Histologic Findings in Surgical Pathology Specimens From Individuals Taking Masculinizing Hormone Therapy for the Purpose of Gender Transition

Abstract

Context.— Transgender men and transmasculine persons experience a discordance between the female sex they were assigned at birth and their gender. They may choose to take hormone therapy and/or undergo surgery to masculinize the body. Understanding the common (and less common) histologic changes present in patients taking masculinizing hormones will empower pathologists to better serve this unique patient population. Objective.— To summarize histologic findings in surgical pathology specimens from persons taking masculinizing hormones as a part of gender transition. Data Sources.— A systematic review of the OVID Medline and PubMed databases was performed to identify all studies describing histologic findings in surgical pathology specimens from transgender men from January 1946 to January 2021. Conclusions.— Publication in this area has markedly increased in the last 2 decades. However, most of the studies identified were descriptive and case reports describing changes seen in specimens removed as a part of masculinizing surgical procedures. Benign histologic findings include stromal hyalinization and epithelial atrophy in the breast, polycystic ovarian syndrome–like changes in the ovary, and transitional cell metaplasia in the cervix. The most commonly reported neoplastic finding was adenocarcinoma of the breast, with rare cases of ovarian, endometrial, cervical, vaginal, pituitary, pancreatic, and cardiovascular neoplasia also reported. Ongoing research in this area is needed to better characterize the histologic findings in persons taking masculinizing hormones to provide a deeper understanding of the effect of these treatments on different tissues and facilitate better patient management.

Cervicovaginal Papanicolaou tests in transgender men: Cytomorphologic alterations, interpretation considerations, and clinical implications

“…34,35 However, even early reports noted its association with androgen and testosterone therapies, and it is now recognized as a common finding in histology specimens from patients undergoing exogenous testosterone therapy, being observed in up to 88.2% of Pap tests from transgender patients. 22,29,36 In this current study, it was found in 43% of cases. Transitional cell metaplasia, as the name implies, is a metaplastic process where the epithelium morphologically resembles urothelium; it is considered by some to be a morphological variant of atrophy or basal cell hyperplasia.…”

“…In the older literature, transitional cell metaplasia was predominantly described in peri‐ and postmenopausal women, the majority of whom were not on exogenous hormones 34,35 . However, even early reports noted its association with androgen and testosterone therapies, and it is now recognized as a common finding in histology specimens from patients undergoing exogenous testosterone therapy, being observed in up to 88.2% of Pap tests from transgender patients 22,29,36 . In this current study, it was found in 43% of cases.…”

Different Forms of TFF3 in the Human Endocervix, including a Complex with IgG Fc Binding Protein (FCGBP), and Further Aspects of the Cervico-Vaginal Innate Immune Barrier

“…Also, the scientific literature concerning individuals taking masculinizing hormone therapy is rather sparse and mainly restricted to histologic changes [60]. For example, prostatic metaplasia was described in the cervical epithelium [60]. Although the RT-PCR results (Figure 5) were obtained from a single individual only, they are of considerable clinical interest, as we show here, for the first time, that mucin and FCGBP expression in the endocervix can be subject to differential regulations due to hormonal treatment.…”

“…However, differential regulation of MUC5AC and MUC5B expression by estradiol has been reported recently [59]. Also, the scientific literature concerning individuals taking masculinizing hormone therapy is rather sparse and mainly restricted to histologic changes [60]. For example, prostatic metaplasia was described in the cervical epithelium [60].…”