Medulloblastoma: Classification (A Review)

Abstract

Medulloblastomas (MBs) represent a heterogeneous group of highly malignant primary tumors of the Central Nervous System (CNS), with prevalence in male and young age patients. MBs are rare tumors with a very aggressive behavior, characterized by a noticeable tendency to metastasize. A proper classification of MBs is important for the establishment of histopathological, diagnostic and clinical criteria, which would ultimately validate standard therapies, clinical trials, and epidemiological studies. Historically, classification of brain tumors has been based on theories related to histogenesis and grades of differentiation and anaplasia. The term “medulloblastoma” provided uniformity of classification to posterior fossa tumors in childhood arising from a hypothetical multipotential embryonal cell, the “medulloblast”, capable to differentiate along neuroblastic or spongioblastic cells. However, the existence of this progenitor cell has never been proven and its location in the developing cerebellum was also debated. The controversy on the origin of MBs raised other debates on the classification of these tumors: one hypothesis was to consider MBs as part of a larger class of Primitive Neuroectodermal Tumors (PNETs), generically indicated as a group of undifferentiated embryonal tumors, arising in different sites of the CNS and at all ages. Another hypothesis supported the idea that different tumors derived from malignant transformation of resident cells in different areas should be categorized separately. Based on the different histopathologic characteristics, the location inside the brain, and the molecular genetic aberrations in the tumor cells, the latest World Health Organization classification of brain tumors lists MB and PNETs as separate entities. According to this classification, MBs are distinct entities listed among the embryonal tumors and are distinguished in multiple variants: classic MB, desmoplastic MB, MB with extensive nodularity, and large cell anaplastic MB. In addition to these two entities, two patterns of differentiation are also defined: MB with myogenic differentiation, and MB with melanotic differentiation. This chapter focuses on the main steps that lead to the actual knowledge on MB and to its proper classification in the context of the brain tumors.