Pseudohyperplastic prostatic adenocarcinoma

Prostatic adenocarcinoma may uncommonly exhibit pseudohyperplastic patterns of growth, including complex large gland formations with papillary infoldings, luminal undulations, branching, and cystic dilatation. The incidence, spectrum of morphologic presentation, and prognostic implications of this histologic variant have not been defined. To characterize prostatic adenocarcinoma with pseudohyperplastic features, we studied 302 cases of prostatic carcinoma including 100 consecutive 18-gauge prostatic needle biopsies with adenocarcinoma and 202 consecutive, completely embedded radical prostatectomy specimens. Histomorphologic attributes of pseudohyperplastic regions were compiled and ranked in order of diagnostic utility. To address the biological potential of this variant, we compared prostatic adenocarcinoma with and without hyperplastic features for differences in histologic grade, tumor size, and pathologic stage. Two of 100 (2%) cases of adenocarcinoma in needle biopsies and 22 of 202 (11%) cases of adenocarcinoma in radical prostatectomies displayed pseudohyperplastic alterations. The pseudohyperplastic foci as sumed deceptively benign-appearing architectural forms, particularly at scanning magnification. At this level of examination, transition to typical, small acinar adenocarcinomas was a diagnostically helpful recognition clue. At higher magnification, the lining cells were cytologically malignant, with significant nucleomegaly and nucleolomegaly. Similar to usual hyperplasia, the malignant cells in the pseudohyperplastic carcinomatous foci were often columnar with pale to slightly granular cytoplasm, and displayed basally situated nuclei. Basal cells were completely lacking in the pseudohyperplastic foci, which was confirmed by immunohistologic staining with antibody 34 beta E12,. The mean diameter of the pseudohyperplastic foci was 1 mm in needle biopsy and 3 mm (range, 1-7 mm) in radical prostatectomy tissues. In the latter tissue samples, the foci were fairly equally distributed in the peripheral zone (n = 12) and transition zone (n = 10) and were in direct continuity with either well-differentiated Gleason pattern 2 or moderately differentiated Gleason 3 pattern adenocarcinoma. Carcinomas with hyperplastic features were of lower Gleason score (median = 5) compared with carcinomas without hyperplastic features (median = 6; p = 0.013). These carcinomas with pseudohyperplastic areas were slightly but significantly larger (mean = 14.2% of gland) than carcinomas without pseudohyperplastic change (mean = 9.9% of gland; p = 0.038). The two groups did not exhibit pathologic stage differences (p = 0.7). We conclude that this unusual pseudohyperplastic variant pattern of prostate carcinoma growth is of slightly lower grade but probably does not impart prognostic information. The diagnostic significance of this pattern is that adenocarcinomas of the prostate with pseudohyperplastic features are lower-grade carcinomas that may be misdiagnosed as benign, usual epithelial hyperplasia.