Radiological, clinical, and molecular analyses reveal distinct subtypes of butterfly glioblastomas affecting the...

Glioblastoma (GB) is known for its highly invasive nature. Images of butterfly GB (bGB) often illustrate this characteristic, but the molecular background and origins of bGB remain unknown.

We analyzed a cohort of 34 bGB patients from our dataset (K-cohort) and 46 bGB patients from publicly available datasets, including TCGA-GBM, CPTAC-GBM, IvyGAP, and UPENN-GBM.

In the K-cohort, the median age was 66 years, and molecular analyses revealed TERT promoter mutations in 55.9% of cases, with no cases exhibiting H3F3A, HIST1H3B, or BRAF mutations. Sequential radiological imaging from the K-cohort provided unique insights, showing one case originating in the corpus callosum (CC) and 3 cases originating in the cerebral hemisphere before developing into bGB. Multi-regional sampling supported a mutational trajectory from the hemisphere to the CC. These observations indicate the presence of 2 distinct radiological origins for bGB. Consequently, we classified cases into CC-type and Hemispheric-type based on the tumor volume ratio within the CC. This subgrouping was clinically meaningful; the CC-type is an independent poor prognostic factor for overall survival, with a hazard ratio of 1.8 (95% confidence interval 1.1-3.0, P = .033), and is molecularly distinct by a higher frequency of methylated MGMTp (P = .0039) compared to the Hemispheric-type.

Our results highlight that the radiological features of bGB are not homogenous and can indicate 2 potential subtypes based on their origins. Further studies are mandatory, but CC-type and Hemispheric-type exhibit distinct clinical backgrounds, outcomes, and molecular features.