软脑膜黑色素瘤转移（LMM）与生存率低相关。诊断基于临床表现、脑部 MRI 和脑脊液 (CSF) 分析。初次就诊时的不确定结果可能会延误治疗。在这个单中心病例系列中，对脑脊液中 BRAFV600 和 NRASQ61 突变无细胞肿瘤 DNA (cfDNA) 的检测作为补充诊断生物标志物进行了评估。使用 Idylla® 平台对 12 名临床怀疑患有 LMM 的患者进行了 MRI、脑脊液细胞学检查和 1 mL 脑脊液 cfDNA 分析的回顾性分析。 9 名患者的 MRI 异常提示 LMM。脑脊液分析发现了三名患者的恶性细胞（其中一名没有 MRI 异常）。在 9 名患者的脑脊液中检测到 BRAFV600 或 NRASQ61 突变体 cfDNA（8 名患者有 MRI 异常，1 名患者没有 MRI 异常；所有患者的脑脊液细胞学结果均为阳性）。随后的随访证实了所有 CSF cfDNA 分析呈阳性的患者和一名 CSF cfDNA 分析呈阴性的患者均患有 LMM（敏感性 81.8%；特异性 100%）。我们的研究结果表明，使用 Idylla® 平台分析 CSF 中的 BRAFV600 和 NRASQ61 突变体 cfDNA 有希望成为 LMM 的敏感且特异的补充诊断生物标志物，特别是在成像和 CSF 细胞学不一致的情况下。 110 分钟的分析可以促进紧急治疗决策。© 2024 John Wiley

Leptomeningeal melanoma metastases (LMM) are associated with poor survival. Diagnosis is based on clinical presentation, brain MRI and cerebrospinal fluid (CSF) analysis. Inconclusive findings at initial presentation can delay treatment. In this single-center case series, detection of BRAFV600- and NRASQ61-mutant cell-free tumor DNA (cfDNA) in CSF was evaluated as a complementary diagnostic biomarker. In 12 patients with clinical suspicion of LMM, a retrospective analysis of MRI, CSF cytology and cfDNA analysis on 1 mL of CSF using the Idylla® platform was carried out. Nine patients displayed MRI abnormalities suggesting LMM. CSF analysis identified malignant cells in three patients (including one without MRI abnormalities). BRAFV600- or NRASQ61-mutant cfDNA was detected in CSF of nine patients (eight with and one without MRI abnormalities; all patients with positive CSF cytology). Subsequent follow-up confirmed LMM in all patients with positive and in one patient with a negative CSF cfDNA analysis (sensitivity 81.8%; specificity 100%). Our findings suggest that analyzing BRAFV600- and NRASQ61-mutant cfDNA in CSF using the Idylla® platform holds promise as a sensitive and specific complementary diagnostic biomarker for LMM, particularly in case of inconsistency between imaging and CSF cytology. The 110-min analysis can facilitate urgent treatment decisions.© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.