Malignant transformation of a gangliocytoma/ganglioglioma into a glioblastoma multiforme: a molecular genetic analysis - Case report

A gangliocytoma/ganglioglioma with no atypical or malignant features was su btotally resected from the right temporal lobe of a 16-year-old woman. A se cond resection was performed 8 years Inter to treat a locally recurrent les ion with increased cellularity that was diagnosed as a World Health Organiz ation Grade II ganglioglioma on the basis of neuropathological examination. Molecular analysis of the recurrent tumor revealed a TP53 gene mutation, b ut no amplification of the epidermal growth factor receptor (EGFR) gene. Ra diotherapy (60 Gy) was administered after the second resection. The patient returned 1 year later with a second focal recurrence. The specimen obtaine d during the third resection of tumor exhibited exclusively astrocytic diff erentiation, cellular pleomorphism with multinucleated cells, high mitotic activity, and endothelial proliferation. Therefore, the tumor was diagnosed to be a glioblastoma multiforme (GBM). Molecular analysis of tumor DNA fro m the second recurrent tumor demonstrated the presence of the TP53 mutation , which previously had been observed in the first recurrent tumor, but agai n no evidence of EGFR amplification. Findings demonstrate that the presence of TP53 mutation in progressed gangliogliomas should be interpreted as a p rogression-associated mutation rather than a consequence of treatment. This is the first report to indicate that the molecular pathways of gangliocyto mas/gangliogliomas progressing to become GBMs may parallel those of diffuse astrocytomas progressing to become GBMs.