Morphological, immunohistochemical, stereological and nuclear shape characteristics of proliferative leydig cell alterations in rats

Abstract

Proliferative Leydig cell (LC) alterations (hyperplasia, adenoma) of laboratory rats often pose diagnostic problems because the progression from normal to hyperplasia to neoplasia is continuous. The LC compartments of 130 Wistar rats (kfm: WIST strain) of approximately 2 years of age were examined. Ten typical cases conventionally classified as being normal or as showing diffuse or focal hyperplasia or small or large adenomata were investigated in more detail. In large adenomata, areas with large and small LC nuclei were identified. Immunohistochemical characterization, EM examination, as well as stereologic and planimetric investigations were performed. Hyperplastic and neoplastic LC essentially retained their normal appearance and immunohistochemical characteristics, but were found to contain more lipid droplets, fibroblast-like cells and patches of collagen than normal LC at the EM level. LC proliferation was accompanied by significant LC hypertrophy. LC nuclei of hyperplastic LC compartments were slightly larger while those of LC adenoma were markedly larger than nuclei of normal LC. The values for circle-related and ellipticity factors indicated that the nuclei of normal and hyperplastic LC were more markedly oval than nuclei of neoplastic LC. Concavity factor and bending energy measurements revealed that the small and oval nuclei of normal and hyperplastic LC had significantly more and deeper indentations than the larger and somewhat rounder nuclei of neoplastic LC. It is concluded that LC proliferations conventionally diagnosed as hyperplasia or adenoma on the basis of their size were composed of cytologically different LC populations.