Melanoma in Horses

What is equine melanoma?

Melanoma is a cancer of melanocytes, specialized skin cells that produce pigments for skin and hair color (among other things). Melanomas appear as small, black, dome-shaped bumps. They often occur under the tail, in anal and genital regions, on lips and eyelids, and under the throatlatch. Tumor location can affect a horse’s quality of life, especially as they get larger over time. Horses can also develop internal melanomas, which are usually life-threatening.

Melanomas are generally slow-growing tumors. They are usually initially benign (melanocytoma) but can become malignant and metastasize (malignant melanoma) to other locations in the body.

Melanomas are the third most diagnosed skin tumors in horses (after sarcoids and squamous cell carcinoma). They are commonly observed in gray horses but can occur in horses of any coat color. Melanomas in solid-colored horses are more severe, often metastasizing to lymph nodes or organs, making them difficult to treat and leading to a poor prognosis.

What causes equine melanoma?

Unlike in humans, melanoma in horses is rarely caused by exposure to ultraviolet (UV) light. The genetic cause of melanoma in gray horses is associated with a large duplication of a region of DNA in the syntaxin 17 (STX17) and nuclear receptor subfamily 4, group A, member 3 (NR4A3) genes.

A supply of stem cells makes new melanocytes as hair grows and sheds. Gray horses possess genetic copy number variants that supercharge this process, prematurely exhausting the stem cell supply. The hair essentially runs out of color and has no way to make more. This explains why these horses are born with pigmented coats that turn gray over time. Unfortunately, supercharging the process can predispose horses to develop malignant cells that lead to melanoma.

Gray is an autosomal dominant trait, meaning that a horse only needs one version of the genetic variant to be gray, regardless of the variants it has for other color genes (chestnut, bay, black). UC Davis researchers at the Veterinary Genetics Laboratory (VGL) participated in a recent study that showed gray is caused by differences in the number of copies of the genetic variant. Some gray horses result from two copies (G2 allele) while others have a version with three copies (G3 allele) (Rubin, 2024). 

Breeds such as Connemara ponies show pronounced variation in the speed of graying. Fast graying horses are white by 10 years of age, whereas slow graying horses stay dappled. Fast graying horses (those with the G3 allele) have a higher incidence of melanoma than slow graying horses (those with the G2 allele). 

Research has shown that speed of graying and melanoma incidence comes down to the number of copies of the gray genetic variant. Up to six copies have been identified in fast-graying individuals, with up to nine copies present locally in the melanomas themselves. The VGL now offers the gray copy number genetic test.

Gray horses that are also black (homozygous a/a at the Agouti locus) are also at higher risk of developing melanomas.

The genetic risk behind melanomas in non-gray horses is not well understood.

What are the clinical signs of melanoma?

Visually, melanomas are tumors characterized by dark pigment, usually in the form of nodules just under the skin. Sometimes these nodules can merge to form clusters or plaques, and they increase in size and number as gray horses age. Commonly affected sites include the base and underside of the tail, genital regions, throatlatch, lips, and eyelids. They may also affect internal organs such as the liver, spleen, and lungs. When melanomas occur in non-gray individuals, they generally appear as single lumps on the trunk and legs of young (< 2 years old) horses.

Other clinical signs of melanomas in horses are variable based on the location and size of the tumor(s). Masses may interfere with the placement of saddles or bridles. Internal tumors can cause digestive issues, such as difficulty defecating.

How is melanoma diagnosed?

Biopsies or fine needle aspirations of melanoma sites may be used for histological and immunohistochemical examination to determine molecular characteristics of masses and identify if they are benign or malignant. 

Ultrasound and rectal palpation are used to look for internal masses.

As with many other equine health issues, early diagnosis is associated with more successful outcomes.

How is melanoma treated?

The first choice for melanoma treatment is surgical excision with wide margins. Tumor regrowth at the same site is unlikely in cases with clean surgical margins. However, surgery at one site does not reduce tumor development at other sites and it may not be an option in advanced cases. Local chemotherapy may be used for small tumors, but melanomas are generally resistant to systemic chemotherapy. Radiation therapy may be used to treat melanomas in some locations, like the throatlatch region. A combination of treatments is often more successful than a single approach.

There is no clear consensus on the best ways to treat melanomas and treatments often show inconsistent results. Even if they are successfully removed, new melanomas develop, especially as horses age. Further research is needed to better understand tumor development and progression and how best to treat the disease.

What is the prognosis for melanoma?

The prognosis for horses with melanomas that are benign and easily removed is usually excellent. The prognosis for those with invasive tumors is generally guarded.

It is important to note that although melanomas are common in gray horses, and in severe cases euthanasia may be necessary, there is no evidence that gray horses have shorter lifespans than non-gray horses.

How can melanoma be prevented?

Melanoma vaccination strategies have been explored, but data interpretation has been challenging due to a lack of control groups and reports of wide-ranging data.

The ONCEPT™ canine melanoma vaccine, licensed for oral melanoma treatment in dogs, can be obtained for off-label use in horses by veterinary oncologists. A small study in unaffected horses demonstrated that the vaccine is safe and generates an immune response but did not test for a clinical response (Lembcke et al. 2012). A clinical trial that used the vaccine to treat 50 horses with melanomas reported tumor shrinkage in most horses (Phillips et al. 2012). More studies are needed to evaluate the effectiveness of melanoma vaccines in horses.

Genetic testing can help breeders identify horses that are homozygous for gray (i.e. will always produce gray offspring). It can also help breeders select for the G2 allele, which still allows for gray but with reduced risk of melanomas.

For more information

UC Davis Veterinary Genetics Laboratory – Horse Genetic Tests

Center for Equine Health Horse Report - Equine Cancer (Fall 2024)