Adrenal gland and paraganglia
Adrenocortical adenoma
Corticomedullary mixed tumor

Author: Carmen Perrino, M.D. (see Authors page)

Editor: Debra Zynger, M.D.

Revised: 15 January 2016, last major update December 2013

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Corticomedullary mixed tumor
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)
Epidemiology
Pathophysiology
  • 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
Laboratory
  • 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
Treatment
  • 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
Gross Images

Well-circumscribed mass with a heterogeneous, tan-yellow cut surface

Micro 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
Micro Images

Images hosted on other servers:

Corticomedullary mixed tumor

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

Images hosted on other servers:

Adrenal medullary cells

Neuroendocrine granules and smooth endoplasmic reticula

Molecular / Cytogenetics Description
  • No reported molecular/cytogenetic analysis
Differential Diagnosis