Embryonal Tumors of the Central Nervous System: The WHO 2016 Classification and New Insights

Abstract

Central nervous system tumors comprise 26% of cancer in children, representing the most frequent solid neoplasms. Embryonal tumors comprise 15% of them, and they are defined as "small round blue cells" in which morphology is reminiscent of the developing embryonic nervous system. They are the most common high-grade central nervous system neoplasms. Over the years, molecular research has been improving our knowledge concerning these neoplasms, stressing the need for tumor reclassification. Indeed, the revised 2016 fourth edition of the World Health Organization classification introduced genetic parameters in the classification. Specific molecular signatures allow a more accurate risk assessment, leading to proper therapeutic approach and potentially improved prognosis. Holding this new approach, medulloblastoma is noteworthy. The present classification combines the previous histologic classification with a new genetic definition in WNT-activated, sonic hedgehog-activated and non-WNT/non-sonic hedgehog. Molecular data are also a defining feature in the diagnosis of atypical teratoid/rhabdoid tumors and embryonal tumors with multilayered rosettes. However, there are still embryonal tumors that challenge the present World Health Organization classification, and new molecular data have been underlining the need for novel tumor entities. Likewise, recent research has been highlighting heterogeneity in recognized entities. How to translate these molecular developments into routine clinical practice is still a major challenge.