Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan.
Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan.
Cancer Med. 2023 Aug;12(16):16972-16984. doi: 10.1002/cam4.6329. Epub 2023 Jul 27.
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.
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.
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 MYD88 and CD79 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).
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.
中枢神经系统淋巴瘤 (CNSL) 与中枢神经系统感染和/或脱髓鞘疾病的鉴别，尽管在临床上很重要，但即使使用影像学策略和常规脑脊液 (CSF) 分析也有时难以进行。为了确定遗传突变的检测是否能够区分这些疾病并早期发现 CNSL，我们使用 CSF 液体活检技术进行了突变分析。
在这项研究中，我们从 CNSL（N=10）、中枢神经系统感染性疾病（N=10）和脱髓鞘疾病（N=10）患者的 CSF 中提取了无细胞 DNA（CSF-cfDNA），并通过液滴数字 PCR 进行了定量突变分析。还使用外周血和 CSF 进行了常规分析，以确认每种疾病的特征。
与中枢神经系统感染性和脱髓鞘疾病相比，CNSL 患者的血液血红蛋白和白蛋白水平显著降低，脑脊液细胞计数在感染性疾病中显著高于 CNSL 和脱髓鞘疾病，脑脊液-cfDNA 浓度在感染性疾病中显著高于 CNSL 和脱髓鞘疾病。使用 CSF-cfDNA 的突变分析检测到 60%的 CNSL 中存在 MYD88 和 CD79 突变，80%的病例中检测到任一突变。40%的病例中存在两种突变的共同存在。这些突变未在感染性或脱髓鞘疾病中检测到，检测 CNSL 中任一 MYD88/CD79B 突变的灵敏度和特异性分别为 80%和 100%。在活检的 4 例中，从收集检测到突变的 CSF 到通过常规方法明确诊断的中位数时间为 22.5 天（范围 18-93 天）。
这些结果表明，使用 CSF-cfDNA 的突变分析可能有助于区分 CNSL 与 CNS 感染/脱髓鞘疾病，并有助于早期发现 CNSL，即使在难以进行脑活检的情况下也是如此。
