Department of Pathology, The University of Chicago, IL, USA.
Department of Pathology, The University of Chicago, IL, USA.
Hum Pathol. 2021 Sep;115:84-95. doi: 10.1016/j.humpath.2020.12.006. Epub 2020 Dec 22.
Unclassified renal cell carcinoma (RCC) accounts for ∼10% of renal tumors, and the most common histologic finding in these cases is eosinophilic cytoplasm. We previously demonstrated that a subset of eosinophilic renal tumors with heterogeneous morphology and immunohistochemical (IHC) staining harbored pathogenic mutations in tuberous sclerosis complex (TSC) or mammalian target of rapamycin (MTOR) as the primary defining mutation. We identified an additional 8 cases of eosinophilic tumors with unusual morphology that were originally diagnosed as chromophobe RCC (CHRCC) or CHRCC, eosinophilic variant. As a comparison, we included four classic CHRCC cases and one CHRCC, eosinophilic variant case. Gross examination revealed solid or solid and cystic patterns. The solid areas were composed of eosinophilic tumor cells divided by congested vessels, whereas the cystic areas were lined by cytologically bland eosinophilic cells with septae containing nests, ribbons, and single eosinophilic tumor cells. The tumor cells had abundant granular eosinophilic cytoplasm with round nuclei and inconspicuous nucleoli. IHC analysis demonstrated diffuse staining for CK7 and negative staining for CK20 and vimentin. Next-generation sequencing identified pathogenic variants in three genes: TSC1, TSC2, and MTOR. They also lacked significant copy number variations in contrast to our control cases. We have demonstrated with our expanded study that cases previously diagnosed as CHRCC or CHRCC, eosinophilic variant with discordant histology and IHC staining patterns may represent a separate subtype of RCC characterized by mutations in the TSC/MTOR pathway.
未分类的肾细胞癌（RCC）占肾脏肿瘤的 10%左右，这些病例中最常见的组织学发现是嗜酸性细胞质。我们之前的研究表明，一组具有异质性形态和免疫组织化学（IHC）染色的嗜酸性肾肿瘤，具有结节性硬化复合物（TSC）或哺乳动物雷帕霉素靶蛋白（MTOR）的致病性突变，作为主要的定义突变。我们又鉴定了 8 例形态异常的嗜酸性肿瘤，最初诊断为嫌色细胞 RCC（CHRCC）或嗜酸性变异型。作为比较，我们纳入了 4 例经典 CHRCC 病例和 1 例 CHRCC，嗜酸性变异型病例。大体检查显示实性或实性伴囊性模式。实性区域由被充血血管分隔的嗜酸性肿瘤细胞组成，而囊性区域由细胞学上温和的嗜酸性细胞组成，间隔含有巢、带和单个嗜酸性肿瘤细胞。肿瘤细胞具有丰富的颗粒状嗜酸性细胞质，圆形核，不明显的核仁。免疫组化分析显示 CK7 弥漫性染色，CK20 和波形蛋白阴性染色。下一代测序鉴定出三个基因的致病性变异：TSC1、TSC2 和 MTOR。与我们的对照病例相比，它们也没有明显的拷贝数变异。通过我们的扩展研究表明，以前诊断为 CHRCC 或 CHRCC，嗜酸性变异型，具有不一致的组织学和 IHC 染色模式的病例，可能代表一种由 TSC/MTOR 通路突变特征的 RCC 亚型。
