Myometrium has rich network of blood vessels; arteries are sometimes found within dilated venous channels, AJSP 2002;26:232; myometrium is PLAP positive

Before puberty: endometrial tissue is inactive and composedof tubular glands, dense fibroblastic stroma, thin bloodvessels

After menopause: inactive (no proliferation or secretion), thin, often with cystic cavities lined by flat or cuboidal cells, fibrotic stroma

Micro images: normal endometrium and cyclin D1 (figures 1A/1B)

Anatomical divisions of uterus

Fundus: cephalad to line connecting the insertion of fallopian tubes

Cornua: lateral regions of fundus associated with intramural fallopian tubes

Isthmus/lower uterine segment: portion of corpus connecting with cervix

Cervix: lower 1/3 of uterus; at and below level of internal cervical os

Uterine cavity: 6 cm long, triangular shape, lined by endometrial mucosa / endometrium, then myometrium, then serosa, which extends to peritoneal reflection

Basalis layer is retained; functionalis layer (superficial 1/2 to 2/3) is shed monthly

Functionalis is divided into spongiosum (near basalis) and compactum (near surface)

Stroma is composed of stromal cells, vessels, stromal granulocytes (T cells, macrophages), foamy cells

Drains to parametrial, paracervical, internal iliac, external iliac, common iliac, periaortic and inguinal lymph nodes

Note: menstruating tissue is replaced by cells from basalis, isthmus and ostio of tubes

Bifid uterus

Gross images: image1

Persistent mullerian duct syndrome

top

Rare form of male pseudohermaphroditism caused by lack of regression of Mullerian ducts in phenotypically and genotypically male individuals

Mullerian ducts normally regress in male fetus at 8 weeks due to anti-Mullerian hormone (AMH), which binds to anti-Mullerian type 2 receptor, causing disappearance of Mullerian ducts at 10 weeks of fetal age; mutations of either AMH or receptor block duct regression

<200 cases described in English literature

Usually associated with unilateral cryptorchidism and contralateral hernia

Rarely is bilateral cryptorchidism, pelvic uterus, 2 testes embedded in broad ligament

Associated with testicular germ cell tumors

Case report: clear cell adenocarcinoma of remnant uterus in clinically normal 67 year old man, AJSP 2002;26:1231

Dating of endometrium

top

To date endometrium, should see surface endometrium, but date based on most advanced area

Must biopsy uterine corpus above the level of the isthmus; must also biopsy functionalis as basalis layer does not respond to progesterone

Dating has low interobserver agreement

Difficult to date in patient with IUD or on hormones or if endometrium is non-uniform

Proliferative phase

Length varies from 10-20 days, “ideal” is 14 days; during this phase, glands become more tortuous due to epithelial proliferation, in response to estrogen production and estrogen receptors on epithelium

Early proliferative (days 4-7): thin surface epithelium, straight short glands, compact stroma, minimal mitotic activity, large nuclei

Micro image: image1

Mid proliferative (days 8-10): columnar surface epithelium; longer curving glands, variable stromal edema, numerous mitotic figures

Late proliferative (days 11-14): undulant surface epithelium, tortuous glands with prominent mitotic activity and pseudostratification; dense stroma, subnuclear vacuoles in less than 50% of glands

Ovulation: presence of subnuclear vacuoles in 50% of glands is evidence of ovulation; must biopsy functionalis layer, not basal layer

To rule out anovulatory cycles, should biopsy 2 days before menstruation

Secretory/luteal phase

Traditionally assumed to be 14 days, but may vary

Progesterone secretion inhibits endometrial proliferative active and induces secretory activity

Note: secretory material in glands is NOT specific for secretory epithelium; seen also in disordered proliferative and hyperplastic endometrium and carcinoma

Gross: lush, polypoid, no necrosis; may be hemorrhagic if close to day 28

Day 15: no changes from late proliferative; aka interval endometrium; presence of scattered nuclear vacuoles is NOT specific for ovulation (must be 50% or mor)

Days 16-17 - “piano key” appearance; subnuclear vacuoles (day 16), vacuoles at level of nuclei (day 17)

Micro image: image1

Day 18: luminal vacuoles, smaller size, nuclei approach base of cell

Day 19: intraluminal secretion begins

Days 20-21: maximal secretion

Micro image: image1

Day 22: maximal stromal edema in luteal phase; best time for implantation (“day 22, I'm ready for you”)

Day 23: prominent spiral arterioles (thickened walls, coiling, endothelial proliferation)

Day 24: perivascular pre-decidualization (stromal cell hypertrophy with accumulation of cytoplasmic eosinophilia); serrated / tortuous glands

Day 25: predecidualization below surface endometrium

Day 26: confluence of predecidual tissue; stromal granulocytes (probably lymphocytes) appear

Day 27: prominent stromal granulocytes; focal necrosis and hemorrhage

Day 28: prominent necrosis and hemorrhage, aka shedding (glandular and stromal breakdown); predecidual stroma and glandular exhaustion; nuclear dust at base of glandular epithelium; condensed stroma with overlying papillary-syncytial change; intravascular fibrin thrombi; stromal granulocytes

Note: don’t confuse shedding (nuclear crowding, squamoid appearance, focal cytoplasmic acidophilia) with malignancy

Note: shedding in perimenopausal women with bloody background is consistent with anovulatory cycle

Note: endometrial tissue within vessels does not imply malignancy

Dyssynchronous endometrium

Glands and stroma out of synchronization by at least 2 to 3 days

Luteal phase defect

top

Due to inadequate progesterone production

Associated with infertility and spontaneous abortions

Lag of histologic endometrial date of 3+ days from actual post-ovulatory date (some say 2+ days)

Must be found in 2 consecutive cycles to be clinically significant

Meaning of this diagnosis has been questioned due to substantial variability present in late luteal phase of menstrual cycle, the usual time to obtain an endometrial biopsy

Micro: either immature endometrium or persistence of proliferative changes; may see dyssynchronous endometrium (dissociation between endometrial glands and stroma)

Pregnancy related changes

top

Similar changes seen with intrauterine pregnancy, ectopic pregnancy, progesterone therapy

Arias-Stella reaction

Exaggerated gestational hyperplasia; endometrial glands are enlarged with abundant clear or eosinophilic cytoplasm and marked nuclear changes (large, hyperchromatic, pleomorphic, smudged) with rare mitotic figures; decidualized stroma; changes usually focal, may occur in cervix, endocervical polyps, adenomyosis, endometriosis, post- abortion curettings (20-70%), pregnancies, moles, choriocarcinoma (endometrial nuclei may be gigantic in moles and choriocarcinoma)

DD: clear cell carcinoma (post-menopausal so not pregnant, mitotic figures, coarsely granular chromatin, no decidual reaction unless patient on progesterone), in situ endometrial carcinoma

Decidua

Bland nuclei, minimal atypia, abundant cytoplasm

Gestational hyperplasia

Gross: lush decidua; placental fragments; gestational sac

Micro: early - prominent glandular secretion, stromal edema and predecidual reaction, all simultaneous; implies fertilized ovum has implanted

later - glands are tubular, not coiled; glandular cells have inclusion-like cleared chromatin resembling HSV infection (see below); may see intermediate trophoblasts or villi

DD: late secretory changes in cycling endometrium

Placental site nodules

Aka implantation site reaction

Usually regresses after delivery or abortion

Micro: numerous extravillous (intermediate) trophoblasts, with large, atypical nuclei arranged in a syncytium, often with mitotic figures, that may invade blood vessels (to keep them patent during pregnancy); also cytotrophoblasts and syncytiotrophoblasts; chronic inflammatory cells

Positive stains: hPL (intermediate trophoblasts), hCG (syncytiotrophoblasts, cytotrophoblasts)

DD: leiomyosarcoma, placental site trophoblastic tumor (large masses of intermediate trophoblasts, no villi), choriocarcinoma (laminar pattern of syncytiotrophoblasts and cytotrophoblasts with extensive hemorrhagic necrosis, no villi)

Viral-like inclusions

Optically clear nuclei, resembling viral inclusions, present during pregnancy

Due to replacement of chromatin by fine filamentous network that is biotin immunoreactive

Endometrial curettage and biopsy

top

D & C (dilatation and curettage) and endometrial biopsy are methods of choice for sampling localized lesions

Fractional curettage: separate sampling from endometrial and endocervical cavities during same procedure; do endocervix first to minimize contamination

Note: report endocervical extension of a tumor only if normal endocervical glands and carcinoma are present in the SAME fragment

Asherman’s syndrome: intrauterine adhesions after D & C, causing amenorrhea; usually postpartum or post-termination, may be due to subclinical uterine infection

Endometrial biopsy: to evaluate infertile or dysmenorrheic patients; sensitive if done properly

Helpful clinical information: patient’s age, date and characteristics of last and current menstrual period, use of hormones/steroids, chief complaint, physical findings

Exogenous hormones

top

Current oral contraceptives

Small doses of estrogen and progesterone

Micro: endometrial glandular arrest with small, straight and inactive glands, no mitotic figures, no secretion; glands lined by immature epithelial cells, nuclei lack thick nuclear membrane or coarse chromatin seen in proliferative endometrium; cytoplasm has randomly distributed vacuoles and smooth, well defined apical border; glands may have dense eosinophilic secretion (abortive secretion); stroma initially edematous, then decidual with granulocytic infiltrates; vessels are thin, later become dilated, lack changes of spiral arterioles (thickening, coiling) at day 23; also endocervical microglandular hyperplasia and squamous metaplasia

Prolonged use: disappearanceof abortive glandular secretion, atrophy of glands and stroma

Micro images: image1

Ovulation Induction Therapy
Treatment for ovulation failure (irregular or infrequentovulation or chronic anovulation due to deficient gonadotropinsor their inability to stimulate follicle maturation)

In polycystic ovary disease patients, may see endometrial hyperplasia with secretory changes of the glands and stroma, or rarely carcinoma

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

Micro images: image1

Estrogens alone for hormone replacement therapy

Used for hormone replacement therapy (post-menopausal, premature ovarian failure, post-oophorectomy, Turner’s syndrome)

Causes hyperplasia, some with 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, reduces risk of hyperplasia and carcinoma

Compared to oral contraceptives, uses lower dosages and different estrogens

Micro: 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

These changes may persist after therapy ends

Micro images: image1, image2

Combined hormone replacement therapy

Variable changes, often with mixed proliferative and secretory endometrium

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

Micro images: image1

DD: carcinoma

Lupron for leiomyomas

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

Micro: leiomyomas initially show edema and necrosis, then hyalinization and mild lymphocytic infiltrate; endometrium becomes weakly proliferative, later inactive, later atrophic

Progestational agents

Used for endometrial hyperplasia and neoplasia, particularly in young women who don’t want hysterectomies or are poor surgical candidates

Micro: lack of glandular proliferation (no mitotic activity), presence of secretory changes inglands, decidual stroma. The endometrialtissue appears quiescent, with no mitotic activity

Note: hyperplasia and carcinoma may persist in sampled or unsampled endometrium

DD: pregnancy (glands not atrophic), sarcoma (nuclear atypia)

Tamoxifen

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: uterine size up to 1 kg

Gross images: image1

Micro: polypoid endometrial proliferation with glandularhyperplasia (simple, complex, with or without atypia), mucinous and squamous metaplasia, fibrotic stroma, diffuse smooth muscle hyperplasia, leiomyomas,adenomyosis; also inactive or atrophic changes

Micro images: image1, carcinoma

Hormonal therapy in the past

Associated with pulmonary emboli, thrombophlebitis (intimal thickening with endothelial proliferation)

Less likely now due to smaller hormonal doses

Reference: Mod Path 2000;13:285

Endometritis

top

Endocervix normally forms barrier to ascending infection

Acute endometritis

Limited to post-delivery or miscarriage

Due to retained products of conception or instrumentation

Must see microabscesses plus infiltration and destruction of glandular epithelium, as neutrophils are common in cycling endometrium

Chlamydia

Associated with severe acute/chronic inflammation

Chronic endometritis

In women with pelvic inflammatory disease (PID), postpartum, post-abortion (retained tissue), IUD, tuberculosis (miliary or TB salpingitis), symptomatic bacterial vaginosis

Probably not associated with Chlamydia trachomatis infection

15% have unknown cause (may be chlamydia, give antibiotics)

Note: lymphoid follicles are normal in functional layers of endometrial mucosa and do not constitute chronic endometritis

Micro: spindly stroma with edema; focal early breakdown with surface neutrophils; associated with weakly proliferative glands; plasma cells are characteristic, but one plasma cell is probably not enough; usually also histiocytes, lymphocytes and lymphoid follicles are present; usually significant glandular alterations make dating impossible; also focal necrosis or focal calcification

Myometrium usually spared unless inflammation severe

DD: hyperplasia

CMV

May be granulomatous

Coccidiomycosis

May be secondary to resolved primary lung infection

Giant cell arteritis

May involve uterus as isolated finding or part of generalized giant cell arteritis

Granulomas

Due to sarcoid, tuberculosis, CMV, post-laser ablation for post-menopausal bleeding

Hematometra

Blood within uterine cavity, usually due to cervical occlusion

Endometrial mucosa is replaced by lipid laden histiocytes (xanthogranulomatous endometritis)

Called “ceroid containing histiocytic granuloma” if histiocytes contain yellow-brown cytoplasmic pigment

Intrauterine device (IUD)

2/3 have abnormal endometrium at biopsy; often focal or extensive chronic endometritis, necrosis, squamous metaplasia

May be associated with PID and tubo-ovarian abscesses

Infection rate is 13%

Actinomyces common

Pyometra

Pus in endometrial cavity

Due to obstruction and infection; occasionally due to carcinoma, more commonly due to benign cervical stricture

Sarcoidosis

Granulomas usually spread to myometrium (in contrast to TB)

Tuberculosis

Rare in US; common in other countries, where it causes infertility

Plasma cells and white blood cells may be present due to secondary infection; acid fast bacilli present in tubercles or culture

Granulomas tend to accumulate in superficial functional layers of endometrium, so biopsy during late secretory phase

Xanthomatous endometritis

Associated with cervical stenosis and pyometra, usually in elderly

Micro: contains sheets of foamy cells

Endometrial metaplasia

top

Must evaluate metaplasia separately from hyperplasia

Tends to be associated with adenocarcinoma and is more common in women at high risk for endometrial carcinoma

Clear cell metaplasia (mesonephric / mesonephroid)

Tall cells, apical nuclei, clear cytoplasm; no atypia

DD: clear cell adenocarcinoma

Eosinophilic (oxyphilic) metaplasia

Estrogen-induced, resembles atypical hyperplasia except there is no atypia

Intestinal metaplasia

Rare

Mucinous metaplasia

Resembles endocervical mucosa; benign features

Associated with hyperestrogen states, endometrial polyps

May produce mucometra if cervical stenosis present

Mucin pools are associated with neutrophils

Papillary proliferation / papillary change

Rare, usually post-menopausal women

Usually benign behavior

Polypectomy or curettage appears to be adequate treatment, AJSP 2001;25:1347

More aggressive treatment may be needed for extensive complex papillary proliferations

Gross: 0.7 cm to 3.0 cm in size, 2/3 occur in endometrial polyps

Micro: focal areas of fibrovascular cores without atypia, usually near endometrial surface

Either simple or complex papillary patterns; often metaplastic epithelial changes

DD: well differentiated / low grade papillary adenocarcinoma, surface syncytial change

Squamous metaplasia

Occurs in normal or hyperplastic endometrium, polyps, leiomyomas

Usually diffuse (adenoacanthosis) or in morules (rounded aggregates of bland cells with indistinct cytoplasmic borders)

Usually in pre-menopausal women, with exogenous hormones or with polycystic ovary disease; also associated with foreign-body reactions, chemical irritants, endometritis

Note: central necrosis of morules is common, and not specific for malignancy

Ichthyosis uteri: complete replacement of endometrium by squamous epithelium

DD: well differentiated endometrial adenocarcinoma with squamous metaplasia

Stromal metaplasia

Formation of smooth muscle, cartilage, bone

DD: retained fetal parts

Syncytial change

Aka papillary syncytial change, surface syncytial change

Reparative change in endometrial biopsies and curettings from patients with uterine bleeding

Associated with anovulatory dysfunctional bleeding, endometrial hyperplasia, estrogen usage, or other hormonal treatment

Micro: denuded endometrial surface produced by breakdown or breakthrough bleeding covered by sheet-like plaque of regenerating epithelial cells, often eosinophilic, without discrete cell boundaries; nuclear debris, neutrophils, rounded clumps of endometrial stromal cells usually present; usually no papillae with fibrovascular cores; may resemble microglandular hyperplasia due to small glandular lumina or pseudolumina

Micro images: image1, image2

Reference: Mod Path 2000;13:309

Tubal (ciliated cell) metaplasia

Markedly increased ciliated cells (non-metaplastic endometrium have some ciliated cells), resembles fallopian tube; often seen with endometrial hyperplasia and other hyperestrogenic states

Micro images: image1

Reference: Mod Path 2000;13:309

Adenomyosis

top

Endometrial glands and stroma deep in myometrium

Causes menorrhagia, pelvic pain during menstruation; rarely causes rupture during pregnancy

15% of uteri

May be a type of diverticulosis

May be involved by hyperplasia or carcinoma

Gross: numerous small cysts in enlarged and globular uterus, associated with myometrial hypertrophy and trabeculated smooth muscle; cannot be shelled out; in elderly women, uterus may appear atrophic;

Gross images: image1

Micro: stroma plus marker glands deep in myometrium (at least one low power field from endomyometrial junction, which is usually irregular); often smooth muscle hypertrophy present around glands; usually consists of basal layer of endometrium that may be connected with mucosa; usually proliferative endometrium, although only 25% is proliferative during secretory phase; microscopic foci may be in vascular spaces resembling endometrial stromal sarcoma

Micro images: imag #1; #2; #3

DD: endometrial stromal sarcoma (no glandular tissue, invades myometrium in tongues, no muscular hypertrophy, unusual to contain diffuse small regular glands )

Endometriosis

top

Endometrial tissue outside the uterus; closely related to adenomyosis

Women 20-30 years old, up to 10% of all women affected

Consists of functional layers of endometrium that go through menstrual changes, although is more proliferative than normal endometrium

Causes pain, infertility (1/3 of women are infertile)

Causes: regurgitation (retrograde menstruation), metaplasia, angiolymphatic dissemination (to lungs, nodes); metaplastic change of secondary mullerian system represented by pelvic mesothelium

Sites: Ovaries > uterine ligaments > rectovaginal septum > pelvic peritoneum > scar

Rarely in lymph nodes, usually with cuboidal epithelium, no stroma, limited to capsule, resembles tubal epithelium; call endosalpingiosis

May undergo malignant transformation (endometrioid > clear cell, endometrial stromal sarcoma, MMMT)

Organizing hemorrhage may cause adhesions, ovarian chocolate cysts

Treatment: hormones, surgery

Diagram

Gross: blue cystic nodules surrounded by fibrosis; rarely polypoid masses simulating a neoplasm

Gross images: image1, image2, image3

Micro: contains at least two of three features - endometrial glands, endometrial stroma, hemorrhage

may be a dense fibrous mass; may undergo mucinous metaplasia aka endocervicosis or myxoid change

Associated with perineurial invasion

Micro images: image1, image2

Cytology images: contributed by Dr. Carmen Luz - sheet of endometrial epithelium in FNA from abdominal wall; sheet of endometrial epithelium besides a group of endocervical epitelium and endometrial stroma from an endometrial direct cytology; round endometrial epithelial group with slight atypia

DD: well differentiated adenocarcinoma if endocervicosis present; pseudomyxoma peritonei if myxoid change

Dysfunctional uterine bleeding (DUB)

top

Definition: bleeding >5 days of unknown cause in women of child bearing age; a clinical term, not a pathologist term

Known causes: endometriosis, submucous myoma, endometrial polyp (5-15%), cancer (5-15% of postmenopausal bleeding), precocious puberty, anovulatory cycle, pregnancy complication, physical lesion (leiomyoma, adenomyosis, endometrial hyperplasia), endocrine disorder, ovarian lesion (granulosa-theca tumor), metabolic disturbance (obesity, malnutrition), exogenous hormones, drugs with hormonal side effects, luteal phase defect, chronic inflammation, ectopic pregnancy, idiopathic stromal predecidualization in postmenopausal women

May be due to degenerative changes in uterine blood vessels associated with atrophy

Can classify based on ovulatory or non-ovulatory cycles:

If patient ovulates, may be due to inadequate proliferative phase, inadequate secretory phase, irregular shedding or membranous dysmenorrhea

Inadequate proliferative phase: disparity between clinical menstrual cycle date and microscopic changes (usually delayed morphologic changes of proliferation)

Inadequate secretory phase: discrepancy of 2+ days between microscopy and clinical cycle date; biopsy shows underdeveloped secretory endometrium or secretory and proliferative endometrium in same specimen; also irregular shedding; due to low progesterone; associated with infertility, amenorrhea; treated with hormones

Irregular shedding: bleeding 7 days or more, due to lag in shedding of secretory endometrium, which is normally completed by day 4 of menstruation; should do biopsy on day 5+ of menstruation; biopsy shows retained secretory endometrium, fragmented menstrual endometrium, proliferative endometrium; occurs in 10-17% of DUB cases; associated with luteal phase defect

Membranous dysmenorrhea: rare, endometrial cast passed during menstruation, resembles decidua; may be due to exogenous progesterone

Anovulatory cycle: proliferative endometrium during chronological secretory phase; usually causes endometrial hyperplasia

Micro: fibrin clumps in endometrial stroma (not present in normal menstrual stroma), stromal crumbling (fragmented pieces with dense stromal cellularity); exogenous hormones cause predecidual stroma, edema, wimpy tubular glands of different sizes

Endometrial hyperplasia

top

Proliferation of glands of irregular size and shape with an increase in the gland to stroma ratio compared with proliferative endometrium

Usually in perimenopausal women

Usual predecessor to endometrial carcinoma, particularly younger women or those with well differentiated endometrioid adenocarcinoma, although most with hyperplasia do NOT develop carcinoma

Risk of developing carcinoma is greater with complex or atypical changes

Even among experts, discordance is common on hyperplasia vs. no hyperplasia in endometrial biopsies of women on hormone replacement therapy, AJSP 2002;26:1269

Often overdiagnosed

Causes: prolonged estrogenic stimulation with reduced progestational activity (usually near menopause or associated with anovulatory cycles), polycystic ovarian disease (Stein-Leventhal syndrome), ovarian granulosa cell tumors (functional), ovarian cortical stromal hyperplasia, estrogen replacement therapy without progestational agents

Disregard cystic changes since they are secondary and can be found without hyperplasia, although presence of cysts usually means hyperplasia is mild

Treatment: progestins (causes sheets of luteinized stroma and dilated glands resembling Swiss cheese) or hysterectomy (for complex atypical hyperplasia only)

Gross: lush, polypoid endometrium

Gross images: image1

Micro: gland to stroma ratio should be 3:1 (i.e. stroma is 1/3 of volume or less); usually associated with proliferative endometrium (pseudostratification or stratification), may have secretory features if patient receiving progesterone; stroma should also be hyperplastic

Metaplasia common: squamous, ciliated cell, mucinous; grade hyperplasia separate from metaplastic changes

DD: polyps, endometritis, artifacts, metaplasia, normal endometrium

Reference: Mod Path 2000;13:309

Disordered proliferative endometrium

Associated with anovulatory cycles, common in perimenopausal and menopausal women; also exogenous estrogen therapy

Resembles normal exuberant proliferative endometrium, but without uniform glandular development (some glands cystically dilated, others have shallow budding)

Increase of cystically dilated glands, but relatively normal ratio of glands to stroma

Sternberg indicates this diagnosis is “insufficient for diagnosis of hyperplasia”, although WHO calls a form of simple hyperplasia

Metaplastic changes (ciliated epithelium) are common

May see endometrial breakdown and hemorrhage with thrombosed, thin walled vessels

Simple hyperplasia

Aka cystic hyperplasia or mild hyperplasia

Usually evolves to cystic atrophy, ~5% to adenocarcinoma without atypia, ~7% to carcinoma with atypia

Usually lacks atypia

Gross: increased endometrial volume, qualitatively different from normal cycling endometrium

Micro: changes in glands and stroma so that glands are not particularly crowded; glands usually round, but may be irregular with cystic dilation; lining epithelium is pseudostratified or mildly stratified; occasional mitotic figures (less than proliferative endometrium); cellular stroma with variable mitotic activity, uniformly distributed blood vessels

Micro images: image1, image2

DD: endometrial polyps (fibrotic stroma with dilated, thick-walled blood vessels), cystic atrophy (glands lined by reduced epithelium, stroma is dense and atrophic), disordered proliferative endometrium (few widely scattered cystic glands, less than hyperplasia), artifacts (fragmented endometrium with artifactually compressed glands-image; telescoping of glands-image), chronic endometritis (may have reactive glandular changes causing crowding, abnormal glandshapes, and variable atypia; but has plasma cells, stromal spindling andedema, surface neutrophils)

Reference: Mod Path 2000;13:309

Complex hyperplasia

Increase in number and size of endometrial glands with crowding of stroma, budding

By definition, some normal stromal cells are present between adjacent glands

~16% without atypia progress to carcinoma; ~47% with atypia progress to carcinoma

Complex pattern may be secretory with eosinophilic metaplasia

High grade (with atypia): rounding of nuclei and formation of nucleoli; stratification, scalloping, tufting, loss of polarity, cytomegaly, hyperchromatism, pleomorphism, mitotic figures; may resemble adenocarcinoma but no stromal invasion or desmoplasia; 23% progress to endometrial adenocarcinoma

Micro images: without atypia

Reference: Mod Path 2000;13:309

Atypical Hyperplasia
If diagnosed at biopsy or curettage, 15%-50% of immediatehysterectomy specimens will have adenocarcinoma, some myoinvasive

Micro: cytologic atypia, usually focal, in a background of complex and rarely simple hyperplasia; usually cellular dyspolarity,irregular stratification, anisocytosis, nuclear rounding, nucleomegaly, hyperchromatism,chromatin clumping, and enlarged nucleoli; may have marked cytoplasmic eosinophilia or eosinophilicnecrotic debris within the atypical cells

Should contrast “atypical” gland with adjacent “non-atypical” glands

Sternberg suggests calling “borderline” if unable to rule out well differentiated carcinoma

Micro images: complex hyperplasia with atypia, atypia

DD: metaplastic changes, atypical hyperplasia with secretory changes resembles secretory carcinoma

Table of Contents

Corpus is upper 2/3 of uterus above level of internal cervical os

Anatomical divisions of uterus

Bifid uterus

Proliferative phase

Secretory/luteal phase

Dyssynchronous endometrium

Arias-Stella reaction

Decidua

Gestational hyperplasia

Placental site nodules

Prolonged use: disappearance of abortive glandular secretion, atrophy of glands and stroma

Estrogens alone for hormone replacement therapy

Combined hormone replacement therapy

Progestational agents

Acute endometritis

Chlamydia

Chronic endometritis

CMV

Giant cell arteritis

Granulomas

Pyometra

Tuberculosis

Xanthomatous endometritis

Eosinophilic (oxyphilic) metaplasia

Mucinous metaplasia

Squamous metaplasia

Tubal (ciliated cell) metaplasia

Disordered proliferative endometrium

Simple hyperplasia

Complex hyperplasia

Prolonged use: disappearanceof abortive glandular secretion, atrophy of glands and stroma