2022年WHO泌尿和男性生殖器肿瘤分类引入了几种新型肾脏实体,表现出具有特定突变背景的嗜酸性粒细胞/嗜酸性细胞特征。因此,分子技术,例如下一代测序(NGS),变得更常用于他们的评估。我们研究了12例肾脏低度嗜酸性细胞肿瘤(LOT)(来自11例患者),在一组210个嗜酸性粒细胞/嗜酸性细胞肾肿瘤中发现,在2019年10月至2023年5月期间在我们机构诊断,在此期间占所有嗜酸性粒细胞/嗜酸性细胞肾肿瘤的5.7%(12/210)。我们回顾了他们的临床病理,组织学,和免疫组织化学特征,以及它们的突变特征。我们还回顾了有关LOT的NGS衍生数据的文献,通过选择根据最初提出的标准进行LOT诊断的论文。中位年龄为65岁(平均:63.5;范围43-79),中位肿瘤大小为2.0cm(平均:2.2;范围:0.9-3.1)。所有肿瘤均为PAX8、CK7和GATA3阳性,CD117/KIT阴性或局灶性阳性。我们发现以下基因突变:MTOR((6/11),54.5%)),TSC1((2/11),18.2%)),1名同时患有NOTCH1和NOTCH4((1/11),9.1%))。在2/11(18.2%)患者中发现了野生型状态,并且一个肿瘤无法分析。对包括79个LOT的8项先前研究的回顾显示,调节哺乳动物雷帕霉素靶蛋白(mTOR)途径的基因中经常发生突变:MTOR(32/79(40.5%)),TSC1(21/79(26.6%)),和TSC2(9/79(11.4%))。其他突变基因包括PIK3CA,NF2和PTEN,通常不知道会影响mTOR途径,但可能充当上游和下游效应物。我们的研究表明,当应用适当的诊断标准时,LOT在常规实践中得到越来越多的诊断。我们还证实mTOR通路主要通过MTOR与该肿瘤的发病机制密切相关。TCS1和TSC2突变,但是其他基因也可能参与该途径的激活,尤其是在没有“规范”突变的LOT中。
The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (
LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of
LOT, by selecting papers in which
LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43-79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9-3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that
LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without \"canonical\" mutations.