The Extent and Zonal Location of Prostatic Intraepithelial Neoplasia and Atypical Adenomatous Hyperplasia: Relationship with Carcinoma in Radical Prostatectomy Specimens

Abstract

High grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH) are considered putative precursors of prostatic adenocarcinoma. We determined the extent and zonal distribution of PIN and AAH in totally-embedded radical prostatectomies with prostate cancer, including 195 cases with PIN and 217 with AAH. PIN was identified in 86% of the cases. The mean volume of PIN was 1.32 cc (range, 0-8.12 cc), and was greater for PIN within 2 mm of cancer (mean, 1.0 cc) than for PIN more than 2 mm from cancer (mean, 0.3 cc). PIN was usually multicentric (64.5% of cases) and located in the non-transition zone (63%) or all zones (36%). The volume of PIN was positively correlated with the volume of cancer, patient age, pathologic stage and Gleason score. AAH was identified in 23.0% of the cases, and was more frequent in the transition zone (19.8% of cases) than in the non-transition (peripheral and central) zone (6.0%). The number of foci of AAH in the transition zone was always greater than that in the non-transition zone. AAH was frequently multicentric (46% of cases), especially in the transition zone (47% of transition zone cases) compared with the non-transition zone (23% of non-transition zone cases). The mean volume of AAH was 0.029 cc (range, 0-1.29 cc), and was much higher in the transition zone than in the non-transition zone. AAH was more common in older patients and those with greater prostatic weight, higher prostatic volume, greater percent of nodular hyperplasia, greater volume of cancer, greater percent of Gleason patterns 4 and 5 cancer, higher volume of prostatic intraepithelial neoplasia and higher serum prostate specific antigen concentration. Our results indicate that the extent and zonal distribution of high grade PIN and carcinoma are strongly associated, and that PIN is frequently multicentric; this supports the hypothesis that PIN is a premalignant lesion. AAH and carcinoma show a weak but significant association; if AAH is a premalignant lesion, it probably is associated with a subset of cancers arising in the transition zone.