伴有色素分化的Xp11易位性肿瘤的临床病理学特征

Xp11 neoplasma with melanocytic differentiation: a clinicopathological analysis

目的 探讨伴有色素分化的Xp11易位性肿瘤(Xp11 neoplasm with melanocytic differentiation)的临床病理特征、免疫表型、分子特征及预后.方法 收集解放军东部战区总医院南京大学医学院附属金陵医院2008年5月至2018年5月诊断的21例伴有色素分化的Xp11易位性肿瘤,进行光镜观察,行免疫组织化学、荧光原位杂交、TFE3相关融合基因扩增研究,并随访.结果 患者男性7例,女性14例.发病年龄4~57岁,平均年龄32.8岁.发病部位:肾脏11例,盆腔3例,胰腺、腹膜后、肾上腺、小肠、前列腺、宫颈及阑尾各1例.组织学上,肿瘤由丰富的纤维血管网分隔呈巢状或腺泡状结构,缺乏乳头状结构,肿瘤细胞呈上皮样,胞质透明至嗜酸,核仁可见,缺乏梭形细胞及脂肪成分.大多数病例中(16/21)出现黑色素沉着.21例均强阳性表达TFE3和Cathepsin K.18例色素性标记HMB45/Melan A中等至强阳性表达,3例HMB45/Melan A灶性阳性.所有病例均不表达平滑肌肌动蛋白、结蛋白、广谱细胞角蛋白、S-100蛋白和PAX8.荧光原位杂交检测:TFE3分离探针显示21例均存在异常TFE3分离信号;TFE3相关融合探针显示16例SFPQ-TFE3融合信号,2例NONO-TFE3融合信号,1例ASPL-TFE3融合信号,1例MED15-TFE3融合信号,另1例未测得融合基因信号.逆转录聚合酶链式反应:9例扩增出SFPQ-TFE3融合基因,1例扩增出NONO-TFE3融合基因,1例扩增出MED15-TFE3融合基因.15例获得随访资料,随访时间12~74个月,6例死亡,3例复发转移,6例无病生存.结论 伴有色素分化的Xp11易位性肿瘤具有独特的形态学特征、免疫表型及分子改变,具有侵袭性的生物学行为,属于恶性的间叶源性肿瘤,应与Xp11易位性肾癌及血管周上皮样细胞肿瘤区分开来,同时密切随访.

Objective To investigate the clinical,histologic and immunophenotypic features,genetic alterations and prognosis of the rare Xp11 neoplasm with melanocytic differentiation.Methods Twenty-one cases were selected from the Department of Pathology,Jingling Hospital,Nanjing University School of Medicine from May 2008 to May 2018.The clinicopathologic,immunohistochemical,molecular analysis and follow-up details were collected.Results There were 7 males and 14 females,with their ages ranging from 4 to 57 years(mean 32.8 years).The tumors were located in kidney(11 cases),pelvis(three cases),and in pancreas,retroperitoneum,adrenal gland,small intestine,prostate,cervix and appendix(one case each).Microscopically,most tumors shared similar morphology such as purely nested or sheet-like architectures separated by a delicate vascular network,purely epithelioid cells with clear to granular eosinophilic cytoplasm,lacks of papillary structures,spindle cell or fat components,uniform round to oval nuclei with small visible nucleoli,and in most of them(16/21)melanin pigment.Immunohistochemically,all cases showed moderately(2+)or strongly(3+)positive staining for TFE3 and Cathepsin K.HMB45 and Melan A were focally expressed in three of 21 cases,while the remaining cases showed typically moderate(2+)or strong(3+)expression.None of the cases were immunoreactive for SMA,desmin,CKpan,S-100 and PAX8.All cases showed TFE3 rearrangement using fluorescence in-situ hybridization(FISH).Fusion FISH assays detected SFPQ-TFE3 gene fusion in 16 cases,NONO-TFE3 gene fusion in two,ASPL-TFE3 and MED15-TFE3 gene fusions in one case each.Polymerase chain reaction and direct sequencing detected SFPQ-TFE3 gene fusion in nine cases,NONO-TFE3 and MED15-TFE3 gene fusions in one case each.Clinical follow-up was available for 15 patients for 12 to 74 months.Six patients died of the disease;and three had recurrences and/or metastases.Six patients were alive with no evidence of disease after initial resection.Conclusions Xp11 neoplasm with melanocytic differentiation has unique morphologic,immunophenotypic and genetic characteristics.The tumor is aggressive,and should be differentiated from Xp11 translocation RCC and perivascular epithelioid cell tumor.