https://phaidra.vetmeduni.ac.at/o:3989 Nuclear pleomorphism in canine cutaneous mast cell tumors: Comparison of reproducibility and prognostic relevance between estimates, manual morphometry, and algorithmic morphometry Haghofer, Andreas Andreas Haghofer Parlak, Eda Eda Parlak University of Veterinary Medicine Vienna Bartel, Alexander Alexander Bartel 0000-0002-1280-6138 Donovan, Taryn A. Taryn A. Donovan 0000-0001-5740-9550 Assenmacher, Charles-Antoine Charles-Antoine Assenmacher 0000-0003-0073-2730 Bolfa, Pompei Pompei Bolfa 0000-0002-2903-1535 Dark, Michael J. Michael J. Dark 0000-0002-6547-1298 Fuchs-Baumgartinger, Andrea Andrea Fuchs-Baumgartinger University of Veterinary Medicine Vienna Klang, Andrea Andrea Klang 0000-0001-5352-5757 University of Veterinary Medicine Vienna Jäger, Kathrin Kathrin Jäger Klopfleisch, Robert Robert Klopfleisch 0000-0002-6308-0568 Merz, Sophie Sophie Merz Richter, Barbara Barbara Richter University of Veterinary Medicine Vienna Schulman, F. Yvonne F. Yvonne Schulman 0000-0002-7454-8517 Janout, Hannah Hannah Janout Ganz, Jonathan Jonathan Ganz 0009-0008-1299-8716 Scharinger, Josef Josef Scharinger Aubreville, Marc Marc Aubreville 0000-0002-5294-5247 Winkler, Stephan M. Stephan M. Winkler Kiupel, Matti Matti Kiupel 0000-0003-4429-9529 Bertram, Christof A. Christof A. Bertram 0000-0002-2402-9997 University of Veterinary Medicine Vienna Sage journal article open access eng 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. Animals Dogs Dog Diseases Pathology Dog Diseases Diagnosis Prognosis Reproducibility of Results Cell Nucleus Pathology Algorithms Skin Neoplasms Veterinary Skin Neoplasms Pathology Skin Neoplasms Diagnosis Male Female Mastocytosis, Cutaneous Veterinary Mastocytosis, Cutaneous Pathology Mastocytosis, Cutaneous Diagnosis http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:3989/download 10.1177/03009858241295399 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Veterinary Pathology issn:1544-2217 VoR Veterinary Pathology 62 2 2.76 MB 2024