Hyperplastic foci in the cortex and medulla are generally rounded, circumscribed areas of variable diameter, characterized by increased numbers of cortical cells. In the cortex, the normal radial cord-like architecture is usually maintained. The hyperplastic foci can be well-demarcated or can blend almost imperceptibly with the adjacent normal tissue; compression is generally absent to minimal. Compared with normal cortical cells, hyperplastic cells are usually but not always smaller, with cytoplasm that can be vacuolated and/or tinctorially different (often more basophilic). In the medulla, foci of hyperplasia are often located at the periphery of the adrenal medulla, at or near the corticomedullary junction (Figure 7 and Figure 8), though they can also occur in the more central medulla (Figure 9 and Figure 10). Compared with normal medullary cells, hyperplastic cells are usually smaller with more basophilic cytoplasm (Figure 7, Figure 8, Figure 9, and Figure 10). In both the cortex and medulla, rare mitotic figures may be present, but the hyperplastic cells typically lack features of cellular atypia.
Cortical and medullary hyperplasia can be a spontaneous aging change, which occurs more commonly in rats than mice. Other causes of cortical hyperplasia include stress, and abnormally elevated adrenocorticotropic hormone (ACTH) levels due to any factor that perturbs the hypothalamic-pituitary-adrenal hormonal axis and/or adrenal steroidogenesis. Medullary hyperplasia can also result from experimental genetic modifications, dietary manipulations, and administration of various chemicals. Hyperplasia may also be a regenerative response to cell loss from degeneration, atrophy, or necrosis.
Focal cortical and medullary hyperplasias are considered proliferative lesions in a morphologic continuum that can progress to neoplasia (adenoma and carcinoma in the cortex and benign and malignant pheochromocytoma in the medulla). Differentiating large focal hyperplasias from smaller adenomas or pheochromocytomas can be challenging, but the neoplasms, compared with hyperplastic foci, are more compressive, exhibit more disorganization, and have some degree of cellular pleomorphism.
Cortical hyperplasia (increased cell numbers) and cortical hypertrophy (increased cell size) can often be concurrent lesions in the same gland or even in the same focus. Thus, as a practical matter, determining whether hyperplasia or hypertrophy is predominant in a given lesion and/or adrenal gland can be very difficult.
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