title: The spectrum of endometrial pathology induced by progesterone receptor modulators.
abstract: Progesterone receptor modulators (PRM) are hormonally active drugs effective in the management of endometriosis and uterine leiomyomata. The endometrial effects of progestin blockade by PRMs in premenopausal women are currently being evaluated in several clinical trials, but few pathologists have had access to these materials and published information of the histological changes is scanty. Eighty-four endometrial specimens from women receiving one of four different PRMs were reviewed by a panel of seven experienced gynecologic pathologists to develop consensus observations and interpretive recommendations as part of an NIH-sponsored workshop. Although the pathologists were blinded to agent, dose, and exposure interval, the review was intended to provide an overview of the breadth of possible findings, and a venue to describe unique features. Endometrial histology included inactive and normal-appearing cycling endometrium. Overtly premalignant lesions (atypical hyperplasia or EIN) were not seen. In a subset of cases, asymmetry of stromal and epithelial growth resulted in prominent cystically dilated glands with admixed estrogen (mitotic) and progestin (secretory) epithelial effects of a type not encountered in contemporary clinical practice. The variety of endometrial appearances suggested that findings might differ by agent and dose over time according to relationships that must be specified for each agent. The constellation of changes seen in those endometria with cystically dilated glands is so novel that new terminology and diagnostic criteria are required for pathologists to recognize them. The panel has designated these changes as PRM-associated endometrial changes (PAEC). Additional follow-up studies will be needed to fully define their natural history and relationship to specific agents and administration regimens.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. gmutter@rics.bwh.harvard.edu
authors.forename: George L
authors.initials: GL
authors.lastname: Mutter
authors.forename: Christine
authors.initials: C
authors.lastname: Bergeron
authors.forename: Liane
authors.initials: L
authors.lastname: Deligdisch
authors.forename: Alex
authors.initials: A
authors.lastname: Ferenczy
authors.forename: Mick
authors.initials: M
authors.lastname: Glant
authors.forename: Maria
authors.initials: M
authors.lastname: Merino
authors.forename: Alistair R W
authors.initials: AR
authors.lastname: Williams
authors.forename: Diana L
authors.initials: DL
authors.lastname: Blithe
mesh_terms: D002986:Clinical Trials as Topic; D004715:Endometriosis / Q000188:drug therapy; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006727:Hormone Antagonists / Q000009:adverse effects*; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy; D011980:Receptors, Progesterone / Q000187:drug effects*; D014594:Uterine Neoplasms / Q000188:drug therapy
chemical_list: D006727:Hormone Antagonists; D011980:Receptors, Progesterone