Application and Limitation of Advanced Diagnostic and Therapeutic Modalities in Zoologic Species with Malignant Melanoma
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA
Melanomas are tumors of melanocytes (pigment-producing cells) and have been reported in both domestic and non-domestic species.1-3 A diagnosis of melanoma is made by histopathologic evaluation of affected tissue. Information on diagnostic and therapeutic modalities of malignant melanomas in zoological species is scant. In most cases, treatment of choice is surgical excision of the mass. Further staging usually includes routine hematology, plasma biochemistry, aspiration of local lymph nodes, thoracic radiography, and abdominal ultrasound to determine evidence of metastatic disease.4 Adjunctive treatment consists of radiation therapy, chemotherapy and/or immunotherapy. In this study, a lion (Panthera leo) with dermal melanoma, a tiger (Panthera tigris) with conjunctival fornix melanoma, and a black-footed penguin (Spheniscus demersus) with melanoma of the uropygial gland were treated with immunotherapy (n=3), strontium-90 brachytherapy (tiger) or external beam hypofractionated radiation therapy (lion). In all cases, a complete blood count, plasma biochemistry panel, thoracic or whole-body radiographs, and a computed tomography (CT) scan (lion and tiger) or PET/CT scan (penguin) were performed to evaluate for distant or regional metastasis. Masses in the penguin and the tiger were surgically excised prior to the start of immunotherapy. In addition, strontium-90 brachytherapy was also administered for one session to treat microscopic disease at the surgical site of the tiger. The lion received weekly external beam hypofractionated radiation therapy for four treatments in conjunction with immunotherapy to reduce the size of the melanoma prior to surgical excision. Following treatment, the melanoma was reduced in size by approximately 50%. No adverse effects associated with radiation therapy were observed.
Immunotherapy is a novel treatment for the management of canine melanomas that utilizes the human tyrosinase enzyme to stimulate the host active immune system against tyrosinase enzyme-producing cells. There are no reports of its use in non-domestic species at this time. The lion and the tiger received 0.5 ml of the melanoma vaccine (Oncept, Merial, Duluth, GA, USA) intramuscular once a week for four initial treatments followed by boosters every 6 mo for the remainder of their lives. The penguin only received two doses of the vaccine (0.5 ml IM) as it was euthanized due to poor quality of life concerns. On post-mortem examination of the penguin, metastatic disease was present in the heart, lung, liver, kidneys, adrenal glands, gastrointestinal tract, skin, and brain. Both immunotherapy and radiation therapy were effective in treating the tumors found in the lion and the tiger as there is no physical evidence of metastatic disease present at 356 days (lion) and 138 days (tiger) since surgical excision of their respective masses. No adverse reactions to the melanoma vaccine such as pain, redness or swelling were observed in any of the patients of this report. The effectiveness of immunotherapy in developing an immune response in non-domestic species is currently under investigation. In the lion and tiger, computed tomography identified primary tumor margins while a PET/CT scan of the penguin did not identify the presence of metastatic disease of the melanoma. Further studies are indicated to evaluate the accuracy of advanced imaging modalities to identify metastatic disease and the application and limitation of radiation therapy and/or immunotherapy in zoological species with melanoma.
The authors thank the bird keepers at the Knoxville Zoological Gardens for the care provided to the penguin in this report and the staff, especially Debbie Chaffins and Mary Lynn Haven at Tiger Haven Inc. for providing the financial support for the protein assay to test for the anti-human tyrosinase antibodies and the care provided to the lion and tiger in this report.
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