A rare case of poorly-differentiated endometrial carcinoma in a female-to-male transgender man on testosterone therapy

Abstract

Abstract Introduction/Objective Testosterone is commonly used as gender-affirming therapy for transmasculine individuals. The effects of testosterone therapy on endometrial tissue are complex, with some experiencing atrophy, and others with abnormal uterine bleeding (AUB). Endometrial carcinomas in transgender men are rarely reported in the literature. Here we present a case of poorly-differentiated endometrial carcinoma in a transgender man on testosterone. Methods/Case Report A 56 year-old female-to-male transgender man who had been on testosterone and finasteride therapy since 2015 developed vaginal discharge in 2022. No history of abnormal pap smears was noted. The patient’s pelvic ultrasound that was subsequently obtained after presenting with the vaginal discharge showed a thickened endometrium of 4 cm thickness. PET-CT revealed hypermetabolic activity corresponding to the endometrial lining of the uterus. Endometrial biopsy was notable for poorly differentiated carcinoma with retained expression of the mismatch repair proteins by immunohistochemical stains. The patient underwent hysterectomy with bilateral salpingo-oophorectomy. Grossly, there was a 9.5 cm necrotic mass occupying the entire endometrial cavity, extending >50% into myometrium thickness and extending into the lower uterine segment, without cervical involvement. Background endometrium was inactive/atrophic. Microscopic examination of the tumor showed sheets of epithelioid tumor cells with extensive necrosis, without any glandular pattern. On immunohistochemical stains, the tumor cells were positive for pankeratin and patchy staining for keratin 7 and keratin 20, without expression of PAX8, estrogen receptor, progesterone receptor or androgen receptor. Results (if a Case Study enter NA) N/A Conclusion Gender-affirming testosterone is a common long-term treatment for transgender men. There is limited understanding of the long-term effects of testosterone therapy on endometrial pathology, particularly regarding the potential for developing malignancy. Positive staining for androgen receptor has been previously reported in endometrial malignancies, and therefore, studies on the potential effects of testosterone therapy on endometrial malignancies is warranted. This case demonstrates the importance of continued gynecologic care in female-to-male transgender individuals who have not undergone previous gender affirming gynecologic surgery.