We report a case of uterine cancer and invasive cervical cancer, detected incidentally during the female-to-male sex reassignment surgery. The management of these patients is presented. Such individuals may not be receiving regular gynecologic care appropriate to their remaining genital organs; symptoms of malignant disease may be missed.
Cancers that involve either the uterine corpus or cervix were reported in more than 50,000 patients in 2009 in the United States. During the female-to-male sex reassignment process, the uterus, cervix, and ovaries are surgically removed. Such individuals are frequently in an amenorrheic state, which has been induced by hormone treatment with androgens.
There have been extremely few reports of gynecologic malignancies in testosterone-treated females to males, including 3 cases of ovarian cancers, a single case of vaginal carcinoma, and a single case of cervical carcinoma in situ. So far, no cases of uterine carcinoma or invasive cervical carcinoma have been reported at the time of hysterectomy for female-to-male reassignment. We report on the evaluation and management of 1 individual with uterine cancer and another individual with invasive cervical cancer that we have treated over the past 2 years. In each case, the malignancy was detected incidentally during the sex reassignment process.
Patient A is a 54 year old transsexual male who began sex reassignment with androgen administration in 2000. Prior to this, he noted menarche at 12 years of age, and he had amenorrhea since 2000. He had not had prior intercourse with women since the age of 18 years. He denied any history of abnormal Papanicolaou smears or sexually transmitted diseases. His most recent normal Papanicolaou smear was in 2007. He denied any history of human immunodeficiency virus, intravenous drug use, or blood transfusions.
He continued the sex reassignment process with a bilateral mastectomy in 2005 and then presented for a hysterectomy in 2009. Prior to this, he had had vaginal spotting since 2007 that had been attributed to fibroids. He underwent a laparoscopic total hysterectomy and bilateral salpingo-oophorectomy in July 2009 at an outside hospital. The presence of an adenoma malignum was noted within the cervix. The tumor had 1-2 cm of horizontal spread and 0.9-1.1 cm of cervical stromal invasion. The resection margins were negative, but the tumor extended to within 1-2 mm of the margin. The tubes and ovaries were negative for tumor spread. No parametrial tissue or lymph nodes were taken.
The patient’s postoperative course was uncomplicated. The patient was initially seen by Stanford physicians following this surgery; at that time, a biopsy of a lesion on the anterior vaginal cuff was negative for malignancy. Additional workup included a computerized axial tomography scan of the abdomen and pelvis, which revealed an indeterminate solitary pulmonary nodule at the right lung base and multiple sclerotic bone lesions in the pelvis. A subsequent bone scan was negative and positron emission tomography (PET) computerized tomography (CT) scan showed no PET avid lesions.
The patient began external beam pelvic radiation in September 2009 and completed his planned dose of 50.4 Gy. He then underwent 3 high-dose rate intracavitary treatments to the upper vagina. Concurrently he was started on chemotherapy with weekly cisplatin. Three months following completion of treatment, he was without evidence of disease.
Patient B is a 51 year old gravida 0 transsexual male who began the sex reassignment process in 2001. The patient had menarche at 13 years of age and denied any prior vaginal intercourse. His body mass index was 31 kg/m 2 . He had no family history of breast, uterine, ovarian, or colon cancers. No routine gynecologic surveillance or Papanicolaou smears were obtained. After being amenorrheic for 7 years because of androgen therapy, he began having 2-3 months of vaginal bleeding. During a preoperative evaluation for a planned sex change operation, he was noted to have a cervical mass on speculum exam. This mass was biopsied and a diagnosis of cervical adenocarcinoma was made.
He then underwent radical hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy on Nov. 28, 2008, at an outside institution. Intraoperative findings included moderate adhesions around the uterus and a fungating cervical mass measuring approximately 5 × 2 cm. Pathology from this surgery revealed International Federation of Gynecology and Obstetrics stage IIIC grade 2 endometrioid adenocarcinoma of the uterus. Histologic sections showed adenocarcinoma characterized predominately by endometrioid morphology with complex cribriform glandular architecture lined by cells with mild to moderately enlarged nuclei and increased mitotic activity. In some areas, the tumor exhibited villoglandular and papillary architecture; the majority of the tumor, however, demonstrated endometrioid morphology. Rare psammoma bodies were also identified. There was lymphovascular space invasion noted, positive parametrial involvement, and a positive vaginal cuff margin. Seven of 12 lymph nodes were positive for metastases. The ovaries and bilateral tubes were negative for involvement. Postoperatively, the patient had a CT abdomen/pelvis in December 2008, which revealed a 1.2 cm low density nodule in the spleen, a tiny pleural based nodule, and right ureteral double-J stent with downward migration. His CA 125 was 285 in December 2008.
The patient was first seen at Stanford University Medical Center in January 2009. Based on recommendations for systemic chemotherapy, the patient underwent 6 cycles of carboplatin and paclitaxel, which were completed in August 2009. He declined additional treatment with radiation. His CA 125 was 16 in September 2009. Unfortunately, at the time of this writing, this patient has evidence of recurrent disease at the vaginal cuff and paraaortic lymph nodes and is undergoing chemotherapy.
Approximately 1 in 30,000 women per year undergo sex reassignment treatment. During the hormonal treatment process, therapy with androgens induces a hypoestrogenic state leading to amenorrhea. Such changes lead to atrophy of the endometrium. Long-term androgen therapy has also been found to be associated with cervical atrophy. Although to the best of our knowledge, there has not previously been reported a case of uterine or invasive cervical carcinoma in a cohort of patients treated with high-dose androgens or in the female-to-male transgender population, the potential carcinogenic risks of androgens on endometrial tissue has been reviewed. In addition, a recent epidemiological study suggested a possible association between testosterone exposure and endometrial cancer. Of course, the possibility exists that the cancers we have reported were incidental findings, but occult malignancies have uncommonly been noted in recent studies. A summary of female-to-male transgender patients developing gynecologic malignancies, all but 1 of whom was reported to be on androgens, is presented in the Table .