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     

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。     

胃肠道间质瘤起源和分化的探讨

目的 探讨胃肠道间质瘤(GIST)的起源或分化。方法 采用免疫组织化学EnVision和电镜的方法对GIST进行研究。结果 212例GIST CD117、CD34、α—平滑肌肌动蛋白(SMA)、肌特异性肌动蛋白、结蛋白阳性率分别为96．7％,77．3％,19．3％,15．6％,1．9％,其中S—100和PGP9．5的阳性反应分别为16．3％及12．3％。超微结构显示瘤细胞含丰富的线粒体,粗面内质网、游离核糖体和中间丝,有的细胞切面可见溶酶体和脂滴,高尔基复合体在核周分布,质膜处偶尔不规则地分布着一些微饮泡、密斑样结构及不连续的基板。部分病例细胞有多量细长指状突起,突起内有胞内成分如线粒体、粗面内质网延续,突起之间或突起与细胞膜有连接结构。细胞外间质内可见胶原原纤维或团丝样纤维。结论 GIST免疫表型及超微结构特征与胃肠壁成熟卡哈尔间质细胞相似,提示GIST可能是起源于幼稚间充质细胞向卡哈尔间质细胞分化的肿瘤,并具有一定的肌性特征。     

Gastrointestinal stromal tumor (GIST) in southern Taiwan: a clinicopathologic study of 93 resected cases

The purpose of this study was to determine the clinicopathologic features of gastrointestinal stromal tumor (GIST) in southern Taiwan. The pathology files from a medical center in southern Taiwan (1993 to 2003) were searched for primary mesenchymal tumors of the gastrointestinal tract. Hematoxylin/eosin sections and history were reviewed, and immunohistochemistry was performed using anti-CD 117, CD34, smooth muscle actin (SMA), and S-100 protein. Only primary resected GISTs were included in this study. Univariate and multivariate analyses were carried out using the T-test to evaluate the significance of primary tumor size and mitotic activity for the prediction of recurrence and metastasis. A total of 121 surgically resected primary mesenchymal tumors were identified, and 93 of these were GISTs. These 93 patients showed a slight female predominance (male: female = 1:1.2). The clinical presentations were variable and site-dependent. The most common tumor locations were the stomach (57%) and the small intestine (39%). Microscopically, 88 tumors (95%) were composed of spindle cells, the remaining five (5%) consisted of mixed epithelioid and spindle cells. No pure epithelioid type GIST was found. In addition to CD117, 66 cases (71%) were positive for CD34, 23 cases (25%) were positive for SMA, and 19 cases (21%) were positive for S-100. In a mean follow-up time of 27.3 months (median: 26 months), 19 cases (20.6%) were clinically malignant and mainly manifested as liver metastases (seven cases, 37% of malignant GISTs). Univariate analysis revealed that both primary tumor size and mitotic activity were significantly increased in the group affected by recurrence and/or metastasis (p = 0.001 and 0.035, respectively). Compared to GISTs in the western countries, those in southern Taiwan are characterized by a slight female predominance, a relatively higher frequency of small intestinal localization, a higher rate of S-100 protein expression, and a less aggressive behavior. Tumor size and mitotic activity were useful predictors of malignancy.     

Gastrointestinal stromal tumors: recent advances in understanding of their biology.

Gastrointestinal stromal tumor (GIST) is the preferred term for mesenchymal tumors specific for the gastrointestinal tract (60% in stomach, 30% small intestine, 10% elsewhere). GISTs include most tumors previously designated as leiomyoma, cellular leiomyoma, leiomyoblastoma, and leiomyosarcoma. However, in the esophagus, leiomyoma is the most common mesenchymal tumor. GISTs are composed of spindle (70%) or epithelioid (30%) cells, and 10%-30% are malignant showing intra-abdominal spread or liver metastases. They are immunohistochemically positive for c-kit (CD117), CD34, and sometimes for actin but are almost always negative for desmin and S100-protein. The malignant GISTs especially show activating mutations in the c-kit gene. GISTs and gastrointestinal autonomic nerve tumors (GANT) overlap. The cell of origin is not fully understood, but resemblance to the interstitial cells of Cajal, expression of some smooth muscle markers, and occurrence outside of the GI-tract suggest origin from multipotential cells that can differentiate into Cajal and smooth muscle cells.     

Gastrointestinal stromal tumor: consistent CD117 immunostaining for diagnosis,and prognostic classification based on tumor size and MIB-1 grade

Gain-of-function c-kit gene mutations and immunoreactivity of the c-kit protein CD117 in many gastrointestinal stromal tumors (GISTs) seem to support the idea that GISTs form a biologically distinct entity. In this study, the clinicopathologic features of 171 cases of GIST at a single institution were investigated for accurate diagnosis, and their relative risk for mortality was estimated by multivariate analysis. A GIST was defined diagnostically as a mesenchymal spindle or epithelioid cell lesion arising in the wall of the gastrointestinal tract with consistent immunoreactivity for CD117. The 171 patients with GISTs comprised 96 males (56.1%) and 75 females (43.9%), with a mean age of 59.4 years. One hundred and forty-five tumors (84.8%) occurred in the stomach, 18 (10.5%) in the small intestine, 6 (3.5%) in the rectum, and 2 (1.2%) in the esophagus. The median tumor size was 4.5 cm (range, 1.2 to 38 cm). Spindle-cell GISTs were present in 132 cases (77.2%); mixed GISTs, in 25 cases (14.6%); and epithelioid GISTs, in 14 cases (8.2%). Ten cases (55.6%) of spindled small intestine GIST contained eosinophilic skeinoid fibers. Immunoreactivity for CD34, h-caldesmon, alpha-smooth-muscle actin (SMA), desmin, and S-100 was observed in 156 (91.2%), 131 (76.6%), 46 (26.9%), 7 (4.1%), and 14 (8.2%) tumors, respectively. The percentage of CD34 positivity (38.8%) was low, in contrast with the high percentage of reactivity for SMA (77.8%) and S-100 (44.4%) in small intestine GISTs. By our histologic grading system using tumor differentiation, MIB-1 score, and necrosis, 129 tumors (75.4%) were classified as low grade and 42 tumors (24.6%) were classified as high grade. With a median follow-up period of 83.5 months for 122 living patients, the 5-year and 10-year survival rates were 81.7% and 67.4%, respectively. Multivariate analysis showed that both tumor size >10 cm and high grade were significantly associated with a poor outcome. As a result, GISTs >10 cm or high grade, 5 to 10 cm and low grade, and < or =5 cm and low grade were regarded as high risk, intermediate risk, and low risk for mortality, respectively. In conclusion, it is important to recognize GISTs that have a specific molecular pathogenesis and to separate them from other mesenchymal tumors with optimal immunostaining for CD117 when making a diagnosis and prognostic classification based on tumor size and MIB-1 grade.     

Schwannomas of the gastrointestinal tract: clinicopathological features of 12 cases including a case of esophageal tumor compared with those of gastrointestinal stromal tumors and leiomyomas of the gastrointestinal tract

We analyzed the clinicopathological features of 12 gastrointestinal (GI) schwannomas and compared them with those of 37 GI stromal tumors (GISTs) and 15 leiomyomas. Grossly, the schwannomas showed rubbery to firm, yellow-white to tan, glistening, and often trabeculated cut surfaces, resembling soft tissue schwannomas. The GISTs were firm to soft or fish-flesh tan, gray-pink, or variegated tumors with a degenerative change, and the leimyomas resembled typical uterine leiomyomas. Histologically, GI schwannomas were moderately cellular tumors with focal significant nuclear pleomorphism and rare mitotic figures. A characteristic peripheral lymphoid cuff was observed in all cases, but was indistinct in two cases. The GISTs were highly cellular spindle cell, epithelioid or, occasionally, pleomorphic tumors with basophilic appearance. Leiomyomas were paucicellular tumors with eosinophilic appearance. Immunohistochemically, schwannomas were S-100 protein- and glial fibrillary acidic protein (GFAP)-positive, but were negative for c-kit, CD34, and smooth muscle actin (SMA). GISTs were all c-kit- and/or CD34-positive, but GFAP-negative. Leiomyomas were SMA-positive and were negative for c-kit, CD34, S-100 protein, and GFAP. The mean Ki-67 index of schwannoma was 0.7, and those of GIST and leiomyoma were 5.9 and 0.3, respectively. The patients with schwannomas and leiomyomas had a favorable outcome, whereas 12 patients with GISTs showed progression and died of disease. The separation of GISTs from schwannomas is clinically important because the former group has a high risk of malignant behavior. GI schwannomas differed from the conventional soft tissue schwannomas in that they had peripheral lymphoid cuffs, lacked fibrous capsule and vascular hyalinization, and rarely showed degenerative changes. GI schwannomas, however, resembled soft tissue schwannomas in many aspects, and the clinical, gross, histological, and immunohistochemical features were different from those of GISTs and leiomyomas.     

Strong PDGFRA positivity is seen in GISTs but not in other intra-abdominal mesenchymal tumors: Immunohistochemical and mutational analyses.

Mutation of the platelet-derived growth factor receptor-alpha (PDGFRA) gene has been well documented as an alternative oncogenic mechanism in a subset of gastrointestinal stromal tumors (GISTs) lacking c-kit mutations. However, the role of PDGFRA immunohistochemistry in the diagnosis of GISTs has not been well studied. We investigated PDGFRA immunoreactivity in GISTs and in other intra-abdominal mesenchymal tumors, and correlated PDGFRA expression with CD117 positivity and with the mutational status of PDGFRA and c-kit genes. In addition, expression of phosphorylated AKT, an activated downstream molecule in the PDGFRA and c-kit signaling pathways, was correlated with PDGFRA and CD117 status. A total of 39 GISTs and 20 other mesenchymal tumors in the abdomen were included in this study. Thirty-five of 39 GIST cases (89.7%) were positive for PDGFRA and 19 of these 35 positive cases were strongly positive. Five of 20 non-GIST lesions (25%) were positive for PDGFRA, but none of these cases were strongly positive. With one exception, PDGFRA-positive cases were also positive for CD117. Phosphorylated AKT positivity was not associated with the immunoreactivity or mutation of PDGFRA and c-kit, suggesting that the activation of AKT is probably independent of the activation of PDGFRA and c-kit in GISTs. Of 14 GISTs assayed, 4 had mutations in c-kit at exons 11 or 17, and 4 had mutations in PDGFRA at exons 12 or 18. Three of 4 GIST cases with PDGFRA mutations show epithelioid morphology and strong PDGFRA immunoreactivity with prominent perinuclear dotlike accentuation (so-called Golgi pattern). In conclusion, strong PDGFRA positivity with Golgi pattern is a useful adjunct in the diagnosis of GISTs with PDGFRA mutation.     

Distinguishing gastrointestinal stromal tumors from their mimics: an update

Since the discovery of activating KIT mutations in gastrointestinal stromal tumors (GISTs) in 1998 and the subsequent demonstration that some malignant GISTs respond to targeted therapy with imatinib, it has become increasingly important for pathologists to correctly diagnose GISTs and separate them from their potential mimics in the gastrointestinal tract and abdominal cavity. Some mesenchymal tumors, such as leiomyomas of the muscularis mucosae, are easily distinguished from GIST on the basis of their anatomic location and morphologic appearance. Others, such as gastrointestinal schwannomas, can significantly overlap with GIST in their gross appearance and morphology and require a panel of immunostains for correct diagnosis. This article will review the most common mimics of GISTs: desmoid tumors, smooth muscle tumors (leiomyomas and leiomyosarcomas), gastrointestinal schwannomas, inflammatory fibroid polyps, and solitary fibrous tumors. Pertinent differences between each of these tumors and GIST in terms of gross appearance, histologic features, and immunophenotype will be emphasized. It is important to separate GISTs from these potential mimics because their treatment and prognosis can differ markedly.     

Mutations in Exon 11 of c-Kit Occur Preferentially in Malignant versus Benign Gastrointestinal Stromal Tumors and Do Not Occur in Leiomyomas or Leiomyosarcomas

Gastrointestinal stromal tumors (GISTs) comprise the largest subset of mesenchymal tumors of the gastrointestinal tract. These neoplasms differ histologically and immunohistochemically from typical leiomyomas and leiomyosarcomas. Most GISTs express CD34 and CD117 (c-kit protein) but not desmin. Recently, gain-of-function mutations of c-kit proto-oncogene have been shown in five solitary GISTs and in tumors and leukocytes from a family with multiple GISTs. An in-frame deletion or a point mutation in exon 11 of c-kit was detected in these cases. Stable transfection of the mutant c-kit complementary DNA was also shown to induce malignant transformation of murine lymphoid cells, suggesting that the c-kit mutations contribute to tumor development. In this study, we evaluated 43 GISTs and 14 smooth muscle tumors for mutations in the exon 11 of c-kit by a PCR-assay. Half of the malignant GISTs (12/24) and only one benign GIST (1/19) revealed mutant bands. No mutant bands were found in 3 leiomyomas and 11 leiomyosarcomas. Sequence analysis confirmed the presence of an in-frame deletion of 3–21 bp in all 13 GISTs with mutant bands. Wild-type bands from 8 malignant and 11 benign GISTs and 7 smooth muscle tumors without mutant bands were cloned and sequenced. Additional mutations were found in 3 malignant and 2 benign GISTs. There were no mutations in 3 leiomyomas and 4 leiomyosarcomas. The mutation status of exon 11 did not correlate with immunohistochemically detectable expression of the CD117, as virtually all GISTs with or without such mutations showed CD117 immunoreactivity. The c-kit mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs. The conservation of the c-kit mutation pattern, observed in consecutive lesions from the same patients, suggests that these mutations might be useful tumor markers in monitoring recurrence or minimal residual disease.     

nestin在胃肠道间质瘤病理诊断中的价值

目的探讨nestin在胃肠道间质瘤（gastrointestinal stromal tumors,GISTs）辅助诊断中的价值。方法用免疫组化EnVision法检测96例CD117阳性、5例CD117阴性的GISTs,以及食管平滑肌瘤（10例）、消化道雪旺瘤（33例）、肠纤维瘤病（6例）以及腹腔平滑肌肉瘤（15例）,观察这些肿瘤中nestin的表达状况。结果96例CD117阳性的GISTs中,94例表达nestin,其中70例弥漫强表达,21例中度阳性,3例局灶阳性,仅2例阴性;5例CD117阴性的GISTs中,4例表达nestin;33例消化道雪旺瘤中26例表达nestin;15例平滑肌肉瘤中3例局灶表达nestin;10例食管平滑肌瘤、6例肠纤维瘤病均为阴性。结论nestin是辅助诊断GISTs的新指标,可鉴别GISTs与平滑肌肿瘤和纤维瘤病,但在GISTs与雪旺瘤的鉴别中需结合S-100蛋白等指标。     

Differential diagnosis of gastrointestinal stromal tumor and other spindle cell tumors in the gastrointestinal tract based on immunohistochemical analysis

To confirm the usefulness of an immunohistochemical panel of antibodies for KIT (c-kit/CD117), CD34, desmin, smooth-muscle actin (SMA), h-caldesmon (HCD), S-100 protein, neuron-specific enolase (NSE), and beta-catenin, 297 mesenchymal and peripheral nerve-sheath tumors of the gastrointestinal tract and intra-abdominal locations including 211 gastrointestinal stromal tumors (GISTs), 12 leiomyomas, 18 leiomyosarcomas, 17 solitary fibrous tumors (SFTs), 14 schwannomas, and 25 desmoid-type fibromatoses (DTFs) were analyzed immunohistochemically. Consistent (100%) immunoreactivity for KIT, CD34, desmin and S-100, and nuclear accumulation of beta-catenin were detected in GISTs, SFTs, smooth-muscle tumors, schwannomas, and DTFs, respectively. Immunoreactivity for SMA, HCD, and NSE was observed in a wide range of these tumors. In addition, 418 bone and soft tissue tumors were enrolled in this study for KIT immunostaining. As a result, a limited number of these tumors were KIT positive, including synovial sarcoma that showed morphological similarity to GISTs. These findings suggest that KIT, CD34, desmin, S-100, and beta-catenin are key markers for clinical diagnosis of GISTs and other spindle cell tumors that may involve the gastrointestinal tract, whereas SMA, HCD, and NSE have only limited value.     

Primary gastrointestinal stromal tumor of the esophagus in an HIV-positive patient

We describe a rare case of malignant gastrointestinal stromal tumor (GIST) of the esophagus presenting in an HIV-positive man. Not only did the tumor arise from an unusual anatomic site for GIST, namely, the esophagus, but it also had a predominant epithelioid cell morphology that is uncommon and preferentially associated with aggressive behavior. Exhaustive immunohistochemical studies showed strong reactivities to the classic GIST marker, CD34, and to the current more sensitive and more specific GIST marker, CD117/ c-kit protein. This immunophenotype corresponded to that of stromal tumors arising in the more common sites like stomach and small intestine as well as to that of a reported series of esophageal GISTs in the general population. Mutations of the c-kit protein was detected in the tumor, confirming previous observations. This further documents that esophageal GIST and the more common benign esophageal spindle cell lesions are pathologically distinct entities and despite its rarity, esophageal GIST should be recognized by pathologists and clinicians. The occurrence of this tumor in an HIV-positive patient is coincidental, and it resulted in an extremely unusual metastatic site that has not been reported for GISTs.     

Cytological, immunohistochemical and mutational analysis of a gastric gastrointestinal stromal tumour in a cat

Gastrointestinal stromal tumours (GISTs) represent a distinctive group of primary mesenchymal tumours of the gastrointestinal tract identified immunohistochemically by expression of CD117. A 10-year-old neutered female domestic shorthair cat with a history of recurrent vomiting was examined. The presence of a gastric mass was recognized and a laparotomy was performed. Cytological examination was consistent with a low-grade malignant mesenchymal tumour and histopathological investigation suggested myogenic differentiation of tumour cells. The diagnosis of GIST was confirmed by immunohistochemical expression of CD117. Sequence analysis of the KIT gene identified a deletion in exon 11. The same mutation is found often in human GISTs.     

Morphological characteristics and prognostic criteria for gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract. Analysis of GIST morphology is necessary for selection of primary patients with the high risk of tumor progression for adjuvant treatment with gleevek following complete gross resection of KIT (CD 117)-positive GIST. In this study we've analyzed morphological parameters and survival of 120 GIST patients before target therapy. According to risk stratification of primary GIST by tumor location, size and mitotic index (mitoses per 50 visual fields) 44% of gastric GISTs, 87,5% of small bowel GISTs and 100% of rectum GISTs have been classified as high risk group. There was no significant difference between survival of patients with different type of GIST, Ki-67 proliferative index and presence of necrosis.     

Gastrointestinal spindle cell tumours of the dog: histological and immunohistochemical study

To assess the relevance of spindle cell tumours in the canine gastrointestinal (GI) tract and to classify them, a retrospective study was carried out on haematoxylin and eosin-stained sections from formalin-fixed paraffin wax-embedded samples of 105 primary GI tumours. Seventeen out of 105 (16%) GI tumours were mesenchymal, 48% were epithelial and 36% were round cell tumours. Spindle cell tumours were stained by Masson trichrome, Orcein-Van Gieson and labelled immunohistochemically (vimentin, desmin, smooth muscle actin, protein S100, glial fibrillar acid protein, CD117 and MIB-1) and the histological grade, mitotic index, nuclear size and cellular density were also assessed. The 17 gastrointestinal mesenchymal tumours were classified as 10 leiomyomas (10/10 positive for desmin and smooth muscle actin; 6/10 positive for vimentin) 2 leiomyosarcomas (2/2 positive for desmin, smooth muscle actin and vimentin) and 5 gastrointestinal stromal tumours (GISTs) (5/5 positive for CD117 and vimentin; 3/5 positive for smooth muscle actin). Canine GISTs appeared as densely packed spindle cell tumours, with a diffuse, strong, cytoplasmic immunopositivity for c-kit protein (CD117). GISTs, defined as CD117-positive spindle cell or epithelioid or pleomorphic neoplasms that presumably derive from interstitial cells of Cajal, are reported in recent medical studies as the most common mesenchymal tumours of the GI tract. Our data suggest that GISTs represent a significant portion of canine GI spindle cell tumours, which can be definitely distinguished from leiomyosarcomas only by their expression of CD117.     

Gastrointestinal stromal tumors: diagnostic challenges and practical approach to differential diagnosis

Over the last decade, gastrointestinal stromal tumors (GISTs) have evolved from histogenetically obscure gastrointestinal mesenchymal tumors to well-defined tumors with distinctive clinical, morphologic, ultrastructural, histogenetic, and molecular characteristics, for which targeted therapy is available. This is largely attributable to the discovery of CD117 overexpression and activating mutations in c-kit or platelet-derived growth factor alpha genes in most of GISTs. The availability of specific diagnostic tests and targeted therapy for GISTs has led to an increased awareness of these tumors. At the same time, the list of potential GIST mimics has lengthened considerably and it has become increasingly important that GISTs be distinguished from their mimics because correct diagnosis has implications for both treatment and prognosis. The purpose of this review is to provide an update of the expanding differential diagnosis of GISTS, to draw attention to unusual GIST variants, to provide a practical approach the differential diagnosis of GISTs and to highlight some of the challenges faced by pathologists in resolving this differential diagnosis.     

Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT).

Gastrointestinal (GI) stromal tumor (GIST) is the designation for the major subset of GI mesenchymal tumors and encompasses most tumors previously classified as GI smooth muscle tumors. Although GISTs typically express CD117 (KIT), often express CD34, and sometimes express alpha-smooth muscle actin (SMA), the relative frequency of these markers has not been characterized in large series of GISTs of different sites, and the CD117 expression has not been fully characterized in intra-abdominal tumors. In this study, we immunohistochemically analyzed 292 GISTs throughout the GI tract, including omentum and mesentery, and compared the immunoreactivities with 211 other tumors that may enter in the differential diagnosis. GISTs were defined in this study as CD117-positive primary spindied or epithelioid mesenchymal tumors of the GI tract, omentum, or mesentery. The CD34 positivity of GISTs varied from 47% in small bowel to 96 to 100% in rectum and esophagus, whereas SMA expression showed the opposite patterns and was most frequent in the GISTs of small bowel (47%) and rarest in the GISTs of rectum and esophagus (10-13%). Desmin was seen only occasionally. S100 positivity was rare but was seen most frequently in small intestinal GISTs (15%). True leiomyomas from esophagus, muscularis mucosae of colorectum, and pericolic leiomyomas similar to uterine leiomyomas were negative for CD117 and CD34 and positive for SMA and desmin (46 of 46). Inflammatory fibroid polyps of stomach and small intestine were negative for CD117 but were often positive for CD34 (6 of 8) and variable for SMA (3 of 8). Inflammatory myofibroblastic tumors involving gastric or colonic wall were negative for CD117 but some showed CD117-positive endothelia. GI schwannomas were all negative for CD117 and positive for S100 protein (11 of 11). Extremely focal CD117 positivity was seen in the neoplastic cells of some retroperitoneal leiomyosarcomas and liposarcomas. Among other CD117-positive tumors were intestinal metastatic melanomas (8 of 11) and extraskeletal Ewing's sarcomas (5 of 11), two of which were abdominal. In conclusion, strong CD117 expression defines most primary GI mesenchymal tumors as GISTs, which show different patterns for CD34 and SMA in various parts of the GI tract. Some unrelated CD117-positive tumors (melanomas, Ewing's sarcomas) should not be confused with GISTs.     

Gastrointestinal stromal tumors – definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. They are defined here as KIT (CD117, stem cell factor receptor)-positive mesenchymal spindle cell or epithelioid neoplasms primary in the GI tract, omentum, and mesentery. GISTs typically present in older individuals and are most common in the stomach (60-70%), followed by small intestine (20-25%), colon and rectum (5%), and esophagus (<5%). Benign tumors outnumber the malignant ones by a wide margin. Approximately 70% of GISTs are positive for CD34, 20-30% are positive for smooth muscle actin (SMA), 10% are positive for S100 protein and <5% are positive for desmin. The expression of CD34 and SMA is often reciprocal. GISTs commonly have activating mutations in exon 11 (or rarely exon 9 and exon 13) of the KIT gene that encodes a tyrosine kinase receptor for the growth factor named stem cell factor or mast cell growth factor. Ligand-independent activation of KIT appears to be a strong candidate for molecular pathogenesis of GISTs, and it may be a target for future treatment for such tumors. Other genetic changes in GISTs discovered using comparative genomic hybridization include losses in 14q and 22q in both benign and malignant GISTs and occurrence in various gains predominantly in malignant GISTs. GISTs have phenotypic similarities with the interstitial cells of Cajal and, therefore, a histogenetic origin from these cells has been suggested. An alternative possibility, origin of pluripotential stem cells, is also possible; this is supported by the same origin of Cajal cells and smooth muscle and by the common SMA expression in GISTs. GISTs differ clinically and pathogenetically from true leiomyosarcomas (very rare in the GI tract) and leiomyomas. The latter occur in the GI tract, predominantly in the esophagus (intramural tumors) and the colon and rectum (muscularis mucosae tumors). They also differ from schwannomas that are benign S100-positive spindle cell tumors usually presenting in the stomach. GI autonomic nerve tumors (GANTs) are probably a subset of GIST. Other mesenchymal tumors that have to be separated from GISTs include inflammatory myofibroblastic tumors in children, desmoid, and dedifferentiated liposarcoma. Angiosarcomas and metastatic melanomas, both of which are often KIT-positive, should not be confused with GISTs.