Embryonal tumours of the Central Nervous System: the WHO 2016 classification and new insights

Abstract

Central nervous system (CNS) tumours comprise 26% of cancer in children representing the most frequent solid tumours in these age groups. Embryonal tumours represent 15% of them and they are defined as "small round blue cells" in which morphology is reminiscent of the developing embryonic nervous system (primitive neuroectodermal tumours). By definition, they are grade IV by the World Health Organization (WHO), considering their aggressive biological behavior. Over the years, molecular research has been improving our knowledge concerning these neoplasms, stressing the need for tumour reclassification and sub-typing. Indeed, the revised 2016 fourth edition of the WHO classification introduced genetic parameters in the classification of embryonal tumours. 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 histological classification with a new genetic definition in WNT-activated, SHH-activated and non-WNT/non-SHH. Molecular data is now a defining feature in the diagnosis of atypical teratoid/rhabdoid tumours, and tumours in the group of the embryonal tumours with multilayered rosettes. Even so, there are still embryonal tumours that challenge the present WHO classification and new molecular data have been underlining the need for novel tumour entities. Likewise, translating these molecular developments into clinical practice is a major challenge for the health care system.