Objective: Pure androgen-secreting adrenal tumors (PASATs) are extremely rare, most reports involving only a single case. This study examined 9 cases of PASAT, with an attempt to characterize its clinical features and to explore the pathogenesis.
Methods: Clinical data of 9 patients with PASAT were retrospectively reviewed. Immunostaining was conducted, and the aryl hydrocarbon receptor-interacting protein gene (AIP) was amplified and directly sequenced.
Results: The onset age of the patients ranged from 3.5 to 64 years. All 8 female patients had virilization, whereas the 7-year-old male patient presented with sexual precocity. Serum testosterone levels were elevated (4.1 to 52.3 nmol/L). Adrenal masses were detected and removed in all patients and histologically diagnosed as adrenocortical adenoma or carcinoma. Two patients had both PASATs and growth hormone (GH)-secreting pituitary adenomas (GH pituitary adenoma). Immunohistochemistry revealed nuclear immunoreactivity for p53 in 3 of 7 patients and nuclear immunoreactivity for cyclin D1 in 2 of 7 patients. Immunostaining of β-catenin showed nuclear, cytoplasmic, and membrane immunoreactivity (2 of 7 patients) or merely cytoplasmic immunoreactivity (1 of 7 patients). The adrenocortical carcinoma showed positive staining for both p53 and cyclin D1 and a high Ki-67 index of 60%. Mutations p.Lys177Argfs*19 and p.Asp287Val in the AIP gene were identified in PASATs of the 2 patients with concomitant presence of GH pituitary adenoma.
Conclusion: Clinical features of PASATs vary with gender and age of the patients. Abnormal p53 and β-catenin expression might be involved in the tumorigenesis of these tumors. AIP mutations might be responsible for the concomitant presence of PASATs and GH pituitary adenoma.
Abbreviations: ACA = adrenocortical adenoma ACC = adrenocortical carcinoma AIP = aryl hydrocarbon receptor-interacting protein DHEAS = dehydroepiandrosterone sulfate; GH growth hormone PASAT = pure androgen-secreting adrenal tumor.