Digital FDG-PET Detects MYD88 Mutation-Driven Glycolysis in Primary CNS Lymphoma

ABSTRACT 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. ABBREVIATIONS: dPET＝ Digital positron emission tomography; PCNSL＝ Primary central nervous system lymphoma; SUVmax＝maximum standardized uptake value; TBR＝ tumor-to background ratio.