Feline Alimentary Lymphomas: Established Concepts and an Underexplored Molecular Landscape

Domestic cats are among the most popular companion animals worldwide, with steadily increasing ownership and life expectancy. Paradoxically, despite their high prevalence and shared environmental exposures with humans, cats remain markedly underrepresented in molecular oncology research. Cancer is a leading cause of feline mortality, and alimentary lymphoma (AL) has emerged as one of the most common feline malignancies, yet its molecular landscape remains poorly characterized. This review summarizes current knowledge on feline AL, including epidemiology, risk factors, classification schemes, diagnostic challenges, treatment outcomes, and survival, with particular emphasis on low-grade alimentary lymphoma (LGAL), the most prevalent subtype. We discuss the complex relationship between chronic inflammatory enteropathies and lymphoma, highlighting diagnostic ambiguities and the inflammatory–neoplastic continuum. Importantly, we provide a critical overview of existing genomic, transcriptomic, epigenomic, proteomic, and metabolomic studies in feline AL, revealing a striking paucity of high-throughput, multi-omics analyses based on clinical material. Recent advances in feline genome assembly and annotation offer new opportunities to address these gaps. Furthermore, we compare feline AL with its human gastrointestinal T-cell lymphoma counterparts, demonstrating substantial molecular homology across key oncogenic pathways, including JAK/STAT signaling. This comparative perspective underscores the potential of feline AL as a naturally occurring model for the human disease. We conclude that comprehensive molecular characterization of feline AL is urgently needed to improve diagnostics, prognostication, and targeted therapies, with likely translational benefits for both veterinary and human oncology. Aim: The goal of this review is to summarize the current knowledge on feline alimentary lymphoma, including its origin, risk, classification, treatment approaches, and especially molecular landscape, which still remains poorly investigated with modern high-throughput techniques.