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    Nuclear pleomorphism in canine cutaneous mast cell tumors:
    comparison of reproducibility and prognostic relevance between estimates, manual morphometry, and algorithmic morphometry (2025)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Haghofer, Andreas
    Parlak, Eda
    Bartel, Alexander (WE 16)
    Donovan, Taryn A.
    Assenmacher, Charles-Antoine
    Bolfa, Pompei
    Dark, Michael J.
    Fuchs-Baumgartinger, Andrea
    Klang, Andrea
    Jäger, Kathrin
    Klopfleisch, Robert (WE 12)
    Merz, Sophie
    Richter, Barbara
    Schulman, F. Yvonne
    Janout, Hannah
    Ganz, Jonathan
    Scharinger, Josef
    Aubreville, Marc
    Winkler, Stephan M.
    Kiupel, Matti
    Bertram, Christof A.
    Quelle
    Veterinary pathology : an internat. journal of natural and experimental disease in animals
    Bandzählung: 62
    Heftzählung: 2
    Seiten: 161 – 177
    ISSN: 0300-9858
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://journals.sagepub.com/doi/10.1177/03009858241295399
    DOI: 10.1177/03009858241295399
    Pubmed: 39560067
    Kontakt
    Institut für Veterinär-Epidemiologie und Biometrie

    Königsweg 67
    14163 Berlin
    +49 30 838 56034
    epi@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Variation in nuclear size and shape is an important criterion of malignancy for many tumor types; however, categorical estimates by pathologists have poor reproducibility. Measurements of nuclear characteristics can improve reproducibility, but current manual methods are time-consuming. The aim of this study was to explore the limitations of estimates and develop alternative morphometric solutions for canine cutaneous mast cell tumors (ccMCTs). We assessed the following nuclear evaluation methods for accuracy, reproducibility, and prognostic utility: (1) anisokaryosis estimates by 11 pathologists; (2) gold standard manual morphometry of at least 100 nuclei; (3) practicable manual morphometry with stratified sampling of 12 nuclei by 9 pathologists; and (4) automated morphometry using deep learning–based segmentation. The study included 96 ccMCTs with available outcome information. Inter-rater reproducibility of anisokaryosis estimates was low (k = 0.226), whereas it was good (intraclass correlation = 0.654) for practicable morphometry of the standard deviation (SD) of nuclear size. As compared with gold standard manual morphometry (area under the ROC curve [AUC] = 0.839, 95% confidence interval [CI] = 0.701–0.977), the prognostic value (tumor-specific survival) of SDs of nuclear area for practicable manual morphometry and automated morphometry were high with an AUC of 0.868 (95% CI = 0.737–0.991) and 0.943 (95% CI = 0.889–0.996), respectively. This study supports the use of manual morphometry with stratified sampling of 12 nuclei and algorithmic morphometry to overcome the poor reproducibility of estimates. Further studies are needed to validate our findings, determine inter-algorithmic reproducibility and algorithmic robustness, and explore tumor heterogeneity of nuclear features in entire tumor sections.