Nuclear Pleomorphism in Canine Cutaneous Mast Cell Tumors: Comparison of Reproducibility and Prognostic Relevance between Estimates, Manual Morphometry and Algorithmic Morphometry

TL;DR

This study compares different methods for measuring nuclear characteristics in canine mast cell tumors, finding that manual stratified sampling and automated morphometry provide more reproducible and prognostically valuable results than traditional estimates.

Contribution

It introduces a deep learning-based automated morphometry method and demonstrates its superior reproducibility and prognostic utility compared to traditional estimates.

Findings

Inter-rater reproducibility of estimates was low (κ=0.226).

Automated morphometry achieved an AUC of 0.943 for prognosis.

Manual stratified sampling of 12 nuclei improved reproducibility.

Abstract

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 (morphometry) can improve reproducibility, but 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 (ccMCT). We assessed the following nuclear evaluation methods for measurement accuracy, reproducibility, and prognostic utility: 1) anisokaryosis (karyomegaly) 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 a deep learning-based segmentation algorithm. The study dataset comprised 96 ccMCT with available outcome information. The study dataset comprised 96 ccMCT with available outcome information. Inter-rater reproducibility of karyomegaly estimates was low ($\kappa$ = 0.226), while it was good (ICC = 0.654) for practicable morphometry of the standard deviation (SD) of nuclear size. As compared to gold standard manual morphometry (AUC = 0.839, 95% CI: 0.701 - 0.977), the prognostic value (tumor-specific survival) of SDs of nuclear area for practicable manual morphometry (12 nuclei) and automated morphometry were high with an area under the ROC curve (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.