The dimorphism of the multinucleated giant cells of gliomas.

Abstract

Extensive research has begun to uncover the molecular characteristics of high grade gliomas. However, an ultrastructural understanding of their pathogenesis remains largely unexplored. Multinucleated giant cells are large cells with multiple nuclei thought to form from the fusion of multiple neoplastic cells. In this study, we aim to elucidate the nature of the multinucleated giant cells (MGCs) within <i>IDH1</i>-wild type glioblastoma (GBM) and <i>IDH1</i>-mutant astrocytoma, grade 4, by characterizing their phenotypes, ontogenies, morphologies, prevalence, significance, and potential impact on tumor progression and treatment resistance. Utilizing transmission electron microscopy (TEM), we examined 30 tumors (18 <i>IDH1</i>-wild type GBMs and 12 <i>IDH1</i>-mutant astrocytomas) and found that they share two types of MGCs. 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. Our results showed that MGCs are abundantly present in 43% of cases, making them less rare than previously believed. The two MGC types occurred solely or in combination in both types of gliomas. Furthermore, MGCs appear non-proliferative; and therefore, their contribution to tumorigenesis and proliferation is not yet fully resolved.