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Prognostic impact of histological review of high-grade endometrial carcinomas in a large Danish cohort

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Abstract

The aim of this study was to investigate the outcome of histological subtype review of high-grade endometrial carcinoma (EC) and its prognostic impact in a large well-documented Danish nationwide cohort. From the Danish Gynecological Cancer Database (DGCD) 2005–2012 cohort, we included 425 patients with an original diagnosis of high-grade EC, independent of histologic subtype. Of these, at least one hematoxylin and eosin (H&E)–stained slide from 396 cases (93.2%) was available for review. The histologic subtype was reviewed by specialized gynecopathologists blinded to the original diagnosis and clinical outcome. Interobserver variability between original and revised histologic subtypes was analyzed using simple Kappa statistics. Hazard ratios (HR), recurrence-free survival (RFS), and overall survival were calculated for original and revised subtypes, respectively. Overall histologic subtype agreement was moderate (kappa = 0.42) with the highest agreement for endometrioid-type EC (EEC; 75.5%) and serous-type EC (SEC; 63.8%). For clear cell carcinoma and un-/dedifferentiated EC, agreement was significantly lower: 30.1% and 33.3% respectively. Of the 396 reviewed cases, only two (0.5%) were re-classified as low-grade EEC upon revision. Interestingly, GR3 EEC had better RFS than SEC with stronger significance after revision (HR 2.36 (95% CI 1.43–3.89), p = 0.001), compared to original diagnosis (HR 1.74 (95% CI 1.07–2.81), p = 0.024). In conclusion, this study confirmed that pathology review results in substantial shift in histological subtype in high-grade EC. After review, a stronger prognostic benefit for GR3 EEC as compared to other histological subtypes was observed. This work supports maintaining a low threshold for pathology revision of high-grade EC in clinical practice.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Pathology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Copenhagen University, Borgmester Ib Juuls Vej 73, 2730, Herlev, Denmark

    Marie Boennelycke, Ib Jarle Christensen & Estrid Høgdall

  2. Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

    Elke E. M. Peters, Alicia Léon-Castillo, Vincent T. H. B. M. Smit & Tjalling Bosse

  3. Department of Pathology, Haaglanden Medical Center, P.O. Box 432, 2501 CK, The Hague, The Netherlands

    Elke E. M. Peters

  4. Department of Gynecology, Copenhagen University Hospital, Rigshospitalet, Juliane Maries Vej 8, 2100, Copenhagen, OE, Denmark

    Gitte Ørtoft & Claus Høgdall

Authors
  1. Marie Boennelycke
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  2. Elke E. M. Peters
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  3. Alicia Léon-Castillo
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  4. Vincent T. H. B. M. Smit
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  6. Ib Jarle Christensen
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  7. Gitte Ørtoft
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  8. Claus Høgdall
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Contributions

Conception and design: MB, EEMP, ALC, TB, GØ, CH, EH.

Acquisition of data: MB, EEMP, ALC, VTHBMS, TB, GØ, CH, EH.

Analysis and interpretation of data: MB, TB, IJC, GØ, EH.

Drafting the article or revising it critically: MB, EEMP, ALC, TB, GØ, EH.

Final approval of the version to be published: All.

Corresponding author

Correspondence to Marie Boennelycke.

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Committee on Health Research Ethics, The Capital Region of Denmark, H-16025909.

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The authors declare no competing interests.

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Boennelycke, M., Peters, E.E.M., Léon-Castillo, A. et al. Prognostic impact of histological review of high-grade endometrial carcinomas in a large Danish cohort. Virchows Arch 479, 507–514 (2021). https://doi.org/10.1007/s00428-021-03133-2

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  • DOI: https://doi.org/10.1007/s00428-021-03133-2

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