Yokohama City University

Digital FDG-PET detects MYD88 mutation-driven glycolysis in primary central nervous system lymphoma

2025.07.30

BACKGROUND AND PURPOSE

The relationship between digital 18F-fluorodeoxyglucose positron emission tomography (dFDG-PET) findings and glucose metabolism-related genetic alterations remains unclear in primary central nervous system lymphoma (PCNSL). This study aimed to evaluate whether dFDG-PET can serve as a noninvasive tool to detect MYD88 mutation-driven glycolytic activity in PCNSL.

MATERIALS AND METHODS

We retrospectively analyzed the imaging and molecular data of 54 patients with PCNSL (55 lesions). MRI and FDG-PET parameters, including the maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR), were assessed. Tumor specimens were subjected to histopathological and genomic evaluations, including the MYD88 mutation status.

RESULTS

Among 55 tumors, 34 (61.8%) were examined with dFDG-PET and 21 (38.2%) with analog 18F-FDG-PET (aFDG-PET). In the dFDG-PET group, MYD88-mutant tumors showed significantly higher SUVmax (30.2 ± 9.9) and TBR (6.1 ± 1.5) compared to wild-type tumors (SUVmax: 19.3 ± 7.2, P = 0.006; TBR: 3.5 ± 1.3, P < 0.001). In the aFDG-PET group, the SUVmax was significantly higher in MYD88-mutant tumors (P = 0.01), whereas the TBR differences were not statistically significant (P = 0.38). Receiver operating characteristic analysis of TBR in dFDG-PET yielded an area under the curve of 0.913 (95% CI: 0.954–1.000) with a cutoff value of 4.49, achieving 88% sensitivity and 88% specificity for MYD88 mutation detection. Multivariate logistic regression identified SUVmax and TBR from dFDG-PET as independent predictors of MYD88 mutation status. The transcriptomic analysis confirmed the significant upregulation of glycolysis-related genes, including hexokinase 2, in MYD88-mutant tumors, supporting increased glycolytic activity.

CONCLUSIONS

dFDG-PET may serve as a valuable noninvasive imaging modality to detect MYD88 mutation-driven enhanced glycolysis in patients with PCNSL.

For inquiries regarding this article

Kensuke Tateishi
Associate Professor
Department of Medicine Neurosurgery, Graduate School of Medicine, Yokohama City University
Yokohama, Japan
Tetsuya Yamamoto
Professor
Department of Medicine Neurosurgery, Graduate School of Medicine, Yokohama City University
Yokohama, Japan
Shingo Kato 
Associate Professor
Department of Medicine Diagnostic Radiology, Graduate School of Medicine, Yokohama City University
Yokohama, Japan
Daisuke Utsunomiya
Professor
Department of Medicine Diagnostic Radiology, Graduate School of Medicine, Yokohama City University
Yokohama, Japan