Original Articles Pathologic Features of Occult Prostatic Carcinoma in Hypogonadal Men Ping L. Zhang, MD, PhD,* Glenn Bubley, MD, † Melissa Upton, MD,* Abraham Morgentaler, MD, ‡ William C. DeWolf, MD, ‡ and Seymour Rosen, MD* *Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, U.S.A. † Division of Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, U.S.A. ‡ Division of Urology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, U.S.A. ABSTRACT Objectives: Androgen therapy in hypogonadal men with low free testosterone levels (< 1.5 ng/dl) is po- tentially dangerous because exogenous androgen may stimulate occult prostatic adenocarcinoma (PA). Our previous study reported occult PA (14% incidence) in hypogonadal men with normal prostate specific anti- gen (PSA) levels and normal findings on digital rectal examination (DRE). The purpose of the current study was to examine the extent and nature of PA in pros- tatectomy specimens of hypogonadal patients. Materials and Methods: PA in these14 patients (the hypogonadal group) was compared to a control group of patients (n = 14). The two groups of patients were matched with similar mean ages, Gleason scores, and percentage of core involvement by PA. Subsequently, PA in prostatectomy specimens was analyzed in the two groups with additional comparison of immuno- histochemical sections for androgen receptors, PSA, and prostatic acid phosphatase. Results: As expected, patients in the hypogonadal group had significantly lower levels of PSA and free testosterone than those in the control group (PSA 2.32 ± 0.60 ng/ml versus 8.06 ± 1.17 ng/ml, respectively; free testosterone 1.17 ± 0.09 ng/dl versus 1.74 ± 0.20 ng/dl, respectively). Prostatectomy specimens in hy- pogonadal patients (n = 9) showed a less extensive PA (0% positive margins, 11% perineural invasion, 78% unilateral tumor, and 22% bilateral tumor) compared to control prostatectomy specimens (n = 14) (21% positive margins, 42% perineural invasion, 21% uni- lateral tumor, and 58% bilateral tumor). However, immunohistochemical studies using anti-androgen re- ceptor, anti-PSA and anti-prostatic acid phosphatase antibodies showed that carcinoma cells stained with equivalent intensity in both groups. Conclusions: PA in hypogonadal patients who had normal DREs and PSA levels appears to be less exten- sive but otherwise is not morphologically different than usual and should be treated in the same manner. The high incidence of occult PA in these hypogonadal patients makes screening prostate biopsies important before the androgen replacement therapy. INTRODUCTION Serum prostate specific antigen (PSA) levels and the digital rectal examination (DRE) are the two most common clinical methods to screen patients for prostatic adenocarcinoma (PA). The influ- ence of testosterone on PSA levels is controver- sial. Although PSA levels for men with sexual dysfunction or PA have been reported to show no correlation with testosterone level, when tes- tosterone level is within the normal range (1,2), medical or surgical androgen ablation produces prompt reduction in PSA levels (3). In addition, the administration of finasteride, a specific com- Address correspondence and reprint requests to: Seymour Rosen, MD, Department of Pathology, Beth Israel Deacon- ess Medical Center, East Campus, 330 Brookline Avenue, Boston, MA 02215, U.S.A. © 2000, Blackwell Science, Inc. 1095-5100/00/$15.00/0 The Prostate Journal, Volume 2, Number 2, 2000 74–79 74