Jenei Alex, Pósfai Boglárka, Dénes Borbála, Somorácz Áron, Forika Gertrud, Fintha Attila, Mészáros Zsófia, Kránitz Noémi, Micsik Tamás, Eizler Kornélia Veronika, Giba Nándor, Semjén Dávid, Kelemen Dóra, Salamon Ferenc, Schubert Anna, Cserni Gábor, Hajdu Adrienn, Varga Luca, Árvai Balázs, Sztankovics Dániel, Sebestyén Anna, Sánta Fanni, Simon Andrea, Engi Helga, Melegh Zsombor, Kuthi Levente
Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Pathol Oncol Res. 2025 Jun 2;31:1612150. doi: 10.3389/pore.2025.1612150. eCollection 2025.
Low-grade oncocytic tumor (LOT) of the kidney is a recently recognized renal neoplasm with distinctive morphologic, immunophenotypic, and molecular features that distinguish it from other eosinophilic tumors such as oncocytoma and chromophobe renal cell carcinoma (chRCC). This study presents a comprehensive analysis of 20 LOTs from 19 patients, integrating clinicopathological, immunohistochemical, and genetic data. LOTs typically appeared as small, unilateral, well-circumscribed tumors with a tan-brown cut surface, composed of uniform eosinophilic cells with round nuclei and occasional perinuclear halos. Key histological hallmarks included an extensive capillary network and central edematous areas without necrosis or significant atypia. Immunohistochemically, all tumors showed strong diffuse CK7 positivity and CD117 negativity, with universal expression of GATA3, GPNMB, and L1CAM. Whole-exome and panel-based sequencing revealed recurrent mutations in the mTOR signaling pathway, including , , and genes. mTORC1 activation was confirmed immunohistochemically in one case. No evidence of aggressive behavior or metastasis was observed during the follow-up period (median: 4.5 years). Comparative analysis demonstrated that LOT patients were diagnosed at an older age than those with chRCC and had smaller tumors overall. This study reinforces the notion that LOT is a distinct renal tumor entity with consistent morphology, immunoprofile, and mTOR-pathway-related genetic alterations. Despite overlapping features with other eosinophilic renal neoplasms, the specific immunohistochemical profile and indolent clinical course support LOT's classification as a unique diagnostic category.
肾低度嗜酸性细胞瘤（LOT）是一种最近才被认识的肾肿瘤，具有独特的形态学、免疫表型和分子特征，使其有别于其他嗜酸性肿瘤，如嗜酸性细胞瘤和嫌色肾细胞癌（chRCC）。本研究对19例患者的20个LOT进行了全面分析，整合了临床病理、免疫组化和基因数据。LOT通常表现为小的、单侧的、边界清楚的肿瘤，切面呈棕褐色，由核圆形、偶见核周晕的均匀嗜酸性细胞组成。关键的组织学特征包括广泛的毛细血管网和中央水肿区，无坏死或明显异型性。免疫组化方面，所有肿瘤均显示弥漫性CK7强阳性和CD117阴性，GATA3、GPNMB和L1CAM均呈普遍表达。全外显子测序和基于基因panel的测序揭示了mTOR信号通路中的复发性突变，包括 、 和 基因。在1例病例中通过免疫组化证实了mTORC1激活。随访期间（中位时间：4.5年）未观察到侵袭性行为或转移的证据。比较分析表明，LOT患者的诊断年龄比chRCC患者大，总体肿瘤较小。本研究强化了这样一种观念，即LOT是一种独特的肾肿瘤实体，具有一致的形态学、免疫表型和与mTOR通路相关的基因改变。尽管与其他嗜酸性肾肿瘤有重叠特征，但特定的免疫组化特征和惰性临床病程支持将LOT归类为一个独特的诊断类别。
