Multicentric malignant melanoma in a grey mare: A case report

Grey coat color in horses, resulting from a 4.6 kb copy number variation (CNV) within the syntaxin 17 (STX17) gene (Grey locus), is linked to progressive hair depigmentation and a markedly increased risk of melanoma, likely to its function as a melanocyte-specific enhancer.

This report details the clinical, pathological, and genomic findings of a 26-year-old flea-bitten grey mare with multiple melanocytic tumors, progressive dyspnea, and congestive heart failure. Due to the poor prognosis the horse was euthanized and submitted for necropsy to the Long Island University - Lewyt College of Veterinary Medicine Pathology services.

Necropsy revealed widespread melanocytic tumors in cutaneous, lymphatic, and visceral sites, including the pericardium and right atrium. Genetic analysis identified a G1/G3 genotype in normal tissue, consistent with an elevated melanoma risk and rapid greying. Tumor tissue exhibited somatic CNV expansions at theGrey locus, with up to 6 total copies.

This case adds to growing evidence that CNV amplification may contribute to malignant transformation in grey horse melanoma. The presence of cardiac metastasis underscores the need for more comprehensive cardiac evaluation in similar cases. Given parallels with underdiagnosed cardiac metastases in humans and canine cases, these findings highlight a potentially underrecognized aspect of metastatic spread in grey horse melanoma. Early genetic screening and monitoring may improve clinical outcomes, especially in horses with high-risk genotypes, supporting the value of integrating genomic and pathological assessments to better understand melanoma progression and metastasis, and underscoring the need for broader population-based investigations.