Benign tumors of the endometrium

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.

• 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 enodmetrial 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 12th–25th day of the menstrual cycle In women with PCOS: administration of hormonal contraceptive	Progestin therapy
	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