中枢神经系统恶性黑色素瘤的临床特征及预后分析

Clinical features and prognostic analysis of malignant melanomas in the central nervous system

目的探讨中枢神经系统恶性黑色素瘤(MM)的临床特征、预后及其影响因素。方法回顾性分析2015年1月至2021年9月郑州大学第一附属医院神经外科收治的26例手术切除并经病理学证实为中枢神经系统MM患者的临床资料,其中颅内MM 23例,椎管内MM 3例。采用Kaplan-Meier法分析颅内MM和椎管内MM患者生存期的差异;并采用单因素log-rank检验和多因素Cox回归分析探讨颅内MM患者的预后影响因素。结果26例中枢神经系统MM患者的临床表现无特异性,术前部分患者的MRI T1、T2像均呈短信号,但仍无法明确诊断。所有患者的手术均顺利完成,其中16例行肿瘤全切除,10例行大部分切除(1例位于椎管内);术后病理学检查均证实为MM,其中3例行BRAF V600E突变基因检测,1例为阳性。26例患者均获得临床随访,中位随访时间为9个月(2~58个月);3例患者术后MM复发行二次肿瘤切除手术;至末次随访,24例患者死亡,2例(颅内MM)存活,其中1例为BRAF V600E突变患者,靶向治疗7个月行头颅MRI检查显示颅内多发转移灶接近消失。23例颅内MM患者的中位生存期为8.0个月(4.9~11.1个月),Kaplan-Meier生存分析结果显示,患者6个月和1年生存率分别为70%和24%;3例椎管内MM患者的生存期分别为49、15、58个月,均较颅内MM患者的中位生存期长。23例颅内MM患者的单因素log-rank检验结果显示,肿瘤切除程度是影响患者生存期的独立危险因素(P=0.002);而性别、年龄、肿瘤起源(原发性或转移性)、肿瘤部位(小脑幕上、幕下)、Ki-67增殖指数(<50%、≥50%)及术后是否辅助治疗等因素的差异均无统计学意义(均P>0.05)。结论中枢神经系统MM患病率低,误诊率高,临床表现及MRI多不典型,需病理学检查确诊;肿瘤切除程度是颅内MM患者的独立预后影响因素,颅内MM的生存期较椎管内MM短,整体预后均较差。

Objective To investigate the clinical characteristics,prognosis and prognostic factors of malignant melanomas(MM)in the central nervous system.Methods A retrospective analysis was conducted on the clinical data of 26 patients with pathologically confirmed central nervous system MM who underwent surgical resection at the Department of Neurosurgery,the First Affiliated Hospital of Zhengzhou University from January 2015 to September 2021.Among the patients,23 had intracranial MM and 3 had intraspinal MM.Kaplan-Meier method was used to explore the difference of survival between intracranial MM and intraspinal MM.Univariate log-rank test and multivariate Cox regression survival analyses were performed to identify prognostic factors of intracranial MM.Results The 26 cases with central nervous system MM had no characteristic clinical manifestations.Preoperative MRI showed short T1 and short T2 signals in some patients,which,however,could not lead to a definite diagnosis.The surgeries were successfully completed in all patients.Total resection was achieved in 16 cases and subtotal resection in 10 cases(including 1 case of intraspinal MM).Postoperative pathological evaluation showed MM in all 26 cases.Detection of the BRAF V600E mutation was carried out in 3 cases and revealed positive in 1 case.All 26 cases were followed up for a median of 9 months(2-58 months).Three patients underwent a second operation after MM recurrence.At the last follow-up,24 cases died and 2 cases(intracranial MM)survived.Out of the 2 cases,1 had BRAF V600E mutation and the multiple intracranial metastases almost disappeared at 7 months post targeted therapy.Median survival for the 23 intracranial cases was 8.0 months(4.9-11.1 months)and Kaplan-Meier survival analysis showed that survival rates at 6 months and 1 year post operation were 70%and 24%respectively.The survival periods of 3 intraspinal cases was 49,15 and 58 months respectively,which were all longer than that of the intracranial cases.Univariate log-rank test analysis for the 23 intracranial cases showed that extent of resection was the only independent prognostic factor for survival(P=0.002),while differences in gender,age,tumor origin(primary or metastatic),tumor location(supratentorial or infratentorial),Ki-67 positive rate(<50%or≥50%),or postoperative adjuvant therapy were not statistically significant(all P>0.05).Conclusions Central nervous system MM is a rare disease with atypical clinical and MRI manifestations and a high misdiagnosis rate.Its established diagnosis should be based on pathological examination.Extent of tumor resection is an independent prognostic factor of intracranial MM.Survival of patients with intracranial MM is shorter than that with intraspinal MM and its overall prognosis remains poor.