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Japanese Journal of Clinical Oncology Pages 350-352

Adenomyomatous Polyp of the Uterus in a Patient Receiving Tamoxifen
Introduction
Case Report
Discussion
References

Adenomyomatous Polyp of the Uterus in a Patient Receiving Tamoxifen

Adenomyomatous Polyp of the Uterus in a Patient Receiving Tamoxifen Kaei Nasu, Kazuyo Arima, Jun Yoshimatsu and Isao Miyakawa

Department of Obstetrics and Gynecology, Oita Medical University, Oita, Japan

We report a case of adenomyomatous polyp that developed during treatment with tamoxifen for breast cancer. A 63-year-old Japanese woman was admitted complaining of atypical genital bleeding. Nine months earlier, she had undergone a modified radical mastectomy for cancer of her right breast, estrogen receptor-positive stage I (T1N0M0). The administration of tamoxifen, 20 mg/day, was started immediately postoperatively. Pelvic examination after tamoxifen administration for 9 months revealed that the uterus was enlarged to the size of a fist. Transvaginal ultrasonography and magnetic resonance imaging revealed a large solid mass with multiple cystic areas in the uterine cavity. The pathological diagnosis of the tumor after total hysterectomy was typical adenomyomatous polyp. It was believed to have developed during tamoxifen administration.

Key Words: tamoxifen - adenomyomatous polyp - breast cancer

INTRODUCTION

Tamoxifen is a nonsteroidal agent with estrogen agonist and antagonist properties (1 ). Its estrogen antagonist properties have qualified tamoxifen as an important treatment modality for patients with breast cancer, especially those whose tumors are positive for estrogen receptors. Fisher and colleagues (2 ) recently recommended that all low-risk patients with breast cancer receive adjuvant therapy, and a large number of premenopausal and postmenopausal women have been placed on 3-5-year regimens of tamoxifen. The potential adverse effects of the drug include the development of endometrial cancer (3 ), endometrial polyps (4 -8 ), adenomyosis (9 ), leiomyoma (10 ,11 ) and ovarian cysts (12 ,13 ).

Adenomyomatous polyp (polypoid adenomyoma) of the endometrium is a rare polypoid lesion in which the stromal component is largely or exclusively composed of smooth muscle (14 ). This report describes a case of adenomyomatous polyp associated with tamoxifen treatment of breast cancer.

CASE REPORT

A 63-year-old Japanese woman, gravida 8, para 2, was admitted complaining of atypical genital bleeding. Nine months earlier, she had undergone a modified radical mastectomy of her right breast for estrogen receptor-positive stage I (T1N0M0) disease. The administration of tamoxifen, 20 mg/day, was started immediately after the operation. There was no history of uterine enlargement prior to tamoxifen administration.


Figure 1. Transvaginal ultrasonography revealed a large solid mass with multiple cystic areas (60 × 50 × 40 mm) in the uterine cavity.

At pelvic examination after tamoxifen administration for 9 months, the patient's uterus was enlarged to the size of a fist. Transvaginal ultrasonography revealed a large solid mass (60 * 50 * 40 mm) with multiple cystic areas in the uterine cavity (Fig. 1 ). Magnetic resonance imaging (MRI) revealed a well circumscribed round tumor (60 * 50 mm) in the uterine cavity. MRI of the tumor demonstrated intermediate to high signal intensity on T2-weighted images and low to high signal intensity on T1-weighted images (Fig. 2 ). The junctional zone was almost completely conserved. High signal intensity areas on T1-weighted images were enhanced by contrast enhancement. Endometrial biopsy revealed no evidence of malignancy.


Figure 2. MRI findings of the pelvis. A T1-weighted image of an axial section revealed a well-circumscribed round tumor (60 × 50 mm) in the uterine cavity. MRI of the tumor demonstrated low to high signal intensity on T1-weighted images. The junctional zone was almost completely conserved.

Routine laboratory data were within normal limits. Levels of CA-125, CA 72-4 and CA 19-9 were 180 U/ml, 31.8 U/ml and 7.2 U/ml respectively. These findings strongly suggested a benign submucous tumor with cystic degeneration, such as a degenerated leiomyoma. Total hysterectomy and bilateral salpingo-oophorectomy were performed because of persistent bleeding and to rule out a malignancy. The patient's postoperative course was uneventful.

Pathologic examination revealed that the polypoid tumor arose from the upper segment of the uterine corpus. The excised lesions were pale, rubbery, well-circumscribed polypoid masses with smooth surfaces (Fig. 3 ). Histologic examination revealed the tumor to be composed of endometrial glands admixed with smooth muscle cells. Cystic dilatation of the endometrial glands occurred frequently (Fig. 4 ). Neither the glandular epithelium nor the stromal cells exhibited atypia. Squamous metaplasia of the glandular epithelium was not observed. The pathological diagnosis was adenomyomatous polyp of the uterus.

DISCUSSION


Figure 3. Adenomyomatous polyp arising in the upper segment of the uterine corpus. The lesion appeared to be a pale, rubbery, well-circumscribed polypoid mass with a smooth surface.


Figure 4. Histological findings of the low signal intensity area on T1-weighted images. Cystic dilatation of the endometrial glands were frequently observed within the adenomyomatous polyp.

Tamoxifen effectively blocks the action of estrogens on target tissue and is therefore used as an adjuvant medication in patients whose breast cancer is positive for estrogen receptors. It is considered to be the antihormonal treatment of choice for patients with advanced cancer, as well as for low-risk patients (2 ). Tamoxifen exhibits both estrogen agonist and antagonist properties (1 ). While tamoxifen is an estrogen antagonist in the breast (15 ), it is an estrogen agonist in the lower genital tract (16 ,17 ). Tamoxifen has an estrogenic effect on the myometrium, and leiomyomas have been reported as developing during its administration (10 ,11 ). The size of the myomas increased rapidly after the initiation of tamoxifen in the reported cases. Tamoxifen also exerts an estrogenic effect on endometrium, and a large number of cases of endometrial cancer development during tamoxifen therapy have been reported (3 ). Endometrial polyps have also been observed during tamoxifen administration in postmenopausal women (4 -8 ). In addition, Cohen et al. (9 ) reported several cases of adenomyosis in postmenopausal patients treated with tamoxifen. They reported that the incidence of adenomyosis was increased with tamoxifen administration.

Adenomyomatous polyps are rare, with an incidence as low as 1.3% in patients with endometrial polyps (18 ). Hertig and Gore (19 ) reported that the lesions are usually found in infertile, young patients. Most of the patients in our previous study were premenopausal (14 ). The adenomyomatous polyps were composed of endometrial glands admixed with smooth muscle cells, which tended to involute after menopause because of the decline in estrogen production. Cohen et al. (9 ) reported a case of postmenopausal adenomyomatous polyp developed during tamoxifen administration. In the present case, the adenomyomatous polyp was also believed to have arisen after menopause as a consequence of tamoxifen administration.

Hulka and Hall (7 ) reported seven cases of endometrial polyp, all of which exhibited small cystic spaces in the polyp by ultrasonography. Our findings on ultrasonography were consistent with their results. MRI was also useful for evaluating endometrial abnormalities in our case. The low signal intensity areas on T1-weighted images may reflect the multiple cystic dilatation of the endometrial gland in the adenomyomatous polyp.

References

1. Pasqualini JR, Sumida C, Giambiagi N. Pharmacodynamic and biological effects of anti-estrogens in different models. J Steroid Biochem 1988;31:613-43. MEDLINE Abstract

2. Fisher B, Constantino J, Remond C, Poisson R, Bowman D, Couture J, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med 1989;320:479-84. MEDLINE Abstract

3. Seoud MA-F, Johnson J, Weed JC Jr. Gynecologic tumors in tamoxifen-treated women with breast cancer. Obstet Gynecol 1993;82:165-9. MEDLINE Abstract

4. Lahti E, Blanco G, Kauppila A, Apaja-Sarkkinen M, Taskinen PJ, Latikainen T. Endometrial changes in postmenopausal breast cancer patients receiving tamoxifen. Obstet Gynecol 1993;81:660-4. MEDLINE Abstract

5. Corley D, Rowe J, Curtis MT, Hogan WM, Noumoff JS, Livolsi VA. Postmenopausal bleeding from unusual endometrial polyps in women on chronic tamoxifen therapy. Obstet Gynecol 1992;79:111-6. MEDLINE Abstract

6. Uziely B, Lewin A, Brufman G, Dorembus D, Mor-Yosef S. The effect of tamoxifen on the endometrium. Breast Cancer Res Treat 1993;26:101-5. MEDLINE Abstract

7. Hulka CA, Hall DA. Endometrial abnormalities associated with tamoxifen therapy for breast cancer: sonographic and pathologic correlation. Am J Roentgenol 1993;160:809-12.

8. Kedar RP, Bourne TH, Powles TJ, Collins WP, Ashley SE, Cosgrove DO, et al. Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomized breast cancer prevention trial. Lancet 1994;343:1318-21. MEDLINE Abstract

9. Cohen I, Beyth Y, Tepper R, Figer A, Shapira J, Cordoba M, et al. Adenomyosis in postmenopausal breast cancer patients treated with tamoxifen: a new entity? Gynecol Oncol 1995;58:86-91. MEDLINE Abstract

10. Dilts PV, Hopkins MP, Chang AE, Cody RL. Rapid growth of leiomyoma in patient receiving tamoxifen. Am J Obstet Gynecol 1992;166:167-8. MEDLINE Abstract

11. Leo L, Lanza A, Re A, Tessarolo M, Bellino R, Lauricella A, et al. Leiomyomas in patients receiving Tamoxifen. Clin Exp Obstet Gynecol 1994;21:94-8. MEDLINE Abstract

12. Barbieri RL, Ferracci AL, Droesch JN, Rochelson BL. Ovarian torsion in a premenopausal woman treated with tamoxifen for breast cancer. Fertil Steril 1993;59:459-60. MEDLINE Abstract

13. Shushan A, Peretz T, Uziely B, Lewin A, Mor-Yosef S. Ovarian cysts in premenopausal and postmenopausal tamoxifen-treated women with breast cancer. Am J Obstet Gynecol 1996;174:141-4. MEDLINE Abstract

14. Nasu K, Sugano T, Miyakawa I. Adenomyomatous polyp of the uterus. Int J Gynecol Obstet 1995;48:319-21. MEDLINE Abstract

15. Baum M. Controlled trial of tamoxifen as single adjuvant agent in the management of early breast cancer: analysis at six years by Nolvadex Adjuvant Trial Organization. Cancer 1985;1:836-9.

16. Boccardo F, Buzzi L, Rubagotti A, Nicolo G, Rosso R. Oestrogen-like action of tamoxifen on vaginal epithelium in breast cancer patients. Oncology 1981;38:281-8. MEDLINE Abstract

17. Gorodeski GI, Beery R, Lunenfeld B, Geier A. Tamoxifen increases plasma estrogen-binding equivalents and has an estradiol agonistic effect on histologically normal premenopausal and postmenopausal endometrium. Fertil Steril 1992;57:320-7. MEDLINE Abstract

18. Peterson WF, Novak ER. Endometrial polyps. Obstet Gynecol 1956;8:40.

19. Hertig AT, Gore H. Tumors of the Female Sex Organs. Part 2-Supplement. Tumors of the Vulva, Vagina and Uterus. Atlas of Tumor Pathology. Washington DC: Armed Forces Institute of Pathology, 1968;322.

Received March 4, 1997; accepted May 13, 1997
For reprints and all correspondence: Kaei Nasu, Department of Obstetrics and Gynecology, Oita Medical University, Hasama-machi, Oita 879-55, Japan
Abbreviation: MRI, magnetic resonance imaging.

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Last modification: 19 May 1998
Copyright© Japanese Journal of Clinical Oncology, 1997.
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