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Benign tumors of the endometrium

Last updated: January 7, 2021

Summary

The most common benign tumors of the endometrium are endometrial hyperplasia and endometrial polyps. Endometrial hyperplasia is caused by an increased estrogen stimulation and manifests with irregular, often heavy vaginal bleeding. There are 2 types of endometrial hyperplasia: endometrial hyperplasia with atypia and endometrial hyperplasia without atypia. Diagnosis involves ultrasound (to assess the thickness of the endometrium) and biopsy (to assess atypia). Treatment of endometrial hyperplasia without atypia consists mainly of progestin therapy, while endometrial hyperplasia with atypia requires hysterectomy. Endometrial polyps are localized overgrowths of endometrial tissue that mainly affect postmenopausal women. Though usually asymptomatic, endometrial polyps can cause irregular vaginal bleeding and, in premenopausal women, infertility. Diagnosis is made with ultrasound or hysteroscopically. Treatment involves watchful waiting in asymptomatic patients and surgical removal in symptomatic patients.

Endometrial hyperplasia

Etiology: increased estrogen stimulation leads to excessive proliferation of the endometrium, e.g., in:
- Follicle persistence in anovulatory cycles
- PCOS
- Estrogen-producing ovarian tumors (e.g., granulosa cell tumors, theca cell tumors)
- Hormone replacement therapy without progestin administration (progestin normally prevents endometrial hyperplasia)
Classification

Classification of endometrial hyperplasia based on histology (WHO 2014) ^[1]
	Endometrial hyperplasia without atypia (benign endometrial hyperplasia)	Endometrial hyperplasia with atypia (endometrial intraepithelial neoplasm)
Histology	Both stromal and glandular cells Appearance varies Simple endometrial proliferation with a few cysts Enlarged, dilated mucous membrane glands (Swiss cheese pattern) located between abundant stromal tissue	Pronounced proliferation of glandular tissue Glands are positioned back-to-back with no separating stroma Clonal, atypical cells with extensive mitosis and loss of cell polarity
Risk of carcinoma	Low (1–3%)	Very high risk of endometrial carcinoma Up to 40% of cases have co-existing invasive endometrial carcinoma ^[2]

Clinical features: vaginal bleeding (intermenstrual, postmenopausal, or constant bleeding)
Diagnosis
- Ultrasonography: to assess endometrial thickening (> 1.5 cm in premenopausal women and > 5 mm in postmenopausal women) ^[3]
- Hysteroscopy-guided or blind endometrial biopsy (rarely dilation and curettage): for histological analysis ^[4]
- Laboratory measures: FSH, estradiol, testosterone
Treatment: : The choice of treatment primarily depends on the presence of atypia and if menopause has occured yet. ^[5]

Treatment of endometrial hyperplasia based on histology
	Premenopausal women	Postmenopausal women
Endometrial hyperplasia without atypia	Progestin therapy: cyclic progestin administration from the 12^th–25^th day of the menstrual cycle In women with PCOS: administration of hormonal contraceptive	Progestin therapy
Endometrial hyperplasia without atypia	All patients receiving progestin therapy should undergo: Ultrasonographic follow-up after 3–6 months Hysteroscopy with biopsy in the case of suspicious findings on ultrasound Just regular surveillance without progestin therapy is indicated if progestin therapy is: Contraindicated (e.g., hormone-responsive cancer, progestin-receptor positive breast cancer) Not tolerated or declined by the patient
Endometrial hyperplasia with atypia	In women with completed childbearing or no future wish to conceive: total abdominal hysterectomy with or without bilateral salpingo-oophorectomy In women with a wish to conceive: progestin therapy and close surveillance with regular endometrial sampling	Total abdominal hysterectomy with bilateral salpingo-oophorectomy

Glandular cystic, simple endometrial hyperplasia Glandular-cystic, simple endometrial hyperplasia (magnified)

Endometrial polyps

Definition: focal overgrowth of localized benign endometrial tissue
Characteristics
- Localized within the uterine wall, extends into the uterine cavity
- Can be pedunculated or sessile, single or multiple, and up to many centimeters in size
- May contain smooth muscle cells and/or blood vessels
- Expresses both estrogen and progesterone receptors (estrogen stimulates growth) ^[6]
Epidemiology: prevalence rises with age (most common in postmenopausal women) ^[6]
Risk factors
- Hypertension
- Obesity
- Tamoxifen ; or hormone replacement therapy (e.g., postmenopausal hormone therapy)
- History of cervical polyps
- Lynch syndrome
Clinical features
- Usually asymptomatic
- Irregular menstrual bleeding, spotting, menorrhagia, and postmenopausal bleeding
- Infertility, difficulty conceiving
Diagnostics
- Transvaginal ultrasound
- Hysteroscopy
- Endometrial biopsy to rule out other conditions (e.g., endometrial hyperplasia, carcinoma)
Treatment
- Asymptomatic women: observation and follow-up
- Symptomatic women: surgical removal
Differential diagnosis
- Endometrial hyperplasia
- Endometrial carcinoma
- Uterine leiomyoma
- Also see “Differential diagnosis of dysmenorrhea and menorrhagia.”
Prognosis: ∼ 0.5–4% of uterine polyps are premalignant or malignant ^[7]

References

G. Emons, M. W. Beckmann, D. Schmidt, P. Mallmann, and for the Uterus commission of the Gynecological Oncology Working Group (AGO). New WHO Classification of Endometrial Hyperplasias. Obstetrics and Gynecology. 2015 .
Emad Rakha, Siew Chee Wong, Irshad Soomro, Zia Chaudry, Aarti Sharma, Suha Deen, Stephen Chan, Jafaru Abu, David Nunns, Karin Williamson, Angus McGregor, Robert Hammond, Laurence Brown. Clinical outcome of atypical endometrial hyperplasia diagnosed on an endometrial biopsy: institutional experience and review of literature. The American Journal of Surgical Pathology. 2012 .
Wendy Wolfman. Asymptomatic Endometrial Thickening. Journal of Obstetrics and Gynaecology Canada. 2010 .
Lee-may Chen, Jonathan S Berek, Barbara Goff, S Dizon. Endometrial carcinoma: Clinical features, diagnosis, prognosis, and screening. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/endometrial-carcinoma-clinical-features-diagnosis-prognosis-and-screening.Last updated: November 1, 2019. Accessed: July 20, 2020.
Reed SD, Urban RR. Management of Endometrial Hyperplasia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-endometrial-hyperplasia.Last updated: November 29, 2017. Accessed: March 1, 2018.
Elizabeth A Stewart. Endometrial polyps. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/endometrial-polyps.Last updated: May 25, 2020. Accessed: July 20, 2020.
Stephanie L Wethington, Thomas J Herzog, William M Burke, Xuming Sun, Jodi P Lerner, Sharyn N Lewin, Jason D Wright. Risk and predictors of malignancy in women with endometrial polyps. Annals of Surgical Oncology. 2011 .
Simple Typical Hyperplasia of Endometrium. http://www.pathologyatlas.ro/simple-hyperplasia-endometrium.php. Updated: January 30, 2009. Accessed: March 1, 2018.
Reed SD, Urban RR. Classification and Diagnosis of Endometrial Hyperplasia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/classification-and-diagnosis-of-endometrial-hyperplasia.Last updated: April 27, 2017. Accessed: March 1, 2018.
Wang Chiang J. Premalignant Lesions of the Endometrium. In: Huh WK, Premalignant Lesions of the Endometrium. New York, NY: WebMD. https://emedicine.medscape.com/article/269919. Updated: May 13, 2016. Accessed: March 1, 2018.
Endometrial Hyperplasia. https://radiopaedia.org/articles/endometrial-hyperplasia-1. Updated: January 1, 2018. Accessed: March 1, 2018.
Sobczuk K. New classification system of endometrial hyperplasia WHO 2014 and its clinical implications. Menopause review. 2017 .