Archives of Gynecology and Obstetrics

, Volume 286, Issue 6, pp 1555–1562 | Cite as

Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch syndrome (LS)

  • Ranjit Manchanda
  • Ertan Saridogan
  • Ahmed Abdelraheim
  • Michelle Johnson
  • Adam N. Rosenthal
  • Elizabeth Benjamin
  • Carol Brunell
  • Lucy Side
  • Sue Gessler
  • Ian Jacobs
  • Usha Menon
Gynecologic Oncology



LS women have a 40–60 % lifetime risk of endometrial cancer (EC). Most international guidelines recommend screening. However, data on efficacy are limited.


To assess the performance of OHES for EC screening in LS and compare it with transvaginal ultrasound (TVS) alone.


A prospective observational cohort study of LS women attending a tertiary high-risk familial gynaecological cancer clinic was conducted. LS women opting for EC screening underwent annual OHES and TVS. Histopathological specimens were processed using a strict protocol. Data of women screened between October 2007 and March 2010 were analysed from a bespoke database. Histology was used as the gold standard. Diagnostic accuracy of OHES was compared with TVS using specificity, and positive (PLR) and negative (NLR) likelihood ratios.


Forty-one LS women underwent 69 screens (41 prevalent, 28 incident). Four (three prevalent, one incident) women were detected to have EC/atypical endometrial hyperplasia (AEH), five had endometrial polyps and two had endometrial hyperplasia (EH) on OHES. TVS detected two of four EC/AEH. OHES had similar specificity of 89.8 % (CI 79.2, 96.2 %), but higher PLR 9.8 (CI 4.6, 21) and lower NLR (zero) compared to TVS: specificity 84.75 %(CI 73, 92.8 %), PLR 3.28 (CI 1.04, 10.35) and NLR 0.59 (CI 0.22, 1.58). No interval cancers occurred over a median follow-up of 22 months. The annual incidence was 3.57 % (CI 0.09, 18.35) for EC, 10.71 % (CI 2.27, 28.23) for polyps and 21.4 % (CI 8.3, 40.1) for any endometrial pathology.


Our findings suggest that in LS, annual OHES is acceptable and has high diagnostic accuracy for EC/AEH screening. Larger international studies are needed for confirmation, given the relatively small numbers of LS women at individual centres. It reinforces the current recommendation that endometrial sampling is crucial when screening these women.


Lynch syndrome Endometrial screening Outpatient hysteroscopy Endometrial sampling OHES 


  1. 1.
    Broaddus RR, Lynch PM, Lu KH, Luthra R, Michelson SJ (2004) Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome. Mod Pathol 17(8):981–989PubMedCrossRefGoogle Scholar
  2. 2.
    Vasen HF, Watson P, Mecklin JP, Lynch HT (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 116(6):1453–1456PubMedCrossRefGoogle Scholar
  3. 3.
    Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, Peltomaki P, Mecklin JP, Jarvinen HJ (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81(2):214–218PubMedCrossRefGoogle Scholar
  4. 4.
    Hendriks YM, Wagner A, Morreau H, Menko F, Stormorken A, Quehenberger F, Sandkuijl L, Moller P, Genuardi M, Van Houwelingen H, Tops C, Van Puijenbroek M, Verkuijlen P, Kenter G, Van Mil A, Meijers-Heijboer H, Tan GB, Breuning MH, Fodde R, Wijnen JT, Brocker-Vriends AH, Vasen H (2004) Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology 127(1):17–25PubMedCrossRefGoogle Scholar
  5. 5.
    Hendriks YM, de Jong AE, Morreau H, Tops CM, Vasen HF, Wijnen JT, Breuning MH, Brocker-Vriends AH (2006) Diagnostic approach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma): a guide for clinicians. CA Cancer J Clin 56(4):213–225PubMedCrossRefGoogle Scholar
  6. 6.
    Vasen HF, Stormorken A, Menko FH, Nagengast FM, Kleibeuker JH, Griffioen G, Taal BG, Moller P, Wijnen JT (2001) MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol 19(20):4074–4080PubMedGoogle Scholar
  7. 7.
    Lindor NM, Petersen GM, Hadley DW, Kinney AY, Miesfeldt S, Lu KH, Lynch P, Burke W, Press N (2006) Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 296(12):1507–1517PubMedCrossRefGoogle Scholar
  8. 8.
    Dove-Edwin I, Boks D, Goff S, Kenter GG, Carpenter R, Vasen HF, Thomas HJ (2002) The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer 94(6):1708–1712PubMedCrossRefGoogle Scholar
  9. 9.
    Gerritzen LH, Hoogerbrugge N, Oei AL, Nagengast FM, van Ham MA, Massuger LF, de Hullu JA (2009) Improvement of endometrial biopsy over transvaginal ultrasound alone for endometrial surveillance in women with Lynch syndrome. Fam Cancer 8(4):391–397PubMedCrossRefGoogle Scholar
  10. 10.
    Rijcken FE, Mourits MJ, Kleibeuker JH, Hollema H, van der Zee AG (2003) Gynecologic screening in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 91(1):74–80PubMedCrossRefGoogle Scholar
  11. 11.
    Renkonen-Sinisalo L, Butzow R, Leminen A, Lehtovirta P, Mecklin JP, Jarvinen HJ (2007) Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome. Int J Cancer 120(4):821–824PubMedCrossRefGoogle Scholar
  12. 12.
    Lecuru F, Le Frere Belda MA, Bats AS, Tulpin L, Metzger U, Olschwang S, Laurent-Puig P (2008) Performance of office hysteroscopy and endometrial biopsy for detecting endometrial disease in women at risk of human non-polyposis colon cancer: a prospective study. Int J Gynecol Cancer 18(6):1326–1331PubMedCrossRefGoogle Scholar
  13. 13.
    Lecuru F, Metzger U, Scarabin C, Le Frere Belda MA, Olschwang S, Laurent Puig P (2007) Hysteroscopic findings in women at risk of HNPCC. Results of a prospective observational study. Fam Cancer 6(3):295–299PubMedCrossRefGoogle Scholar
  14. 14.
    Baxter NP, Duffy SR, Sheridan E (2002) Endometrial abnormalities in three sisters from a family with hereditary non-polyposis colorectal cancer syndrome. BJOG 109(9):1076–1078PubMedCrossRefGoogle Scholar
  15. 15.
    Gulumser C, Narvekar N, Pathak M, Palmer E, Parker S, Saridogan E (2010) See-and-treat outpatient hysteroscopy: an analysis of 1,109 examinations. Reprod Biomed Online 20(3):423–429. doi:10.1016/j.rbmo.2009.11.024 PubMedCrossRefGoogle Scholar
  16. 16.
    Zaino RJ, Kauderer J, Trimble CL, Silverberg SG, Curtin JP, Lim PC, Gallup DG (2006) Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group Study. Cancer 106(4):804–811PubMedCrossRefGoogle Scholar
  17. 17.
    Trimble CL, Kauderer J, Zaino R, Silverberg S, Lim PC, Burke JJ 2nd, Alberts D, Curtin J (2006) Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group Study. Cancer 106(4):812–819PubMedCrossRefGoogle Scholar
  18. 18.
    Gupta JK, Chien PF, Voit D, Clark TJ, Khan KS (2002) Ultrasonographic endometrial thickness for diagnosing endometrial pathology in women with postmenopausal bleeding: a meta-analysis. Acta Obstet Gynecol Scand 81(9):799–816PubMedCrossRefGoogle Scholar
  19. 19.
    Dimitraki M, Tsikouras P, Bouchlariotou S, Dafopoulos A, Liberis V, Maroulis G, Teichmann AT (2011) Clinical evaluation of women with PMB. Is it always necessary an endometrial biopsy to be performed? A review of the literature. Arch Gynecol Obstet 283(2):261–266. doi:10.1007/s00404-010-1601-3 PubMedCrossRefGoogle Scholar
  20. 20.
    Jacobs I, Gentry-Maharaj A, Burnell M, Manchanda R, Singh N, Sharma A, Ryan A, Seif MW, Amso NN, Turner G, Brunell C, Fletcher G, Rangar R, Ford K, Godfrey K, Lopes A, Oram D, Herod J, Williamson K, Scott I, Jenkins H, Mould T, Woolas R, Murdoch J, Dobbs S, Leeson S, Cruickshank D, Skates SJ, Fallowfield L, Parmar M, Campbell S, Menon U (2011) Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case–control study within the UKCTOCS cohort. Lancet Oncol 12(1):38–48. doi:10.1016/S1470-2045(10)70268-0 PubMedCrossRefGoogle Scholar
  21. 21.
    Vasen HF, Moslein G, Alonso A, Bernstein I, Bertario L, Blanco I, Burn J, Capella G, Engel C, Frayling I, Friedl W, Hes FJ, Hodgson S, Mecklin JP, Moller P, Nagengast F, Parc Y, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Wijnen J (2007) Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet 44(6):353–362PubMedCrossRefGoogle Scholar
  22. 22.
    Kerlikowske K, Smith-Bindman R, Ljung BM, Grady D (2003) Evaluation of abnormal mammography results and palpable breast abnormalities. Ann Intern Med 139(4):274–284PubMedGoogle Scholar
  23. 23.
    Chu K, Brown AF (2005) Likelihood ratios increase diagnostic certainty in pulmonary embolism. Emerg Med Australas 17(4):322–329PubMedCrossRefGoogle Scholar
  24. 24.
    Clark TJ, Voit D, Gupta JK, Hyde C, Song F, Khan KS (2002) Accuracy of hysteroscopy in the diagnosis of endometrial cancer and hyperplasia: a systematic quantitative review. JAMA 288(13):1610–1621PubMedCrossRefGoogle Scholar
  25. 25.
    Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP (2000) The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 89(8):1765–1772PubMedCrossRefGoogle Scholar
  26. 26.
    Vasen HF, Watson P, Mecklin JP, Jass JR, Green JS, Nomizu T, Muller H, Lynch HT (1994) The epidemiology of endometrial cancer in hereditary nonpolyposis colorectal cancer. Anticancer Res 14(4B):1675–1678PubMedGoogle Scholar
  27. 27.
    Tahir MM, Bigrigg MA, Browning JJ, Brookes ST, Smith PA (1999) A randomised controlled trial comparing transvaginal ultrasound, outpatient hysteroscopy and endometrial biopsy with inpatient hysteroscopy and curettage. Br J Obstet Gynaecol 106(12):1259–1264PubMedCrossRefGoogle Scholar
  28. 28.
    Pasqualotto EB, Margossian H, Price LL, Bradley LD (2000) Accuracy of preoperative diagnostic tools and outcome of hysteroscopic management of menstrual dysfunction. J Am Assoc Gynecol Laparosc 7(2):201–209PubMedCrossRefGoogle Scholar
  29. 29.
    Lacey JV Jr, Sherman ME, Rush BB, Ronnett BM, Ioffe OB, Duggan MA, Glass AG, Richesson DA, Chatterjee N, Langholz B (2010) Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. J Clin Oncol 28(5):788–792. doi:10.1200/JCO.2009.24.1315 PubMedCrossRefGoogle Scholar
  30. 30.
    Elmasry K, Davies AJ, Evans DG, Seif MN, Reynolds K (2009) Strategies for endometrial screening in the Lynch syndrome population: a patient acceptability study. Fam Cancer 8(4):431–439PubMedCrossRefGoogle Scholar
  31. 31.
    Kremer C, Duffy S, Moroney M (2000) Patient satisfaction with outpatient hysteroscopy versus day case hysteroscopy: randomised controlled trial. BMJ 320(7230):279–282PubMedCrossRefGoogle Scholar
  32. 32.
    Saridogan E, Tilden D, Sykes D, Davis N, Subramanian D (2010) Cost-analysis comparison of outpatient see-and-treat hysteroscopy service with other hysteroscopy service models. J Minim Invasive Gynecol 17(4):518–525. doi:10.1016/j.jmig.2010.03.009 PubMedCrossRefGoogle Scholar
  33. 33.
    Wood NJ, Munot S, Sheridan E, Duffy SR (2008) Does a “one-stop” gynecology screening clinic for women in hereditary nonpolyposis colorectal cancer families have an impact on their psychological morbidity and perception of health? Int J Gynecol Cancer 18(2):279–284PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ranjit Manchanda
    • 1
  • Ertan Saridogan
    • 2
  • Ahmed Abdelraheim
    • 1
    • 3
  • Michelle Johnson
    • 1
  • Adam N. Rosenthal
    • 1
    • 4
  • Elizabeth Benjamin
    • 5
  • Carol Brunell
    • 6
  • Lucy Side
    • 1
  • Sue Gessler
    • 1
  • Ian Jacobs
    • 1
  • Usha Menon
    • 1
  1. 1.Department of Gynaecological Oncology, EGA Institute for Women’s HealthGynaecological Cancer Research Centre, University College LondonLondonUK
  2. 2.Department of GynaecologyUniversity College London Hospital (UCLH)LondonUK
  3. 3.Department of Obstetrics and GynaecologyElMinia University HospitalsElMiniaEgypt
  4. 4.Institute of Cancer, Barts and the London School of Medicine and Dentistry, Queen MaryUniversity of LondonLondonUK
  5. 5.Department of Pathology, Cancer Institute, Rockefeller BuildingUniversity College LondonLondonUK
  6. 6.Department of RadiologyUniversity College London Hospital (UCLH)LondonUK

Personalised recommendations