Argani Pedram, Aulmann Sebastian, Karanjawala Zarir, Fraser Robert B, Ladanyi Marc, Rodriguez Maria M
Department of Pathology, The Johns Hopkins Hospital, The Johns Hopkins University, Baltimore, MD 21231-2410, USA.
Am J Surg Pathol. 2009 Apr;33(4):609-19. doi: 10.1097/PAS.0b013e31818fbdff.
We describe 2 cases of malignant melanotic epithelioid renal neoplasms bearing TFE3 gene fusions. Both neoplasms occurred in children (an 11-y-old boy and a 12-y-old girl), and presented with disseminated metastatic disease including mediastinal and mesenteric adenopathy. Both neoplasms featured sheets of epithelioid cells with clear to finely granular eosinophilic cytoplasm set in a branching capillary vasculature. The neoplastic cells contained variable amounts of finely brown pigment confirmed to be melanin by histochemical stains. By immunohistochemistry, the neoplastic cells labeled for melanocytic markers HMB45 and Melan A, but not for S100 protein, MiTF, or any epithelial marker (cytokeratins, epithelial membrane antigen), renal tubular marker (CD10, PAX8, PAX2, RCC Marker) or muscle marker (actin, desmin). Both neoplasms demonstrated nuclear labeling for TFE3 protein by immunohistochemistry, and the presence of TFE3 gene fusions was confirmed by TFE3 fluorescence in situ hybridization analysis. These distinctive neoplasms combine morphologic features of perivascular epithelioid cell neoplasms (PEComas), Xp11 translocation carcinoma, and melanoma, though the phenotype most closely approaches PEComa. These neoplasms represent the first documented examples in which TFE3 gene fusions coexist with melanin production, and their identification raises the possibility that TFE3 gene fusions may underlie an aggressive subset of lesions currently classified as PEComa in young patients.
我们描述了2例携带TFE3基因融合的恶性黑素性上皮样肾肿瘤。这2例肿瘤均发生于儿童（1例11岁男孩和1例12岁女孩），表现为播散性转移性疾病，包括纵隔和肠系膜淋巴结肿大。这2例肿瘤均具有成片的上皮样细胞，其胞质清亮至细颗粒状嗜酸性，位于分支状毛细血管脉管系统中。肿瘤细胞含有不同量的细棕色色素，经组织化学染色证实为黑色素。免疫组织化学检测显示，肿瘤细胞表达黑素细胞标志物HMB45和Melan A，但不表达S100蛋白、MiTF或任何上皮标志物（细胞角蛋白、上皮膜抗原）、肾小管标志物（CD10、PAX8、PAX2、RCC标志物）或肌肉标志物（肌动蛋白、结蛋白）。这2例肿瘤经免疫组织化学检测均显示TFE3蛋白核染色阳性，且通过TFE3荧光原位杂交分析证实存在TFE3基因融合。这些独特的肿瘤兼具血管周上皮样细胞瘤（PEComas）、Xp11易位癌和黑色素瘤的形态学特征，尽管其表型最接近PEComa。这些肿瘤是首次记录的TFE3基因融合与黑色素生成并存的病例，它们的发现提示TFE3基因融合可能是目前归类为年轻患者PEComa的侵袭性病变亚群的潜在原因。
