<i>IDH</i>-wildtype secondary glioblastoma arising in <i>IDH</i>-mutant diffuse astrocytoma: a case report

Primary glioblastoma develops <i>de novo</i> without clinical or histological evidence of a low-grade precursor lesion, whereas secondary glioblastoma develops from a low-grade glioma. The present report describes an extraordinary case of <i>IDH</i>-wildtype secondary glioblastoma arising in <i>IDH</i>-mutant diffuse astrocytoma. A 31-year-old female had a surgical history of <i>IDH</i>-mutant diffuse astrocytoma on the left frontal lobe six years before. Magnetic resonance imaging revealed new infiltrative lesions in the left frontal lobe adjacent to the previous lesion. The patient underwent tumourectomy, and the new infiltrative lesion was diagnosed as glioblastoma. Interestingly, the <i>IDH</i>-1 (p.Arg132His) mutation was found in diffuse astrocytoma but not in glioblastoma based on next generation sequencing. <i>ATRX</i> (p.Gln1670Ter) and <i>TP53</i> (p.His193Arg) mutations were found in both lesions. Additionally, the <i>PTEN</i> (p.His296Pro) mutation was identified only in glioblastoma. A well-accepted hypothesis is that the <i>IDH</i> mutation initiates in glial progenitor cells and causes secondary glioblastoma harboring the <i>IDH</i> mutation to develop from low grade glioma with <i>IDH</i> mutation. However, this case showed that the other genetic mutations can be initiated before the <i>IDH</i> mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of <i>IDH</i>-wildtype secondary glioblastoma arising in <i>IDH</i>-mutant diffuse astrocytoma.