Alghamdi Mohammed, Chen Jie-Fu, Jungbluth Achim, Koutzaki Sirma, Palmer Matthew B, Al-Ahmadie Hikmat A, Fine Samson W, Gopalan Anuradha, Sarungbam Judy, Sirintrapun S Joseph, Tickoo Satish K, Reuter Victor E, Chen Ying-Bei
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania.
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Mod Pathol. 2024 May;37(5):100467. doi: 10.1016/j.modpat.2024.100467. Epub 2024 Mar 7.
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.
肾低度嗜酸细胞瘤（LOT）是一种最近才被认识的肾细胞肿瘤，在2022年世界卫生组织分类系统中被归类为“其他嗜酸细胞瘤”。尽管已报道的LOT的临床病理、免疫组化和分子特征在很大程度上是一致的，但相关数据相对有限。LOT与其他低度嗜酸细胞瘤，特别是嗜酸性嫌色肾细胞癌（E-chRCC）之间的形态学重叠，在肾肿瘤分类中仍然是一个有争议的领域。为了解决这一不确定性，我们对大量的LOT（n = 67）和E-chRCC（n = 69）队列进行了特征分析和比较，揭示了这两种实体之间的显著差异。临床上，LOT主要影响女性，而E-chRCC则以男性为主。组织学上，尽管几乎所有的LOT都以小巢状模式为主，但E-chRCC主要表现为实性和管状结构。分子分析显示，87%的LOT病例在结节性硬化复合物（TSC）-mTOR复合物1（mTORC1）途径中存在突变，最常见于MTOR和RHEB基因；一部分LOT病例有染色体7和19q增益。相比之下，E-chRCC缺乏mTORC1突变，60%的病例显示出嫌色肾细胞癌特征性的染色体缺失。我们还探索了LOT的起源细胞，并确定L1细胞粘附分子（L1CAM），一种集合管和连接小管主细胞标志物，作为区分LOT与E-chRCC的高度敏感和特异的辅助检测方法。这种独特的L1CAM免疫组化标记表明主细胞是LOT的起源细胞，这与E-chRCC和嗜酸细胞瘤的闰细胞起源不同。LOT的超微结构分析显示线粒体外观正常，胞质内有带微绒毛的管腔，这与已描述的嫌色肾细胞癌不同。我们的研究进一步支持LOT是一种具有良性临床病程的独特实体。基于可能的起源细胞及其临床病理特征，我们建议将LOT的命名改为“肾嗜酸主细胞腺瘤”可能是定义和描述该实体的更好方式。
