Spermatogenesis in pre-pubertal boys with Leydig cell neoplasms suggests paracrine stimulation by testosterone

Abstract

Pediatric Leydig cell tumors (LCTs) represent approximately 4% of pre-pubertal testicular tumors and are known to cause precocious puberty secondary to testosterone production. While gonadotropins and testosterone are known to initiate spermatogenesis beginning in puberty, it is yet to be determined if a similar phenomenon is triggered by isolated testosterone production in prepubescent boys. To determine if testicular pathology in pre-pubertal pediatric patients with LCTs exhibit spermatogenesis secondary to paracrine testosterone stimulation. We reviewed patients who underwent orchiectomy for a testicular tumor from 2003-17. We included patients with LCTs and compared them to children with non-LCT pathology (teratomas and epidermoid cysts). We excluded other pathologies and tumors in pubertal patients. Data were collected on the presence of spermatogenesis on pathology, tumor markers and serum hormone results. Orchiectomy for testicular tumors were completed in 66 patients, of which 20 were included in the non-LCT group and 9 in the LCT group. Two of the 9 LCT patients had bilateral pathology. Age at presentation was 6.3±5.8 years for the non-LCT group vs. 8.4±1.6 years for LCTs (p=0.261). Spermatogenesis was detected in 7 (64%) LCT specimens vs 2 (10%) non-LCT specimens (p=0.002). Age of the spermatogenesis patients in the non-LCT group (11.08±2.5 years) was older than LCT ones (8.3±2.0 years), suggesting that spermatogenesis in the non-LCT group may be due to early pubertal development. The summary figure demonstrates spermatogenesis identified in a pre-pubertal LCT patient. In this study, pre-pubertal males with LCTs were identified to have pathology evidence of spermatogenesis compared to controls with non-LCT pathology. This represents the first study assessing paracrine testosterone effects on spermatogenesis in pre-pubertal patients with LCTs. In contrast, adult literature on LCTs primarily report on resulting concerns for fertility, gynecomastia and testicular atrophy. LCTs can induce spermatogenesis in prepubertal patients. This reinforces the hypothesis that paracrine testosterone signaling plays a role in spermatogenesis. Our findings could help explore novel fertility preservation opportunities in children.