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Primary glioblastoma develops  de novo  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  IDH -wildtype secondary glioblastoma arising in  IDH -mutant diffuse astrocytoma. A 31-year-old female had a surgical history of  IDH -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  IDH -1 (p.Arg132His) mutation was found in diffuse astrocytoma but not in glioblastoma based on next generation sequencing.  ATRX  (p.Gln1670Ter) and  TP53  (p.His193Arg) mutations were found in both lesions. Additionally, the  PTEN  (p.His296Pro) mutation was identified only in glioblastoma. A well-accepted hypothesis is that the  IDH  mutation initiates in glial progenitor cells and causes secondary glioblastoma harboring the  IDH  mutation to develop from low grade glioma with  IDH  mutation. However, this case showed that the other genetic mutations can be initiated before the  IDH  mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of  IDH -wildtype secondary glioblastoma arising in  IDH -mutant diffuse astrocytoma.

IDH -wildtype secondary glioblastoma arising in IDH -mutant diffuse astrocytoma: a case report