A 28-year-old 706-g (1.55-lb) blue-fronted Amazon parrot (Amazona aestiva) of unknown sex was evaluated because of nonproductive regurgitation-like movements of the neck of 1 week's duration. The owners had also noted an odd sound, described as 2 stones rubbing together, when the bird swallowed. The bird was quieter than normal, and its plumage was slightly fluffed at home. The bird's appetite and droppings were considered normal. It had been examined by a veterinarian 1 month earlier because of beak malocclusion and had appeared otherwise healthy at that time.
On initial physical examination, the parrot was bright, alert, and responsive. The crop was distended with air, and the gnathotheca was slightly overgrown and deviated to the left. There was moderate pododermatitis on the plantar aspect of both feet. Mild absence of the covert and down feathers in the axillary region was evident bilaterally, and a repetitive, regurgitation-like motion of the neck and tongue was observed approximately every 15 to 30 minutes. When the bird was placed in left lateral recumbency for blood collection from the right jugular vein, a 1.0 × 0.5-cm, firm, nonmoveable, subcutaneous mass was palpable near the crop.
Hematologic and serum biochemical testing revealed moderate monocytic leukocytosis (15.3 × 103 WBCs/μL; reference interval, 6 × 103 WBCs/μL to 10 × 103 WBCs/μL) and high creatine kinase activity (1,849 U/L; reference interval, 45 to 265 U/L). The parrot was anesthetized with sevoflurane, and full-body radiography revealed that the cardiohepatic silhouette was widened with suspected hepatic enlargement and gas dilation of the crop, intestines, and cloaca. An ovoid, 2.4-cm-long soft tissue structure was detected in the right side of the neck, cranial to the crop, and was visible on lateral and dorsoventral views (Figure 1).
Primary differential diagnoses for the neck mass included neoplasia and granuloma. A crop swab specimen was submitted for cytologic examination, which revealed a high number of bacteria with a large proportion of gram-negative rods, consistent with ingluvitis. Mild epithelial dysplasia was also present. A fine-needle aspirate specimen of the mass was obtained for cytologic evaluation while the bird was restrained. On the basis of the cytologic findings, epithelial neoplasia was diagnosed. The degree of atypia among the neoplastic cells was indicative of squamous cell carcinoma.
Owing to the parrot's poor long-term prognosis and the difficulty with resection of the mass because of its location, the owners elected euthanasia and necropsy. The parrot was sedated with ketamine hydrochloride (10 mg/kg [4.5 mg/lb], IM) and midazolam hydrochloride (1 mg/kg [0.45 mg/lb], IM), and pentobarbital sodium was administered IV via the right jugular vein. On necropsy, a 2 × 0.8 × 0.5-cm, soft to firm, tan mass was present in the cranial portion of the esophageal lumen and intimately associated with the esophageal mucosa. On cut section, the mass was lobulated and had an approximately 1-mm-diameter central area of necrosis. There was no food material present within the crop. The distal portion of the esophagus and the proventriculus were diffusely thickened and red to dark purple. The ventriculus contained a mix of seed and pelleted ingesta. The mucosa of the ventriculus and intestines was grossly normal. Histologic examination of sections of the mass and proventricular tissue revealed cohesive aggregates of atypical, medium to large, polygonal epithelial cells that had moderate anisocytosis, anisokaryosis, and occasional binucleation. The cells had moderately abundant, medium-blue cytoplasm and a large, ovoid to round, central to eccentric, hyperchromatic nucleus with variably prominent, single or multiple, small to large, round to angular nucleoli. A small proportion of neoplastic cells had evidence of squamous differentiation. A diagnosis of invasive esophageal squamous cell carcinoma was made. No evidence of metastatic disease was detected on gross or histologic evaluation of the submitted tissues (heart and great vessels, lungs, air sacs, liver, kidneys, reproductive tract, and spleen).
Six months after the case involving the blue-fronted Amazon parrot, a 34-year-old 586-g (1.29-lb) DNA-sexed male mealy Amazon parrot was evaluated because of regurgitation and distention of the crop of 1 to 2 days' duration. Anorexia and lethargy starting 12 hours prior to evaluation were also reported. The bird had a history of a toe amputation and rhinothecal fracture. It was last evaluated by a veterinarian 2 years earlier and was clinically normal on physical examination at that time.
On initial physical examination, the parrot was quiet but alert and responsive. The crop was markedly distended with air and fluid. Peristaltic movements of the crop were exaggerated and occurred with greater than normal frequency. Respiratory effort was mildly increased, although auscultation of the lungs and air sacs revealed no abnormalities. Phalanx 1 of digit 1 on the left pes was missing. Plumage was unkempt, and the parrot was moderately underconditioned (body condition score, 3/9).
For this parrot, primary differential diagnoses included heavy metal toxicosis, neoplasia, and infection (eg, aspergillosis, mycobacteriosis, or infection with avian bornavirus or herpesvirus). A blood sample was collected from the right jugular vein. Results of an avian bornavirus ELISA and real-time PCR assay and a psittacid herpesvirus panel were negative. Results of a CBC and blood lead and zinc concentration assessments were within reference limits. Serum sodium concentration was mildly high (159 mmol/L; reference interval, 136 to 152 mmol/L). An overgrowth of gram-positive rods was evident on microscopic examination of a crop swab specimen. Coryneform bacteria were cultured from the crop swab specimen.
Radiography, performed when the parrot was anesthetized with sevoflurane, revealed a potentially enlarged esophagus (Figure 2). Computed tomographya with a soft tissue algorithm was also performed during a second anesthetic event the following day. Computed tomographic images were obtained before and after administration of 1.7 mL of contrast agent (ioversol [350 mg/mL]). Severe esophageal thickening was confirmed, and the list of differential diagnoses was shortened to neoplasia, specifically squamous cell carcinoma given the location and appearance of the mass or, less likely, mycobacterial infection. Because of the parrot's poor prognosis and the potential for mycobacterial infection, the owner elected euthanasia and necropsy.
Necropsy revealed that the crop was markedly dilated, measuring 7 × 4 × 4 cm, and filled with a mixture of liquid ingesta and seeds. The esophagus was notably enlarged with a diffuse wall thickness of 4 cm and a stenotic lumen measuring 0.2 cm (Figure 3). The esophageal mucosa was pale tan to white with 3 to 5 pinpoint depressions. The serosa of the proventriculus appeared hypervascular with moderate thickening of the proximal 2-cm-long portion. The ventriculus contained only pink to orange liquid digesta and a small amount of grit. Black liquid digesta was found in the intestines. Coloring of the digesta was confirmed histologically as a postmortem change. Histologic examination of sections of the esophagus confirmed squamous cell carcinoma with invasion into the proximal portion of the proventriculus. Polygonal cells formed solid nests and trabeculae that extended from the mucosal surface to the level of the tunica adventitia (Figure 4). Neoplastic cells had abundant, eosinophilic cytoplasm and large nuclei. Anisocytosis and anisokaryosis with scattered mitotic figures were seen. The mucosal surface was eroded with heavy bacterial colonization.
Discussion
Squamous cell carcinoma is a malignant tumor of squamous epithelial cells. Generally, these neoplasms are aggressive and have been described in the skin, gastrointestinal tract, urinary bladder, vagina, lungs, and prostate of numerous mammalian species.1,2 Although skin is the most commonly reported primary site, squamous cell carcinoma has also been identified in the alimentary tract of many domestic species. It is the most common oral neoplasm in cats and is frequently located in the oral cavity and esophagus of dogs, humans, and poultry.3–5
Squamous cell carcinomas are generally characterized by solid nests, cords, and islands of pleomorphic epithelial cells. Intracellular keratin and intercellular bridging can be present but are not always evident histologically.6,7 Grossly, lesions are often ulcerated. Although they are slow-growing and do not commonly metastasize, squamous cell carcinomas are quite aggressive and can invade deep into surrounding tissues,6,8 making complete surgical excision difficult in locations such as the esophagus. Loss of expression of and reduction in the adhesion molecule e-cadherin have been associated with higher tumor grade and likelihood of metastasis of squamous cell carcinoma in people and animals.9
Multiple risk factors for squamous cell carcinoma development in the upper alimentary tract of various species have been identified. Diet, geographic location, and certain viral infections have been associated with increased risk of upper alimentary tract squamous cell carcinoma in cats, humans, and poultry.4,10,11 Concurrent increased prevalences of that disease in both humans and chickens in regions of Iran and northern China suggest common etiologic factors across species, most likely exposures in the environment, although these have not been specifically identified.5,11
Birds, domestic mammals, and humans with squamous cell carcinoma of the upper alimentary tract are most often evaluated because of dysphagia, and lesions are typically advanced at the time of diagnosis.8,11,12 Nonspecific signs, including anorexia, weight loss, and vomiting or regurgitation, are also common. In the limited avian reports3,7,13,14 available, secondary ingluvitis is often present in affected birds. It is important to remember that primary ingluvitis is rare in adult birds of most species, and crop infections most often indicate an underlying disease process.
Despite the gastrointestinal tract being a common site of primary squamous cell carcinoma in poultry,5 there are scant reports of this tumor type in that location in psittacines. To our knowledge, there is only 1 report13 of a squamous cell carcinoma in the distal portion of the esophagus in a yellow-naped Amazon parrot. In psittacines, neoplasms of the neck region (especially as discrete masses) are generally uncommon, and most of those detected are sarcomas, such as fibrosarcomas,12,15 although thymomas and a cutaneous squamous cell carcinoma of the neck have also been described.16,17 Traditional diagnostic testing (as used in human and small animal medicine) including radiography, fluoroscopy after oral barium administration, endoscopy, and CT, are relatively safe in avian patients and, in the case of radiography, can be performed at most veterinary clinics. Fluoroscopy following oral barium administration can be easily performed in awake birds and provides information regarding whether masses compressing the esophagus are intra- or extraluminal. Endoscopy and CT require general anesthesia or sedation, and the risk in debilitated birds must be weighed carefully; however, the information obtained from such diagnostic procedures can be used to determine the type of neoplasm as well as guide collection of biopsy aspirate and tissue samples. As in the case of most neoplastic diseases, definitive diagnosis requires histologic examination of samples of the mass. Because squamous cell carcinomas typically exfoliate well, examination of fine-needle aspirate specimens is often rewarding without the need for more invasive biopsy techniques.18,19
The prognosis for any animal with squamous cell carcinoma is generally poor, with a 5-year survival rate of only 5% in humans,18 and with much lower survival rates in domestic animals.4 Aggressive resection, often accompanied by esophageal reconstruction, is the treatment of choice for esophageal squamous cell carcinoma in humans and is associated with the longest survival rates.8,20 Radiation or chemotherapy may be used alone or in combination with surgery, with mixed results regarding survival times in human clinical studies.8,21 Most of the surgical techniques for treatment of esophageal squamous cell carcinoma are not feasible in avian patients at this time, but radiation and chemotherapy do have the potential to provide relief from dysphagia and improve the quality of life of affected domestic animals. Specific treatments for esophageal squamous cell carcinoma in birds have not been described, but cobalt-60 radiation, administration of carboplatin or cisplatin, and photodynamic therapy with ether pyropheophorbide-a have been used on cutaneous lesions with mixed results.22 In humans with resectable esophageal squamous cell carcinoma, a combination of chemotherapy (often administration of cisplatin and 5-fluorouracil) and tumor resection is considered the gold-standard treatment and offers the best survival times.20 Early diagnosis, however, is required, and further research of treatment options is needed.
To our knowledge, this is the first report of esophageal squamous cell carcinoma that was detectable as a discrete mass palpable in the neck of 2 psittacines. In the previous report13 of squamous cell carcinoma in the distal portion of the esophagus of a yellow-naped Amazon parrot, the parrot had comparatively more pronounced systemic signs (collapse, opisthotonos, torticollis, and lateral recumbency) and did not have an obvious neck mass that was palpable on physical examination. For the bird in the previous report, an esophageal mass was detected radiographically, but a definitive diagnosis of squamous cell carcinoma was made only after necropsy. Because the clinical signs of esophageal squamous cell carcinoma are similar to those of infection with avian bornavirus or mycobacteria, esophageal squamous cell carcinoma in birds could be underreported. The cases described in the present report illustrated the need to consider esophageal carcinomas as differential diagnoses for parrots with upper gastrointestinal tract signs or gastrointestinal motility issues. These cases also highlighted the possibility that esophageal squamous cell carcinoma may not be as rare in parrots as previously thought and that antemortem diagnosis is feasible and important to help guide treatment choices for affected birds.
Footnotes
Aquilion 16-slice CT scanner, Toshiba, Otawara, Tochigi, Japan.
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