摘要目的 探讨von Hippel-Lindau(VHL)综合征及散发性中枢神经系统(CNS)血管母细胞瘤(HB)的临床病理特征、诊断及鉴别诊断、治疗及预后.方法 应用光镜、电镜及免疫组织化学EnVision法染色,对21例VHL综合征和63例散发性HB进行观察分析,分别获得18例和42例随访资料.结果 21例VHL综合征患者中除4例确诊外均漏诊.平均首诊年龄29.5岁,男11例,女10例.21例患者共发生87个CNS-HB,最多者13年新发12个.10例患者存在其他VHL相关病变:6例视网膜HB、4例胰腺肿瘤(内分泌肿瘤、微囊性腺瘤)、1例透明细胞性肾细胞癌、4例肾囊肿、1例内淋巴囊肿瘤.1例患者4年间发生5种VHL相关肿瘤.63例散发性HB,平均年龄43.0岁,男34例,女29例.随访18例VHL综合征中生存14例,病死4例,生存者中残障(失明、偏瘫)4例、再发11例.42例散发性HB,生存39例(92.9%),其中残障3例;病死3例(7.2%).病理学特征HB间质细胞胞质泡沫样,血管丰富.部分HB可见异形核瘤细胞.HB侵犯脑组织者32例,随访21例患者均生存.HB间质细胞阳性表达:波形蛋白、表皮生长因子受体(EGFR)、Inhibin α及D2-40,CD34及CD68均阴性,3例瘤细胞表达胶质纤维酸性蛋白(GFAP).30例行Ki-67免疫组织化学标记,Ki-67标记指数除7例为2%,2例为5%,余均为1%,随访22例患者均生存.结论 VHL综合征是一组多系统多发性良恶性肿瘤症候群,预后差,漏诊率高.CNS-HB多发于小脑.VHL相关性HB较散发性HB就诊年龄小10岁,易发生于脑干和脊髓.HB肿瘤中异形核细胞、Ki-67标记指数稍高及侵犯脑组织均与预后无关.VHL综合征患者终生存在新发VHL相关肿瘤的可能,因此强调对确诊患者终生随访及定期全面检查,早期发现,早期治疗.

abstractsObjective To study clinicopathologic features, diagnosis, treatment and prognosis of von Hippel-Lindau (VHL) syndrome-related and sporadic hemangioblastomas of the central nervous system(CNS-HB). Methods Histopathological, ultrastructural, immunohistochernical ( EnVision method) and clinical features of 21 VHL syndrome and 63 sporadic CNS-HB cases were studied with correlation of the available follow-up information. Results Twenty-one VHL patients accompanied with a total of 87 CNS-HBs, including one patient of developing 12 HBs within 13 years. There were 10 patients presenting other lesions related to VHL, including 6 retinal HBs, 4 pancreatic tumors ( endocrine tumor and mierocystic cystadenoma), 1 clear renal cell carcinoma, 4 renal cysts and 1 endolymphatic sac tumor. One patient developed 5 different tumors related to VHL within a period of 4 years. In the 63 cases of sporadic CNS-HB(34 male and 29 female), the mean age was 43.0 years. Among the 18 VHL syndrome patients with available follow-up information, 14 were still alive and within them, 4 became disabled and 11 had developed new lesions. The other 4 patients died. Among the 42 patients of sporadic HB with follow-up information, 39 were alive including 3 disabled cases, and the other 3 died. Histologically, the tumors showed large and vacuolated stromal ceils. Some tumors showed atypical nuclei. Involvement of the brain tissue was seen in 32 cases, among which, 21 patients with available follow-up information were learnt to be alive. Tumor cells of HB stained positive for vimentin, EGFR, Inhibin a and D2-40, but negative for CD34 and CD68. In 3 cases of HB, some stromal cells were positive for GFAP. All cases showed a low expression for Ki-67, except 2 cases with 2% and 1 case with 5% Ki-67 indices. Conclusions VHL syndrome is a multisystem disorder with a poor prognosis and a high rate of missed diagnosis. The syndrome is characterized by development of various benign and malignant tumors. The most common tumor is CNS-HB,which occurs predominantly in the cerebellum. Patients with VHL syndrome tend to present at a younger age than patients with sporadic CNS-HBs, and VHL related HB occurs more predominantly in the brain stem and spinal cord. Prognosis of CNS-HB patients is not correlated with the nuclear atypicality, expression for Ki-67 and involvement of the brain tissue. Because new lesions may develop during the patient's lifetime. So that,regular clinical inspection is recommended in order to check up the development of any new lesions.