Effect of combination endocrine therapy (LHRH agonist and flutamide) on normal prostate and prostatic adenocarcinoma. A histopathologic and immunohistochemical study.

The histopathology of 23 radical prostatectomies from patients with prostatic adenocarcinoma pretreated for 3-6 months with combination therapy including a luteinizing hormone-releasing hormone agonist and the antiandrogen drug flutamide was reviewed and compared with the pretreatment biopsies or transurethral resection material. After combination therapy, benign prostatic glands showed marked atrophy with prominent basal-cell layers, basal-cell hyperplasia, and epithelial-cell vacuolization. Immature squamous-cell metaplasia was present in seven cases. Residual carcinoma, on the other hand, was found in 19 of the 23 cases, and in 8 of these, tumor cells were either vacuolated or had scanty cytoplasm. Residual tumor was present as only one focus in 13 cases, and in 3 of these it was composed of single cells with a "hemangiopericytoma-like" pattern. An immunohistochemical study for prostatic acid phosphatase and prostatic-specific antigen could be carried out on paraffin blocks from 19 biopsies and 18 prostatectomies. After combination therapy, a reduction in staining (intensity and number of positive cells) was observed for the two markers in both normal prostate and carcinoma but with more pronounced effects on the latter. The present data show that temporary combination therapy before radical prostatectomy causes marked and very characteristic changes in normal prostatic tissue as well as in the prostatic tumor. These histologic patterns enter the differential diagnosis of a variety of atrophic, metaplastic, and proliferative lesions of the prostate gland. The pathologist must be aware of these histologic changes when looking at biopsy or resection material of treated patients.