Gliomatosis Cerebri: Current Understanding and Controversies

Abstract

Gliomatosis cerebri (GC) is a rare, extensively infiltrating glioma involving multiple contiguous lobes of the brain. This lethal disease affects all age groups, and the majority of patients have a poor outcome despite aggressive treatment. Despite its initial recognition in 1938, GC remains a controversial entity with little consensus in its definition, histology, or treatment. The majority of GC tumors are astrocytic, although mixed phenotypes have been identified. Treatment of GC is challenging as surgery is generally not an option due to the extensive areas of brain involved, the benefit of radiation therapy is unclear, and no chemotherapy has proven efficacy. Due to the rarity of the disease and its heterogeneity, both at histopathological and molecular levels, it is difficult to conduct clinical trials tailored for this diagnosis. This review summarizes our current knowledge, examines clinical studies focusing on the treatment of GC, highlights ongoing challenges, and discusses the recent molecular insights into adult and pediatric GC. We conclude that, although no longer recognized as a distinct pathological entity, GC represents a unique disease phenotype. Given the histologic and molecular overlap with other diffuse gliomas, the research emphasis should be on investigating its unique invasive biology.

Keywords: glioma; gliomatosis cerebri; primary gliomatosis cerebri; review; secondary gliomatosis cerebri.

Figure 1

Gliomatosis cerebri presenting in a 43-year-old man as a syncopal episode, insidious onset of slurred speech and left leg weakness. Pathology was consistent with IDH-wildtype anaplastic astrocytoma. (1A–1C) are FLAIR sequences demonstrating extensive abnormalities in the white matter of both cerebral hemispheres presenting as high signal intensity. There is also an involvement of midbrain and the right thalamus. The right temporal lobe shows more extensive abnormality as compared to the left temporal lobe. (2A–2C) are T1 sequences postcontrast and show no abnormal increased enhancement in the brain parenchyma or in the meninges.

Figure 2

This is a pathology slide of a World Health Organization (WHO) grade II astrocytoma manifesting as gliomatosis cerebri. The left-hand panel shows hematoxylin–eosin-stained section of cortical tissue with a slight increase in cellularity (objective ×2.5). The right-hand panel shows GFAP staining for astrocytic cells (objective ×40), demonstrating somewhat irregular, atypical positive-staining cells. Buis et al. (18) © The Author(s) 2011. Reproduced with permission of Springer.