Mixed Sertoli-Leydig cell tumor and rete testis adenocarcinoma in rats treated with CdCl2.

Abstract

Sertoli cell tumors are, except in dogs,' rare testicular neoplasms; two have been reported in rats.' Tumors of the rete testis are even rarer. Not reported in rats, they have been described to occur spontaneously in old JCL : ICR mice,'O in Mustornys,y or in mice treated prenatally with diethylstilbestrol.' This report describes the morphology of a mixed SertoliLeydig cell tumor and a rete testis adenocarcinoma in Wistar rats [Crl : (WI)BR] from two long-term experiments on the carcinogenic potential of cadmium in males. A single subcutaneous (s.c.) injection of cadmium can induce acute vascular lesions in the testis and ischemic necrosis of the seminiferous tubules. Following resolution of the necrotic debris, periand intratubular fibrosis and mineralizations occur that may also involve the rete testis. Leydig cells, however, survive and give rise to interstitial cell t ~ m o r s . ~ The first study on cadmium carcinogenesis, started to determine the dose-response relationships for cadmium chloride (CdCl,) injected subcutaneously at approximately 8 weeks of age, involved 315 rats and lasted for 104 weeks. The second study, designed to investigate effects of zinc pretreatment on cadmium carcinogenesis, involved 364 rats for 104 weeks. Most organs and all altered tissues were fixed in neutral buffered formalin, trimmed, and processed for light microscopic investigation of hematoxylin and eosin (HE)-stained paraffin sections. Periodic acid-Schiffs (PAS) reaction with or without diastase pretreatment and the alcian blue-periodic acid-Schiff's reaction were also used. Toluidine blue-stained semithin sections were obtained from the Sertoli-Leydig cell tumor that was reembedded in epoxy resin. The mixed Sertoli-Leydig cell tumor was found in a 112week-old rat that had been treated with a single S.C. injection of 30 pmol CdClJkg and three S.C. injections of 0.1 mmol Zn-acetate 6 hours before, at the same time, and 18 hours after the CdCI, injection. At necropsy, the testes appeared atrophied. A red-brown nodule, 1-cm in diameter, was in one testis. By light microscopy, both testes had bilateral diffuse, severe peritubular fibrosis and intratubular mineralizations. One testis had a single Leydig cell tumor and the other had two separate neoplasms: a small Leydig cell tumor and a larger mixed Sertoli-Leydig cell tumor (Fig. 1). The tumor consisted mainly of variably sized and shaped tubuli expanding beyond the tunica vaginalis via the rete testis (Fig. 1). Intermixed were areas of round cells with eosinophilic cytoplasm that appeared to be of Leydig cell origin. Larger, more mature tubules were lined by spindle-shaped Sertolilike cells (Figs. 1-4) with basally oriented nuclei and pale vacuolated cytoplasm extending towards a lumen. Vacuola-