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Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance
  1. Melanie Boxberg1,
  2. Christine Bollwein1,
  3. Korinna Jöhrens2,
  4. Peer-Hendrik Kuhn1,
  5. Bernhard Haller3,
  6. Katja Steiger1,
  7. Klaus-Dietrich Wolff4,
  8. Andreas Kolk4,
  9. Moritz Jesinghaus1,5,
  10. Wilko Weichert1,5
  1. 1 Institute of Pathology, Technical University of Munich (TUM), Munich, Germany
  2. 2 Institute of Pathology, University Carl Gustav Carus, Dresden, Germany
  3. 3 Institute of Medical Informatics, Statistics and Epidemiology, Technical University of Munich (TUM), Munich, Germany
  4. 4 Department of Oral- and Maxillofacial Surgery, Klinikum Rechts der Isar, Munich, Germany
  5. 5 German Cancer Consortium (DKTK), Munich, Germany
  1. Correspondence to Dr Melanie Boxberg, Institute of Pathology, Technical University of Munich, Munich 81675, Germany; Melanie.Boxberg{at}


Aims Squamous cell carcinoma of the oral cavity (OSCC) is a common tumour entity with a variable, partially highly aggressive clinical course. Recently, we proposed a novel (three-tiered) clinically useful grading scheme strongly associated with patient outcome in OSCC, consisting of a sum score of the histomorphological patterns tumour budding and cell nest size which outperforms WHO based grading algorithms currently in use. The aim of our study was to probe for interobserver and intraobserver reliability of this novel grading system.

Methods 108 OSCC were retrospectively scored according to the proposed grading scheme by three independent pathologists—two experienced head and neck pathologists and one pathologist in training—blinded to each other’s scoring results.

Results The Cohen’s Kappa (κ) values for concordance rates between experienced pathologists were κ=0.97 for the overall grade, κ=0.97 for budding activity and κ=0.91 for cell nest size, indicating a strong interobserver reliability of our proposed grading system. Initial interobserver agreement was markedly lower with the pathologist in training (κ=0.55 for overall grade) but improved significantly after a training session (κ=0.87 for overall grade). Intraobserver concordance was high (κ=0.95 for overall grade), indicating a high reproducibility of the algorithm.

Conclusions In conclusion, our study indicates that OSCC grading based on our proposed novel scheme yields an excellent inter-reader and intrareader agreement, further supporting the suitability of this grading system for routine pathological practice.

  • squamous cell carcinoma
  • oral cavity
  • histomorphological grading
  • tumor cell budding
  • cell nest size
  • interobserver agreement
  • intraobserver reliability

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  • Handling editor Dr Cheok Soon Lee.

  • Contributors MB and WW designed this study and wrote this paper with assistance from CB and KJ. MB, CB and KJ performed tissue analyses with assistance from MJ, P-HK and KS. K-DW and AK helped gain clinical data, BH contributed to statistical analysis.

  • Funding This study has been supported by the German Cancer Consortium (to WW) and the Else-Kröner Fresenius-Stiftung (to MB).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Ethics Committee TU Munich, Faculty of Medicine.

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

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