Medulloblastoma

Roger J Packer MD (Dr. Packer of George Washington University; Senior Vice President, Center for Neuroscience and Behavioral Medicine; and Gilbert Endowed Distinguished Professor in Neurofibromatosis and Director, Gilbert Neurofibromatosis Institute and Brain Tumor Institute, Children’s National Health System, has no relevant financial relationships to disclose.)
Originally released November 22, 1993; last updated September 15, 2017; expires September 15, 2020

This article includes discussion of medulloblastoma and embryonal childhood brain tumor. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Medulloblastoma is the most common malignant childhood brain tumor. There has been a marked improvement in overall survival for patients with this tumor, but a major challenge remains quality-of-life of survivors. There has also been an explosion in the understanding of the neurobiology of the tumor, and in this article, the author has attempted to capture the potential clinical significance of these new molecular discoveries, how they have significantly altered classification, how they will be incorporated into care, and the challenges that lie ahead.

Historical note and terminology

Medulloblastoma was introduced as a specific nosologic entity in 1925 by Bailey and Cushing (Bailey and Cushing 1925). Twenty-nine patients were reported with a densely cellular, primarily small round cell tumor, of which 24 were located in the cerebellar vermis. Although initially considered a subtype of glioma and called "spongioblastoma cerebelli," the tumor was later renamed "medulloblastoma." Over the years, there has been considerable debate concerning the most appropriate classification for small round cell tumors of the posterior fossa. Rorke suggested that because histologically similar or identical tumors could be found in other regions of brain, especially the pineal region and cerebral cortex, it would be most reasonable to classify all small round cell tumors of the central nervous system as primitive neuroectodermal tumors and then subdivide them on the basis of location within the nervous system and other histological or clinical features, such as evidence for cellular differentiation (Rorke 1983). Based on biological data, there is clear evidence that the vast majority of small blue cell tumors that arise in the posterior fossa are molecularly different than those arising in other regions of the brain. For this reason, medulloblastoma is now considered an entity that only arises in the posterior fossa. The 2007 WHO classifications of tumors of the nervous system, medulloblastoma has been further subdivided into medulloblastoma and subtypes, including desmoplastic/nodular medulloblastoma; medulloblastoma with extensive nodularity; anaplastic medulloblastoma; and large-cell medulloblastoma (Louis et al 2007). Cortical small cell tumors within the embryonal classification are now classified as embryonal tumors with subvarieties, including CNS neuroblastoma; medulloepitheliomas; and ependymoblastomas (Louis et al 2016). Another tumor type, the atypical teratoid/rhabdoid tumor, is now considered a distinct biological entity. Tumors of the pineal region that resemble medulloblastoma histologically, termed “pineoblastoma,” are classified with tumors of the pineal region.

The WHO 2017 classification of central nervous system tumors, which was summarized in 2016, utilizes a dual classification of medulloblastoma for the first time, attempting to combine both histological and molecular features; however, at the same time, they have kept them somewhat separate (see Table 1). The routinely utilized histological classification of medulloblastoma has been maintained as 1 means of characterizing the tumor, and well-established subclassifications, including “desmoplastic/nodular,” “large cell/anaplastic,” and “classic,” are maintained. There is also a poorly characterized subgrouping described as “Medulloblastoma, NOS.” There is further subcategorization of the sonic hedgehog variant into the tumor subtype that has mutant TP53 distinguishing it from TP53 wildtype medulloblastoma. Although this classification is a major step forward, it does not account for all the nuances suggested by new molecular insights and will likely be altered in the near future. Specifically, the new classification system does not recognize that there are subgroups of medulloblastoma that can be characterized molecularly (Cavalli et al 2017; Northcott et al 2017; Schwalbe et al 2017).

Table 1. Medulloblastoma

Medulloblastomas, genetically defined

 

Medulloblastoma, WNT-activated
Medulloblastoma, SHH-activated and TP53-mutant
Medulloblastoma, SHH-activated and T53-wildtype
Medulloblastoma, non-WNT/non-SHH

 

Medulloblastoma, group 3
Medulloblastoma, group 4

Medulloblastomas, histologically defined

 

Medulloblastoma, classic
Medulloblastoma, desmoplastic/nodular
Medulloblastoma with extensive nodularity
Medulloblastoma, large cell/anaplastic

Medulloblastoma, NOS

(Louis et al 2016)

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