title: Genetic and Histopathologic Intertumor Heterogeneity in Primary Aldosteronism.
abstract: Whether primary aldosteronism (PA) is the consequence of a monoclonal or multiclonal process is unclear.
  
  
  
  A 48-year-old man with severe bilateral PA refractory to medical therapy underwent unilateral adrenalectomy of the dominant adrenal. Although computed tomography showed three left-sided cortical nodules, postsurgical histopathology and genetic analysis revealed five different adrenocortical adenomas. Two zona fasciculata (ZF)-like aldosterone-producing adenomas (APAs) each harbored distinct known somatic KCNJ5 mutations (L168R and T158A). A zona glomerulosa-like APA harbored a known CACNA1D G403R somatic mutation, whereas a zona reticularis-like adenoma, which was grossly black in pigmentation with histologic characteristics more associated with cortisol-producing adenomas, expressed CYP11B2, CYP17, and DHEA-ST by immunohistochemistry (IHC) and harbored no known somatic mutations. The fifth adenoma was ZF-type, negative for CYP11B2 and CYP17 IHC, and harbored no known somatic mutations.
  
  
  
  This case highlights complex intertumor heterogeneity in histology, steroidogenesis, and somatic mutations in multiple adrenocortical adenomas arising in a single patient with PA. These findings suggest that the syndrome of PA can involve heterogeneous and multiclonal functional adrenal adenomas.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109.|Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University, 980-0872 Sendai, Japan.|Division of Clinical Hypertension, Endocrinology, and Metabolism, Tohoku University, 980-0872 Sendai, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Omata
authors.affiliation: Department of Pathology, Tohoku University, 980-0872 Sendai, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Pathology, Tohoku University, 980-0872 Sendai, Japan.|Division of Pathology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 981-8558 Sendai, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Sharath K
authors.initials: SK
authors.lastname: Anand
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Barletta
authors.affiliation: Department of Pathology, Tohoku University, 980-0872 Sendai, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109.|Department of Medicine, University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: William E
authors.initials: WE
authors.lastname: Rainey
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109.|Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109.|Department of Urology, University of Michigan, Ann Arbor, Michigan 48109.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.affiliation: Center for Adrenal Disorders, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Anand
authors.initials: A
authors.lastname: Vaidya
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D020746:Calcium Channels, L-Type / Q000235:genetics; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism; D015383:Zona Fasciculata / Q000473:pathology; D015384:Zona Glomerulosa / Q000473:pathology; D015385:Zona Reticularis / Q000473:pathology
chemical_list: C472073:CACNA1D protein, human; D020746:Calcium Channels, L-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D019405:Cytochrome P-450 CYP11B2; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase