The role of architectural patterns and cytologic features in the prognosis of clear cell renal cell carcinoma.

Abstract

632 Background: Clear cell renal cell carcinoma (ccRCC) exhibits a spectrum of clinical behavior and intratumoral heterogeneity histologically. Pathologic grading for ccRCC is primarily based on nucleolar size. Sarcomatoid and rhabdoid changes are known to be associated with aggressive behavior, the significance of the histopathologic heterogeneity occurring in ccRCC remains largely unknown. We evaluated the prognostic role of architectural patterns and cytologic features in ccRCC. Methods: We identified sequential ccRCC cases at our institution between 2006 and 2015 for which follow-up information was available beyond 1.5 years, excepting those who died sooner. Architectural patterns and cytologic features were predefined and quantitated in nephrectomy specimen slides, which were reviewed by an experienced GU pathologist. Nine novel architectural patterns and ten cytologic features were correlated with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves were generated to visualize survival distributions. Results: 549 cases met selection criteria and were comprehensively reviewed including 16 grade 1 (2.9%), 278 grade 2 (50.6%), 201 grade 3 (36.6%) and 54 grade 4 (9.8%). Pathologic tumor stage distribution included 63.9% pT1 (n = 351), 6.0% pT2 (n = 33), 27.5% pT3 (n = 151), and 2.6% pT4 (n = 14). Microcystic, tubular, bleeding follicles, and small compact nest patterns (n = 309), were associated with better DFS and OS. In contrast, large nests, thick trabecular, solid sheet, alveolar or papillary/pseudopapillary patterns (n = 240) were associated with worse DFS and OS (p < 0.0001). In addition to multinucleated giant cells, and sarcomatoid and rhabdoid changes, cytologic features including large intracytoplasmic eosinophilic inclusions, voluminous cytoplasm, cytoplasmic spindling, a giant nucleus with perinuclear halo, and a wrinkled nucleus with perinuclear halo were associated with worse DFS and OS (p < 0.0004). Conclusions: Architectural patterns and cytologic features observed in ccRCC predict tumor behavior and are associated with clinical prognosis. Evaluation of histopathologic heterogeneity may shed light on tumor biology and complement prognostic models.