Clinical and Pathologic Effects of Diethylstilbestrol and Diethylstilbestrol Dipropionate on Carcinoma of the Prostate Gland. A Continuing Study

Abstract

The authors report on the clinical and histological findings on patients with adenocarcinoma of the prostate treated with diethylstilbestrol or diethylstilbestrol dipropionate. The drug was administered in large doses, one instance amounting to 1000 mg. (25,000,000 i.u.). In all 5 cases, including the fatal case, serial histologic examination showed definite regression in the carcinomatous tissues. There was a regression of metastic osseous lesions, as demonstrated by serial roentgenologic examination, in the single case in which such lesions were present, and a regression of metastases to the lymph nodes in another instance. Massive doses of diethylstilbestrol and diethylstilbestrol dipropionate were used without ill effects except for transient gyneco-mastia in a single instance. In a single patient who presented an apparent recurrence of the carcinomatous process a 2d course of treatment was as effective as the first in controlling symptoms and causing a demonstrable regression of the malignant neoplasm. The regressive histologic changes observed in stilbestrol-treated carcinomas of the prostate, as compared to the histology in untreated carcinoma, may be outlined as follows: (1) In the untreated specimen the neoplastic cells present large vesicular nuclei, prominent nucleoli, and granular, reticular cytoplasm. (2) In the first stage of regression there is a decrease in the size of the nuclei associated with condensation of the nuclear chromatin. Nucleoli are no longer visible and mitoses are absent. Cytoplasmic vacuoles appear and are located predominantly at the bases of the cells. (3) In the 2d stage of regression the nuclei are pyknotic. The cytoplasm is practically clear and the cell membranes have ruptured, with resulting coalescence of vacuoles. With the rupture of all the cell membranes, the pyknotic nuclei and the fragments of the membranes are clustered in the centers of the acinar spaces. (4) In the next stage of regression clear acinar spaces contain only remnants of pyknotic nuclei. (5) In the final stage, as the authors have so far observed it, only stroma, consisting of smooth muscle and fibrous tissue, remains. Accumulations of lymphocytes and macrophages and deposits of brown pigment are present in some parts of the stroma.