PATH-47. The Dimorphism of the Multinucleated Giant Cells of Gliomas

Abstract Gliomas are highly aggressive brain tumors with limited treatment options and a poor prognosis. Despite extensive research into their molecular characteristics, their ultrastructural basis of pathogenesis remains largely unexplored. In this study, we aim to elucidate the nature of the multinucleated giant cells (MNGCs) within IDH1-wt glioblastoma (GBM) and IDH1-mutant astrocytoma; thus, shedding light on their types, ontogenies, morphologies, prevalence, significance, and potential impact on tumor progression and treatment resistance. Utilizing transmission electron microscopy (TEM), we examined 30 tumors (18 IDH1-wt GBMs and 12 IDH1-mt astrocytomas) and found that they share two types of MNGCs. Type 1 is formed by the fusion of several tumor cells. Type 2 seems to be produced by tumor fibrillar cells filled with intermediate filaments (IF) and lipids through two processes, either by cell fusion or by the immigration of naked nuclei to a larger IF-filled tumor cell. Both MNGC types lack bounding membranes, and their mitochondria had degenerate inner membranes and were occasionally filled with lipids. Our results showed that MNGC is not as rare as has been speculated; we found them in 43% of the studied cases and in a wide age range from 26 to 60. The two MNGC types occurred solely or in combination in both types of gliomas. Furthermore, MNGCs appear non-proliferative; and therefore, their contribution to tumorigenesis and metastasis is not yet fully resolved.