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Management of SILThomas C. Wright, Jr.
Page # 1
Pathology of the Endometrium
Thomas C. WrightColumbia University, New York, NY
Changes in the Uterus
Thoughout life there are marked changes in thechanges in the size of the uterus
Endometrium
Abnormal uterine bleeding
Most common diseases:
Abnormal uterine bleedingInflammatory conditionsBenign neoplasmsEndometrial cancer
Anatomical Regions
Corpus: Responsive to hormones Thickness changes with cyclecycle
LUS: Thinner than corpusLess hormonally
responsive Hybrid between endocervix and endometrium
Changes in the Uterus
Thoughout life there are marked changes in thechanges in the size of the uterus
Cellular Components
Epithelium: Basalis-type cellSecretory cellsSecretory cellsCiliated cells
Stroma: Stromal cellsStromal granulocytes
Management of SILThomas C. Wright, Jr.
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Endometrium
Composed of both glandular and stromalglandular and stromal elements
Cyclical Changes in the Endometrium
Cyclical Changes in the Endometrium
Early Proliferative PhaseSmall circular glands with numerouswith numerous mitoses are present.
16 Day
Glands are somewhat dilated with secretions
S b l lSubnuclear vacuolesMany mitosesCan't tell if ovulation
has occurred
23 Day
Stroma shows prominent sprial arterioles with predecidual changepredecidual change adjacent to them
Glands contain secretions
Management of SILThomas C. Wright, Jr.
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23 Day
Stroma shows prominent sprial arterioles with predecidual changepredecidual change adjacent to them
Glands contain secretions
26 Day
Stroma shows predecidual change that bridges surface to spiral arteriolesto spiral arterioles
Glands still contain secretions
Cyclical Changes in the Endometrium
Dysfunctional Bleeding
Abnormal bleeding - Dx of exclusion
Definition:
Most patients are anovulatory or short duration cycles
Most common in postpubertal period and perimenopausal period
Can be associated with PCO, stress
Dysfunctional Bleeding
Weakly proliferative endometrium
Endometrium:
Normal proliferative endometriumDisordered proliferative Endometrial hyperplasiaAsynchronously developed endometrium
Persistent ProliferativeDilated proliferative type glands, with pseudostratification p
Focal breakdown common
Due to unopposed estrogen
Management of SILThomas C. Wright, Jr.
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Irregularly Developed
Secretory type glands co-exist with proliferative glands.
This pattern is sometimes seen in women with dysfunctional bleeding
Non-neoplastic Disorders
Iatrogenic endometriumExogenous hormones TamoxifinTamoxifinIUD's
EndometritisMetaplasiasHyperplasia
Progestational Agents
Marked pseudo-decidualization of stroma.
Glands are small with secretory exhaustion
Metaplasias
Tubal metaplasia occurs in setting of estrogen excess or
postmenopausal.Squamous metaplasia frequently occurs in
hyperplasia, neoplasia, CEMI.Mucinous, papillary and eosinophic types
are less common
Tubal Metaplasia
The endometrium looks very much like the epithelium of thethe epithelium of the fallopian tube. Cilia are present.Post-menopausal women with estrogen excess
Squamous Metaplasia
A morule of squamous differentiation isdifferentiation is present in the center of a group of glands with atypical hyperplasia
Management of SILThomas C. Wright, Jr.
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Endometritis
Acute: Microabcesses - stroma / glandsClassically postabortalClassically postabortalStrep., Staphy., GC
Stroma: Stromal cellsStromal granulocytes
Acute Endometritis
This is a post-abortion septic uterus. Abortion wasAbortion was performed by non-medical personnel.
Chronic Endometritis
Multiple plasma cells are identified. These are notThese are not normally seen in the endometrium and when present indicate chronic endometritis
Tubercular EndometritisA caseating granuloma is present with giant
ll TB f thcells. TB of the endometrium is uncommon in the U.S. but is seen not infrequently in many areas of the world
Endometrial Hyperplasia
Abnormal proliferation of endometrialAbnormal proliferation of endometrial glandular epithelium (and often stroma) that lacks stromal invasion.
Endometrial Hyperplasia
Wide spectrum of patients
Associated with prolonged, unopposed exposure to estrogen
Therapy depends on type / patient / setting
Management of SILThomas C. Wright, Jr.
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Endometrial Hyperplasia
The endometrium is markedly thickened and is folded intoand is folded into prominent polypoid masses
Endometrial Hyperplasia
Simple hyperplasia
Current Terminology:
Simple hyperplasiaComplex hyperplasia (adenomatous)Simple atypical hyperplasiaComplex atypical hyperplasia
Simple HyperplasiaDilated proliferative type glands, with pseudostratification
Increased gland:stroma ratio and some "budding"
Due to unopposed estrogen
Complex Hyperplasia
The volume of glands is increased and the glands areand the glands are "crowded"Glands are dilated and have irregular outlines
Complex Hyperplasia
Some glands have papillary projections into theminto themOutlines are complex
AtypicalHyperplasia
There is both cytological and architectural atypiaarchitectural atypia present.The architectural atypia is demonstrated by the cribiforming.
Management of SILThomas C. Wright, Jr.
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AtypicalHyperplasia
"Glands within glands" are seenglands are seen.
There is squamous metaplasia in the center gland.
Endometrial Hyperplasia
Early studies had lots of problems
Understanding its impact:
Early studies had lots of problemsEndometrium is histologically complexCytologic changes are difficult to judgeCan't follow without biopsy
Progression of Hyperplasia*
Simple ("Cystic") 13%
Type of Hyperplasia % to CA
Complex ("Adenomatous") 27%Atypical 75%AdenoCA in situ 100%
Wentz, AJOG, 1984
Progression of Hyperplasia
Simple 80% 19% 1%
Type Regress Persist CA
pComplex 80% 17% 3%Simple atypical 69% 23% 8%Complex atyp. 57% 14% 29%
Progression of Hyperplasia
EndometriumConstant estrogen
Hyperplasia
Simple Hyperplasia Atypical HyperplasiaAdenocarcinoma
Otherfactors
Neoplastic Disorders
Endometrial polypsEndometrial stromal lesionsEndometrial stromal lesionsEndometrial carcinomasMesenchymal tumorsMixed tumors
Management of SILThomas C. Wright, Jr.
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Endometrial Polyps
Are quite common, especially 40 - 50 yrs.
Develop as focal hyperplasia of basalis.
F l i f tFour classic features:
Fibrotic stroma
Prominent vascularity
Glands out of phase
Irregular gland architecture
Endometrial Polyp
Small soft polyp arises from the fundus of thefundus of the uterus
Endometrial Polyp
Endometrial Polyp
Uterine Leiomyoma
Proliferation of smooth muscle cells
Lesion of reproductive yearsLesion of reproductive years
20 - 30% of women 30 years and older
More common in blacks
Present with bleeding, pain, pressure
Uterine Leiomyomas
In reproductive yrs - rare after menopause
Pathogenesis:
In reproductive yrs rare after menopauseContain estrogen / progesterone receptorsHormones thought to play a roleGonadotropin releasing hormone agonists
cause regression
Management of SILThomas C. Wright, Jr.
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Uterine Leiomyomas
Lesions are monoclonal - G6PD or PCR
Pathogenesis:
Non-random chromosomal abnormalities quite common (40% of cases)
30% of abnormal karotypes involve region 12q14-15 (same area as involved in lipomas and rhabdosarcomas)
Fibroid Uterus
The uterus is distorted by multiple intramuralmultiple intramural leiomyomas.
Fibroid Uterus
Cut section through this leiomyoma showsleiomyoma shows a well-demarcated firm mass with a whorled appearance
Leiomyoma of the Uterus
Endometrial Carcinomas
Most common genital tract cancer
Clinical features:
High incidence in North America / EuropeAssociated with ERT, obesity, diabetes,
hypertension, nulliparity, tamoxifinTwo clinico-pathologic forms
Endometrial Adenocarcinoma
A necrotic mass arises from the posterior wall of theposterior wall of the uterus and protudes into the endometrial cavity.
Management of SILThomas C. Wright, Jr.
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Extensive and Deeply Invasive Cancer
WHO Classification
Endometrioid carcinomaSerous carcinomaClear cell adenocarcinomaClear cell adenocarcinomaMucinous adenocarcinomaSquamous cell carcinomaMixed carcinomaUndifferentiated carcinoma
Endometrial Cancer - Types
Age Young Old
Type I Type II
g gUnopposed estrogen Yes NoDiabetes / obesity Yes NoGrade / stage Low HighSurvival Good Poor
EndometrioidAdenocarcinomaThis is a well-
differentiated lesionBack-to-back glands
with little intervening stroma
No solid areasDifficult to identify
"stromal invasion"
EndometrioidAdenocarcinoma
Glands are pseudo-stratified with multiple layers
Enlarged, round nucleiCoarse chromatinProminent nucleoli
Uterine Serous Carcinoma
Usually papillaryLooks like ovarian CAHigh nuclear gradePoor prognosis
Management of SILThomas C. Wright, Jr.
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Uterine Serous Carcinoma
Very high nuclear grade tumor
Histology resemblesHistology resembles that of ovarian papillary serous CA
Endometrial Cancer
Based predominantly on architecture:
Histological grading:
< 5% solid well-differentiated5 - 50% solid moderately diff> 50% solid poorly differentiated
High nuclear grade can increase the grade
Endometrial Cancer
Age Depth of in asion
Prognostic features:
Age Depth of invasionStage Peritoneal cytologyRace Vascular invasionGrade
FIGO Staging - Corpus Cancer
IA Tumor limited to endometriumIB Invasion to <1/2 of myometriumIC Invasion to > 1/2 myometriumII Involvement of corpus and cervixIII Extension outside of uterus, but not
outside of true pelvisIV Extends outside true pelvis or involves
mucosa of bladder or rectum
FIGO Stage: 5 Year Survival
Stage 1 11,035 73%
No. % Survival
Stage 2 2,014 56%Stage 3 921 32%Stage 4 409 11%
