Genetic evidence of the neoplastic nature of gemistocytes in astrocytomas

Gemistocytic astrocytoma is characterized by a predominance of large astroc ytes with plump processes and massive accumulation of glial fibrillary acid ic protein (gemistocytes). This histological variant of low-grade diffuse a strocytoma (WHO grade II) is prone to more rapid progression to anaplastic astrocytoma and glioblastoma than the ordinary fibrillary astrocytoma. The biological basis of this unfavorable prognosis is unclear, since gemistocyt es themselves have low proliferative activity, even if present in anaplasti c astrocytomas or glioblastomas. This has raised the question of whether ge mistocytes are neoplastic cells or dysplastic reactive astrocytes. In this study, gemistocytes and non-gemistocytic neoplastic cells were separated by laser-assisted microdissection from six gemistocytic astrocytomas carrying TP53 mutations. In all cases, identical TP53 mutations were identified in both cell types, indicating that gemistocytes are indeed neoplastic cells. Their lack of proliferative activity may indicate terminal differentiation.