High WHO/ISUP Grade and Unfavorable Architecture, Rather Than Typing of Papillary Renal Cell Carcinoma, May Be Associated With Worse Prognosis

Conflicting data have been published on the prognostic significance of histologic parameters in papillary renal cell carcinoma (PRCC). We conducted a comprehensive evaluation of clinical and histologic parameters in PRCC in nephrectomies and their impact on prognosis, with an emphasis on World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade, tumor architecture (solid, micropapillary, and hobnail), and PRCC type. A total of 185 PRCC cases were evaluated, 117 (63.2%) type 1, 45 (24.3%) type 2, and 11 (5.9%) mixed type 1 and type 2. Using WHO/ISUP grading criteria, PRCCs were graded as follows: 6 (3.2%) grade 1; 116 (62.7%) grade 2; 61 (33.0%) grade 3; and 2 (1.1%) grade 4. The solid architecture was present in 3 cases (1.6%) and comprised 10%, 10%, and 30% of the tumor area. Micropapillary architecture was present in 10 cases (5.4%), ranging from 5% to 30% of the tumor (mean=11%; median=10%). Hobnail architecture was seen in 9 cases (4.9%), with mean percentage of 23% (median=15%; range: 5% to 50%) involvement of tumor area. Parameters associated with worse disease-free survival (DFS) and overall survival (OS) in the univariate analysis included WHO/ISUP grade, pathologic stage, tumor size, and solid, micropapillary, or hobnail architecture (P<0.05). The pathologic stage and WHO/ISUP grade were significantly associated with both DFS and OS in stepwise multivariate Cox regression analysis (P<0.05). In addition, micropapillary architecture and type 1 histology were linked with an adverse impact on OS (P<0.05). We found no difference in DFS (P=0.8237) and OS (P=0.8222) for type 1 versus type 2 PRCC in our patient cohort. In addition, we performed a meta-analysis with data from studies with reported hazard ratios (HRs) on PRCC type in relation to DFS and OS. We identified 5 studies that reported DFS and found no significant effect for type 2 PRCC (P=0.30; HR=1.43; 95% confidence interval: 0.73-2.80). We identified 7 studies that reported OS and found no significant association between type 2 PRCC and worse OS (P=0.41; HR: 1.21; 95% confidence interval: 0.77-1.91). Our findings suggest that high WHO/ISUP grade and unfavorable architecture (solid, micropapillary, or hobnail), rather than typing of PRCC, are associated with worse outcomes.