Prostatic Metaplasia of the Vagina and Uterine Cervix

Abstract

Prostatic-type differentiation in the lower female genital tract is encountered rarely and its causes and clinical associations are not well established. Within the vagina, reports to date have invariably described ectopic prostatic-type differentiation as restricted to the lamina propria. We recently encountered a patient receiving testosterone for gender dysphoria whose vaginectomy specimen showed a prostatic glandular proliferation within the surface epithelium. To elucidate its potential association with androgen exposure, we sought similar lesions, resected over a 26-year period, from patients with exogenous or endogenous androgen excess. Thirteen cases were identified, involving the vagina (n=12) and exocervix (n=1). The most common clinical context was gender dysphoria with long-term testosterone therapy; the lesion was present in 7 of 8 gender-dysphoric patients examined. Four other patients had congenital disorders of sexual development associated with endogenous androgen excess (congenital adrenal hyperplasia, 46,XY disorder of sexual development, and ovotesticular disorder of sexual development). Two had no known exposure to androgen excess. Immunohistochemically, glands stained for NKX3.1 (100% of cases), androgen receptor (100%), CK7 (92%), and prostate-specific antigen (69%). Follow-up (median duration, 11 mo) showed no masses or neoplasia. We propose the designation “androgen-associated prostatic metaplasia” for this form of prostate tissue with distinctive clinical, histologic and immunohistochemical features. It is novel and previously unrecognized within the vagina. It is strikingly prevalent among patients undergoing gender-affirming surgery, an increasingly common procedure. Recognition is important to distinguish it from other potentially neoplastic glandular lesions and facilitate accrual of more follow-up data to better understand its natural history.

Endometrioid Endometrial Carcinoma With NKX3.1 Expression in a Transgender Man: A Case Report

“…NKX.3.1 was also expressed in glandular structures within the exocervical squamous epithelium (Figs. 3A, B); these features have been previously reported in transgender men using exogenous testosterone (3)(4)(5). As a positive control, we confirmed that NKX3.1 was positive in prostate acinar cells and NKX3.1 positive cells were completely absent in 5 cases of endometrioid endometrial carcinoma (Supplementary Fig.…”

“…To the best of our knowledge, this is the first report of an endometrial cancer with NKX3.1 positivity in a transgender man. There have been several reports in recent years of histologic changes in the uterus and adnexa of FTMs that are believed to be caused by exogenous testosterone (3)(4)(5)(6)(7)(8). However, there are few reports of cancer in FTMs (9,10), and the relationship between exogenous testosterone and cancer in FTMs has not been fully elucidated.…”

“…Exogenous testosterone has been shown to cause the following in FTMs in recent years: proliferative phase-like changes in the endometrium (6)(7)(8), decidual changes in endometrial stromal cells (8), epididymallike changes in the mesonephric duct remnants (3), polycystic ovaries (7,8), and transitional cell metaplasia or "prostatic metaplasia" in the squamous epithelium of the exocervix and vagina (3)(4)(5). However, the effects of exogenous testosterone on tumor histology have not been reported.…”

Vagina reconstruction by decellularization of healthy human vaginal tissue

“…Our included donors were presurgically exposed to testosterone for mean=5,9 (range 2-11) years, with no vaginal atrophy (thinned squamous epithelium) or prostatic metaplasia (epithelial or subepithelial stroma glands) present in our samples. Induced structural alterations have been reported as prostatic metaplasia in 7 MtF-patients (18-34 years) after 24-72 months of presurgical exposure to testosterone cypionate and metastatic glands located predominantly in epithelial layers [133] or as 80% atrophy, 40% urothelial metaplasia and 70% prostate-like glands in 10 MtF-patients (22-74 years) after 2-10 years of preoperative androgen receival [134].…”

Transgender Data Collection in the Electronic Health Record (EHR): Current Concepts and Issues

“…For instance, assigned female at birth (AFAB) persons have shown some evidence of prostatic tissue growth following extended testosterone therapy [198]. 18 Such is the case following many forms of chest reconstruction or contouring, in which there is still a chance of chest cancer because some tissue is left behind post-mastectomy [199,200].…”