Equine Melanomas with Camilla Jamieson DVM, BVS(Hons) MRCVS DACVIM
Equine Melanomas
Dr. Camilla Jamieson MRCVS DACVIM-LAIM
Equine melanocytic tumors, predominantly found in adult gray horses, are significant due to their health and economic implications. There is a consensus that nearly all gray horses will eventually develop these tumors as they age. Depending on the location and extent of the melanomas, they can affect performance, ability to eat and drink, defecate and urinate normally, and can extend to the abdominal and thoracic cavities, as well as neurologic system and other vital organs. Approximately 80% of equine tumors are cutaneous, with 15% being melanocytic. Although over 90% are benign, about 66% can progress to malignancy and metastasize.
Etiology
Cutaneous melanocytic tumors are neoplastic disease. The graying phenotype in horses, an autosomal dominant trait, is linked to a 4.6 kb duplication in the STX17 gene, leading to overexpression of STX17 and NR4A3. This mutation increases melanocyte proliferation, contributing to melanocytic tumor development. The interaction between STX17 mutation and other coat color controlling gene mutations in ASIP and MC1R genes further enhances the likelihood of the development of melanomas. The ASIP gene reduces MC1R activation, which is involved in eumelanin production. Loss-of-function mutations in ASIP, combined with STX17G, increase melanoma susceptibility due to unrestricted MC1R activity and enhanced melanocyte proliferation.
The copy number of STX17G correlates with the severity of these traits. Studies on Lipizzaner breed horses indicate moderate heritability for melanoma, with homozygous horses showing a higher prevalence and severity of melanomas.
Clinical Presentation and Diagnosis
Equine melanocytic tumors are classified into four types: naevus (or mole-like), dermal melanoma, dermal melanomatosis, and anaplastic malignant melanoma, with dermal melanomas being the most common, and what we traditionally think of as melanomas, however it is important to remember that melanomas come in multiple different forms. Equine melanomas present usually between 3-8 years old, at the age when the coat begins to fully gray out and 80% of gray horses will have at least one melanoma by age 15.
Diagnostic methods include clinical examination, fine needle aspirate and histopathology, with immunohistochemistry (IHC) playing a crucial role in identifying key biomarkers such as RACK1 and PNL2. It has become increasingly popular and important to perform IHC especially in cases with unusual presentations, for the clinician to develop the most comprehensive understanding of the extent and drivers of each individual horse's condition.
Treatment Options
Treatment modalities for equine melanocytic tumors include surgery, chemotherapy, particularly intralesional cisplatin, immunotherapy and radiotherapy. Research is ongoing to identify new immunological and inflammatory pathway therapeutic targets like CD47, PD-1, and COX-2.
Future Perspectives
Future research aims to better understand the genetic basis of these tumors and develop more effective treatments. The identification of new biomarkers and therapeutic targets holds promise for improving the management of equine melanocytic tumors.
Conclusion
Ongoing research into the genetic drivers of, and treatment for equine melanocytic tumors aims to improve outcomes for affected horses. The identification of genetic markers and the development of novel therapies are crucial for advancing the management of melanoma in gray horses. Melanomatosis is a very common condition of gray horses, and one that can range in severity from mildly unsightly masses in inconspicuous regions of the horse, to fatal.
