Department of Neurosurgery, Massachusetts General Hospital, Boston, MA.
Department of Neurosurgery, University of California San Diego, La Jolla, CA.
Blood. 2021 Aug 5;138(5):382-386. doi: 10.1182/blood.2020010137.
Diagnosing primary central nervous system lymphoma (PCNSL) frequently requires neurosurgical biopsy due to nonspecific radiologic features and the low yield of cerebrospinal fluid (CSF) studies. We characterized the clinical evaluation of suspected PCNSL (N = 1007 patients) and designed a rapid multiplexed genotyping assay for MYD88, TERT promoter, IDH1/2, H3F3A, and BRAF mutations to facilitate the diagnosis of PCNSL from CSF and detect other neoplasms in the differential diagnosis. Among 159 patients with confirmed PCNSL, the median time to secure a diagnosis of PCNSL was 10 days, with a range of 0 to 617 days. Permanent histopathology confirmed PCNSL in 142 of 152 biopsies (93.4%), whereas CSF analyses were diagnostic in only 15/113 samplings (13.3%). Among 86 archived clinical specimens, our targeted genotyping assay accurately detected hematologic malignancies with 57.6% sensitivity and 100% specificity (95% confidence interval [CI]: 44.1% to 70.4% and 87.2% to 100%, respectively). MYD88 and TERT promoter mutations were prospectively identified in DNA extracts of CSF obtained from patients with PCNSL and glioblastoma, respectively, within 80 minutes. Across 132 specimens, hallmark mutations indicating the presence of malignancy were detected with 65.8% sensitivity and 100% specificity (95% CI: 56.2%-74.5% and 83.9%-100%, respectively). This targeted genotyping approach offers a rapid, scalable adjunct to reduce diagnostic and treatment delays in PCNSL.
诊断原发性中枢神经系统淋巴瘤（PCNSL）常因影像学特征不典型和脑脊液（CSF）研究阳性率低而需要神经外科活检。我们对疑似 PCNSL 患者（N=1007 例）进行了临床评估，并设计了一种快速多重基因分型检测方法，用于 MYD88、TERT 启动子、IDH1/2、H3F3A 和 BRAF 突变，以促进 CSF 中 PCNSL 的诊断，并在鉴别诊断中发现其他肿瘤。在 159 例确诊的 PCNSL 患者中，确诊 PCNSL 的中位时间为 10 天，范围为 0 至 617 天。永久性组织病理学证实 152 例活检中有 142 例（93.4%）为 PCNSL，而 CSF 分析的诊断率仅为 113 例中的 15 例（13.3%）。在 86 份存档的临床标本中，我们的靶向基因分型检测法准确地检测出了血液系统恶性肿瘤，其敏感性为 57.6%，特异性为 100%（95%置信区间：44.1%至 70.4%和 87.2%至 100%）。MYD88 和 TERT 启动子突变分别在 80 分钟内从 PCNSL 和胶质母细胞瘤患者的 CSF 中提取的 DNA 中得到了前瞻性的鉴定。在 132 个标本中，65.8%的敏感性和 100%的特异性（95%置信区间：56.2%-74.5%和 83.9%-100%）检测到了提示恶性肿瘤存在的标志性突变。这种靶向基因分型方法为减少 PCNSL 的诊断和治疗延迟提供了一种快速、可扩展的辅助方法。
