c-kit immunocytochemical staining in the cytologic diagnosis of metastatic gastrointestinal stromal tumor. A report of two cases

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a distinct group of mesenchymal neoplasms recently shown to exhibit differentiation toward interstitial cells of Cajal (ICC). C-kit (CD117), an immunocytochemical marker consistently expressed in normal ICC, is demonstrable in 81-100% of GISTs. We report two cases wherein immunocytochemical staining for c-kit aided in the diagnosis of metastatic GIST in the liver. CASES: Two patients, a 37-year-old female (case 1) and a 76-year-old male (case 2), presented with multiple nodules in the liver. They had a history of small bowel GIST resected 11 and 1 year earlier, respectively. Fine needle aspiration of the liver nodules showed loose aggregates or fascicles of spindle cells with elongated to oval nuclei, rare paranuclear vacuoles and eosinophilic cytoplasm. The spindle cells showed minimal (case 1) to moderate nuclear pleomorphism (case 2), with occasional mitotic figures seen in case 2. Immunocytochemical staining revealed strong and diffuse staining for c-kit; it was negative for actin, desmin, CD34 and S-100 protein. Thus, a diagnosis of metastatic GIST was rendered. Histologic review of the primary small bowel GISTs of both cases and the subsequently resected liver nodules in case 1 confirmed the diagnosis. CONCLUSION: Metastatic GIST may pose diagnostic problems due to its broad morphologic spectrum and variable cytologic atypia; in particular, distinction from leiomyosarcoma and other mesenchymal tumors is difficult. The diagnostic difficulty is compounded when the prior history of gastrointestinal tumor is not available or forgotten and when GIST is the initial presentation of the tumor. C-kit is a highly sensitive and reliable immunocytochemical marker that can aid in the diagnosis.     

50例胃肠道间质瘤的临床病理分析

目的：探讨胃肠道间质瘤（GIST）的组织形态学特征及对该类肿瘤的诊断及预后问题。方法：对发生于2001年4月至2010年4月间的50例GIST进行临床病理及免疫组化分析。结果：50例GIST免疫组化检查结果,肿瘤均不表达CK而表达为Vimentin;CD117阳性表达43例,CD34阳性表达38例;S100均有不同程度表达,SMA阳性表达22例,Desmin阳性表达15例;Ki-67均有表达,其阳性度从＋．＋＋不等。结论：本组肿瘤中所有病例均不同程度表达Ki-67和PCNA,高危险性的阳性表达强、低危险性的阳性表达弱。这说明GIST的预后除与肿瘤的大小、组织形态学的改变及肿瘤的发生部位有关外,还与Ki-67和PCNA在肿瘤中的表达程度有关。     

CD117、CD34、DOG-1、WT-1 在胃肠道间质瘤中的表达及意义

目的:探讨DOG-1、CD117、CD34、WT-1在胃肠道间质瘤(GIST)中的表达及临床意义。方法:应用免疫组织化学SP法检测DOG-1、CD117、CD34、WT-1在39例GIST患者肿瘤组织中的表达。结果:GIST光镜下主要由梭形细胞和(或)上皮样细胞或多形性细胞混合或单一性组成。DOG-1、CD117、CD34和WT-1在GIST肿瘤组织中阳性表达率分别为92.3%(36/39)、71.7%(28/39)、64.1%(25/39)、23.1%(9/39),四者的阳性表达率在各风险程度组(极低及低度危险性GIST、中度危险性GIST、高度危险性GIST)两两比较中差异均无统计学意义(P>0.05)。DOG-1与CD117相比,在极低及低度危险组中表达有显著差异(P<0.05),DOG-1与CD34相比,在极低及低度危险组、高度危险组中表达有显著差异(P<0.05);WT-1与CD117相比,在中度及高度危险组中表达有显著差异(P<0.05),WT-1与CD34相比,在中度危险组中表达有显著差异(P<0.05)。对照组平滑肌瘤、纤维瘤、神经鞘瘤中CD117、DOG-1在GIST中的表达明显高于其他多种梭形细胞的表达(P<0.05)。结论:DOG1是GIST较为敏感和特异的标记物,WT-1在极低及低度危险性GIST中有一定的诊断价值,在GIST的诊断中加入两者将使患者更加受益。     

Old and new immunohistochemical markers for the diagnosis of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are generally CD117-positive and KIT or PDGFRA mutation-driven mesenchymal tumors of the gastrointestinal tract, probably originating in interstitial cells of Cajal or related precursors. CD117 is the best diagnostic marker for GISTs, but 5-10% are negative. Staining pattern may be cytoplasmic, membrane, and paranuclear (Golgi pattern). PDGFRA expression can be located in the cytoplasm, membrane, and paranuclear region (Golgi pattern), but the lack of specificity, ubiquity of the staining, and technical problems have pushed it a second plane. In GISTs, the staining pattern of PKCO is cytoplasmic, diffuse, and granular, although a Golgi pattern may be seen. Global expression varies. The staining pattern of DOG1 varies from cytoplasmic to membranous, with usually strong, diffuse intensity. The positivity rate is almost identical in some series to CD117 positivity. Currently, it is considered the most specific and sensitive marker for GIST. The current panel for GIST includes CD117, smooth muscle actin, CD34, desmin, and S-100. Some authors also include PDGFRA, PKC0, and DOG1. The last two can be of value in a subset of GISTs, mainly in CD117-negative cases.     

Diagnosis of gastric glomus tumor by endoscopic ultrasound-guided fine needle aspiration biopsy. A case report with cytologic,histologic and immunohistochemical studies

BACKGROUND: The majority of glomus tumor are small, benign neoplasms that arise from modified smooth muscle cells. They usually occur in the dermis or subcutis of the extremities. However, rare cases have been reported in the visceral locations, most often in the stomach. CASE: A 32-year-old woman presented with episodes of right upper quadrant pain. She was found to have a gastric tumor that was biopsied at another hospital, where the diagnosis of gastrointestinal stromal tumor (GIST) was made. Endoscopic ultrasound (EUS) performed at our institution revealed a gastric submucosal tumor that was then biopsied by fine needle aspiration (FNA). Cytology revealed cohesive clusters of uniform, round, small cells with ill-defined cytoplasmic borders and scanty, amphophilic cytoplasm. Nuclei were round, with smooth nuclear membranes and evenly distributed, dusty chromatin. Intermingled with those epithelioid cells were small, short, spindled, normal endothelial cells. Immunohistochemical studies performed on cell block showed that the tumor cells were negative for CD34, CD117, chromogranin, synaptophysin, desmin and AE1/AE3 and were strongly positive for SMA, HHF-35 and collagen type IV. Glomus tumor was diagnosed and later confirmed by histology. CONCLUSION: EUS-guided FNA biopsy is efficient and permits adequate sampling for accurate diagnosis of gastric glomus tumor. Although rare, glomus tumor should be in the differential diagnosis among other gastric lesions, such as well-differentiated adenocarcinoma, epithelioid GIST and carcinoid tumor.     

Analysis of KIT mutation and protein expression in fine needle aspirates of gastrointestinal stromal/smooth muscle tumors

OBJECTIVE: To determine if sequencing the KIT gene could facilitate more definitive FNA diagnosis. STUDY DESIGN: Sixteen cases of gastrointestinal stromal/smooth muscle tumor (GIST) in which fine needle aspiration (FNA) was performed (mean age, 67; M/F = 12/4) were studied. DNA was extracted from cytologic preparations from all patients (15 cell blocks, 1 alcohol-fixed smear) and seven subsequent resection specimens. DNA was amplified by polymerase chain reaction, using primers designed to amplify a segment of the KIT gene exon 11 and sequenced on an ABI Prism 377 DNA sequence analyzer (Applied Biosystems, Indianapolis, Indiana, U.S.A.). Immunocytochemical staining for CD 117 (the KIT gene product) was performed on sections from 12 cell blocks and 7 surgical resections. RESULTS: In-frame deletion of exon 11 was detected in eight cases (7 monoalleic, 1 bialleic); a point mutation was found in one case. Mutation was found only in histologically malignant (6 of 10 cases) and borderline GISTs (3 of 4 cases). No mutation was identified in benign tumors. In three cases, scant cellularity or blood precluded sequencing. CD 117 was expressed in 12 of 15 cases. CONCLUSION: Immunocytochemical staining for CD 117 is useful in confirming a cytologic diagnosis of GIST but does not facilitate diagnosis of malignancy. FNA biopsy specimens are suitable for KIT gene sequencing; detection of a KIT mutation favors a malignant diagnosis, though absence of mutation does not preclude malignancy.     

胃肠道间质瘤组织S100A4、CD55的表达及与临床病理参数及预后的关系研究

摘要 目的：探讨胃肠道间质瘤组织S100A4、衰变加速因子（CD55）的表达及与临床病理参数及预后的关系。方法：选取2011年1月-2015年12月在陆军军医大学附属西南医院江北院区/陆军第958医院行手术切除并经术后病理确诊的124例GIST组织和对应的瘤旁正常组织病理蜡块,采用免疫组化法检测S100A4、CD55在GIST组织及瘤旁正常组织中的表达,分析其表达与GIST患者临床病理参数及预后的关系。结果：S100A4、CD55在GIST组织中的高表达率明显高于瘤旁正常组织,差异有统计学意义（P<0.05）。S100A4、CD55表达与GIST患者肿瘤大小、核分裂相、NIH分级及远处转移有关（P<0.05）,与GIST患者年龄、性别、发生部位、组织学类型无关（P>0.05）。S100A4、CD55低表达的GIST患者术后复发率和转移率低于S100A4、CD55高表达的GIST患者,差异有统计学意义（P<0.05）;S100A4、CD55低表达组患者5年中位无进展生存期明显高于S100A4、CD55高表达组,差异有统计学意义（P<0.05）。结论：S100A4、CD55在GIST组织存在高表达, 二者可能参与了GIST的侵袭与转移,并与患者术后的预后有关。     

CD133在胃肠间质瘤的表达及其临床意义

目的 探讨胃肠间质瘤（gastrointestinal stromal tumor,GIST）中的CD133的表达及其与GIST临床病理特征的关系.方法 采用免疫组织化学法,检测122例胃肠间质瘤患者组织中的CD133、CD117、CD34、DOG-1、KI-67的表达情况.结果 CD133、CD117、CD34 、DOG-1、KI-67的阳性表达率分别为74.6%（91/122）、98.4%（120/122）、86.9%（106/122）、95.1%（116/122）、47.5%（58/122）.CD133的表达水平与胃肠间质瘤危险度分组高低、核分裂像数目、肿瘤部位有关（P〈0.05）,而与患者性别、年龄、肿瘤大小无明显相关性（P〉0.05）.CD133的表达水平与DOG-1的表达水平无明显相关性（P〉0.05）,而与CD117、CD34、KI-67的表达水平呈正相关.结论 CD133蛋白的表达可能与GIST的恶性行为与预后有关,与CD117、CD34和DOG-1联合检测对于判断GIST的病理性质可能具有重要价值.     

A rare giant gastrointestinal stromal tumor (GIST) of the stomach traversing the upper abdomen: a case report and literature review

ABSTRACT: This article presents a 66-year-old woman with a huge GIST of stomach that traverses the upper abdomen. With only the predominant abdominal sign featuring a palpable huge mass, but none special physical findings and routine blood as well as biochemical markers, it could hardly judge where the mass drive from upon the images. Furthermore, many important blood vessels had a complex relationship with the mass according to radiological findings. An exploratory laparotomy revealed a huge tumor that protrude from prior wall of stomach fundus, lesser curvature of stomach side, measuring approximately 21 x 34 x 11 cm in diameter and weighing 5.5Kg. A completely resection was decided on the tumor and the department of pathology immunohistochemically characterized it (CD117, CD34, Dog-1, etc) as a GIST of stomach. Preoperatively diagnosis of GISTs is still sometimes puzzling. Hoping the presentation of this rare case and the literature review could benefit others in similar problems.     

Selected immunohistochemical markers in stromal neoplasms of the gastrointestinal tract.

We studied immunohistochemical reactions to vimentin, desmin and protein S-100 in 43 cases of stromal tumors of the gastrointestinal tract. The material studied included: 1 esophageal tumor, 18 gastric tumors, 19 small intestinal tumors and 5 colonic tumors, classified in 13 cases as benign and in 30 cases as malignant neoplasms of various degree of malignancy. Mean age of the patients was 58.9 years. A positive reaction to vimentin was found in 37 cases, a negative reaction concerned an esophageal tumor, two benign tumors (gastric and small intestinal) and three malignant tumors (gastric and two small intestinal). A positive reaction to desmin was detected in an esophageal tumor and in nine gastric tumors. Only one benign small intestinal tumor and three benign colonic tumors showed a positive reaction to desmin. Protein S-100 was found in an esophageal tumor and in 7 out of 18 gastric tumors and in 12 out of 24 intestinal tumors. Coexpression of vimentin and desmin was found in 8 gastric tumors, only in one small intestinal tumor and in three colonic tumors. Three gastric tumors showing both these reactions were all benign. Coexpression of desmin and protein S-100 was found in 7 out of 43 tumors of the alimentary tract. In six cases these tumors were benign. Basing on the results we may say that the presence of these antigens reflects the degree of differentiation of gastrointestinal stromal tumors of the gastrointestinal tract, though it does not allow to choose unequivocally conclusions as to their histogenesis.     

A gastrointestinal stromal tumor (GIST) masquerading as an ovarian mass

Background

Malignant gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors originating in the wall of the gastrointestinal tract. Myogenic gastrointestinal stromal tumor, a distinctive morphologic variant is characterized by an unusually prominent myxoid stromal background.

Case presentation

We report a case of myxoid variant of GIST in a 42 years old woman presenting as an epigastric mass associated to an ovarian cyst and elevated CA-125. Histologically, the lesions was composed of a proliferation of spindle cells in an abundant myxoid stroma, without evidence of atypia or anaplasia. Immunohistochemical stains showed strong positive staining with muscle actin, positive staining with CD34 and weak positive staining with CD117, while showed negative for S-100.

Conclusion

At surgery every effort should be made to identify the origin of the tumor. A complete surgical removal of the tumor should be obtained, as this is the only established treatment that offers long term survival.     

A case of gastrointestinal stromal tumor with spontaneous rupture in the greater omentum

Background

Although GIST generally occurs in the digestive tract, such as the stomach, and small and small intestine primarily, Omental GIST tumours are very rare.

Case Presentation

A 63-year-old male patient, who recognized an abdominal tumor 1 year before admission, had a slight expansion of the tumor, reduction of the body and malaise, was consulted to our hospital. Abdominal CT and MRI revealed a cystic lesion of 26 cm in diameter with a clear boundary from immediately below the interseptum to the pelvic cavity, and imaged the septum and cystic wall. We considered that the patient had a cystic tumor in the abdomen, of which the primary lesion was unknown, and scheduled surgery. The patient unfortunately deteriorated with shock and sudden pain in the abdomen. Wediagnosed tumor rapture, and emergency surgery was performed. The tumor, weighing 3,600 g, was mostly cystic, and filled with sanguinous fluid and clot. Histologically, the tumor was composed of spindle cells, and was positive for c-KIT (CD117), slightly positive for alpha-smooth muscle actin (SMA), and S-100 protein positive. Based on these findings, the tumor was diagnosed as GIST primarily occurring in the greater omentum.

Conclusion

We experienced a rare case of GIST which originated from the greater omentum. Recently, the prognosis of GIST has been improved since the treatment with Imatinib.It is necessary to consider the diagnosis of GIST on encountering a mass in the greater omentum.

     

Malignant epithelioid gastrointestinal stromal tumors: report of a case with cytologic and immunohistochemical studies

BACKGROUND: Gastrointestinal stromal tumors (GISTs) may exhibit a fusiform, epithelioid or mixed pattern of growth. Only rare articles report the cytologic and immunohistochemical features of malignant epithelioid tumors. CASE: A 57-year-old woman presented with a tumor mass in the small intestine omentum measuring 8 x 7 cm; it was surgically removed. Five years later 2 mesenteric relapses were studied by fine needle aspiration biopsy and later surgically excised. Cytologically the smears contained small clusters of epithelioid and plasmacytoid cells with round nuclei. The presence of nucleoli and occasional nuclear grooves were prominent. Focally the background was myxoid. Histologically the tumor showed an epithelioid pattern with moderate pleomorphism and mitoses in 6 of 50 high-power fields. Immunohistochemical study showed positivity for c-kit (CD117), vimentin, smooth muscle actin and caldesmon, and focally for desmin and cytokeratin. CONCLUSION: This case illustrates the difficulty in making a reliable diagnosis of the epithelioid variant of GIST by cytology alone. The immunohistochemical panel (apart from c-kit) should include smooth muscle markers and cytokeratins because they are more likely to be reactive. A complete cytoimmunohistochemical evaluation is mandatory to make an accurate diagnosis.     

Fine needle aspiration of gastrointestinal stromal tumors

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal tract. Fine needle aspiration (FNA) is one option for diagnosing GISTs before surgery. This study was designed to evaluate the clinical utility of FNA in the diagnosis of GISTs. STUDY DESIGN: FNAs from 19 GISTs originating in the stomach, small bowel and colon obtained from 1988 to 1998 were studied. Immunocytochemistry was performed on 12 cases. The GISTs were classified as benign, borderline and malignant, according to location, size, mitotic activity and clinical outcome. RESULTS: Benign (three) and borderline (five) GISTs were all spindle cell type; malignant GISTs included five spindle cell type and six epithelioid type. Most smears contained abundant cellular material. Benign and borderline GISTs of spindle cell type tended to have cells arranged in tightly cohesive clusters, while malignant GISTs were more likely to exhibit loosely cohesive groups with many single cells, occasional nuclear pleomorphism, hyperchromasia and irregular nuclear contours. Epithelioid-type GISTs mimicked adenocarcinoma. Mitoses were seldom observed in either type. CD117 (KIT protein product) was demonstrated by immunocytochemistry in 9 cases, CD34 in 11, desmin in 3, S-100 protein in 2 and smooth muscle actin in 6 cases. CONCLUSION: FNA can be used to diagnose GISTs as spindle cell and epithelioid types, but cytomorphology alone cannot be used to assess malignant potential. Immunocytochemical staining for CD117 is helpful in confirming the diagnosis. Care must be taken to differentiate epithelioid-type GISTs from adenocarcinoma.     

Telocytes in the human sinoatrial node

The sinoatrial node (SAN) is composed mostly of pacemaker, transitional and Purkinje‐like cells. Pacemaker cells, especially in the centre of the SAN, are surrounded by dense fibrous tissue and do not have any contact with transitional cells. We hypothesize that the SAN contains telocytes that have contacts with pacemaker cells and contractile myocardium. Immunohistochemistry using antibodies against HCN4 and antibody combinations against CD34 and HCN4 was carried out on 12 specimens. Confocal laser scanning microscopy (CLSM) with two mixtures of primary antibodies, namely CD34/S100 and vimentin/S100, was performed in three cases. In two cases, CLSM was carried out with CD117 antibody. Specimens for electron microscopy and immunocytochemistry with HCN4 immunogold labelling were taken from another three patients. In our study, we found cells with the immunophenotype of telocytes in the SAN. There were twice as many of these cells in the centre of the SAN as in the periphery (20.3 ± 4.8 versus 10.8 ± 4.4 per high‐power field). They had close contact with pacemaker cells and contractile cardiomyocytes and expressed HCN4. The ultrastructural characteristics of these cells are identical to those of telocytes observed earlier in other organs. Our study provides evidence that telocytes are present in the SAN.     

嫌色性肾细胞癌17例临床病理学分析

目的探讨嫌色性肾细胞癌的临床病理特征、诊断与鉴别诊断要点。方法对17例嫌色性肾细胞癌进行组织形态学、免疫组化染色及Hale’s胶样铁染色观察,结合文献对其临床表现、病理形态特点及鉴别诊断进行探讨。结果嫌色性肾细胞癌17例,大体肿瘤直径3-10.5cm。镜下肿瘤由嫌色细胞和嗜酸细胞构成,呈片状、梁状和腺泡状分布。嫌色细胞体积较大,多角形,胞膜清晰,胞质半透明细网状,胞核皱缩,可见核沟及核异型,核仁不明显;而嗜酸细胞胞质嗜酸,可见明显的核周空晕。免疫组化:EMA 100%阳性,CD10 52.9%阳性,Vimentin阴性,CK7 88.2%阳性,P504S29.4%阳性,CD11794.1%阳性。Hale’s胶样铁染色100%阳性。17例中12例随访6个月到3年,仅1例在术后15个月发现肝脏转移,其余均未发现复发及转移。结论嫌色性肾细胞癌是一种少见的肾肿瘤,恶性程度相对较低,预后良好。掌握该肿瘤独特的病理学特征,对鉴别其他肾上皮性肿瘤有重要帮助。     

腹壁肿瘤及瘤样病变的CT 诊断（附44 例报道）

目的:分析腹壁肿瘤及瘤样病变的CT表现,旨在提高医师对腹壁肿瘤及瘤样病变的认识,并评价CT在腹壁肿瘤诊断及鉴别诊断中的价值。方法:回顾性分析44例经病理证实的腹壁肿瘤及肿瘤样病变的CT表现,并与病理结果对照。结果:(1)CT扫描对腹壁肿瘤及瘤样病变的定位诊断率达到100%(44/44),定性诊断率约84.1%(37/44)。(2)良恶性病变在边界清晰与否、大小等方面并没有差异,边界不清的29例病例中,14例为良性,15例为恶性。(3)腹壁病变呈较高密度影者均为良性(7/7),血管源性多见。(4)血管瘤、纤维肉瘤、韧带样纤维瘤亦为渐进性强化,腹壁脓肿、结核为环状强化,转移瘤为不均匀强化。结论:CT是目前诊断腹壁肿瘤及肿瘤样病变的主要手段,能较准确定位病变,但对病变定性仍有一定的困难,最终需要病理证实。     

Giant gastrointestinal stromal tumor with predominantly cystic changes: a case report and literature review

Background

Gastrointestinal stromal tumors (GISTs) rarely present with predominantly cystic changes. Here, we report a case of giant GIST of the stomach with predominantly cystic changes in a 74-year-old female patient.

Case presentation

The tumor was 10 cm?×?15 cm in size and positive for CD117, H-caldesmon, and DOG-1. Complete surgical resection was performed without regional lymphadenectomy. The patient recovered uneventfully and no recurrence occurred.

Conclusions

The case illustrates that GIST with cystic changes should be considered in the diagnoses of hepatic and pancreatic lesions. Furthermore, immunohistochemistry with CD117, DOG1, and other molecular markers is critical for diagnosis of GIST of the stomach and facilitates optimization of treatments for GIST.

     

原发性十二指肠恶性肿瘤的临床分析

目的:探讨原发性十二指肠恶性肿瘤的临床特点、诊断方法和预后影响因素。方法:回顾性分析随访资料完整的45例原发性十二指肠恶性肿瘤患者的临床病理资料。结果:腺癌33例(73.3%)为主要的病理类型。主要临床表现为腹痛、上腹部不适、黄疸、消化道出血等。胃十二指肠镜、内镜逆行胰胆管造影(Endoscopic Retrograde Cholangio-Pancreatography,ERCP)、十二指肠低张造影、超声内镜、CT及B超确诊率分别为91.1%(41/45),93.3%(42/45),82.2%(37/45),75.6%(34/45),68.9%(31/45)及26.7%(12/45)。本组45例均行开腹手术,包括根治性手术,胰十二指肠切除术36例;姑息性手术,胃肠吻合术2例、肿瘤局部切除术5例、短路手术2例。根治术和姑息术后5年生存率分别为46.7%和4.4%,两组生存率差异有统计学意义(P<0.05)。对全组45例患者的预后因素进行Cox回归分析的结果显示,手术方式、肿瘤浸润深度和淋巴节转移是影响预后的独立危险因素(均P<0.05)。结论:原发性十二指肠恶性肿瘤缺乏特异性临床表现;胃十二指肠镜、ERCP以及十二指肠低张造影等联合检查可提高诊断率;根治性手术远期疗效较好;淋巴结转移和局部侵犯是肿瘤预后不良的重要影响因素。