Histopathological and genetic characterization of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion: a case series

Fallo, Francesco; Castellano, Isabella; Gomez-Sanchez, Celso E.; Rhayem, Yara; Pilon, Catia; Vicennati, Valentina; Santini, Donatella; Maffeis, Valeria; Fassina, Ambrogio; Mulatero, Paolo; Beuschlein, Felix und Reincke, Martin (2017): Histopathological and genetic characterization of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion: a case series. In: Endocrine, Bd. 58, Nr. 3: S. 503-512

Abstract

Purpose Aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion are reported in an increasing number of patients. Five aldosterone-producing adenomas from patients with primary aldosteronism and subclinical hypercortisolism were examined. The aims of our study were: (1) to analyze pathological features and immunohistochemical expression of CYP11B1 (11 beta-hydroxylase) and CYP11B2 (aldosterone synthase) in these tumors;(2) to investigate somatic mutations involved in adrenal steroid hypersecretion and/or tumor growth. Methods Archival micro-dissected paraffin-embedded slides from tumor specimens were used for histological and molecular studies. Immunohistochemistry was performed using monoclonal anti-CYP11B1 and anti-CYP11B2 antibodies. Cellular composition was determined by examining for known features of zona fasciculata and zona glomerulosa, and immunoreactivity for CYP11B1 and CYP11B2 by McCarty H-score. Spot regions for mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, PRKACA, and CTNNB1 gene sequences were evaluated. Results Four APAs showed a predominant (>= 50%) zona fasciculata-like cell pattern: one tumor had CYP11B1 H-score = 150, no detectable CYP11B2 expression, and harbored a PRKACA p.Leu206Arg mutation (that we have reported previously elsewhere), one had no CYP11B1 expression, CYP11B2 H-score = 40, and no mutations;the remaining two adenomas had high CYP11B1 H-score (160 and 240, respectively) and low CYP11B2 H-score (30 and 15, respectively), with the latter harboring a CTNNB1 p.Ser45Phe activating mutation. One of five aldosterone-producing adenomas had a predominant zona glomerulosa-like pattern, CYP11B1 H-score = 15, CYP11B2 H-score = 180, and no mutations. Conclusions The majority of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion were composed mainly of zona fasciculata-like cells, while CYP11B1 and CYP11B2 immunostaining demonstrated clear heterogeneity. In a subset of cases, different somatic mutations may be involved in hormone excess and tumor formation.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1355-008X
• Sprache: Englisch