Relationship between flow cytometric DNA ploidy and nuclear grade with endocrine dysfunction in adrenal cortical adenomas

Abstract

Objectives. To determine the relationship among the DNA ploidy, histopathologic features, and clinical syndrome in adrenal cortical adenomas, because the cells often show variability in nuclear size and configuration. Methods. Our study included 44 adenomas associated with primary aldosteronism and 23 adenomas associated with Cushing syndrome. Normal adrenal glands from patients with renal carcinoma served as the controls. Paraffin-embedded tissues were examined for DNA content by flow cytometry. The mean percentage of G 2/M (4C%) of the control samples was 3.8%. Tetraploid was represented by a histogram with both a 4C peak greater than 9% (mean + 2.4 SD of control samples) and a small 8C peak. Results. Flow cytometric analysis revealed diploidy in 30, tetraploidy in 27, and aneuploidy in 8 of the 67 adenomas; 2 adenomas could not be classified. All 17 normal adrenal glands showed diploidy. A significant relationship was noted between DNA ploidy and the clinical syndrome (ie, a larger proportion of adenomas with primary aldosteronism had a tetraploid DNA histogram compared with adenomas with Cushing syndrome, P <0.0001). Adenomas with primary aldosteronism had a significantly higher nuclear grade (III or IV) than did tumors with Cushing syndrome ( P = 0.033). A significant relationship was also observed between DNA ploidy and nuclear grade in 57 euploid tumors, with tetraploid tumors often showing the highest nuclear grade ( P = 0.037). Conclusions. Our results have demonstrated that adrenal cortical adenomas associated with primary aldosteronism often reveal severe nuclear pleomorphism, indicating that nuclear pleomorphism might be due to a tetraploid stemline.