Signalment:  

Two-month-old, Duroc-Hampshire crossbred, barrow, hog (Sus scrofa domestica)The animal presented and culled for necropsy was from a farrow to finish swine herd in central Taiwan. Piglets were born healthy and began developing skin lesions and weight loss 6-7 days prior to necropsy. Four piglets from a batch of 60 piglets in the nursery pen were affected. Two piglets were found dead. Recent management changes included new farrowing and nursery houses and pens for batch production.

Gross Description:  

The piglet was in fair body condition. The integument of the piglet had multiple 1 to 3_ diameter, slightly raised, crusted skin lesions affecting all parts of the body. Lesions had dark-brown friable surfaces. There were multiple, black, raised, smooth, shiny nodules disseminated throughout the thoracic viscera, affecting the lungs and myocardium. Some dark, melanin like lesions were noted on the liver. All other organs were normal. 

Histopathologic Description:

Microscopically, the skin mass is well demarcated, nonencapsulated. The intact epidermis of skin section exhibits mild epidermal hyperkeratosis while large coalescing zone of superficial epidermal necrosis with inflammatory infiltration of neutrophils and histiocytes is observed in the affected skin. The skin mass is focally expanding the subcutaneous fat, compressing the underlying subcutaneous tissue and elevating the overlying dermis. The mass is composed of closely packeted large, polygonal to spindle-shaped cells arranged in sheets and short bundles contained within a scant intervening fibrous stroma. Most tumor cells (melanocytes) contain variable amount of brown to black intracytoplasmic pigment. The pigmentation varies from fine dusting to large quantities of granular to coarse material. Some of the spindle cells are less pigmented. Nuclei vary considerably in size; many nuclei are large, round to oval. Most nuclei contain one or rarely two large and round nucleoli. Cells along the superficial margins of the dermis abut on and occasionally surround the bulbs of hair follicles. The morphology of the tumor cells (melanocytes) is applicable to the metastatic focus in myocardium. Some myocardial tissue is destroyed and replaced by the growing metastases. 

Morphologic Diagnosis:  

Skin: Melanoma and moderate subacute necrotizing epidermatitis, Duroc-Hampshire cross, swine.
Myocardium: Melanoma, metastatic. 

Lab Results:  

Specimens of skin, lung and liver were submitted for aerobic bacterial culture. No bacterial organism was cultured from these organs.

Condition:  

Melanoma

Contributor Comment:  

Melanomas have been reported in a variety of domestic and wild animals ^4,7,8. It is a devastating disease frequently encountered with both veterinary and human medicine. The Sinclair miniature and Duroc breeds have a genetic predisposition for melanomas, besides, the Sinclair miniature pig has served as a model for spontaneous cutaneous melanoma in humans. Melanomas occur as congenital lesions and sporadically in all ages of Duroc-Jersey, Hormel, Sinclair and their crossbreeds, whereas these tumors are rare in other swine breeds. Regression of such tumors are common and in some breeds may occur in utero and at various times after birth ¹. Other tumors arising from the skin may look clinically very similar to melanoma. These include melanocyoma, dermal hemangioma, hemangiosarcoma as well as pigmented lesions of the epidermis and adnexa ^2,4.

Specific immunohistochemistry (IHC) to identify melanocytic tumors of swine is needed. In a resent study, normal and neoplastic porcine melanocytes were vimentin positive, cytokeratin negative, S-100 positive and alpha-1-antitrypsin (AIAT) negative, similar to the immunophenocyte reported for human normal and neoplastic melanocytes ⁶.

JPC Diagnosis:  

1. Haired skin and subcutis: Melanoma, Duroc-Hampshire crossbreed (Sus scrofa domestica), swine.
2. Heart: Melanoma, metastatic.

Conference Comment:  

The contributor provides a complete, concise description of melanomas in pigs. In dogs, 56% of melanomas develop in the oral cavity.^3,5 It is also the second most common subungual neoplasm.^3,7 Known as the "great imitator", melanoma may appear with or without melanin granules; in an interwoven, whorled, or nested pattern; with round, polygonal, and/or spindled cells; or any combination of these types.^3,7 Malignancy of canine cutaneous melanocytic neoplasms is often determined by number of mitoses (>3/10 HPF).^3,7 Melanocytic neoplasms involving the oral cavity, subungual region, and mucocutaneous junctions are almost always malignant.7 In feline cutaneous melanocytic neoplasms, extensive nuclear atypia, high mitotic activity, and an epithelioid cell type are suggestive of malignancy.⁷ When numbers and size of melanin granules obscure the mitotic rate, an H&E stained slide pre-treated with bleach can aid in evaluation. In this Wednesday Slide Conference case, the neoplasm has a mitotic rate of 1 per HPF, with some fields containing up to 3 mitotic figures.

Melanocytes are dendritic cells that are derived form neuroectodermal melanoblasts, and are normally found within the basal layer of the epidermis.⁷ Neoplastic transformations have been linked to various molecular changes such as mutation in the INK4a and INK4b and Waf-1 genes resulting in malfunction of two tumor suppressor proteins (retinoblastoma protein and p53), protooncogene mutation to oncogene, altered expression of epithelial cadherin and CD44 adhesion molecules, and upregulation of angiogenic and other growth factors.⁷ A recent study by van Kempen et al. has linked the increased expression of Type I collagen to the angiogenic switch that facilitates the progression of microinvasive to deeply invasive tumors in a porcine cutaneous melanoma model.⁹

Malignant melanomas in canines and humans may show chondroid or osseous metaplasia.^3,5 Oyamada et al. shows that the cartilaginous matrix transitions from the myxoid matrix produced by dedifferentiated neoplastic melanocytes.⁵ Since the osseous matrix is not associated with either the cartilagenous matrix or the myxomatous matrix, it is theorized that the osteoid matrixes are formed form dense collagenous connective tissue that is also produced by the dedifferentiated neoplastic melanocytes. ⁵

Melanomas are common in gray or white horses.⁷ More than 90% of these tumors are benign at initial presentation, but approximately two-thirds are thought to progress to malignancy.⁷ German Shepherd Dogs and Boxers are more prone to develop oral melanoma.⁷ Sinclair miniature and Duroc breeds of swine have a genetic predisposition to developing melanomas.⁷ Melanomas have also been reported in cats, cattle, sheep, and alpaca.⁷

References:

1. Das Gupta TK, Ronan SG, Beattie CW, Shilkaitis A, Amos MS Jr: Comparative hiotopathology of porcine and human cutaneous melanoma. Pediatr Dermatol 6:289- 299, 1989
2. Fisher LF, Olander HJ: Spontaneous neoplasm of pigs-a study of 31 cases. J Comp Path 88:505-517, 1978
3. Goldschmidt MH, Dunstan RW, Stannard AA, von Tscharner C, Walder EJ, Yager JA: Histological Classification of Epithelial and Melanocytic Tumors of the Skin of Domestic Animals, Second series, vol. III, pp. 39-40. Armed Forces Institute of Pathology, Washington D.C., 1998
4. Goldschmidt MH, Hendrick MJ: Tumors of the skin and soft tissues. In: Tumors in Domestic Animals, ed. Meuten DJ, 4th ed., pp. 78-84. Blackwell Publishing, Ames, IA, 2002
5. Oyamada T, Tanaka H, Park C-H, Ueki H, Komiya T, Arai S: Pathology of canine oral malignant melanoma with cartilage and/or osteoid formation. J Vet Med Sci 69:1155-1161, 2007
6. P+�-�rez J, Garcia PM, Bautista MJ, Mill+�-�n Y, Ordas J, de las Mulas M: Immunohistochemical characterization of tumor cells and inflammatory infiltrate associated with cutaneous melanocytic tumors of Duroc and Iberian swine. Vet Pathol 39:445-451, 2002
7. Smith SH, Goldschmidt MH, McManus PM: A comparative review of melanocytic neoplasms. Vet Pathol 39:651-678, 2002
8. Thirloway L, Rudolph R, Leipold HW: Malignant melanomas in a Duroc boar. J Am Vet Med Assoc 170:345-347,1997
9. van Kempen LC, Rijntjes J, Mamor-Cornelissen I, Vincent-Naulleau S, Gerritsen MJ, Ruiter DJ, van Dijk MC, Geffrotin C, van Muijen GN: Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma. Int J Cancer 122:1019-1029, 2008

A virtual slide is not available for this case.

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