Genetic and Histopathologic Intertumor Heterogeneity in Primary Aldosteronism

Abstract

Context:

Whether primary aldosteronism (PA) is the consequence of a monoclonal or multiclonal process is unclear.

Case Description:

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.

Conclusions:

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.

Abstract

This study of a patient with multiple aldosterone-producing adenomas revealed complex intertumor heterogeneity in genetics, histology, and steroidogenesis, suggesting a multiclonal process.