RESIDENT CASE STUDIES

Week 5 May 19 - May 23, 2003: Case 3  

Table of Contents | List of Diagnoses | Case 1 | Case 2 | Case 3 | Case 4

Patient is a 64 year old female with a history of breast cancer

Discussion:
Tamoxifen is a selective estrogen receptor mediator (SERM) used in the treatment of breast cancer to minimize recurrence. Tamoxifen, a weak estrogen agonist, acts as an antiestrogenic agent in the breast and a weak estrogen agonist in the endometrium. In the premenopausal female with high levels of endogenous estrogen, it competes for the estrogen receptor and blocks the effects of endogenous estrogen on the breast. However, in the postmenopausal female with low estrogen and atrophic endometrium, the drug acts as an estrogen agonist primarily on the endometrium. Therefore, tamoxifen is associated with a higher incidence of endometrial polyps, hyperplasia and carcinoma.

Vaginal ultrasound may demonstrate a thickening of the endometrium. An endometrial thickness of 9 mm and a report of vaginal bleeding are independent predictors of endometrial pathology and could be used to select women for hysteroscopy and biopsy during tamoxifen therapy (1). The current recommendation is that the endometrium should be biopsied if the endometrium is greater than 9 mm by transvaginal ultrasonogram, or if tamoxifen therapy exceeds 24 months regardless of symptoms.  

Tamoxifen is associated with unusual endometrial polyps, which are two or more centimeters in size. Histologically, the polyp may have cystically dilated glands, glandular hyperplasia, fibrosis, luminal secretions, various metaplasias, serous epithelial atypia and decidualized stroma. Malignancies are found at a higher rate in users vs. non-users, 3.0% and 0.5% respectively. This increased risk especially of endometrial carcinoma is related to the duration of therapy and increases by four fold when therapy exceeds 5 years. Most cancers are low-grade endometroid adenocarcinoma or small serous carcinomas. This is an endometrial polyp which demonstrates cystic atrophy of glands with fibrosis, glandular crowding and serous epithethelial atypia. The glands in tamoxifen polyps do not have higher expression of ER and PR. However, in postmenopausal women treated with tamoxifen, there was an increase in the overexpression of epidermal growth factor receptors when compared with premenopausal women treated with tamoxifen. This was also associated with a higher Ki-67 index in postmenopausal females.

The differential diagnosis to consider include, endometrial hyperplasia, endometrial carcinoma, and bordeline serous tumor. The glandular crowding does not exceed the 3:1 glandular to stroma ratio making endometrial hyperplasia unlikely. Nor do the glands fuse or show nuclear atypia severe enough to consider endometroid carcinoma. The focus of serous epithelial atypia is focal and is not severe enough to consider borderline or serous carcinoma. Other differential diagnosis to consider are, cystic atrophy of the endometrium, disordered proliferation of the endometrium.

 References:

1. Franchi M, et al. Endometrial thickness in tamoxifen-treated patients: an independent predictor of endometrial disease. Obstet Gynecol June 1999;93:1004-8.

2. Ito T, Murata Y, Hamazoe R, et al. Indication for histological examination of endometrium in breast carcinoma patients receiving tamoxifen therapy. J Obstet Gynaecol Res. June 2001;27:141-5.

3. Hachisuga T, Hideshima T, Kawarabayashi T. Expression of steroid receptors, Ki-67, and epidermal growth factor receptors in tamoxifen-treated endometrium. Int J Gynecol Pathology. Oct 1999; 18(4):297-303.

4. Blaustein’s pathology of the female genital tract – 4^th edition/Robert J Kurman, editor.

5. Robboy.

6. Clement Pand Young R, eds. Atlas of gynecologic surgical pathology. W.B. Saunders Company, Philadelphia PA, 2000:146-7.