基于基因诊断的儿童原发性弥漫性软脑膜 黑色素瘤病一例并文献复习

Genetic Diagnosis-Based Management of Primary Diffuse Leptomeningeal Melanomatosis in a Pediatric Patient: A Case Report and Literature Review

摘要: 目的：报道儿童原发性弥漫性软脑膜黑色素瘤病(PDLM)的临床特征，探讨基因检测在本病诊断中的核心价值及靶向治疗的研究前景。方法：回顾1例经手术活检、病理及基因检测确诊的儿童PDLM临床资料，并系统复习相关文献。结果：本例11岁男性患儿以头痛、呕吐为主要表现，影像学示双侧脑膜弥漫增厚强化，手术活检病理示肿瘤细胞富含黑色素，免疫组化Melan-A(+)、S-100(+)、SOX-10(+)，基因检测提示NRAS Q61R突变(突变频率84.7%)。患儿确诊后保守治疗，2个月后死亡。结论：PDLM临床罕见、侵袭性强，儿童患者缺乏特异性表现易误诊，脑膜活检联合基因检测是确诊关键；NRAS为儿童PDLM核心突变基因，以MEK抑制剂为核心的靶向联合治疗为该病提供新方向，需进一步临床研究验证疗效。

Abstract: Objective: To investigate the clinical characteristics of primary diffuse leptomeningeal melanomatosis (PDLM) in a pediatric patient and to elucidate the pivotal role of genetic testing in diagnosis, as well as the potential of targeted therapy. Methods: The clinical data of a pediatric case confirmed by surgical biopsy, histopathology, and genetic testing were retrospectively analyzed, and a systematic literature review was conducted. Results: An 11-year-old male patient presented with headache and vomiting. Neuroimaging revealed diffuse thickening and enhancement of the bilateral meninges. Histopathological examination of the surgical biopsy showed melanin-rich tumor cells, with immunohistochemistry positive for Melan-A, S-100, and SOX-10. Genetic testing identified an NRAS Q61R mutation with a variant allele frequency of 84.7%. The patient received conservative treatment and died two months after diagnosis. Conclusion: PDLM is a rare and highly aggressive entity. Pediatric patients often present with non‑specific symptoms, leading to a high risk of misdiagnosis. Meningeal biopsy combined with genetic testing is essential for a definitive diagnosis. NRAS is a core driver gene in pediatric PDLM. MEK inhibitor‑based combination targeted therapy may offer a novel treatment strategy, warranting further clinical investigation.