Gray Horse Disease--Melanoma

It is interesting that Federico Tesio in his book Breeding The Race Horse described the inheritance of the gray coat color like a disease or defect, since melanoma skin tumors are so common in the gray horse. On the other hand, the gray horse survives these tumors better than any other species that develops them. While horse owners worry about gray horses' tumors, scientists recognize that the horse must harbor the secret to surviving melanoma.

In the 1970s, I experimented on healthy, melanoma-bearing, retired gray horses by administering tumor vaccines made from a horse's existing tumors, presumably to stimulate a protective immune response against further tumors. The vaccines were made by Vincent Saurino, PhD, an emeritus professor in the College of Science at Florida Atlantic University in Boca Raton, Fla. One horse, after receiving vaccinations made from his own tumor, lost black pigment in some areas of his skin, including the tumors on his tail. This is a process called vitiligo. More recent research shows this might hold the key to the cure for melanoma.

One researcher, John Powderly, MD, has expertise on melanoma in several species, including man, that has led him to do more work on immunotherapy and the possible triggering of vitiligo. In mice, man, horse, and a special breed of swine called Sinclair swine, vitiligo has been associated with melanoma regression.

These miniature swine are the most dramatic example of vitiligo curing melanoma. About 84% of them are born with cutaneous nevi (pigmented skin areas), which develop into melanomas in the first six weeks of life. More than 50% of the tumors spread to internal organs, and some of these pigs die by the age of six weeks.

Many survive malignancy as vitiligo begins around six months of age. Then the black pigs turn totally white as the tumors shrink. Experiments in these swine have shown that the vitiligo process, although not well understood, is enhanced by hormones and immune competence. I've seen unusually developing white skin in horses due to hormones, inflammatory insults from infestations to trauma, and even post-surgical procedures. These all are situations that would involve a serious immune response.

Melanoma-associated vitiligo and immune mechanisms against pigment cell antigens occur in the gray horse as well. If vitiligo is a manifestation of the immune system's breaking of self-tolerance, then the white patterns mean that melanoma cell antigens are being seen by the immune system as targets. The melanoma cells bearing black pigment are thus destroyed, leaving the skin white.

In mouse and human studies, the immune response to melanocytes (cells carrying black pigment) can be even more specific. Non-pigmented skin can occur in body stripes, which correspond to a dermatome (area of skin innervated by a single sensory nerve) or body segment. The striped vitiligo patterns suggest unique dermatome-specific antigens. Since melanocytes originate embryologically at the site of the central nervous system (neural crest), it makes sense to derive a vaccine from nervous (dendritic) tissue.

Powderly is working on a dendritic melanoma vaccine in an effort to immunologically turn on the vitiligo process to achieve regression of the melanoma.

There have been four documented human cases of spontaneous melanoma regression associated with vitiligo. In all cases, vitiligo had crept over the dermatome where the primary melanoma was situated, and the tumor regressed. These are rare cases in man, but it is the pattern of regression seen in Sinclair swine where the vitiligo is generalized.

Vitiligo in the horse is sometimes bilaterally symmetrical and segmental when it appears to be immunologically and/or hormonally regulated. In my experience, it's not as common in other coat colors as it is in gray horses, where the pattern is often random. Although I haven't seen spontaneous total regression of melanomas in the horse as occurs in Sinclair swine, I have seen retarded growth and even partial regression of melanomas in horses which have had some form of immunotherapy.

I was aware of the role that vitiligo could play in the process; however, when I have debulked (removed) a rapidly growing melanoma from the perineum or tail and left it to heal as an open wound, the remaining black tumor tissue is replaced by healthy pink granulation tissue (skin then heals over the pink tissue). I've always believed that granulation tissue in the secondary healing process has an increased immune capability, and it would appear to be true when this tissue replaces melanoma in the gray horse.

As we anticipate some breakthrough in development of an immune stimulant in the fight against melanoma in man, we continue to look to animal models for some clues on the direction the research should take. Veterinarians will continue to use their tools of immunotherapy and surgery to enhance the gray horses' ability to coexist with his melanoma. The gray horse might hold the secret to survival from melanoma for us, his caretakers.

About the Author

Fred McCashin, VMD, MSc

Fred McCashin, VMD, MSc, is a private practitioner at Carolina Equine Clinic in Southern Pines, N.C., and a member of the AAEP's Purchase Examination Committee.

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