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Ovarian Hemangiosarcoma in an Orange-winged Amazon Parrot (Amazonaamazonica)Author(s): Kimberly Mickley DVM, Melanie Buote DVM, Dipl ACVP, Matti Kiupel Dr Med Vet, MS,PhD, Dipl ACVP, Jennifer Graham DVM, Dipl ABVP (Avian), Dipl ACZM, and Connie Orcutt DVM,Dipl ABVP (Avian)Source: Journal of Avian Medicine and Surgery, 23(1):29-35. 2009.Published By: Association of Avian VeterinariansDOI: http://dx.doi.org/10.1647/2008-013R.1URL: http://www.bioone.org/doi/full/10.1647/2008-013R.1

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Ovarian Hemangiosarcoma in an Orange-winged AmazonParrot (Amazona amazonica)

Kimberly Mickley, DVM, Melanie Buote, DVM, Dipl ACVP, Matti Kiupel, Dr MedVet, MS, PhD, Dipl ACVP, Jennifer Graham, DVM, Dipl ABVP (Avian), Dipl

ACZM, and Connie Orcutt, DVM, Dipl ABVP (Avian)

Abstract: A 25-year-old intact female orange-winged Amazon parrot (Amazona amazonica)

presented for a 2-week history of straining to defecate, lethargy, open-beak breathing, decreased

vocalization, and ruffled feathers. On physical examination, the parrot had a heart murmur,

increased air sac and lung sounds, open-beak breathing, increased respiratory rate and effort,

and coelomic distension. An ultrasound revealed intracoelomic fluid, and hemorrhagic fluid was

aspirated from the coelom. Cytologic analysis indicated hemocoelom. Pericardial effusion was

observed during the sonogram, and pericardiocentesis was performed. The bird was

euthanatized upon the owner’s request because of a poor prognosis. At necropsy, several

masses that involved the ovary and oviduct were observed, as well as a thickened pericardium

and a thickened, fibrinous epicardium. Results of a histopathologic examination of the masses

that involved the reproductive tract revealed ovarian hemangiosarcoma, which was confirmed

by immunohistochemical staining. To our knowledge, ovarian hemangiosarcoma has not been

reported in a psittacine species, nor has immunohistochemistry confirmed ovarian hemangio-

sarcoma in avian species, specifically in an orange-winged Amazon parrot.

Key words: Hemangiosarcoma, ovarian, neoplasia, pericardial effusion, immunohistochemistry,

avian, orange-winged Amazon parrot, Amazona amazonica

Clinical Report

A 25-year-old intact female orange-winged

Amazon parrot (Amazona amazonica) presented

for a 2-week history of progressive dyspnea,

open-beak breathing, lethargy, ruffled feathers,

decreased appetite, decreased vocalization, and

straining to defecate. The parrot’s diet consisted

of mostly seed, fresh fruits, and vegetables. On

presentation, the parrot weighed 558 g and was

bright, alert, and responsive. Occasional open-

beak breathing was apparent in the examination

room, but the parrot did not appear to be in

severe respiratory distress. Increased eyelid turgor

indicated mild dehydration. The choanal papillae

were blunted, the choanal slit appeared inflamed,

and the keratin layers of the rhamphotheca were

flaking. The parrot’s feathering was dull. The

heart rate was .250 beats per minute, and a

prominent holosystolic murmur was auscultated.

The parrot had a sternal lift with increased

respiratory rate and effort while resting. On

auscultation of the air sacs, crackles and wheezes

were noted. Lung sounds were apparent bilater-

ally, with the left side more prominent than the

right. The coelom was distended, and fluid was

palpable.

The parrot was admitted to the hospital for

further supportive care and diagnostic testing. An

ultrasound study was performed while the parrot

was supplemented with flow-by oxygen. Intra-

coelomic fluid was observed, and 60 ml of

hemorrhagic fluid was aspirated and submitted

to the laboratory for cytologic analysis. Ultra-

sound examination of the heart revealed pericar-

dial effusion and fibrinous material on the

epicardium (Fig 1). A pericardiocentesis was

performed on the awake parrot, and approxi-

From the Angell Animal Medical Center, 350 S Hunting-

ton Avenue, Boston, MA 02130, USA (Mickley, Buote,

Graham, Orcutt); and the Department of Pathobiology and

Diagnostic Investigations, Diagnostic Center for Population

and Animal Health, Michigan State University, 4125 Beau-

mont Road, Room 152A, Lansing, MI 48910, USA (Kiupel).

Journal of Avian Medicine and Surgery 23(1):29–35, 2009

’ 2009 by the Association of Avian Veterinarians

29

mately 10 ml of hemorrhagic fluid was retrieved.

Soft-tissue masses were suspected near the repro-

ductive tract, but the parrot could not tolerate

further ultrasound examination. By the end of the

examination, the parrot seemed to exhibit less

open-beak breathing but appeared more stressed.

The parrot was placed in a warmed, oxygenated

incubator. The owner was informed of the

ultrasound findings and the poor prognosis. The

owner elected euthanasia and agreed to a

necropsy.

A broad differential list for the symptoms listed

included but was not limited to primary cardiac

disease, respiratory disease (bacterial, fungal, or

viral), metabolic disease (liver, kidney), neoplasia,

reproductive disease, other types of infection or

inflammation, and nutritional deficiencies. When

considering the clinical signs and physical exam-

ination findings, cardiac disease, respiratory

disease, neoplasia, and reproductive disease were

placed at the top of the differential list. Even

though gross evidence of hepatic disease was not

evident on ultrasound examination, metabolic

disease (hepatic) was also considered because of

the parrot’s dietary issues and distended abdo-

men. Cytologic examination of the coelomic fluid

was composed of erythrocytes admixed with small

numbers of macrophages, occasional heterophils,

and small, rare lymphocytes. The macrophages

often contained intracytoplasmic hemosiderin

pigment and occasional erythrocytes (erythro-

phagocytosis). These findings were indicative of

chronic hemorrhage (ie, chronic hemocoelom).

Postmortem examination of the parrot was

performed within 30 minutes of euthanasia. The

pericardial sac contained dark red, opaque fluid

(hemopericardium). The epicardium was thick-

ened by a friable tan material presumed to be the

Figure 1. Ultrasound image of an orange-winged Amazon parrot with ovarian hemangiosarcoma. Severe peri-

cardial effusion (E) and fibrinous material (F) on the epicardium of the heart (H) are visible.

30 JOURNAL OF AVIAN MEDICINE AND SURGERY

result of chronic fibrinous pericarditis (Fig 2).

The coelomic cavity contained dark-red fluid

similar to that observed in the pericardial sac

(presumptive hemocoelom). A large, 3.5 3 3.5-

cm, multicystic, irregular, hemorrhagic mass

infiltrated the hilar region of the left ovary

(Fig 3). Several similar cystic masses were scat-

tered along the serosal surface of the left oviduct.

The air sacs appeared thickened and cloudy, and

the lungs were congested. The liver was diffusely

pale red and irregular in shape. Samples from the

heart, ovarian mass, reproductive tract (oviduct

and ovary), liver, spleen, lung, air sac, and kidney

were submitted for histopathologic examination.

Histopathologic analysis revealed the following

abnormalities in the organs submitted. The mass

located in the reproductive tract was composed of

anastomosing capillary-sized to cavernous, con-

gested, vascular channels lined by neoplastic cells

supported by small amounts of collagenous

stroma (Fig 4). The neoplastic cells were spindle

cells with small-to-moderate amounts of eosino-

philic cytoplasm and fairly indistinct cell borders.

The cell nuclei were irregularly oval with finely

stippled chromatin and 1 or 2 small, magenta

nucleoli. Mitotic figures were rare (,1 mitotic

figure per 10 high-power fields), and mild

anisocytosis and anisokaryosis were observed.

The neoplasm infiltrated the ovarian hilus with

occasional follicles entrapped within the mass.

The neoplasm infiltrated the wall of the adjacent

oviduct, with formation of several pedunculated,

large, cavernous, vascular spaces similar to those

seen within the primary mass along the serosal

margin of the oviduct. Several of the cavernous

vascular spaces had undergone necrosis with local

infiltration of small numbers of epithelioid

macrophages, multinucleate giant cells, and oc-

casional lymphocytes. The epithelioid macro-

phages often contained intracytoplasmic hemo-

siderin pigment (hemosiderophages). The result-

ing histopathologic diagnosis was ovarian he-

mangiosarcoma. A portion of this mass was sent

to the Diagnostic Center for Population and

Animal Health at Michigan State University for

immunohistochemical analysis. Endothelial dif-

ferentiation of neoplastic cells was confirmed by

immunohistochemical staining for factor VIII–

related antigen on sections of formalin-fixed,

paraffin-embedded tissue from the ovarian neo-

plasm. Deparaffinization, antigen retrieval and

immunostaining were performed on the Bond

maX Automated Staining System (Vision Bio-

Systems, Norwell, MA, USA) by using the Bond

Polymer Detection System (Vision BioSystems)

and a rabbit polyclonal antibody against factor

VIII-related antigen (Dako Cytomation, Carpin-

teria, CA, USA) at a dilution of 1 : 500. Antigen

retrieval was achieved by using the Bond Epitope

Retrieval Solution 2 (Vision BioSystems) for

20 minutes. The immunoreaction was visualized

with 3,3-diaminobenzidine substrate (Vision Bio-

Systems), and sections were counterstained with

hematoxylin. Positive immunohistochemical con-

trols included normal arteries and veins to which

the appropriate antisera were added. For negative

controls, the primary antibody was replaced with

homologous nonimmune serum. For comparison,

tissue from a canine hemangioma was processed

along with the parrot tissue. There was strong

Figure 2. Gross specimen of the heart (H) of the

Amazon parrot described in Figure 1 showing the heart

with tan, fibrinous material on the epicardium and the

thickened pericardial sac (PS).

Figure 3. Gross specimen of the multicystic, hemor-

rhagic mass (HM) in the coelomic cavity that infiltrates

the hilar region of the left ovary of the Amazon parrot

described in Figure 1. The thickened pericardial sac

(PS) and follicles (F) are visible.

MICKLEY ET AL—OVARIAN HEMANGIOSARCOMA IN A PARROT 31

positive staining of the neoplastic cells lining the

vascular spaces in the ovarian neoplasm that

supported the diagnosis of hemangiosarcoma

(Fig 5).

The epicardium was diffusely thickened by

fibrosis, which was expanded by moderate amounts

of edema fluid. The mesothelial lining of the

epicardial surface was diffusely lost (ulcerated),

with infiltration of moderate numbers of macro-

phages accompanied by fewer multinucleate giant

cells, plasma cells, small lymphocytes, occasional

heterophils, and small-to-moderate amounts of

fibrin. The macrophages occasionally contained

small amounts of intracytoplasmic hemosiderin

pigment (erythrophagocytosis). The histopatholog-

ic diagnosis was chronic organizing fibrinous

epicarditis. The liver exhibited mild-to-moderate,

acute, periportal-to-random, necrotizing and het-

erophilic hepatitis (highly suggestive of embolic

hepatitis). The spleen exhibited lymphoid depletion.

The kidney, lung, and air sacs appeared normal.

Discussion

Hemangiosarcomas are malignant neoplasms

that arise from the vascular endothelium and are

also known as angiosarcomas or hemangioendo-

theliomas.1,2 Hemangiosarcomas can occur in the

skin, liver, myocardium, lungs, spleen, muscle,

mesentery, kidney, oviduct, or in the diaphysis of

long bones, and these tumors can metastasize to

other organs.1,3 Ovarian hemangiosarcoma is not

well recognized in psittacine birds, and, to our

knowledge, there are no reports of ovarian

hemangiosarcoma in an orange-winged Amazon

parrot. This clinical report is intended to describe

ovarian hemangiosarcoma in an orange-winged

Amazon parrot. Although hemangiosarcoma hasbeen reported in psittacine birds, this type of

tumor is still considered rare in psittacine

species.4–7 Recently, there have been reports of

hemangiosarcomas located in other organ sys-

tems of birds, such as intrathoracic hemangiosar-

coma in an ostrich (Struthio camelus),8 heman-

giosarcoma of the leading edge of the pro-

patagium in a golden pheasant (Chrysolophus

pictus),9 and subcutaneous hemangiosarcoma in a

cockatiel (Nymphicus hollandicus).10 Neoplasms

that affect the reproductive tract, such as oviduct-

associated fibroid tumors, leiomyomas, leiomyo-

sarcomas, adenomas, and adenocarcinomas, seem

to be best documented in gallinaceous species like

domestic chickens and turkeys (Meleagris gallo-

pavo).1,11–13 To our knowledge, ovarian hemangio-sarcomas have not yet been reported in gallina-

ceous birds. There is evidence that hemangiosar-

comas are induced by retroviruses in poultry, but

this has not yet been studied in other avian

species.1,14,15 Neoplasms that involve the repro-

ductive tract of pet birds have been most

Figure 4. Photomicrograph of the ovarian hemangiosarcoma in the Amazon parrot described in Figure 1. Variably

sized vascular channels (capillary [CA] and cavernous [C]) lined by neoplastic cells are visible (hematoxylin and

eosin, 3100).

32 JOURNAL OF AVIAN MEDICINE AND SURGERY

commonly seen in budgerigars (Melopsittacus

undulatus) and cockatiels (Nymphicus hollandi-

cus).13,16 The most commonly reported neoplasms

are granulosa cell tumors followed by adenocar-

cinomas.1 In a study of tumors of the ovary and

oviduct, 37 pet birds were evaluated, and there

were no reports of ovarian hemangiosarcoma.13

This parrot had an increased respiratory effort

and rate, most likely resulting from compression

of the air sacs by intracoelomic fluid. The heart

murmur and tachycardia were most likely related

to the pericardial effusion. Additional clinical

signs not observed in this case but also associated

with reproductive-tract neoplasms include unilat-

eral or bilateral leg paresis and polyostotic

hyperostosis.1,17 To avoid additional stress on

the parrot, radiographs and blood work were not

performed. Coelomic ultrasound was particularly

helpful in this case, because it allowed visualiza-

tion and aspiration of coelomic and pericardial

effusions. In a recent study, transvaginal ultra-

sound was used to detect ovarian tumors and

ascites in chickens.18 In that study, ultrasound

findings correlated with histologic examination of

the ovaries, indicating that ultrasound is a viable

diagnostic tool for evaluating the reproductive

tract in large birds.18 In this parrot, the small vent

size precluded the use of transvaginal ultrasound.

Cytologic analysis of the intracoelomic fluid

confirmed chronic hemorrhage. Neoplastic cells

were not seen in the fluid sample. Histopathologic

examination confirmed ovarian hemangiosarco-

ma with local invasion into the adjacent oviduct.

No other obvious metastatic lesions were observed

in the other organs. The ovarian hemangiosarco-

ma was the source of the hemocoelom. Interest-

ingly, the patient also had hemopericardium.

Hemopericardium is commonly associated with

trauma, rupture of the left atrium, or neoplasia, or

can be idiopathic.1 In this case, the hemopericar-

dium was suspected to be secondary to the ovarian

hemangiosarcoma or the hemocoelom resulting

from the ovarian hemangiosarcoma, but the

etiopathogenesis of the hemopericardium is un-

clear. In addition to the hemopericardium, the

underlying surface of the heart exhibited chronic

fibrinous epicarditis. In this case, chronic irritation

due to the hemorrhagic intrapericardial fluid may

have resulted in the epicarditis. Other possible

causes of fibrinous pericarditis are bacterial, viral,

mycotic, parasitic, mycoplasmal, and mycobacte-

rial infections.1 However, no histologic evidence of

an infectious disease process was observed in this

case to support any of these possible differential

diagnoses.

There are inconclusive reports of immunohis-

tochemical endothelial mammalian markers used

for avian patients and a case in which immuno-

histochemistry confirmed subcutaneous heman-

giosarcoma in a cockatiel.4,7,9,10 In this Amazon

Figure 5. Photomicrograph of immunohistochemical staining for factor VIII-related antigen in the ovarian tissue

sample from the Amazon parrot described in Fig 1. Neoplastic cells lining the vascular spaces stain strongly positive.

The dark color and arrows indicate positive staining for the endothelial marker (3200).

MICKLEY ET AL—OVARIAN HEMANGIOSARCOMA IN A PARROT 33

parrot, results of immunohistochemical staining

for factor VIII-related antigen were positive.

Factor VIII-related antigen has been established

as a useful marker for endothelial cells in

paraffin-embedded sections in various mammali-

an species. Positive staining of the neoplastic cells

lining the vascular spaces in the ovarian neoplasm

supports the diagnosis of a neoplasm of endothe-

lial origin (Fig 5). To our knowledge, this is the

first case report in which factor VIII-related

antigen positively identified an ovarian heman-

giosarcoma in a psittacine species.

Treatment for hemangiosarcomas is not well

documented. Before treatment is initiated, he-

mangiosarcoma must be distinguished from

nonneoplastic conditions, such as vascular mal-

formations, hematomas, vascularized granulation

tissue, or other neoplasms with a rich blood

supply.1 It has been suggested that tumors located

internally are more malignant than external

tumors.19 Internal tumors can restrict treatment

options, particularly in smaller species. Depend-

ing on the tumor location, patient status, and

patient size, treatment options could include

surgical excision of the tumor, radiation therapy,

and systemic or intralesional chemotherapy.4,6,16,20

Carboplatin and cisplatin have been used in birds

with malignant neoplasms.21 To our knowledge,

neither of these chemotherapeutics have been

used to manage hemangiosarcomas in avian

species. All of these possible treatments come

with varying degrees of risks, such as incomplete

surgical excision that could allow for tumor

regrowth. Frequent anesthesia, the need for

accurate radiation doses, and financial consider-

ations for both the client and the hospital are

important factors when considering radiation

therapy. Appropriate dosing and administration

of chemotherapeutics and the need for sequential

blood sampling are important aspects to consider

with chemotherapeutic protocols, as are adverse

effects such as post-treatment leukopenia, gastro-

intestinal upset, and fatigue. In conjunction with

surgical excision in this case, radiation or

chemotherapy may have also been recommended

because of the potential for micrometastasis.

However, surgery would have been considered

high risk because of the parrot’s debilitated

condition. The large volume of intracoelomic

fluid would have also impeded entry into the air

sacs. A complete ovariohysterectomy would have

eliminated the tumors in the reproductive tract,

but it would not have corrected the problems in

the cardiac system. In addition, an ovariohyster-

ectomy is a high-risk procedure in a bird because

of the close proximity of the ovary to the caudal

vena cava.

Neoplastic disease, specifically hemangiosarco-

ma, should be considered on a differential list when

taking into account the clinical signs described in

this case and coupling them with the diagnostic

results obtained. At this time, no definitive

protocol or information on medical management

or treatment of avian hemangiosarcoma is readily

available. Additional research and information is

needed on this neoplasm to further formulate a

treatment plan in avian species. Given the aggres-

sive biological behavior seen with internal heman-

giosarcomas in other species, informing owners of

the potential of this malignant neoplasm to

metastasize to other organs and eventually lead

to the death of the patient is important. Thus, a

guarded prognosis should be given to avian

patients with ovarian hemangiosarcoma.

Acknowledgments: We thank Drs. Kathy Beck, Greg

Rapport, and Nevena Nikolajevic for their help

obtaining the ultrasound images.

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