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  • Updated 12.19.2021
  • Released 11.22.1993
  • Expires For CME 12.19.2024

Medulloblastoma

Introduction

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 (07). 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 (86). 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 (52). 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 most recent 2021 WHO classification of tumors of the central nervous system continues to build on the changes incorporated over the past decade. There is further incorporation of molecular changes, although the classification system does not recommend specific methods for molecular assessment. Immunohistochemical findings can be used. Methylome profiling, which uses arrays to determine DNA methylation patterns across the genome, has become a preferred method for molecular subclassification of embryonal and other tumors including medulloblastoma, but is not explicitly included in the 2021 classification. Classification has evolved into an integrated and layered diagnostic approach. Within the present classification system, 4 major molecularly defined subgroups of medulloblastoma are identified, which include: medulloblastoma, WNT-activated; medulloblastoma, SHH-activated and TP53-wild type; medulloblastoma, SHH-activated and TP53 mutant; and medulloblastoma non-WNT/non-SHH. Another classification subgroup is medulloblastoma, histologically defined. However, it is recognized that within these subgroups other molecular subdivisions may be important for clinical characterization; having prognostic value in this regard are the 4 subgroups of SHH medulloblastoma and 8 subgroups of the non-WNT/non-SHH medulloblastoma (10; 61; 90; 44; 92; 54).

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

Medulloblastomas, histologically defined


(54)

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