Distinguishing features of endometrial pathology after exposure to the progesterone receptor modulator mifepristone

Abstract

There is growing interest in the use of progesterone receptor modulators such as mifepristone for treatment of gynecologic and other conditions, but interest in progesterone receptor modulators is dampened by the effects of the agents on the endometrium. In this study, we examined the endometria of women exposed to mifepristone for treatment of leiomyomas in doses of 2.5 and 5 mg and compared them to unexposed endometria. We assessed the reliability of these features by comparing agreement in ratings between pathologists who were blinded to each other's readings. We assessed distinguishing features between exposed and unexposed groups by comparing frequency of features between groups. We found that key features could be reliably assessed by pathologists experienced in endometrial pathology. We observed several features (nonsynchronous endometrium, large fluid filled glands, and abnormal blood vessels) that distinguished endometrial samples that were and were not exposed to the drug. These findings suggest several features that can be tracked during studies involving mifepristone and, potentially, other progesterone receptor modulators.

Figure 1

Study Sample

Figure 2

The hallmark of the glandular alterations was the presence of multiple cystic glands lined by a variable appearance of the epithelium.(A,B) The glands were frequently lined by a pseudostratified epithelium similar to the normal proliferative pattern but minimal mitotic activity was noted. Apoptotic bodies were often numerous (B). A rare mitotic figure in a gland with considerable apoptotic bodies is noted in (C). Similar glands sometimes displayed subnuclear secretory type vacuoles.

Figure 3

Vascular changes were a prominent feature in mifepristone exposed patients. A common pattern was the presence of thick walled vessels of the type usually associated with endometrial polyps or normally located in the basalis area distributed throughout the biopsies with no evidence of polyp formation. (A,B). Other vascular changes that were less common included the presence of an interlaced proliferation of fine capillary channels in the stroma (C) or dilated thin walled stromal vessels (D).

Figure 4

Ki-67 staining of endometrium biopsy prior to mifepristone exposure. (A) and example of staining pattern in biopsy taken after drug exposure (B) demonstrating minimal proliferative activity.