编者按：原发性中枢神经系统（central nervous system，CNS）黑色素瘤非常罕见，每年发病率约为0.01/10万^[1,2]，占所有黑色素瘤的1% ^[3-5]。临床症状和影像学表现缺乏特异性，目前诊断主要依靠组织或细胞病理学活检、免疫组化检测和分子病理学检测。原发性CNS黑色素瘤尚无标准的治疗方案，临床上多采用手术、放射治疗和化学治疗，但疗效并不理想。

本期「专家组稿」由吉林大学第一医院吴荻教授担任执行主编，与吉林大学第一医院肿瘤内科硕士郭鹏娜共同分享原发性CNS黑色素瘤的流行病学、临床病理特征及现有的诊疗方法，并提出了潜在的治疗策略。

一、疾病特点

一项回顾性研究中分析发现原发性CNS黑色素瘤发病年龄存在两个高峰，分别为第1个十年和第4个十年^[1,6-9]，占比为16.7%和21.8% ^[6]。对59名患者进行性别分析发现男女比例为1.46:1^[6]。也有一些小样本或个案报道的研究结果与其并不一致^[10-15]。主要发病部位以脑膜为主，其次为脑实质和脊柱。颞叶和额叶也是常被报道的发病部位^[16]。

大多数原发性CNS黑色素瘤直接由黑色素细胞恶性转化而来，少数与脑膜黑色素细胞瘤有关^[7-10,17-23]。临床表现主要取决于肿瘤的解剖位置和受压神经的结构^[22]。当肿瘤位于脑部时，多表现为颅内高压、脑积水、局灶性神经功能缺损、蛛网膜下腔出血和癫痫发作^[1,6,24,25]。位于脊柱的病变常与背部疼痛、肢体无力、感觉和运动障碍有关^[6,26]。

二、影像学表现

MRI是原发性CNS黑色素瘤诊断首选的影像学方法^[4]，但影像学表现受黑色素含量的多少以及有无出血的影响^[2,14,27]。当黑色素含量＞10%的肿瘤多表现为T1加权图像高信号，T2加权图像低信号，称之为“黑素细胞”模式，反之亦然^{[2,14,19,23,27-31]}。原发性CNS黑色素瘤瘤内出血的顺磁产物高铁血红蛋白、含铁血黄素可以降低T1、T2的弛豫时间，影响原发性CNS黑色素瘤的诊断^{[10,22,32-35]}。

三、诊断和鉴别诊断

根据1976年Hayward提出的标准，原发性CNS黑色素瘤的诊断需具备CNS外或CNS其他部位不存在黑色素瘤，同时组织病理学证实为黑色素瘤^[1,10,36-38]。原发性CNS黑色素瘤的临床症状和影像学表现与黑色素瘤脑转移、CNS色素性病变非常相似，仅凭组织细胞病理学及免疫组化检测难以鉴别。当CNS和CNS外共存黑色素瘤或CNS多发黑色素瘤时，明确诊断CNS肿瘤是否原发及原发部位极为困难。

四、治疗

1.传统治疗

早期原发性CNS黑色素瘤首选手术切除，肿瘤的位置和大小决定肿瘤的手术方式^[39] 。无法完全切除的肿瘤附加根治性放疗，有利于肿瘤局部控制及改善预后^[40,41]。在目前为止样本量最大的回顾性研究中，Carolina等纳入了54例原发性CNS黑色素瘤。7例进行活检（biospy，B），4例接受部分切除（subtotal rep，STR），活检术后和部分切除的患者平均生存期（mean survival）相近，分别为10、9.5个月。22例接受完全切除（gross total rep ，GTR）的患者平均生存期明显提高，可达31个月。其中接受GTR、化疗（chemotherapy，CT）和放疗（radiation therapy，RT）综合治疗的平均生存期为17.5个月，GTR+CT为15个月，而GTR+RT可达34.5个月^[42]。结果表明接受GTR的原发性CNS黑色素瘤患者临床获益明显，而无法完成 GTR的患者，采用STR + RT能够显著改善患者预后。然而由于原发性CNS黑色素瘤的罕见性及高级别循证医学证据的缺乏，标准治疗方案尚无法确定。

晚期CNS黑色素瘤的治疗以全身化疗为主。目前为止，文献中尚未发现有充分证据的化疗方案，大多采用替莫唑胺、达卡巴嗪、铂类药物及鞘内注射甲氨蝶呤进行化疗，随访时间在2 -48个月之间，中位无进展生存期（progress free survival，PFS）为5个月，中位总生存期（overall survival，OS）为12.5个月 ^{[1,2,23,43-49]}。

2.靶向治疗与免疫治疗

原发性CNS黑色素瘤中只有极少数病例采用靶向治疗和免疫治疗。6例接受靶向治疗的原发性CNS黑色素瘤，所有患者均有不同程度症状、体征改善，中位OS为7.2个月（4.8-9.6个月）。其中1例NRAS突变患者PFS为5个月^[50-52]。5例接受免疫治疗的5例原发性CNS黑色素瘤^[5,53-56]，中位OS为58个月（5-63个月）。

总结

原发性CNS黑色素瘤发病罕见^[1,2]，临床表现和影像学表现不典型，诊断多依靠病理组织活检。目前原发性CNS黑色素瘤尚无标准治疗方案，手术切除是第一治疗选择，术后辅助放疗似乎会带来一些生存获益。靶向治疗和免疫治疗有望成为原发性CNS黑色素瘤潜在的治疗选择，接受多学科综合治疗疗效可能更佳。但目前仍缺乏针对原发性CNS黑色素瘤患者的大样本临床研究。深入研究原发性CNS黑色素瘤发病机制、分子病理学和肿瘤免疫微环境特征，可为未来治疗策略的发展提供理论基础。

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