Sarcomatous Transformation of an IDH-Mutant Astrocytoma With an Oligosarcoma-Like Methylation Profile

We report a rare case of oligosarcoma, IDH-mutant, arising from a recurrent astrocytoma in a male in his 50s. The patient was originally diagnosed with IDH-mutant astrocytoma, CNS WHO grade 2, lacking 1p/19q co-deletion. At recurrence, the tumor exhibited a pure spindle cell sarcoma morphology, with retained IDH1 R132H, ATRX, and TP53 mutations, homozygous CDKN2A/B deletion, and a methylation profile classifying it as oligosarcoma, IDH-mutant. Although next-generation sequencing (NGS) suggested non-specific partial 1p/19q deletion signals, a true whole-arm 1p/19q co-deletion was not confirmed by fluorescence in situ hybridization (FISH) or methylation-based copy-number analysis, as shown in Figure 4E. Only two prior reports describe oligosarcoma arising from astrocytoma. Based on the sarcomatous morphology, astrocytic molecular background, and methylation clustering, we interpret this case as post-treatment sarcomatous transformation of an IDH-mutant astrocytoma, CNS WHO grade 2, rather than a canonical oligosarcoma. This case highlights the limitations of methylation profiling in heavily treated gliomas and underscores the importance of multimodal molecular confirmation in diagnostically challenging tumors.