- Email: [email protected]
Use of Standing Computed Tomography for the Diagnosis of a Primary Respiratory Adenocarcinoma in a Scarlet Macaw (Ara macao)
CASE REPORT USE OF STANDING COMPUTED TOMOGRAPHY FOR THE DIAGNOSIS OF A PRIMARY RESPIRATORY ADENOCARCINOMA IN A SCARLET MACAW (ARA MACAO) Matt Marinkovich, DVM, Katherine Quesenberry, DVM, MPH, Dip. ABVP (Avian), Taryn A. Donovan, DVM, Dip. ACVP, and Alexandre B. Le Roux, DVM, MS, Dip. ECVDI, Dip. ACVR
Abstract An adult female scarlet macaw (Ara macao) was referred for evaluation of increased respiratory noise. Previous treatment with antibiotic agents by the referring veterinarian did not improve clinical signs. Upon presentation, when manually restrained, the patient became severely tachypneic with increased respiratory effort. Standing whole-body radiographic images revealed a soft tissue mass at the cranial aspect of the cardiac silhouette, but the origin of the mass could not be ascertained because of superimposed structures. Owing to the birdʼs significant respiratory compromise and concern for risks of general anesthesia, a standing computed tomography (CT) scan was performed without sedation to further assess the origin of the suspected mass. The CT images showed the presence of a large infiltrative intracoelomic soft tissue mass with adjacent keel osteolysis. After attempts at supportive care with nebulization, antibiotic therapy, and antifungal agents, the patientʼs condition declined and was subsequently euthanized. The results of the postmortem examination confirmed a large intracoelomic neoplasm with involvement of the keel, lungs, and adjacent air sacs. The mass was diagnosed as a primary respiratory adenocarcinoma, believed to have originated from the intraosseous air sac epithelium, with local pulmonary, air sac, and intracoelomic metastasis. Copyright 2017 Elsevier Inc. All rights reserved. Key words: Adenocarcinoma; Air sac; Ara macao; Computed tomography; Neoplasia; Scarlet macaw
A
30-year-old female scarlet macaw (Ara macao) was referred to The Animal Medical Center for evaluation of a 2-week history of increased, “moist” respiratory noise. There had been no changes in respiratory pattern observed at home. One other bird, a cockatoo (Cacatua sp.), was also in the same house as the macaw. The macaw had been acquired as a chick by the present owner with no previous history of a significant medical problem during the approximate 30-year period of ownership. The birdʼs diet consisted of commercial pellets, vegetables, fruits, and some table foods.
The referring veterinarian had performed blood tests including a complete blood count (CBC) and plasma biochemical analysis 3 days before presentation. Results of the CBC were within
reference intervals. Results of the plasma biochemical analysis indicated that the patient was suffering from hypoproteinemia (total protein ¼ 2.6 g/dL, reference interval: 3.4 to 4.2 g/dL) and
From the The Animal Medical Center, New York, NY USA. Address correspondence to: Matt Marinkovich, DVM, The Animal Medical Center, 510 E. 62nd St., New York, NY 10065. Email: [email protected]. Ó 2017 Elsevier Inc. All rights reserved. 1557-5063/17/2101-$30.00 http://dx.doi.org/10.1053/j.jepm.2017.01.028
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hypoalbuminemia (albumin ¼ 1.1 g/dL, reference interval: 1.3 to 1.7 g/dL) with a normal globulin concentration, hyperkalemia (5.4 mEq/L; reference interval: 2.9 to 3.9 mEg/L), and a mild increase in the uric acid concentration (10.1 mg/dL; reference interval: 1 to 6 mg/dL).1 The referring veterinarian then placed the patient on a twice-daily course of enrofloxacin (unknown dose); no improvement had been appreciated during the 2-week treatment period. On presentation, the bird was bright, alert, weighed 1036 g, and was in good body condition (BCS 3/5). Although minimally restrained for physical examination, the macaw became extremely dyspneic, with harsh respiratory sounds heard diffusely on pulmonary auscultation. Cardiac auscultation was difficult because of the increased respiratory noise. The midkeel was widened with a rounded margin. The remainder of the physical examination was unremarkable. Standing dorsoventral and lateral whole-body radiographs revealed an increased soft tissue lesion in the cranial coelomic cavity, dorsal to the keel, effacing the cardiac silhouette margins (Figs. 1 and 2). However, it was difficult to determine the origin of this suspected mass because of positioning and superimposition with the adjacent
FIGURE 1. Standing dorsoventral whole-body radiograph of a scarlet macaw exhibiting severe dyspnea. A large lobulated soft tissue mass obscures the normal margination of the cardiohepatic silhouette in the cranial coelomic cavity (white arrowheads).
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FIGURE 2. Standing lateral whole-body radiograph of the macaw described in Figure 1. The wings are superimposed over the keel on the lateral view; however, an increased soft tissue opacity is noted in the cranial coelomic cavity (white arrowheads). The caudal aspect of the coelomic cavity is also distended (white arrow).
anatomic structures within the birdʼs body. Decreased coelomic detail was also noted, caused by either coelomic effusion, organomegaly, a coelomic mass, or lack of coelomic fat. Owing to the patientʼs respiratory status, properly positioned orthogonal whole-body radiographs or computed tomography (CT) examination under general anesthesia could not be safely performed. Rather, a standing whole-body CT was performed by placing the bird in a plexiglass induction box with flow-by oxygen supplementation. However, because the macaw was not anesthetized, intravenous (IV) contrast could not be administered. Pending radiologistʼs review of the standing CT scan and further diagnostic imaging, the patient was treated initially with terbutaline (0.01 mg/kg intramuscular), enrofloxacin (20 mg/kg subcutaneous, Baytril; Bayer Heathcare LLC, Fort Dodge, KS USA), 1 dose of furosemide (0.25 mg/ kg intramuscular), and nebulized with cefotaxime (100 mg in 10 mL sterile saline for 15 minute). The bird was discharged on continued treatment with enrofloxacin, amoxicillin-clavulanic acid (125 mg/kg orally, every 12 hours), cefotaxime nebulization, itraconazole (10 mg/kg orally, every 24 hours), and terbutaline (0.02 mg/kg orally, every 8 to 12 hours) for empirical treatment of pneumonia and air sacculitis. Four days later, the patient was presented for re-examination. The owner reported little change in clinical signs since discharge from the hospital, and the bird had coughed occasionally after the owner administered the oral medications. As before, the macaw became dyspneic during light manual restraint. Physical examination findings were similar to those identified when the patient
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was first presented (harsh respiratory noise, rounded keel, and tachycardia). To determine if a component of heart disease and coelomic fluid were present in addition to the suspected mass, a coelomic ultrasound examination was performed. The bird was administered terbutaline (0.01 mg/kg intramuscular), and sedated with midazolam (1.5 mg/kg intramuscular), and then restrained manually, with oxygen flow-by used throughout the procedure. The ultrasound examination of the macaw revealed hepatomegaly and coelomic effusion. A sample of the coelomic fluid was aspirated for cytologic evaluation. The heart was subjectively normal, but examination was limited because of the patientʼs respiratory compromise. A blood sample was collected for an Aspergillus panel, plasma protein electrophoresis, CBC, and plasma biochemical analysis. Based on the results of the ultrasound examination, and because a component of cardiac disease could not be completely ruled out due to the presence of coelomic effusion, hepatic enlargement, and history of coughing, furosemide (0.5 mg/kg intramuscular) was administered and pimobendan (0.25 mg/kg orally, every 12 hours) was added to the previously established treatment protocol before discharging the patient and pending test results. An evaluation of the standing CT images confirmed an ill-defined bony lysis of the keel
FIGURE 3. Transverse CT image of a lung window at the level of the cranial coelomic cavity of the macaw described in Figure 1, showing a large faintly mineralized soft tissue mass (black arrowheads) with adjacent keel osteolysis and irregular new bone formation (large single black arrow). This mass is extending dorsally and infiltrates the left cranial thoracic air sac as well as left lung, with complete effacement of the left lung normal architecture compared to the right (thin single black arrow).
FIGURE 4. Maximum intensity projection in a sagittal plan in a CT soft tissue window of the macaw described in Figure 1, showing a soft tissue mass in the cranial coelomic cavity (white arrowheads) with adjacent keel osteolysis and new bone formation (black asterisk). This mass is displacing the heart (H), the liver (L), and the ventriculus (V) dorsally and caudally. A mild amount of coelomic effusion is noted between the coelomic organs (white #). The head of the bird is to the left and dorsal region is at the top of the image.
bone associated with irregular dorsal new bone formation and foci of mineralization extending into the adjacent soft tissue structures (Figs. 3 and 4). An ill-defined soft tissue mass was visible dorsal to this lytic lesion, caudally and somewhat dorsally displacing the cardiac silhouette and liver (Fig. 4). This mass extended dorsally, displacing the caudal trachea to the right and compressing the left mainstem bronchus, and was infiltrating the cranial aspect of the left lung and left cranial thoracic and left clavicular air sacs, with complete effacement of the normal pulmonary parenchymal architecture (Fig. 3). Several peripheral soft tissue attenuations, relatively well-defined, were observed in the rest of the lungs (Fig. 5). Mild coelomic effusion was noted (Fig. 4). Based on the CT findings, a malignant metastasized neoplasm, either a primary bone tumor originating from the keel or a soft tissue neoplasm of the left cranial lung, cranial coelomic soft tissue, or left clavicular air sac with secondary bony infiltration, was considered the top differential disease diagnosis. The pulmonary lesions were considered most likely to represent metastatic neoplasia because of their distribution. However, pulmonary thromboemboli or multifocal pneumonia could not be completely ruled out. Despite the left mainstem bronchial compression, atelectasis was deemed unlikely considering the multifocal distribution of the pulmonary lesions and lack of associated decreased pulmonary volume. Finally, a pyogranulomatous disease, such as aspergillosis, was considered much less likely but was still considered a possible cause of the macawʼs condition.
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FIGURE 5. Dorsal CT image in a lung window at the level of the cranial coelomic cavity. The large single black arrow is pointing at the infiltration of the left cranial lung lobe by the large soft tissue cranial coelomic mass, previously showed in Figure 4. The 2 thin black arrows are pointing at soft tissue attenuating pulmonary lesions, which were not directly related to the large cranial coelomic mass and were considered to represent pulmonary metastasis.
Abnormal results of the biochemical analysis were increased activities of aspartate aminotransferase (249 U/L; reference interval: 90 to 180 U/L), creatine kinase (1035 U/L; reference interval: 180 to 500 U/L), and amylase (918 U/L; reference interval: 239 to 564 U/L). An inflammatory leukogram with a leukocytosis (33.7 103 cells/μL, reference interval: 7 to 22 103 cells/μL), absolute heterophilia (28.0 103 cells/μL; reference interval: 2.8 to 13.2 103 cells/μL), and band heterophilia (2.0 103 cells/μL, reference interval: 0 to 0 103 cells/ μL) were reported.1 Avian aspergillus antibody testing yielded a weak positive result with a negative galactomannan result. Plasma protein electrophoresis findings were unremarkable. Results of cytologic examination of the coelomic effusion obtained by ultrasound-guided abdominocentesis indicated that the fluid was a modified transudate with histiocytic inflammation. The bird was presented 9 days after the second discharge from the hospital (13 days after first presentation) with progressive coughing, dyspnea, and weight loss. Since there was a high suspicion of a malignant, metastasized, and infiltrating tumor through CT imaging and the poor response 1 0 4
to the prescribed treatment protocol, euthanasia was elected. A comprehensive postmortem examination was performed on the macaw. Gross examination confirmed the presence of a large (6.6 3.7 4 cm3), firm to friable, multilobulated, focal neoplasm adhered to the inner portion of the keel, extending into the surrounding pectoral muscles with infiltration into the keel bone, and severe intralesional hemorrhage and necrosis (Figs. 6 and 7). Some sections of the tumor contained red to black, gelatinous material. Sectioning of the keel bone revealed that the neoplasm was present on the internal and external surfaces of the bone (Fig. 7). Two pedunculated nodules extended from the primary mass, with one 2.5 1.5 1.5 cm3 nodule free-floating in the coelom. The lungs were multifocally discolored tan to dark red with a wet consistency (left more severe than the right) and had tan material adhered to the pleura when sectioned. These findings were presumed to represent a combination of pneumonia and neoplastic infiltration. Moderate amounts (20 mL) of light yellow, serous coelomic effusion was present. Additional findings included moderate hepatomegaly and mild splenomegaly. Histologic examination of the intracoelomic mass revealed an epithelial neoplasm. In the sections from the left lung, neoplastic populations were observed adjacent to the left mainstem bronchus and formed tubuloacinar structures and occasionally larger cysts among variable amounts of fibrovascular stroma. The cells exhibited
FIGURE 6. Postmortem image of the adult macaw described in Figure 1 with a cranial intracoelmic soft tissue mass. The ribs have been cut and keel bone reflected cranially to demonstrate the mass involving the keel (vertical arrow) as well as the left lung, regional pleura, and air sac (horizontal arrow).
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moderate pleomorphism, were round to cuboidal or columnar, with moderate amounts of amphophilic cytoplasm and round to oval basilar or central nuclei. Nuclei exhibited moderate pleomorphism, contained vesicular chromatin, and typically a single nucleolus. The mitotic count was 14 per 10 high-power fields, with occasional severe anisocytosis and anisokaryosis. Scattered regions of hemorrhage and necrosis were observed. Some of the neoplastic cells appeared ciliated. Neoplastic cells were present within airways, but no definitive intravascular invasion could be confirmed. In the lungs and air sacs, neoplastic cells were often embedded within a fibrous stroma (desmoplasia) and exhibited loss of polarity (Fig 8 inset). Decalcified sections of the keel bone showed extensive infiltration by the neoplastic populations, frequently with columnar morphology, forming tubules, acini, and larger cysts with a pattern of lining bony trabeculae (Fig. 8). Cysts contained eosinophilic proteinaceous material and cell debris. The neoplastic populations most commonly formed single layers, but occasionally were stacked upon one another. There was multifocal effacement of the trabecular bone and bone remodeling. These findings indicated adenocarcinoma, suspected to have arisen from the air sac epithelium, possibly from the pneumatized portion of the keel. The neoplasm underwent pulmonary metastasis more prominently in the left lung and infiltration into surrounding structures including the syrinx, keel, and pectoral muscles. Granulomatous, heterophilic pneumonia with intralesional fungal hyphae (presumed Aspergillus sp.) was also observed. Inflammation was appreciated in many
FIGURE 7. The keel bone of the adult macaw described in Figure 1. Upper image. Ventral view of the keel bone with multilobular, infiltrative mass (vertical arrow). Lower image. Sectioned keel bone after formalin fixation. There is severe neoplastic infiltration on the internal and external aspects of the keel bone (horizontal arrow). Bar ¼ 1 cm.
FIGURE 8. Decalcifed section of sternum from the macaw described in Figure 1. Neoplastic cells diffusely infiltrate the sternum, forming tubuloacinar structures composed of tall columnar epithelial cells, which line bony trabeculae (large arrow). H&E stain. Bar ¼ 50 um Inset: section of infiltrated lung. Neoplastic cells form acinar structures exhibit pleomorphism and loss of nuclear polarity, consistent with adenocarcinoma. The cells are embedded within a fibrous stroma (desmoplasia). A mitotic figure is shown (thin arrow). H&E stain. Bar ¼ 20 um.
intracoelomic structures including the surrounding air sacs, liver, spleen, heart, adrenal glands, and kidneys. The necropsy findings in this macaw were consistent with primary respiratory adenocarcinoma, presumed to have originated from the intraosseous air sac epithelium, with local pulmonary, air sac, and intracoelomic metastasis. DISCUSSION Primary respiratory neoplasia is a reported but uncommon finding in birds compared with other companion species.2 Retrospective data from a specialty diagnostic laboratory showed that 5% (20/428) of all avian tumor submissions were of respiratory origin. Of note, all tumors in this category were identified as malignant.3 Neoplasms more prevalent in macaws from this study included cloacal papillomas, biliary adenocarcinomas, and cloacal adenomatous polyps.3 Examples of reported respiratory neoplasia in macaws include a nasal adenocarcinoma, bronchogenic adenocarcinoma, and a pulmonary adenocarcinoma.4-6 The significance of this case is based not only on its atypical diagnosis of primary respiratory adenocarcinoma, presumed to have originated from the intraosseous air sac epithelium, but also in the diagnostic methodology of a standing CT taken to achieve a diagnosis. CT has been increasingly used as a diagnostic tool in dogs and cats, as well as in avian
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companion animals. This modality allows 3-dimensional visualization of intrathoracic and intra-abdominal structures as opposed to 2-dimensional standard radiographic techniques. Specifically in avian species, CT scans have shown to be valuable in diagnosing small pulmonary lesions and defining margins of larger masses.7 However, a persistent drawback to performing a CT scan has been the necessity for general anesthesia. The need for general anesthesia is based on concerns that motion artifact caused by patient movement as well as inappropriate positioning will make image interpretation difficult. In some cases, such as the one described in this report, general anesthesia is not possible because of the patientʼs health status. Specifically, in patients with concurrent respiratory compromise, general anesthesia potentially could be fatal. A recent study by Kusmierczyk et al.8 investigated the potential use of sedated CT examinations in avian patients without IV contrast media administration. Their findings showed no meaningful difference in image quality between birds placed under general anesthesia and those chemically sedated and placed in a restraint device. Similar results from scans in patients not under general anesthesia or any sedation, but positioned within a restraining device, have been reported in cats and swans.9,10 Owing to the significant respiratory compromise in the macaw described in this report, neither general anesthesia nor manual restraint was a justifiable risk. Instead, a standing CT scan without sedation or a restraint device was performed. In this case, allowing the bird to stand in a plexiglass box with oxygen flow-by allowed sufficient immobilization for quality image collection without inducing respiratory compromise. Light sedation with either intranasal or intramuscular midazolam could have been used if the bird had not remained sufficiently immobile for the CT examination. However, this case illustrates that some birds can be successfully imaged by CT without sedation, either by placing the patient in a plexiglass box or by providing a perch on which to stand. The authors have used this technique with good results for clinical cases involving psittacine birds that were considered to be a high anesthetic risk. The disadvantage of the standing CT is that contrast media cannot be given intravenously for comparative evaluation. CT examinations without contrast media administration are most helpful to assess bony or pulmonary structures, as images acquired without IV contrast media administration lack soft tissue 1 0 6
contrast resolution, which is helpful in evaluating soft tissue changes (e.g., inflammation, neoplastic infiltration, necrosis, and hemorrhage) and the cardiovascular system. However, despite this limitation, a standing CT scan without contrast resulted in a diagnosis with relatively minor compromise or risk to the patient in this case. Evaluation of the CT images by a veterinary radiologist led to the diagnosis of a large, intracoelomic soft tissue mass with surrounding bony infiltration. These findings were later confirmed at necropsy. However, the CT machine used in this case was a helical multislice CT scanner (64-slice CT), allowing an increased generation of images per second compared with a conventional CT scanner, and as a result, a much shorter time of acquisition (less than 5 seconds for the entire body of the bird), therefore limiting motion artifact induced by patient movement and enabling higher resolution of the images. This type of standing CT imaging examination may therefore not be suitable with older and slower CT units. The unique respiratory anatomy of avian species presents an additional complicating factor in tumor growth and attempts at treatment. In this case, this neoplasm was confirmed to have originated from the epithelium of the respiratory tract, but because of cell morphology and concurrent air sac and pulmonary involvement, definitive confirmation of the site of origin could not be achieved. Given the predominant involvement of the sterum and histologic pattern of lining bone trabeculae, this adenocarcinoma was presumed to be of intraosseous air sac origin. The sternum is pneumatized by respiratory epithelium that lines bony trabeculae, continuous with the interclavicular, thoracic, and abdominal air sacs.11 The histomorphologic features of this neoplasm were similar to those in a recent report of an air sac adenocarcinoma of the sternum in a Quaker parrot (Myiopsitta monachus).11 The present case report describes the unique presentation of a presumptive air sac adenocarcinoma in a macaw, likely arising from the pneumatized portion of the sternum, extensively infiltrating the sternum and undergoing metastasis to the lungs, nonosseous air sacs, and coelomic cavity. Air sac neoplasms including a humeral mucinous adenocarcinoma, humeral cystadenocarcinoma, axillary cystadenocarcinoma, and primary adenocarcinoma (with sternal invasion) have been reported in other psittacine species.11-15 Adenocarcinomas are the most common type of lung tumor diagnosed in small animal patients, but can also involve the larynx, nasal cavity, and
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trachea.16 Treatment modalities for these tumors range from surgical excision or debulking to chemotherapy and radiation therapy, depending on the location and size of the mass. Based on the size and extent of the neoplasm, surgical excision was not possible in the macaw described in this report, and in all likelihood chemotherapy and radiation therapy would have provided little to no treatment benefit. The intralesional and intrapulmonary fungal hyphae observed in this case are believed to have originated from a secondary, opportunistic invasion by Aspergillus sp. In birds with respiratory signs that are minimally or nonresponsive to appropriate antibiotic and antifungal treatment, respiratory neoplasia should be considered and appropriate diagnostic modalities pursued. Based on this case report, the use of a standing CT scan in birds appears to be a safe alternative to standard radiography or CT imaging under general anesthesia to localize and determine the full extent of a disease without risking the patientʼs life. ACKNOWLEDGMENTS We thank Dr. Linda Lowenstine for her thoughful review of gross and histopathology images from this case report. REFERENCES 1. Carpenter JE (ed): Hematologic and serum biochemical values of selected psittacines, in Carpenter JE (ed): Exotic Animal Formulary. (ed 4). St. Louis, MO, Elsevier, pp 338-341, 2013 2. Lightfoot TL: Overview of tumors: section 1. Clinical avian neoplasia and oncology, in Harrison GJ, Lightfoot TL (eds): Clinical Avian Medicine, Vol II. Palm Beach, FL, Spix Publishing, pp 560-565, 2006 3. Garner MM: Overview of tumors: section 2. Clinical avian neoplasia and oncology, in Harrison GJ, Lightfoot TL
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(eds): Clinical Avian Medicine, Vol II. Palm Beach, FL, Spix Publishing, pp 566-571, 2006 Noonan BP, de Matos R, Butler BP, et al: Nasal adenocarcinoma and secondary chronic sinusitis in a hyacinth macaw (Anodorhynchus hyacinthinus). J Avian Med Surg 28 (2):143-150, 2014 Baumgartner WA, Guzman DSM, Hollibush S, et al: Bronchogenic adenocarcinoma in a hyacinth macaw (Anodorhynchus hyacinthinus). J Avian Med Surg 22(3): 218-225, 2008 Fredholm DV, Carpenter JW, Schumacher LL, et al: Pulmonary adenocarcinoma with osseous metastasis and secondary paresis in a blue and gold macaw (Ara ararauna). J Zoo Wildl Med 43(4):909-913, 2012 Newell SM, Roberts GD, Bennett RA: Imaging techniques for avian lower respiratory diseases. Semin Avian Exot Pet Med 34:382-390, 1999 Kusmierczyk J, Wall CR, Hoppes S, et al: Comparison of computed tomographic images of birds obtained with sedation vs general anesthesia. J Exotic Pet Med 22: 251-257, 2013 Oliviera CR, Mitchell MA, OʼBrien RT: Thoracic computed tomography in feline patients without use of chemical restraint. Vet Radiol Ultrasound 52(4):368-376, 2011 Gumpenberger M, Scope A: Computed tomography of coxofemoral injury in five mute swans (Cygnus olor). Avian Pathol 41(5):465-468, 2012 Loukopoulos P, Okuni JB, Micco T, et al: Air sac adenocarcinoma of the sternum in a Quaker parrot (Myiopsitta monachus). J Zoo Wildl Med 45(4):961-965, 2014 Marshall K, Daniel G, Patton C, et al: Humeral air sac mucinous adenocarcinoma in a salmon-crested cockatoo (Cacatua moluccensis). J Avian Med Surg 18(3):167-174, 2004 Azmanis P, Stenkat J, Hubel J, et al: A complicated, metastatic, humeral air sac cystadenocarcinoma in a timneh African grey parrot (Psittacus erithacus timneh). J Avian Med Surg 27(1):38-43, 2013 Raidal SR, Shearer PL, Butler R, et al: Airsac cystadenocarcinomas in cockatoos. Aust Vet J 84(6):213-216, 2006 Powers LV, Merrill CL, Degernes LA, et al: Axillary cystadenocarcinoma in a moluccan cockatoo (Cacatua moluccensis). Avian Dis 42(2):408-412, 1998 Miles KG: A review of primary lung tumors in the dog and cat. Vet Radiol Ultrasound 29(3):122-128, 1988
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Abstract An adult female scarlet macaw (Ara macao) was referred for evaluation of increased respiratory noise. Previous treatment with antibiotic agents by the referring veterinarian did not improve clinical signs. Upon presentation, when manually restrained, the patient became severely tachypneic with increased respiratory effort. Standing whole-body radiographic images revealed a soft tissue mass at the cranial aspect of the cardiac silhouette, but the origin of the mass could not be ascertained because of superimposed structures. Owing to the birdʼs significant respiratory compromise and concern for risks of general anesthesia, a standing computed tomography (CT) scan was performed without sedation to further assess the origin of the suspected mass. The CT images showed the presence of a large infiltrative intracoelomic soft tissue mass with adjacent keel osteolysis. After attempts at supportive care with nebulization, antibiotic therapy, and antifungal agents, the patientʼs condition declined and was subsequently euthanized. The results of the postmortem examination confirmed a large intracoelomic neoplasm with involvement of the keel, lungs, and adjacent air sacs. The mass was diagnosed as a primary respiratory adenocarcinoma, believed to have originated from the intraosseous air sac epithelium, with local pulmonary, air sac, and intracoelomic metastasis. Copyright 2017 Elsevier Inc. All rights reserved. Key words: Adenocarcinoma; Air sac; Ara macao; Computed tomography; Neoplasia; Scarlet macaw
A
30-year-old female scarlet macaw (Ara macao) was referred to The Animal Medical Center for evaluation of a 2-week history of increased, “moist” respiratory noise. There had been no changes in respiratory pattern observed at home. One other bird, a cockatoo (Cacatua sp.), was also in the same house as the macaw. The macaw had been acquired as a chick by the present owner with no previous history of a significant medical problem during the approximate 30-year period of ownership. The birdʼs diet consisted of commercial pellets, vegetables, fruits, and some table foods.
The referring veterinarian had performed blood tests including a complete blood count (CBC) and plasma biochemical analysis 3 days before presentation. Results of the CBC were within
reference intervals. Results of the plasma biochemical analysis indicated that the patient was suffering from hypoproteinemia (total protein ¼ 2.6 g/dL, reference interval: 3.4 to 4.2 g/dL) and
From the The Animal Medical Center, New York, NY USA. Address correspondence to: Matt Marinkovich, DVM, The Animal Medical Center, 510 E. 62nd St., New York, NY 10065. Email: [email protected]. Ó 2017 Elsevier Inc. All rights reserved. 1557-5063/17/2101-$30.00 http://dx.doi.org/10.1053/j.jepm.2017.01.028
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hypoalbuminemia (albumin ¼ 1.1 g/dL, reference interval: 1.3 to 1.7 g/dL) with a normal globulin concentration, hyperkalemia (5.4 mEq/L; reference interval: 2.9 to 3.9 mEg/L), and a mild increase in the uric acid concentration (10.1 mg/dL; reference interval: 1 to 6 mg/dL).1 The referring veterinarian then placed the patient on a twice-daily course of enrofloxacin (unknown dose); no improvement had been appreciated during the 2-week treatment period. On presentation, the bird was bright, alert, weighed 1036 g, and was in good body condition (BCS 3/5). Although minimally restrained for physical examination, the macaw became extremely dyspneic, with harsh respiratory sounds heard diffusely on pulmonary auscultation. Cardiac auscultation was difficult because of the increased respiratory noise. The midkeel was widened with a rounded margin. The remainder of the physical examination was unremarkable. Standing dorsoventral and lateral whole-body radiographs revealed an increased soft tissue lesion in the cranial coelomic cavity, dorsal to the keel, effacing the cardiac silhouette margins (Figs. 1 and 2). However, it was difficult to determine the origin of this suspected mass because of positioning and superimposition with the adjacent
FIGURE 1. Standing dorsoventral whole-body radiograph of a scarlet macaw exhibiting severe dyspnea. A large lobulated soft tissue mass obscures the normal margination of the cardiohepatic silhouette in the cranial coelomic cavity (white arrowheads).
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FIGURE 2. Standing lateral whole-body radiograph of the macaw described in Figure 1. The wings are superimposed over the keel on the lateral view; however, an increased soft tissue opacity is noted in the cranial coelomic cavity (white arrowheads). The caudal aspect of the coelomic cavity is also distended (white arrow).
anatomic structures within the birdʼs body. Decreased coelomic detail was also noted, caused by either coelomic effusion, organomegaly, a coelomic mass, or lack of coelomic fat. Owing to the patientʼs respiratory status, properly positioned orthogonal whole-body radiographs or computed tomography (CT) examination under general anesthesia could not be safely performed. Rather, a standing whole-body CT was performed by placing the bird in a plexiglass induction box with flow-by oxygen supplementation. However, because the macaw was not anesthetized, intravenous (IV) contrast could not be administered. Pending radiologistʼs review of the standing CT scan and further diagnostic imaging, the patient was treated initially with terbutaline (0.01 mg/kg intramuscular), enrofloxacin (20 mg/kg subcutaneous, Baytril; Bayer Heathcare LLC, Fort Dodge, KS USA), 1 dose of furosemide (0.25 mg/ kg intramuscular), and nebulized with cefotaxime (100 mg in 10 mL sterile saline for 15 minute). The bird was discharged on continued treatment with enrofloxacin, amoxicillin-clavulanic acid (125 mg/kg orally, every 12 hours), cefotaxime nebulization, itraconazole (10 mg/kg orally, every 24 hours), and terbutaline (0.02 mg/kg orally, every 8 to 12 hours) for empirical treatment of pneumonia and air sacculitis. Four days later, the patient was presented for re-examination. The owner reported little change in clinical signs since discharge from the hospital, and the bird had coughed occasionally after the owner administered the oral medications. As before, the macaw became dyspneic during light manual restraint. Physical examination findings were similar to those identified when the patient
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was first presented (harsh respiratory noise, rounded keel, and tachycardia). To determine if a component of heart disease and coelomic fluid were present in addition to the suspected mass, a coelomic ultrasound examination was performed. The bird was administered terbutaline (0.01 mg/kg intramuscular), and sedated with midazolam (1.5 mg/kg intramuscular), and then restrained manually, with oxygen flow-by used throughout the procedure. The ultrasound examination of the macaw revealed hepatomegaly and coelomic effusion. A sample of the coelomic fluid was aspirated for cytologic evaluation. The heart was subjectively normal, but examination was limited because of the patientʼs respiratory compromise. A blood sample was collected for an Aspergillus panel, plasma protein electrophoresis, CBC, and plasma biochemical analysis. Based on the results of the ultrasound examination, and because a component of cardiac disease could not be completely ruled out due to the presence of coelomic effusion, hepatic enlargement, and history of coughing, furosemide (0.5 mg/kg intramuscular) was administered and pimobendan (0.25 mg/kg orally, every 12 hours) was added to the previously established treatment protocol before discharging the patient and pending test results. An evaluation of the standing CT images confirmed an ill-defined bony lysis of the keel
FIGURE 3. Transverse CT image of a lung window at the level of the cranial coelomic cavity of the macaw described in Figure 1, showing a large faintly mineralized soft tissue mass (black arrowheads) with adjacent keel osteolysis and irregular new bone formation (large single black arrow). This mass is extending dorsally and infiltrates the left cranial thoracic air sac as well as left lung, with complete effacement of the left lung normal architecture compared to the right (thin single black arrow).
FIGURE 4. Maximum intensity projection in a sagittal plan in a CT soft tissue window of the macaw described in Figure 1, showing a soft tissue mass in the cranial coelomic cavity (white arrowheads) with adjacent keel osteolysis and new bone formation (black asterisk). This mass is displacing the heart (H), the liver (L), and the ventriculus (V) dorsally and caudally. A mild amount of coelomic effusion is noted between the coelomic organs (white #). The head of the bird is to the left and dorsal region is at the top of the image.
bone associated with irregular dorsal new bone formation and foci of mineralization extending into the adjacent soft tissue structures (Figs. 3 and 4). An ill-defined soft tissue mass was visible dorsal to this lytic lesion, caudally and somewhat dorsally displacing the cardiac silhouette and liver (Fig. 4). This mass extended dorsally, displacing the caudal trachea to the right and compressing the left mainstem bronchus, and was infiltrating the cranial aspect of the left lung and left cranial thoracic and left clavicular air sacs, with complete effacement of the normal pulmonary parenchymal architecture (Fig. 3). Several peripheral soft tissue attenuations, relatively well-defined, were observed in the rest of the lungs (Fig. 5). Mild coelomic effusion was noted (Fig. 4). Based on the CT findings, a malignant metastasized neoplasm, either a primary bone tumor originating from the keel or a soft tissue neoplasm of the left cranial lung, cranial coelomic soft tissue, or left clavicular air sac with secondary bony infiltration, was considered the top differential disease diagnosis. The pulmonary lesions were considered most likely to represent metastatic neoplasia because of their distribution. However, pulmonary thromboemboli or multifocal pneumonia could not be completely ruled out. Despite the left mainstem bronchial compression, atelectasis was deemed unlikely considering the multifocal distribution of the pulmonary lesions and lack of associated decreased pulmonary volume. Finally, a pyogranulomatous disease, such as aspergillosis, was considered much less likely but was still considered a possible cause of the macawʼs condition.
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FIGURE 5. Dorsal CT image in a lung window at the level of the cranial coelomic cavity. The large single black arrow is pointing at the infiltration of the left cranial lung lobe by the large soft tissue cranial coelomic mass, previously showed in Figure 4. The 2 thin black arrows are pointing at soft tissue attenuating pulmonary lesions, which were not directly related to the large cranial coelomic mass and were considered to represent pulmonary metastasis.
Abnormal results of the biochemical analysis were increased activities of aspartate aminotransferase (249 U/L; reference interval: 90 to 180 U/L), creatine kinase (1035 U/L; reference interval: 180 to 500 U/L), and amylase (918 U/L; reference interval: 239 to 564 U/L). An inflammatory leukogram with a leukocytosis (33.7 103 cells/μL, reference interval: 7 to 22 103 cells/μL), absolute heterophilia (28.0 103 cells/μL; reference interval: 2.8 to 13.2 103 cells/μL), and band heterophilia (2.0 103 cells/μL, reference interval: 0 to 0 103 cells/ μL) were reported.1 Avian aspergillus antibody testing yielded a weak positive result with a negative galactomannan result. Plasma protein electrophoresis findings were unremarkable. Results of cytologic examination of the coelomic effusion obtained by ultrasound-guided abdominocentesis indicated that the fluid was a modified transudate with histiocytic inflammation. The bird was presented 9 days after the second discharge from the hospital (13 days after first presentation) with progressive coughing, dyspnea, and weight loss. Since there was a high suspicion of a malignant, metastasized, and infiltrating tumor through CT imaging and the poor response 1 0 4
to the prescribed treatment protocol, euthanasia was elected. A comprehensive postmortem examination was performed on the macaw. Gross examination confirmed the presence of a large (6.6 3.7 4 cm3), firm to friable, multilobulated, focal neoplasm adhered to the inner portion of the keel, extending into the surrounding pectoral muscles with infiltration into the keel bone, and severe intralesional hemorrhage and necrosis (Figs. 6 and 7). Some sections of the tumor contained red to black, gelatinous material. Sectioning of the keel bone revealed that the neoplasm was present on the internal and external surfaces of the bone (Fig. 7). Two pedunculated nodules extended from the primary mass, with one 2.5 1.5 1.5 cm3 nodule free-floating in the coelom. The lungs were multifocally discolored tan to dark red with a wet consistency (left more severe than the right) and had tan material adhered to the pleura when sectioned. These findings were presumed to represent a combination of pneumonia and neoplastic infiltration. Moderate amounts (20 mL) of light yellow, serous coelomic effusion was present. Additional findings included moderate hepatomegaly and mild splenomegaly. Histologic examination of the intracoelomic mass revealed an epithelial neoplasm. In the sections from the left lung, neoplastic populations were observed adjacent to the left mainstem bronchus and formed tubuloacinar structures and occasionally larger cysts among variable amounts of fibrovascular stroma. The cells exhibited
FIGURE 6. Postmortem image of the adult macaw described in Figure 1 with a cranial intracoelmic soft tissue mass. The ribs have been cut and keel bone reflected cranially to demonstrate the mass involving the keel (vertical arrow) as well as the left lung, regional pleura, and air sac (horizontal arrow).
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moderate pleomorphism, were round to cuboidal or columnar, with moderate amounts of amphophilic cytoplasm and round to oval basilar or central nuclei. Nuclei exhibited moderate pleomorphism, contained vesicular chromatin, and typically a single nucleolus. The mitotic count was 14 per 10 high-power fields, with occasional severe anisocytosis and anisokaryosis. Scattered regions of hemorrhage and necrosis were observed. Some of the neoplastic cells appeared ciliated. Neoplastic cells were present within airways, but no definitive intravascular invasion could be confirmed. In the lungs and air sacs, neoplastic cells were often embedded within a fibrous stroma (desmoplasia) and exhibited loss of polarity (Fig 8 inset). Decalcified sections of the keel bone showed extensive infiltration by the neoplastic populations, frequently with columnar morphology, forming tubules, acini, and larger cysts with a pattern of lining bony trabeculae (Fig. 8). Cysts contained eosinophilic proteinaceous material and cell debris. The neoplastic populations most commonly formed single layers, but occasionally were stacked upon one another. There was multifocal effacement of the trabecular bone and bone remodeling. These findings indicated adenocarcinoma, suspected to have arisen from the air sac epithelium, possibly from the pneumatized portion of the keel. The neoplasm underwent pulmonary metastasis more prominently in the left lung and infiltration into surrounding structures including the syrinx, keel, and pectoral muscles. Granulomatous, heterophilic pneumonia with intralesional fungal hyphae (presumed Aspergillus sp.) was also observed. Inflammation was appreciated in many
FIGURE 7. The keel bone of the adult macaw described in Figure 1. Upper image. Ventral view of the keel bone with multilobular, infiltrative mass (vertical arrow). Lower image. Sectioned keel bone after formalin fixation. There is severe neoplastic infiltration on the internal and external aspects of the keel bone (horizontal arrow). Bar ¼ 1 cm.
FIGURE 8. Decalcifed section of sternum from the macaw described in Figure 1. Neoplastic cells diffusely infiltrate the sternum, forming tubuloacinar structures composed of tall columnar epithelial cells, which line bony trabeculae (large arrow). H&E stain. Bar ¼ 50 um Inset: section of infiltrated lung. Neoplastic cells form acinar structures exhibit pleomorphism and loss of nuclear polarity, consistent with adenocarcinoma. The cells are embedded within a fibrous stroma (desmoplasia). A mitotic figure is shown (thin arrow). H&E stain. Bar ¼ 20 um.
intracoelomic structures including the surrounding air sacs, liver, spleen, heart, adrenal glands, and kidneys. The necropsy findings in this macaw were consistent with primary respiratory adenocarcinoma, presumed to have originated from the intraosseous air sac epithelium, with local pulmonary, air sac, and intracoelomic metastasis. DISCUSSION Primary respiratory neoplasia is a reported but uncommon finding in birds compared with other companion species.2 Retrospective data from a specialty diagnostic laboratory showed that 5% (20/428) of all avian tumor submissions were of respiratory origin. Of note, all tumors in this category were identified as malignant.3 Neoplasms more prevalent in macaws from this study included cloacal papillomas, biliary adenocarcinomas, and cloacal adenomatous polyps.3 Examples of reported respiratory neoplasia in macaws include a nasal adenocarcinoma, bronchogenic adenocarcinoma, and a pulmonary adenocarcinoma.4-6 The significance of this case is based not only on its atypical diagnosis of primary respiratory adenocarcinoma, presumed to have originated from the intraosseous air sac epithelium, but also in the diagnostic methodology of a standing CT taken to achieve a diagnosis. CT has been increasingly used as a diagnostic tool in dogs and cats, as well as in avian
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companion animals. This modality allows 3-dimensional visualization of intrathoracic and intra-abdominal structures as opposed to 2-dimensional standard radiographic techniques. Specifically in avian species, CT scans have shown to be valuable in diagnosing small pulmonary lesions and defining margins of larger masses.7 However, a persistent drawback to performing a CT scan has been the necessity for general anesthesia. The need for general anesthesia is based on concerns that motion artifact caused by patient movement as well as inappropriate positioning will make image interpretation difficult. In some cases, such as the one described in this report, general anesthesia is not possible because of the patientʼs health status. Specifically, in patients with concurrent respiratory compromise, general anesthesia potentially could be fatal. A recent study by Kusmierczyk et al.8 investigated the potential use of sedated CT examinations in avian patients without IV contrast media administration. Their findings showed no meaningful difference in image quality between birds placed under general anesthesia and those chemically sedated and placed in a restraint device. Similar results from scans in patients not under general anesthesia or any sedation, but positioned within a restraining device, have been reported in cats and swans.9,10 Owing to the significant respiratory compromise in the macaw described in this report, neither general anesthesia nor manual restraint was a justifiable risk. Instead, a standing CT scan without sedation or a restraint device was performed. In this case, allowing the bird to stand in a plexiglass box with oxygen flow-by allowed sufficient immobilization for quality image collection without inducing respiratory compromise. Light sedation with either intranasal or intramuscular midazolam could have been used if the bird had not remained sufficiently immobile for the CT examination. However, this case illustrates that some birds can be successfully imaged by CT without sedation, either by placing the patient in a plexiglass box or by providing a perch on which to stand. The authors have used this technique with good results for clinical cases involving psittacine birds that were considered to be a high anesthetic risk. The disadvantage of the standing CT is that contrast media cannot be given intravenously for comparative evaluation. CT examinations without contrast media administration are most helpful to assess bony or pulmonary structures, as images acquired without IV contrast media administration lack soft tissue 1 0 6
contrast resolution, which is helpful in evaluating soft tissue changes (e.g., inflammation, neoplastic infiltration, necrosis, and hemorrhage) and the cardiovascular system. However, despite this limitation, a standing CT scan without contrast resulted in a diagnosis with relatively minor compromise or risk to the patient in this case. Evaluation of the CT images by a veterinary radiologist led to the diagnosis of a large, intracoelomic soft tissue mass with surrounding bony infiltration. These findings were later confirmed at necropsy. However, the CT machine used in this case was a helical multislice CT scanner (64-slice CT), allowing an increased generation of images per second compared with a conventional CT scanner, and as a result, a much shorter time of acquisition (less than 5 seconds for the entire body of the bird), therefore limiting motion artifact induced by patient movement and enabling higher resolution of the images. This type of standing CT imaging examination may therefore not be suitable with older and slower CT units. The unique respiratory anatomy of avian species presents an additional complicating factor in tumor growth and attempts at treatment. In this case, this neoplasm was confirmed to have originated from the epithelium of the respiratory tract, but because of cell morphology and concurrent air sac and pulmonary involvement, definitive confirmation of the site of origin could not be achieved. Given the predominant involvement of the sterum and histologic pattern of lining bone trabeculae, this adenocarcinoma was presumed to be of intraosseous air sac origin. The sternum is pneumatized by respiratory epithelium that lines bony trabeculae, continuous with the interclavicular, thoracic, and abdominal air sacs.11 The histomorphologic features of this neoplasm were similar to those in a recent report of an air sac adenocarcinoma of the sternum in a Quaker parrot (Myiopsitta monachus).11 The present case report describes the unique presentation of a presumptive air sac adenocarcinoma in a macaw, likely arising from the pneumatized portion of the sternum, extensively infiltrating the sternum and undergoing metastasis to the lungs, nonosseous air sacs, and coelomic cavity. Air sac neoplasms including a humeral mucinous adenocarcinoma, humeral cystadenocarcinoma, axillary cystadenocarcinoma, and primary adenocarcinoma (with sternal invasion) have been reported in other psittacine species.11-15 Adenocarcinomas are the most common type of lung tumor diagnosed in small animal patients, but can also involve the larynx, nasal cavity, and
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trachea.16 Treatment modalities for these tumors range from surgical excision or debulking to chemotherapy and radiation therapy, depending on the location and size of the mass. Based on the size and extent of the neoplasm, surgical excision was not possible in the macaw described in this report, and in all likelihood chemotherapy and radiation therapy would have provided little to no treatment benefit. The intralesional and intrapulmonary fungal hyphae observed in this case are believed to have originated from a secondary, opportunistic invasion by Aspergillus sp. In birds with respiratory signs that are minimally or nonresponsive to appropriate antibiotic and antifungal treatment, respiratory neoplasia should be considered and appropriate diagnostic modalities pursued. Based on this case report, the use of a standing CT scan in birds appears to be a safe alternative to standard radiography or CT imaging under general anesthesia to localize and determine the full extent of a disease without risking the patientʼs life. ACKNOWLEDGMENTS We thank Dr. Linda Lowenstine for her thoughful review of gross and histopathology images from this case report. REFERENCES 1. Carpenter JE (ed): Hematologic and serum biochemical values of selected psittacines, in Carpenter JE (ed): Exotic Animal Formulary. (ed 4). St. Louis, MO, Elsevier, pp 338-341, 2013 2. Lightfoot TL: Overview of tumors: section 1. Clinical avian neoplasia and oncology, in Harrison GJ, Lightfoot TL (eds): Clinical Avian Medicine, Vol II. Palm Beach, FL, Spix Publishing, pp 560-565, 2006 3. Garner MM: Overview of tumors: section 2. Clinical avian neoplasia and oncology, in Harrison GJ, Lightfoot TL
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