Combining MYD88 L265P mutation detection and clonality determination on CSF cellular and cell‐free DNA improves diagnosis of primary CNS lymphoma

Abstract

Summary Diagnosis of primary central nervous system lymphoma (PCNSL) is challenging, and although brain biopsy remains the gold standard, cerebrospinal fluid (CSF) constitutes a less invasive source of lymphomatous biomarkers. In a retrospective cohort of 54 PCNSL cases tested at diagnosis or relapse, we evaluated the contribution of immunoglobulin heavy chain (IGH) gene clonality and MYD88 L265P detection on both CSF cell pellets and supernatants, in comparison with cytology, flow cytometry, interleukin (IL)‐10 and IL‐6 quantification. Clonality assessment included a new assay to detect partial IGH‐DJ rearrangements. Clonal IGH rearrangements and/or MYD88 L265P mutation were detected in 27 (50%) cell pellets and 24 (44%) supernatant cell‐free (cf) DNA. Combining analyses on both compartments, 36 (66%) cases had at least one detectable molecular marker, present only in cfDNA for 9 (16%) of them. While cytology and flow cytometry were positive in only 7 (13.0%) and 9 (17.3%) cases respectively, high IL‐10 levels were observed in 36 (66.7%) cases. Overall, taking into account molecular and cytokine results, 46/54 (85%) cases had at least one lymphomatous biomarker detectable in the CSF. These results show that this combination of biomarkers evaluated on both cell pellet and supernatant CSF fractions improves significantly the biological diagnosis of PCNSL.

Primary central nervous system lymphoma in elderly: An illustrative case of the new role of surgery and integrative medical management

“…[ 12 , 18 ] Recent research underscores the utility of CSF-based diagnostics, particularly related to the myeloid differentiation primary response gene 88 (MYD88) L265P mutation. [ 1 ] For instance, Yamaguchi et al . reported a novel rapid genotyping system, GeneSoC, which uses real-time polymerase chain reaction to detect the MYD88 mutation effectively.…”

“…[12,18] Recent research underscores the utility of CSFbased diagnostics, particularly related to the myeloid differentiation primary response gene 88 (MYD88) L265P mutation. [1] For instance, Yamaguchi et al reported a novel rapid genotyping system, GeneSoC, which uses real-time polymerase chain reaction to detect the MYD88 mutation effectively. [19] is innovation reinforces the evolving landscape of PCNSL diagnostics, offering potential advancements for both intra-and preoperative diagnosis through CSF analysis.…”

Diagnostic, Pathologic, and Therapeutic Considerations for Primary CNS Lymphoma

“…Molecular testing for Myd88 and IgH mutations and cytokine analysis for IL-10 may support a diagnosis of CNS lymphoma in the absence of histologic and cytologic confirmation. 31,32 Ultimately, there are inevitable situations where a biopsy cannot be safely performed and CSF analysis is unrevealing. In these situations, we will arrive at a presumed diagnosis together in multidisciplinary discussion with radiology, neurosurgery, and oncology.…”