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Updated: May 16, 2026

Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Cortical Diffusion-Enhancement Mismatch Sign: A Specific Imaging Biomarker for Differentiating Primary Central
Novita I Khairunnisa1, Fumiyuki Yamasaki1, Ushio Yonezawa1
1Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima city, Hiroshima, Japan.
Background And Objectives:
Previous studies have focused on differentiating glioblastoma (GBM), isocitrate dehydrogenase-wildtype from primary central nervous system lymphoma (PCNSL) based on contrast-enhanced patterns, and/or peritumoral white matter invasion. In this study, we focused on the peritumoral area of superficially located PCNSL and GBM.
Methods:
We retrospectively reviewed the preoperative images of patients with pathologically confirmed GBM and PCNSL. The cortical diffusion-enhancement mismatch sign was defined as a high-intensity diffusion-weighted imaging lesion that involves both gray and white matters, with the corresponding gadolinium-enhanced lesion limited to the subcortical white matter, delineating the gray-white matter junction.
Results:
In total, 61 cases of histologically confirmed PCNSL and 65 cases of GBM were identified between August 2009 and June 2023. Thirteen cases (21.3%) of PCNSL and 35 cases (53.8%) of GBM presented with superficial lesions. Seven (53.8%) of the 13 superficial PCNSL cases presented with the cortical diffusion-enhancement mismatch sign. This sign appeared exclusively in PCNSL and was not observed in GBM (P < .001; sensitivity: 53.85%; specificity: 100%). This sign was primarily observed in diffuse large B-cell lymphoma, nongerminal center B-cell type (n = 5, 71.4%) with a mean age of 60.42 ± 15.2 years.
Conclusion:
The cortical diffusion-enhancement mismatch sign could serve as a specific imaging diagnostic biomarker for PCNSL. This sign may suggest that PCNSL involving the cortical area developed from the white matter, not directly from the gray matter.

