Canine Oral Osteocartilaginous Malignant Amelanotic Melanoma with Pulmonary Metastasis

Abstract

Background: Melanomas are typically malignant neoplasms commonly observed in the oral cavity of dogs. The classical presentation of melanomas with characteristic melanin pigmentation is easy to diagnose; however, in some cases, the lack of melanin production in the amelanotic oral tumors cause a delay in establishing the precocious diagnosis and consequent treatment. The aim of this report was to evaluate the histopathological and immunohistochemical aspects of an oral amelanotic melanoma with osteocartilaginous formation and metastasis in a dog, in a temporal way.

Case: A 10-year-old male German Shepherd dog, presenting mouth bleeding with an amelanotic melanoma located between the upper incisors was received at the Veterinary Hospital of the Catholic University Dom Bosco (UCDB), Campo Grande, MS, Brazil. The animal was clinically evaluated and radiography was performed. The tumor was surgically removed and a sample was collected for histopathological examination that revealed spindloid and some epithelioid morphological cell types surrounded by a fibromatous matrix with moderate amounts of fibrovascular stroma. Approximately 1 month after surgical removal, recovery of the tumor was observed, and a second clinical analysis and collection of sample were performed. These procedures were repeated three times showing the same histopathological characteristics added by myxoid, chondroid, fibromatous tissue, and small groups of chondrocytes as well as central areas of irregular mineralized spicules. X-ray examination revealed proliferative and lytic bone infiltration in the jaw. Immunohistochemical analysis for melanocytic differentiation markers was performed showing positivity to Melan-A, tyrosinase and HMB-45 immunoreactivity, while no S100 reactivity was detected. After 11 months of the first biopsy, pleural effusion and radiopaque disseminated nodules of 1cm in the lungs were detected by X-ray. The animal died and necropsy was conducted. Multiple masses were observed in the lung and at the parietal pleura, suggesting lung metastasis by the positivity for Melan-A.

Discussion: The dog was first diagnosed with fibromatous epulis based on the observation of fibroblastic tissue and spindle cells with intense vascularization associated to the site of the tumor and its macroscopic aspect. In the subsequent follow-ups the tumor displayed malignant characteristics observed by recurrence after each surgery, as the tumor returned even larger, aggressive, and infiltrative. From the second biopsy, the histopathological analysis showed the undifferentiated character of epithelioid neoplastic cells, demonstrated by the increase of cartilage and osteoid tissue and the mineral deposit. The phenomenon of the tumor stroma to form cartilage and bone is highlighted here because myxoid change and cartilage formation were frequently observed at the site where amelanotic spindle cells were actively proliferating. It is possible that neoplastic melanocytic cells themselves were involved in the development of the osteocartilaginous areas. Although no cytoplasmic melanin pigmentation was found in the tumor fragments, specific melanocytic markers for melanoma detected neoplastic melanocytes and unmelanized melanosomes. The positive reaction for Melan-A, HMB-45, and tyrosinase in the epithelioid, spindle, and cartilaginous cell groups of the neoplasia indicated amelanotic melanoma with osteocartilaginous differentiation. The negative HMB-45, S100, and tyrosinase expression in lung metastasis may be due to the fact that melanomas express aberrant markers and are also known to display occasional loss of their classic immunophenotype. Amelanotic melanoma can be underdiagnosed due to rapid progression of the tumor allied to the dedifferentiation ability of melanocytes. Thus, the follow up study of cell morphology and immunohistochemical analysis for melanogenic factors can be important determinants in diagnosis.