JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC # 1903951): 10-year-old German shepherd dog
HISTORY: Incidental finding
HISTOPATHOLOGIC DESCRIPTION: Adrenal gland: Multifocally, expanding the subcapsular, intracapsular, and extracapsular cortical regions, there are unencapsulated nodules of polygonal cells arranged in nests and packets that resemble normal cells of the zona glomerulosa and zona reticularis. Nodules vary from 50um to 1mm in diameter and are separated into nests and packets by a fine fibrovascular stroma. In the largest extracapsular nodule there are small aggregates of basophilic granular material (mineral). There are multifocal nests of cells in the zona fasciculata and reticularis with abundant microvacuolated clear to yellow cytoplasm which peripheralizes the nucleus (lipoidal degeneration).
MORPHOLOGIC DIAGNOSIS: Adrenal gland: Hyperplasia, cortical, nodular, multifocal, mild, German shepherd dog, canine.
- Nodular adrenocortical hyperplasia is common in older dogs, horses, and cats
- Occurs as well-defined spherical nodules in the cortex, or attached to the capsule and can involve any of the three zones; nodules near the capsule resemble zona glomerulosa
- Nodular hyperplasia of the zona reticularis has been seen in animals with functional disturbances suggestive of androgen excess (i.e. greater muscle mass, well-developed crest, clitoral hypertrophy & mammary gland involution)
- Hypertrophy and hyperplasia of cells of the zona fasciculata & zona reticularis occur in response to an autonomous hypersecretion of ACTH by a corticotroph adenoma of the pituitary gland
- Hypertrophy and hyperplasia of the cells of the zona glomerulosa are often associated with long-term renin-angiotensin II excess
- In a recent study, the prevalence of adrenocortical hyperplasia increased with the increase in degree of adenohypophyseal proliferation from hyperplasia through microadenoma to macroadenoma
- Accessory cortical nodules may be seen in the capsule, cortex or medulla and may represent evaginations or invaginations of the outer cortex respectively
- Unknown; suggested that hyperplasia is due to hypersecretion of ACTH by the pituitary or that local ischemic atrophy triggers compensatory hyperplasia
- Accessory or ectopic nodules may be derived from mesenchymal tissue during embryonic migration
- In mice, gonadectomy at an early age can cause nodular cortical hyperplasia or neoplasia; pituitary gonadotropin is constantly produced due to the reduction in negative feedback; as the gonads and adrenal glands develop from the same embryonic structures, residual gonadal cells in the adrenal cortex may differentiate to form nodules or tumors due to the effects of gonadotropin
TYPICAL CLINICAL FINDINGS:
- Nodular cortical hyperplasia is usually an incidental lesion with no clinical evidence of adrenal cortical hyperfunction
TYPICAL GROSS FINDINGS:
- Well-defined, yellow, spherical, usually multiple and bilateral and can involve any of the three cortical zones
- May measure up to 2 cm in diameter and be subcapsular, intracapsular, or
attached to and prolapsing through the capsule
- Extracapsular accessory cortical nodules are also common and may extend into the periadrenal and perirenal adipose tissue
- Ectopic adrenocortical tissue may occur throughout the peritoneal cavity, especially in the reproductive tract, and occasionally in the kidneys of some rodents (choristoma); with age, nodules become larger, more numerous and more frequently extracapsular
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Hyperplastic nodules are multiple, usually bilateral, unencapsulated foci of adrenocortical cells that do not compress normal adjacent tissue
- Cells may be normal size or hypertrophied, but are often refractory to lipid depleting stresses that reduce lipid in the rest of the cortex
For gross finding of adrenal enlargement and/or adrenal gland nodules (note: Nodular hyperplasia may occur concurrently):
- Adenoma: These are well demarcated, encapsulated, single (normally unilateral), and often compress adjacent parenchyma; the cells resemble those of the zonae fasciculata or reticularis and are arranged in broad trabeculae or nests; adenomas may contain foci of mineralization, hematopoiesis, necrosis, or hemorrhage; functional adenomas can cause hyperadrenocorticism with atrophy of the affected and the contralateral gland
- Diffuse cortical hyperplasia: Uniform, bilateral hypertrophy/hyperplasia of cells in the zonae fasciculata and reticularis with compression of the outer zona glomerulosa
- Myelolipoma: Well-differentiated adipocytes and hematopoietic (both myeloid and lymphoid) tissue, often with focal mineralization or bone; most often in cattle and non-human primates; nonneoplastic
- Cortical carcinoma: Capsular invasion, indiscrete nodules, peripheral fibrosis, trabecular growth pattern, hemorrhage, swathes of necrosis; may be bilateral
- Ganglioneuroma in rats (rare)
- Nodular cortical hyperplasia and accessory/ectopic nodules have been described in horses, dogs, cats, rabbits, golden hamsters, rats, mice, beluga whales, and nonhuman primates
- Ferrets: Ectopic adrenocortical tissue is seen in 15% of clinically normal ferrets
- Proliferative adrenocortical lesions (hyperplasia, adenoma, or carcinoma) may cause truncal alopecia, vulvar swelling with mucoid discharge, and generalized pruritus; lesions are due to increased estrogens, NOT increased corticosteroids; may resemble intact females with prolonged estrus. Most consistent endocrinological change is increase in estradiol-17-beta.
- Miller MA, Bruyette DS, Scott-Moncrieff JC, et al. Histopathologic Findings in Canine Pituitary Glands. Vet Pathol. 2018; 55(6):871-879.
- Miller MA. Endocrine system. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier, Inc; 2017:707-709.
- Rosol TJ, Gröne, A. Endocrine glands. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed, St. Louis, MO: Elsevier; 2016: 343-345.
- Rosol TJ, Meuten DJ. Tumors of the endocrine glands. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: John Wiley & Sons, Inc; 2017: 782-778.