Comparative Differences in Tumor Biology Between Dogs and Cats: Clinical Practice and Translational Oncology Insights

Abstract

Background: Companion animals develop spontaneous tumors while sharing the same environmental carcinogenic exposures as humans. This positions dogs and cats as naturally occurring, immunocompetent models of cancer progression. However, tumors with identical histological labels can display distinctly different biological behaviors across species. Understanding these interspecies differences is essential both for veterinary clinical management and for harnessing dogs and cats as translational models relevant to human oncology. Methods: A retrospective analysis of 3525 histopathological cases (2861 dogs and 664 cats) diagnosed between 2020 and 2025 was conducted. Tumors were classified using ICD-O and Vet-ICD-O systems, and histological grading followed accepted veterinary adaptations of Elston–Ellis, Nagamine, and Kiupel criteria where applicable. Comparative evaluation focused on mammary gland carcinoma, squamous cell carcinoma (SCC), and lymphoma due to their high clinical relevance and cross-species translational significance. Results: Mammary gland carcinoma was prevalent in both species; however, feline tumors showed markedly higher malignancy rates (approximately 80–95%), early lymphovascular invasion, and predominance of solid and comedo patterns. In contrast, canine mammary tumors exhibited broader morphological heterogeneity and variable clinical courses. Squamous cell carcinoma was nearly three times more common in cats, typically affecting the oral cavity and nasal planum, and demonstrated aggressive local invasion comparable to human head and neck SCC. Lymphoma patterns diverged by species: canine lymphoma was predominantly multicentric with nodal enlargement, while feline lymphoma was primarily alimentary, often clinically resembling chronic enteropathy and requiring biopsy and immunophenotyping for accurate diagnosis. Conclusions: Although dogs and cats share environmental risks, the biological behavior of their tumors differs fundamentally. Feline mammary carcinoma should be approached as a systemic disease from the outset, oral SCC in cats provides a spontaneous model of locally aggressive human head and neck cancer, and feline alimentary lymphoma offers translational insight into immune-mediated gastrointestinal lymphomas. These distinctions reinforce the importance of species-specific diagnostic and therapeutic strategies and highlight the value of companion animals in comparative and translational oncology.