Do adenocarcinomas of the prostate with Gleason score (GS) ≤6 have the potential to metastasize to lymph nodes?

Although rare, there are cases within reported series of men with Gleason score (GS) ≤6 on radical prostatectomies that show pelvic lymph node (LN) metastases. However, there are no studies on whether pelvic LN metastases occur in tumors with GS ≤6 using the International Society of Urological Pathology (ISUP) updated GS system. We performed a search of the radical prostatectomy databases at 4 large academic centers for cases of GS ≤6. Only prostatectomies submitted and embedded in entirety with pelvic LN dissections were included. A combined total of 14,123 cases were identified, of which 22 cases had a positive LN. Histopathologic review of 19 cases (3 cases unavailable for review) showed higher grade than originally reported by the pathologists in all cases. Of the 17 pre-ISUP reviewed cases, 2 were upgraded to 4+3=7 with both cribriform and poorly formed glands. One case was upgraded to 4+3=7 with tertiary pattern 5 displaying cribriform glands, poorly formed glands, and cords of single cells. Eleven cases were upgraded to 3+4=7 with glomeruloid structures and small to large cribriform glands (1 of these also had features of ductal adenocarcinoma). Two cases had tertiary pattern 4 with small cribriform glands. One case had a prominent colloid component that would currently be graded as 4+5=9 because of large cribriform glands and solid sheets of cells within the mucin. Of the 2 post-ISUP cases, 1 demonstrated tertiary pattern 4, and the other showed GS 3+4=7 with irregular cribriform glands. Undergrading is the primary reason for LN positivity with GS ≤6, which has decreased significantly since the adoption of the ISUP grading system in 2005. Of over 14,000 totally embedded radical prostatectomies from multiple institutions, there was not a single case of a GS ≤6 tumor with LN metastases. In contrast to prevailing assumptions, GS ≤6 tumors do not appear to metastasize to LNs. Rather, Gleason pattern 4 or 5, as better defined by the current ISUP updated grading system, is required for metastatic disease.