General
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• Normal cortex in adults is 2 cm thick
• Cortical extrusions: common into periadrenal fat; usually maintain attachment to adrenal gland
• Cortical cuff: adrenal cortical cells around adrenal central vein and its branches
• Richly vascularized; capsular blood vessels, nerves and lymphatics penetrate along connective tissue septae

• Zona glomerulosa: just beneath the adrenal capsule; secretes mineralocorticoids; composed of small clusters and short trabeculae of relatively small, well-defined cells, less cytoplasm than other cortical cells, lipid-poor and 15% of cortical volume
• Zona fasciculata: middle zone of adrenal cortex; secretes glucocorticoids; forms broad band of large cells with distinct membranes arranged in cords two cells wide; cytoplasm has numerous small lipid vacuoles, which may indent the central nucleus and resemble lipoblasts; 70-80% of cortical volume, lipid stores are depleted by ACTH
• Zona reticularis: innermost layer of cortex, secretes androgens and small amounts of glucocorticoids; grossly brown; haphazardly arranged cells, smaller than zona fasciculata cells, with granular and eosinophilic cytoplasm with lipofuscin but minimal lipid; thinner than zona glomerulosa or fasciculata

Micro images
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Fasciculata

Reticularis

Reticularis lipid stain

Fasciculata, reticularis and medulla

   

Cortical layers

Cross section

Positive stains
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• Low molecular weight cytokeratin, alpha inhibin, MelanA / A103, bcl2, synaptophysin (weak); variable vimentin

Negative stains
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• Chromogranin, epinephrine

Cytology description
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• May have aggregates of bare nuclei resembling metastatic small cell carcinoma (Mod Pathol 1991;4:594)

Electron microscopy description
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• Zona glomerulosa: sparse intracellular lipid, elliptical mitochondria with lamellar (plate-like) cristae; may have microvillous projections; no / rare lysosomes, lipofuscin or smooth endoplasmic reticulum
• Zona fasciculata: round / oval mitochondria with short and long tubular cristae; prominent lipid droplets, prominent smooth endoplasmic reticulum, moderate amounts of rough endoplasmic reticulum, microvillus cytoplasmic projections and more lysosomes than zona glomerulosa
• Zona reticularis: spherical / ovoid mitochondria with short and long tubular invaginations of inner membrane; abundant lipofuscin granules, lysosomes and microvilli; sparse lipid droplets

General
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• Region with basophilic staining cells with granular cytoplasm and no stored lipid
• Composed of neural crest cells called chromaffin cells (also called pheochromocytes, medullary cells) with a multilineage differentiation potential; also sustentacular cells
• Chromaffin cells: arranged in small nests and cords separated by prominent vasculature; take up chromium salts strongly, turns brown-black after exposure to Zenker's solution (potassium dichromate); large polygonal cells with poorly outlined borders, abundant granular and usually basophilic cytoplasm, mild variation in cell size; occasionally has PAS+ hyaline droplets
• Sustentacular cells: supporting cells, spindle cells at periphery of nests of chromaffin cells; associated with rich vasculature; S100+, difficult to identify with routine staining
• Ganglion cells: occasional single cells or small clusters associated with myelinated nerve bundles
• Central vein: has thick wall of smooth muscle
• Also many venous channels which drain blood from cortical sinusoids, pass through medulla to drain into medullary vein

Micro images
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Adrenal medulla

Positive stains
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• Chromogranin, synaptophysin, neurofilament, tyrosine hydroxylase, epinephrine and S100 (sustentacular cells)

Negative stains
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• Keratin, vimentin

Electron microscopy description
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• Numerous mitochondria
• Norepinephrine producing cells have 250 nm electron opaque neurosecretory granules, with prominent halo between granule membrane and dense core
• Epinephrine producing cells have 190 nm finely granular neurosecretory granules, filling the enclosing membrane and no halo
• Moderate amount of rough endoplasmic reticulum, interdigitating blunt cytoplasmic processes with poorly developed cell junctions
• Sustentacular cells have moderate amounts of rough endoplasmic reticulum and occasional lipid droplets, but no neurosecretory granules

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