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Integrated histological parameters define prognostically relevant groups in atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia
  1. Antonio Raffone1,2,
  2. Luigi Insabato3,
  3. Diego Raimondo4,
  4. Irene Del Piano3,
  5. Marialuisa Ricciardiello3,5,
  6. Pasquale Cretella3,
  7. Daniele Neola1,
  8. Damiano Arciuolo6,7,
  9. Angela Santoro6,7,
  10. Renato Seracchioli2,4,
  11. Maurizio Guida1,
  12. Antonio Travaglino3,8 and
  13. Gian Franco Zannoni6,7
    1. 1Department of Neurosciences and Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy
    2. 2Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
    3. 3Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Campania, Italy
    4. 4Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
    5. 5Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
    6. 6Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
    7. 7Department of Life Sciences and Public Health, Catholic University of the Sacred Heart, Roma, Italy
    8. 8Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
    1. Correspondence to Professor Antonio Travaglino, Department of Advanced Biomedical Sciences, University of Naples Federico II, Napoli, Campania, Italy; antonio.travaglino{at}


    Objective To assess the risk of endometrial carcinoma following a diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasia by endometrial biopsy, stratified based on integrated histological parameters.

    Methods All women with atypical hyperplasia/endometrioid intraepithelial neoplasia undergoing hysterectomy within 1 year of diagnosis without progestin treatment were included. Patients were subdivided into three study groups, based on two criteria: (a) grade of nuclear atypia and (b) foci (<2 mm) of confluent glands with no intervening stroma: low-grade, high-grade, and confluent glands. The rate of endometrial carcinoma on the subsequent hysterectomy was assessed in each study group, and differences between study groups were assessed using Fisher’s exact test, with a significant p value <0.05. Reproducibility was assessed by using Cohen’s κ.

    Results Ninety-six patients were included. Overall, 36 of 96 patients (37.5%) had endometrial carcinoma on the subsequent hysterectomy. The number of endometrial carcinomas was 4 of 42 (9.5%) in the low-grade group, 14 of 28 (50.0%) in the high-grade group, and 18 of 26 (69.2%) in the confluent glands group. The rate of endometrial carcinoma was significantly higher in the high-grade group than in the low-grade group (p<0.001), whereas it did not significantly differ between the high-grade group and the confluent glands group (p=0.176). The reproducibility among pathologists was moderate for low-grade versus high-grade (κ=0.58) and substantial for confluent glands versus low-grade (κ=0.63) and high-grade (κ=0.63).

    Conclusion Atypical hyperplasia/endometrioid intraepithelial neoplasia can be stratified into prognostically relevant groups based on integrated histological parameters, with a possible major impact on patient management.

    • Uterine Cancer
    • Endometrial Hyperplasia
    • Pathology

    Data availability statement

    Data are available upon reasonable request.

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    Data availability statement

    Data are available upon reasonable request.

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    • Correction notice This article has been corrected since it was first published, Author affiliation 4 has been corrected.

    • Contributors The authors confirm contribution to the paper as follows: study conception and design: AR, LI, DR, RS, MG, AT, GFZ; data collection: IDP, ML, PC, DN, DA; analysis and interpretation of results: AT, AT, AS, PC; draft manuscript preparation: AR, LI, DR, DN, DA, AS, RS, MG, AT, GFZ. Guarantor: LI. All authors reviewed the results and approved the final version of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.