CIC重排肉瘤十例临床病理学分析

CIC-rearranged sarcoma:a clinicopathological analysis of 10 cases

目的探讨CIC重排肉瘤(CIC-rearranged sarcoma,CRS)的临床病理学特征、免疫表型和预后。方法回顾性分析复旦大学附属肿瘤医院病理科2017年1月至2018年12月间诊断的10例CRS的临床病理学资料,行免疫组织化学检测和荧光原位杂交检测,并复习相关文献。结果(1)男性5例,女性5例,平均年龄28岁(范围5~63岁)。8例发生于软组织,包括躯干3例、头颈部3例和下肢2例;分别发生于小肠和大脑枕叶各1例。肿瘤平均直径4.9 cm(范围1.5~8.0 cm)。(2)镜下由结节状、分叶状或片状分布的小至中等大圆形、卵圆形或短梭形细胞组成。核形不规则,常可见核仁。核分裂象易见。4例内可见坏死,其中1例显示大片地图状坏死。(3)免疫表型:9例表达CD99(9/10),其中8例为灶性或斑驳状表达,1例呈弥漫阳性。2例弥漫性表达WT1(2/4),Ki-67阳性指数70%(范围30%~90%)。(4)采用断裂分离探针荧光原位杂交(FISH)检测显示9例有CIC基因重排,1例可能存在CIC基因重排。(5)7例获得随访结果,平均随访12.1个月,5例发生局部复发;2例发生远处转移,发生复发/转移的平均和中位时间分别为8个月和4个月。2例患者死亡,1例带瘤生存,4例无瘤生存。结论CRS是EWSR1阴性小圆细胞肉瘤中最常见的一种类型,在临床表现和病理学上与骨外尤因肉瘤非常相似,但预后相对较差。对CD99灶性阳性但WT1弥漫阳性的小圆细胞肉瘤需考虑CRS的可能性,确诊需经FISH检测。

Objective To investigate the clinicopathologic features, immunophenotype and prognosis of CIC-rearranged sarcoma (CRS). Methods The clinical and pathological data of 10 cases of CRS diagnosed between January 2017 and December 2018 at the Department of Pathology,Fudan University Shanghai Cancer Center were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The literature was reviewed. Results There were five males and five females with a mean age of 28 years (range, 5 to 63 years). Eight tumors developed in the somatic soft tissues, including trunk (n=3),head and neck (n=3),and extremities (n=2). One case each arose in the small intestine and the occipital lobe. The average size was 4.9 cm (range,1.5-8.0 cm). Microscopically,all cases were composed of small to medium-sized round, oval to short spindled cells, showing nodular or lobular architecture, or were arranged in sheets. Compared with Ewing sarcoma, tumor cells of CRS usually showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Necrosis was present in four cases with one showing geographic necrosis. Immunohistochemically, tumor cells usually showed focal or patch staining of CD99 (9/10),diffuse and strong nuclear expression of WT1 in half cases (2/4),and a high Ki-67 index (median 70%). By FISH, nine cases demonstrated convincing break-apart signal of CIC gene. Follow-up data available in seven cases (mean 12.1 months);of these two patients died of disease (2/7), whereas one patient was alive with unresectable recurrent tumor,the remaining four patients were alive with no evidence of disease. Five patients (5/7) experienced local recurrence and two patients (2/7) developed metastasis. The mean and median intervals to recurrence/metastasis were eight months and four months, respectively. Conclusions CRS is the most common type of EWSR1-negative small round cell sarcoma (SRCS). Although it has clinical and pathological overlapping features with Ewing sarcoma,the prognosis is comparatively poor. Focal or patch staining of CD99 but diffuse staining of WT1 in a case of small RCS should raise the possibility of CRS. FISH assay is required for the final diagnosis.