YAP1::MAML2 fusion, a newly identified genetic anomaly in a posterior fossa infant tumor, associated with the methylation class “embryonal tumor with multilayered rosettes, non-C19MC-altered” in the Heidelberg central nervous system tumor classifier

Embryonal tumors with multilayered rosettes (ETMR) are rare embryonal tumors that usually affect children under two years old. They are characterized histologically by the presence of multilayered rosettes and by the immunohistochemical expression of LIN28A. Their genetic hallmarks include C19MC amplification, which is most common, followed by DICER1 mutation. Each of these alterations correlates with a specific methylation class in the Heidelberg central nervous system tumor classifier and the National Institutes of Health brain tumor classifier. Meanwhile, 2.5 percent of LIN28A-positive embryonal tumors lack the previously mentioned genetic alterations associated with ETMR. Here, we present and discuss a case of this type. A posterior fossa tumor was found in a five-month-old infant. Histologically, the lesion appeared as an embryonal tumor, lacking multilayered rosettes but showing focal positivity for LIN28A. It did not show C19MC amplification or DICER1 mutation, yet it clustered within the ETMR non-C19MC-altered methylation class of the Heidelberg classifier (V12.5) and the ETMR-DICER class of the NIH classifier. Additionally, a YAP1::MAML2 fusion was identified, a finding not yet associated with these methylation classes.