Gliomatosis Cerebri: Implications of Genetic Findings

Abstract

Gliomatosis cerebri (GC) is defined as a glioma that intensely infiltrates the brain with expansion in at least three cerebral lobes. In the current version of the WHO classification of brain tumors GC is listed among astrocytic tumors due to morphological similarities. Because of the malignant course of the disease the WHO assigned an anaplastic grade (WHO grade III) to this tumor entity. Due to the various settings in which the definition criteria of GC are fulfilled it was suggested to divide GC in primary and secondary GC. Furthermore, the definition of primary GC (pGC) contains subgroups classified by diffuse growth without (type I, the ‘classical’ variant) or with a solid tumor portion (type II). A diffuse infiltration initiating from a solid tumor is classified as secondary GC (sGC). Various studies analysed genetic alterations in GC that typically occur in diffusely infiltrating gliomas. Some findings suggested genetically a relation between GC and low-grade astrocytomas. However, the frequency of identified genetic glioma-like alterations in GC was rather low. Recently, mutations in the IDH1 gene were identified in a high frequency nearly only in diffusely infiltrating gliomas of the WHO grades II and III and in secondary glioblastomas. The marker was successfully used to separate these tumors from other entities that may show morphologically similarities. Therefore, IDH1 mutations seem to be a promising marker to determine the relationship of GC to diffusely infiltrating gliomas. Interestingly, IDH1 mutations were identified only in pGC type II, but not in ‘classical’ pGC type I. These findings support the notion that the current definition of GC allows inclusion of different tumor entities and indicates that ‘classical’ pGC type I is rather not that related to diffusely infiltrating gliomas as formerly assumed.