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Malignant melanoma of the syrinx and liver in an African grey parrot (Psittacus erithacus erithacus).

Abstract: A 20-year-old, female African grey parrot (Psittacus erithacus erithacus) was examined because of ataxia and weakness. Radiographs were unremarkable, and results of a complete blood cell count revealed leukocytosis and heterophilia. Because of poor response to therapy with meloxicam, doxycycline, and enrofioxacin; deteriorating condition; and poor prognosis, the parrot was euthanatized. Postmortem examination revealed 2 dark red nodules in the liver. No grossly visible mass was observed in the syrinx. Histologic examination of the liver and syrinx revealed similar foci of round, oval, and polygonal cells exhibiting severe pleomorphism, with poorly demarcated cytoplasmic borders and moderate amounts of eosinophilic cytoplasm containing brown to black granules (melanin). The mitotic index was 15. The presence of melanin pigment is consistent with a diagnosis of melanoma at both sites. The multifocal distribution and intravascular invasion indicate metastasis; however, the site of origin was unknown. To our knowledge, this is the first recorded case of melanoma in an avian syrinx.

Key words: melanoma, neoplasia, syrinx, avian, African grey parrot, Psittacus erithacus erithacus

Clinical Report

A 20-year-old, female African grey parrot (Psittacus erithacus erithacus) was examined by a local veterinarian for decreased movement of the left wing, depressed attitude, and inability to perch. Radiographs were unremarkable, and results of concurrent blood work showed leukocytosis. Because the patient failed to improve with enrofloxacin (16 mg/kg PO q12h; Baytril, Bayer Health Care, Shawnee, KS, USA) and meloxicam (0.3 mg/ kg PO q12h) therapy, it was referred to the Veterinary Health Center, Kansas State University.

On presentation, the bird was quiet, alert, and well conditioned with a body condition score of 3 of 5 and a weight of 425 g. Appetite and stool appearance were normal. Primary findings on physical examination were weak vocalizations, increased upper respiratory sounds, generalized weakness, and overgrown upper beak. The parrot could not stand upright and was particularly weak in the legs, more so on the right side, during grasping or climbing. A blood sample was collected for a complete blood cell count (CBC) and biochemical profile, whole-body radiographs were obtained, and a tracheal swab was collected for cytologic examination and aerobic bacterial culture.

Results of the CBC revealed leukocytosis (33 000 cells/[micro]L; reference interval, 5000-15 000 cells/[micro]L). (1) No clinically significant abnormalities were present in the biochemical profile. Radiographs showed a soft tissue mass in the cranial coelom, superimposed with the gastrointestinal tract, but were otherwise unremarkable. Cytologic examination of the tracheal swab sample appeared nonpathologic and noninflammatory, composed of a variable background of lysed cells, occasional small epithelial cells, and rare erythrocytes. Results of the bacterial culture of the trachea were negative.

Based on the available data, an infectious process was suspected. Meloxicam (0.75 mg/kg PO q12h), enrofioxacin (15 mg/kg PO q12h), and doxycycline (25 mg/kg PO q12h) were prescribed. The patient was discharged, and the owner was instructed to monitor the bird closely. Unfortunately, the parrot's ataxia, weakness, and depressed attitude continued to progress. Reexamination by the referring veterinarian 21 days later resulted in the addition of an antifungal agent to the previously described regimen.


Thirty-five days after initial discharge from the Veterinary Health Center, the patient presented again for severe worsening of clinical signs, including hunched posture, ataxia, louder upper respiratory sounds, and an inability to perch. The patient weighed 420 g. Results of a CBC indicated a mild heterophilia (25 100 cells/pF; 78% [reference range, 45%--75%]), (1) and the biochemical profile results were unremarkable. Radiographs were performed but remained unchanged from the previous radiographic study. Euthanasia was elected because of the poor response to therapy, deteriorating condition, and poor prognosis.

Postmortem examination revealed 2 raised, dark-red nodules approximately 0.5 cm in diameter in the liver. No grossly visible masses were observed in the trachea or syrinx, and the mucosa was diffusely dark brown. An approximately 1-cm-long segment of mineralization was present at the root of the aorta and brachiocephalic trunks. Tissues were collected, fixed in 10% buffered formalin, routinely processed for sectioning, and stained with hematoxylin and eosin.

Microscopic examination of the liver revealed many multifocal, variably sized, well-demarcated, but not encapsulated, neoplasms, in addition to the 2 grossly visible nodules (Fig 1) composed of markedly anaplastic, round to oval to polygonal cells, ranging in size from 20 pm to 60 pm in diameter (giant cells), with eosinophilic cytoplasm containing variable amounts of small, brown to black granules of melanin. Nuclei were round to oval, variably sized, and contained finely stippled chromatin and 1 prominent nucleolus. There were occasional binucleated and multinucleated neoplastic cells; 15 mitotic figures in ten x400 fields were counted. Infiltration of the neoplastic cells into blood vessels of the liver was observed (Fig 2).

Sections from the trachea and syrinx contained an infiltrative neoplasm composed of markedly anaplastic, round to oval to polygonal cells, ranging in size from 20 pm to 60 pm in diameter (giant cells), with eosinophilic cytoplasm containing variable amounts of small, brown to black granules of melanin. There was an increased nuclear to cytoplasm ratio, and the nuclei were round to oval to pleomorphic, ranging from 10 [micro]m to 40 [micro]m in diameter, and contained finely stippled chromatin and 1 prominent nucleolus, which sometimes measured up to 5 [micro]m in diameter. The neoplastic cells in the syrinx exhibited histomorphologic characteristics similar to those observed in the liver. The neoplastic cells infiltrated and moderately expanded the submucosa of the trachea and syrinx and the underlying skeletal muscle and replaced most of the underlying hyaline tracheal and syrinx cartilage (Fig 3). The remaining tracheal cartilaginous rings were partially or completely ossified, and many of them were infiltrated by neoplastic cells. Degeneration of myofibers was noted within regions of the skeletal muscle infiltrated by neoplastic cells (Fig 4).



The subintima and elastic tunica of the aorta were markedly expanded with fibrous connective tissue, a large amount of myxomatous material, cholesterol crystals surrounded by foamy macrophages, and chondroid tissue with mild amounts of mineral deposits. The lumen of the aorta was mineralized and severely decreased in size, characteristic of type TV atherosclerosis. (2)


In this report, we describe a malignant melanoma in the syrinx and liver of an African grey parrot. Melanomas have been reported in the following avian species: African grey parrot, (3) thick-billed parrot (Rhynchopsitta pachyrliyncha), (4) umbrella cockatoo (Cacatua alba), (5) budgerigar (Melopsittacus undulatus), (6) zebra finch (Taeniopygia guttata), (7) lesser black-backed gull (Larus fuscus), (8) muscovy (Catrina moschata) and Peking (Anas platyrhynchos) duck cross, (9) Mandarin duck (Aix galericulata), (10) combed duck (Sarkidiornis melanotos), (11) southern Bahama pintail duck (Anas bahama bahamensis), (12) red-tailed hawk (Buteo jamaicensis), (13) merlin (Falco columbarius), (14) rock hopper penguin (Eudyptes chrysocome), (15,16) macaroni penguin (Eudyptes chrysolophus), (13,16) and Humboldt penguin (Spheniscus humboldti). (16-18) To our knowledge, no previous case of avian malignant melanoma affecting the syrinx has been described. Melanomas in psittacine birds have been found to affect multiple organ systems and to be markedly malignant, featuring widespread distribution in tissues, aggressive local invasiveness, and cellular pleomorphism. (5) In this case, we confirmed the malignant nature of this melanoma by the presence of invasion of neoplastic cells into hepatic vasculature. Whether the primary neoplasm in this patient arose from the liver or syrinx is unknown. Liver has been suggested as the most commonly affected and principle organ in birds (19); however, because of the pigmented nature of the syrinx in this species, it is reasonable to suspect the syrinx as the organ of origin. The exact tissue of origin in other reports of melanoma in birds was also unknown. (7)


Several pathogeneses of melanoma have been described in dogs. (20) Exposure to ultraviolet radiation across all breeds and genetic factors in purebred dogs have been implicated in mutations that lead to melanoma. The underlying cause of neoplastic transformation in the African grey parrot we describe is unclear because both exposure to ultraviolet radiation and genetic predisposition are unlikely, based on the location of the tumors and the rarity of melanoma in avian species. It is possible that melanomas in birds are the result of spontaneous neoplastic transformation.

The cause of the ataxia and weakness observed in this patient was not determined, although atherosclerosis causing decreased cardiac output is suspected. Intermittent claudication-like syndrome has been described in a yellow-naped Amazon parrot (Amazona ochrocephala auropalliata). (21) This African grey parrot may have suffered from a similar condition; however, the signs exhibited by this patient were persistent rather than intermittent, and no peripheral vasculature was examined at necropsy.

No sites of malignancy were identified in the brain or sciatic nerves grossly or histopathologically, but a neoplastic cause of ataxia cannot be ruled out in this case because of the malignant potential of the tumor in this bird. Ataxia was reported as a clinical sign in a budgerigar with a melanoma, (6) but no metastases were identified in that animal, although spinal cord involvement was suspected. Experimentally, melanoma has been induced in the brains of mice (22) and has been found in the brain of a dog as an extension of a primary ocular lesion, (22) but no reports of melanomas, to our knowledge, were found in the central nervous system of birds. Given the malignant nature of this neoplasm, which was confirmed by intravascular invasion into a hepatic blood vessel, it is also possible that the neoplasm metastasized to the bone or spinal cord, causing ataxia. However, these tissues were not examined histologically in this bird.

Atherosclerosis was also diagnosed at necropsy in this parrot. Atherosclerosis is a common postmortem finding in Psitttaciformes (24) and has been characterized through histochemical and immunohistochemical methods in African grey parrots and Amazon parrots (Amazona species). (25) Although clinical signs in birds with atherosclerosis are uncommon, several of the vague clinical signs, including dyspnea, progressive paresis of the hind limbs, and exercise intolerance observed in the parrot in this case, have been associated with atherosclerosis in psittacine birds. (26)

Respiratory tract disease, specifically of the tracheal submucosa and adjacent skeletal muscle, may affect syrinx vocalization. The melanoma identified in this African grey parrot suggests that this neoplasm should be included as a differential diagnosis for changes in vocalization. Metastatic melanomas have caused respiratory tract disease in Psittaciformes, (3,4) Anseriformes, (11) and Falconiformes, (14) although primarily affecting the lungs and nasal cavities. Other differentials for syrinx dysfunction in birds include mycoses, inhaled foreign bodies, parasitism, viral tracheitis, and goiter. (27) Mycoses, in particular, can be difficult to treat and require long-duration therapy. Available diagnostic tests to aid in the differentiation of these conditions include tracheal endoscopy, radiography (with or without contrast), and exploratory surgery.

Most literature on melanoma in veterinary patients is focused on canine oral malignant melanoma. Surgical excision with wide margins, followed by radiation in cases of incomplete margins, is the treatment of choice in dogs. (28) Radiation therapy with 6 to 9 Gy, once weekly to every other week, has been successful in achieving local tumor control. (28) Unfortunately, most of these dogs suffered from metastasis or local tumor regrowth.

In birds, nonsurgical treatment has been unsuccessful in achieving remission from melanoma. In a penguin with melanoma near the naris, radiation therapy was attempted. (16) The tumor in that bird ultimately regressed, but metastatic lesions arose 29 months later. Radiation therapy with oral antitumor drugs have been previously attempted in a thick-billed parrot with stage IV malignant melanoma, as described by the World Health Organization staging for canine oral melanoma. (4) Although the primary tumor showed significant reduction in size with aggressive radiation protocol paired with oral piroxicam and cimetidine, the parrot ultimately died from metastatic lesions. Surgical excision of the tumor was deemed impossible based on location. Although the tumors described in the African grey parrot we describe were not detected antemortem, they also would have been surgically inaccessible.

Surgical excision of a melanoma of smaller than 2 cm in diameter and showing no signs of metastasis was curative in 2 of 3 penguins. (16) Ten penguins were identified in that report, and metastasis was found in every animal with a tumor larger than 2 cm in diameter. The World Health Organization classification system for canine oral malignant melanoma classifies any tumor smaller than 2 cm in diameter as a grade I tumor. (28) This grading system is of uncertain prognostic value in birds. The apparently aggressive nature of this neoplasm and the common involvement of the liver may decrease the likelihood of identifying an appropriate size tumor before metastasis. Surgical excision has also been attempted in a zebra finch, but the tumor in that bird was adhered to much of the viscera, and the patient died under anesthesia. (7) Classification of melanoma as having a mucosal, visceral, or cutaneous form has prognostic and therapeutic value in domestic animals, but the distinction between forms has not been declared in previous reports of melanoma in birds.

Most reported cases of melanoma in birds were identified as a mass on physical examination, and several were able to identify the tumor type through biopsy. (4,7,9,10,16) If an antemortem diagnosis of melanoma is made, potential chemotherapeutic modalities may be considered. In dogs and people, melanomas appear to be very resistant to chemotherapy protocols. (28) In horses, cimetidine has been successfully used to decrease the number and size of melanomas, (29) and cisplatin has been remarkably successful in the treatment of cutaneous melanoma as an intratumoral treatment, having a cure rate of 81%. (30) Melanomas appear to be highly malignant in birds, and patients may not present with an accessible, discrete tumor for intratumoral chemotherapy.

In dogs, immunotherapy has been attempted for the treatment of oral malignant melanoma. Dogs receive 4 doses of transdermal vaccine, delivered with a needle-free device, as part of an initial vaccine series and receive a booster every 6 months. (31) Because of the force with which the vaccine is propelled through the skin, alternative methods of delivery may need to be explored if the melanoma vaccine is attempted in avian patients. Additionally, a retrospective study of 45 dogs with local disease controlled through surgery suggests that progression-free survival, disease-free interval, and median survival time were not improved by vaccination. (31)

In the African grey parrot we describe, a definitive diagnosis was found on histopathologic examination of tissues collected at necropsy. A reasonable next step in diagnostic testing could have been computed tomography because this modality has been successfully used to identify melanoma tumors in a gull. (8) However, the neoplastic lesion of the syrinx in this parrot was not identified radiographically or on gross necropsy, and it is unlikely that computed tomography would have provided any valuable diagnostic information. Fine-needle aspiration of a liver nodule, however, may have yielded a diagnosis, but there was little indication to further image the liver based on radiographic findings and biochemical profile.

Although avian melanomas are uncommon, they should remain a differential diagnosis for masses of unknown origin affecting the respiratory tract of psittacine birds. In birds, melanomas appear locally invasive and prone to metastasis. The aggressive nature of this neoplasm and the frequently nonspecific signs appear to result in diagnoses at an advanced stage and with metastatic lesions. Although there are a limited number of cases available, no reports in birds, to our knowledge, identified a nonsurgical therapy that resulted in the remission of this neoplasia. The grave prognosis associated with this disease illustrates a need for further investigation into therapy considerations of avian melanomas.

Acknowledgment: We thank Dr Rodney Schnellbacher for his contributions in the management of this case.


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Trenton C. Shrader, DVM, James W. Carpenter, MS, DVM, Dipl ACZM, Ada Giselle Cino-Ozuna, DVM, Dipl ACVP, and Gordon A. Andrews, DVM, PhD, Dipl ACVP

From the College of Veterinary Medicine (Shrader) and the Departments of Clinical Sciences (Carpenter) and Diagnostic Medicine/Pathobiology (Cino-Ozuna, Andrews [deceased]), College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA.
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Title Annotation:Clinical Report
Author:Shrader, Trenton C.; Carpenter, James W.; Cino-Ozuna, Ada Giselle; Andrews, Gordon A.
Publication:Journal of Avian Medicine and Surgery
Article Type:Clinical report
Date:Jun 1, 2016
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