Adrenal gland & paraganglia

Adrenal cortical adenoma

Corticomedullary mixed tumor

Topic Completed: 1 December 2013

Minor changes: 12 November 2020

Copyright: 2003-2021,, Inc.

PubMed Search: Corticomedullary mixed tumor

Carmen Perrino, M.D.
Debra L. Zynger, M.D.
Page views in 2020: 1,341
Page views in 2021 to date: 1,346
Cite this page: Perrino C, Zynger D. Corticomedullary mixed tumor. website. Accessed December 2nd, 2021.
Definition / general
  • Single adrenal mass comprised of intimately intermixed adrenal cortical cells and pheochromocytes, which show histologic features of their respective neoplasms (Ann Diagn Pathol 2001;5:304)
  • Not well understood - most common theory is collision tumor, based on distinct embryologic origins of adrenal cortex (mesoderm) and medulla (neural crest/ectoderm)
  • Another theory is that tumor is a pheochromocytoma mixed with adrenal cortical tissue, caused by pheochromocytoma production of ACTH or catecholamines, which stimulate pituitary corticotroph cells to produce ACTH, which leads to adrenocortical hyperplasia or an adrenal cortical adenoma
  • Both components are believed to be neoplastic (Ann Diagn Pathol 2001;5:304)
Clinical features
  • Variable, include symptoms attributed to adrenal cortical or adrenal medullary cells
  • Most common: hypertension, diabetes (Surg Today 2013;43:1232)
  • Also abdominal pain, amenorrhea, Cushing syndrome, flank pain, hair loss, hyperglycemia, hypertension, irritability, weight loss
  • Variable, related to functioning adrenal cortical or adrenal medullary cells
  • Reported elevated laboratory values:
    • Serum: cortisol, norepinephrine/noradrenaline, epinephrine/adrenaline, metanephrine, normetanephrine, aldosterone
    • Urine: cortisol, norepinephrine/noradrenaline, epinephrine/adrenaline, metanephrines, dopamine, vanillylmandelic acid (VMA), glucocorticoids
Radiology description
  • Adrenal mass detected by CT or MRI
Case reports
  • Surgical resection
Gross description
  • No obvious gross findings to distinguish from other adrenal lesions
  • Solitary, well-circumscribed
  • Color: tan, dark brown, yellow-orange, patchy gray areas
  • Size: 2.5 – 9 cm
  • Weight: 22 - 65 gm
  • Mixed corticomedullary carcinoma (Surg Today 2013;43:1232, Endocr Pract 2012;18:e37):
    • Size: 8 - 10 cm
    • Weight: 125 – 325 gm
    • Necrosis, focal hemorrhage
Microscopic (histologic) description
  • Cortical component: compact clear cells with uniform nuclei and clear to lightly eosinophilic cytoplasm, arranged in nests and cords
  • Medullary component: chromaffin cells are polygonal with larger nuclei and granular basophilic cytoplasm, arranged in the typical growth pattern of pheochromocytoma
  • High incidence of co-existing neoplasms (myelolipoma, ganglioneuroma, spindle cell sarcoma) in same or contralateral adrenal gland (Surg Today 2013;43:1232)
  • Mixed corticomedullary carcinoma: geographic necrosis, marked pleomorphism, capsular invasion, lymphovascular space invasion, high mitotic rate, atypical mitotic figures
Microscopic (histologic) images

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Clear cytoplasm and coarse chromatin

Pheochromocytoma component

Adrenocortical adenoma component

Tumor thrombosis and recanalization of vascular channels

Pheochromocytoma cells are positive for chromogranin, synaptophysin, NSE

Sustentacular cells, S100+

Positive stains
  • Cortical component: inhibin, MelanA, synaptophysin, calretinin; also mitochondrial antigen 113-1, P450C21
  • Medullary component: chromogranin, synaptophysin
  • Sustentacular cells: S100
Negative stains
  • Vimentin, cytokeratin, adrenocorticotropic hormone (ACTH), calcitonin, somatostatin, serotonin
Electron microscopy description
  • 2 distinct cell populations (Arch Pathol Lab Med 2003;127:e329)
    • Adrenocortical cells: moderate amounts of lipid droplets, mitochondria with tubulovesicular cristae, lysosomes in cytoplasm
    • Medullary cells: numerous dense-core granules in cytoplasm, some partially filled with electron-dense secretory product
Electron microscopy images

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Neuroendocrine granules and smooth endoplasmic reticula

Molecular / cytogenetics description
  • No reported molecular/cytogenetic analysis
Differential diagnosis
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