Authors
Gianluca Marucci, Rosina Paterra, Maria Assunta Lacavalla, Nadia Puma, Paolo Ferroli, Maura Massimino, Valeria Barresi
Published in
Virchows Archiv : an international journal of pathology. Jul 17, 2026. Epub Jul 17, 2026.
Abstract
We report a case of astrocytoma IDH-mutant grade 2, which progressed to an IDH-mutant sarcomatous neoplasia after multiple treatments, including radiotherapy. The last recurrence histologically exhibited sarcomatous morphology, characterized by spindle cells, necrosis, and brisk mitotic activity. The neoplastic cells were negative for GFAP and OLIG2, positive for IDH1p.R132H and P53, with loss of ATRX expression and focal loss of H3 K27me3. Focal immunoreactivity for smooth muscle actin, desmin, and YAP1 was also observed. DNA methylation profiling yielded subthreshold scores suggestive of oligosarcoma, IDH-mutant, using the Heidelberg classifier and undifferentiated sarcoma using the sarcoma classifier. The Bethesda classifier did not provide a confident match. Nevertheless, UMAP analysis showed proximity of the recurrent tumor to the oligosarcoma methylation cluster. Overall, the sarcomatous recurrent neoplasia retained immunophenotypic and molecular features of astrocytomas IDH-mutant, while exhibiting an epigenetic divergent profile. This case expands the spectrum of sarcomatous progression in IDH-mutant diffuse gliomas and raises the possibility that astrocytomas, similar to oligodendrogliomas, may rarely undergo sarcomatous transformation. Additional cases and integrated molecular studies will be required to determine whether such tumors represent a distinct biological subgroup.
PMID:
42467228
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.
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