title: Long-term risk of endometrial cancer following postmenopausal bleeding and reassuring endometrial biopsy.
abstract: BACKGROUND
  Women with postmenopausal bleeding and endometrial thickness >4 mm undergo endometrial sampling to exclude endometrial cancer. The aim of this study is to investigate the relative risk of developing endometrial cancer in a prospective cohort after initial work-up for postmenopausal bleeding showing reassuring histology or insufficient sampling.
  
  
  METHODS
  All women presenting with postmenopausal bleeding were prospectively included from January 2009 to April 2011. Follow-up data were collected from patient charts and PALGA (Dutch Pathology Registry). Hazard ratios for endometrial cancer were determined by calculating standardized incidence ratios.
  
  
  RESULTS
  A total of 668 women were included and 568 women were available for follow-up [median follow-up time 47 (range 7-63) months]. Women who presented with postmenopausal bleeding, endometrial thickness >4 mm and hyperplasia without atypia on biopsy at the first presentation showed a significantly increased risk (standardized incidence ratio 17.15, 95% confidence interval 1.96-61.93) of being diagnosed with endometrial cancer during the first four years of follow up compared with the age-specific population. All women that developed endometrial cancer after initial reassuring histology presented with recurrent postmenopausal bleeding. None of the women with endometrial thickness >4 mm and no or insufficient sample for histology at the first presentation developed endometrial cancer during the follow up.
  
  
  CONCLUSIONS
  Although in general, women with endometrial hyperplasia without atypia are considered to have a low risk for cancer, we observed a significant long-term risk of endometrial cancer after postmenopausal bleeding. Whether additional diagnostics or a more stringent follow-up regimen would be cost-effective, needs to be studied.
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Nicole C M
authors.initials: NC
authors.lastname: Visser
authors.affiliation: Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Sparidaens
authors.affiliation: Department of Obstetrics and Gynecology, Canisius-Wilhemina Hospital, Nijmegen, The Netherlands.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: van den Brink
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Breijer
authors.affiliation: Department of Obstetrics and Gynecology, Máxima Medical Center, Veldhoven, The Netherlands.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Boss
authors.affiliation: Department of Obstetrics and Gynecology, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Veersema
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Albert G
authors.initials: AG
authors.lastname: Siebers
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Bulten
authors.affiliation: Department of Obstetrics and Gynecology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands.
authors.forename: Johanna M A
authors.initials: JM
authors.lastname: Pijnenborg
authors.affiliation: Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ruud L M
authors.initials: RL
authors.lastname: Bekkers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D004714:Endometrial Hyperplasia / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology*; D004717:Endometrium / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D017698:Postmenopause; D011230:Precancerous Conditions / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D014592:Uterine Hemorrhage / Q000209:etiology* / Q000473:pathology
keywords: Endometrial cancer; endometrial hyperplasia without atypia; endometrial sampling; long-term incidence; postmenopausal bleeding