Prevalence and Clinicopathologic Features of Canine Metastatic Melanoma Involving the Central Nervous System: A Retrospective Analysis and Comparative Review.

Background: Central nervous system (CNS) involvement is the leading cause of death in malignant melanoma. Rodent models, while vital to mechanistic investigation, have had limited success identifying effective therapies for melanoma brain metastases. The companion dog with Methods: Medical records of dogs diagnosed with malignant melanoma from 1985-2019 at the University of California Davis Veterinary Medical Teaching Hospital were assessed retrospectively. Clinicopathologic features were compared between dogs with CNS metastasis (CNS+) and dogs without CNS metastasis (CNS-). Site of CNS involvement and associated neurological signs were analyzed Results: CNS metastasis was identified in 38% of dogs in this study (20/53). The oral cavity was the most common site of primary melanoma in both groups [CNS+: n=12 (60%) vs. CNS-: n=22 (67%); p>0.99]. The total burden of metastatic disease was higher in the CNS+ group (CNS+: 4, 95% CI 3-5 vs. CNS-: 3, 95% CI 1-3; p<0.001). The cerebrum was the most common site of CNS metastasis (n=15, 75%) and seizures were the most observed neurological sign (n=9, 64%). There was no difference in overall survival between CNS+ and CNS- groups. However, the median survival time following onset of neurological signs was 9.5 days (95% CI 1-43), with 5 dogs euthanized within 24 hours of the onset of neurological signs. Conclusions: Canine and human MM patients share similar rates of CNS metastasis and clinical presentation. This study will guide clinical management of canines with malignant melanoma and inform future studies using dogs with spontaneously occurring melanoma as a preclinical model for human melanoma brain metastases.