子宫炎症性肌纤维母细胞瘤的临床病理学特征及分子病理学研究

Clinicopathological Characteristics and Molecular Pathology of Inflammatory Myofibroblastic Tumor of the Uterus

目的:探讨子宫炎症性肌纤维母细胞瘤(inflammatory myofibroblastic tumor,IMT)的临床病理及分子病理学特征.方法:收集5例子宫IMT,回顾性分析其临床资料、观察组织形态学改变、进行免疫组化染色和ALK基因荧光原位杂交(fluorescence in situ hybridization,FISH)检测,并采用二代测序(next-generation sequencing,NGS)方法检测包括ALK在内的507个癌基因点突变、插入、缺失、基因融合情况.结果:该组病例发病年龄为32~47岁,平均(39.60±5.12)岁,3例肿瘤位于子宫体肌壁间,2例位于子宫内膜下.显微镜下见梭形细胞肿瘤,富于黏液基质或者局部间质黏液样变.初始诊断3例为平滑肌肿瘤,2例为内膜间质肉瘤.5例免疫组织化学染色均为ALK阳性,ER、PR、Desmin阳性表达;4例患者的SMA免疫组化染色呈阳性表达,1例不表达;3例CD10染色呈阳性表达,2例不表达;5例患者均不表达CD117和CK;Ki-67的增殖指数除一例为40%外,其余均较低.ALK分离探针FISH检测显示4例阳性,1例阴性,后者经NGS检测证实存在ALK基因的融合.结论:ALK阳性是子宫IMT的一种高度特异的免疫组化标记,子宫IMT的免疫组化和RNA测序具有较高的一致性,可借此将IMT与子宫梭形细胞肿瘤鉴别.

Objective: To investigate the clinicopathological and molecular pathological features of inflammatory myofibroblastic tumor(IMT) of the uterus. Methods: Clinical data, histomorphological changes and immunohistochemical staining in 5 cases of uterine IMT were analyzed;fluorescence in situ hybridization(FISH) was used to assay ALK gene;next-generation sequencing(NGS) was used to detect the point mutation, insertion, deletion and gene fusion of 507 oncogenes including ALK. Results: The onset age of the patients was 32 ~ 47 years. The tumor in 3 patients was located between the muscular walls of the uterine body, and that in 2 patients was located between the muscular wall of the uterine body and the endometrium. Microscopically, all tumors were composed of spindle cells. Some parts were rich in mucus matrix or showed myxoid degeneration in local areas. Three cases were initially diagnosed as smooth muscle tumors, and 2 cases were endometrial stromal sarcoma. Immunohistochemical staining showed positive expression of ALK, ER, PR and Desmin in 5 cases. Immunohistochemical staining of SMA was positive in 4 patients. CD10 was positively expressed in 3 cases. CD117 and CK were not expressed in 5 patients. Ki-67 proliferative index was low except for one case, which was 40%. FISH showed 4 ALK-positive cases and one ALK-negative case, and the fusion of ALK gene was detected by NGS. Conclusion: IMT can be used for the differential diagnosis of spindle cell tumor of the uterus. Positive ALK expression is a highly specific immunohistochemical marker of uterine IMT. Results of immunohistochemistry is highly consistent with those of RNA sequencing of uterine IMT.