Cytomorphologic comparison of upper urinary tract urothelial carcinomas and renal cell carcinomas on urine cytology

Abstract

Introduction: Compared to urothelial carcinomas (UCs), the cytomorphology of renal cell carcinomas (RCCs) is underdescribed. This study aims to investigate whether UCs and RCCS of the upper urinary tract can be differentiated cytologically, and to identify distinguishing cytomorphological features. Methodology: Consecutive urine cytology specimens with atypical/C3, suspicious/C4 or malignant/C5 diagnoses matched with a nephrectomy or ureterectomy specimen with UC or RCC over a 15-year period were reviewed for cellularity, architecture, background composition and cytomorphologic features. Results: Totally 132 specimens were retrieved, comprising 24 RCCs and 108 UCs. Clear cell RCC (CCRCC) (n = 18) was the most common RCC. Urine cytology specimens from UC showed a trend of higher cellularity (p = 0.071) against RCC and was significant in subgroup analysis with CCRCC (p <.001). Epithelial structures in sheets, tubules, and papillae were exclusive in specimens of UC (p <.05). For background features, squamous cells were more common for RCC (p =.006) including CCRCC (p =.003), whereas polymorphs (p =.011) and necrotic material (p =.010) were associated with UC. Average nuclear size was larger and nuclear size variation (p <.001) and nuclear-cytoplasmic ratio (p =.001) were greater in UC (p =.001) than RCC. Comparing RCC to high-grade UCs only, nuclear-cytoplasmic ratio maintained statistical significance (p =.006) while average nuclear size showed a trend (p =.063). Conclusion: A clean background free of tumor necrosis and polymorphs, and the lack of complex tumor fragments favors RCC. UCs also display larger nuclear size, higher nuclear size variation and nuclear-cytoplasmic ratio. These cytomorphological features with corroboration of clinical/radiological findings, can aid in raising a diagnosis of RCC.