differentiated cells with scant cytoplasm and hyperchromatic nuclei with high proliferative indices. The histological subtypes include classic, which is the most common, followed by desmoplastic/nodular, predominantly seen in infants and adults, large cell/anaplastic and rarely medulloblastoma with extensive nodularity which is exclusively seen in infants. At the molecular level, MB clusters into four principal groups: WNT/Wingless activated, SHH/Sonic Hedgehog activated, Group 3, and Group 4. These groups have apodictic differences, not only at genetic, transcriptomic, and epigenetic levels but also differ in demographics and clinical profiles including patient outcomes. WNT tumors have the best prognosis while Group 3 have the worst outcomes. Recent advancements have led to identification of subgroups within groups, relevant in SHH and non-WNT/non-SHH tumors. The molecular classification has led to better and improved risk stratification of MB patients. Many clinical trials are underway to tailor therapy according to risk stratification and use of personalized targeted therapy.