A Posterior Fossa Mass in a 6-Year-Old

Abstract Medulloblastoma is a high-grade embryonal tumor of the central nervous system arising in the infratentorium of patients of all ages with a peak incidence in childhood. Within the last decade, advances in molecular profiling of gene expression and epigenetics have advanced general understanding of previously perceived intertumoral heterogeneity. Currently, 4 subtypes of medulloblastoma are recognized: wingless (WNT)–activated, sonic hedgehog (SHH)–activated, and the non-WNT/non-SHH group, which combines groups 3 and 4. The new subgroups, which continue to evolve, have greatly complicated the process of rendering a pathologic diagnosis through integration of histopathologic and molecular data. The criterion-standard techniques for identifying these subgroups include gene expression and methylation profiling; however, such complicated and expensive laboratory techniques may not be accessible to all laboratories. Although recommendations for the approach to an integrated diagnosis have been made, no specific algorithm has been put forth. We present a case of pediatric medulloblastoma in which hematoxylin-eosin–stained tissue sections, reticulin special stain, immunohistochemistry, cytogenetics, and next-generation sequencing were implemented for the purpose of identifying subgroup and other markers of prognosis, such as TP53 mutation and MYC family member amplification. The discussion herein is aimed at reviewing current opinions on the integration of histomorphologic and molecular subgroups of medulloblastoma and providing a foundation for designing a practical and clinically meaningful approach to diagnosis.