Evidence that Leydig cells in Sertoli-Leydig cell tumors have a reactive rather than a neoplastic profile

BACKGROUND. Leydig cells are a variable and an inconstant feature of Sertol i-Leydig cell tumors (SLCT). Controversy exists regarding their neoplastic versus reactive nature, and their molecular biologic profile is unknown. METHODS, Six SLCT and one pure Leydig cell tumor were studied. Mitotic coun ts and immunohistochemistry for Ki-67 were performed in all cases. Leydig c ells, neoplastic tissues, and normal nonneoplastic tissues were microdissec ted. DNA extracts of these samples were assessed for loss of heterozygosity (LOH) by polymerase chain reaction amplification with ten polymorphic DNA markers that have shown high rates of LOH in a variety of human tumors. Thr ee SLCT and the Leydig cell tumor were assessed for clonality by examining the DNA methylation pattern at a polymorphic site on the androgen receptor gene. RESULTS. Leydig cells in SLCT had a low mitotic count (0-1/50 high-power fi elds [HPF]) compared with the neoplastic stroma (median, 40/50 HPF). Ki-67 was positive in < 2% of Leydig cells in all SLCT, compared with a median of 7% in the neoplastic stroma. Clonality analysis confirmed the monoclonalit y of the neoplastic cells in the Leydig cell tumor. However, the Leydig cel ls from three SLCT were polyclonal, whereas the monoclonal nature of the ne oplastic Sertoli tubules was confirmed in one of these cases and that of mu cinous heterologous elements in another case. The Leydig cell tumor showed LOH at four of the eight loci evaluated. Leydig cells from five SLCT were e valuated: one showed LOH at one locus, two showed LOH at two loci, and the remaining two showed no LOH. CONCLUSIONS. The demonstration that Leydig cells from SLCT are polyclonal s trongly suggests that they are nonneoplastic in nature. This is supported b y a IOW proliferation fraction and a lower fraction of LOH compared with th e truly neoplastic Leydig cells. (C) 1999 American Cancer Society.