Urothelial Carcinoma with Divergent Histologic Differentiation (Mixed Histologic Features) Predicts the Presence of Locally Advanced Bladder Cancer When Detected at Transurethral Resection

Objectives: The histologic classification of bladder tumors remains an important predictor of treatment response and patient outcome, with pure nonurothelial tumors associated with poorer outcome compared with pure urothelial carcinoma (UC). Little, however, is known about the significance of UC with divergent (mixed) histologic features at transurethral resection of bladder tumor (TURBT). This study examined the incidence, pathologic spectrum, and clinical significance of this phenomenon. Methods: The histologic patterns of 448 consecutive TURBT and 295 subsequent cystectomy specimens from this subgroup were analyzed. The type of divergent tumor differentiation observed in the mixed histologic type cases was categorized and quantified. Pure non-UC cases were excluded. Various clinicopathologic parameters were compared between the mixed histologic type and pure UC cohorts. Results: UC with mixed histologic features was identified in 25% of all TURBT specimens and was uniformly (100%) high grade and invasive (99%). The most common mixed histologic components were squamous (40%) and glandular (18%). Eleven percent of cases had multiple mixed histologic types. Compared with the pure high-grade UC, UCs with mixed histologic features were associated with muscle invasion at TURBT (chi-square test, P <0.001) and with extravesical disease at cystectomy (chi-square test, P = 0.0001). The presence of mixed histologic features at TURBT was an independent predictor of extravesical disease in a multivariate logistic model (P = 0.007). However, it was not significant for disease-specific survival in the univariate (P = 0.17) or multivariate (P = 0.68) models. Conclusions: The results of our study have shown that the presence of mixed histologic features at TURBT indicates locally aggressive disease. Patients with mixed histologic features might benefit from an aggressive multimodality treatment strategy.