INNV-62. Molecular diagnosis of primary central nervous system lymphoma: two cases

Abstract While primary central nervous system lymphoma (PCNSL) has characteristic magnetic resonance imaging findings, diagnosis typically requires histopathology via stereotactic brain biopsy in the setting of glucocorticoid avoidance. Cytological diagnosis using flow cytometry and molecular markers such as MYD88 and IL-10 have been proposed but not widely adopted. CSF Circulating tumor DNA (ctDNA) testing is a promising emerging modality. We present two cases of PCNSL with atypical imaging features in which diagnosis was achieved with CSF ctDNA analysis. Both patients presented with rapid onset neurological decline. The first patient’s MRI showed expansile mass with patchy linear enhancement centered in the corpus callosum concerning for high grade glioma versus intravascular lymphoma. CSF EBV, MYD88, and flow cytometry were nondiagnostic, likely due to specimen paucicellularity. However, CSF ctDNA analysis detected mutation in the CD79B gene suggestive of PCNSL which was later confirmed on biopsy. The second patient’s MRI showed a heterogeneously enhancing frontoparietal mass with marked surrounding edema. Lymphoma was initially deemed less likely due to intralesional flow voids. The patient declined surgical biopsy due to age and initial improvement with steroids, which she had been taking for over a month before clinical decline. CSF analysis was positive for EBV PCR and MYD88 mutation; flow cytometry was nondiagnostic due to specimen paucicellularity. Based on these findings, the patient was empirically treated for PCNSL. These cases highlight the diagnostic utility of CSF ctDNA analysis in PCNSL, particularly when imaging and cytological results are inconclusive and tissue biopsy is not feasible. Our experience supports the expanded use of CSF ctDNA testing in the diagnostic algorithm for suspected PCNSL. Larger prospective studies are needed to validate its broader clinical application.