Yang W P, Chang K T E, Xu H Y, Kuick C H, Ng E H Q, Huang H, Xiong F, Wu Y, Zeng S T, Fan J X, Loh X Y
Department of Pathology, Jiangxi Children's Hospital, Nanchang 330006, China.
Department of Pathology and Laboratory, KK Women's and Children's Hospital, Singapore 229899, Singapore.
Zhonghua Bing Li Xue Za Zhi. 2020 Jul 8;49(7):693-698. doi: 10.3760/cma.j.cn112151-20191217-00807.
To study clinical pathological characteristics, immunohistochemical, molecular genetical changes and prognosis in pediatric eosinophilic solid and cystic renal cell carcinoma (ESC RCC) with TSC2 gene mutations. The tissue samples were collected from two pediatric ESC RCC patients between 2017 and 2018. The tissues were subjected to histological examination and immunohistochemistry using EnVision system. The TFE3, TFEB gene rearrangements were tested using FISH and molecular genetic study. The paraffin sections were used for DNA extraction, PCR amplification and NGS sequencing. The two patients with ESC RCC were both male, aged at 9 years and 8 months, and 13 years, respectively. The tumors were from the right kidney, 5 cm and 7 cm in size, respectively, with solid and cystic changes in cross section, and grey-reddish or grey-whitish fish meat appearance. Microscopic observation revealed the tumors had fibrous capsules, which were infiltrated by the tumor cells. The tumor cells were diffusely distributed, round-shaped, or polygon-shaped, and had voluminous cytoplasm, eosinophilic cytoplasm, various sizes of vacuoles and clear cell-like appearance. There were papillary structures in some areas, with visible fiber septa. The nuclei were round and vesicular, with multi-nucleated cells and megakaryocytes. The mitoses were not seen. A few cystic structures were visible in different sizes, and capsule walls were covered with a single layer of spike-like tumor cells. Thick-walled blood vessels were seen in the stroma, with focal lymphocytic infiltration, eosinophilic necrosis, calcifications and cholesterol crystals. Immunohistochemistry of the tumor cells was positive for PAX8 (diffuse), CK20 (focal), CKpan (focal), CK10 (1 focal, 1 diffuse), INI1, vimentin, CD68, and Ki-67 (5%~10%); the tumor cells were negative for HMB45, S-100, Melan A, p53, desmin, TFE3, CK7, CK19, EMA, CD56, CgA, Syn, CD30, CD117, WT1 and SMA. Molecular genetic study showed that TFE3 and TFEB gene rearrangements were not detected by FISH. NGS sequencing showed TSC2 p.Lys574Ter (0.198) was found in patient one and TSC2 p.Arg406Ter (0.355) in patient two. ESC RCC in children is a rare disease, and can be misdiagnosed easily. It has unique pathological characteristics, and immunohistochemical, molecular and genetic changes. The prognosis is relatively good.
研究伴有TSC2基因突变的儿童嗜酸性实性和囊性肾细胞癌（ESC RCC）的临床病理特征、免疫组化、分子遗传学改变及预后。收集2017年至2018年间2例儿童ESC RCC患者的组织样本。对组织进行组织学检查及采用EnVision系统进行免疫组化。采用荧光原位杂交（FISH）和分子遗传学研究检测TFE3、TFEB基因重排。石蜡切片用于DNA提取、PCR扩增和二代测序（NGS）。2例ESC RCC患者均为男性，年龄分别为9岁8个月和13岁。肿瘤均来自右肾，大小分别为5 cm和7 cm，横断面有实性和囊性改变，呈灰红色或灰白色鱼肉样外观。显微镜观察显示肿瘤有纤维性包膜，肿瘤细胞浸润包膜。肿瘤细胞弥漫分布，呈圆形或多边形，胞质丰富，嗜酸性，有大小不一的空泡，呈透明细胞样外观。部分区域有乳头结构，可见纤维间隔。细胞核圆形，呈泡状，有多核细胞和巨核细胞。未见核分裂象。可见不同大小的一些囊性结构，囊壁覆盖单层钉状肿瘤细胞。间质中可见厚壁血管，有局灶性淋巴细胞浸润、嗜酸性坏死、钙化和胆固醇结晶。肿瘤细胞免疫组化PAX8（弥漫阳性）、CK20（局灶阳性）、CKpan（局灶阳性）、CK10（1例局灶阳性，1例弥漫阳性）、INI1、波形蛋白、CD68和Ki-67（5%~10%）阳性；肿瘤细胞HMB45、S-100、Melan A、p53、结蛋白、TFE3、CK7、CK19、EMA、CD56、嗜铬粒蛋白A、突触素、CD30、CD117、WT1和平滑肌肌动蛋白阴性。分子遗传学研究显示FISH未检测到TFE3和TFEB基因重排。NGS测序显示患者一发现TSC2 p.Lys574Ter（0.198），患者二发现TSC2 p.Arg406Ter（0.355）。儿童ESC RCC是一种罕见疾病，易被误诊。它具有独特的病理特征、免疫组化、分子和遗传学改变。预后相对较好。
