Adrenocortical carcinoma as a manifestation of Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome (BHDS) is characterized by fibrofolliculomas, trichodiscomas, renal tumors, lung cysts, and spontaneous pneumothoraces. Other than renal cell carcinoma, no cancers have been confirmed as part of the BHDS tumor spectrum. Here, we set out to uncover if adrenocortical carcinoma (ACC) is associated with BHDS. A retrospective review at a single tertiary care center between 2010 and 2024 was performed using search terms describing the clinical manifestations of BHDS, adrenal tumors, and iterations thereof. The initial review identified 1,010 patients with ACC. Of these patients, 466 were evaluated by a genetic counselor, and 346 underwent genetic testing-seven of which were found to have either characteristic clinical features of BHDS or a confirmed diagnosis. The literature review over the same time period demonstrated five additional cases of malignant adrenal tumors in patients with BHDS. We observed BHDS, confirmed by a pathogenic FLCN variant in 0.7% of all ACC patients, or 1.5% of patients evaluated by a genetic counselor and 2.0% of all patients who underwent genetic testing. Testing for FLCN pathogenic variants should be considered during routine genetic evaluation of patients with ACC, and special attention should be paid to adrenal tumors in BHDS patients during surveillance for renal neoplasms as more than 50% of patients in this series developed metastatic disease.