单纯性骨囊肿临床影像病理与分子特征分析

Clinical,imaging and pathological and molecular characteristics of simple bone cyst

目的探讨单纯性骨囊肿(simple bone cyst,SBC)的临床影像学、病理形态学、分子遗传学特点、诊断及鉴别诊断。方法收集南京医科大学第一附属医院病理学部2017—2022年诊断为SBC的病例14例,行荧光原位杂交(FISH),回顾性分析影像学、病理学及分子遗传学特征。结果14例SBC中,男性7例,女性7例,年龄7~45岁(中位年龄29岁)。临床表现以局限性疼痛最为常见,其中4例伴有病理性骨折,5例伴有既往创伤史。最大径3.4~13.5 cm(中位5.6 cm),累及肱骨(5例)、髂骨(5例)、股骨(4例)。影像学诊断有SBC、动脉瘤性骨囊肿、骨巨细胞瘤、骨巨细胞瘤合并动脉瘤性骨囊肿样区域,以及纤维结构不良。形态学上,低倍镜下囊壁由纤维结缔组织构成,可以见到纤维蛋白样沉积物,部分有骨样基质及编织骨的形成。高倍镜下,囊壁可见呈胖梭形、卵圆形病变细胞,散在的破骨样巨细胞,堆积的泡沫样组织细胞,含铁血黄素的沉积以及胆固醇裂隙,6例可见类似结节性筋膜炎样的形态。免疫表型上,囊壁内衬细胞可见平滑肌肌动蛋白、上皮细胞膜抗原、SATB2不同程度的表达。14例均行FISH检测,发现9例涉及FUS或ESRW1基因的重排,其中1例行二代测序发现FUS::NFATC2融合。9例发生重排的SBC细胞密度略高,其中FUS::NFATC2融合患者复发标本可见核分裂象。14例随访5~105个月(平均46个月),其中FUS::NFATC2重排患者术后2次局部复发,第2次复发后行瘤段切除术34个月未复发,其余13例均无复发。结论SBC中有很大一部分存在EWSR1或FUS的重排,提示SBC可能是一个肿瘤性疾病。当影像学和形态学特征对于鉴别诊断SBC和动脉瘤性骨囊肿困难时,可结合FISH检测辅助鉴别。

Objective To investigate the radiologic,pathologic,and molecular features of simple bone cysts(SBC),and their differential diagnoses.Methods Fourteen cases of SBC were collected at the Department of Pathology,the First Affiliated Hospital of Nanjing Medical University from 2017 to 2022,and fluorescence in situ hybridization(FISH)was performed for retrospective analysis.Results There were 14 patients,including 7 females and 7 males,with age range of 7 to 45(median 29)years.The most common complaint was pain,including 4 cases with pathological fracture and 5 with history of previous trauma.The tumor size ranged from 3.4 to 13.5(median 5.6)cm.The lesion involved the femur(n=4),humerus(n=5)and iliac bone(n=5).Radiologic diagnoses included SBC,aneurysmal bone cyst,and giant cell tumor of the bone or its combination with aneurysmal bone cyst-like region and fibrous dysplasia.Histologically,the cyst walls of the lesions were composed of fibrous tissue,fibrin-like collagen deposits,bone-like matrix and occasional woven bone.The lesional cells were spindled to ovoid,with scattered osteoclast-like giant cells,foamy histiocytes,hemosiderin deposits and cholesterol clefts.In 6 cases there were nodular fasciitis-like areas.Immunohistochemically,the spindled to ovoid cells were positive for SMA,EMA and SATB2 in varying degrees.FISH detection was performed in all 14 cases and EWSR1/FUS rearrangement were found in 9 cases.One case of FUS::NFATC2 fusion was detected by next-generation sequencing.Nine cases of SBC with the rearrangement were more cellular,and there were more mitotic figures in the recurrent FUS::NFATC2 fusion tumor.Clinical follow-up was obtained in all 14 cases with the time ranging from 5 to 105(mean 46)months.Amongst them,the tumor with FUS::NFATC2 rearrangement had local recurrence twice after the first local excision,but had no more recurrence or metastasis 34 months after the subsequent segmental resection.The other 13 cases had no recurrence.Conclusions EWSR1 or FUS rearrangement is most commonly identified in SBC,suggesting that SBC might be a neoplastic disease.In cases where the radiologic appearance and histomorphology are difficult to differentiate from aneurysmal bone cyst,FISH detection can aid in the definitive diagnosis.