Endometrial hyperplasia is believed to produce a continuum of lesions that may be precursor to endometrial carcinoma of endometrioid histology. The classification of endometrial hyperplasia has had numerous terminology. The classification below is currently the most commonly accepted system and is accepted by the World Health Organization (WHO) and the International Society of Gynecologic Pathologists. This system characterizes the glandular architectural pattern as simple or complex and describes the presence or absence of nuclear atypia.
- Simple hyperplasia - Increased number of glands but regular glandular architecture
- Complex hyperplasia - Crowded irregular glands
- Simple hyperplasia with atypia - Simple hyperplasia with presence of cytologic atypia (prominent nucleoli and nuclear pleomorphism)
- Complex hyperplasia with atypia - Complex hyperplasia with cytologic atypia
The original study by Kurman et al found that lesions with varying degrees of complexity and presence of atypia, when left untreated, progressed to adenocarcinoma at different rates. Simple hyperplasia was associated with a 1% rate of progression to cancer, 3% rate of progression to complex hyperplasia, and 8% rate of progression to simple atypical hyperplasia, whereas complex atypical hyperplasia had a 29% rate of progression to cancer.
Once a tissue diagnosis of endometrial hyperplasia is made, treatment depends on the patient's symptoms such as degree of bleeding, presence of cytologic atypia, patient's surgical risks, and wish for future childbearing. Progestins can effectively treat endometrial hyperplasia, and they can serve as prevention of recurrence in those with continued risk factors. Hyperplasia without atypia responds well to progestins. More than 98% of women with hyperplasia treated with cyclic progestins experienced regression of the disease in 3-6 months. The PEPI trial showed a 94% normalization of complex or atypical hyperplasia in 45 women treated with progestins. Multiple regimens of progestin therapy have been found effective in reversing hyperplasia.
- Medroxyprogesterone acetate (Provera), 10-20 mg qd, or cyclic 12-14 days per month
- Micronized vaginal progesterone (Prometrium), 100-200 mg qd or cyclic 12-14 days per month
- Levonorgestrel-containing IUD (Mirena), 1-5 years
- Megestrol acetate (Megace), 40-200 mg per day, usually reserved for women with atypical hyperplasia
If hyperplasia with atypia is found on dilation and curettage (D&C) or endometrial biopsy, definitive treatment with hysterectomy
is recommended due to the high rate of concurrent endometrial cancer. However, if the patient has not completed childbearing or is not a surgical candidate, then concurrent cancer must first be ruled out by D&C with hysteroscopy
prior to medical management. Because D&C and Pipelle biopsy only sample 50-60% of the endometrial lining, focal lesions containing adenocarcinoma may be missed. Biopsy is recommended after 3 months to check for response to medical therapy, and continued surveillance after regression of the lesion is recommended every 6-12 months if risk factors persist.
The need for hysterectomy to exclude concurrent myoinvasive endometrioid adenocarcinoma presents a barrier to nonsurgical management of endometrial hyperplasia. A recent Gynecologic Oncology Group study examined the histomorphometric 4-class rule ("4C", which measures epithelial abundance, thickness, and nuclear variation) as applied to diagnostic biopsies to predict myoinvasive cancer outcomes at hysterectomy.
Women with endometrial biopsies or curettages with a community diagnosis of atypical endometrial hyperplasia were enrolled in a clinical trial in which subsequent hysterectomy was scored for endometrial adenocarcinoma, and 4C rule ability to predict cancer outcomes was measured.
Qualifying biopsies were stratified into high- and low-risk histomorphometric subgroups. Assignment to a high-risk category by 4C rule was highly sensitive in predicting any (71%) or deeply (92%) myoinvasive adenocarcinoma at hysterectomy, and assignment to a low-risk group had a high negative predictive value for absence of any (90%) or deeply (99%) myoinvasive disease.
At present, this use of histomorphometry is most suited to a centralized reference laboratory performing histomorphometry for a variety of diagnostic applications. However, in the future, formal histomorphometry of endometrial biopsies using the 4C rule may become a more common method to identify a subset of women with premalignant disease who are unlikely to have concurrent myoinvasive adenocarcinoma and therefore may qualify for nonsurgical therapy.