Does GATA3 Expression Contribute to the Diagnosis of Renal Tumors With Eosinophilic/Oncocytic Features?

In recent years, the emergence of newly characterized entities with eosinophilic/oncocytic cytoplasm has posed significant diagnostic challenges, particularly due to the overlapping morphologic features of chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). In this study, we analyzed the clinicopathological and immunohistochemical (IHC) characteristics of 49 eosinophilic renal tumors to determine whether GATA3 expression could aid in the differential diagnosis of these neoplasms. On the basis of integrated morphologic and IHC evaluation, the tumors were reclassified into the following diagnostic categories: ChRCC (n=15), RO (n=13), unclassified eosinophilic/oncocytic renal cell carcinoma (U-EO-RCC; n=9), low-grade oncocytic tumor (LOT; n=5), and eosinophilic clear cell renal cell carcinoma (E-CCRCC; n=3). In addition, the cohort included single cases of papillary renal neoplasm with reverse polarity (PRNRP), unclassified RCC with MiT family translocation-like features (U-MiTFL-RCC), SDHB-deficient RCC, and FH-deficient RCC. Notably, one of the U-EO-RCC cases was further characterized by the presence of a TSC mutation. All LOT cases, one SDHB-deficient RCC, one FH-deficient RCC, one PRNRP, and one of fifteen chromophobe RCC's had diffuse/strong staining with GATA3. In contrast, all E-CCRCC (n=3), renal oncocytoma (n=13), and U-MiTFL-RCC (n=1) cases demonstrated complete GATA3 negativity. In conclusion, GATA3 serves as a valuable diagnostic adjunct in the differential diagnosis of emerging eosinophilic renal tumor entities. However, due to its expression across diverse subtypes, GATA3 results must be interpreted within the morphologic context and as part of a comprehensive immunohistochemical panel-including K7, K20, CD117, vimentin, FH, SDHB, and cathepsin K-to avoid potential diagnostic pitfalls and ensure the accurate identification of clinically significant syndromes.