Related Experiment Video
Updated: Jun 6, 2026
Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation
Published on: January 14, 2014
MRI and Clinical Features of Nonenhancing IDH-Wild-Type Glioblastomas: How to Make an Early Diagnosis and Distinguish
James Ryan Loftus1, Kanwar P Singh2, Sohil H Patel3
1Department of Radiology (J.R.L., K.P.S., M.D.L., R.J.), New York University Grossman School of Medicine, New York, New York james.loftus@nyulangone.org.
Background And Purpose:
A small subset of isocitrate dehydrogenase-wild-type (IDH-wt) glioblastomas (GBMs) initially present as nonenhancing, T2 FLAIR hyperintense cortical/superficial lesions on MRI, potentially leading to misdiagnosis on the initial imaging and hence delayed treatment. This study aimed to characterize the clinical and MRI features of nonenhancing IDH-wt GBMs to help radiologists in differentiating them from nonmalignant mimic diagnoses (eg, encephalitis). Additionally, the histologic, genomic, and survival profiles of nonenhancing GBMs were compared with those of enhancing GBMs.
Materials And Methods:
Clinical and MRI features from 32 patients, each with nonenhancing and enhancing GBMs, and 16 patients with nonmalignant mimic differential diagnoses from a single institution and publicly available data set were retrospectively analyzed. Imaging features were reviewed using the Visually Accessible Rembrandt Images features and the split ADC sign. χ2 tests and a binary logistic regression model were used to compare nonenhancing IDH-wt GBMs with nonmalignant mimics. Histopathologic and genomic analyses were performed on institutional cases. Overall survival between nonenhancing and enhancing GBMs was compared using Kaplan-Meier analysis.
Results:
No significant difference in age, clinical presentation, or duration of symptoms was found between nonenhancing GBMs and nonmalignant mimics. Imaging features favoring nonenhancing GBMs included a greater proportion of non-contrast-enhancing tumor (OR, 7.4), larger anterior-posterior tumor dimension (OR, 8.4), restricted diffusion (OR, 3.6), and eloquent brain involvement (OR, 3.0) while features favoring mimics included greater edema (OR, 0.07), infiltrative T1 FLAIR ratio (OR, 0.68), hemorrhage (OR, 0.76), satellite lesions (OR, 0.84), and the split ADC sign (OR, 0.89). The logistic regression model achieved a mean area under the receiver operator characteristic curve of 0.89 (SD, 0.20) (accuracy 0.84, sensitivity 0.91, specificity 0.70, and precision 0.88). Twelve of 18 nonenhancing GBMs lacked histologic evidence of necrosis or microvascular proliferation ("molecular GBMs"). Genomic profiles were similar between nonenhancing and enhancing GBMs. Median overall survival was nonsignificantly longer in nonenhancing GBMs compared with enhancing GBMs (39 versus 21 months, P = .078).
Conclusions:
Nonenhancing GBMs demonstrate distinct MRI features that must be recognized for early diagnosis and differentiation from nonmalignant mimics. Nonenhancing GBMs demonstrated longer overall survival compared with enhancing GBMs, though they were not statistically significant.
