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

Area of Science:

• Neuro-oncology
• Molecular imaging
• Genetics

Background:

• The link between digital 18F-fluorodeoxyglucose positron emission tomography (dFDG-PET) findings and genetic alterations in glucose metabolism is not well understood for primary central nervous system lymphoma (PCNSL).
• MYD88 mutations are implicated in the pathogenesis of PCNSL, potentially influencing tumor metabolism.

Purpose of the Study:

• To investigate if dFDG-PET can serve as a noninvasive method to identify MYD88 mutation-associated glycolytic activity in PCNSL.
• To correlate dFDG-PET imaging parameters with MYD88 mutation status in PCNSL patients.

Main Methods:

• Retrospective analysis of 54 PCNSL patients (55 lesions) with available imaging and molecular data.
• Assessment of MRI and FDG-PET parameters, including maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR).
• Histopathological and genomic evaluation of tumor specimens to determine MYD88 mutation status.

Main Results:

• MYD88-mutant PCNSL tumors showed significantly higher SUVmax and TBR on dFDG-PET compared to wild-type tumors.
• Receiver operating characteristic analysis for TBR on dFDG-PET demonstrated high accuracy (AUC=0.913) for MYD88 mutation detection.
• Transcriptomic analysis confirmed increased glycolysis-related gene expression in MYD88-mutant tumors.

Conclusions:

• dFDG-PET is a promising noninvasive imaging technique for detecting MYD88 mutation-driven enhanced glycolysis in PCNSL.
• SUVmax and TBR derived from dFDG-PET are independent predictors of MYD88 mutation status in PCNSL.
• These findings support the use of dFDG-PET in the diagnostic workup of PCNSL, potentially guiding treatment strategies.