髓母细胞瘤与幕上原始神经外胚叶肿瘤中RASSF1A基因的甲基化差异

目的通过研究髓母细胞瘤与幕上原始神经外胚叶肿瘤（SPNET）中RASSF1A基因的甲基化改变,探讨颅内原始神经外胚叶肿瘤（PNET）的不同亚型中该基因的表遗传学差异及其意义。方法收集25例原发髓母细胞瘤,9例原发SPNET,3株髓母细胞瘤细胞系和2株SPNET细胞系。采用甲基化特异性聚合酶链反应（MSP）检测RASSF1A基因启动子区的甲基化状态。应用去甲基化试剂5-aza-2’deoxycytidine处理存在基因表达缺失的细胞系,探讨基因表达与甲基化之间的关系。结果100％（25／25）的原发髓母细胞瘤、6／9的原发SPNET及全部PNET细胞系中均检测到RASSFIA基因的甲基化。相反,该基因甲基化在全部正常组织（包括2例小脑,5例大脑）中均未检测到。并且,RASSF1A在SPNET中的甲基化率明显低于髓母细胞瘤（Fisher精确检验,P=0．014）。在经去甲基化试剂处理的PNET细胞中,该基因表达得以恢复,证明甲基化与该基因沉默相关。结论RASSF1A甲基化是肿瘤特异性的,RASSF1A甲基化与PNET的发生有一定关联,不同亚型的PNET之间RASSF1A基因的不同甲基化状态提示髓母细胞瘤和SPNET是表遗传学上存在差异的两类肿瘤。     

原始神经外胚叶肿瘤

原始神经外胚叶肿瘤（ｐｒｉｍｉｔｉｖｅｎｅｕｒｏｅｃｔｏｄｅｒｍａｌｔｕｍｏｒｓ，ＰＮＥＴｓ）的研究资料已经不少。但对原始神经外胚叶肿瘤是不是一个独立的类型，它在中枢神经系统肿瘤的组织学分类中有什么特别的意义，各家意见不一。原始神经外胚叶肿瘤有中枢型...     

颅内原始神经外胚叶肿瘤中TIG1启动子的高甲基化

目的检测颅内原始神经外胚叶肿瘤(primitive neuroectodermal tumor,PNET)中TIG1(tazarotene induced gene-1)基因启动子的甲基化状态。方法使用甲基化特异PCR(MSP)法检测25例原发髓母细胞瘤(medulloblastoma,MB)、9例原发幕上原始神经外胚叶肿瘤(supratentorial primitive neuroectodermal tumor,SPNET)和7株PNET细胞系中TIG1的甲基化水平。用RT-PCR方法检测PNET细胞中TIG1的转录水平。并用去甲基化试剂处理PNET细胞,观察基因转录水平与甲基化状态间的关系。结果原发MB及SPNET中TIG1启动子的异常甲基化率分别为40%(10/25)和44%(4/9)。该基因在PNET中的甲基化异常是肿瘤特异性的。PNET细胞系中均有TIG1高甲基化,并伴有转录水平的表达减少或丢失(7/7)。TIG1的表达水平与启动子甲基化状态呈明显负相关。并且,这种相关性得到去甲基化试剂处理实验的支持。经去甲基化试剂5-aza-2′-deoxycyti-dine处理的全部细胞系中TIG1的表达都得到了恢复。结论大部分PNET细胞系中都有TIG1表达的减少和缺失,且该基因缺失与启动子高甲基化密切相关。同时,TIG1的高甲基化率在原发PNET中也能检测到,提示TIG1可能在颅内PNET的肿瘤发生中起重要作用。     

腹腔原始神经外胚叶瘤广泛转移1例

患儿女,１１岁,无任何诱因下发生脐周隐痛、阵发性加剧１个月,以肠蛔虫症收住院。Ｂ超提示：子宫直肠凹见囊实性占位病变。手术发现：乙状结肠根部有一１２ｃｍ×８ｃｍ×８ｃｍ大小包块,不规则,呈菜花状;位于子宫后、骶骨前及双侧附件周有１０余个大小不等的包块,...     

肾脏原始神经外胚叶肿瘤一例

患者男,31岁。因右腰痛伴小便带血1年余于2005年8月8日入院。入院前行放射治疗1个月。体检：右肾区扣击痛,右肋缘下可触及肿大肾体,质硬。B超检查：膀胱充盈差,壁光滑,右肾上极探及9．5cm×6．9cm实性不均质回声团块,左肾未见异常,右肾实性占位。患者曾于6月6日行肾脏CT扫描：右肾上中极肿块约12cm×12cm×11cm大小,外上缘突破肾包膜与腹膜及肝下内缘分界不清,其内密度欠均匀,腹膜后无明显肿大淋巴结。诊断：右肾癌周围侵犯。7月25日肾脏CT扫描：右肾中上部可见一约8．0cm×6．5cm大小弱低密度肿块,CT值约28Hu,其内可见不规则更低密度灶肿块,上缘向后上膨突并与肝脏分界不清,肾门及腹膜后无肿大淋巴结,与前片比较瘤灶明显缩小,诊断：右肾癌放疗后所见。在连续硬膜外麻醉下行右肾切除术,手术所见：右侧腹膜后肾脏区巨大肿块,与肝脏下缘粘连,质地硬。将右肾完整切除送检。     

大脑和脊髓原始神经外胚叶肿瘤临床病理学

目的：探讨原发于大脑和脊髓原始神经外胚叶肿瘤的临床病理特征、组织学发生及生物学行为。方法：采用组织病理学、免疫组化标记和电镜观察对１１例原发于大脑及脊髓的原始神经外胚叶肿瘤进行研究。结果：组织学特征为弥漫原始的小细胞,并形成Ｈｏｍｅｒ－Ｗｒｉｇｈｔ菊形团和明显的纤维组织分隔成小叶。免疫组化标记：ＮＳＥ阳性,Ｓｙｎ阳性,部分瘤组织中散在ＧＦＡＰ阳性。电镜：瘤细胞胞浆内可见致密核心的分泌颗粒。结论：该     

小脑髓母细胞瘤的形态学观察

目的;探讨髓母细胞瘤细胞的分化潜能。方法：对40例髓母细胞瘤行光镜观察,并采用免疫血清CFAP（胶质纤维酸性蛋白）、NF（神经纤维细胞蛋白）、NSE（神经元特异性烯醇化酶）、S-100蛋白,分别对其进行免疫组化染色。结果：按WHO分类标准,光镜下将髓母细胞瘤分为两类;（1）经典型（24例）;（2）促纤维增生型（16例）。免疫组化染色结果阳性率分别为：GFAP55%（22例）、NF70%（28例）,NSE57%（23例）、S-100蛋白40%（16例）。结论：髓母细胞瘤细胞具有向神经元和神经胶质细胞双向分化的潜能。     

外周原始神经外胚叶瘤和尤因肉瘤的新进展

外周原始神经外胚叶瘤 (ｐｅｒｉｐｈｅｒａｌｐｒｉｍｉｔｉｖｅｎｅｕｒｏｅｃｔｏ ｄｅｒｍａｌｔｕｍｏｒｓ,ｐＰＮＥＴ)和尤因肉瘤 (Ｅｗｉｎｇ’ｓｓａｒｃｏｍａ,ＥＷＳ)是软组织和骨常见的高度恶性肿瘤 ,两者关系密切 ,发生在儿童、青少年 ,有共同的神经外胚层起源 ,形态相似 ,都有ｔ(11;2 2 ) (ｑ2 4 ;ｑ12 )易位的染色体标记 ,属于ＰＮＥＴ/ＥＷＳ家族肿瘤。包括骨尤因肉瘤 (Ｅｗｉｎｇ’ｓｓａｒｃｏｍａｏｆｂｏｎｅ ,ＥＳＢ)、骨外尤因肉瘤 (ｅｘｔｒａｏｓｓｅｏｕｓＥｗｉｎｇ’ｓｓａｒｃｏｍａ ,ＥＯＥ)、外周神经上皮瘤 (…     

大脑原始神经外胚叶瘤伴有砂粒小体1例

患者男，50岁。四肢乏力1年，头痛、头晕伴恶心半月。半月前病人出现头部胀痛，呈阵发性，能自行缓解。同时伴有头晕、恶心，肢体乏力症状有所加重，走路时略有蹒跚。2002年9月30日出现呕吐，来我院就诊。CT检查考虑为少枝胶质细胞瘤。MRI检查考虑为转移瘤，不除外丘脑囊虫病。专科检查：意识清楚，对答切题。GCS评分15分     

伴有多量神经毡和真菊形团的胚胎性肿瘤:一种具有组织学特征性的中枢神经系统原始神经外胚叶肿瘤

中枢神经系统（CNS）胚胎性肿瘤通常发病年龄较小，虽组织学形态不尽相同，但均表现出侵袭性的临床生物学行为。已有几组报道发现伴有复合性室管膜母细胞瘤和神经母细胞瘤组织学特征的胚胎性肿瘤病例，这又被称为是伴有多量神经毡和真菊形团结构的胚胎性肿瘤（ETANTR）。     

Renal primitive neuroectodermal tumors

Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.     

Lipomatous supratentorial primitive neuroectodermal tumor with glioblastomatous differentiation

Cases of cerebral neuroblastoma or supratentorial primitive neuroectodermal tumor with malignant gliomatous components are relatively uncommon. Less frequent is the combination of these 2 elements with a mesenchymal component. This is a case report of a lipomatous supratentorial primitive neuroectodermal tumor with glioblastomatous differentiation occurring in a 48-year-old woman. She presented with headaches and confusion. A right parietal lobe mass was excised and subsequently recurred, requiring additional surgery 10 months later. The patient died 13 months after initial surgery. Histologic findings showed a proliferation of small rounded synaptophysin-positive neural cells consistent with neuroblastoma. These cells were arranged against a benign lipomatous background. The second resection consisted primarily of glioblastomatous-like tissue with intermixed lipomatous component. The glioblastoma component was marked by prominent cellularity, moderate nuclear pleomorphism, readily identifiable mitotic activity, vascular proliferative changes, and necrosis. The glioblastomatous component of the tumor demonstrated glial fibrillary acidic protein immunoreactivity. A Ki-67 labeling index of 18.9% was noted in the initial resection. The literature on similar-appearing lesions is reviewed.     

Molecular markers of primitive neuroectodermal tumors and other pediatric central nervous system tumors. Monoclonal antibodies to neuronal and glial antigens distinguish subsets of primitive neuroectodermal tumors

Seventy-one tumors of the central nervous system in children were studied immunohistologically. Thirty-seven were classified histologically as PNETs, of which 35 were located in the cerebellum (medulloblastomas), one in the cerebrum, and one in the spinal cord. The 34 non-PNETs included five ependymomas, seven gangliogliomas, 15 astrocytomas, and seven tumors of other histology. We used monoclonal antibodies specific for neurofilament (NF) triplet proteins, for microtubule associated protein 2 and tau protein and for glial fibrillary acidic protein (GFAP) and myelin basic protein. In addition, a monoclonal antibody to epithelial membrane antigen was applied. The presence or absence of these antigens defined four major groups of PNETs: 1) PNETs not otherwise specified (10 cases), 2) PNETs with neuronal differentiation (eight cases), 3) PNETs with astrocytic differentiation (six cases), and 4) PNETs with both neuronal and astrocytic differentiation (12 cases). One case showed ependymal differentiation. The pattern of expression of NF isoforms in PNETs was reminiscent of that seen during normal mammalian development, such that phosphorylated NF-H was only present in combination with NF-M and NF-L. Among the other central nervous system tumors, all astrocytomas and gangliogliomas were positive for GFAP, and the gangliogliomas also expressed all NF isoforms. Three atypical teratoid tumors and two rhabdoid tumors showed strong positivity for epithelial membrane antigen and also for GFAP. We conclude that the differentiation antigens described here serve to distinguish PNETs from other pediatric central nervous system tumors and to identify subsets of PNETs. Accordingly, PNETs represent a heterogeneous group of pediatric brain tumors capable of neuronal and glial differentiation.     

外周性原始神经外胚层瘤的形态及免疫组化观察

目的 :观察外周型原始神经外胚层瘤 (pPNET)的临床病理及免疫组化特征。 方法 :对 10例 pPNET进行组织形态学观察及免疫组织化学和组织化学染色。结果 :形态学上表现为小圆细胞性呈大片状排列 ,其间可见纤维结缔组织间隔 ,瘤细胞呈非典型性菊形团样结构 ;免疫组化显示NSE呈 10 0 %表达 ,Syn、S 10 0蛋白和Vim分别为 80 % (8/ 10 )、6 0 % (6 / 10 )和6 6 7% (6 / 9)。结论 :根据临床表现、组织形态学特征及其免疫组化表型有助于 pPNET的诊断。     

Ultrastructural study of cerebellar medulloblastoma

21 cases of medulloblastoma were studied by both light microscopy and electron microscopy, with observations on 10 cases of human fetal brain and neural tube as controls. Differentiation of medulloblastoma was determined according to the ultrastructural features of normal neuroblast and glial cells of human embryo. 21 cases of medulloblastoma were divided into two categories: 13 cases with no differentiation and 8 cases with differentiation in various extent (including 4 cases with astrocytic differentiation, 2 cases with neuronal differentiation, and 2 cases with both astrocytic and neuronal differentiation). In addition, surviving astrocytes and neuronal fibers were frequently observed in the tumor tissue.     

Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system

AIMS: Medulloblastoma (MB), a kind of infratentorial primitive neuroectodermal tumour (PNET), is the most frequent malignant brain tumour in childhood. In contrast, supratentorial PNET (sPNET) are very infrequent tumours, but they are histologically similar to MB, although they present a worse clinical outcome. We investigated the differences in genetic abnormalities between sPNET and MB. METHODS AND RESULTS: We analysed 20 central PNET (14 MB and six sPNET) by conventional comparative genomic hybridization (CGH) in order to determine whether a different genetic profile for each tumour exists. Isochromosome 17q was detected in four of the 14 MB cases, but not in any sPNET. Gains at 17q and 7 happened more frequently in MB, and those at 1q in sPNET. Losses at chromosome 10 were detected only in MB, while losses at 16p and 19p happened more frequently in sPNET. A new amplification site, on 4q12, was detected in two MB. CONCLUSIONS: Central PNET are a heterogeneous group of tumours from the genetic point of view. The present and previous data, together with further results from larger series, might contribute to the establishment of specific treatments for supratentorial and infratentorial PNET.     

中枢性原始神经外胚层肿瘤的临床病理分析

目的探讨小脑髓母细胞瘤（ＭＢ）和大脑原发性小细胞肿瘤的组织起源，形态特征及生物学行为的异同。方法采用组织病理学和免疫组织化学方法对２１０例ＭＢ和９例大脑原发性小细胞肿瘤的组织形态特征和标志物表达进行比较研究。结果组织形态学观察显示两者均可向神经元和神经胶质分化。免疫组化标记显示６３２％（６７／１０６例）的ＭＢ和５／８例的大脑原发性小细胞肿瘤可同时表达神经元标志物———突触素（Ｓｙｎ）和神经胶质标志物———胶质纤维酸性蛋白（ＧＦＡＰ）。随访结果显示两者均为高度恶性肿瘤，１年生存率分别为３４６３％和２５６５％，统计分析表明肿瘤有灶状坏死、增殖细胞核抗原标记指数高及术后未进行放疗者预后差（Ｐ＜０００１，Ｐ＜００５，Ｐ＝０．０００１）。结论小脑ＭＢ和大脑原发性小细胞肿瘤的形态特征、标志物表达及生物学行为相同，同意将这类肿瘤归类于原始神经外胚层肿瘤