膀胱炎性肌纤维母细胞肿瘤临床病理及分子遗传学分析

Inflammatory myofibroblastic tumor of urinary bladder: clinicopathological and molecular genetic analyses

目的研究膀胱炎性肌纤维母细胞肿瘤(IMT)的临床病理及免疫表型特征,探讨其病理诊断、鉴别诊断、分子遗传学改变及其与预后的关系。方法回顾性分析收集7例膀胱IMT的临床和病理资料,应用免疫组化En Vision法染色检测ALK(D5F3)、AE1/AE3、vimentin、SMA、h-Caldesmon、Calponin、desmin、Ki-67以及鉴别诊断相关的其他标志物,运用荧光原位杂交(FISH)检测7例IMT中间变性淋巴瘤激酶(ALK)基因的易位情况。观察分析其病理形态特征、免疫表型特点并随访,同时复习相关文献。结果患者7例,男性4例,女性3例,年龄1267岁,中位年龄34岁。临床症状主要是肉眼血尿和排尿困难,无手术及外伤史,随访5例无复发,1例复发,1例失访。光镜下主要由增生的胖梭形纤维母细胞和肌纤维母细胞组成,呈束状或漩涡状排列,疏松或致密,细胞异型性不明显,可见核分裂象(<3个/10HPF),但无病理性核分裂象。肿瘤内均可见体积较大、核仁明显的节细胞样肌纤维母细胞。间质不同程度的炎细胞弥漫浸润,以成熟的浆细胞、淋巴细胞为主,可见明显的黏液样背景、组织疏松区及不同程度的玻璃样变。免疫组化:梭形细胞vimentin、SMA和h-Caldesmon均弥漫强(+),多数desmin和Calponin(+),AE1/AE3强(+),约多半数ALK(D5F3)(+)。FISH检测显示5例免疫组织化学ALK阳性的肿瘤存在ALK分离信号,其余2例为(-)。结论膀胱IMT是一种少见的中间型肿瘤且具有复发倾向及恶变潜能,术后应密切随访。该病需与其他多种梭形细胞肿瘤进行鉴别,以避免误诊及过度诊断。

Objective To investigate the clinicopathological features,immunohistochemic phenotypes,diagnosis,differential diagnosis,genetic alterations of inflammatory myofibroblastic tumor( IMT) of the urinary bladder and its correlation with prognosis. Methods The clinicopathologic features of seven cases of IMT of the urinary bladder were evaluated by histopathological, immunohistochemical and gene investigations with correlation of clinical follow-up.Immunohistochemistry was performed using En Vision method for ALK( D5 F3),AE1/AE3,vimentin,SMA,h-caldesmon,calponin,desmin,Ki-67,and other markers related to differential diagnosis. Fluorescence in situ hybridization( FISH)was used to detect the translocation of intermediate degeneration lymphoma kinase( ALK) gene in 7 cases of IMT. The biologic behavior was analyzed with follow-up data. The relevant literatures were reviewed. Results There were four males and three females among the seven patients. The age of the patients was 12 to 67 years,and the median age was 34 years. The main clinical symptoms were gross hematuria and dysuria. There was no history of surgery and trauma. Five cases were followed-up without recurrence,one case with recurrence,but one case was lost. Histologically,the majority of cases were composed of fat spindled fibroblasts and myofibrobhsts,arranged in bundles or spiral-shaped,loose or tight. It was not obvious nuclear atypia. The median mitotic figure was < 3/10 HPF,but no pathological mitotic fiigures. The lesion was frequently misdiagnosed as sarcoma,but the lack of nuclear atypia. Larger ganglion cell-like myofibroblasts were noted with prominent nucleoli. There was varying degrees of interstitial diffuse infiltration of inflammatory cells,mainly mature plasma cells and lymphocytes,with obvious myxoid background,and different degrees of hyaline degeneration in the interstitial tissue. Immunohistochemically,the tumor cells were positive diffusely for vimentin,SMA and h-caldesmon. Most tumor cells were positive for desmin and calponin. AE1/AE3 was strongly and diffusely positive. About more than half expressed ALK( D5F3). FISH detection showed that 5 cases of immunohistochemical ALK-positive tumors had ALK separation signals,which were positive cases,and the remaining 2 cases were negative. Conclusions IMT of the urinary bladder is a rare benign tumor,but a few cases have a tendency to recur and malignant potential. Therefore,patients should be closely followed up after operation. The disease must be distinguished from a variety of other spindle cell tumors,and more attention should be paid to avoid misdiagnosis and overdiagnosis.