Antemortem diagnosis of esophageal squamous cell carcinoma in a blue-fronted Amazon parrot (Amazona aestiva) and a mealy Amazon parrot (Amazona farinosa)

Anne M. Staudenmaier 1Department of Avian and Exotic Animal Medicine, Angell Animal Medical Center, 350 S Huntington Ave, Boston, MA 02120.

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Elisabeth A. Simone-Freilicher 1Department of Avian and Exotic Animal Medicine, Angell Animal Medical Center, 350 S Huntington Ave, Boston, MA 02120.

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Brendan P. Noonan 1Department of Avian and Exotic Animal Medicine, Angell Animal Medical Center, 350 S Huntington Ave, Boston, MA 02120.

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Patty J. Ewing 2Department of Pathology, Angell Animal Medical Center, 350 S Huntington Ave, Boston, MA 02120.

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Abstract

CASE DESCRIPTION

A 28-year-old blue-fronted Amazon parrot (Amazona aestiva) with a 1 -week history of regurgitation-like movement of the neck and a 34-year-old mealy Amazon parrot (Amazona farinosa) with a 1- to 2-day history of regurgitation and crop distention were evaluated.

CLINICAL FINDINGS

Full-body radiography of the blue-fronted Amazon parrot revealed a soft tissue structure in the right side of the neck, cranial to the crop. Results of cytologic examination of a fine-needle aspirate specimen of the mass were diagnostic for an epithelial sarcoma involving the esophagus. For the mealy Amazon parrot, CT revealed diffuse esophageal thickening that was most consistent with esophageal squamous cell carcinoma on the basis of its location and appearance. Both parrots had secondary bacterial ingluvitis.

TREATMENT AND OUTCOME

Given the location and extent of the neoplasm in each bird, surgical excision was not undertaken. Options of chemotherapy and radiation therapy were explored but declined by the owners owing to concerns regarding the parrots' quality of life. Both parrots were euthanized, and necropsy findings confirmed the diagnosis of esophageal squamous cell carcinoma in both cases.

CLINICAL RELEVANCE

Both parrots of the present report had a palpable esophageal squamous cell carcinoma detected during physical examination. Although rare, esophageal squamous cell carcinoma should be included as a differential diagnosis for psittacines with upper gastrointestinal tract signs. Treatment to extend duration or quality of life of affected parrots hinges on antemortem diagnosis, which appears feasible in clinical practice.

Abstract

CASE DESCRIPTION

A 28-year-old blue-fronted Amazon parrot (Amazona aestiva) with a 1 -week history of regurgitation-like movement of the neck and a 34-year-old mealy Amazon parrot (Amazona farinosa) with a 1- to 2-day history of regurgitation and crop distention were evaluated.

CLINICAL FINDINGS

Full-body radiography of the blue-fronted Amazon parrot revealed a soft tissue structure in the right side of the neck, cranial to the crop. Results of cytologic examination of a fine-needle aspirate specimen of the mass were diagnostic for an epithelial sarcoma involving the esophagus. For the mealy Amazon parrot, CT revealed diffuse esophageal thickening that was most consistent with esophageal squamous cell carcinoma on the basis of its location and appearance. Both parrots had secondary bacterial ingluvitis.

TREATMENT AND OUTCOME

Given the location and extent of the neoplasm in each bird, surgical excision was not undertaken. Options of chemotherapy and radiation therapy were explored but declined by the owners owing to concerns regarding the parrots' quality of life. Both parrots were euthanized, and necropsy findings confirmed the diagnosis of esophageal squamous cell carcinoma in both cases.

CLINICAL RELEVANCE

Both parrots of the present report had a palpable esophageal squamous cell carcinoma detected during physical examination. Although rare, esophageal squamous cell carcinoma should be included as a differential diagnosis for psittacines with upper gastrointestinal tract signs. Treatment to extend duration or quality of life of affected parrots hinges on antemortem diagnosis, which appears feasible in clinical practice.

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).

Figure 1—
Figure 1—

Right lateral (A) and dorsoventral (B) radiographic views of a 28-year-old blue-fronted Amazon parrot (Amazona aestiva) that was evaluated because of nonproductive regurgitation-like movements of the neck of 1 week's duration. The owners had also noted an odd sound when the bird swallowed. In these views, notice a widening of the cardiohepatic silhouette and soft tissue mass cranial to the crop (arrow).

Citation: Journal of the American Veterinary Medical Association 254, 11; 10.2460/javma.254.11.1324

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.

Figure 2—
Figure 2—

Right lateral radiographic view (A) and postcontrast sagittal CT image (B) of a 34-year-old mealy Amazon parrot that was evaluated because of regurgitation and distention of the crop of 1 to 2 days' duration. Anorexia and lethargy had started 12 hours prior to the evaluation. The parrot was anesthetized to undergo diagnostic imaging. In the radiographic view, notice the enlarged esophagus (arrow) with crop distension orad to the lesion. In the CT image, the wall of the esophagus appears markedly thickened (arrow).

Citation: Journal of the American Veterinary Medical Association 254, 11; 10.2460/javma.254.11.1324

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.

Figure 3—
Figure 3—

Postmortem photograph of the thickened esophagus (arrow) and distended crop (left cranial margin) in the parrot in Figure 2.

Citation: Journal of the American Veterinary Medical Association 254, 11; 10.2460/javma.254.11.1324

Figure 4—
Figure 4—

Photomicrograph of a section of the esophageal mass in the parrot in Figure 2. Polygonal cells have invaded the tunica muscularis. H&E stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 254, 11; 10.2460/javma.254.11.1324

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

a.

Aquilion 16-slice CT scanner, Toshiba, Otawara, Tochigi, Japan.

References

  • 1. Higuchi K, Koizumi W, Sasaki T, et al. Current management of esophageal squamous-cell carcinoma in Japan and other countries. Gastrointest Cancer Res 2009;3:153161.

    • Search Google Scholar
    • Export Citation
  • 2. Allen JW, Richardson JD, Edwards MJ. Squamous cell carcinoma of the esophagus: a review and update. Surg Oncol 1997;6:193200.

  • 3. Anderson WI, Steinberg H. Primary glossal squamous-cell carcinoma in a Spanish cochin hen. Avian Dis 1989;33:827828.

  • 4. Bertone ER, Snyder LA, Moore AS. Environmental and lifestyle risk factors for oral squamous cell carcinoma in domestic cats. J Vet Intern Med 2003;17:557562.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Priester WA. Esophageal cancer in northern China; high rates in human and poultry populations in the same areas. Avian Dis 1975;19:213215.

  • 6. Ide H, Nakamura T, Hayashi K, et al. Esophageal squamous cell carcinoma: pathology and prognosis. World J Surg 1994;18:321330.

  • 7. Laura N, Marta V, Giacomo B, et al. Squamous cell carcinoma of the oropharynx and esophagus with pulmonary metastasis in a backyard laying hen. Avian Dis 2016;60:694697.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Stathopoulos GP, Tsiaras N. Epidemiology and pathogenesis of esophageal cancer: management and its controversial results. Oncol Rep 2003;10:449454.

    • Search Google Scholar
    • Export Citation
  • 9. Kaur G, Carnelio S, Rao N, et al. Expression of e-cadherin in primary oral squamous cell carcinoma and metastatic lymph nodes: an immunohistochemical study. Indian J Dent Res 2009;20:7176.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Manucy T, Bennett A, Greenacre C, et al. Squamous cell carcinoma of the mandibular beak in a Buffon's macaw (Ara ambigua). J Avian Med Surg 1998;12:158166.

    • Search Google Scholar
    • Export Citation
  • 11. Hafner S, Reece RL, Williams SM. Neoplastic diseases. In: Swayne DE, ed. Diseases of poultry. 13th ed. Ames, Iowa: Wiley-Blackwell, 2013;513674.

    • Search Google Scholar
    • Export Citation
  • 12. Latimer KS. Oncology. In: Ritchie BW, Harrison GJ, Harrison LR, eds. Avian medicine: principles and application. 2nd ed. Philadelphia: Elsevier Limited, 2009;640672.

    • Search Google Scholar
    • Export Citation
  • 13. Murtaugh RJ, Ringler DJ, Petrak ML. Squamous cell carcinoma of the esophagus in an Amazon parrot. J Am Vet Med Assoc 1986;188:872873.

    • Search Google Scholar
    • Export Citation
  • 14. Vázquez S, Quiroga MI, Aleman N, et al. Squamous cell carcinoma of the oropharynx and esophagus in a Japanese bantam rooster. Avian Dis 2003;47:215217.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Strafuss AC, Ladds PW. Fibrosarcoma in a young chicken. Avian Dis 1970;14:406409.

  • 16. Latimer K, Rakich M, Weiss R. Thymoma in a finch. J Avian Med Surg 2001;15:3739.

  • 17. Zubaidy AJ. An epithelial thymoma in a budgerigar (Melopsittacus undulatus). Avian Pathol 1980;9:575581.

  • 18. Khan N, Afroz N, Haider A, et al. Role of fine needle aspiration, imprint and scrape cytology in the evaluation of intraoral lesion. J Cytol 2013;30:263269.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Kolbusz R, Reyes CV, Hakky MM, et al. Asymptomatic esophageal squamous cell carcinoma masquerading as a rare primary pancreatic carcinoma: diagnosis by percutaneous fine needle aspiration. Acta Cytol 1988;32:399402.

    • Search Google Scholar
    • Export Citation
  • 20. Matsuda S, Takeuchi H, Kawakubo H, et al. Current advancements in multidisciplinary treatment for resectable cStage II/III esophageal squamous cell carcinoma in Japan. Ann Thorac Cardiovasc Surg 2016;22:275283.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Kato K. Chemotherapy and chemoradiotherapy. In: Ando N, ed. Esophageal squamous cell carcinoma: diagnosis and treatment. New York: Springer, 2015;197225.

    • Search Google Scholar
    • Export Citation
  • 22. Zehnder A, Graham J, Reavill D, et al. Neoplastic diseases in avian species. In: Speers B, ed. Current therapy in avian medicine and surgery. St Louis: Elsevier, 2016;107141.

    • Search Google Scholar
    • Export Citation
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