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Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics

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Abstract

Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia—which we called mixed polyp—and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi)genetic events. A study set was created from a consecutive series of colorectal polyps (n = 1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good inter-observer agreement for polyp classification (κ = 0.56 to 0.63), but for single criteria, this varied considerably (κ = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated adenomas showed significant correlation with BRAF mutation (all p ≤ 0.001), and those for classical adenomas or traditional serrated adenoma correlated significantly with KRAS mutation (all p < 0.001). Therefore, single well-defined morphological criteria are predictive for genetic alterations in colorectal polyps.

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Acknowledgments

We would like to thank Angela Neumann and Madeleine Demleitner for their excellent technical assistance and especially Fred T. Bosman for his thorough and distinguished editing of the manuscript. This study was supported by the Interdisciplinary Centre for Clinical Research at the University Hospital Erlangen.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Pathology, Friedrich Alexander Universität Erlangen-Nürnberg, Krankenhausstraße 8-10, 91054, Erlangen, Germany

    Tilman T. Rau, Abbas Agaimy, Carol Geppert, Katharina Knobloch, Regine Schneider-Stock & Arndt Hartmann

  2. Comprehensive Cancer Center Erlangen, European Metropolitan Region Nuremberg, Erlangen, Germany

    Tilman T. Rau, Abbas Agaimy, Carol Geppert, Katharina Knobloch, Regine Schneider-Stock, Michael Vieth & Arndt Hartmann

  3. Institute of Pathology Nordhessen, Kassel, Germany

    Anastasia Gehoff & Josef Rüschoff

  4. Department of Medical Statistics, Universitätsmedizin Göttingen, Göttingen, Germany

    Klaus Jung

  5. Institute of Pathology, Medical University Graz, Graz, Austria

    Cord Langner

  6. Institute of Pathology, University Bern, Bern, Switzerland

    Alessandro Lugli

  7. Department of Pathology, Erasmus MC, Rotterdam, The Netherlands

    Irene Groenbus-Lurkin & Ellen C. Zwarthoff

  8. Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    Iris D. Nagtegaal

  9. Institute of Pathology, Katholieke Universiteit Leuven, Leuven, Belgium

    Xavier Saegert

  10. Pathologie München-Nord, Munich, Germany

    Mario Sarbia

  11. Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany

    Michael Vieth

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  1. Tilman T. Rau
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Rau, T.T., Agaimy, A., Gehoff, A. et al. Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics. Virchows Arch 464, 663–672 (2014). https://doi.org/10.1007/s00428-014-1569-7

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