Diagnostic challenges in an adult infratentorial pilocytic astrocytoma with a novel ZBTB20 BRAF fusion

Unusual case of 46-year-old male presenting with histologically diagnosed infratentorial pilocytic astrocytoma. Unusual for the age group, radiological findings and lack of methylation match, this case brings to questions whether these findings are associated with the unusual, albeit novel ZBTB20::BRAF fusion. Zinc Finger and Bric-a-brac domain containing 20 (ZBTB20) expression has recently been demonstrated to be expressed in neuron precursor cells and regulate astrocytogenesis, while being absent in oligodendritic lineage. An overexpression of ZBTB20 promotes astrocytogenesis. A fusion with B-Raf Proto-oncogene Serine/Threonine-protein Kinase (BRAF) results in a dysregulation of the MAPK pathway and ultimately neoplasia, which is largely associated with BRAF mutations. Such novel mutations with non-classifying methylation profiling brings diagnostic and prognostic challenges. With the rise of molecular testing and analysis, further mutations and fusions will be identified. Identifying novel molecular findings, as this ZBTB20::BRAF fusion, may shed light onto novel glial and broader neoplasia and possibly act as a site for targeted therapy.