Endometrial Hyperplasia
Etiology / Epidemiology:
- Prolonged estrogen exposure unopposed by
progesterone
- Atypical hyperplasia may emerge as a clonal
process usually in a background of hyperplasia without atypia
- Perimenopause most common
- Mean 53 years for atypical hyperplasia
- Risk factors for endometrial hyperplasia:
- Obesity
- Polycystic ovarian syndrome
- Diabetes
- Hereditary tumour
syndromes predispose to atypical hyperplasia and endometrioid
endometrial carcinoma:
Common sites:
Gross features:
- Varies from uniform 5 mm thick to highly
thickened (up to 1 cm) with sometimes polypoid or spongy with cysts
- typically diffuse thickening of endometrium
- may simulate a polyp or have concurrent endometrial
polyp (1/3)
- velvety, knobby surface of pale, spongy
tissue with vague borders
Histologic features:
- Hyperplasia without atypia (previously simple
non-atypical hyperplasia, or complex endometrial hyperplasia without
atypia):
- Spectrum of changes is typical
- Proliferation of glands of irregular size and
shape
- Varying density of glands to stroma
- Increase in gland to stroma ratio compared
with proliferative endometrium
- Separated by varying amounts of stroma
including back-to-back crowding
- Varying size and shape
- Some normal coiled, some branching or cystically dilated
- No significant cytologic
atypia
- Epithelium stratified columnar type
- Focal hemorrhage and stromal breakdown commonly
- Disordered proliferative-phase: proliferation
of glands that exceeds that of normal proliferative endometrium but
falls short of the crowding seen in hyperplasia
- Atypical hyperplasia / Endometrioid
intraepithelial neoplasia (EIN) (formerly complex atypical hyperplasia):
- Cytologic
atypia (variable) superimposed on endometrial hyperplasia:
- Nuclear atypia may include:
- Enlargement
- Pleomorphism
- Rounding
- Loss of polarity
- Nucleoli
- Metaplastic changes often accompanying (no
bearing on clinical outcome)
- May be difficult to distinguish nuclear
features in metaplastic changes from nuclear atypia in atypical
hyperplasia
- Distinction from endometrioid
endometrial carcinoma:
- Loss of intervening stroma (confluent
glandular or cribriform pattern)
- Desmoplastic reaction
- Papillary architecture
- (Old classification):
- Without cytological (nuclear) atypia:
- pseudostratified epithelium (2-4 layers)
- nuclei similar to proliferative endometrium:
- oval or cigar-shaped
- basally oriented
- smooth, uniform contours
- homogenous chromatin
- With cytological (nuclear) atypia:
- Loss of polarity of nuclei
- Greater N:C ratio
- Pleomorphic nuclei, tend to be round rather
than cigar shaped
- Vesicular appearance with chromatin clumping,
thickened irregular nuclear membrane, and prominent nucleoli
- These features should be identified without a
diligent search
- Simple hyperplasia:
- Increased gland:stroma
ratio (but not back-to-back)
- Typically variation in gland size and shape
- some cystically
dilated glands with occasional outpouchings, AND/OR
- focal crowding of glands
- stroma more densely packed than proliferative
endometrium
- Complex hyperplasia:
- Defined by back-to-back glandular crowding,
compressing the intervening stroma
- Usually complex glandular outlines, with
branching and papillary infoldings
Immunophenotype:
Marker:
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Sensitivity:
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Specificity:
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Molecular features:
- Hyperplasia without atypia:
- Low levels of somatic mutations in scattered
histologically unremarkable glands
- Atypical Hyperplasia:
- Many of the same genetic changes seen in endometrioid endometrial carcinoma
- Microsatellite instability
- PAX2 inactivation
- PTEN mutation
- KRAS mutation
- CTNNB1 (Beta-catenin) mutation
Other features:
- Hyperplasia without atypia:
- 1-3% progression to endometrial carcinoma (WD)
- Atypical hyperplasia:
- 25-35% of biopsies with atypical hyperplasia
will have cancer at hysterectomy or 1 year follow-up
- 14 to 45- fold risk in long term
- Coexisting endometrial carcinoma in 25-40%
- Coexisting hyperplasia without atypia maybe
- 30% risk of progression to malignancy
in complex atypical hyperplasia
- 8% risk of progression to malignancy
in simple atypical hyperplasia
- 1% risk of progression to malignancy
in simple/complex typical hyperplasia
- Abnormal non-cyclical vaginal bleeding
perimenopause most common
References:
- ?Blaustein
- WHO Classification of Tumours
of Female Reproductive Organs (2014)