Endometrial hyperplasia and atypia: WHO 2014 classification and management

Also known as Endometrial hyperplasia · Atypical hyperplasia · Endometrial intraepithelial neoplasia · EIN · Complex atypical hyperplasia · Endometrial precancer

Exam-exhaustive FRANZCOG fellowship foundation on endometrial hyperplasia and atypia: the WHO 2014 two-tier classification (hyperplasia without atypia vs atypical hyperplasia/EIN), the Kurman 1985 progression-risk data, the 42.6% concurrent-cancer rate of the GOG cohort, and the management pathway anchored by the Gallos 2010 systematic review and Gallos 2013 cohorts — progestin doses, surveillance intervals, and hysterectomy thresholds. RANZCOG-primary, globally tagged to MRCOG, ABOG, FRCSC and MRCPI.

high13 referencesUpdated 27 July 202614 min readVerification in progress

Practise this topic

10 MCQs

One-line fellowship answer

Endometrial hyperplasia is an irregular proliferation of endometrial glands with an increased gland-to-stroma ratio. Use the revised 2014 WHO classification — it splits hyperplasia into hyperplasia without atypia and atypical hyperplasia (AH, also termed endometrial intraepithelial neoplasia, EIN) — because cytologic atypia, not architectural complexity, is the dominant predictor of progression to carcinoma. Treat EH without atypia with the LNG-IUS (preferred) or continuous oral progestogen for at least 6 months, with 6-monthly biopsy surveillance. Treat AH with total hysterectomy (BSO if postmenopausal), because the concurrent-cancer rate at hysterectomy is 42.6%; reserve progestin (LNG-IUS first-line) for the woman preserving fertility, with 3-monthly biopsy until two consecutive negatives. ^[1]^[2]^[7]

A 52-year-old with irregular heavy bleeding walks in with an outpatient biopsy report: complex atypical hyperplasia. Your job is not to start a progestin and review in clinic — it is to counsel her about the chance that there is already a carcinoma in the uterus, to organise a gynaecological-oncology referral, and to plan a hysterectomy that may become a cancer operation on the table. This topic turns a histology report into a defensible management plan.^[2]^[7]

Overview and definition

Endometrial hyperplasia is the precursor of type I (endometrioid) endometrial cancer — defined as irregular proliferation of the endometrial glands with an increase in the gland to stroma ratio when compared with proliferative endometrium. It is the most common precursor of endometrial cancer, the commonest gynaecological malignancy in high-income countries, and its incidence is at least three times that of cancer itself.^[7]^[12]

The clinical question is always the same: is there atypia or not? Because atypia — cytologic atypia, the nuclear change — is what separates a lesion that progresses in 1–3 percent of women from one that progresses in 25–50 percent. Everything else, the management, the surveillance, the threshold for surgery, flows from that one histologic call.^[1]^[8]

The numbers you must walk into the station knowing

1.6%Progression without atypia2 of 122, Kurman 1985 — complex non-atypical still only 3%

23%Progression with atypia11 of 48 — and complex atypical 29% (10/35)

42.6%Concurrent carcinoma at hysterectomy for AHGOG cohort, Trimble 2006 — 30.9% of those myoinvasive

94.8%LNG-IUS regressionvs 84.0% oral progestogen, Gallos 2013

^[1] ^[2] ^[4]

References13Show

[1]Kurman RJ, Kaminski PF, Norris HJ The behavior of endometrial hyperplasia. A long-term study of 'untreated' hyperplasia in 170 patients. Cancer, 1985.PMID 4005805
[2]Trimble CL, Kauderer J, Zaino R, et al. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer, 2006.PMID 16400639
[3]Gallos ID, Shehmar M, Thangaratinam S, et al. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol, 2010.PMID 20934679
[4]Gallos ID, Krishan P, Shehmar M, et al. LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study. Hum Reprod, 2013.PMID 23975691
[5]Gallos ID, Krishan P, Shehmar M, et al. Relapse of endometrial hyperplasia after conservative treatment: a cohort study with long-term follow-up. Hum Reprod, 2013.PMID 23466671
[6]Pennant S, Manek S, Kehoe S Endometrial atypical hyperplasia and subsequent diagnosis of endometrial cancer: a retrospective audit and literature review. J Obstet Gynaecol, 2008.PMID 19003662
[7]Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers. Obstet Gynecol, 2012.PMID 23090535
[8]Raffone A, Travaglino A, Saccone G, et al. Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis. Arch Gynecol Obstet, 2019.PMID 30810881
[9]Gallos ID, Ofinran O, Shehmar M, et al. Current management of endometrial hyperplasia-a survey of United Kingdom consultant gynaecologists. Eur J Obstet Gynecol Reprod Biol, 2011.PMID 21658836
[10]Gallos ID, Devey J, Ganesan R, et al. Predictive ability of estrogen receptor (ER), progesterone receptor (PR), COX-2, Mlh1, and Bcl-2 expressions for regression and relapse of endometrial hyperplasia treated with LNG-IUS: a prospective cohort study. Gynecol Oncol, 2013.PMID 23603367
[11]Jain V, Munro MG, Critchley HOD Contemporary evaluation of women and girls with abnormal uterine bleeding: FIGO Systems 1 and 2. Int J Gynaecol Obstet, 2023.PMID 37538019
[12]Marnach ML, Laughlin-Tommaso SK Evaluation and Management of Abnormal Uterine Bleeding. Mayo Clin Proc, 2019.PMID 30711128
[13]Papakonstantinou E, Adonakis G Management of pre-, peri-, and post-menopausal abnormal uterine bleeding: When to perform endometrial sampling? Int J Gynaecol Obstet, 2022.PMID 34669187