Architectural Heterogeneity and Cribriform Pattern Predict Adverse Clinical Outcome for Gleason Grade 4 Prostatic Adenocarcinoma

Gleason grade 4 defines a group of prostatic adenocarcinomas with a variety of architectural patterns, including poorly formed glands, fused glands, and cribriform pattern. To address the relative contribution to clinical prognosis by these distinct patterns, the histology of 241 consecutive radical prostatectomy specimens with the highest Gleason grade of 4 was reviewed. The presence of poorly formed glands, fused glands, and cribriform pattern was recorded for each case, and the types of architectural patterns present were associated with patient outcome. In this population, prostatic adenocarcinomas demonstrated architectural heterogeneity, with 17% of cases exhibiting a single Gleason grade 4 pattern, and 41% of cases exhibiting all 3 morphologic patterns. Patients exhibiting all 3 architectural patterns had lower rates of biochemical disease-free survival (66% vs. 76% at 5 y; log rank P= 0.006). Twenty-two of 165 patients (13.3%) with cribriform pattern adenocarcinoma developed metastasis, whereas 2 of 76 patients (2.6%) without cribriform pattern developed metastasis at a median postoperative follow-up of 10.0 years. The presence of a cribriform pattern was an independent predictor for biochemical recurrence (hazard ratio 2.41; 95% confidence interval, 1.34-4.32; P = 0.003) as well as metastasis after radical prostatectomy (hazard ratio 5.62; 95% confidence interval, 1.29-24.5; P = 0.02). These results suggest that the morphologic sub-classification of distinct Gleason grade 4 architectural patterns provides prognostic information beyond the current Gleason classification system.