Adrenal Gland, Cortex - Hyperplasia, Subcapsular

Adrenal cortical subcapsular hyperplasia (Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, and Figure 8) has been seen only in mice, and not in rats. It is a very common spontaneous finding in older mice of most strains, so incidences and severity generally increase with age. The lesion is also much more common and typically more extensive in female than in male mice. Subcapsular cell proliferation (hyperplasia and neoplasia) can be induced in certain mouse strains by gonadectomy.

This change is characterized by increased numbers of adrenal cortical subcapsular cells, generally considered to be the multipotential stem/progenitor cells that replenish senescent cells in the inner cortical zones. Under appropriate hormonal stimulation, the subcapsular cells can transdifferentiate into sex-steroid–producing cells resembling stromal gonadal cells. Two morphologically different types of subcapsular cells may be present in subcapsular hyperplastic lesions: elongated, spindle or fusiform type A cells (Figure 5) with elliptical nuclei and scanty basophilic cytoplasm, and larger, round or polygonal type B cells (Figure 6) with more abundant, pale to clear cytoplasm and round nuclei. Early hyperplastic lesions (Figure 1 and Figure 2) consist of small, often linear foci composed primarily of the spindle-like type A cells. The cell clusters are located initially in the zona glomerulosa adjacent to the capsule (Figure 1 and Figure 2), but as the cell aggregates enlarge due to proliferation, they extend centripetally as narrow to broad wedges intercalated between the underlying zona fasciculata cell cords and in linear sheets parallel to the adrenal capsule (Figure 1, Figure 2, and Figure 3). As the hyperplastic lesions enlarge, type B cells appear, and with further progression the ratio of polygonal type B cells to spindle type A cells usually increases (Figure 3 and Figure 4). Multiple foci in a given adrenal gland may coalesce to form an almost continuous band of hyperplastic cells subjacent to the capsule (Figure 7). Very large foci (Figure 8) are often composed almost entirely of polygonal type B cells, with few elongated type A cells, and can exhibit some degree of compression and expansion.

Focal subcapsular hyperplasia is considered a proliferative lesion in a morphologic continuum that can progress to adenoma and, rarely, to carcinoma. Subcapsular adenomas are also composed of variable mixtures of well-differentiated "spindle" and "polygonal" cells, so differentiating large focal hyperplasias from smaller adenomas can be challenging. Compared with hyperplastic foci, adenomas are larger, are more discretely nodular, clearly compress the adrenal parenchyma, and may even bulge prominently above the capsular surface due to pronounced expansile proliferation.