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:
      • Cowden
      • Lynch

 

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
        • Frequent mitotic figures
      • 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:

Sensitivity:

Specificity:

 

 

 

 

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)