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Non tumor

Endometrial hyperplasia

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 31 December 2011, last major update December 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.


● Ranges from mild, reversible glandular proliferations to direct cancer precursors (Semin Diagn Pathol 2010;27:199)
● Proliferation of glands of irregular size and shape with an increase in the gland to stroma ratio compared with proliferative endometrium
● Incidence: simple-142/100,000 woman-years, complex-213/100,000 woman-years (both in the early 50s); atypical-56/100,000 woman-years (in early 60s, (Am J Obstet Gynecol 2009;200:678)
● Comparing curettage to subsequent hysterectomy, false positive rate of 1.8% and false negative rate of 13.2%; less accurate if use Pipelle endometrial sampler (Eur J Obstet Gynecol Reprod Biol 2011;159:172)
● Disregard cystic changes, since they are secondary and can be found without hyperplasia, although presence of cysts usually means hyperplasia is mild
● Classified based on WHO or EIN systems (J Gynecol Oncol 2010;21:97)
● Poor diagnostic reproducability (Am J Surg Pathol 2008;32:691)


● 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 (Ann Epidemiol 2009;19:1)
● Also associated with higher body mass index (J Reprod Med 2011;56:110)
● Progression from normal to simple to complex hyperplasia associated with reduced levels of von Hippel-Lindau mRNA and protein (Int J Gynecol Cancer 2011;21:430)

Prognostic factors

● 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
● For nonatypical endometrial hyperplasia, risk was 1.2% at 4 years, 1.9% at 9 years, 4.6% at 19 years after diagnosis; for atypical hyperplasia, risk was 8.2% at 4 years, 12.4% at 9 years, 27.5% at 19 years (J Clin Oncol 2010;28:788)
● Focal gland crowding, that does not fulfill all criteria for EIN, carries substantial risk of EIN and occasionally malignancy (Mod Pathol 2010;23:1486)


● Complex hyperplasia: progestins or LNG-IUS (Jpn J Clin Oncol 2011;41:817)
● Atypical complex hyperplasia: hysterectomy

Gross description

● Lush, polypoid endometrium

Gross images

Endometrial hyperplasia

Micro description

● See topics on simple, complex and atypical hyperplasia
● 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
● Progestin treatment causes sheets of luteinized stroma and dilated glands resembling swiss cheese (Mod Pathol 2009;22:450, Mod Pathol 2008;21:591); also reduction of hyperplastic changes and metaplasia (Am J Surg Pathol 2007;31:988)
● Presence of squamous morules is associated with carcinoma (Mod Pathol 2009;22:167)
● Metaplasia common: squamous, ciliated cell, mucinous; grade hyperplasia separate from metaplastic changes

Micro images

Focal gland crowding

Squamous morules


Progesterone receptor modulator associated endometrial changes

Differential diagnosis

● Endometrial polyps
● Endometritis
● Artifacts
● Metaplasia
● Normal endometrium

Additional references

Mod Pathol 2000;13:309

End of Uterus > Non tumor > Endometrial hyperplasia - general

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