Prevalence and clinical characteristics of Lynch syndrome-associated adrenocortical carcinoma

Lynch syndrome is the result of pathogenic variants in mismatch repair genes that increase the risk of cancer, including adrenocortical carcinoma. Little is known, however, about the clinical characteristics of patients with Lynch syndrome-associated adrenocortical carcinoma. In order to understand the clinical characteristics and prevalence of Lynch syndrome-associated adrenocortical carcinoma, we conducted a retrospective chart review of patients with adrenocortical carcinoma and germline genetic testing results, indicating pathogenic variants in mismatch repair genes consistent with Lynch syndrome at a single academic tertiary-care institution. In total, 21 patients with Lynch syndrome-associated adrenocortical carcinoma were identified from 2003 to 2024. Three patients met Amsterdam I criteria, and 12 patients met Amsterdam II criteria (including adrenocortical carcinoma as a Lynch syndrome-associated cancer). More than 90% of patients with available histopathology had high-grade tumors, suggesting a more aggressive nature. The prevalence of Lynch syndrome-associated adrenocortical carcinoma is estimated at 2.6%. This study further demonstrates that adrenocortical carcinoma is a Lynch syndrome-associated cancer and may be associated with a high-grade disease. Furthermore, our findings suggest that further research should be pursued to investigate the potential utility of immunotherapy for adrenocortical carcinoma, especially in the presence of microsatellite instability.