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

AJNR Am J Neuroradiol. 2026 Jan 5;47(1):117-125. doi: 10.3174/ajnr.A8935.

Abstract

Background and purpose: The relationship between digital 18F-FDG-PET findings and glucose metabolism-related genetic alterations remains unclear in primary CNS lymphoma (PCNSL). This study aimed to evaluate whether digital FDG-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 histopathologic and genomic evaluations, including the MYD88 mutation status.

Results: Among 55 tumors, 34 (61.8%) were examined with digital FDG-PET and 21 (38.2%) with analog 18F-FDG-PET. In the digital FDG-PET group, MYD88-mutant tumors showed statistically higher SUVmax (30.2 ± 9.9) and TBR (6.1 ± 1.5) compared with wild-type tumors (SUVmax: 19.3 ± 7.2, P = .006; TBR: 3.5 ± 1.3, P < .001). In the analog FDG-PET group, the SUVmax was higher in MYD88-mutant tumors (P = .01), whereas the TBR differences were not statistically significant (P = .38). Receiver operating characteristic analysis of TBR in digital FDG-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 digital FDG-PET as independent predictors of MYD88 mutation status. The transcriptomic analysis confirmed the up-regulation of glycolysis-related genes, including hexokinase 2, in MYD88-mutant tumors, supporting increased glycolytic activity.

Conclusions: Digital FDG-PET may serve as a valuable noninvasive imaging technique to detect MYD88 mutation-driven enhanced glycolysis in patients with PCNSL.

MeSH terms

  • Adult
  • Aged
  • Central Nervous System Neoplasms* / diagnostic imaging
  • Central Nervous System Neoplasms* / genetics
  • Central Nervous System Neoplasms* / metabolism
  • Female
  • Fluorodeoxyglucose F18*
  • Glycolysis* / genetics
  • Humans
  • Lymphoma* / diagnostic imaging
  • Lymphoma* / genetics
  • Lymphoma* / metabolism
  • Male
  • Middle Aged
  • Mutation / genetics
  • Myeloid Differentiation Factor 88* / genetics
  • Positron-Emission Tomography* / methods
  • Radiopharmaceuticals
  • Retrospective Studies
  • Sensitivity and Specificity

Substances

  • Myeloid Differentiation Factor 88
  • Fluorodeoxyglucose F18
  • MYD88 protein, human
  • Radiopharmaceuticals