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Non tumor

Exogenous hormones

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 14 January 2012, last major update January 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

Hormonal therapy in the past

● Associated with pulmonary emboli, thrombophlebitis (intimal thickening with endothelial proliferation)
● Less likely now due to smaller hormonal doses (Mod Pathol 2000;13:285)

Oral contraceptives

● Have small doses of estrogen and progesterone

Micro description:
● Endometrial glandular arrest with small, straight and inactive glands, no mitotic figures and usually no secretions
● Glands are lined by immature epithelial cells
● Cytoplasm has randomly distributed vacuoles and smooth, well defined apical border
● Nuclei lack thick nuclear membrane or coarse chromatin seen in proliferative endometrium
● Glands may have dense eosinophilic secretion (abortive secretion)
● Stroma initially edematous, then decidual with granulocytic infiltrates
● Vessels are thin, later become dilated and lack changes of spiral arterioles (thickening, coiling) at day 23
● Also endocervical microglandular hyperplasia and squamous metaplasia
● Prolonged use: disappearance of abortive glandular secretion, atrophy of glands and stroma

Atrophic epithelium, stromal decidual reaction, thin dilated blood vessels

High potency progesterone oral contraceptive

● Used for endometrial hyperplasia

Micro description:
● Small inactive glands, hyperplastic stroma, thickened blood vessels
● May cause squamous metaplasia (Arch Pathol Lab Med 1995;119:458)

Small inactive glands, hyperplastic stroma, thickened blood vessels

Ovulation induction therapy

● Used to treat ovulation failure (irregular or infrequent ovulation or chronic anovulation due to deficient gonadotropins or their inability to stimulate follicle maturation)
● In polycystic ovary disease patients, may see endometrial hyperplasia with secretory changes of glands and stroma, or rarely carcinoma

Micro description:
● Dyssynchronous endometrium (stromal maturation [day 22-23] more advanced than glandular maturation [day 16-17])

Stroma more mature than endometrial glands

Estrogens alone for hormone replacement therapy

● Hormone replacement for menopause, premature ovarian failure, post-oophorectomy and Turnerís syndrome
● Causes hyperplasia with variable atypia in 15% of postmenopausal women; also increased risk (4-8x) of endometrial carcinoma, usually superficial and well differentiated with excellent prognosis; also increased risk of breast neoplasms
● Adding progesterone protects the endometrium and reduces risk of hyperplasia and carcinoma
● Compared to oral contraceptives, uses lower dosage and different estrogens

Micro description:
● Proliferative or weakly proliferative endometrium, often with stromal breakdown; endometrial hyperplasia (simple or complex, with or without atypia), occasional squamous metaplasia (squamoid morules), stromal foam cells; endometrial polyps with hyperplastic changes
● Changes may persist after therapy ends

Endometrial complex glandular hyperplasia with squamoid morules

Same patient after combined therapy

Combined hormone replacement therapy

● Variable changes, often with mixed proliferative and secretory endometrium
● May resemble endometrial carcinoma

Micro description:
● Glands may be crowded or hyperplastic with edematous, hyperplastic or decidualized stroma; also tubal, eosinophilic, mucinous or papillary metaplasia; also changes of shedding

Mixed endometrium: secretory endometrium with focally hyperplastic glands

Lupron for leiomyomas

● Gonadotropin releasing hormone agonist that usually reduces size of uterine leiomyomas by suppressing estrogen stimulation and inducing a temporary menopause

Micro description:
● Leiomyomas initially show edema and necrosis, then hyalinization and mild lymphocytic infiltrate
● Endometrium becomes weakly proliferative, later inactive and later atrophic

Progestational agents

● Used for endometrial hyperplasia and neoplasia, particularly in young women who donít want hysterectomies or are poor surgical candidates

Micro description:
● Lack of glandular proliferation; endometrium appears quiescent with no mitotic activity
● Presence of secretory changes in glands, decidual stroma
● Note: hyperplasia and carcinoma may persist in sampled or unsampled endometrium
Differential diagnosis: pregnancy (glands not atrophic), sarcoma (nuclear atypia)

Selective progesterone receptor modulators

● Drugs with progesterone antagonist activity (example: CDB-4124, also known as Proellex) that may confer therapeutic benefit for reproductive disorders (endometriosis, leiomyomas) in premenopausal women
● Produces "progesterone receptor modulator associated endometrial changes"

Micro description:
● Inactive or atrophic endometrium, less frequently proliferative or secretory (Mod Pathol 2009;22:450)
● Cystically dilated glands, secretory changes coexisting with mitoses and apoptotic bodies
● With increasing dose and exposure, epithelium becomes more atrophic and cysts more prominent
● May resemble disordered proliferative or hyperplastic endometrium
● Not associated with endometrial hyperplasia or carcinoma (Mod Pathol 2008;21:591)
● Mifepristone related changes include nonsynchronous endometrium, large fluid filled glands, and abnormal blood vessels (Hum Pathol 2011;42:947)

Endometrial changes

Vascular changes


● Used for breast cancer treatment / prevention
● Binds to estrogen receptors with both agonist and antagonist effects
● Associated with endometrial carcinoma (well to poorly differentiated, may have irregular glandular changes) and MMMT

Gross description:
● Uterine size up to 1 kg

Diffuse adenomyosis, myometrial hyperplasia, endometrial polyps

Micro description:
● Polypoid endometrial proliferation with glandular hyperplasia (simple, complex and with or without atypia), mucinous and squamous metaplasia, fibrotic stroma, diffuse smooth muscle hyperplasia, leiomyomas and adenomyosis; also inactive or atrophic changes
● May produce small blue cells on Pap smear (Arch Pathol Lab Med 2001;125:1047)

Mucinous and squamous metaplasia, resembling endocervical tissue

Fig 1: exuberant pink-tan, friable, bosselated soft tissue bulging into endometrial cavity
Fig 2/3: cystic atrophy of glands with diffuse infiltration of the endometrial stroma by large polyhedral eosinophilic cells, sparse lymphoplasmacellular infiltrate, occasional eosinophils, no atypia

End of Uterus > Non tumor > Exogenous hormones

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