Kitawaki Y, et al. - The role of the tumor microenvironment in benign tumors, particularly hormone-secreting endocrine tumors, was determined based on a histologic analysis of cortisol-producing adrenocortical adenomas (CPAs) and aldosterone-producing adrenocortical adenomas (APAs). It was shown that intratumoral immune cell infiltration (ICI) was more prominent in CPAs compared to APAs. Moreover, the status of senescence markers, p16 and p21, appeared to be considerably more abundant in CPAs compared to APAs. All CPA cases examined were positive for senescence-associated β-galactosidase. Exposure to local excessive cortisol could lead to senescence of tumors cells, thereby playing a vital role in constituting the characteristic tissue microenvironment of CPAs.