Melanoma
Stephen D. White
Equine Melanomas
Melanomas occur in all domestic animals, but among the large domesticated species, they are most important in the horse. Excessive exposure to sunlight has not been definitively proven to predispose horses to the development of melanoma.
A disturbance in melanin metabolism associated with graying has been hypothesized to stimulate formation of new melanoblasts or to stimulate their activity, resulting in focal areas of overproduction in the dermis and epidermis, with subsequent tumor formation.1 A higher incidence is observed in the Arabian, Lipizzaner, and Percheron breeds, probably because gray coat color occurs more often in these breeds. There is no gender predilection.Melanocytic skin tumors of horses traditionally have been described in aging gray horses in typical locations: ventral tail, perineum, external genitalia, lip, udder, and periocular and parotid gland regions. These tumors have been the subject of several classification schemes in attempts to correlate histopathologic appearance with clinical behavior (i.e., benign or malignant). One study distinguished three basic types of melanocytic skin tumors, as discussed next.2
Melanocytic nevi (melanocytoma) occur in the superficial dermis or at the epidermal-dermal junction and frequently have epithelial involvement, with nests of relatively large, mildly to moderately pleomorphic cells showing variable cytoplasmic pigmentation and occasional mitoses. More than 70% of these occur in horses younger than 6 years of age and may occur in horses of any color (not just gray). Most of these tumors occurred in atypical locations. Of 28 melanocytic nevi, only one became invasive; the rest exhibited benign behavior.
Dermal melanomas are found in the deep dermis and are composed of small, homogeneous, indistinct tumor cells, either round or dendritic, with no mitoses.
(If there are multiple confluent dermal melanomas, this is referred to as dermal melanomatosis). About 80% of these tumors are in horses older than 6 years2 or between 5 and 15 years3 and are much more common in gray horses. Most of these tumors occurred in typical locations. Of 14 cases available for follow-up in one study,2 eight had malignant behavior, as demonstrated by metastases.In another study, clinicopathologic characteristics of cutaneous melanomas occurring in 83 Camargue-type gray-skinned horses showed that the tumors occurred most frequently underneath the tail (93.9%) and at high rates in the perianal region (43.0%), lips (33.0%), and eyelids (24.0%) but rarely in the vulva (3.8%).4 Microscopic examination indicated that these tumors were composed mostly of melanocytes and numerous melanophages, and that these cells manifested a remarkable cellular atypia. Early stages of the tumors occurred in close association with apocrine sweat glands but not at the dermal-epidermal junction.
A clinical study was conducted on 296 gray horses of the Lipizzaner breed.5 Of the 296 horses, dermal melanomas were present in 148 horses (50%), 68 of which were older than 15 years; 51 of these were melanoma bearing. In 75.6% of cases, melanotic tumors were detected underneath the tail. None of the affected individuals had any severe clinical effect or was handicapped in performance. The authors concluded that in contrast to melanomas in solid-colored horses, characterized by early metastases, melanomas in gray horses showed less malignancy. Affected individuals often had encapsulated nodules or structures similar to human blue nevi. This finding at least partially reflects confusion in terminology between true malignant melanomas and dermal melanomas.
Anaplastic malignant melanomas are composed of sheets of extremely pleomorphic epithelioid cells with poor pigmentation and many mitoses. These are usually seen in horses older than 20 years and occur in horses of any color.
Metastasis usually occurs first to the regional lymph nodes, then to the lungs, spleen, and liver. Hematogenous spread may also occur. Metastatic growths may be larger than the primary lesions and softer in consistency.In regard to treatment, one study reported good success with excising dermal melanomatosis from the perineal, perianal, perirectal, or ventral tail regions.6 In a study of three horses, cimetidine (2.5 mg/kg PO q8h) was shown to decrease the number and size of melanoma growth.7 However, another study of 10 horses found that cimetidine had no consistent effects on either the number of tumors or the tumor surface area over the 16 weeks of treatment at 5 mg/kg PO q12h.8 Another article noted a cure rate of 81% for melanomas treated with intratumoral injections of cisplatin.9 A recent article reported significant tumor regression when injecting interleukin-18- and interleukin-12-encoding plasmid DNA into the tumors of horses with metastatic melanomas.10
Bovine Melanomas
Melanomas represented a large proportion of the cutaneous neoplasms of cattle in an older study.11 The majority are benign, well-differentiated tumors, subcutaneous in location, and without site predilection. Dark-haired cattle are predisposed, particularly the Aberdeen Angus breed. There is no gender predilection.11 Melanomas usually occur in young cattle and are occasionally recognized as congenital lesions.12
Caprine and Ovine Melanomas
Melanomas have been observed only rarely in sheep and goats.11-14 A survey of 800,000 slaughtered goats revealed only 5 melanomas.12 The most common site for melanomas in the goat is the perineal region,13 although there is a case report of a malignant melanoma occurring in the coronary band region.14 Melanomas in Angora goats histologically resemble the corresponding tumors in humans.15