Histopathologic Features of Breast Tissue from Transgender Men and Their Associations with Androgen Therapy

Objectives: To assess the histopathologic features of breast tissue of transgender men (TM) undergoing gender-Affirming bilateral mastectomies in relation to androgen therapy (AT). Methods: We reviewed 374 transgender bilateral mastectomy cases from 2017 to 2020. Of these, 314 (84.4%) patients received preoperative AT. We compared these with 127 cases of cisgender females undergoing elective breast reduction. Results: Breast specimens from TM on AT, compared with cisgender women, showed a median higher gross percentage of fibrous tissue (P<.001), reduced lobular density (P=.004), higher amount of lobular atrophy (P<.001), and lower incidence of cysts (P<.001), apocrine metaplasia (P<.001), calcifications (P<.001), columnar cell change (P=.002), and atypia (P=.003). Each additional month of AT was associated with a 2% decrease in the odds of having nonapocrine cysts (P=.02), a 5% decrease in the odds of having usual ductal hyperplasia (P=.007), and a 0.14% decrease in median lobular density (95% confidence interval,-0.18 to-0.05). Conclusions: In this study, breast specimens from TM, particularly with a history of AT, had a higher proportion of fibrous tissue, fewer lobules, and a higher degree of lobular atrophy than cisgender females. Rare cases of atypia were not predicted by preoperative imaging or gross findings, supporting routine microscopic evaluation of these specimens.