胃肠、泌尿、会阴部间质瘤临床病理及免疫组织化学分析

目的 探讨胃肠道间质瘤(GIST)与胃肠道外GIST型间质瘤的组织学起源与病理特征。方法 对46例胃肠道及13例泌尿道、会阴部原诊断平滑肌瘤、平滑肌肉瘤、许旺瘤的病例作回顾性研究,观察其病理特点,应用免疫组织化学方法观察4种抗体(CD117、CD34、平滑肌肌动蛋白、S—100)的表达,对发生于不同部位的间质瘤进行对比分析。结果 45例为GIST组,CD117阳性表达率为93．3％,CD34阳性率88．9％;12例为胃肠道外GIST型间质瘤组,CDll7阳性表达率为83．3％,CD34阳性率75．0％;2例(其中1例为胃肠道)平滑肌瘤组,CDll7和CD34均为阴性,平滑肌肌动蛋白瘤细胞呈弥漫性强阳性表达。结论 CDll7和CD34标记阳性是确诊间质瘤最具有诊断价值的依据。推测GIST和胃肠道外GIST型间质瘤均系起源于一种非定向分化的、原始间充质干细胞。     

胃肠道间质瘤76例的临床病理及免疫组织化学特征

目的：探讨胃肠道间质瘤（GIST）的临床表现、病理组织形态学和免疫组织化学特点及良恶性参考指标。方法：用CD117、CD34等抗体,通过免疫组织化学EnVision法对原发性消化道间叶源性肿瘤进行研究,确诊76例GIST,并结合随访资料,对其生物学行为进行分析。结果：本组GIST均为成年人,年龄32－81岁（平均54岁）,男性39例,女性37例,发生于胃34例,小肠23例,结肠2例,直肠17例,最常见症状为腹部肿块、腹部胀痛不适及消化道出血。黏膜下生长者3例,浆膜外生长者25例,余48例主要位于肌壁。大体上,肿瘤较易出现出血、坏死、囊性变等继发性改变。镜下观察,梭形细胞型46例,上皮样细胞型9例,梭形／上皮样细胞混合型21例,呈交叉束状、弥漫片状、栅栏状、漩涡状、小巢状、器官样及假菊形团样排列,瘤细胞胞质空亮、淡伊红、轻至中度嗜伊红及略嗜碱,核梭形、卵圆、圆形或镰状。CD117和CD34多为弥漫强阳性,阳性率分别为98．7％、68．4％,α-平滑肌肌动蛋白（ α-SMA）、肌特异性肌动蛋白、S-100、蛋白基因产物9．5呈片状或局灶阳性,阳性率分别为25．0％、19．7％、23．7％、17．1％,波形蛋白均阳性,结蛋白、胶质纤维酸性蛋白、神经丝蛋白均阴性。76例GIST中,良性9例,交界性19例,恶性48例。良性及交界性获访20例均健在,恶性组获访34例,10例无瘤生存,10例复发及转移,14例死亡。各组之间术中黏连、瘤体直径大于5cm、核分裂象大于5／50HPF差异有显著性意义,肿瘤性坏死、核分裂象大于10／50HPF、细胞密集明显异型者均在恶性组。恶性组内,肿瘤性坏死或核分裂象大于5／50HPF者3年生存率的差异有显著性意义。结论：GISF好发于中老年人,肿瘤细胞形态多变,排列结构多样;免疫组织化学特征为CD117、CD34阳性,结蛋白阴性;除转移和浸润外,肿瘤性坏死、核分裂象大于10／50HPF、细胞密集明显异型等提示恶性,此外,术中粘连、瘤体直径大于5cm、核分裂象大于5／50HPF可作为良恶性参考指标。     

十二指肠间质瘤的临床病理及免疫组织化学研究

目的：研究十二指肠间质瘤临床病理学特点和免疫组织化学表达特征。方法：对18例十二指肠间质瘤作了临床病理形态学观察和免疫组织化学分析。结果：18例肿瘤良性3例，恶性15例，基本细胞类型为梭形细胞，1例肿瘤细胞外基质可见丝团样纤维。免疫表型特征为：C-kit18例（100％）胞质强阳性表达；CD347例（38．9％）阳性；S－100蛋白9例（50％）呈局灶性或散在阳性，其中包括2例良性，7例恶性；SMA仅1例阳性。结论：十二指肠间质瘤恶性发生率较高，细胞类型以梭形细胞为主。C-kit因其敏感性高、特异性强成为十二指肠间质瘤的可靠标记物，但不能作为良恶性判断指标，CD34阳性表达率低；神经化生率较高平滑肌方向分化率低。     

胃肠间质瘤临床病理及免疫组化观察

胃肠道间质瘤 (ｇａｓｔｒｏｉｎｔｅｓｔｉｎａｌｓｔｒｏｍａｌｔｕｍｏｒｓ ,ＧＩＳＴｓ)是起源于消化道间叶组织中具有多向分化潜能的原始间质干细胞的一类良恶性肿瘤。自 1985年作为消化道独立的一类间叶瘤以来 ,病理界对其认识并非一致 ,部分学者〔1～ 4〕认为ＧＩＳＴｓ包括发生于胃肠道向平滑肌细胞、雪旺细胞、神经元以及不定向分化或未分化的所有间叶瘤 ,即广义ＧＩＳＴｓ ;另有部分学者〔5～ 8〕则认为不应包括典型平滑肌和神经源性肿瘤 ,即狭义ＧＩＳＴｓ。笔者试图通过光镜观察 ,总结和讨论ＧＩＳＴｓ临床病理和免疫组化特征及…     

小肠间质瘤的免疫组织化学特征其意义

目的探讨小肠间质瘤的临床病理诊断及免疫组织化学特征。方法收集我校附属医院临床病理科6年来对外科手术切除的小肠肿瘤标本,光镜观察、免疫组织化学方法检测Vimentin、desmin、S-100、actin、CD117、CD34和SMA的表达。结果13例肿瘤中良性3例,潜在恶性4例,恶性6例;其中黏膜下生长3例,浆膜下生长5例,肠系膜处生长2例,肌壁内生长3例,常见症状是上腹部肿块和上消化道出血,免疫表形特征为:CD11713例(100%)胞质阳性表达;CD3410例阳性(76.9%)表达,S-100蛋白2例(15.4%)呈局灶表达,10例SMA阴性表达。结论小肠间质瘤发生率较高,多为恶性,有必要和肠的雪旺细胞瘤、平滑肌瘤相区别,CD117、CD34可作为诊断小肠间质瘤免疫标记物,而肿瘤大小、有无出血和坏死、核分裂像等均可作为良恶之判断的参照指标。     

CD117阴性胃肠道间质瘤的临床病理及免疫组织化学研究

目的 探讨免疫组织化学在形态学典型、免疫组织化学CD117阴性胃肠道间质瘤(GIST)诊断中的意义.方法 对10例CD117阴性、形态学典型的GIST进行c-kit基因第9、11、13、17号外显子及血小板源性生长因子受体α(PDGFRA)基因第12和18号外显子的基因检测,同时所有病例均进行CD117、CD34、平滑肌肌动蛋白(SMA)、结蛋白、S-100蛋白、WT-1、DOG-1 的免疫组织化学染色(EnVision法).结果 10例中8例完成c-kit及PDGFRA基因的检测,仅1例有c-kit基因第9号外显子突变,余未发现基因突变.10例CD117阴性的病例9例CD34阳性,2例SMA局灶阳性.结蛋白和S-100蛋白均阴性.DOG1弥漫阳性者5例,1例弥漫弱阳性,2例局灶阳性,2例阴性.4例WT-1弥漫阳性,2例局灶阳性,1例有散在肿瘤细胞阳性,3例阴性.结论 对胃肠道及胃肠道外形态学典型、但CD117阴性的GIST病例,联合应用多种免疫组织化学标记有助于诊断.DOG-1和WT-1可作为补充加入到CD117阴性GIST的诊断中.

Abstract：

Objective To study the immunophenotype and c-kit or platelet derived growth factor receptor alpha(PDGFRA)gene mutations in CD117-negative gastrointestinal stromal tumors(GISTs).Methods Ten cases of GISTs with typical histologic features but no CD117 expression were retrieved from the archival of Department of Pathology,Peking Union Medical College Hospital,China.The Cages were further evaluated for the presence of c-kit exons 9.11, 13 and 17 mutations and PDGFRA exons 12 and 18mutations.DNA was extracted from the paraffin-embedded tuinor tissue.The PCR products were sequenced directly for the mutations.An immunohistochemical study for CD117,CD34,smooth muscle actin,desmin,S-100 protein.WT-1 and DOC-1 Was also performed.Results Eight of the 10 Cases had the mutation tests completed.C-kit mumfion in exon 9 Wag detected in only one case.Amongst the 10 cases studied, CD34Wag expressed in 9 cases. Smooth muscle actin was focally positive in 2 cases.None of them expressed desmin or S-100 protein.DOG-1 and WT-1 were diffusely positive in 5 and 4 Cages.respectively.In addition.DOG1 Was diffusely but weakly positive in 1 case and focally expressed in 2 cages.Three cases were focally positive for WT-1.Conclusion Pathologic diagnosis of CD117-negative GISTs can be facilitated with the application of a panel of immunohistochemical markers.including DOG-1 and WT-1.     

CD117阴性胃肠道间质瘤的临床病理及免疫组织化学研究

目的 探讨免疫组织化学在形态学典型、免疫组织化学CD117阴性胃肠道间质瘤(GIST)诊断中的意义.方法 对10例CD117阴性、形态学典型的GIST进行c-kit基因第9、11、13、17号外显子及血小板源性生长因子受体α(PDGFRA)基因第12和18号外显子的基因检测,同时所有病例均进行CD117、CD34、平滑肌肌动蛋白(SMA)、结蛋白、S-100蛋白、WT-1、DOG-1 的免疫组织化学染色(EnVision法).结果 10例中8例完成c-kit及PDGFRA基因的检测,仅1例有c-kit基因第9号外显子突变,余未发现基因突变.10例CD117阴性的病例9例CD34阳性,2例SMA局灶阳性.结蛋白和S-100蛋白均阴性.DOG1弥漫阳性者5例,1例弥漫弱阳性,2例局灶阳性,2例阴性.4例WT-1弥漫阳性,2例局灶阳性,1例有散在肿瘤细胞阳性,3例阴性.结论 对胃肠道及胃肠道外形态学典型、但CD117阴性的GIST病例,联合应用多种免疫组织化学标记有助于诊断.DOG-1和WT-1可作为补充加入到CD117阴性GIST的诊断中.     

胃肠道间质瘤的光镜、免疫组织化学和超微结构的观察

目的 研究胃肠道间质瘤（GISTs）的光镜,电镜形态特点和免疫组织化学在诊断中的价值,探讨肿瘤的组织来源和分型。方法 对GISTs进行光镜和超微结构的观察,用EnVision二步法免疫组织化学方法检测波形蛋白,CD117（c-kit),CD34等8种抗原标记物在肿瘤中的表达情况。结果 65例GISTs占同期消化系统间叶性肿瘤的85．5％（65／76）;其中梭形细胞为主的有46例,伴有上皮样细胞的有13例,单纯由上皮样细胞组成的有6例,瘤细胞呈长,短梭形和圆形,胞质弱嗜酸,常见核端空泡,有时呈印戒样或透明细胞样;排列呈旋涡状,栅栏状或弥漫性巢状。超微结构表现出树枝样突起,神经内分泌颗粒,桥粒样连接等神经分化特点,或（和）胞质内出现密斑,密体等肌性分化。免疫组织化学显示肿瘤组织中抗原标记物表达阳性率波表蛋白为100％（65／65）,CD11793．8％（61／65）,CD3478．5％（51／65）。结论 GISTs是消化道最常见的间叶性肿瘤,光镜形态与真性肌源性和神经源性肿瘤极为相似,电镜和CD117,CD34等免疫标记物配合使用可对其做作出正确诊断,GISTs可能起源于多潜能的,卡哈尔间质细胞样的前体细胞。     

阑尾胃肠间质瘤—4例临床病理及免疫组化研究

阑尾的间叶性肿瘤十分罕见 ,特殊性间质肿瘤 (即胃肠间质瘤ＧＩＳＴ)尚无报道。作者复习ＡＦＩＰ自 1970年至 1998年间阑尾原发性间叶肿瘤 ,发现阑尾ＧＩＳＴ 4例。 4例均为男性 ,年龄 5 6～ 72岁。 2例临床拟诊阑尾炎 ,行阑尾切除时被发现 ;1例死于肺腺癌转移及支气管肺炎 ,于尸检中意外发现阑尾肿瘤 ;1例因巨大胃上皮样ＧＩＳＴ行手术时发现阑尾病变。眼观 :阑尾壁或呈偏心性增厚 (病灶范围 0 9ｃｍ×0 5ｃｍ) ,或见实性结节 (直径 1 2～ 1 4ｃｍ) ,或呈息肉状。镜检 :4例肿瘤均由梭形细胞组成 ,3例含有明显的细胞外胶原小球 ,即所谓丝…     

胃肠道间质瘤的电镜和免疫组织化学研究

目的 探讨胃肠道间质瘤的组织起源和神经分化特征。方法 应用电镜和免疫组织化学对20例胃肠道间质瘤的超微结构和神经分化相关抗原表达进行研究。结果 20例胃肠道间质瘤c—kit表达均阳性。其中7例超微结构存在神经分化,12例未见神经或肌细胞分化,仅有1例存在向平滑肌纤维分化。神经分化形态表现为瘤细胞胞质和胞质突起内可见散在或簇状分布的致密核心颗粒,并形成突触样结构。并可见神经元样突起、饮液空泡和团丝样纤维。神经分化伴有致密核心颗粒病例在良性、交界性和恶性组各有1例、1例和5例。神经分化组病例神经分化相关抗原神经元特异性烯醇化菌、CD99、S—100和CD56阳性表达分别有7例、7例、5例和4例,均高于未定分化组。结论 胃肠道间质瘤和所谓的胃肠道自主神经肿瘤在组织形态和免疫表型都存在相互重叠现象,神经分化超微结构观察和神经分化相关抗原分析有助于确定胃肠道间质瘤的神经分化改变以及潜在的生物学行为。     

77例胃肠道间质肿瘤的病理形态学及免疫组化研究

目的：研究胃肠道间质瘤（GIST）的病理形态及免疫组化特点,方法：应用光镜观察77例GIST的形态特征,用免疫组化S－P法检测c-kit(CD117),CD34,vimentin,SMA及S－100蛋白在GIST中的表达情况。结果：GIST的瘤细胞较经典的平滑肌瘤更丰富,胞质嗜酸较弱,瘤细胞为酸形或上皮样,或酸形与上皮样细胞混合存在,胞质内常见空泡形成;排列成交织刺状、弥散片状、栅栏状或轮辐状、较为特征的是细胞团巢形成。常见间质或见管壁玻变。原发于肠系膜者恶性潜力较高。CD117和CD34的阳性率分别为90％和92％,结论：胃肠道间质肿瘤有较为特独的组织学形态,CD117和CD34联合使用可协助鉴别诊断。     

Gastrointestinal stromal tumors: a contemporary review

The literature on gastrointestinal stromal tumors (GISTs) has rapidly expanded and has demonstrated how scientific advancements in diagnosis can revolutionize the understanding of disease, while paving the way for effective treatment. While KIT (CD117) immunohistochemistry has established our definition of GISTs, molecular genetics continue to refine it. Elucidation of the aberrant receptor tyrosine kinase (RTK) model of GIST pathogenesis through mutations in c-kit and platelet-derived growth factor alpha PDGFR proto-oncogenes has been prerequisite to the use of imatinib mesylate (STI571, Gleevec; Novartis, Switzerland), a molecular inhibitor of several tyrosine kinases, in the treatment of GISTs. In addition to providing a means for effective treatment, clarification of the molecular pathology of GISTs may potentially offer a new classification of these tumors by correlating genotype with histological, immunohistochemical, and clinical phenotype. This article seeks to review current knowledge of GISTs, offering a practical guide to their diagnosis and describing current epidemiological, molecular biological, and therapeutic aspects.     

Gastrointestinal stromal tumours: an immunohistochemical study of 165 cases

The phenotype of 165 gastrointestinal stromal tumours was studied by immunohistochemistry. In each case the phenotype was compared to the histological diagnosis. The phenotype was muscle in 49 tumours (30%), neural in 18 (11%), histiocytic in 20 (12%) and mixed in five (3%); 68 tumours (41%) were positive for vimentin only, four tumours had no markers and one tumour was positive for keratin only. Histologically, the tumours were classified as smooth muscle, probably smooth muscle, probably nerve sheath tumours or tumours of undetermined differentiation. In 30 histologically unequivocal muscle tumours, the phenotype was muscle in 28. Half of them, all benign, arose in the oesophagus or gastric cardia. Apart from this group, there was no correlation between phenotype, site of tumour and histological differentiation. Actin was a more sensitive muscle marker than desmin. With the exception of oesophageal tumours, the histological appearances alone could not establish a diagnosis of malignancy and were inadequate in evaluating differentiation. Immunohistochemical examination determined differentiation in 54% of the tumours, but this finding should be interpreted with caution in terms of histogenesis. It allowed us, however, to specify the differential diagnosis in 57 tumours in which the histological diagnosis was uncertain.     

子宫内膜间质肿瘤35例临床病理分析

目的 探讨子宫内膜间质肿瘤(endometrial stromal tumours, ESTs)的临床病理学特征,以期提高对ESTs的诊断和治疗水平.方法 回顾性分析35例子宫内膜间质肿瘤患者的临床及病理资料,部分辅以免疫组织化学染色分析.结果 患者平均年龄45岁,临床主要表现为子宫占位和阴道出血,35例ESTs中子宫内膜间质结节(endometrial stromal nodule, ESN)4例、低级别子宫内膜间质肉瘤(low-grade endometrial stromal sarcoma,ESS)26例、未分化子宫内膜肉瘤(undifferentiated endometrial sarcoma,UES)5例.ESN和ESS均由类似增生期子宫内膜间质的肿瘤细胞构成,并伴有丰富的螺旋小动脉,UES则具有明显的细胞异型性并缺乏螺旋动脉.18例辅以免疫组化标记的病例中17例CD10阳性,7例SMA局灶阳性,4例desmin局灶阳性.结论 ESTs是一组诊断可能具有困难的子宫间叶肿瘤,确诊依靠组织病理和一组免疫组化抗体标记,诊断上应与平滑肌肿瘤、PEComa等肿瘤相鉴别.     

bcl-2和p16在胃肠道间质瘤中的表达及其临床意义

目的 探讨bcl-2和p16的表达与胃肠道间质瘤(gastrointestinal stromal tumor，GIST)的良恶性及发生发展的关系。方法 应用免疫组织化学技术EnVision微波二步法检测40例GIST(良性20例，恶性20例)中bcl-2和p16蛋白的表达。结果 40例GIST中有29例表达bcl-2，23例表达p16，阳性率分别为72．5％和57．5％。bcl-2阳性信号定位于细胞质，p16阳性信号定位于细胞质和细胞核。bcl-2、p16的表达与GIST的良恶性、组织学分型、部位、性别及年龄均无关。结论 bcl-2及p16可能在GIST的早期阶段即参与肿瘤的发生发展，但两者不能作为判断肿瘤良恶性的指标。     

PKC theta, a novel immunohistochemical marker for gastrointestinal stromal tumors (GIST), especially useful for identifying KIT-negative tumors

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the digestive tract and the majority of GIST has characteristic gain-of-function mutations of the c-kit gene, which encodes the KIT receptor for stem cell factor. The present study aimed to establish the usefulness of protein kinase C theta (PKC theta) as an immunohistochemical marker for GIST in comparison with KIT immunohistochemistry. PKC theta immunohistochemistry was carried out not only on 48 cases of GIST and another 40 cases of gastrointestinal mesenchymal tumors, but also on 24 cases of various tumors known to be immunohistochemically positive for KIT. Immunohistochemically, 41 out of 48 cases (85%) of GIST were positive for PKC theta, and its expression was confirmed by Western blot analysis using six cases of surgically resected GIST. In the present study there were six GIST immunohistochemically negative for KIT, which histologically revealed a myxoid epithelioid appearance characteristic to that of GIST with platelet-derived growth factor receptor alpha mutation. All six GIST were immunohistochemically positive for PKC theta. No PKC theta immunoreactivity was observed in other gastrointestinal mesenchymal tumors and various KIT-positive tumors except for three cases (14%) of gastrointestinal schwannomas. The present study revealed that PKC theta is an immunohistochemically novel and useful marker for GIST, especially for GIST negative for KIT.     

Gastrointestinal autonomic nerve tumors: Immunohistochemical and ultrastructural studies in cases of gastrointestinal stromal tumor

The gastrolntestlnal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor with a morphological feature resembling the cell processes of the enteric plexus, and was originally teimed a plexoma or plexosarcoma. Light microscoplc studies show the GAN tumor most often consists of spindle-shaped cells indistinguishable from a smooth muscle tumor or Schwann cell tumor. Immunohistochemical and ultrastructural examinations of 18 cases of gastrointestinal stromal tumor (GIST) were performed. During ultrastructural examination, all of the 12 cases which were immunohisto-chemically positive for S-100 protein or neuron-specific eno-lase (NSE) showed synapse-like structures containing dense core neurosecretory granules measuring 100–200 nm, and 40–60 nm endocytoplasmic vesicles. These results suggest that most GIST of neurogenlc origln are tumors derived from the myenteric nerve plexus.     

胃肠道间质瘤中p53和bcl-2表达与预后的关系

目的探讨细胞凋亡相关基因p53和bc l-2在胃肠道间质瘤(gastrointestinal strom al tumors,G ISTs)中的表达与预后关系。方法对194例G ISTs构建组织微阵列(TMA),采用免疫组化EnV ision法检测G ISTs组织中p53和bc l-2基因蛋白的表达。结果在p53 TMA中,184例可评估(94.8%),在bc l-2 TMA中181例可评估(93.3%)。p53和bc l-2基因蛋白阳性率分别为34.8%和59.1%。p53蛋白阳性表达率与肿瘤大小、NIH分级、肿瘤部位、坏死、细胞密集程度、核分裂象和转移复发有关。bc l-2阳性表达率与肿瘤大小、NIH分级、肿瘤部位、坏死和黏膜受累及有关。p53蛋白阳性和阴性表达者的5年生存率分别为40.1%和76.5%,两者比较差异有显著性(P<0.01)。bc l-2阳性和阴性表达者的5年生存率分别为55.1%和76.2%,两者比较差异有显著性(P<0.05)。p53蛋白阳性组和阴性组与bc l-2蛋白的阳性表达差异有显著性(P<0.01)。结论p53、bc l-2表达与G ISTs预后有关,p53、bc l-2可作为判断G ISTs预后的标志物。     

Cyclooxygenase‐2 expression and connection with tumor recurrence and histopathologic parameters in gastrointestinal stromal tumors

Tissue cyclooxygenase‐2 (COX‐2) is a rate‐limiting enzyme in prostaglandin synthesis and has been shown to have roles in carcinogenesis and tumor progression. Evaluation of COX‐2 overexpression in malignancies has been performed mostly on tumors of epithelial origin, and little is known about its presence in mesenchymal tumors, especially gastrointestinal stromal tumors (GIST). COX‐2 has been reported to be widely expressed in GIST and has been suggested as a potential diagnostic marker. We evaluated the overexpression and roles of COX‐2 in tumorigenesis in GIST with regard to its relation to prognostic parameters and tumor recurrence. We studied the presence of COX‐2 expression immunohistochemically and its relation to clinicopathologic prognostic variables in 41 cases of GIST. COX‐2 was overexpressed in 21 (51%) of 41 tumors. The extent of overexpression was greater in tumors that recurred after surgical resection. COX‐2 overexpression was also higher in tumors with coagulative necrosis, high mitotic index and an infiltrative pattern of growth. The observation of greater COX‐2 expression levels in GIST with unfavorable histopathologic variables is contrary to previous reports and consistent with the reported roles of COX‐2 in carcinogenesis of epithelial malignancies.