Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors.

Simple Summary: The aim of this study was to evaluate a new microscopic parameter (atypical mitotic figures) in canine cutaneous mast cell tumors regarding the ability to predict patient survival (prognosis). Mast cell tumors are one of the most common skin tumors in dogs. Counting the number of tumor cells undergoing division (mitotic figures) is of prognostic importance for this tumor type. While normal cells have a highly regulated cell division (normal mitotic figures), tumor cells might exhibit errors during chromosome separation into daughter cells. These errors can be identified microscopically as atypical mitotic figures and are described as a malignancy criterion for some human tumors. In this study, we have shown that a high number of atypical mitotic figures in canine cutaneous mast cell tumors is predictive of shorter patient survival. As compared to enumerating all mitotic figures, increased numbers of atypical mitotic figures (≥3 per 2.37 mm²) had a higher specificity for tumor-related death. These findings should be validated in future studies. Cell division through mitosis (microscopically visible as mitotic figures, MFs) is a highly regulated process. However, neoplastic cells may exhibit errors in chromosome segregation (microscopically visible as atypical mitotic figures, AMFs) resulting in aberrant chromosome structures. AMFs have been shown to be of prognostic relevance for some neoplasms in humans but not in animals. In this study, the prognostic relevance of AMFs was evaluated for canine cutaneous mast cell tumors (ccMCT). Histological examination was conducted by one pathologist in whole slide images of 96 cases of ccMCT with a known survival time. Tumor-related death occurred in 11/18 high-grade and 2/78 low-grade cases (2011 two-tier system). The area under the curve (AUC) was 0.859 for the AMF count and 0.880 for the AMF to MF ratio with regard to tumor-related mortality. In comparison, the AUC for the mitotic count was 0.885. Based on our data, a prognostically meaningful threshold of ≥3 per 2.37 mm² for the AMF count (sensitivity: 76.9%, specificity: 98.8%) and >7.5% for the AMF:MF ratio (sensitivity: 76.9%, specificity: 100%) is suggested. While the mitotic count of ≥ 6 resulted in six false positive cases, these could be eliminated when combined with the AMF to MF ratio. In conclusion, the results of this study suggests that AMF enumeration is a prognostically valuable test, particularly due to its high specificity with regard to tumor-related mortality. Additional validation and reproducibility studies are needed to further evaluate AMFs as a prognostic criterion for ccMCT and other tumor types. [ABSTRACT FROM AUTHOR]