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.     

胃肠道间质瘤临床病理及免疫组织化学特征

目的 探讨胃肠道间质瘤的免疫组织化学特征，为其诊断及鉴别诊断和预后提供依据。方法 对消化道内169例间叶源性肿瘤进行免疫组织化学标记和形态学观察，确诊113例胃肠道间质瘤。结果 肿瘤多见于胃，临床常见首发症状为消化道出血及腹部包块。瘤细胞主要有梭形细胞及上皮样细胞两种形态，梭形细胞型70例，上皮样细胞型10例，混合细胞型33例。相对良性33例，交界性26例，恶性54例。免疫表型：CD117阳性112例，CD34阳性102例，阳性率分别为99．1％及90．2％，且呈弥漫强阳性表达。结论 胃肠道间质瘤是消化道最常见间叶源性肿瘤，以胃内多见；主要有2种细胞形态和3种组合形式；确诊需要依靠CD117、CD34等免疫标记物配合。     

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。     

DOG-1在胃肠道间质瘤中的表达及其临床意义

目的 探讨DOG-1在胃肠道间质瘤(GIST)中的表达及其临床意义.方法 应用免疫组织化学EnVision法检测DOG-1在84例GIST患者肿瘤组织中的表达,并与CD117、CD34标记进行比较观察.结果 GIST患者手术切除肿瘤组织主要由数量不等的梭形细胞和上皮样细胞组成,两种细胞可按不同比例混合性或单一性组成肿瘤的实体.DOG-1、CD117和CD34在极低度及低度危险性GIST组织中阳性表达率分别为91.3%(42/46)、95.7%(44/46)和82.6%(38/46),在中度及高度危险性GIST组织中其阳性表达率分别为100%(38/38)、100%(38/38)和78.9%(30/38),对照组真性平滑肌瘤、神经鞘瘤、纤维瘤病及正常胃肠道黏膜组织中DOG-1、CD117、CD34均无表达,DOG-1标记GIST的敏感性及特异性与CD117相似,差异无统计学意义(P＞0.05),而标记中度及高度危险性GIST的敏感性与特异性明显高于CD34,其表达差异有统计学意义(P＜0.01).结论 DOG-1是一种新的诊断GIST比较特异的标记,尤其是对中度及高度危险性GIST比CD34有更高的敏感性和特异性.与CD117联合应用将有利于进一步提高GIST的诊断水平.

Abstract：

Objective To investigate the expression of DOG-1 in gastrointestinal stromal tumors (GIST)and its diagnostic application.Methods Immunohistochemical EnVision technique was used to assess the expression of DOG-1 in 84 cases of GIST in comparison with CD117 and CD34.Results All 84cases of GIST consisted of variable proportions of spindle and epithelioid tumor cells or iust one type of the tumor cell. The expression rates of DOG-1,CD117 and CD34 were 91.3%(42/46),95.7%(44/46)and 82.6%(38/46),in the group of very low and low risk GIST,and were 100%(38/38),100%(38/38)and 78.9%(30/38),respectively,in the group of moderate and hiish risk GIST. leiomyomas,schwannomas,fibromatosis and normal gastrointestinal mucoca did not express these markers.Moreover, the sensitivity and specificity of DOG-1 in the detection of GIST were similar to those of CD117.without statistical difference(P＞0.05)between the two markers.However,the sensitivity and specificity of DOG-1 detection of moderate and high risk GIsT were significandy higher than those of CD34(P＜0.01).Conclusions DOG-1 is a novel marker of gastrointestinal stromal tumors.It has the sensitivity and specificity hisher than CD34,especially in the detection of moderate and high risk GIST.Combined DOG-1and CD117 immunohistochemistry will likely improve the diagnostic accuracy of GIST.     

74例胃肠道间质瘤临床病理与生物学行为评价

目的　探讨在胃肠道间质瘤(GIST)的病理诊断和预后分析上采用一种简单实用且重复性好的病理学“标准”,以利于GIST的日常病理诊断和生物学行为评价及指导治疗,并对Fletcher等推荐的GIST生物学行为评价表进行评估。方法　85例消化道间叶组织肿瘤,复习其病理形态学并应用CD117、CD34、平滑肌肌动蛋白(SMA)、结蛋白、S 100等进行免疫组织化学标记,结合 31例随访资料进行分析。结果　85例消化道间叶组织肿瘤中,GIST74例,平滑肌瘤和交界性平滑肌瘤 8例(食管),平滑肌肉瘤 1例(直肠 ),神经鞘瘤 1例 (胃 ),恶性纤维组织细胞瘤 1例 (肠系膜 )。74例GIST中,发生在胃和小肠的分别为 34例和 30例,占 86. 5%,食管 3例,胃肠道外(肠系膜、网膜、后腹膜)7例。年龄 23~80岁,平均 52 5岁, 40岁以上者占 85%,男性 45例,女性 29例。镜下观察:梭型细胞型 48例,上皮样细胞型 10例,混合细胞型 16例。瘤细胞呈长、短梭形和圆形,胞质丰富弱嗜酸性,排列呈旋涡状、栅栏状或弥漫巢状。免疫组织化学: 85例消化道间叶组织肿瘤波形蛋白均阳性,其中 74例表达CD117,诊断为GIST,表达形式有弥漫胞膜 /胞质强阳性、散在阳性、胞质点状着色等,其中 54例同时表达CD34 (阳性率 72. 9% ), 25例表达SMA, 5例表达结蛋白, 5例表达S 100蛋白。在 85例     

DOG-1在胃肠道间质瘤中的表达及其临床意义

Objective To investigate the expression of DOG-1 in gastrointestinal stromal tumors (GIST)and its diagnostic application.Methods Immunohistochemical EnVision technique was used to assess the expression of DOG-1 in 84 cases of GIST in comparison with CD117 and CD34.Results All 84cases of GIST consisted of variable proportions of spindle and epithelioid tumor cells or iust one type of the tumor cell. The expression rates of DOG-1,CD117 and CD34 were 91.3%(42/46),95.7%(44/46)and 82.6%(38/46),in the group of very low and low risk GIST,and were 100%(38/38),100%(38/38)and 78.9%(30/38),respectively,in the group of moderate and hiish risk GIST. leiomyomas,schwannomas,fibromatosis and normal gastrointestinal mucoca did not express these markers.Moreover, the sensitivity and specificity of DOG-1 in the detection of GIST were similar to those of CD117.without statistical difference(P＞0.05)between the two markers.However,the sensitivity and specificity of DOG-1 detection of moderate and high risk GIsT were significandy higher than those of CD34(P＜0.01).Conclusions DOG-1 is a novel marker of gastrointestinal stromal tumors.It has the sensitivity and specificity hisher than CD34,especially in the detection of moderate and high risk GIST.Combined DOG-1and CD117 immunohistochemistry will likely improve the diagnostic accuracy of GIST.     

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。     

胃肠道间质瘤诊断中CD117表达检测的标准化及其免疫组织化学技术

胃肠道间质瘤(gastrointestinal stromal tumor,GIST)是起源于胃肠道间质非上皮性、非淋巴造血组织、非一般血管脂肪组织的间叶性肿瘤,但不包括真正的平滑肌瘤和神经鞘瘤。1998年Hirota等提出GIST可能是起源于胃肠道卡哈尔间质细胞(interstitial cells of Cajal,ICC)。在免疫表型上ICC与GIST肿瘤细胞有共同的特征即均表达CD117,     

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。     

胃肠道间质瘤病理及CD117和CD34表达与意义

目的：对本院病案资料中GIST重新分类，加 强对胃肠道间质瘤的认识。方法：用CD117、CD34、α-SMA、S-100等抗 体对56例GIST进行标记、分类，根据GIST的临床病理及形态学特点，正确诊断，并探讨 GIST的临床特点。结果:56例GIST CD117、CD34弥漫强表达，抗体 阳性率分别为CD117（50/56，89.3%）、CD34（37/56，66.1%），部分病例局灶表达α-SM A、S-100，阳性率分别为（17/56，30.4%）、（4/56，7.1%），结蛋白desmin均阴性。其 中良性及交界性29例，恶性27例。本组病例中胃及小肠GIST共达91.1％，其它部位少见。 结论：CD117、CD34在GIST表达显著，可作为GIST诊断的一个辅助指标。 胃和小肠GIST最常见，胃镜等影像学无特异性，诊断主要依靠病理诊断。组织病理不仅有助 于诊断，而且有助于预后的判断。     

CD117阴性的胃肠道间质瘤的超微结构特点及基因突变检测

目的探讨CD117阴性的胃肠道间质瘤（GIST）的超微结构及c-kit和血小板源性生长因子受体A（PDGFRA）基因的突变情况。方法用免疫组织化学方法（EnVision法和SP法）从101例GIST中筛选到6例CD117阴性的GIST,观察了6例CD117阴性的胃肠道间质瘤的电镜变化,用PCR直接测序的方法检测6例CD117阴性的胃肠道间质瘤的c-kit基因外显子9、11、13、17和PDGFRA基因外显子12和18突变。结果电镜下观察到6例GIST的超微结构特点与卡哈尔细胞相似,通过PCR直接测序检测揭示c-kit基因9、11、13和17外显子均无突变,而3例GIST的PDGFRA有突变,其中2例D842V突变,1例R841S突变。结论PDGFRA基因的突变可能是CD117阴性的胃肠道间质瘤发生的重要分子基础。     

胃肠道间质瘤156例临床病理学特征与预后的分析

目的探讨胃肠道问质瘤（GIST）的生物学行为,分析临床病理特征对于GIST患者生存率的影响,同时检测c—kit基因11号外显子的突变,试图发现对GIST预后判断有意义的指标。方法收集解放军总医院病理科156例发生于胃与小肠的GIST,总结临床病理特征包括年龄、临床分期、肿瘤直径、核分裂象计数、坏死、风险分级等,并进行统计学分析。套式PCR扩增c—kit基因11号外显子,变性高效液相色谱法筛查,并进行DNA直接测序检测突变。结果胃GIST83例,平均年龄55．4岁,62例获得随访,17例复发或转移,5年生存率为66．5％±17．1％。小肠GIST73例,平均年龄50．6岁,43例获得随访,22例发生复发或转移,5年生存率为61．8％4-18．3％。对于胃GIST患者,年龄小于50岁（P=0．046）,临床分期晚（P=0．0001）,肿瘤直径大（P=0．0001）,核分裂象计数多（P=0．0001）,肿瘤组织出现坏死（P=0．0001）和风险分级高（P=0．004）提示生存率低。COX风险比例模型发现临床分期晚（P=0．001）、肿瘤直径大（P=0．001）、核分裂象计数多（P=0．002）、风险分级高（P=0．018）与患者预后差相关。在小肠GIST中,肿瘤组织坏死（P=0．036）、临床分期晚（P=0．010）与患者生存率低相关,其中临床分期为独立的预后提示因子。c—kit基因11号外显子突变检测发现共25例患者存在突变,胃GIST的突变率为32．0％,主要发生于50岁以上患者,小肠GIST的突变率为22．5％,主要发生于40～49岁患者。结论根据临床病理特征可以对GIST患者的预后进行判断,其中胃GIST患者可以根据临床分期、肿瘤直径、核分裂象计数、风险分级来判断预后,小肠GIST患者可依据临床分期及肿瘤组织坏死来判断预后。小肠GIST比胃GIST更易复发或转移。胃与小肠GIST基因的突变可能与患者的年龄相关。     

29例上皮样胃肠间质瘤的临床病理特征

目的:探讨29例上皮样胃肠间质瘤(gastrointestinal stromal tumors,GIST)的组织学形态和免疫组织化学特点以及诊断和鉴别诊断,对临床正确诊断治疗和判断预后具有十分重要的临床意义.方法:回顾性分析安阳市肿瘤医院病理科2009年月3月至2016年8月321例完整切除GIST标本,经筛查并重新阅片诊断上皮样GIST 29例.结果:29例上皮样GIST,发生胃部15例,小肠2例,肠系膜3例,直肠4例,腹腔3例,腹膜后1例,盆腔1例.恶性GIST 25例,良性4例.瘤细胞丰富,胞质嗜酸或透明,部分瘤细胞核质比高,核大小不等具有多形性,核分裂较多,可伴有多灶凝固性坏死,间质多数伴有黏液样变性.组织结构形成器官样、片状、巢状及腺泡状等.免疫组织化学CD34,DOG-1在上皮样GIST均弥漫阳性(阳性率100%),CD117阳性率(86%).结论:上皮样GIST发生部位广泛,形态多变,易误诊其他上皮样分化的肿瘤;免疫组织化学CD34,DOG-1,CD117在上皮样GIST诊断及鉴别诊断中具有重要价值;如肿物较大、细胞丰富、核分裂多、间质黏液样变性;绝大多数要考虑恶性GIST.     

Prognostic significance of MCM6 expression in gastrointestinal stromal tumor

Minichromosome maintenance (MCM) proteins are essential for the initiation of DNA replication and they are prognostic markers in various human cancers. The aim of this study was to investigate the role of the MCM6 protein in gastrointestinal stromal tumor (GIST) and its clinical and prognostic significance. We evaluated MCM6 expression in 211 GIST samples using immunohistochemistry. We used the receiver operating characteristic curve (ROC) to identify optimal cut-off values. High MCM6 expression was associated with tumor size, mitosis, tumor necrosis, presence of recurrence/metastasis, and the National Institute of Health (NIH) and Armed Forces Institute of Pathology (AFIP) malignant risk criteria. Patients with high MCM6 expression had significantly shorter overall survival (OS) and disease-free survival (DFS) than those with low MCM6 expression. Univariate analysis indicated that tumor size, mitosis, AFIP and NIH malignant risk criteria, and high MCM6 expression were significantly associated with poor OS and DFS. High MCM6 expression and high-risk group categorization based on the NIH criteria were independent prognostic factors for OS and DFS. High MCM6 expression is significantly associated with tumor progression and aggressiveness and is an independent factor for shorter survival in GIST patients. MCM6 expression could be a predictive biomarker for tumor aggressiveness as well as a treatment target.     

CD117在胃肠道间质瘤和其他肿瘤中的表达

CD117是由c—kit基因（4q11-q21）编码的Ⅲ型跨膜酪氨酸激酶受体家族成员,目前CD117已成为诊断胃肠道间质瘤（gastrointestinal stromal tumors,GIST）不可缺少的参考指标。大部分病理医师对CD117的认识是从GIST开始的,可能会认为CD117是GIST的特异标记物。而且,最初认为除GIST外,其他肿瘤尤其是梭形细胞肿瘤很少表达CD117,但随着近年的广泛运用,已发现许多表达CD117的肿瘤。为促进对CD117的了解和在实际工作中的正确使用,有必要就CD117的表达谱等问题作一综述。     

HER-2 status in gastrointestinal stromal tumor

Human epidermal growth factor receptor–2 (HER-2) encodes for the transmembrane glycoprotein HER-2 that is involved in activation of intracellular signal transduction pathways that control cell growth and differentiation. HER-2 is overexpressed in approximately 20% of patients with breast cancer and has been associated with poorer prognosis. Since 1998, the anti–HER-2 antibody trastuzumab has been used for the treatment of patients with HER-2–positive breast cancers. However, little information is available about the relationship between HER-2 and gastrointestinal stromal tumors. This study's purpose was to determine the HER-2 status in gastrointestinal stromal tumors. We found that all 477 cases included in this study were negative (score 0) by immunohistochemistry using HercepTest, and no HER-2 gene amplification was detected in 71 cases submitted to fluorescence in situ hybridization. These results show that HER-2 may not have any role in gastrointestinal stromal tumor pathogenesis and that the neoplasm may not be suitable for treatment with trastuzumab.     

Analysis of clinicopathologic features and gene mutations in gastrointestinal stromal tumor: a series of 58 patients

Background: In gastrointestinal stromal tumor (GIST), mutually exclusive gain-of-function mutations of c-kit and PDGFRα are associated with different mutation-dependent clinical features. We analyzed clinico-pathologic features and genotypes of GIST among patients in China. Methods: Adult patients with GIST in the stomach, small intestine, colorectum, or extra-gastrointestinal areas were enrolled in this study. These patients had been subjected to surgical resection without imatinib (Gleevec) treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2009 to January 2019. Samples were obtained for histopathologic examination. Mutations in c-kit and PDGFRα genes were analyzed by PCR and next generation sequencing (NGS). Clinico-pathologic characteristics of each gene were also analyzed. Results: A total of 58 GIST patients was enrolled in this study. In terms of genotypes, there were 51 (87.9%) c-kit mutations, 5 (8.6%) PDGFRα mutations, and 2 (3.4%) wild-type mutations. In terms of cell types, there were 40 cases (69.0%) with spindle cell type, 3 cases (5.2%) with epithelioid cell type and 3 cases (5.2%) with mixed spindle-epithelioid cell type. Among the 4 mutant forms of c-kit exon-11, the most common were point mutations in 16 cases (38.1%), deletion mutations in 13 cases (31.0%), insertion mutations in 4 cases (9.5%), and mixed mutations in 9 cases (21.4%). Based on risk grade classification of the National Institutes of Health (NIH), 3 cases (5.2%) were very-low risk, 9 cases (15.5%) were low risk, 19 cases (32.8%) were medium risk, and 23 cases (39.7%) were high risk. Significant differences in cell type were identified across different gene types (P = 0.022). Similarly, differences in tumor risk were found among different mutant forms of c-kit gene exon-11 (P = 0.039). Conclusion: With c-kit mutations, spindle cell type prevalence exceeded that of the epithelioid cell type and mixed spindle-epithelioid cell type. Spindle and mixed spindle-epithelioid cell types were the most prevalent in the category of PDGFRα mutations. In wild type cases, spindle and epithelioid cell types were the most common. A high risk of deletion and mixed mutations, and intermediate risk of point and insertion mutations were observed in c-kit exon-11 mutation type.     

Dedifferentiated gastrointestinal stromal tumor arising de novo from the small intestine

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and usually display monotonous cytologic features and immunoactivity for CD117. Anaplastic GIST, with pleomorphic cells and loss of CD117, until recently have only been reported in patients with chronic imatinib mesylate treatment. Dedifferentiated GISTs arising de novo is a newly identified entity that may prove to be difficult to diagnose. We present the case of a 52-year-old female found to have a dedifferentiated GIST without prior imatinib mesylate therapy. This case is the first reported dedifferentiated GIST arising de novo from the small bowel, and at 30 cm in greatest diameter, the largest reported to date. Additionally, we demonstrate for the first time the loss of DOG1 in the anaplastic component of the tumor. De novo dedifferentiated GIST is a rare and diagnostically challenging tumor that may be mischaracterized unless considered in the differential diagnosis.