Adenocarcinoma of the distal esophagus and esophageal-proventricular junction in a yellow-naped parrot

Abstract

A 57-y-old male yellow-naped parrot (Amazona auropalliata) was presented because of lethargy, inappetence, and weight loss. Hematology and serum biochemistry were unremarkable, and imaging revealed a mass in the distal esophagus at the coelomic inlet. The luminal diameter of the esophagus was reduced in this area, and passage of ingesta was limited. Following gavage feeding, the patient died and was submitted for autopsy. At postmortem examination, the noted mass effect was a thickening of the distal esophagus with adherent, coalescing, soft, pale-tan plaques on the mucosal surface. Additional gross findings included pale-tan, opaque feed material oozing from the dorsum of the lungs and covering the cranial air sacs. Histology of the esophagus, esophageal-proventricular junction, and proximal proventriculus revealed an unencapsulated, infiltrative, transmural neoplasm that extended from the mucosal surface deep into the muscularis, almost to the adventitia. The neoplasm was composed of cuboidal cells arranged in islands and tubules, consistent with an adenocarcinoma, a rarely reported entity in the esophagus of psittacine birds and to our knowledge not reported previously at the esophageal-proventricular junction.

Neoplasia in general is rarely reported in psittacines. As in domestic species, neoplasia is diverse in its cell of origin, anatomic location, and its relation to viral and other oncogenic factors. Neoplasms are particularly common in budgerigars and cockatiels.^8,9 Notable entities include testicular tumors in budgerigars and pigeons, as well as seminomas, sustentacular (Sertoli) cell tumors, and primary renal tumors in budgerigars. ⁹ The most common oral and cloacal neop-lasia of macaws, conures, and amazon and hawk-headed parrots is papillomatosis, which is etiologically linked to herpesvirus.^8,9

Alimentary neoplasms of birds include smooth muscle tumors, squamous cell carcinomas (SCCs) in a variety of sites, cholangiocarcinomas, pancreatic tumors, and carcinomas and adenocarcinomas of the proventriculus, ventriculus, and proventricular-ventricular junction; the last of these is most common in budgerigars, parakeets, lovebirds, cockatiels, conures, and amazon parrots.^6,8,9 Ulceration, perforation, and metastasis to the pancreas and lungs have been reported with gastric adenocarcinomas. ⁸

Esophageal neoplasms are uncommon in psittacines and include infrequent reports of distal esophageal SCC, oral and pharyngeal papilloma, smooth muscle tumors of the crop and esophagus, and rarely esophageal submucosal gland carcinomas.^2,11,13 Alimentary SCC is described in Amazona sp., Nymphicus hollandicus, Ara sp., Eupsittula sp., and Poicephalus sp., in the oral cavity, crop, esophagus, and proventriculus, and is associated with regurgitation, dysphagia, dyspnea, lethargy, and weight loss. ¹ Secondary bacterial infection of the ulcerated mucosa with associated poor clinical outcomes is common in psittacine alimentary SCCs. ¹ Esophageal and crop papilloma is reported in macaws and amazon parrots, leiomyomas and leiomyosarcomas are infrequently reported in the crop and alimentary tract (not further specified) of budgies and lovebirds, and fibrosarcomas are reportedly rare in the esophagus and alimentary tract (not further specified) of budgies and parrots.^8,11,14 There is limited literature on carcinomas arising from the esophageal submucosal glands, ¹¹ with no published case reports of this entity, to our knowledge. In a search of Google Scholar, PubMed, CAB Abstracts, Web of Science, and Scopus, using the search terms “distal esophagus, esophagus, esophageal-proventricular, proventriculus, adenocarcinoma, carcinoma, yellow-naped parrot, amazon parrot, parrot,” and “psittacine,” in various combinations, we retrieved no reports of esophageal submucosal gland carcinoma in this species. The only mention of avian esophageal submucosal gland carcinomas we retrieved was a paragraph stating that submucosal gland carcinomas can occur in psittacines generally. ¹¹ Overall, these findings support our conclusion that this condition has not been reported at this site in this species.

Our case was a 57-y-old, male, yellow-naped parrot (syn. yellow-naped amazon parrot; Amazona auropalliata) that was presented because of lethargy, inappetence, and weight loss. On clinical examination, the patient was emaciated, lethargic, and dehydrated with unkempt feathers and a mildly distended, fluid-filled crop. Radiographs showed possible microhepatica; a mass effect, interpreted as thickening or distention, was identified at the distal esophagus to proximal proventricular region. Fluoroscopy, a barium study, and CT all supported focally extensive thickening of the coelomic esophagus with reduced luminal diameter that impaired passage of ingesta. Hematology revealed toxic heterophils and reactive monocytosis. Serum biochemistry revealed a grossly lipemic sample but was otherwise unremarkable. Fecal examination yielded overgrowth of gram-negative bacteria and budding yeasts (species not identified, presumed Candida), and a fecal PCR screening panel for Mycobacterium (including M. avium subsp. avium, M. genavense, and > 13 others) was negative. Primary differentials included neoplasia and infectious disease, including avian bornavirus (based on clinical signs) and Cryptosporidium (based on a positive fecal PCR result). Due to progressive loss of body condition, the patient was hospitalized with supportive care. During a gavage feeding, the patient aspirated feed material and died. Aspiration most likely occurred secondary to the esophageal lesion limiting food passage. The patient was submitted for postmortem examination.

On gross examination, the patient was in thin body condition, with mildly atrophic pectoral muscles and a prominent keel. The wall of the distal esophagus, at approximately the level of the coelomic inlet, was thickened with adherent, coalescing, soft, pale-tan plaques of up to ~2 × 4 mm on the mucosal surface. This thickened area was grossly limited to the esophagus and esophageal-proventricular junction, with no appreciable adhesions to, or extensions into, the surrounding tissue (Fig. 1). In addition, a small amount of tan, opaque feed material covered the dorsal aspect of the lungs and surrounding air sacs. A swab of the affected air sac was submitted for aerobic culture. Microscopic evaluation confirmed the opaque material to be feed material with minimal-to-no inflammatory cells, and culture returned abundant growth of Enterococcus faecium and Candida glabrata, consistent with commensal gastrointestinal organisms. Although the aspirated feed material outside the airways raised suspicions of an esophageal or proventricular rupture, a rupture was not seen grossly and the feed material was attributed to the clinically reported aspiration, presumed secondary to the distal esophageal mass.

Figure 1.

Esophageal-proventricular junction adenocarcinoma in a yellow-naped parrot. A. A tan, irregular mass (arrowhead) with a roughened surface narrows the lumen of the esophageal-proventricular junction. Esophagus is to the left, proventriculus is on the right. B. Transverse section of the distal esophagus and esophageal-proventricular junction. The neoplasm (asterisk) is visible in the tunica muscularis of the esophagus. H&E. C. The submucosa and tunica muscularis of the esophagus are expanded markedly by infiltrative neoplastic tubules. H&E. D. The neoplastic tubules often contain scant amounts of degenerate cellular debris and eosinophilic secretory product. H&E.

Histologically, the distal esophageal mass was an unencapsulated, poorly demarcated, infiltrative, transmural neoplasm that extended from the mucosal surface of the esophagus deep into the inner and outer layers of the muscularis externa (Fig. 1). The neoplasm was composed of cuboidal cells arranged in islands and tubules in a moderate amount of pre-existing stroma. Neoplastic cells had variably distinct cell borders, a moderate amount of pale basophilic cytoplasm, and round-to-reniform nuclei with finely stippled chromatin and typically one prominent nucleolus. Anisocytosis and anisokaryosis were moderate, and occasional neoplastic cells were binucleate. Six mitotic figures were seen in ten 400× fields (10× ocular field number 22 mm; 2.37 mm² equivalent). Neoplastic tubules were lined by one cell layer and frequently contained heterogeneous eosinophilic material in addition to variable numbers of sloughed cells and foamy histiocytes. Small numbers of lymphocytes and plasma cells dissected through the neoplasm, and the overlying submucosa contained small numbers of granulocytes. The overlying mucosal epithelium was markedly thickened, ~600–800-μm thick compared to the unaffected, ~150–200-μm thick mucosal epithelium elsewhere in the section. A small amount of proteinaceous feed material and free keratin were present in the esophageal lumen, along with a few bacterial cocci cross-arranged in tetrads. In addition, in the lumen of the distal esophagus, there were moderate numbers of budding, PAS-positive yeasts (presumed Candida).

Based on the histologic appearance of the neoplasm, the diagnosis of adenocarcinoma, suspected as arising from the esophageal mucous glands, was made. On follow-up sectioning of the esophageal-proventricular junction and additional proximal proventricular sections, the neoplasm was noted to extend in nests and tubules within the tunica muscularis of the proximal proventriculus. This expanded the differential list to include proventricular adenocarcinoma, a more common tumor in psittacines, which to our knowledge has not been reported effacing the esophageal-proventricular junction.^9,11 Histochemical stains of potential diagnostic utility in cases of proventricular adenocarcinoma include Alcian blue–periodic acid-Schiff (AB-PAS) and galactose oxidase–Schiff (GOS) staining. AB-PAS has been reported as variably highlighting neutral or acidic mucin granules in the proventricular epithelium. ³ In our case, AB-PAS highlighted neutral mucin granules in the proventricular epithelium, with no mucin granules in the neoplastic cells, supporting a non-proventricular origin for the neoplasm. Proventricular adenocarcinomas in 2 birds have been reported as positive on GOS staining, with GOS highlighting some cells that AB-PAS did not. ¹⁶ However, GOS is unavailable at our institution and was not performed.

There is a report of a distal esophageal SCC infiltrating the proventriculus in a macaw (Ara severus), but no reports of esophageal adenocarcinomas doing the same. ¹ Carcinomas arising from the esophageal submucosal glands, which are rarely described in the literature, may feature large amounts of hemorrhage and necrosis not seen in our case. ¹¹ Although we could not determine the definitive origin of this neoplasm, the most likely origins are the proventricular glands or the esophageal mucous glands. We favor the esophageal submucosal glands as the likely origin, given the nearly transmural invasion of the esophagus by neoplastic cells, compared to the less-extensive neoplastic invasion of the wall of the proventriculus. Additionally, the lack of mucin staining on AB-PAS supports this conclusion. Adenocarcinoma of the esophageal-proventricular junction has not been reported arising from either the proventricular glands or the esophageal mucous glands.

In our case, a possible differential diagnosis for the esophageal mass is an air sac carcinoma, although this is considered unlikely due to the gross lack of a mass effect in the cervical or intraclavicular air sacs and no clear extension of the neoplasm beyond the esophagus and proventriculus or extension to the adventitia. Air sac carcinomas are rare, most common in mature captive psittacines, and it is often difficult to prove that the air sac is the tissue of origin.^7–9 Typically, these tumors are associated with bony invasion and radiographic osteolysis and osteoproliferation,^7,8 neither of which we saw in our case. The tumor in our case also did not have clear apical cilia, and was not visualized in the pulmonary parenchyma, 2 other useful indicators of air sac origin. ⁸

From a comparative point of view, neoplasms of the esophagus are rare in domestic animals except for papillomas in dogs (uncommonly reported) and cattle (commonly reported); in the latter, papillomas are associated with bovine papillomavirus 4 (BPV4). ¹⁵ Malignant neoplasms of the esophagus are rare, with the exception of SCC in cattle, associated with BPV4-induced papilloma and ingestion of bracken fern (Pteridium aquilinum) or possibly other carcinogenic plants. ¹⁵ SCC is also reported in the mid-thoracic esophagus of cats, in the terminal esophagus of horses with gastric SCC, and rarely in dogs. ¹⁵ Adenocarcinomas of the esophageal glands are reported rarely in dogs. ¹⁵ Other esophageal neoplasms are rare in domestic animals and include Spirocerca-associated fibrosarcomas and osteosarcomas, as well as non-parasite–asso-ciated leiomyomas, osteosarcomas, and plasmacytomas in dogs. ¹⁵ Mesenchymal neoplasms of the ruminant esophagus and forestomachs are also rare. ¹⁵

In humans, esophageal cancers are divided into SCCs, which comprise 80% of human cases and are declining in incidence, and esophageal adenocarcinoma, a subtype that is increasing in incidence in many countries. ¹² Esophageal adenocarcinoma in humans typically occurs distally and is associated with columnar and mucous cell metaplasia (intestinal metaplasia) of the terminal esophagus, a reaction pattern that occurs in human patients with chronic gastroesophageal reflux, termed Barrett esophagus (BE). ¹⁵ Similar chronic, spontaneous reflux with BE-like lesions have been reported in baboons; however, esophageal adenocarcinoma development has not been reported in this or any other veterinary species in association with intestinal metaplasia of the distal esophagus.^4,15 Intestinal metaplasia was not seen in our case.

An important additional differential for a psittacine with this clinical presentation is proventricular dilation disease (PDD), a chronic and often fatal disease that can cause neurologic signs and reduced gastrointestinal motility. ¹⁰ PDD is caused by a group of pathogenic avian bornaviruses, of which parrot bornavirus 4 (Bornaviridae, Orthobornavirus alphapsittaciforme) is the most commonly detected variant. ¹⁰ Other differentials for this clinical presentation include bacterial enteritis, mycobacteriosis, fungal infections (e.g., Macrorhabdus ornithogaster), parasitic diseases such as cryptosporidiosis, and foreign body or impaction. ⁵

In our case, however, the esophageal-proventricular mass effect was considered the reason for the patient’s clinical presentation and aspiration. Therefore, although neoplasia is uncommon-to-rare in the esophagus of psittacines, it should be considered a potential cause of aspiration or regurgitation.