ArticleFrontiers in immunology2026
Integrated clinicopathological, genomic, and immunophenotypic landscape of renal tubulocystic oncocytoma.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Renal tubulocystic oncocytoma (RTO) is an exceptionally rare variant of renal oncocytoma (RO) with poorly understood genetic underpinnings. This study aimed to characterize the clinicopathological features and genomic landscape of RTO to enhance diagnostic precision and elucidate its molecular profile. Methods: Whole-exome sequencing (WES) was performed on a pathologically confirmed case of RTO to identify somatic mutations. Bioinformatics filtering identified single-nucleotide variants (SNVs) and insertions/deletions (INDELs), which were screened against databases such as the Cancer Gene Census (CGC) to identify potential driver and predisposing genes. Findings were validated via Sanger sequencing. Immunohistochemistry (IHC) was utilized for diagnostic marker assessment and tumor microenvironment (TME) characterization. Furthermore, a literature-based analysis of reported RTO cases was conducted across multiple databases, including PubMed, Ovid, Google Scholar, EMBASE, and Scopus. Results: WES analysis identified 399 somatic SNVs and 91 INDELs, as well as mutations in 14 candidate predisposing genes and 27 candidate driver genes, including mutations in 3 predisposing genes (COL7A1, CSF3R, and MKL1) and 11 driver genes (ZFHX3, TSC2, NFATC2, TCF7L2, TLR4, RANBP17, ITK, NEB [Chr2:152499355], NUP214, FBN2, and NEB [Chr2:152544903]). Drug-target prediction and resistance analysis identified several variants with potential therapeutic relevance. IHC staining confirmed positive expression of CD117, EMA, and E-cadherin, supporting the differential diagnosis. TME profiling revealed an "immune-cold" phenotype characterized by low densities of CD4+, CD8+, and FOXP3+ T cells, CD19+ and CD20+ B cells, CD56+ and CD57+ NK cells, and CD163+ tumor-associated macrophages, alongside minimal checkpoint activity and focal fibroblast activation. A comparative analysis with eight previously reported cases further contextualized these clinicopathological and immunophenotypic findings. Conclusions: This study provides a comprehensive genomic characterization of RTO. The integration of molecular profiling, histopathology, and literature-based comparison broadens the understanding of RTO's molecular and immunophenotypic landscape, providing a foundation for future hypothesis-driven research.
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