【作者】 陈军；

【导师】 王煜；

【作者基本信息】 华中科技大学 ， 神经外科， 2019， 硕士

【摘要】 目的:椎管内尤因肉瘤/外周原始神经外胚层肿瘤(Ewing sarcoma/peripheral primitive neuroectodermal tumors,ES/p PNETs)是一种罕见的高度恶性肿瘤。由于国内外对椎管内ES/p PNETs的研究多为个案报道,尚无大宗病例的长期随访和总结,很难对椎管内ES/p PNETs有一个全面深刻的认识。本文通过系统研究椎管内ES/p PNETs的临床病理、免疫组化及超微结构特点,并统计分析不同因素对ES/p PNETs患者的预后影响,这对指导临床治疗及改善患者预后具有重要意义。方法:回顾性分析华中科技大学同济医学院附属同济医院2003年1月至2018年12月经手术治疗且病理检查及免疫组化染色证实的40例椎管内原发尤因肉瘤/原始神经外胚层肿瘤的临床资料。所有病例患者的肿瘤标本均行HE染色和免疫组化分析,其中有6例肿瘤标本应用荧光原位杂交(fluorescence in situ hybridization,FISH)技术进行易位基因检测。采用Kaplan—Meier法估计40例患者的总生存时间(overall survival,OS)和无进展生存时间(progression-free survival,PFS),Log-rank检验进行单因素生存分析,将单因素分析结果中P≤0.1的因素采用Cox比例风险模型进行多因素生存分析。结果:FLI-1的阳性率为65%,CD99的阳性率为100%。6例行易位基因检测的患者均有t(11;22)(q24;q12)染色体易位,并检测到其产生的EWS/FLI-1融合基因。40例患者中,男24例、女16例,男:女=3:2。患者年龄为1~45岁,平均21.9岁。本组患者PFS和OS的中位数分别为14个月和25个月。1年,2年和5年的PFS率分别为57.7%,30.4%和9.5%。1年,2年和5年的OS率分别为74.8%,50.7%和12.2%。单因素Log-rank分析结果显示,肿瘤切除程度、术后Frankel score、术后放疗和化疗均为患者OS和PFS的影响因素(均P<0.05)。多因素Cox逐步回归分析显示,术后辅助放疗及肿瘤切除程度均为患者OS和PFS的独立影响因素(均P<0.05)。结论:椎管内原发ES/p PNETs是极其罕见的高侵袭性及高度恶性肿瘤,生长迅速、病程短、进展快、误诊率高、预后极差。CD99联合FLI-1对ES/p PNETs的诊断具有重要价值,易位基因(EWS/FLI-1融合基因)检测是其诊断的金标准。显微手术全切除肿瘤是治疗首选。手术的目的是明确病理诊断,减少肿瘤负荷,改善压迫症状。术后联合放、化疗等综合治疗可提高患者的生存质量和延长生存期。更多还原

【Abstract】 Objective: Primary spinal Ewing sarcoma(ES)/peripheral primitive neuroectodermal tumors(p PNETs)are extremely rare malignant tumor.Because most of the studies about primary spinal ES/p PNETs are small sample clinical studies and case reports,there is still a lack of large-scale case studies,so it is difficult to have a comprehensive and profound understanding of primary spinal ES/p PNETs.The purpose of this study was to illustrate the clinicopathologic,immunohistochemical and ultrastructural features of primary spinal ES/p PNETs,and to discuss prognostic factors by survival analysis.It is important for guiding clinical treatment and improving patient prognosis.Methods: The clinical data of 40 patients,who had been surgically treated from January 2003 to December 2018 and in whom immunohistochemical staining results had confirmed the diagnosis of primary spinal ES/p PNETs,were retrospectively analyzed.A fluorescence in situ hybridization(FISH)analysis was performed in 6 cases.Progression-free survival(PFS)and overall survival(OS)were estimated by the Kaplan–Meier method to identify potential prognostic factors.Factors of p values ≤ 0.1 in the Log-rank tests were subjected to multivariate analysis by Cox regression analysis.Results: Forty(100%)patients were positive for CD99 and 26(65%)patients were positive for Friend Leukemia Virus Integration 1(FLI-1).EWS/FLI1 translocation was detected in 6 cases.The population comprised 24 men and 16 women with a mean age of 21.9(range,1–45)years.The median PFS was 14 months.The 1-,2-,and 5-year PFS rates were 57.7%,30.4%,and 9.5%,respectively.The median OS was 25 months.The 1-,2-,and 5-year OS rates were 74.8%,50.7%,and 12.2%,respectively.The univariate analysis suggested that postoperative Frankel score,adjuvant chemotherapy,adjuvant radiotherapy,and extent of resection were potential prognostic factors for PFS and OS.However,after these factors were subjected to multivariate analyses,only adjuvant radiotherapy and extent of resection remained as independent prognostic factors.Conclusions: Primary spinal ES/p PNETs are extremely rare and have a poor prognosis.The clinical manifestations of patients included acute onset,short duration,and rapid progression.CD99 combined with FLI-1 is of great value in the diagnosis of ES/p PNETs.The golden standard for diagnosing ES/p PNET is the identification of the tumor type-specific fusion genes EWSR1/FLI-1.Surgical treatment is the cornerstone of therapy for primary intracranial ES/p PNETs.The aim of surgery is to relieve symptoms,control local recurrence,achieve a sufficient volume reduction for further oncological management,and prolong patient survival.Gross total resection combined with adjuvant radiotherapy and chemotherapy can improve the quality of life and prolong survival time.更多还原