乳腺隆突性皮肤纤维肉瘤21例临床病理及分子学特征

Dermatofibrosarcoma protuberans of the breast:clinicopathologic,and molecular analysis of 21 cases

目的探讨乳腺隆突性皮肤纤维肉瘤(dermatofibrosarcoma protuberans of the breast,DFSP-B)的临床病理学及分子学特征。方法回顾性分析21例DFSP-B的临床病理学、免疫表型及分子学特征,行HE、免疫组化及分子检测,并复习相关文献。结果21例DFSP-B患者男性6例,女性15例,年龄22~75岁(平均39.76岁,中位年龄36岁)。肿瘤最大径1~15 cm(平均4.7 cm,中位3 cm)。镜下瘤细胞呈席纹状、漩涡状及束状排列,核分裂象2~15个/10 HPF,侵犯脂肪及乳腺组织,符合DFSP-B;其中经典型DFSP-B 15例,经典型伴巨细胞纤维母细胞瘤(giant cell fibroblastoma,GCF)1例,黏液型2例,纤维肉瘤型隆突性皮肤纤维肉瘤(fibrosarcomatous-dermatofibrosarcoma protuberans,FS-DFSP)2例,FS-DFSP伴黏液型1例。免疫表型:CD34(21/21)、H3K27Me3(21/21)、β-catenin(21/21,胞膜)和WT-1(4/8,胞质)均阳性,Ki-67增殖指数为5%~50%。FISH检测DFSP-B中PDGFB基因分离阳性(7/8);3例FS-DFSP中PDGFB基因分离阳性(1/1),COL1A1-PDGFB融合阳性(1/1)。2例行NGS检测,其中1例FS-DFSP检测到CDKN2A基因(p.L16fs)突变及MSH6基因(p.F1088fs)突变;1例经典型伴GCF型检测到MLH1基因(p.R487)突变及TP53基因p.R273H体系突变。结论DFSP-B诊断需结合临床病理、免疫表型及PDGFB基因检测,治疗以手术切除为主,必要时可行放疗及靶向治疗,预后较好。

Purpose To investigate the clinicopathological,molecular features of dermatofibrosarcoma protuberans of the breast(DFSP-B).Methods The clinicopathological,immunophenotypic and molecular characteristics of DFSP-B in 21 cases were retrospectively analyzed with HE staining,immunohistochemical stainint and molecular detection,and relevant literatures were reviewed.Results There were 6 males and 15 males,aged 22-75 years(average 39.76 years,median 36 years).The maximum diameter of tumor was 1-15 cm(average 4.7 cm,median 3 cm).Pathologically,the tumor cells were arranged in story-form,swirling and fascicular,with mitotic figures 2-15/10 HPF.The tumors invaded adipose and mammary tissue.There were classic type(15/21),classic with giant cell fibroblastoma(GCF)(1/21),myxoid type(2/16),fibrosarcomatous-dermatofibrosarcoma protuberans(FS-DFSP)(2/16)and FS-DFSP with mucus type(1/16).Immunophenotype:tumor cells were positive for CD34(21/21),H3K27Me3(21/21),β-catenin(21/21,membrane)and WT-1(4/8,cytoplasm).Ki-67 proliferation index was about 5%-50%.PDGFB gene apart was detected by FISH in DFSP-B(7/8)and FS-DFSP(1/1).COL1A1-PDGFB fusion was detected in one case of FS-DFSP.Two cases were performed with NGS tests,in which mutations in CDKN2A gene(p.L16fs)and MSH6 gene(p.F1088fs)were detected in one case of FS-DFSP,and mutations in MLH1 gene(p.R487)and TP53 gene p.R273H system were detected in one case of classic with GCF type.Conclusion The diagnosis of DFSP-B should be combined with clinical,pathological,immunophenotype and PDGFB gene detection.Surgical resection is the main treatment,and radiotherapy and Gleevec targeted therapy could be used if necessary.The prognosis is good.