74例胃肠道间质瘤临床病理与生物学行为评价

Gastrointestinal stromal tumor: a clinicopathological study of 74 cases

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,GIST 74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例消化道间叶组织肿瘤中,有9例SMA和结蛋白阳性,而CD117和CD34均无表达,诊断为平滑肌肿瘤;1例S-100蛋白阳性,CD117和CD34阴性,诊断为神经鞘瘤.1例除波形蛋白和溶菌酶阳性外,其他抗体都阴性的多形性肉瘤诊断为恶性纤维组织细胞瘤.74例GIST生物学行为评价分为:极低度侵袭危险性3例,低度侵袭危险性15例,中度侵袭危险性36例,高度侵袭危险性20例.31例GIST有随访资料,随访率41.9%,随访时间18～72个月,不同侵袭危险性病例各组以随访结果做出 Kaplan-Meier生存曲线,log-rank检验进行组间生存率比较,P＜0.01,显示生物学行为的病理学参数评价与随访结果有很好的相关性,侵袭危险性极低、低、中、高各组间生存曲线差异明显.结论 GIST主要见于中老年人,男性多于女性.CD117阳性对诊断有确定作用.CD34表达对诊断也有重要意义.Fletcher等推荐的GIST生物学行为评价表与随访结果有很好的相关性,其实用、简单,重复性好.

Objective To explore a simplified and reproducible approach for the diagnosis and morphologic prognostication of gastrointestinal stromal tumor (GIST). Methods Eighty-five cases of gastrointestinal mesenchymal tumors including 74 cases of GIST, 8 esophageal smooth muscle tumor, 1 rectal leiomyosarcoma, 1 Schwannoma, and 1 malignant fibrous histiocytoma were studied by histological evaluation along with an immunohistochemistry panel including vimentin, CD117 (c-kit), CD34, SMA, desmin and S-100. Clinicopathological correlation was performed in 31 cases of GIST that had accompanied with the available follow-up data. Results Among 74 GISTs, 34 arose principally from the stomach, 30 from the small intestine, and 10 other cases found in the esophagus, retroperitoneum, mesenterium and omentum. The patients′ age ranged from 23 to 80 years (mean 52.5 years), with 45 males and 29 females. Histologically, the tumors composed of either spindle or oval to round cells arranged in interlacing fascicles forming whorls or cellular clusters, cytoplasm generally abundant and eosinophilic. There were 48 cases of spindle cell type, 10 cases of epithelioid cell type and 16 cases of mixed cell type. All 74 cases of GIST were positive for CD117 in a cell membranous pattern, however, some variable staining patterns of CD117 had been noticed in a few cases. In addition, 54 GISTs were also positive for CD34 (72.9%), 25 cases positive for SMA , 5 cases positive for S-100 and 5 cases positive for desmin. According to the Fletcher′s scheme, GISTs in this study were divided into 4 subcategories including groups of very low risk of aggressive behavior (3 cases), of low risk (15 cases), of intermediate risk (36 cases) and of high risk (20 cases) respectively. Kaplan-Meier survival analysis of 31 GIST cases whom had been followed up for 16 to 72 months showed a statistically significant difference present among the subcategories (P<0.01). Conclusions GISTs predominantly occur in the middle and old age patients, more common in male, and positive CD117 staining is considered to be the defining marker to differentiate GIST from other mesenchymal tumors of the GI tract. Positive CD34 immun-staining, plus a CD117 positivity, strengthens further a diagnosis of GIST. Subclassification of GISTs using Fletcher′s scheme appears to be simple, reproducible, and correlates well with the clinical behavior of the tumor.