Obstet Gynecol Sci.  2021 May;64(3):300-308. 10.5468/ogs.20294.

Non-atypical endometrial hyperplasia: risk factors for occult endometrial atypia and malignancy in patients managed with hysterectomy

• Hui LS
• Chin SHM
• Goh C
• Hui LX
• Mathur M
• Kuei TLY
• Xian FCH

• KMID: 2515982
• DOI: http://doi.org/10.5468/ogs.20294

Abstract

Objective
To determine the risk factors for occult endometrial atypia and malignancy in patients diagnosed with non-atypical endometrial hyperplasia (NEH) on endometrial biopsy.
Methods
All new cases of NEH diagnosed between April 2015 and March 2016 at KK Women’s and Children’s Hospital, who underwent hysterectomy as first-line treatment, were included in the study. Patients with a history of endometrial hyperplasia or malignancy were excluded from the study. Patient demographics (e.g., age, parity, body mass index [BMI]), medical history, and clinical presentation were obtained for analysis.
Results
In total, 262 patients were diagnosed with NEH, of which 18.3% (n=48) underwent hysterectomy as first-line management. The average time to surgery was 77.0±35.7 days. All cases were diagnosed by dilation and curettage, and hysteroscopy. The mean age was 51 years, and the mean BMI was 26.9±5.8 kg/m². Histology from the hysterectomy specimen showed 9 (18.8%) patients with atypical hyperplasia and 2 (4.2%) with grade 1, stage 1A endometrioid adenocarcinoma. Patients with higher grade final pathology had significantly lower median parity (1 vs. 2, P=0.039), higher mean BMI (30.1±6.5 vs. 25.9±5.3 kg/m², P=0.033), and BMI ≥30 kg/m² (54.5% vs. 13.5%, P=0.008, odds ratio 7.68), compared to patients whose final histology showed NEH or no residual hyperplasia.
Conclusion
Occult endometrial atypia and malignancy were found in 18.8% and 4.2% of patients with an initial diagnosis of NEH, respectively. High BMI and low parity were identified as significant risk factors for high-grade endometrial lesions in patients with NEH.

Keyword

Endometrial hyperplasia; Endometrial neoplasms; Dilation and curettage

Reference

References

1. Emons G, Beckmann MW, Schmidt D, Mallmann P. Uterus commission of the Gynecological Oncology Working Group (AGO). New WHO classification of endometrial hyperplasias. Geburtshilfe Frauenheilkd. 2015; 75:135–6.

2. Vereide AB, Arnes M, Strame B, Maltau JM, Ørbo A. Nuclear morphometric changes and therapy monitoring inpatients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol. 2003; 91:526–33.

3. Ozdegirmenci O, Kayikcioglu F, Bozkurt U, Akgul MA, Haberal A. Comparison of the efficacy of three progestins in the treatment of simple endometrial hyperplasia without atypia. Gynecol Obstet Invest. 2011; 72:10–4.

4. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of “untreated” hyperplasia in 170 patients. Cancer. 1985; 56:403–12.

5. Amant F, Mirza MR, Koskas M, Creutzberg CL. Cancer of the corpus uteri. Int J Gynecol Obstet. 2018; 143(Suppl 2):37–50.

6. Lacey JV Jr, Sherman ME, Rush BB, Ronnett BM, Ioffe OB, Duggan MA, et al. Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. J Clin Oncol. 2010; 28:788–92.

7. Ilavarasi CR, Jyothi GS, Alva NK. Study of the efficacy of pipelle biopsy technique to diagnose endometrial diseases in abnormal uterine bleeding. J Midlife Health. 2019; 10:75–80.

8. Demirkiran F, Yavuz E, Erenel H, Bese T, Arvas M, Sanioglu C. Which is the best technique for endometrial sampling? Aspiration (Pipelle) versus dilatation and curettage (D&C). Arch Gynecol Obstet. 2012; 286:1277–82.

9. Gungorduk K, Asicioglu O, Ertas IE, Ozdemir IA, Ulker MM, Yildirim G, et al. Comparison of the histopathological diagnoses of preoperative dilatation and curettage and Pipelle biopsy. Eur J Gynaecol Oncol. 2014; 35:539–43.

10. Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy A, Gupta JK. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010; 203:547.e1–10.

11. Royal College of Obstetricians & Gynaecologists. Management of Endometrial Hyperplasia [Internet]. London (UK): Royal College of Obstetricians & Gynaecologists;c2016. [cited 2021 Jan 31]. Available from: https://www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg_67_endometrial_hyperplasia.pdf .

12. Gundem G, Sendag F, Kazandi M, Akercan F, Mgoyi L, Terek MC, et al. Preoperative and postoperative correlation of histopathological findings in cases of endometrial hyperplasia. Eur J Gynaecol Oncol. 2003; 24:330–3.

13. Dolanbay M, Kutuk MS, Uludag S, Bulut AN, Ozgun MT, Ozcelik B, et al. Concurrent endometrial carcinoma in hysterectomy specimens in patients with histopathological diagnosis of endometrial hyperplasia in curettage specimens. Ginekol Pol. 2015; 86:753–8.

14. Çakmak Y, Öge T, Uslu E, Kavak Cömert D, Aydin tosun Ö. Evaluation of concurrent endometrial cancer in patients with endometrial hyperplasia; 10 years experience as a tertiary center. Zeynep Kamil Tıp Bülteni. 2019; 50:222–6.

15. Chen YL, Wang KL, Chen MY, Yu MH, Wu CH, Ke YM, et al. Risk factor analysis of coexisting endometrial carcinoma in patients with endometrial hyperplasia: a retrospective observational study of Taiwanese Gynecologic Oncology Group. J Gynecol Oncol. 2013; 24:14–20.

16. Travaglino A, Raffone A, Saccone G, D’Alessandro P, Arduino B, de Placido G, et al. Significant risk of occult cancer in complex non-atypical endometrial hyperplasia. Arch Gynecol Obstet. 2019; 300:1147–54.

17. Kleebkaow P, Maneetab S, Somboonporn W, Seejornj K, Thinkhamrop J, Kamwilaisak R. Preoperative and postoperative agreement of histopathological findings in cases of endometrial hyperplasia. Asian Pac J Cancer Prev. 2008; 9:89–91.

18. Saygili H. Histopathologic correlation of dilatation and currettage and hysterectomy specimens in patients with postmenopausal bleeding. Eur J Gynaecol Oncol. 2006; 27:182–4.

19. Kadirogullari P, Atalay CR, Ozdemir O, Sari ME. Prevalence of co-existing endometrial carcinoma in patients with preoperative diagnosis of endometrial hyperplasia. J Clin Diagn Res. 2015; 9:QC10–4.

20. Epstein E, Ramirez A, Skoog L, Valentin L. Dilatation and curettage fails to detect most focal lesions in the uterine cavity in women with postmenopausal bleeding. Acta Obstet Gynecol Scand. 2001; 80:1131–6.

21. Lee DO, Jung MH, Kim HY. Prospective comparison of biopsy results from curettage and hysteroscopy in post-menopausal uterine bleeding. J Obstet Gynaecol Res. 2011; 37:1423–6.

22. Barut A, Barut F, Arikan I, Harma M, Harma MI, Ozmen Bayar U. Comparison of the histopathological diagnoses of preoperative dilatation and curettage and hysterectomy specimens. J Obstet Gynaecol Res. 2012; 38:16–22.

23. Lee N, Lee KB, Kim K, Hong JH, Yim GW, Seong SJ, et al. Risk of occult atypical hyperplasia or cancer in women with nonatypical endometrial hyperplasia. J Obstet Gynaecol Res. 2020; Sep. 17. [Epub]. https://doi.org/10.1111/jog.14474 .

24. Gallos ID, Krishan P, Shehmar M, Ganesan R, Gupta JK. Relapse of endometrial hyperplasia after conservative treatment: a cohort study with long-term follow-up. Hum Reprod. 2013; 28:1231–6.

25. Ørbo A, Arnes M, Vereide AB, Straume B. Relapse risk of endometrial hyperplasia after treatment with the levonorgestrel-impregnated intrauterine system or oral progestogens. BJOG. 2016; 123:1512–9.

26. Gallos ID, Ganesan R, Gupta JK. Prediction of regression and relapse of endometrial hyperplasia with conservative therapy. Obstet Gynecol. 2013; 121:1165–71.

27. Iversen ML, Dueholm M. Complex non atypical hyperplasia and the subsequent risk of carcinoma, atypia and hysterectomy during the following 9–14 years. Eur J Obstet Gynecol Reprod Biol. 2018; 222:171–5.

28. Rotenberg O, Fridman D, Doulaveris G, Renz M, Kaplan J, Gebb J, et al. Long-term outcome of postmenopausal women with non-atypical endometrial hyperplasia on endometrial sampling. Ultrasound Obstet Gynecol. 2019; 55:546–51.