JPC SYSTEMIC PATHOLOGY

ENDOCRINE SYSTEM

January 2025

E-N08 (NP)

 

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 50µm 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.

 

GENERAL DISCUSSION: 

• Nodular adrenocortical hyperplasia is common in older dogs, cats, and horses
• Occurs as well-defined spherical nodules in the cortex, or attached to the capsule and can involve one or more of the three cortical zones 
• 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 may 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
• Accessory cortical nodules may be seen in the capsule, cortex or medulla and may represent evaginations or invaginations of the outer cortex respectively

PATHOGENESIS:

• Unknown; common finding is unregulated hypersecretion of ACTH by the anterior pituitary gland due to hyperplastic or neoplastic corticotrophs. 
• It is proposed that dogs without a pituitary gland lesion have an increased hypothalamic catabolism of dopamine leading to disruption of negative feedback control in the hypothalamic-pituitary-adrenal axis 

TYPICAL CLINICAL FINDINGS:

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; most commonly affected areas are the zona fasciculata and zona reticularis
• Nodules near the capsule most often resemble zona glomerulosa; sometimes it may also have areas that resemble the zona fasciculata
• Nodular hyperplasia of the zona reticularis may appear as discrete foci of cortical parenchyma extending into the medulla and result in an irregular corticomedullary junction. 
• Diffuse hyperplasia has irregular corticomedullary junction with projections of cortical cells often extending into the medulla
• May be extracapsular, subcapsular, or intracapsular

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Hyperplasia can be diffuse or nodular
• Hyperplastic nodules are usually multiple, bilateral, unencapsulated foci of 

adrenocortical cells that do not (usually) compress normal adjacent tissue

• Hyperplasia is often paler than adjacent unaffected cortical tissue
• Hyperplasia of the zona fasciculata and zona reticularis can compress the zona glomerulosa
• Cells may be normal size but are frequently hypertrophied; they are often refractory to lipid depleting stresses that reduce lipid in the rest of the cortex
• Cytology: Cellular samples with cells may be more tightly arranged compared with typical adrenocortical cells; cells have moderate to abundant amount of pale cytoplasm laden with discrete lipid vacuoles which can also punctate the background; background may contain naked nuclei
• Differentiation of adrenocortical nodular hyperplasia from well-differentiated adrenal neoplasm may be challenging cytologically

DIFFERENTIAL DIAGNOSIS: 

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
• Pheochromocytoma
• Ganglioneuroma in rats (rare)

 

COMPARATIVE PATHOLOGY:

• Mustelids: Ectopic adrenocortical tissue is common in ferrets and sea otters; adrenocortical nodular hyperplasia common age-related finding in otters
• Ferrets: Adrenal associated endocrinopathy is common in middle aged and older ferrets; early neutering causes chronic LH secretion due to loss of gonadal inhibitory feedback loop
  1. Multifocal proliferative adrenocortical (hyperplastic, adenoma or carcinoma) lesions in ferrets < 1 year of age; nodules of primitive adrenocortical cells found at the juxtamedullary region
  2. Clinical signs include 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
  3. Most consistent endocrinological change is increase in estradiol-17-beta
• Dolphins: Adrenal hyperplasia common in older delphinids; diffuse or nodular (cortical, medullary, extracapsular) hyperplasia of primarily the zona glomerulosa and zona fasciculata (but can affect all 3); no atypia or mitosis  incidental finding
• Rock hyraxes: Adrenal cortical hyperplasia reported in adults, similar to other species; concurrent pancreatic islet fibrosis and/or diabetes mellitus common

References:

1. Agnew D, Nofs S, Delaney MA, Rothenburger JL. Xenartha, Erinacoemorpha, Some Afrotheria, and Phloidota. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:523. 
2. Choi U, Arndt T. Chapter 17: Endocrine and Neuroendocrine Systems. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:609.
3. Little EK, Wills TB, Haldorson GJ. The Adrenal Gland. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:507-508. 
4. Miller MA. Endocrine System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:791-792.e1.
5. 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: 343-344.
6. St. Leger J, Raverty S, Mena A. Cetacea. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:533-568. 
7. Williams BH, Burek-Huntington KA, Miller M. Mustelids. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:288-289. 

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