Clinicopathologic analysis and digital pathology evaluation of orchiectomy specimens in gender-affirmation surgery

Gender-affirmation therapies for transgender and gender diverse (TGD) individuals has been increasing in numbers in recent years. TGD patients usually undergo various forms of hormonal replacement therapy (HRT) followed by bilateral orchiectomy. We aimed to characterize the histological and biochemical alterations in these specimens. From 2018-2023, 63 TGD individuals undergone gender-affirming orchiectomy. Atrophic changes, decreased spermatogenesis, and reduced mean tubule diameter with basement membrane thickening, as well as maturation arrest and aspermatogenesis were identified. A subset of specimens (n = 81, 64.8 %) showed germ cell nucleomegaly with cytological atypia mimicking germ cell neoplasia in situ, and detailed digital pathology and immunohistochemical were performed to distinguish this finding from true neoplastic processes. To our knowledge, this is the largest single-center cohort of gender-affirming orchiectomy specimens.