Mucinous and clear cell adenocarcinomas of the endometrium in patients receiving antiestrogens (tamoxifen) and gestagens.

In recent years, tamoxifen therapy for breast carcinoma has been associated with endometrial carcinoma with increasing frequency. We describe 10 cases of this association as well as 12 cases of endometrial carcinoma after therapy with synthetic gestagens. All but one of the 22 carcinomas we describe here were of the mucinous or clear cell type, and arose in atrophic endometria containing foci of mucinous (endocervical) and clear cell metaplasia. In the endometrium, the antiestrogenic action of tamoxifen closely resembles the antiproliferative action of synthetic gestagens on the endometrium. In the endocervix, tamoxifen as well as synthetic gestagens, stimulate the endocervical mucosa to proliferate. In the endometrium, both tend to produce mucinous (endocervical) and clear cell metaplasia. A weak estrogenic action of tamoxifen may be expected to augment its own antiestrogenic gestagen-like action. Consequently, the antiestrogenic effect of tamoxifen is most likely responsible for the development of endocervical metaplasia and possibly corresponding endocervical and clear cell types of carcinomas within an atrophic endometrium. We believe that gestagen therapy administered to patients with endometrioid type carcinoma is contraindicated in patients with mucinous adenocarcinoma of the endometrium and that this is another reason to distinguish between these two types of carcinoma.