Thursday, April 29, 2010

4/28/2010 Equine Melanoma

Vet tip of the Day: Equine Melanoma
Key Words: Melanoma, skin tumor, metastasis, cisplatin, cimetidine, laser

Many of you may have had experience over the years with melanoma in grey horses.  This form of melanoma, the dermal melanoma, is a very common skin tumor, usually slow growing, and usually confined to the site of origin.  Dermal melanomas are tumors of the black pigment cells, melanin cells, that are present in high numbers in the skin of grey horses.  The tumors typically are round, hard, and dense black when cut open.  They occur most frequently around the tail base and rectum, but also are seen in the throat latch region and at the base of the ear, where they most commonly arise in the parotid salivary gland.  While dermal melanomas often are solitary, some horses are afflicted with multiple tumors.  This condition is called dermal melanomatosis, and horses with multiple melanomas are more likely to have metastasis of tumors to remote locations, including lymph nodes, liver, spleen, and skeletal muscle.  Surgical removal of individual tumors in such horses may be locally curative, but the remaining tumors continue to grow and more tumors may develop.
There are two less common types of melanomas that occur in horses. The first is the melanocytic nevus, which is a benign tumor that occurs as a single, discrete, nodular mass in young horses. They may arise anywhere on the body and when removed surgically rarely recur.  At the other end of the spectrum are anaplastic malignant melanomas, which occur in older horses (usually over 20 years of age) of any color.  These tumors are uncommon, but usually metastasize to distant sites within a year and carry a poor prognosis.

While most horses with dermal melanomas tolerate them well, occasionally these tumors can be life threatening.  This happens most often when the tumors metastasize and grow in internal organs, or when they become so large that they cause mechanical obstruction to breathing in the throat region or impair defecation by obstructing the anus.

Dermal melanomas present an excellent example of how variable the behavior of tumors can be in different species.  As you probably are aware, melanoma in people often presents as a highly malignant tumor which may carry a poor prognosis for long term survival, even in the face of aggressive treatment.  Similarly, in dogs, oral melanoma is a malignant neoplastic process with a high fatality rate.  Many of you knew my wonderful dog Sticky, who died last year within three months of her diagnosis with malignant melanoma.  Luckily for our horses, this is NOT the case with equine dermal melanoma.  However, the common occurrence of melanoma in horses has made it a useful research tool for scientists investigating treatments for melanoma in other species.

One of the areas of intense investigation is the role of the immune system (immunomodulation) in treating melanomas in humans, dogs, and to a lesser degree, horses.  There is a melanoma vaccine currently under conditional license for malignant melanoma in dogs which I gave to Sticky during her treatment.  There also have been limited investigations using vaccines made directly from tumors removed from a particular horse then administered back to the same horse to control widespread melanomas. However, at this time there is no commercially available equine melanoma vaccine and the use of individual melanoma vaccines is not considered standard therapy.

There are many medications used for other purposes which exhibit immunomodulatory activity in addition to their primary mode of action.  One of these is cimetidine.  Cimetidine is an H2 histamine antagonist which reduces acid production in the stomach and is available over the counter as Tagamet, used in people and horses to treat gastric ulcers.  Cimetidine also acts in several complex ways to alter the body's immune  response to certain neoplastic (cancerous) processes.  It has been used with some success in the treatment of equine dermal melanoma at a dosage of 2.5 mg/kg given orally every 8 hours.  Unfortunately, after some promising initial studies, it appears that the activity of cimetidine against equine melanomas is very variable from horse to horse.  While the medication is unlikely to have adverse effects, its efficacy in each case is unpredictable, and therefore, it also no longer is widely used in the treatment of melanomas.

Dr. Robertson, a veterinarian at the Virginia Tech School of Veterinary Medicine did his PhD research on comparative melanoma (across species) and continues to conduct clinical research using Frankincense Oil as an immunomodulatory agent in the treatment of equine melanoma.  The oil is injected into the tumors and causes their regression.  The overall effectiveness of this treatment is not yet determined, but it is an interesting avenue holding promise for the future.  

In addition to immunomodulation, chemotherapy has been used in the treatment of equine melanoma. One chemotherapy agent used in horses is cisplatin, which is very effective in the treatment of squamous cell carcinoma (blog coming up on this soon).  Cisplatin has poor effectiveness against melanomas in dogs and people, but has been used with success in at least one clinical trial in horses.  In this study, 13/14 horses with melanoma had a positive response to the implantation of slow release cisplatin beads into the tumor mass.

The definitive treatment for melanomas is wide surgical excision.  With the advent of surgical lasers, it has become possible to remove larger tumors in challenging anatomic locations, such as the parotid salivary gland.
Traditionally, many veterinarians do not recommend the removal of small melanomas when they are first detected.  I disagree with this approach.  Melanomas tend to be very well isolated and complete surgical excision is often possible when the tumors are addressed early and are relatively small.  While excision does not prevent the development of new tumors at other sites, in my experience recurrence of the tumor at the site of excision is rare.

In summary, if you have a grey horse with melanomas, ask your veterinarian to evaluate them. I strongly recommend early surgical removal.  Consider cimetidine as an adjunctive therapy because it is safe, and may be effective.  Cimetidine can be obtained from reputable compounding pharmacies at a reasonable price.   For more advanced tumors, discuss the options of laser surgery and/or cisplatin bead implantation and consider seeking the opinion of a  veterinary specialist, an ACVS boarded surgeon and/or ACVIM boarded large animal internist.

I believe that education is the key to evolution. I believe that animals are the key to compassion. I believe the learning never stops.


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