Exploring the metastatic potential of isolated tumour cells and clusters-cords patterns of ISUP Grade 5 acinar adenocarcinoma of the prostate: a comprehensive morphological analysis

Gleason pattern 5 (GP5) prostatic adenocarcinoma (PC) includes distinct morphologies: undifferentiated solid pattern (US), solid and cribriform with necrosis (CN), clusters and cords (CC), and isolated single tumour cells (ISTC). The role of these patterns in the metastatic setting is still poorly understood. We conducted a case-control retrospective histological characterization of two cohorts of ISUP Grade Group 5 PC, one with nodal metastases (N1) and one without (N0), comparing GP5 sub-patterns distribution, from robot-assisted radical prostatectomies with extended lymphadenectomy diagnosed between January 2013 and February 2023. A series of PC distant metastases was also retrieved and analyzed. The different GPs and their percentage were determined in lymph nodes, primary tumours, and distant metastases. A total of 88 PC N1, 70 PC N0, and 51 distant metastases were identified. Among the N1 cohort, GP5 was documented in 28/88 nodal metastases (32%), with US and CN documented in 16/88 (18%) and 9/88 (10%) cases, respectively. Overall, 79/88 patients had ISTC/CC in primary PC, but only 11 cases (14%) developed ISTC/CC in corresponding nodal metastases (p < 0.00001). In contrast, cribriform (CR) pattern was present in 75/88 lymph nodes (87%). In distant metastases, US predominated (27/51, 53%), while ISTC/CC were detected only in 6/51 cases (12%) and as a secondary pattern. Our results might suggest the existence of an intrinsic different metastatic potential of the ISTC/CC pattern, compared with CR or US, or of extrinsic environmental factors preventing their development in metastatic settings. These findings may support reconsideration of ISTC/CC as part of GP5.