Bilateral Malignant Seminoma With Ventricular Metastasis in a Bald Eagle (Haliaeetus leucoceplialus).
Key words: seminoma, metastases, neoplasia, aviam, bald eagle, Haliaeetus leucocephalus
An approximately 30-year-old male bald eagle (Haliaeetus leucocephalus) was examined after a 2-week history of hyporexia, lethargy, and allowing its mate to steal its food. It also exhibited other abnormal behaviors, such as isolating itself and not seeking shelter during adverse weather conditions. The eagle had been in captivity for 26 years after right wing trauma that required amputation of the wing above the cubital joint. The bird had been at the current zoological facility since 1992 and had been housed with several different mates, with the most recent pairing in 2005. While at this facility, the eagle was housed in a natural substrate exhibit with native vegetation and cut branches and logs for perching as well as an indoor holding area that was left open as shelter during inclement weather. Shade was provided by surrounding trees. The diet was consistent while at this zoological facility, comprised mostly of a commercial bird-of-prey (Bird of Prey Diet; Nebraska Brand, N Platte, NE, USA). A rotating selection of rodents, various fish, quail, and rabbit also was offered.
On physical examination, the eagle demonstrated a body condition score of 3/9 and weighed 3.1 kg. Results of a blood sample obtained from the left basilic vein and submitted for complete blood count (CBC) and plasma biochemical analysis were largely within reference limits except for increased creatine kinase (CK; 1099 U/L; reference range, 156-927 U/L) and lactate dehydrogenase (1661 U/ L; reference range, 148-1640 U/L) levels. (1) No treatments were initiated at this time other than separating the 2 birds during feeding. Fecal examination demonstrated a moderate amount of Capillaria species oocytes. Fenbendazole (40 mg/ kg PO) was prescribed for both birds at two doses given 14 days apart. The bird also was started on ceftiofur (20 mg/kg IM).
A second examination 1 week later revealed several changes, including weight loss (weight, 2.8 kg) and a grade II/VI holosystolic murmur. Dyspnea and lethargy were observed for several minutes after handling. During this examination, repeat CBC and plasma biochemical analysis showed a decreased albumin concentration (0.5 g/ dL; reference range, 0.7-2.7 g/dL), further increased CK activity (1224 U/L), (1) and a subjectively elevated bile acid level (131 [micro]mol/L). Plasma protein electrophoresis (EPH) and an aspergillosis panel demonstrated decreased albumin (0.6 g/dL; reference range, 1.29-2.32 g/dL; University of Miami--Avian & Wildlife Laboratory--Division of Comparative Pathology, Miami, FL, USA), a decreased albumin/globulin ratio (0.43; reference range, 0.70-1.59; University of Miami--Avian & Wildlife Laboratory--Division of Comparative Pathology), a weakly positive aspergillus antibody titer (1.5; reference range, 0-1.39 = negative, 1.4-1.6 = weak positive, 1.7-1.9 = moderate positive, [greater than or equal to] 2 = strongly positive; University of Miami Avian & Wildlife Laboratory--Division of Comparative Pathology), and a negative Galactomannan antigen result (0.1; mean [+ or -] standard error [SE], 0.64 [+ or -] 0.18 = negative case, 1.12 [+ or -] 0.11 = suspect case, 1.68 [+ or -] 0.33 = confirmed case; University of Miami--Avian & Wildlife Laboratory --Division of Comparative Pathology).
Orthogonal radiographs revealed microhepatica and possible ventricular distension as well as a multilobular soft tissue opacity in the area of the gonads and kidneys (Fig 1). Three small, metal opacities were noted in the soft tissues, which were present on previous radiographs. Two days later, a transcoelomic echocardiogram and coelomic endoscopy were attempted. Diagnostic quality images could not be obtained during the echocardiogram.
After the echocardiogram, the eagle was sedated with butorphanol (1 mg/kg IM) and anesthesia was induced with isoflurane administered by mask until intubation for endoscopic examination. For endoscopic examination, a left lateral approach was made just caudal to the last rib. Marked opacity and thickening of the air sac was observed with apparent adhesions of the coelomic organs, making definitive identification of coelomic structures difficult. Subsequently, a keyhole approach caudal to the keel was performed to obtain a liver biopsy. Grossly, the liver had a green-to-maroon marbled appearance and was friable when a biopsy sample was obtained. Hemorrhage was controlled with direct pressure, and clotting was achieved within 3 minutes.
During recovery, the eagle remained minimally responsive, although respiratory rate and effort allowed extubation. The bird's condition did not improve despite supplemental heat, flow-by oxygen, and administration of dexamethasone (1 mg/ kg IO). Because of the poor prognosis for recovery, euthanasia was elected and the carcass was submitted for necropsy.
Necropsy revealed a body condition score of 3/9 with a prominent keel bone. The right and left testes were enlarged, approximately 3 X 2.5 X 1.5 cm, and soft with multifocal tan ridges compressing the tunica albuginea and associated abdominal air sacs. On cut sections, the testicular parenchyma moderately bulged and occasional irregular soft necrotic areas were present within the parenchyma (Fig 2A). The abdominal air sacs and mesentery were thickened, cloudy, and opaque with numerous fibrous adhesions to the liver, intestines, and testes. The ventriculus and proventriculus were firmly adherent to the air sacs with fibrous adhesions. Diffusely, the ventricular mucosa was moderately thickened, rough, and irregular with markedly reduced thickness of the koilin layer. Multifocally, within the mucosa and occasionally on the serosa and associated abdominal air sacs, multiple variably-sized granulomas were present, ranging from pinpoint to 3 X 2 mm, with dark brown, necrotic centers. The liver was diffusely enlarged, moderately firm, dark green-mahogany with multifocal white fibrous plaques measuring 2 X 1 cm on the parietal surface. The gallbladder was markedly engorged and the visceral capsule was firmly attached to air sacs and mesentery.
Histologic examination of the right and left testicular masses revealed a densely cellular, infiltrative, partially encapsulated, multilobulated neoplasm composed of sheets of pleomorphic polygonal-to-round cells arranged in lobules separated by thin fibrovascular stroma (Fig 2B). The neoplastic cells had a large round vesicular nucleus with stippled and marginated chromatin, indistinct nucleoli, moderate eosinophilic slightly vacuolated cytoplasm, and indistinct cell borders. The cells exhibited moderate anisokaryosis and anisocytosis with abundant mitotic figures, with an average of 8 per high power (X400) field. Multifocal variably-sized areas of necrosis and lymphocytic infiltrates were interspersed with neoplastic cells. The neoplastic cells were negative on periodic acid-Schiff (PAS) staining. At the peripheral rim of the masses, the rete testis and epididymis showed marked compression. Beneath the ventricular serosa and associated abdominal air sacs, islands of polygonal to round cells with similar cytologic and histochemical features as described in the testicular masses were identified (Fig 2C, D, E).
The ventricular lumen, subjacent glands, muscularis, serosa, and associated abdominal air sacs were expanded by multifocal to coalescing granulomas, which contained a solid mat of filamentous, branching, parallel-walled, dichotomous hyphae that were 3 to 6 pm wide and regularly septated within an amorphous eosinophilic necrotic matrix (Fig 2F). Within the eosinophilic core, clusters of brown conidiospores and occasional birefringent oxalate crystals were surrounded at the rim by layers of epithelioid macrophages, giant cells, heterophils, eosinophils, lymphocytes, and macrophages. The hyphae and conidiospores were Gomori methenamine silver (GMS) positive. Similar variably-sized, multifocal granulomas were scattered within the hepatic parenchyma, with markedly distended and clogged bile canaliculi and multifocal periportal and random lymphocytic infiltrates.
We describe a case of bilateral malignant seminoma with metastasis to the ventriculus in a bald eagle. A seminoma is a neoplasm derived from benign or malignant transformation of the spermatogenic germinal epithelium. Seminomas can be classified grossly based on distribution as either unilateral or bilateral. Microscopically, they are subdivided into intratubular or diffuse categories based on the organization of the neoplastic cells. The current case is a diffuse seminoma, also referred to as spermatocytic seminoma, which also is the most prevalent form of canine seminomas. These tumors generally have large polyhedral cells with vesicular nuclei admixed with intratumoral lymphocytic aggregates and "starry sky" appearance of necrotic neoplastic cells. These diagnostic features were observed in the current case. Seminomas have been reported in avian species including budgerigars (Melopsittacus undulatus), mallard ducks (Anas platyrhynchos), domestic fowl, turtle dove (Streptopelia risoria), guinea fowl (Numida meleagris), and trumpeter hornbills (Bycanistes buccinator). (2-6) Metastasis is not common in avian seminomas; however, in reported cases of malignant avian seminomas, the liver is the most common site for metastasis through hematogenous or lymphatic dissemination of tumor emboli. (6) Metastasis in our case is unique because, while there are occasional neoplastic cells in testicular lymphatic vessels, definitive visceral metastasis was observed only in the ventriculus. This may have resulted from transcoelomic dissemination and implantation of neoplastic cells on the ventricular serosa. Compressive and traumatic disruption of the tunica albuginea by expansile and infiltrative neoplastic cells or fibrous adhesions of coelomic viscera may have enhanced the exfoliation and consequent implantation of neoplastic cells on the ventricular serosa. Transcoelomic metastasis has been reported extensively in mammalian and avian ovarian neoplasms. (7-9)
No potential influences or causes of neoplasia have been identified in this particular case. Case reports of seminomas in birds have involved older birds of various species, geographic regions, and dietary requirements. Because this particular case involved a long-term captive animal, its diet and medical history are well documented, although genetics and potential familial links to this condition are unknown.
Because of the presence of adhesions and chronic inflammatory changes, coelomic endoscopy was limited in diagnostic capability. Similarly, the anatomy precluded obtaining diagnostic images during transcoelomic echocardiography. Based on these findings, transesophageal echocardiography should be considered in this species. (10) Radiography provided the most sensitive tool, clearly demonstrating a soft tissue mass in the area of the gonads.
Seminomas, which originate from the spermatogenic epithelium, are one of the 3 most common types of testicular tumors in birds, the other 2 being Sertoli cell and interstitial cell tumors. (11) Seminomas were observed most frequently in a colony of pigeons (Columba livia). (12) Reported clinical signs in avian species include coelomic distension, dyspnea, lethargy, and unilateral-to-bilateral pelvic limb paresis. (11) In this eagle, no lameness was noted clinically, likely because of the mass sparing the route of the ischiatic nerve, and no coelomic distension was observed. Single case reports of seminomas in avian patients commonly describe metastases, particularly to the liver and/or kidneys. (3,12-14) In this case, no evidence of metastasis to the liver or kidneys was present, despite cellular presence in lymphatic vessels. To our knowledge, metastasis of seminoma to the ventriculus has not been reported previously.
Fungal air sacculitis was most likely caused by Aspergillus species; the intralesional septate fungal hyphae have acute angle, dichotomous branching with parallel walls of relatively uniform width (3 X 6 pm), and conidiospores that are GMS-positive. Occasional birefringent oxalate crystals within granulomas on the air sacs and ventricular mucosa are consistent with growth of Aspergillus spores in a high oxygen tension environment. Presumably, this fungal infection was secondary to the chronic neoplastic disease process because of immunosuppression. Results of antibody and galactomannan testing for a premortem aspergillosis diagnosis were not consistent with infection in this case. This may be due to granuloma location and immunosuppression, and it highlights the limitations in sensitivity of premortem testing using blood tests alone.
While chronicity of the fungal infection cannot be definitively determined, this was suspected based on the type and location of lesions found during necropsy. The gross and microscopic features of bilateral seminoma with ventricular metastasis suggested a prolonged neoplastic transformation and associated immunosuppression with metabolic alterations. These conditions were conducive to fungal propagation on the air sacs due to localized disruption of abdominal air sac epithelial immunity by implantation of metastatic neoplastic cells. This pathogenesis is consistent with the preponderance of the fungal hyphae and conidiospores on the abdominal air sacs rather than the lungs in this case.
Fungal infections often can occur in the face of immunosuppression, such as is seen in some avian species during high dose or prolonged use of fenbendazole. (15) In this particular case, the association with fenbendazole was not consistent with that of published reports because of the short duration of treatment, lack of clinical signs noted in the second bird treated, as well as the histologic features and severity of the granulomatous air sacculitis. These symptoms were most suggestive of neoplasm-mediated immunosuppression leading to Aspergillus propagation.
This case demonstrated an unusual presentation of metastatic seminoma in a bald eagle. The clinical presentation and blood test results were not specific to this process, but radiographs were useful in identifying the mass. To our knowledge, ventricular metastasis is a previously unreported complication of metastatic seminoma and highlights an unusual pattern of malignancy. Veterinary clinicians should consider metastases to this area in cases with suspected or confirmed seminomas.
Patrick J. Sullivan, DVM, Olufemi O. Fasina, DVM, PhD, and Andrew C. Cushing, BVSc, CertAVP (ZooMed), Dipl ACZM
From the Departments of Small Animal Clinical Sciences (Sullivan, Cushing) and Biomedical and Diagnostic Services (Fasina), College of Veterinary Medicine, University of Tennessee, 2407 River Drive. Knoxville, TN 37996. USA.
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Caption: Figure 1. Right lateral radiograph of an approximately 30-year-old male bald eagle. A multilobulated mass is visible in the caudal coelomic cavity (arrow), along with microhepatia and a markedly small cardiohepatic silhouette. The ventriculus, located ventral to the mass, appears distended. Three focal metallic opacities are visible from a presumed prior gunshot injury.
Caption: Figure 2. Gross and microscopic examinations of bilateral malignant seminoma with ventricular metastasis in the bald eagle described in Figure 1. (A) Gross necropsy image of the testes and kidneys; the right and left testicles (asterisks) are markedly enlarged with multifocal tan projections compressing the tunica albuginea and surrounding cranial lobe of the kidneys and adrenal gland. (B) Testis. The parenchyma is effaced by neoplastic polygonal to round pleomorphic cells organized in sheets separated by thin fibrovascular stroma and interspersed with multifocal lymphocytic infiltrates (asterisk; hematoxylin and eosin stain; bar = 50 [micro]m). (C) Ventriculus. The ventricular lumen, subjacent glands, muscularis, serosa, and associated abdominal air sacs are expanded by multifocal to coalescing granulomas and marked focally extensive necrosis of the mucosa. A metastatic band and focus of polygonal to round cells with histologic features similar to the neoplastic testicular cells (asterisk) are present above the granuloma (arrow). The metastatic cells are admixed with lymphocytic infiltrates and interspersed with tunica muscularis smooth fibers infiltrated with heterophils, macrophages, and lymphocytes (hematoxylin and eosin stain; X20). (D) Ventriculus. Higher magnification of metastatic foci (asterisk; hematoxylin and eosin stain; X100). (E) Ventriculus. Metastatic neoplastic cells (asterisk) are organized in sheets separated by thin fibrovascular stroma admixed with heterophils, lymphocytes, macrophages, and smooth muscle myofibers in the ventricular lamina propria, and tunica muscularis (hematoxylin and eosin stain; X200). (F) Ventriculus. The mucosa is expanded and contains a solid mat of filamentous branching, 3-6 pm wide, regularly septate, parallel-walled, dichotomous hyphae within an amorphous eosinophilic necrotic matrix and occasional conidiophore (asterisk; hematoxylin and eosin stain; X200). Inset: Stain highlighting black fungal hyphae and conidiophore embedded within eosinophilic debris in the mucosa (Gomori methenamine silver stain; X200).
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|Author:||Sullivan, Patrick J.; Fasina, Olufemi O.; Cushing, Andrew C.|
|Publication:||Journal of Avian Medicine and Surgery|
|Date:||Sep 1, 2018|
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