The microenvironment in canine mast cell tumors: association between tumor-associated tissue eosinophilia and histological grade

Vollständiger Abstract

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Introduction Canine mast cell tumors (MCTs) are common neoplasms with heterogeneous biological behavior, and histological grading alone may not fully reflect their aggressiveness. The tumor microenvironment, particularly tumor-associated tissue eosinophilia (TATE), may provide complementary information on MCT biology. Methods This study evaluated whether intratumoral eosinophil infiltration, expressed as the eosinophil-to-mast cell ratio (EMR), was associated with histological grade in canine MCTs. A secondary objective was to assess the relationship between peripheral blood inflammatory markers and tumor grade. A total of 117 surgically excised MCTs from 73 dogs were included. Tumors were classified according to the Patnaik and Kiupel grading systems. Eosinophils and mast cells were counted in 10 consecutive high-power fields of neoplastic tissue, and the EMR was calculated. Histopathological variables, peripheral blood eosinophil counts, and inflammatory ratios were also evaluated. Univariable and multivariable regression models were used to assess associations with tumor grade, and receiver operating characteristic curve analysis was performed to identify an exploratory, data-derived EMR cutoff, which was internally validated using bootstrap resampling. Results A higher EMR was associated with high-grade tumors in both grading systems and remained independently associated with tumor grade after adjustment for confounding variables. An exploratory EMR cutoff value of 0.38 showed good discriminatory ability for distinguishing low- from high-grade tumors according to Kiupel grading and showed stable overall discrimination on internal bootstrap validation, although the exact threshold remained imprecisely estimated. In contrast, peripheral blood eosinophil counts were not significantly related to tumor grade, and most systemic inflammatory markers showed no significant association with tumor grade. Discussion These findings suggest that the local eosinophilic component of the tumor microenvironment, assessed through the EMR, may provide complementary information for the histological characterization of canine MCTs. Larger multicenter studies are needed to validate the proposed EMR cutoff and clarify its prognostic and biological relevance.