Aldosterone-Producing Adenomas: Histopathology-Genotype Correlation and Identification of a Novel Mutation.

Mutations in , , , , and are thought to cause the excessive autonomous aldosterone secretion of aldosterone-producing adenomas (APAs). The histopathology of mutant APAs, the most common and largest, has been thoroughly investigated and shown to have a zona fasciculata-like composition. This study aims to characterize the histopathologic spectrum of the other genotypes and document the proliferation rate of the different sized APAs. Adrenals from 39 primary aldosteronism patients were immunohistochemically stained for CYP11B2 to confirm diagnosis of an APA. Twenty-eight adenomas had sufficient material for further analysis and were target sequenced at hot spots in the 5 causal genes. Ten adenomas had a mutation (35.7%), 7 adenomas had an mutation (25%), and 4 adenomas had a mutation (14.3%). One novel mutation in exon 28 of (V1153G) was identified. The mutation caused a hyperpolarizing shift of the voltage-dependent activation and inactivation and slowed the channel's inactivation kinetics. Immunohistochemical stainings of CYP17A1 as a zona fasciculata cell marker and Ki67 as a proliferation marker were used. mutant adenomas showed a strong expression of CYP17A1, whereas / mutant adenomas had a predominantly negative expression ( value =1.20×10). / mutant adenomas had twice the nuclei with intense staining of Ki67 than mutant adenomas (0.7% [0.5%-1.9%] versus 0.4% [0.3%-0.7%]; value =0.04). Further, 3 adenomas with either an mutation or a mutation had >30% nuclei with moderate Ki67 staining. In summary, similar to mutant APAs, and mutant adenomas have a seemingly specific histopathologic phenotype.