Endometrial Intraepithelial Neoplasia

Endometrial intraepithelial neoplasia is a clonal, premalignant proliferation of endometrial glands with cytological atypia. It is equivalent to atypical endometrial hyperplasia.

• Roughly one quarter or more of women with it on biopsy have an endometrial cancer found at hysterectomy.
• Risk factors are obesity, diabetes, anovulation, unopposed oestrogen, tamoxifen and Lynch syndrome.
• The standard treatment is hysterectomy; fertility sparing treatment is possible in selected women.

Abnormal uterine bleeding, postmenopausal bleeding, heavy menses, or no symptoms.

• Obesity, hypertension and diabetes are frequent.
• Differential diagnosis: endometrial cancer, hyperplasia without atypia, endometrial polyp, submucosal fibroid, atrophic bleeding, cervical or ovarian cancer.
• Complications: coexisting or later endometrial cancer, anaemia, recurrence after conservative treatment.

Diagnosis is by endometrial biopsy reviewed by an experienced pathologist.

• Transvaginal ultrasound.
• Endometrial biopsy with histology; hysteroscopic biopsy for focal lesions; review by an experienced pathologist.
• Pelvic MRI to exclude myometrial invasion before conservative treatment.
• Full blood count; liver and renal function; fasting glucose; CA-125 if an ovarian mass is present.
• Family history for Lynch syndrome.

Offer hysterectomy as standard treatment, with conservative progestogen therapy only for selected women.

• Supportive: weight loss; control of diabetes and blood pressure; counselling on cancer risk and fertility; plan multidisciplinary review.
• Pharmacological: for women who decline or cannot have surgery, or who wish to preserve fertility after MRI excludes invasion: levonorgestrel 52 mg intrauterine system, with or without megestrol acetate 160 mg oral daily, for at least 6 months. Anaemia: ferrous sulphate 200 mg oral 8-hourly, continued for 3 months after haemoglobin normalises.
• Procedures: total hysterectomy with bilateral salpingectomy, and bilateral oophorectomy for women after menopause or aged 45 or over, with the specimen examined for cancer. For conservative treatment, repeat hysteroscopic biopsy every 3 to 6 months; hysterectomy after childbearing or if there is no response at 6 to 12 months.
• Special groups: in pregnancy wanted after treatment, refer for assisted reproduction and give cyclic progestogen after delivery. In women with venous thromboembolism avoid oral progestogens and use the intrauterine system.
• Red flags: cancer on hysterectomy specimen, progression on repeat biopsy, myometrial invasion on MRI, persistent bleeding.
• Follow-up: biopsy every 3 to 6 months while treated conservatively until two negative biopsies; yearly review after hysterectomy for symptoms.