Cancer Medicine (Aug 2023)

Utility of cerebrospinal fluid liquid biopsy in distinguishing CNS lymphoma from cerebrospinal infectious/demyelinating diseases

  • Chisako Iriyama,
  • Kenichiro Murate,
  • Sachiko Iba,
  • Akinao Okamoto,
  • Naoe Goto,
  • Hideyuki Yamamoto,
  • Toshiharu Kato,
  • Keichiro Mihara,
  • Takahiko Miyama,
  • Keiko Hattori,
  • Ryoko Kajiya,
  • Masataka Okamoto,
  • Yasuaki Mizutani,
  • Seiji Yamada,
  • Tetsuya Tsukamoto,
  • Yuichi Hirose,
  • Tatsuro Mutoh,
  • Hirohisa Watanabe,
  • Akihiro Tomita

DOI
https://doi.org/10.1002/cam4.6329
Journal volume & issue
Vol. 12, no. 16
pp. 16972 – 16984

Abstract

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Abstract Background Distinguishing between central nervous system lymphoma (CNSL) and CNS infectious and/or demyelinating diseases, although clinically important, is sometimes difficult even using imaging strategies and conventional cerebrospinal fluid (CSF) analyses. To determine whether detection of genetic mutations enables differentiation between these diseases and the early detection of CNSL, we performed mutational analysis using CSF liquid biopsy technique. Methods In this study, we extracted cell‐free DNA from the CSF (CSF‐cfDNA) of CNSL (N = 10), CNS infectious disease (N = 10), and demyelinating disease (N = 10) patients, and performed quantitative mutational analysis by droplet‐digital PCR. Conventional analyses were also performed using peripheral blood and CSF to confirm the characteristics of each disease. Results Blood hemoglobin and albumin levels were significantly lower in CNSL than CNS infectious and demyelinating diseases, CSF cell counts were significantly higher in infectious diseases than CNSL and demyelinating diseases, and CSF‐cfDNA concentrations were significantly higher in infectious diseases than CNSL and demyelinating diseases. Mutation analysis using CSF‐cfDNA detected MYD88L265P and CD79Y196 mutations in 60% of CNSLs each, with either mutation detected in 80% of cases. Mutual existence of both mutations was identified in 40% of cases. These mutations were not detected in either infectious or demyelinating diseases, and the sensitivity and specificity of detecting either MYD88/CD79B mutations in CNSL were 80% and 100%, respectively. In the four cases biopsied, the median time from collecting CSF with the detected mutations to definitive diagnosis by conventional methods was 22.5 days (range, 18–93 days). Conclusions These results suggest that mutation analysis using CSF‐cfDNA might be useful for differentiating CNSL from CNS infectious/demyelinating diseases and for early detection of CNSL, even in cases where brain biopsy is difficult to perform.

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