Is Gliomatosis Cerebri a Diffuse Low-Grade Glioma?

Before addressing the issue about whether gliomatosis cerebri (GC) belongs to the group of diffuse low-grade gliomas (DLGG), I would like to examine what is known about GC, and in particular the similarities and differences between them and DLGG. In 1897, Rossolimo was the first to report the lesion that later Nevin labeled “gliomatosis cerebri.” In the most recent WHO classification, GC is considered as an extensively infiltrating glioma of astrocytic differentiation. Diagnosis of GC is challenging, not only because its clinical and radiological symptoms are frequently nonspecific, but also because GC tends to mimic other neurological conditions. GC shares with DLGG glial cell lineage, epidemiology, and some radiological features. In a subset of GC, as indeed of DLGG, IDH1 mutation was recognized as an early genetic alteration. Identification of this mutation made it clear that GC constitutes a heterogeneous group of tumors. In addition, this mutation establishes a genetic link between GC and DLGG. On the other hand, on a clinical basis, these two entities differ considerably for their infiltrative behavior. It is more likely that there are yet unidentified factors, not shared between GC and DLGG, that would favor the former to be more invasive, and the latter to be more expanding locally. The candidate role of VEGF and of HGF/c-Met pathway in tumor invasion is discussed. We also took into due consideration how IDH1 mutation may protect tumor cells from anoxia. Finally, there appears to be clinical and radiological evidence showing that both GC and DLGG evolve from a less malignant tumor at the time of first diagnosis to a more malignant neoplasm, which is the concept of low-grade tumors. Although many issues still deserve clarification, and evidence is lacking for others, we ­suggest that GC be included in the group of DLGG.