Atrophy is the most common finding in those on tamoxifen.
Endometrial polyps from treated patients can be edematous, mxyoid or fibrous. In this example, the stroma is quite edematous.
Myxoid change is seen admixed with the edematous stroma.
A hysterectomy specimen from a tamoxifen-treated patient shows prominent cystic alteration. The surrounding glands have irregular staghorn-shaped contours.
The cysts are unusually large and irregularly shaped. Often cysts are back to back.
A different patient on tamoxifen demonstrates an admixture of dilated closely pack cysts with more hyperplastic areas.
Again, some of the cysts are strikingly large, while other glands are small with some branching.
The glandular epithelium lack cytological atypia.
Tamoxifen, a selective estrogen receptor modulator (SERM), is a potent antiestrogenic agent and is employed successfully in the adjuvant therapy of breast cancer. However, its effects on the uterus are more complicated, acting both as an agonist and antagonist of estrogen depending on the menopausal status of the woman and dose/duration of drug administration.
In pre-menopasual women with high estrogen levels, tamoxifen competes for estrogen binding at the receptor and blocks the effects of estrogen (antagonist action). In post-menopausal women with low estrogen levels, tamoxifen stimulates the estrogen receptor and acts as a weak agonist. With continued tamoxifen therapy, some post-menopausal women will develop pathologic changes in the endometrium associated with unopposed estrogenic stimulation.
In a review of 700 women treated with tamoxifen conducted by Deligdisch and colleagues, 61.14% of cases demonstrate non-pathologic changes such as atrophy. Pathologic changes were found in the remaining 39.86% of cases and included polyps (23.14%), glandular hyperplasia (8%) and metaplasia (3%). Endometrial carcinoma was found in 4.71% (33 cases), of which 9 were well-differentiated endometrioid adenocarcinomas, and 24 were moderately or poorly differentiated (of which 13 had non-endometrioid components such as serous, clear cell, MMMT components). From this data, the authors concluded that 1/3 of patients developed endometrial polyps, hyperplasia and metastatic consistent with hyperestrogenism. Endometrial cancers induced by tamoxifen were uncommon (4.71%), however, the tumors were often high-grade and invasive (Deligdisch).
In asymptomatic women, atrophy of the endometrium is the most common finding. In symptomatic women (vaginal bleeding, abdominal/pelvic discomfort), endometrial pathologies are more frequently found including polyps, endometrial hyperplasias and endometrial carcinomas. The risk of endometrial carcinoma is increased by four-fold after more than 5 years of exposure to tamoxifen therapy.1
1 Robboy SJ, Anderson MC, Russell P. Pathology of the Female Reproductive Tract. London, UK: Churchill Livingstone; 2002: 276-7.
2 Mazur MT, Kurman RJ. Diagnosis of Endometrial Biopsies and Curettings. New York, NY: Springer; 2005: 133-5.
Deligdisch L, et al. Endometrial histopathology in 700 patients treated with tamoxifen for breast cancer. Gynecol Oncol. 2000 Aug;78(2):181-6.