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Abstract：
Renal low-grade oncocytic tumor (LOT) is a recently recognized renal cell neoplasm designated within the \"other oncocytic tumors\" category in the 2022 World Health Organization classification system. Although the clinicopathologic, immunohistochemical, and molecular features reported for LOT have been largely consistent, the data are relatively limited. The morphologic overlap between LOT and other low-grade oncocytic neoplasms, particularly eosinophilic chromophobe renal cell carcinoma (E-chRCC), remains a controversial area in renal tumor classification. To address this uncertainty, we characterized and compared large cohorts of LOT (n = 67) and E-chRCC (n = 69) and revealed notable differences between the 2 entities. Clinically, LOT predominantly affected women, whereas E-chRCC showed a male predilection. Histologically, although almost all LOTs were dominated by a small-nested pattern, E-chRCC mainly showed solid and tubular architectures. Molecular analysis revealed that 87% of LOT cases harbored mutations in the tuberous sclerosis complex (TSC)-mTOR complex 1 (mTORC1) pathway, most frequently in MTOR and RHEB genes; a subset of LOT cases had chromosomal 7 and 19q gains. In contrast, E-chRCC lacked mTORC1 mutations, and 60% of cases displayed chromosomal losses characteristic of chRCC. We also explored the cell of origin for LOT and identified L1 cell adhesion molecule (L1CAM), a collecting duct and connecting tubule principal cell marker, as a highly sensitive and specific ancillary test for differentiating LOT from E-chRCC. This distinctive L1CAM immunohistochemical labeling suggests the principal cells as the cell of origin for LOT, unlike the intercalated cell origin of E-chRCC and oncocytoma. The ultrastructural analysis of LOT showed normal-appearing mitochondria and intracytoplasmic lumina with microvilli, different from what has been described for chRCC. Our study further supports LOT as a unique entity with a benign clinical course. Based on the likely cell of origin and its clinicopathologic characteristics, we propose that changing the nomenclature of LOT to \"Oncocytic Principal Cell Adenoma of the Kidney\" may be a better way to define and describe this entity.
摘要：
肾脏低度嗜酸细胞肿瘤（LOT）是一种最近公认的肾细胞肿瘤，在2022年WHO分类中被指定为“其他嗜酸细胞肿瘤”类别。虽然临床病理，免疫组织化学，报道的LOT的分子特征基本一致，数据相对有限。LOT和其他低度嗜酸细胞肿瘤的形态学重叠，特别是嗜酸性嗜色细胞肾细胞癌（E-chRCC），肾肿瘤分类仍是一个有争议的领域。为了解决这种不确定性，我们对LOT(n=67)和E-chRCC(n=69)的大型队列进行了表征和比较,发现两个实体之间存在显著差异.临床上,LOT主要影响女性，而E-chRCC表现出男性好感。组织学上,虽然几乎所有的大部分都由小嵌套模式主导，E-chRCC主要表现为固体和管状结构。分子分析显示，87％的LOT病例在TSC-mTOR复合物1（mTORC1）途径中存在突变，在MTOR和RHEB基因中最常见；LOT病例的一个子集具有染色体7和19q增益。相比之下,E-chRCC缺乏mTORC1突变，60％的病例表现出chRCC特有的染色体丢失。我们还探索了LOT的起源细胞，并鉴定了L1CAM，收集管和连接小管的主要细胞标记，作为区分LOT和E-chRCC的高度敏感和特异性的辅助测试。这种独特的L1CAM免疫组织化学标记表明主要细胞是LOT的起源细胞，与E-chRCC和嗜酸细胞瘤的嵌入细胞起源不同。LOT的超微结构分析显示线粒体和胞浆内腔正常，有微绒毛，与chRCC描述的不同。我们的研究进一步支持LOT作为良性临床过程的独特实体。根据可能的细胞来源及其临床病理特征，我们建议将LOT的命名法改为“肾嗜酸细胞主要细胞腺瘤”可能是定义和描述该实体的更好方法。
