Abstract：
Acquired cystic disease associated renal cell carcinomas (ACD-RCC) are rare and their molecular and histopathological characteristics are still being explored. We therefore investigated the clinicopathologic and molecular characteristics of 31 tumors. The patients were predominantly male (n = 30), with tumors mainly left-sided (n = 17), unifocal (n = 19), and unilateral (n = 29) and a mean tumor size of 25 mm (range, 3-65 mm). Microscopically, several histologic patterns were present, including pure classic sieve-like (n = 4), and varied proportions of mixed classic sieve-like with papillary (n = 23), tubulocystic (n = 9), compact tubular (n = 4) and solid (n = 1) patterns. Calcium-oxalate crystals were seen in all tumors. Molecular analysis of 9 tumors using next generation sequencing showed alterations in SMARCB1 in 3 tumors (1 with frameshift deletion and 2 with copy number loss in chromosome 22 involving SMARCB1 region), however, INI1 stain was retained in all. Nonrecurrent genetic alterations in SETD2, NF1, NOTCH4, BRCA2 and CANT1 genes were also seen. Additionally, MTOR p.Pro351Ser was identified in one tumor. Copy number analysis showed gains in chromosome 16 (n = 5), 17 (n = 2) and 8 (n = 2) as well as loss in chromosome 22 (n = 2). In summary, ACD-RCC is a recognized subtype of kidney tumors, with several histological architectural patterns. Our molecular data identifies genetic alterations in chromatin modifying genes (SMARCB1 and SETD2), which may suggest a role of such genes in ACD-RCC development.
摘要：
获得性囊性疾病相关肾细胞癌（ACD-RCC）很少见，其分子和组织病理学特征仍在探索中。因此，我们研究了31个肿瘤的临床病理和分子特征。患者主要为男性（n=30），肿瘤主要为左侧（n=17），单焦点(n=19)，单侧（n=29），平均肿瘤大小为25mm（范围，3-65毫米）。微观上,存在几种组织学模式，包括纯经典筛状(n=4)，以及不同比例的经典筛状与乳头状混合(n=23)，微管细胞(n=9)，紧凑的管状（n=4）和固体（n=1）模式。在所有肿瘤中均可见草酸钙晶体。使用下一代测序对9种肿瘤进行的分子分析显示，3种肿瘤中SMARCB1的变化（1种具有移码缺失，2种具有22号染色体中涉及SMARCB1区域的拷贝数丢失），然而,INI1染色全部保留。在SETD2，NF1，NOTCH4，BRCA2和CANT1基因中也观察到非复发性遗传改变。此外,在一个肿瘤中鉴定出MTORp.Pro351Ser。拷贝数分析显示染色体16（n=5）增加，17(n=2)和8(n=2)以及22号染色体的缺失(n=2)。总之,ACD-RCC是公认的肾脏肿瘤亚型，通过几种组织学结构模式，我们的分子数据还确定了染色质修饰基因（SMARCB1和SETD2）的遗传改变，这可能表明这些基因在ACD-RCC发育中的作用。
