Table 3_Case Report: Somatic GNAS and CACNA1D mutations responsible for adrenal cortisol-producing adenoma with multiple aldosterone-producing micronodules—concurrence of primary aldosteronism and mild autonomous cortisol secretion.docx

Adjacent to the main tumor, a histologically similar 0.4 cm cortical nodule rich in clear cells was observed. Immunohistochemical analysis revealed diffuse CYP11B1 staining in the main tumor, whereas adjacent scattered cortical cell clusters and nodules exhibited distinctively diffuse CYP11B2 positivity. Next-generation sequencing results revealed missense mutations in the GNAS (p.R201H) and CACNA1D genes (p.F1131L).</p>Conclusion<p>Our molecular findings from bulk tissue analysis identified somatic mutations in the GNAS and CACNA1D genes.

Although the lack of microdissection precludes definitively assigning each variant to a specific pathological component, we hypothesize that these mutations may serve as key drivers for concurrent PA and MACS associated with cortisol-producing adenoma and adjacent MAPM/APN. Furthermore, our data support the emerging concept that primary aldosteronism can originate from MAPM rather than just from conventional adrenal cortical adenomas.</p>