Cytological Features of Metastatic Clear Cell Renal Cell Carcinoma Diagnosed on Cytology: A Single-Center Experience with Literature Review

Introduction: Renal cell carcinoma frequently metastasizes to multiple sites, which often poses significant diagnostic challenges, particularly when the primary tumor is unknown or occult. This retrospective study analyzed 43 fine-needle aspiration (FNA) cases of metastatic ccRCC from a single institution to characterize metastatic patterns and evaluate the diagnostic utility of cytology combined with immunocytochemistry. Materials and methods: We retrospectively reviewed FNA cases diagnosed as metastatic RCC from January 2003 to December 2024. Cytopathological evaluation included cellularity, architectural patterns, cytoplasmic and nuclear features, background elements, and immunocytochemical analysis when available. Results: Cytology demonstrated excellent diagnostic performance. The majority of cases were reported as Malignant (91%), while the remaining 9% were classified as Suspicious for Malignancy (SFM) or Atypia of Undetermined Significance (AUS). Notably, in 42% of cases, FNA established the initial diagnosis of RCC, highlighting its value in detecting occult primary tumors. Diagnostic accuracy relied on cytomorphologic evaluation, complemented by immunocytochemical profiling, which was performed on cell blocks in 60.4% of cases. Discussion: Key markers such as PAX8, CD10, and RCCma were critical in confirming renal origin and differentiating ccRCC from morphologically similar neoplasms in each organ. Conclusion: FNA cytology, corroborated by focused immunocytochemistry, plays a key role in diagnosing metastatic ccRCC, particularly when the presentation is uncommon or the primary tumor is hidden. This integrated method supports effective clinical management, avoiding unnecessary surgery in cases that may benefit from systemic therapy.