Al-Obaidy Khaleel I, Bridge Julia A, Cheng Liang, Sumegi Janos, Reuter Victor E, Benayed Ryma, Hameed Meera, Williamson Sean R, Hes Ondrej, Alruwaii Fatimah I, Segal Jeremy P, Wanjari Pankhuri, Idrees Muhammad T, Nassiri Mehdi, Eble John N, Grignon David J
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Division of Molecular Pathology, ProPath, Dallas, TX, USA.
Mod Pathol. 2021 Oct;34(10):1921-1934. doi: 10.1038/s41379-021-00833-7. Epub 2021 Jun 7.
Thyroid-like follicular renal cell carcinoma is an uncommon kidney tumor with no distinct molecular alteration described to date. This cohort of eight women with mean and median ages of 45 and 46 years, respectively (range 19-65 years), had unencapsulated, well-circumscribed tumors composed of tightly packed anastomosing follicle-like cysts filled with eosinophilic colloid-like material and lined by cuboidal cells with high nuclear to cytoplasmic ratios, oval to elongated nuclei with perpendicular arrangement toward the lumens, and prominent nuclear overlapping. The stroma between these was minimal with the exception of two tumors. Calcifications and necrosis were absent. Immunohistochemically, the tumors were positive for KRT19 (7/7), PAX8 (5/5), cyclin D1 (6/6), KRT7 (5/7), and AMACR (1/5; focal, weak), and were negative for WT1, TTF1 (transcription termination factor-1), and thyroglobulin. In three of three tumors tested molecularly, EWSR1-PATZ1 fusion was identified by RNA sequencing and confirmed by RT-PCR and Sanger sequencing. Over a follow-up period of 1-7 years, no evidence of recurrence or metastasis has been detected. The EWSR1-PATZ1 fusion has been recognized as a recurrent alteration in a subset of round to spindle cell sarcomas with EWSR1-non-ETS fusions (EWSR1-PATZ1 sarcoma) and in several central nervous system tumors. The finding of an EWSR1-PATZ1 fusion in all three of the thyroid-like follicular renal cell carcinomas for which sufficient tissue was available for genomic profiling provides the first distinct molecular abnormality in thyroid-like follicular renal cell carcinomas, supporting its designation as a distinct diagnostic entity.
甲状腺样滤泡性肾细胞癌是一种罕见的肾肿瘤，迄今为止尚未发现明确的分子改变。该队列中的8名女性，平均年龄和中位年龄分别为45岁和46岁（范围19 - 65岁），患有未被包膜、边界清晰的肿瘤，由紧密排列的相互吻合的滤泡样囊肿组成，囊肿内充满嗜酸性胶体样物质，内衬立方体细胞，核质比高，核呈椭圆形至细长形，向管腔垂直排列，核重叠明显。除两个肿瘤外，其间质极少。无钙化和坏死。免疫组化显示，肿瘤KRT19（7/7）、PAX8（5/5）、细胞周期蛋白D1（6/6）、KRT7（5/7）和AMACR（1/5；局灶性、弱阳性）呈阳性，WT1、TTF1（转录终止因子-1）和甲状腺球蛋白呈阴性。在三个进行分子检测 的肿瘤中，通过RNA测序鉴定出EWSR1-PATZ1融合，并经RT-PCR和桑格测序证实。在1至7年的随访期内，未发现复发或转移迹象。EWSR1-PATZ1融合已被认为是圆形至梭形细胞肉瘤（EWSR1-非ETS融合，EWSR1-PATZ1肉瘤）和几种中枢神经系统肿瘤中的一种复发性改变。在所有三个有足够组织进行基因组分析的甲状腺样滤泡性肾细胞癌中均发现EWSR1-PATZ1融合，这为甲状腺样滤泡性肾细胞癌提供了首个明确的分子异常，支持将其指定为一个独特的诊断实体。
