Tamoxifen and the endometrium: Review of 102 cases and comparison with HRT-related and non-HRT-related endometrial pathology

Tamoxifen, a synthetic anti-estrogen that paradoxically acts as a partial e strogen agonist on the endometrium, is associated with an increased frequen cy of proliferative endometrial lesions, including hyperplasias, neoplasms, and polyps. Tamoxifen-related polyps ale characteristically multiple and f ibrotic. A variety of metaplasias and periglandular stromal condensation ma y be seen. Relatively few articles have focused on the descriptive morpholo gy of the full range of tamoxifen-associated lesions. The present study fur ther defines the histologic features in both endometrial polyps and nonpoly p endometrium. One hundred and two specimens (including 50 polyps) were rev iewed using hormone replacement therapy-related endometrial specimens and c onventional polyps as the control groups. The most characteristic findings of tamoxifen-associated lesions included polarized glands along the long ax is of polyps (40%). a cambium layer (72%), frequent and diverse metaplasias , staghorn glands (36%), myxoid degeneration (12%), and small glands (36%). Similar morphologic features were identified in the hormone replacement th erapy and control groups but to a variable, lesser extent. Overall, the tam oxifen group consisted of 18 cases of hyperplasia (11 complex, 7 simple) an d one case each of adenofibroma, adenosarcoma, endometrial stromal sarcoma, and leiomyosarcoma. Although none of the features is diagnostic, the prese nce of diverse metaplasias, polarized glands, staghorn glands, and a cambiu m layer strongly suggest tamoxifen exposure especially if a number of these features are present concurrently within the same material.