Risk of progression in complex and atypical endometrial hyperplasia: clinicopathologic analysis in cases with and without progestogen treatment

Abstract

In most cases, the endometrioid adenocarcinoma of the endometrium is preceded by hyperplasia with different risk of progression into carcinoma. The original histologic slides from 560 consecutive cases with complex and atypical hyperplasia were re-examined to assess the interobserver-correlation. The hyperplasias were analyzed separately for their likelihood of progression to carcinoma in patients with and without progestogen hormonal therapy. In all cases, a fractional re-curreting was performed to establish the state of the disease.The leading symptom was vaginal bleeding in 65.5% of the cases in the postmenopausal period. Eighty-six percent of the patients presented with obesity (BMI > 30 kg/m2), 23% had had an exogeneous use of estrogens. Twenty-two cases were reclassified as simple hyperplasia and excluded from further analysis. The interobserver-correlation was 91% for complex, 92% for atypical hyperplasia, and 89% for endometrioid carcinoma, representing an overall correlation of 90%. Two percent of the cases with complex hyperplasia (8/390) progressed into carcinoma and 10.5% into atypical hyperplasia. Fifty-two percent of the atypical hyperplasias (58/112) progressed into carcinomas. In the case of progestogen treatment (n = 208; P < 0.0001) 61.5% showed remission confirmed by re-curetting, compared with 20.3% of the cases without hormonal treatment (n = 182; P < 0.0001).Endometrial hyperplasia without atypia is likely to respond to hormonal treatment. Especially in postmenopausal situation, atypical hyperplasia should be treated with total hysterectomy.

The endometrial hyperplasias revisited

“…Further support for this conclusion was obtained by Horn et al [40] who, after using the WHO94 classification, reached an overall (interobserver) correlation of 90% which is far better than the overall interobserver agreement of the study of Bergeron et al (70-82%) [40]. Kurman et al [35], Ferenczy and Gelfand [36] and Lacey et al [39] reported comparable results, as these have been analysed in "Classification schemes of endometrial hyperplasia: from anarchy to WHO".…”

“…Despite claims to the contrary, these morphological features could be recognized and reproduced with a fair degree of precision by several independent groups of workers [35,36,39,40,68].…”

“…Simple and complex endometrial hyperplasia can safely be treated with progestins [40,[90][91][92]. Lindahl and Willen presented the 5-year follow-up of 82 patients with endometrial hyperplasia without cytological atypia treated with 500 mg medroxyprogesterone acetate (MPA) i.m.…”

“…Atypical endometrial hyperplasia is traditionally treated by hysterectomy [40,90,92]. Yet, medical treatment (highdose MPA) may be offered to patients with a contraindication to surgery and to young women who wish to retain fertility [92,94,95].…”

“…The study included 138 cases initially diagnosed as endometrial hyperplasia and subsequently evolved to carcinoma . Using the same classification scheme, Horn et al found that 2% of the cases with complex endometrial hyperplasia (eight of 390) progressed into carcinoma as compared to 52% of the atypical hyperplasia cases (58 of 112) [40]. There were also a percentage of cases (10.5%) which from complex endometrial hyperplasia transformed into atypical hyperplasia.…”