Abstract：
OBJECTIVE: TFE3-rearranged renal cell carcinomas (RCCs) harbor gene fusions between TFE3 and 1 of many partner genes. MED15::TFE3 fusion RCC is rare, often cystic, and easily misdiagnosed.
METHODS: This study aimed to characterize 2 cases of MED15::TFE3 fusion RCC with extensive cystic change using fluorescence in situ hybridization and targeted RNA sequencing.
RESULTS: Both patients were young adult women aged 29 and 35 years. Radiologically, both presented with a cystic Bosniak category II renal lesion. The cysts measured 9.3 cm and 4.8 cm in greatest dimension. Both patients underwent cyst enucleation, and neither had tumor recurrence or metastasis at 26 and 6 months of follow-up, respectively. Microscopically, both tumors were entirely cystic, with thick, fibrous cystic walls lined by small clusters of cells with clear to eosinophilic cytoplasm and uniform, round nuclei with inconspicuous nucleoli. There were also small aggregations of similar clear cells within the cystic walls. Foci of basement membrane-like material depositions were noted in 1 case; calcifications were observed in both cases. Both cases demonstrated nuclear positivity for PAX8 and TFE3 and cytoplasmic staining for Melan-A; HMB45, CAIX, and CK7 were negative. Fluorescence in situ hybridization revealed that both tumors were positive for TFE3 rearrangements. RNA sequencing identified MED15::TFE3 gene fusions in both cases.
CONCLUSIONS: The main differential diagnosis of MED15::TFE3 fusion RCC includes multilocular cystic renal neoplasm of low malignant potential and atypical renal cysts. Molecular confirmation of TFE3 fusion is essential for establishing the correct diagnosis.
METHODS: This study aimed to characterize 2 cases of MED15::TFE3 fusion RCC with extensive cystic change using fluorescence in situ hybridization and targeted RNA sequencing.
RESULTS: Both patients were young adult women aged 29 and 35 years. Radiologically, both presented with a cystic Bosniak category II renal lesion. The cysts measured 9.3 cm and 4.8 cm in greatest dimension. Both patients underwent cyst enucleation, and neither had tumor recurrence or metastasis at 26 and 6 months of follow-up, respectively. Microscopically, both tumors were entirely cystic, with thick, fibrous cystic walls lined by small clusters of cells with clear to eosinophilic cytoplasm and uniform, round nuclei with inconspicuous nucleoli. There were also small aggregations of similar clear cells within the cystic walls. Foci of basement membrane-like material depositions were noted in 1 case; calcifications were observed in both cases. Both cases demonstrated nuclear positivity for PAX8 and TFE3 and cytoplasmic staining for Melan-A; HMB45, CAIX, and CK7 were negative. Fluorescence in situ hybridization revealed that both tumors were positive for TFE3 rearrangements. RNA sequencing identified MED15::TFE3 gene fusions in both cases.
CONCLUSIONS: The main differential diagnosis of MED15::TFE3 fusion RCC includes multilocular cystic renal neoplasm of low malignant potential and atypical renal cysts. Molecular confirmation of TFE3 fusion is essential for establishing the correct diagnosis.
摘要：
目的：TFE3重排的肾细胞癌（RCC）在TFE3和许多伴侣基因中的1之间存在基因融合。MED15::TFE3融合RCC是罕见的，通常是囊性的，容易误诊。
方法：本研究旨在通过荧光原位杂交和靶向RNA测序来表征2例具有广泛囊性改变的MED15::TFE3融合RCC。
结果：两名患者均为29岁和35岁的年轻成年女性。放射学上,两者均表现为囊性BosniakII类肾脏病变。囊肿的最大尺寸为9.3厘米和4.8厘米。两名患者都接受了囊肿摘除术，随访26个月和6个月均无肿瘤复发或转移，分别。微观上,两种肿瘤都是完全囊性的，厚厚的，纤维囊壁内衬小细胞簇，细胞质清晰至嗜酸性细胞，均匀，核仁不明显的圆形核。囊壁内也有类似透明细胞的小聚集。在1例中发现了基底膜样物质沉积的病灶；在两种情况下都观察到钙化。两例均显示PAX8和TFE3的核阳性和Melan-A的细胞质染色；HMB45，CAIX，CK7为阴性。荧光原位杂交显示两个肿瘤对TFE3重排均为阳性。RNA测序在两种情况下都鉴定了MED15::TFE3基因融合体。
结论：MED15::TFE3融合肾癌的主要鉴别诊断包括低恶性潜能的多房性囊性肾肿瘤和不典型的肾囊肿。TFE3融合的分子确认对于建立正确的诊断至关重要。
方法：本研究旨在通过荧光原位杂交和靶向RNA测序来表征2例具有广泛囊性改变的MED15::TFE3融合RCC。
结果：两名患者均为29岁和35岁的年轻成年女性。放射学上,两者均表现为囊性BosniakII类肾脏病变。囊肿的最大尺寸为9.3厘米和4.8厘米。两名患者都接受了囊肿摘除术，随访26个月和6个月均无肿瘤复发或转移，分别。微观上,两种肿瘤都是完全囊性的，厚厚的，纤维囊壁内衬小细胞簇，细胞质清晰至嗜酸性细胞，均匀，核仁不明显的圆形核。囊壁内也有类似透明细胞的小聚集。在1例中发现了基底膜样物质沉积的病灶；在两种情况下都观察到钙化。两例均显示PAX8和TFE3的核阳性和Melan-A的细胞质染色；HMB45，CAIX，CK7为阴性。荧光原位杂交显示两个肿瘤对TFE3重排均为阳性。RNA测序在两种情况下都鉴定了MED15::TFE3基因融合体。
结论：MED15::TFE3融合肾癌的主要鉴别诊断包括低恶性潜能的多房性囊性肾肿瘤和不典型的肾囊肿。TFE3融合的分子确认对于建立正确的诊断至关重要。
