Features and molecular genetic study of low-grade oncocytic tumor of the kidney.

内容摘要

To analyze the clinicopathological features of low-grade oncocytic tumor of the kidney (LOT) and to explore its cellular origin, immunohistochemical, and molecular characteristics. A retrospective analysis was conducted on the clinicopathological features and immunophenotypes of 7 cases of LOT diagnosed at two institutions from 2022 to 2025. The immunohistochemical expression of L1 cell adhesion molecule (L1CAM) was supplemented in LOT and control groups. High-throughput DNA targeted sequencing was applied to analyze the molecular genetic characteristics, and relevant literature was reviewed. Among the 7 patients, there were 2 males and 5 females, aged 52 to 74 years (median age 61 years). Tumor diameter ranged from 1.0 to 7.0 cm (mean diameter 3.9 cm). Grossly, the tumors were well-circumscribed, solid, and gray-brown. Microscopically, they exhibited a solid nested growth pattern with focal tubular structures. Edematous areas were observed in the stroma. Tumor cells had uniform round to oval nuclei and eosinophilic cytoplasm with perinuclear halos. Occasional binucleated cells were noted. Immunohistochemical staining showed that all cases were diffusely positive for CK7 and L1CAM, negative for CD117, and positive for PAX8, SDHB, and FH. Other markers including Vimentin, CD117, CD10, CAIX, P504S, TFE3, TFEB, and ALK (D5F3) were negative. High-throughput sequencing detected MTOR gene mutations in 6 cases, while non-mTOR pathway-related molecular alterations, including BRAF, LRP1B, and XRCC1, were identified in one case. Up to the last follow-up (median follow-up time 11 months), all patients were alive without disease progression. This study suggests that LOT may originate from principal cells of the collecting duct and distal renal tubule. Morphologically, it is characterized by a nested growth pattern with stromal edema, and immunohistochemically, it shows positivity for CK7 and negativity for CD117. The consistent positive expression of L1CAM in this study serves as a useful complementary marker for the differential diagnosis of LOT from other morphologically similar eosinophilic renal tumors. Regarding molecular genetics, this study not only explored the characteristics of mTOR pathway gene mutations in LOT but also identified one case with non-mTOR pathway-related molecular alterations, providing new supplementary information for the molecular landscape of LOT. Considering the cellular origin and indolent biological behavior of LOT, these findings contribute to further refinement of the classification system and nomenclature for this type of tumor. Additionally, this study provides important case data supporting LOT in the Chinese population.