Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Am J Surg Pathol. 2013 Jun;37(6):804-15. doi: 10.1097/PAS.0b013e31827e17cb.
Renal cell carcinoma (RCC) associated with Xp11.2 translocation is uncommon, characterized by several different translocations involving the TFE3 gene. We assessed the utility of break-apart fluorescence in situ hybridization (FISH) in establishing the diagnosis for suspected or unclassified cases with negative or equivocal TFE3 immunostaining by analyzing 24 renal cancers with break-apart TFE3 FISH and comparing the molecular findings with the results of TFE3 and cathepsin K immunostaining in the same tumors. Ten tumors were originally diagnosed as Xp11.2 RCC on the basis of positive TFE3 immunostaining, and 14 were originally considered unclassified RCCs with negative or equivocal TFE3 staining, but with a range of features suspicious for Xp11.2 RCC. Seventeen cases showed TFE3 rearrangement associated with Xp11.2 translocation by FISH, including all 13 tumors with moderate or strong TFE3 (n=10) or cathepsin K (n=7) immunoreactivity. FISH-positive cases showed negative or equivocal immunoreactivity for TFE3 or cathepsin K in 7 and 10 tumors, respectively (both=3). None had positive immunohistochemistry but negative FISH. Morphologic features were typical for Xp11.2 RCC in 10/17 tumors. Unusual features included 1 melanotic Xp11.2 renal cancer, 1 tumor with mixed features of Xp11.2 RCC and clear cell RCC, and other tumors mimicking clear cell RCC, multilocular cystic RCC, or high-grade urothelial carcinoma. Morphology mimicking high-grade urothelial carcinoma has not been previously reported in these tumors. Psammoma bodies, hyalinized stroma, and intracellular pigment were preferentially identified in FISH-positive cases compared with FISH-negative cases. Our results support the clinical application of a TFE3 break-apart FISH assay for diagnosis and confirmation of Xp11.2 RCC and further expand the histopathologic spectrum of these neoplasms to include tumors with unusual features. A renal tumor with pathologic or clinical features highly suggestive of translocation-associated RCC but exhibiting negative or equivocal TFE3 immunostaining should be evaluated by TFE3 FISH assay to fully assess this possibility.
Xp11.2 易位相关性肾细胞癌（RCC）不常见，其特征为涉及 TFE3 基因的几种不同易位。我们通过分析 24 例具有 TFE3 断裂分离荧光原位杂交（FISH）的肾细胞癌，比较了同一肿瘤中 TFE3 和组织蛋白酶 K 免疫染色的结果，评估了 TFE3 断裂分离 FISH 对可疑或未分类的 TFE3 免疫染色阴性或不确定病例诊断的应用。10 例肿瘤最初根据 TFE3 免疫染色阳性诊断为 Xp11.2 RCC，14 例最初被认为是未分类的 RCC，其 TFE3 染色阴性或不确定，但具有一系列疑似 Xp11.2 RCC 的特征。17 例病例通过 FISH 显示 TFE3 重排与 Xp11.2 易位相关，包括 13 例 TFE3（n=10）或组织蛋白酶 K（n=7）免疫反应性中等或强的肿瘤。FISH 阳性病例在 7 例和 10 例肿瘤中分别显示 TFE3 或组织蛋白酶 K 的阴性或不确定免疫反应性（均=3）。没有病例的免疫组化阳性但 FISH 阴性。10/17 例肿瘤的形态特征为 Xp11.2 RCC 典型。不常见的特征包括 1 例黑色素 Xp11.2 肾细胞癌、1 例 Xp11.2 RCC 与透明细胞 RCC 混合特征的肿瘤和其他模仿透明细胞 RCC、多房囊性 RCC 或高级尿路上皮癌的肿瘤。这些肿瘤中形态学模仿高级尿路上皮癌以前没有报道过。与 FISH 阴性病例相比，FISH 阳性病例中更优先识别出砂粒体、玻璃样基质和细胞内色素。我们的结果支持应用 TFE3 断裂分离 FISH 检测诊断和确认 Xp11.2 RCC，并进一步扩展这些肿瘤的组织病理学谱，包括具有不常见特征的肿瘤。具有强烈提示易位相关性 RCC 的病理或临床特征但 TFE3 免疫染色阴性或不确定的肾肿瘤应通过 TFE3 FISH 检测进行评估，以充分评估这种可能性。
