33
eoplasia is an abnormal, uncontrolled, pro- gressive proliferation of cells in any tissue or organ. Classification of neoplasms is based upon general tissue origin (epithelial vs. mesenchymal), specific cell lineage and whether the neoplasm is benign (-oma) or malignant (sarcoma or carcinoma). Classification of some neoplasms as benign or malignant may require knowledge of the biological behavior of the neoplasm. The majority of the veterinary medical literature has reported the incidence, gross appearance and micro- scopic characteristics of neoplasms of domesticated birds, especially poultry. 20,22,23,101,109 Furthermore, the study of retroviral-induced neoplasia in poultry has advanced medical knowledge of retroviral molecular biology, as well as that of neoplasm development, growth and metastasis. 91,101 Similar information con- cerning neoplasms of captive and free-ranging birds is almost nonexistent. One ultrastructural survey of various budgerigar neoplasms failed to disclose retroviral particles, but sampling errors are a known complication of such studies. 52 More recently, papil- lomaviruses have been demonstrated as the etiologic agents of cutaneous papillomas in African Grey Par- rots, Chaffinches and Bramblings. 73,87,94,96 Reports of neoplasia are extant for captive as op- posed to free-ranging birds, 5,6,7,12,15,49,51,83,102,108 espe- cially budgerigars, where the overall incidence of neoplasia ranges from 16.8% to 24.2%. 12,15,51 In a veterinary diagnostic laboratory with a diverse avian caseload, budgerigars accounted for 69.7% of all psit- tacine neoplasms and 41% of all avian neoplasms recorded. The overall incidence of neoplasia approxi- mated 3.8% in all avian submissions. 108 Compared to free-ranging birds, neoplasia is re- ported more frequently in companion and aviary birds because such birds are observed closely for abnormalities, have a longer life span and may have a genetic predisposition to neoplasia through in- breeding. Little is known, however, concerning the etiology, predisposing factors, development, biologi- cal behavior or treatment of neoplasms in companion and aviary birds. As more cases of avian neoplasia are studied and reported, our clinicopathologic knowledge will increase and treatment regimens will improve. N CHAPTER 25 ONCOLOGY Kenneth S. Latimer

Oncology - Avian Medicine

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eoplasia is an abnormal, uncontrolled, pro-gressive proliferation of cells in any tissueor organ. Classification of neoplasms isbased upon general tissue origin (epithelial

vs. mesenchymal), specific cell lineage and whetherthe neoplasm is benign (-oma) or malignant (sarcomaor carcinoma). Classification of some neoplasms asbenign or malignant may require knowledge of thebiological behavior of the neoplasm.

The majority of the veterinary medical literature hasreported the incidence, gross appearance and micro-scopic characteristics of neoplasms of domesticatedbirds, especially poultry.20,22,23,101,109 Furthermore, thestudy of retroviral-induced neoplasia in poultry hasadvanced medical knowledge of retroviral molecularbiology, as well as that of neoplasm development,growth and metastasis.91,101 Similar information con-cerning neoplasms of captive and free-ranging birdsis almost nonexistent. One ultrastructural survey ofvarious budgerigar neoplasms failed to discloseretroviral particles, but sampling errors are a knowncomplication of such studies.52 More recently, papil-lomaviruses have been demonstrated as the etiologicagents of cutaneous papillomas in African Grey Par-rots, Chaffinches and Bramblings.73,87,94,96

Reports of neoplasia are extant for captive as op-posed to free-ranging birds,5,6,7,12,15,49,51,83,102,108 espe-cially budgerigars, where the overall incidence ofneoplasia ranges from 16.8% to 24.2%.12,15,51 In aveterinary diagnostic laboratory with a diverse aviancaseload, budgerigars accounted for 69.7% of all psit-tacine neoplasms and 41% of all avian neoplasmsrecorded. The overall incidence of neoplasia approxi-mated 3.8% in all avian submissions.108

Compared to free-ranging birds, neoplasia is re-ported more frequently in companion and aviarybirds because such birds are observed closely forabnormalities, have a longer life span and may havea genetic predisposition to neoplasia through in-breeding. Little is known, however, concerning theetiology, predisposing factors, development, biologi-cal behavior or treatment of neoplasms in companionand aviary birds. As more cases of avian neoplasiaare studied and reported, our clinicopathologicknowledge will increase and treatment regimens willimprove.

NC H A P T E R

25ONCOLOGY

Kenneth S. Latimer

This chapter is written to provide a systems ap-proach to avian neoplasia, with an emphasis on neo-plasms of companion, aviary and free-ranging birds.Information is presented to assist the clinician inunderstanding the complexities and treatment ofavian neoplasms (see Table 25.1). Lesions that mimicneoplasia also are discussed briefly. Lastly, the cy-tologic and histologic features of various neoplasmsare presented to assist veterinary pathologists in thediagnosis of these neoplasms (see Table 25.2).

Integumentary System

Neoplasms of the integumentary system are commonand account for 12% to 70% of all avian neo-plasms.6,12,15,108 Of the various neoplasms reported,lipomas and fibrosarcomas are observed most fre-quently.

Adipose Neoplasms and MassesNeoplasms associated with fatty tissue and lipiddeposition in companion birds include lipoma,myelolipoma, liposarcoma and hibernoma. Lesionsthat mimic these neoplasms include xanthomas andlipogranulomas. Definitive diagnosis of each of theseneoplasms or masses requires histopathologic exami-nation of surgical biopsy specimens (Figure 25.1).

Lipoma: Lipomas are benign proliferations of welldifferentiated adipocytes (lipocytes) that may exhibitslow-to-rapid, progressive growth over time. Lipomasare the most frequently observed neoplasm of com-panion birds, with a reported incidence of 10% to 40%in budgerigars.143 Besides budgerigars, lipomas maybe observed frequently in Rose-breasted Cockatoos(galahs) and Amazon parrots.98,143 Obesity, advancingage, species of bird and high-energy diets appear tobe predisposing factors for tumor development.Based upon clinical observations, a genetic predispo-sition to lipoma development may exist in budgeri-gars.

Lipomas usually arise in the subcutis of the sternalor abdominal skin, but may also be observed on thewings, back, neck, legs or near the uropygialgland.6,12,15,30,49,51,69,72,86,102,108,127 In addition, lipomasmay occur in the thoracoabdominal cavity (arisingfrom thoracic or mesenteric fat, ovary, ventriculusand liver) or in association with skeletal mus-

cle.12,40,102,108,127 Tumor size typically ranges from 0.3to 4.0 cm in diameter (Color 25.2).

Lipomas occur as single or multiple masses. Affectedbirds may be presented for diagnosis of a visible skinor subcutaneous mass or abdominal distention.Large tumors may interfere with leg movement,perching or flight. On palpation, lipomas are usuallywell defined and soft; the overlying skin is freelymobile.143

Grossly, excised lipomas appear soft, round-to-mul-tilobulated and pale yellow. On cut surface, they arethinly encapsulated and fatty. Histologically, lipomasappear as thinly encapsulated masses composed oflobules of well differentiated adipocytes. Scattered

FIG 25.1 A 15-year-old Amazon parrot was referred for evaluationof a tumor. A previous veterinarian had advised euthanasia. Alarge, pendulated, ulcerative mass was present on physical exami-nation. The bird was in overall good condition, and abnormalclinicopathologic findings were limited to a mild heterophilia(18,000/µl). Cytology of a fine-needle aspirate revealed an accumu-lation of necrotic debris and reactive macrophages. The mass wassurgically incised, and a piece of wood was found penetrating theesophageal wall. The granuloma was surgically removed, theesophageal defect was repaired and the surgical site was managedas an open wound. A mass should be considered of neoplastic originonly with the cytologic or histologic identification of suggestivecells.

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blood vessels are also present. Central necrosis maybe present in larger masses, especially those neo-plasms that grow rapidly or are subjected to trauma.

Dietary changes and increased exercise are fre-quently curative in early cases and should be imple-mented prior to surgery to reduce the size of themass. Because lipomas are often accompanied bybody fat that may interfere with caudal air sac vol-ume, exercise programs should be initiated withcare, especially in tachypneic patients. Surgical exci-sion is necessary if the tumor is causing clinicalproblems that are not resolved with diet change andincreased exercise.25,30 Lipomas may be vascular;therefore, attention to hemostasis through the use ofbipolar radiosurgery is important. Feeding formu-lated diets should prevent goiter and may also reducethe likelihood of a bird developing lipomas. Non-spe-cific use of thyroxine should be avoided, and treat-ment of lipomas in the absence of hypothyroidism isnot an indication for thyroxine administration.66,113

Myelolipoma: Myelolipomas are composed of adiposeand hematopoietic tissues that may arise in the sub-cutis of the trunk, wings and legs. Occasionally theymay occur in the liver or spleen. The outward appear-ance is similar to a lipoma.

Liposarcoma: Liposarcomas are malignant, fattyneoplasms composed of lipoblasts and immatureadipocytes. These neoplasms are firm on palpation,poorly encapsulated, highly vascularized and usuallyarise in the subcutis of the sternum or uropygialgland area.102 Infrequently, liposarcomas may pre-sent as poorly demarcated nodules in the thoracoab-dominal cavity, liver or skeletal muscles.47,108

Liposarcomas are locally invasive, have the potentialto metastasize and may arise in a multicentric pat-tern. Multicentric origin or widespread metastasis istypical.47

Histologically, neoplastic cells appear spindle-like,stellate, round or polyhedral. Cell nuclei are round tooval and contain multiple nucleoli. The cytoplasmstains lightly eosinophilic or contains variably sizedvacuoles. Larger vacuoles may cause peripheral nu-clear displacement. Mitotic figures may be presentbut are not numerous. The presence of lipid withinthe cytoplasmic vacuoles may be demonstrated byfat-soluble stains, such as oil red O or Sudan IV,applied to frozen tissue sections. Alternatively, osmi-cated tissue specimens may be processed routinelyand stained with hematoxylin and eosin. In theselatter tissue sections, osmicated lipid will appearbrown-black.

Hibernoma: A hibernoma is a rare benign tumor ofbrown fat origin. A subconjunctival hibernoma wassuccessfully excised from a two-year-old male whitegoose. The neoplasm involved the ventrolateral as-pect of the right sclera and protruded through thepalpebral fissure, interfering with eyelid closure.89

Histologically, neoplastic cells stained faintly eosino-philic, appeared foamy, had central-to-paracentralnuclei and had a voluminous cytoplasm containingnumerous, fine vacuoles and birefringent eosino-philic material. The neoplasm was well vascularizedand contained a delicate stromal framework. Lipidwas demonstrated within the cytoplasmic vacuolesby oil red O staining.89

Xanthoma/Xanthomatosis: The term xanthomameans “yellow mass.” An xanthoma is not a trueneoplasm, but an inflammatory intumescence result-ing from the accumulation of lipid-laden macro-phages, giant cells, free cholesterol and variable de-grees of fibrosis. Xanthomas occur frequently ingallinaceous and psittacine birds, appearing as yel-low, single-to-multiple, discrete subcutaneous nod-ules or diffuse thickenings of skin that may befeatherless, ulcerated or hemorrhagic (Color25.15).25,143 These masses may occur anywhere on theskin or overlie other neoplasms, especially lipomas(Color 25.2).143 Infrequently, xanthomas may have aperiarticular arrangement or involve the oral cav-ity.60,111

Although the precise etiology of xanthoma formationis unknown, various theories have been proposedincluding high-lipid diets or ingestion of toxic fat-sol-uble substances (such as aromatic chlorinated hydro-carbons) that might incite inflammation andtrauma.25,98,117,143 Cellular infiltrates, lipid accumula-tion and fibroplasia give rise to the nodular or tumor-ous appearance of these lesions. Unresectable ormultiple skin xanthomas may respond to irradiation(low-energy X-rays; 20 to 30 Gy) or hyperthermia.143

Dietary restriction of oily seeds may be beneficial inthe medical management of xanthomatosis.34

Connective TissueNeoplasms and Masses

Connective tissue neoplasms (fibrosarcoma, fibroma,myxosarcoma and myxoma) arise from the prolifera-tion of fibroblasts or undifferentiated mesenchymalcells, which frequently assume a spindle-like appear-ance. These neoplasms contain a collagenous or mu-cinous stroma. Cellular morphology, mitotic index

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and biological behavior are used to classify theseneoplasms as benign or malignant.

In chickens, connective tissue neoplasms can arisefollowing infection with specific strains of avian leuk-osis or sarcoma virus.101 The etiology of similar neo-plasms in aviary and free-ranging birds is unknown.

Fibrosarcoma: Fibrosarcoma is a malignant neo-plasm of fibroblast or mesenchymal cells, which pos-sess the ability to produce collagen fibers. Fibrosarco-mas occur commonly in budgerigars,cockatiels, macaws and parrots.7,

25,49,108,110,143 Fibrosarcomas may con-stitute 3 to 14% of all neoplasms inbudgerigars.143

Clinically, fibrosarcomas are firm,single-to-multiple, broad-based,relatively immobile nodules ormasses. Superficial fibrosarcomasmay be covered by an intact-to-ulcer-ated epidermis accompanied by hem-orrhage and secondary bacterial in-fections. Fibrosarcomas commonlyarise from the soft tissues of thewing, leg, head, beak, cere and trunk( Co l or 25 .1 , 25 . 5 ,24.19).6,11,12,15,72,75,102,108,110 They alsomay arise in the viscera and deeptissues including thoracoabdominalcavity, spleen, liver, mouth, tongue,syrinx, lung, small intestine, proven-tricular wall, testes and ovary (Fig-ure 25.2).12,27,102,108 These neoplasmsare locally invasive and may eventu-ally metastasize, especially to the ab-dominal cavity, lungs, liver, kidney,heart base and bone (Figure25.3).12,102,108,110,143 Intra-abdominalneoplasms also have been observedenveloping bowel loops and adheringto the pancreas.82,127 These neo-plasms have been reported asneurofibrosarcomas based upon cel-lular arrangement or pattern, but aneural origin has not been demon-strated.

Fibroma: A fibroma is an uncommonbenign neoplasm composed of welldifferentiated fibroblasts distributedwithin a collagenous matrix. Fibro-mas are firm on palpation and mayarise almost anywhere, but usually

involve a firm mass in the skin and subcutaneous tissuesof the wing, leg, face, beak, neck or sternum.12,32,69,72,143

Myxoma and Myxosarcoma: These neoplasms are offibroblast or mesenchymal cell origin, but possessabundant mucinous stroma. These rare neoplasmsmay arise wherever connective tissue exists includ-ing the foot pad, cranium, leg, kidney, commissure ofthe beak and within the thoracic cavity.15,108 Clini-cally, these masses may appear soft on palpation andgelatinous on cut surface. In myxosarcomas, neoplas-

FIG 25.2 A ten-year-old Amazon parrot was presented with a one-year history of aprogressive swelling of the head and face (see Color 25.1). Physical examination revealednumerous masses throughout the body that were confirmed by radiographs. Histopathol-ogy indicated an invasive fibrosarcoma involving the soft tissues and bones of the head(courtesy of Jane Turrel).

FIG 25.3 An adult female dove was presented with a soft tissue swelling involving theright scapulohumeral region. Radiographically, a large, uniform, soft tissue mass withosteolysis involving the humoral head and diaphysis was noted. The increased medullarybone density was considered normal for a laying hen. Cytology of a fine-needle aspirateconfirmed fibrosarcoma (courtesy of Marjorie McMillan).

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tic cells appear to be more numerous and containplump nuclei. Metastasis may occur, but is infrequentto rare.

Reactive Fibroplasia: Granulation tissue exempli-fies healing by second intention. Granulation tissuemay be highly vascular and proliferative with vari-able degrees of inflammation. Grossly, granulationtissue may have a proliferative or neoplastic-likeappearance. Cytologic specimens often contain apleomorphic population of immature fibroblasts thatmimic neoplasia. Inflammatory cells may be admixedwith blood. Histologically, tissue architecture is adifferentiating feature of the lesion wherein bloodvessels are oriented at right angles to the surface ofthe lesion, while fibroblasts are oriented parallel tothe surface of the lesion. Marked, proliferative fibro-plasia with granuloma formation also may be ob-served in the ceca of gallinaceous birds, especiallypheasants, infected with Heterakis isolonche (seeColor 14). In such instances, nematode-induced reac-tive fibroplasia may be difficult to distinguish fromneoplasia.57,62

Epithelial Neoplasms and CystsPapillomas and Papilloma-like Lesions: Cutan-eous papillomas are observed occasionally in domes-tic, captive and free ranging birds.4,6,11,15,46,73,98 Multi-ple papillomas most frequently originate from the skinof the eyelids, at the junction of the beak and face, andon the feet and legs. The anatomic location of thesebenign neoplasms may interfere with vision, prehen-sion of food or perching if the lesions are severe (Color25.17). Histologically, these lesions consist of folds ofhyperplastic stratified squamous epithelium over a fi-brovascular stroma. Cutaneous papillomas are viral-in-duced, at least in African Grey Parrots, Chaffinches andBramblings (Color 25.10) (see Chapter 32).73,87,96

Squamous Cell Carcinoma: Squamous cell carci-noma is observed most frequently in chickens but hasalso been described in captive and free-ranging birdsin the skin of the head, eyelids, neck, chest, wings oraround the beak (Color 25.9).6,7,15,29,49,59,108,135,142

Grossly, these neoplasms appear as multiple, raisedmasses with central craters or ulceration (Color 25.7).Multiple neoplasms usually are present, involvingboth feathered and unfeathered areas of the skin. Aninteresting recent study indicates that these neo-plasms originate as elevated keratin-filled cysts thatsubsequently ulcerate and flatten. Some lesions maysubsequently resolve as dermal scars.59

Histologically, these dermal squamous cell carcino-mas are characterized by epidermal ulceration andinfiltration of the subjacent dermis by squamouscells. These cells are scattered singly or arranged innests and cords. Infiltration of underlying skeletalmuscle is rare. Laminated keratin pearls may beobserved within epithelial cell cords in companionand free-ranging birds.108 The etiology of multifocal,dermal squamous cell carcinoma of chickens has notbeen determined.

Uropygial Gland Adenoma and Adenocarcinoma:Uropygial gland neoplasms occur sporadically in cap-tive birds, especially budgerigars and canaries.6,102,108

On physical examination, the uropygial gland mayappear enlarged, ulcerated and hemorrhagic (Color25.11). Neoplasia must be distinguished from adeni-tis, which usually requires histologic examination.Partial or complete removal of the affected gland isrecommended (Figure 25.4).

Feather Folliculoma: Feather folliculomas occur pri-marily in canaries and budgerigars.18,108,149 These neo-plasms may appear as discrete, mobile, single or mul-tiple dermal nodules that may ulcerate or hemorrhage(see Color 14). Microscopically, these lesions appearmultilobulated and are lined with irregular, hyperplas-tic, basaloid cells that exhibit feather formation. Basalcells are arranged in barb ridges and undergo abruptsquamous differentiation in the center of the mass,forming laminations of free keratin.108,149

Miscellaneous Basal Cell Tumors and CutaneousCysts: All of these neoplasms present as discrete skinnodules. Basal cell tumors are composed of sheets,nests or cords of basaloid epithelial cells. This cellpopulation does not exhibit terminal cellular or struc-tural differentiation.5,25,108

Intradermal cystic lesions occasionally are observedin captive and free-ranging birds. Histologically,these lesions often appear cystic as a result of glan-dular differentiation or keratin production. Thosebenign neoplasms that exhibit glandular differentia-tion are cystadenomas.67 Cystic lesions with keratinproduction are classified on the basis of gradual orabrupt keratinization. Gradual keratinization is ob-served with epidermal inclusion cysts, follicular cystsand intracutaneous cornifying epitheliomas.88,108,130

Those cystic lesions with abrupt keratinization in-clude trichoepithelioma and pilomatrixoma.88,108

Miscellaneous NeoplasmsCutaneous Lymphosarcoma: Cutaneous lymphosar-coma is observed in chickens as a manifestation of

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Marek’s disease and may occasionally occur in cap-tive and free-ranging birds.9,100,105 Neoplastic lympho-cytes may exhibit multifocal to diffuse follicular andperifollicular infiltration, producing numerous skinnodules that may ulcerate along feather tracts.20,98 Inpsittacine birds, cutaneous neoplasms may developunder the skin of the face or neck, often in associationwith generalized or systemic lymphosarcoma.9

Mast Cell Tumor: Mast cell tumors have been re-ported in three owls and a chicken.99,124,139 In owls,mast cell neoplasms usually are associated with theskin of the eyelid or auditory meatus, but may alsobe observed in the mouth.124,139 Generally, animalspecies with a higher circulating basophil count havefewer tissue mast cells, which may explain the rarityof mast cell tumors in avian species. Mast cell tumorsappear grossly as raised-to-spherical, pink-to-red,dermal or submucosal masses. In some instances,neoplastic margins may be indistinct or the neoplasmwill demonstrate marked local tissue invasion.124,139

Attempted surgical excision of a mast cell tumor wasunsuccessful in one owl.124

Respiratory System

The avian lung serves as a metas-tatic site for many neoplasms includ-ing fibrosarcoma, adenocarcinoma,hemangiosarcoma, malignant mela-noma, mesothelioma and osteosar-coma (Figure 25.5).12,78,81,102,108,127 Incontrast, primary neoplasms of theavian respiratory system are rare inspecies other than chickens.

Lymphosarcoma and Hemangiosar-coma: Chickens with Marek’s dis-ease (Marek’s lymphoma) often haveherpesvirus-induced pulmonarylymphoid tumors.109 Multicentric he-mangiosarcomas of chickens alsomay originate in the pulmonary pa-renchyma.74,129 Hemangiosarcomasoccur in fowl infected with retrovirusand are discussed under the circula-tory system.

Papilloma: Laryngeal papillomas are observed occa-sionally in psittacine birds, especially Amazon par-rots and macaws.36,55,102 Papillomas also may occurwithin the nares and choanal area.36,55 Clinically,laryngeal papillomas may cause dyspnea. These le-sions may be surgically excised, but will recur ifexcision is incomplete.102

Bronchiolar Adenoma and Adenocarcinoma: Abronchiolar adenoma has been reported in a parrot.108

The neoplasm appeared as a large, lobulated, ade-nomatous nodule within a major bronchus. A bron-chiogenic adenocarcinoma has been reported in aquail, but histologic features of the neoplasm werenot described.49

Fibrosarcoma: A solitary pulmonary fibrosarcomahas been described in a cockatiel. Due to the absenceof other neoplastic nodules, primary pulmonary ori-gin was suggested.27

Ectopic Pulmonary Ossification: Ectopic pulmo-nary ossification may be confused radiographicallywith pulmonary metastasis. This subject is discussedbelow (bone proliferation resembling neoplasia; mus-culoskeletal system).

FIG 25.4 A 36-year-old macaw was presented for evaluation of a progressive mass overthe dorsal spine and straining to defecate. On physical examination, a large mass wasnoted in the area of the uropygial gland and dried excrement had accumulated around thevent. Tenesmus was noted during the physical examination. Radiographs indicated a largemass that had invaded the synsacrum and was displacing the cloaca ventrally. Thehistopathologic diagnosis was adenocarcinoma of the uropygial gland (courtesy of JaneTurrel).

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Ultimobranchial Cyst: Ultimobranchial cysts de-velop from branchial pouch remnants following em-bryogenesis. A large ultimobranchial cyst has beenobserved in the lower neck of a lorikeet. The thyroidgland was displaced by this mass. Histologically, theneoplasm was lined by squamous epithelium andcontained laminated keratin material anddesquamated cells within the cyst lumen.108

Circulatory System

Vasoformative neoplasms originate from endothelialcell proliferation with subsequent formation of ir-regular vascular channels and spaces filled withblood (or rarely with lymph). These neoplasms mayform wherever endothelium exists; however, pre-ferred sites of origin are apparent. Vasoformativeneoplasms are classified as benign (hemangioma,lymphangioma) or malignant (hemangiosarcoma,lymphangiosarcoma).

Vasoformative neoplasms must be distinguishedfrom non-neoplastic conditions such as vascular mal-formations (arteriovenous fistulas and aneurysms),hematomas, excessively vascularized granulationtissue or other neoplasms with a rich blood sup-ply.84,88 Definitive diagnosis requires histopathology.

In chickens, vasoformative neoplasms may arise as asequela to avian leukosis virus,subgroup F infection. These virus-induced neoplasms may progressfrom benign growths to fibrosar-coma-like neoplasms, analogousto Kaposi’s sarcoma in human be-ings.42 In contrast, reports of vaso-formative neoplasms in captiveand free-ranging birds are spo-radic and of undetermined etiol-ogy.14,72,85, 102,108,127,143

On gro ss insp e ct i o n , he-mangiomas and hemangiosarco-mas may appear as single-to-mul-tiple; variably-sized; pink, red orblue-black nodules (blood blis-ters), swellings or multiloculatedmasses within the skin or abdomi-nal viscera.22,74 Internal neo-

FIG 25.5 Radiographs of a four-year-old female African Grey Parrot indicated a large, softtissue mass in the right thoracic area. Histopathology revealed a renal tubular adenocarci-noma with metastasis to the lung, liver and myocardium (see Color 25.13).

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plasms may present as primary abdominal disten-tion from tumor mass or secondary abdominal dis-tention from hemorrhage (hemoperitoneum). Vaso-f o r mat ive n e o p las ms may he mor rhagespontaneously or following minor trauma (palpation)resulting in anemia or exsanguination.19,25,98

Hemangioma: Cutaneous hemangiomas often arisewithin subcutaneous tissues of the dorsum of theneck, wing or legs.15,25,102 Feather follicles also may beinvolved.25 Abdominal hemangiomas may arise in thespleen, liver, kidney or testicular capsule. These lat-ter neoplasms may cause abdominal distention bytumor mass or hemorrhage (hemoperitoneum).22,49,102

External hemangiomas, particularly on the wingtips, are subject to trauma and may bleed profusely.

Cytologic aspirates of hemangiomas are of limiteddiagnostic value and generally consist of blood. En-dothelial cells are rarely observed. Erythrophagocy-tosis, hemosiderin-laden macrophages and hema-toidin crystals may be observed if concomitanthemorrhage is present. Hemosiderin is an iron pig-ment derived from erythrocyte catabolism. This pig-ment appears globular and blue, golden-brown orgreenish-black in Romanowsky-stained cytologypreparations. Hematoidin, a hemoglobin breakdownproduct, appears as small, bright-yellow, parallelo-gram-shaped crystals that are observed most fre-quently within the cytoplasm of macrophages. He-matoma, hemangioma and hemangiosarcoma maybe difficult or impossible to distinguish cytologically.

Histologically, hemangiomas are composed of vari-ably-sized vascular spaces and channels that arelined by flattened endothelium. Occasional solid ar-eas of plump endothelial cells also may be observed.Vascular spaces typically contain blood, plasma orfibrin thrombi. On rare occasions, immature he-matopoietic precursor cells may be adherent to theendothelium.

Hemangiosarcoma: Hemangiosarcomas may arisesingly or in a multicentric pattern. These neoplasmsoften arise in the skin, liver, lungs, spleen, muscle,mesentery, kidney, heart, oviduct, bone orsynovium.19,49,74,102,108,127,128,129,143 Hemangiosarcomasthat develop in the distal diaphysis of long bones mayexhibit aggressive osteolysis and surface hemorrhage(Figure 25.6).143 Hemangiosarcomas may metastasizeto distant tissues including lung, liver or myocar-dium.102,143

Cytologic aspirates are similar to those described forhemangiomas; however, widely scattered pleomor-

phic endothelial cells may be present. These endothe-lial cells usually appear polyhedral-to-spindle-shaped with round-to-oval nuclei and dark-blue, oc-casionally finely vacuolated, cytoplasm. Aspirationsites may hemorrhage profusely.

Histologically, vascular spaces in hemangiosarcomasare lined by plump endothelial cells with hyperchro-matic nuclei. Mitoses may be observed. Neoplastic cellsoften dissect surrounding structures and exhibit vascu-lar invasion. Secondary hemorrhage is common.

Lymphangioma: Birds possess lymphatic channelsbut they appear less well developed than correspond-ing structures in mammals. Lymphangiomas are be-nign neoplasms wherein endothelial cells form lym-phatic channels. These neoplasms are extremely rarein all species, especially birds. Lymphangioma hasbeen reported in the mesentery and spleen of a rheaand budgerigar, respectively.72,102 However, the budg-erigar neoplasm closely resembled an he-mangioma.102

Histologically, these neoplasms consist of vascularchannels lined by flattened epithelium and filledwith lymph. Lymph appears as a homogeneous, light-pink substance.

Musculoskeletal System

Neoplasms of Smooth and Striated MuscleNeoplasms originating from striated or smooth mus-cle that are benign or malignant are observed occa-sionally in captive and free-ranging birds. Muscleneoplasms presumably arise from embryonic rem-nants of myotomes, from pluripotential cells of em-bryologic structures or from neoplastic transforma-tion of myoblasts during degeneration or repairprocesses.88 Generally, smooth muscle neoplasms arereported about twice as frequently as striated muscletumors. Furthermore, malignant neoplasms are re-ported twice as frequently as their benign counterparts.

Leiomyoma: Leiomyomas are benign neoplasmsthat generally are nodular and may arise fromsmooth muscle of the gastrointestinal or female re-productive tract, especially the oviduct. Other sitesof origin include smooth muscle trabeculae within thespleen or smooth muscle associated with vessels or

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ducts in the pancreas.15,102,108 Leiomyomas usuallyexhibit slow growth and may be associated with ab-dominal distention, gastrointestinal or reproductivetract obstruction, or organ displacement.

Cytologic aspirates and imprints are sparsely cellu-lar, containing only scattered free nuclei or a fewspindle cells with elongate nuclei. Histopathologyreveals a uniform population of elongate cells ar-ranged in broad, interlacing bands. These cells havecigar-shaped nuclei and eosinophilic cytoplasm. Mi-toses are observed infrequently.

Leiomyosarcoma: Leiomyosarcomas are the mostcommon muscle neoplasm reported in captive andfree-ranging birds.15,102 They may arise from smoothmuscle in any location, but usually arise from splenicsmooth muscle trabeculae.12,15,102 Other sites of origininclude crop, intestinal tract, trachea, pancreas, ovi-duct, ventral ligament of the oviduct, vas deferensand testicular capsule.12,15,25,102,133 Leiomyosarcomasmay be locally invasive. Metastasis is a late and infre-quent event, but has been documented to involve theliver, spleen, thoracic cavity and bone marrow.15,119

Cytologic imprints of leiomyosarcomas may containfree nuclei and a pleomorphic but sparse populationof spindle cells. Distinguishing leiomyosarcomasfrom fibrosarcomas may be difficult cytologically.Grossly, excised neoplasms appear firm, pink, poorlydelineated and unencapsulated. Microscopically,leiomyosarcomas are hypercellular with spindle cellsarranged in sheets, interlacing bundles or whorls.Neoplastic myocytes have plump often pleomorphicnuclei, occasional nucleoli and variable amounts ofeosinophilic cytoplasm.

Rhabdomyoma: Rhabdomyomas are benign neo-plasms of striated muscle and are the rarest muscleneoplasm reported in captive birds. Reported sites oforigin include the wing, tongue and eyelid.12,15,108

These neoplasms may be solitary or multinodular,blending with surrounding skeletal muscle.

Cytologic aspirates are unrewarding except for pos-sible fragments of striated muscle cells. Histologi-cally, rhabdomyomas are composed of cells rangingfrom a fibroblast appearance to multinucleated cells.Most cells have distinct fibrillar cross striations.Some cells may appear vacuolated and have highglycogen content demonstrated by diastase-labile,periodic acid Schiff (PAS)-positive granules.88

Rhabdomyosarcoma: Rhabdomyosarcomas are ofskeletal muscle origin and frequently present as ir-regular, elevated, lobulated, relatively firm subcuta-neous swellings of the wing or shoulder that limit theuse of the wing.12,15,51,102 Because these neoplasmsblend with surrounding skeletal muscle, they areimmobile or firmly attached on palpation. Less fre-quently, neoplasms will arise from other sites suchas the dorsal lumbar musculature.107 Metastasis tothe abdominal cavity and liver was reported in onebird.107

Cytologic studies of rhabdomyosarcomas have notbeen reported. Microscopically, the neoplasms arecomposed of a pleomorphic population of fusiform-to-elongated cells. Anisokaryosis may be prominentwith plump oval-to-elongated nuclei. Some elongatedor “strap cells” will retain cross striations typical ofskeletal muscle cells. Phosphotungstic acid hema-toxylin (PTAH) staining may facilitate identificationof these cross striations.

Neoplasms of Cartilage and BoneNeoplasms arising from cartilage and bone are ob-served occasionally. Osseous neoplasms usually arisefrom the long bones, while cartilaginous neoplasmsoften arise on the foot. Cytology may suggest the

FIG 25.6 A dove was presented with lameness and a large swellingof the metatarsal area. Radiographically, the mass involved prolif-eration of soft tissues and osteolysis resulting in a pathologicfracture. The histologic diagnosis was hemangiosarcoma (courtesyof Jane Turrel).

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presence of mesenchymal neoplasia by demonstratinga pleomorphic population of spindle-to-polyhedral cellsand possible matrix material; however, histopathologyis required to determine whether the neoplasm origi-nates from cartilage or bone and to determine whetherthe neoplasm is benign or malignant.

Chondroma: Chondromas are reported occasionallyin captive and free-ranging birds, especially of theorder Anseriformes.108 Grossly, these neoplasms maybe single or multiple. They often arise on the plantarsurface of the foot pad where they may be subjectedto trauma with subsequent hemorrhage and ulcera-tion of the overlying epidermis.108 Other sites of originof chondromas include the cranium (especially incanaries) and proximal humerus (Figure 25.7).108

Histologically, these neoplasms consist of nodular,encapsulated foci of developing chondrocytes sepa-rated by connective tissue septa. Variable amounts ofsulfated mucopolysaccharide matrix and lacunaemay be observed.

Chondrosarcoma: Chondrosarcomas are very rare incomparison to chondromas. A chondrosarcoma hasbeen reported involving the metatarsal-phalangealjoint of a ruffed grouse; however, the histologic ap-pearance of the lesion is similar to a multilobularchondroma.25,127

Osteoma: Osteomas are observed infrequently inbirds compared to osteosarcomas. Osteomas mayoriginate from the cranium, scapula, tarsometatar-sus, plantar foot pad and elbow joint.6,12,49,51,108 His-tologically, osteomas are small, well encapsulatednodules composed of disorganized bony trabeculaeand are attached to adjacent bone.108 Surgical exci-sion is the treatment of choice.

Osteosarcoma: Osteosarcomas occur 3.5 times morefrequently than osteomas and usually originate fromthe proximal or distal portion of long bones includingthe radius, humerus, femur, tibiotarsus and tar-sometatarsus (Figure 25.8).5,6,12,51,72,81,102,108 Less fre-quent sites of origin include the ribs, phalanges,cranium, orbit and coccyx.6,102,108 Osteosarcomas maymetastasize widely to such sites as the lungs, liver,kidney, ovary, mesentery and other bones (Color25.16).81

Histologically, osteosarcomas are composed of poly-hedral-to-spindle mesenchymal cells that produceosteoid. Bony trabeculae may be present but disor-ganized. Scattered islands of cartilage, fibrous con-nective tissue, and myxomatous matrix also may bepresent.108 Scattered mitotic figures may be ob-served.

Bone Proliferation Resembling NeoplasiaRadiographically, skeletal hyperostostosis is recog-nized by increased medullary bone density, increasedbone thickness and deformities involving one or mul-tiple long bones. The differential diagnosis for in-creased medullary opacity of long bones includesosteopetrosis, polyostotic hyperostosis, metastaticneoplasia, hypertrophic osteopathy and metabolicbone disease.

Osteopetrosis: Osteopetrosis is defined as markedsubperiosteal proliferation of bone resulting in loss ofmedullary space, increased bone thickness and de-formity. Osteopetrosis in chickens occurs sporadi-cally and is caused by leukosis/sarcoma virus infec-tion. Depending upon the strain of virus,osteopetrosis may be experimentally induced withinone to three months of virus inoculation with a dis-ease frequency of 60-100%.125,126

Histologically, decalcified sections of bone demon-strate marked proliferation of porous subperiostealbone. Osteoclast numbers are normal, but a markedincrease in osteoblastic activity exists.109,125,126

FIG 25.7 A mature cockatiel from an aviary flight was presentedwith a mass that had been progressing in size for a year. The masswas fluid-filled (serosanguinous), and cytologic evaluation of thefluid was nondiagnostic. The mass was excised and the craniumformed the base of the mass. The bird recovered uneventfully.Histopathology indicated a bone cyst. Trauma was considered themost likely cause (courtesy of Tom Tully).

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Ovarian and Oviductal Neoplasms and Cysts:Cystic ovaries, oviductal carcinoma and ovarian neo-plasms may induce generalized or localized bone for-mation in companion birds.5,12,132 Increased medul-lary bone density is apparent on survey radiographs.Histologically, the increased medullary density is theresult of formation of bone spicules throughout themarrow cavity.

Ectopic Pulmonary Cartilage and Bone: E c t o p i cpulmonary cartilage and bone formation may be ob-served in the lung parenchyma of chickens, especiallybroilers.16,109,150 The incidence varies with the strainof bird, suggesting a genetic predisposition to thiscondition. This condition probably represents abnor-mal embryonic induction of mesenchyme or germcells displaced from adjacent bronchi during develop-ment.150 Alternatively, osseous or cartilaginous meta-plasia also may explain the development of this con-dition. Histologically, nodules of cartilage or bone arepresent within the pulmonary parenchyma.109,150

Ectopic pulmonary ossification has been observed inan Orange-winged Amazon Parrot and a SenegalParrot. Survey radiographs in both birds detectedmultifocal opacities throughout the lung fields, sug-gesting deep mycosis or metastatic neoplasia. Lungbiopsy specimens, however, contained only small fociof osseous tissue within the parenchyma.

Urogenital System

Neoplasms of the urogenital system are reportedfrequently, especially in budgerigars. In a recent sur-vey, urogenital tumors accounted for 12.5% (7.3%renal and 5.2% genital) of all neoplasms in a diverseavian population.108 Surveys in budgerigars indicatean 11.2 to 66.0% incidence of urogenital neo-plasia.7,12,15,92 Testicular neoplasms of captive andfree-ranging birds are approximately three times ascommon as ovarian and oviductal neoplasms. Thisobservation may be explained partially by the pres-ence of bilateral testes in the male but only onefunctional ovary and oviduct in the normal hen.

Larger neoplasms may cause abdominal distentionor respiratory embarrassment. Some renal, testicu-lar, ovarian and oviductal neoplasms may cause uni-lateral or bilateral leg paresis or paralysis with diffi-culty or inability to perch.12,51,92 This occurs becausethe nerves of the sacral plexus pass through the midportion of the kidney where they are subject to com-pression or infiltration by neoplastic cells. Lastly,gonadal neoplasms may be associated with variousparaneoplastic syndromes such as feminization or

FIG 25.8 A nine-year-old Sulphur-crested Cockatoo was presented with a left limb lameness. An initial radiograph (left) indicated osteolysisof the distal femur that was diagnosed as osteomyelitis. A second radiograph (middle) taken seven weeks later indicated increased softtissue swelling and osteolysis. A biopsy was non-diagnostic. A third radiograph (right) taken three months after initial presentationindicated a pathologic fracture with marked osteolysis. The histologic diagnosis was anaplastic sarcoma.

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masculinization and localized or polyostotic hyperos-tosis (Figure 25.9).5,6,12,92,102,132 Feminization or mas-culinization is most apparent in budgerigars wherethe male’s cere may change from blue to brown, or thefemale’s cere may turn from brown to blue (see Color24).6,12,102

Renal NeoplasmsRenal neoplasms are observed occasionally in free-ranging and captive birds, especially budgerigars.Renal neoplasms usually occur unilaterally, but mayoccur bilaterally, and presenting complaints gener-ally include an inability to perch or ambu-late.12,51,102,108 Abdominal enlargement and articulargout also may occur.12

The etiology of renal neoplasms is obscure, but theymay originate from embryonal nests in the aviankidney. In poultry, renal neoplasia is usually a se-quela to avian leukosis virus infection.101

Renal neoplasms are difficult to manage surgically.Renal carcinomas may aggressively invade adjacentmuscle and bone. Because the kidneys are located inthe renal fossae, neoplasms are difficult to isolate andexcise (Figure 25.10). The sacral plexus passes throughthe mid portion of the kidney and is subject to trauma.Finally, the kidneys are highly vascular and markedhemorrhage is expected. Treatment of renal neoplasmsusing radioisotope implants appears promising, butwill require further evaluation.143

Renal Carcinoma: Renal carcinoma is the most fre-quently observed renal neoplasm in captive and free-ranging birds.7,12,41,49,69,71,85,102,108,144 Renal adenocarci-nomas may infiltrate adjacent muscle and bone withextension into the spinal canal. Distant metastasis tothe liver and oviduct may occur, but is unusual (Color25.13).69,71

Affected kidneys contain large, pale, multilobulatedmasses. Histologically, these neoplasms are com-posed of vesicular epithelial cells arranged in sheets,nests, cords or tubules. Epithelial cells may be cuboi-dal to columnar, especially those cells involved intubular formation. Fibrovascular stroma may beprominent. A few multinucleated cells and scatteredmitoses may be observed within the neoplasm.102,108

Renal Adenoma: Renal adenomas are benign neo-plasms that are observed infrequently compared torenal adenocarcinomas.7,49,85 Although gross enlarge-ment of a portion of the kidney is apparent, themicroscopic appearance of the tissue may be unre-markable-to-subtle in comparison to the normal kid-ney. Epithelial cell cytoplasm may be slightly morebasophilic. Compression of adjacent normal paren-chyma occurs as the neoplasm slowly enlarges.

Embryonal Nephroma: Embryonal nephroma(nephroblastoma, Wilms’s tumor) has been observedmost commonly in chickens infected with leukosis(sarcoma) virus. In chickens, these neoplasms usu-

ally are unilateral but may arise bi-laterally.23,101,109 In captive and free-ranging birds, these neoplasms areobserved occasionally, especially inbudgerigars.12,15,102 The literaturesuggests they are more frequent thanadenomas but less common than ade-nocarcinomas. These neoplasms arebelieved to arise from themetanephric blastema.88

On gross inspection, embryonalnephromas cannot be distinguishedfrom renal adenocarcinomas. His-tologically, epithelial cells are ar-ranged in solid masses of variably-sized tubules or cords. Characteristicfeatures include the formation of tu-bules and glomerulus-like struc-tures. Variable quantities of me-senchymal stroma may be present,which further undercores the em-bryonal nature of the neoplasm.88,102

Rare metastasis to the liver and

FIG 25.9 A five-year-old male budgerigar was presented because of a change in cere color(from blue to pink), abdominal distention and unilateral leg paresis. Radiographs indi-cated a large soft-tissue opacity in the abdomen and polyostotic endosteal hyperostosis ofthe long bones. The clinical and radiographic findings were highly suggestive of a gonadaltumor. Histopathology confirmed a sertoli cell tumor, which was probably secreting lowlevels of estrogen (courtesy of Jane Turrel).

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spleen may occur, but is poorly docu-mented.15

Testicular NeoplasmsTesticular neoplasms are usuallyunilateral, but may occur bilaterally.With unilateral neoplasms, atrophyof the contralateral testis may be ob-served. In rare instances, a collisiontumor may be observed in which twoor more cell lines are involved in theneoplastic process.12 Cytologic stud-ies have not been performed on aviantesticular neoplasms. Definitive di-agnosis of the following neoplasms isdependent upon histopathologic ex-amination. Orchiectomy is the treat-ment of choice but must be initiatedearly for a successful outcome.

Sertoli Cell Tumor: Sertoli cell tumor is one of themost frequent testicular neoplasms encountered incaptive and free-ranging birds.5,12,49,51,53,102,108 Thesecells constitute a portion of the intratubular gonadalstroma, secreting testicular fluid and nourishing de-veloping spermatids. If neoplastic Sertoli cells aresynthesizing estrogen, feminization may be present.This phenomenon is most noticeable in male budgeri-gars in which the cere color changes from blue tobrown (Figure 25.11).12

Neoplastic testes appear as enlarged, pale, firm,nodular masses. Neoplasms may have a pink tingesecondary to central necrosis and hemorrhage. Vari-ably sized, fluid-filled cystic spaces also may be pre-sent.53,108 Serosal metastases are unusual but mayoccur.108

Histologically, Sertoli cell tumors are composed ofsheets, lobules and islands of cells. Cells withinseminiferous tubule remnants may palisade. Individ-ual neoplastic cells are elongate with round-to-ovalbasal nuclei. Cytoplasm is abundant, eosinophilic, andoccasionally vacuolated. The mitotic rate is variable. Adelicate-to-dense fibrovascular stroma is present.53,108

Seminoma: Seminomas are neoplasms of germ cellorigin. These tumors also occur frequently in captiveand free-ranging birds.5,12,44,49,51,54,85,102,108,141 The mostcommon clinical signs include dyspnea, lethargy,anorexia, ascites and abdominal enlargement (occa-sionally with a palpable intra-abdominal mass).44

Seminomas infrequently may be associated withsigns of feminization in budgerigars.12

FIG 25.10 A Quaker Parakeet was presented for evaluation of apericloacal and abdominal swelling. Radiographs indicated a renalmass that had invaded the synsacrum, causing osteolysis craniallyand sclerosis caudally. The mass extended dorsally to the syn-sacrum and ventrally into the abdomen. The histopathologic diag-nosis was renal carcinoma (courtesy of Jane Turrel).

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Neoplastic testes appear large, white-to-gray, firmand oval. Small cystic spaces also may be present.Occasionally, adherence to the kidneys, ureters anddorsal body wall may be observed.44,108 Seminomasare generally considered benign; however, metasta-sis to the liver may occur, presumably as a lateevent.5,49,54,102

Histologically, seminomas are composed of pleomor-phic germinal epithelial cells arranged in sheets,nests and irregularly shaped tubules. Seminiferoustubules may be filled, distended or disrupted by neo-plastic cells. Nests and tubules of neoplastic germcells are separated by thin bands of connective tissue.Individual cells are round-to-polygonal and exhibitanisocytosis. Nuclei are large and round with hyper-chromatic, coarsely clumped chromatin and indis-tinct nucleoli. Multinucleated tumor cells and bi-zarre mitotic figures may be observed frequently.44

Interstitial Cell Tumor: Interstitial (Leydig) cell tu-mor is the least frequently reported gonadal stromaltesticular neoplasm of birds.12,102,108 Neoplastic testesappear enlarged, fleshy, and occasionally cystic.12,108

The contralateral testis may be atrophied (Color25.4).12

Microscopically, interstitial tumors have a dense fi-brovascular stroma that divides the neoplasm intolobules. Individual neoplastic cells are large andpolyhedral, containing eccentric nuclei and vacuo-lated eosinophilic cytoplasm.108 The vacuolated cyto-plasm is a reflection of steroid hormone (testoster-one) production.

Miscellaneous Testicular Neoplasms: Lympho- sar-coma (Marek’s disease, Marek’s lymphoma) is the

most frequent testicular neoplasm of chickens. Thisneoplasm is herpesvirus-induced.20,109

The testicular capsule or testis may be the site oforigin for hemangioma, fibrosarcoma and leiomyo-sarcoma.102,108 Both carcinoma and leiomyosarcomahave been reported to arise from the epididymis andvas deferens, respectively.12 Teratomas also mayarise in the testis and are discussed under neoplasmsof the nervous system.23,63,112

Ovarian and Oviductal NeoplasmsOvarian neoplasms are reported more frequentlythan neoplasms arising from the oviduct. Clinicalsigns may include abdominal distention, ascites,dyspnea, intra-abdominal mass and leg paresis orparalysis. Usually the left leg exhibits paresis orparalysis initially, but both limbs ultimately may beaffected. Paraneoplastic syndromes that may be ob-served in conjunction with ovarian and oviductalneoplasms include localized exostosis or polyostotichyperostosis.5,132

Ovarian neoplasms are classified histologically ac-cording to cell lineage. Granulosa cell tumors aregonadal stromal neoplasms that originate from sup-portive tissues and are the most common type ofovarian neoplasm. Ovarian carcinomas are of epithe-lial cell origin and comprise the second most frequentclassification of ovarian neoplasia. Dysgerminomasare germ cell tumors that are analogous to seminomain males. This neoplasm is very rare and has beenreported only in poultry and budgerigars.7,23 Oviduc-tal neoplasms are also described, and most of thesetumors are of epithelial cell origin. Ovariectomy orsalpingectomy is the treatment of choice.

Granulosa Cell Tumor: Granulosa cell tumors arethe most frequently reported ovarian neoplasm incaptive and free-ranging birds.12,28,49,51,102,108 These go-nadal stromal neoplasms appear as large, pale, nodu-lar masses. Central necrosis and hemorrhage may bepresent and impart a pink color to the neoplasm.

Histologically, these neoplasms are composed of is-lands of epithelial-like cells separated by fibrovascu-lar stroma. Cells may form tubules or palisadesaround blood vessels. Individual neoplastic cells havecytoplasmic vacuoles. Plump, theca-like cells may bescattered throughout the neoplasm.108

Ovarian Carcinoma: Ovarian carcinomas or ade-nocarcinomas are the second most frequently re-ported neoplasm originating in theovary.12,28,31,51,102,108,134,145 These neoplasms may appear

FIG 25.11 A mature male budgerigar was presented with a pro-gressive growth and discoloration of the cere. Brown hypertrophyof the cere is frequently encountered in older budgerigars withgonadal neoplasms. The hypertrophied tissue can be moistenedwith skin-softening creams and gently peeled away.

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as large, firm, cystic, multilobulated-to-pedunculatedmasses.

Limited cytologic study of one ovarian cystadenocar-cinoma in a budgerigar demonstrated putative neo-plastic cells in abdominal effusion fluid.28 A few largeepithelial cells were observed that had oval nuclei,prominent nucleoli and abundant blue cytoplasm.Anisocytosis and occasional mitotic figures also wereobserved.28 Histologically, ovarian carcinomas are com-posed of epithelial cells arranged in nests, cords, tu-bules and cysts. Foci of epithelial cell proliferation areseparated by connective tissue septa. Papillary projec-tions of epithelial cells may protrude into the cysts.Cystic spaces may contain a homogeneous eosinophilicsecretory product. The mitotic rate is variable.

Ovarian carcinomas may metastasize to the mesen-tery, intestinal serosa, liver, lung, pancreas, muscleand bone.31,134,145

Miscellaneous Ovarian/Oviductal Neoplasms:Stromal tissues of the ovary are infrequent sites oforigin for lipomas and fibrosarcomas.12,108 Teratomasalso may originate in the ovary and are discussedunder neoplasms of the nervous system.23

The oviduct and ventral ligament of the oviduct occa-sionally are the sites of origin of leiomyomas andleiomyosarcomas.102,108

Oviductal Dysplasia, Adenomatous Hyperplasia,Adenoma and Adenocarcinoma: Studies of repro-ductive tracts from turkey hens suggest a progressionof oviductal lesions in the development of neoplasia.13

Preneoplastic changes include epithelial dysplasiaand adenomatous hyperplasia. With time, these le-sions may progress to oviductal adenoma and adeno-carcinoma.12,13,15,49,108,132 Oviduct adenocarcinomasmay metastasize to abdominal serosal surfaces.15

Grossly, oviduct adenomas and adenocarcinomasmay appear as firm nodular masses. Carcinomatosis,if present, will appear as multiple, small white nod-ules on serosal surfaces. Polyostotic hyperostosis is arare paraneoplastic syndrome associated withoviductal adenocarcinoma.132

Histologically, oviductal adenomas and adenocarci-nomas are composed of sheets, nests, cords and tu-bules of cuboidal-to-elongate epithelial cells. Fi-brovascular stroma is variable, but fibroplasia ismore intense with adenocarcinomas.

Carcinomatosis: Carcinomatosis is the seeding ofthe thoracoabdominal cavity with neoplastic cells

that subsequently proliferate, forming variably sizedwhite nodules. Carcinomatosis may be observed withovarian and oviductal adenocarcinomas, intestinaladenocarcinoma, pancreatic adenocarcinoma,mesothelioma and undifferentiated adenocarcinoma(Figure 25.12).15,31,56,77,85,108,127,134 The pattern of metas-tasis may be governed partially by serosal mem-branes within the body cavity.77 Both disseminatedmycobacteriosis and egg-related peritonitis of hensmay mimic neoplasia clinically and at necropsy. Bothcytology and histopathology can confirm the presenceof carcinomatosis.77

FIG 25.12 Carcinomatosis secondary to an anaplastic pancreaticcarcinoma in a mature cockatiel (see Color 25.6) (courtesy CherylGreenacre).

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Digestive System

Oral CavityPapilloma: Papillomas are composed of proliferativesquamous epithelium with a fibrovascular stroma.Oral papillomas are occasionally encountered, espe-cially in psittacine birds, and may involve the oro-pharyngeal, choanal or laryngeal regions of the phar-ynx.24,36,55 Papillomas may undergo malignanttransformation to squamous cell carcinoma.

Squamous Cell Carcinoma: Squamous cell carcino-mas are second to papillomas in frequency and mayinvolve the oral cavity and tongue.3,33,72 These carci-nomas appear as ulcerative-to-cauliflower-like, pain-ful lesions or masses that are associated with inap-petence, dysphagia, regurgitation, halitosis andfrequent head shaking.3,33,143 The differential diagno-sis for this lesion should include oral neoplasia, hy-povitaminosis A, trauma, candidiasis or protozoalinfection (trichomoniasis).

Cytologic examination may demonstrate a pleomor-phic population of epithelial cells, but squamous cellhyperplasia and squamous cell carcinoma may bedifficult or impossible to distinguish. Histologically,squamous cell carcinomas are composed of sheets,nests and cords of pleomorphic epithelial cells thatinfiltrate adjacent tissues. Anisocytosis, an-isokaryosis, dyskeratosis and intercellular bridgesusually are observed. Keratin pearl formation andadenoid patterns are observed less frequently. Themitotic rate is variable. Squamous cell carcinomasmay be accompanied by inflammation and a scir-rhous reaction. Local infiltration of surrounding tis-sues is common, but metastasis is rare.

Miscellaneous Neoplasms: Miscellaneous oral neo-plasms include a mast cell tumor in an owl and afibrosarcoma in a budgerigar.102,124 These neoplasmsare discussed in detail under the integumentary sys-tem. Mucinous adenocarcinoma of the tongue alsohas been described in an owl (Figure 25.13).45

Esophagus and CropSquamous Plaque: Squamous plaques are focal ormultifocal thickening of stratified squamous epithe-lium that may be accompanied by dysplastic change.This lesion has been described as an “epithelioma” inthe crop of a pigeon.108 Squamous plaques are caused

by chronic irritation and may undergo neoplastictransformation.

Papilloma: Papillomas account for the vast majorityof neoplasms observed on the mucosal surfaces of theesophagus and crop, especially in psittacine spe-cies.24,36,55,108 Papillomas may undergo malignanttransformation.

Squamous Cell Carcinoma: Squamous cell carci-noma of the crop has been observed in a budgerigarand an Amazon parrot.15,90 The most detailed descrip-tion is given for the Amazon parrot.90 Grossly, theesophageal wall was thickened (Figure 25.14). Theneoplasm was circumferential with a dry, white, cau-liflower-like surface (Color 25.8). Microscopically, theneoplasm was composed of aggregates of pleomorphicsquamous epithelial cells that extended into the sub-mucosa.

Leiomyosarcoma: A multifocal leiomyosarcoma hasbeen reported to originate in the crop wall of a budg-erigar. The only clinical sign attributed to this neo-plasm was difficulty in swallowing.102

Proventriculus and VentriculusNeoplasms of the proventriculus are approximatelytwice as common compared to neoplasms of the ven-triculus. Adenocarcinomas are most commonly ob-

FIG 25.13 Radiographs of the head of an Umbrella Cockatoo indi-cate the extent of a sublingual mass. Granulomatous response isconsidered a precursor to some oral tumors (see Color 25.20).

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served and often arise from the junction of these twoorgans.

Proventricular Carcinoma: Proventricular carci-noma is the most frequent neoplasm observed in thisorgan.79,80,104,108,123,143 These neoplasms are more com-mon in psittacine species, especially Grey-cheekedParakeets.79,104,123

On gross inspection, proventricular carcinomas ap-pear as ulcerated, thickened, raised or depressedlesions. Clinically, gastrointestinal bleeding, as de-termined by observation of melena, anemia or a posi-tive fecal occult blood test, should alert the clinicianto the possibility of gastrointestinal neoplasia. Se-vere bleeding, hypovolemic shock or exsanguinationmay occur.79,104 Proventricular carcinomas may ex-hibit rare transmural extension with serosal metas-tasis to the ventriculus, intestine and pancreas orhematologic metastasis to the spleen, liver, lungs andheart base.79,108

Microscopically, these neoplasms are composed ofcolumnar-to-cuboidal-to-squamous epithelial cellsarranged in a tubuloacinar pattern. Individual cellshave vesicular nuclei and eosinophilic-to-basophiliccytoplasm. Mitotic figures may be observed fre-quently. Many neoplasms are associated with a scir-rhous reaction. The luminal surface of the neoplasmis often ulcerated, while deep margins of the neo-plasm exhibit invasion of the muscularis.79,104,108 Pe-

riodic acid-Schiff (PAS) and alcianblue staining may help differentiateproventricular and ventricular carci-nomas. Proventricular carcinomacells and the secretory product arestrongly PAS-positive and stain darkpink. In contrast, the koilin secretoryproduct of ventricular epithelial cellsis alcian blue-positive and appearsbright blue.79,104

Ventricular Carcinoma:Ventricular carcinomas are infre-quent in comparison to proventricu-lar carcinomas but the clinical signsare similar (Figure 25.15).79,104 Theseneoplasms have not been reported tometastasize. Microscopically, the ap-pearance of ventricular carcinoma issimilar to proventricular carcinomaexcept secretory cells are PAS-nega-tive. The koilin secretory product isstrongly alcian blue-positive. A sin-gle ventricular adenoma has been re-ported in a parrot but the neoplasm

was not characterized.49

Papillomas: Papillomas are reported to occur withinthe proventriculus and ventriculus.24,55 They are ap-parently more common in the ventriculus.55

Proventricular Adenoma: A proventricular ade-noma has been observed in a teal. On gross examina-tion, the proventriculus was spherical instead of fusi-form. The luminal surface was covered by ahemorrhagic, fibrillated, plaque-like mass. Histologi-cally, the mass was composed of tubuloacinar struc-tures lined by one-to-four layers of short, columnarepithelial cells. Cellular nuclei were centrally lo-cated, vesicular and had a small nucleolus. Cellularcytoplasm was basophilic. Few mitotic figures wereobserved and fibrovascular stromal tissue was mini-mal. Hemorrhage and necrosis were present near theluminal surface.8

IntestineAlthough rare, some neoplasms originating in thesmall intestine have been reported. Intestinal neo-plasms can best be managed by surgical excision andintestinal anastomosis if the lesions are diagnosedearly, if metastasis has not occurred and if the sitecan be adequately exposed.

FIG 25.14 An esophagram of an adult Amazon parrot indicated an irregular mucosalfilling pattern in the distal esophagus suggestive of a mass (see Color 25.8) (courtesy ofJane Turrel).

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Leiomyosarcoma: Primary intestinal leiomyosarco-mas have been observed in budgerigars. Metastaticlesions were not observed.15,133

Intestinal Carcinoma: Intestinal carcinoma hasbeen reported in a budgerigar, duck and gull.15,49,72

Metastatic foci were observed within the lung, liverand spleen.72

CloacaCloacal neoplasms and masses, including papillo-mas, adenocarcinomas, and adenomatous polyps andhyperplasia are observed most commonly in psitta-cine birds, especially Amazon parrots.35,37,49,51,55,65,102,136

Cloacal Papilloma: Cloacal papillomas are recog-nized frequently in psittacine birds.37,55,65,102,136 Cloa-

cal papillomas and bile duct carcinoma may showconcurrent development, especially in Amazon par-rots.55,65 Grossly, cloacal papillomas appear as broad-based, pink-to-red, proliferative-to-ulcerativemasses. They may closely resemble granulation tis-sue (see Color 19). Major clinical signs associatedwith cloacal papillomas are straining, bleeding fromthe vent and cloacal prolapse. A viral etiology hasbeen suggested for these neoplasms, but has yet to beconfirmed.136

Histologically, cloacal papillomas are composed ofhyperplastic epithelium over a base of fibrovascularstroma. The epithelium may vary from 10- to 50-celllayers in thickness. Depending upon the biopsy site,epithelial cells may exhibit a transition from colum-nar to squamous morphology. Epithelial cells on theluminal surface may contain basophilic intracyto-plasmic mucin granules that can be demonstrated byalcian blue and mucicarmine staining.136

Cloacal Carcinoma: Cloacal carcinomas are ob-served infrequently compared to papillomas.49,51,102,136

Histologically, these neoplasms contain a more pleo-morphic epithelium, characterized by dysplasia andbizarre mitoses.136 Transmural cellular invasion andpenetration of the cloaca may be associated withsclerosing fibroplasia.51,102

Cloacal Adenomatous Polyp or Hyperplasia:Histologically, these lesions are characterized by epi-thelial cell hyperplasia resulting in a visiblemass.35,102 It seems reasonable that a progression ofcloacal lesions occurs, ranging from hyperplasia toneoplasia (usually benign papillomas). Furthermore,cloacal papillomas may rarely undergo malignanttransformation to adenocarcinomas.

Hepatic NeoplasmsBoth primary and metastatic neoplasia occur in theliver. The most frequent primary hepatic neoplasmsare hepatocellular carcinoma and bile duct carci-noma. Conditions that must be differentiated fromneoplasia include hepatic nodular hyperplasia, bileduct hyperplasia and biliary cysts (see Color 20).

Cholangiocarcinoma: Cholangiocarcinoma (cho-langiocellular carcinoma, bile duct carcinoma) origi-nates from bile duct epithelium. This is the mostfrequent hepatic neoplasm reported in captive andfree-ranging birds (lymphoid neoplasms are mostcommon in gallinaceous birds).1,2,5,49,50,72,102,103,108,147,148

Specific clinical signs are infrequent, although ema-ciation, weakness, hepatomegaly, ataxia, trembling

FIG 25.15 A six-year-old male budgerigar was presented with ahistory of regurgitation and weight loss. Radiographs taken 30minutes after the administration of barium sulfate indicated fill-ing defects in the proventriculus (consistent with ingesta) and anindistinct and irregular mucosal pattern in the lateral wall of theventriculus (arrows) (consistent with neoplasm) (courtesy of JaneTurrel).

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and seizures have been observed.2,50,148 Some neu-rologic signs are suggestive of hepatoencephalopathy.

On gross inspection, the hepatic parenchyma con-tains numerous, variably sized, firm, white-to-tannodules. Histologically, these neoplasms consist ofcolumnar-to-cuboidal epithelial cells arranged in rib-bons, cords, tubules or ducts. Infiltration of the he-patic parenchyma is apparent. A few mitotic figuresmay be observed. In some neoplasms, a scirrhousreaction may be present.1,2,50,148

Cholangiocarcinomas may exhibit vascular invasionwith subsequent widespread metastasis to the lungs,brain, kidney, pleura and serosa of the ventricu-lus.1,43,72,102,147,148 There is no available treatment forcholangiocarcinoma.

Cholangioma: Cholangiomas are of bile duct epi-thelial origin and are rare in comparison to cholangio-carcinoma.49,108 Cholangiomas may occur as single ormultiple, firm nodules. Histologically, they appear asepithelial-lined tubular structures with a dense fi-brous stroma.108

Bile Duct Hyperplasia: Bile duct hyperplasia is ob-served with some frequency in psittacine birds withliver disease. Bile duct hyperplasia is often seenconcurrently with hepatic fibrosis and hepatocellularlipidosis. The gross and microscopic appearance ofsome livers may mimic cholangiocarcinoma. The eti-ology of bile duct hyperplasia is often undetermined;however, ingestion of mycotoxin-contaminated feedshould be considered in the differential diagnosis (seeChapter 20).

Biliary Cyst: Biliary cysts are reported infrequentlyin birds.95 Such cysts are generally congenital andmay be intra- or extra-hepatic. Biliary cysts may beobserved in conjunction with polycystic kidneys.

Hepatocellular Carcinoma: In captive and free-ranging birds, the incidence of hepatocellular carci-noma is superseded only by cholangiocarci-noma.12,43,51,108 Birds with hepatocellular carcinomafrequently present in a debilitated state with enlarge-ment of one liver lobe. Abdominal enlargement maybe apparent on physical examination.

Antemortem liver lobe enlargement may be con-firmed by radiography, ultrasound, endoscopy or la-parotomy. Postmortem confirmation of liver lobe en-largement is made by visual inspection at necropsy.Neoplasms may vary in size and color, ranging fromlight tan to a more normal red-brown. Microscopi-

cally, these neoplasms are composed of cords of hepa-tocyte-like cells with effacement of normal tissuearchitecture. Bizarre-to-multinucleated hepatocytesmay be observed. Variable numbers of mitotic figuresare present.43,108

Metastases are rare, but when they occur the lungsare usually involved.43,147 Partial or full hepatic lobec-tomy may be attempted to excise these neoplasms.

Hepatocellular Adenoma: Hepatocellular adenoma(hepatoma) is poorly documented in birds, havingbeen reported in a cissa, guineafowl, hornbill andmynah bird.49,72,131,147 The multiple nodules within thehepatic parenchyma of the mynah bird were associ-ated with osseous metaplasia and extramedullaryhematopoiesis. These nodules probably representedhepatic nodular hyperplasia.131

Nodular Hyperplasia: Nodular hyperplasia of theliver may be viewed as attempted parenchymal re-generation following injury. Nodular hyperplasia isusually an incidental finding at necropsy in birdswith evidence of chronic liver disease.64 The grossappearance of these pale nodules may be mistakenfor hepatocellular adenoma or adenocarcinoma. Themost common associations with nodular hyperplasiaare mycotoxin exposure and iron-accumulating hepa-topathy.

Miscellaneous Hepatic Neoplasms: Miscellaneousneoplasms described in the liver include malignantlymphoma, fibrosarcoma, hemangioma, he-mangiosarcoma and lipoma.12,64,102,108,109 Myelolipo-mas also may arise within the hepatic parenchyma.Furthermore, the liver may be involved in hema-tologic neoplasia, which can be difficult to distinguishfrom extramedullary hematopoiesis.

Pancreatic NeoplasmsMost pancreatic neoplasms reported in birds arisefrom the exocrine pancreas, especially ductularstructures. These neoplasms may be single or multi-ple. Neoplasms arising from the endocrine pancreasare rare.

Pancreatic Adenoma: Pancreatic adenomas occur inpsittacine birds, especially Amazon parrots, macawsand budgerigars.15,49,56 In Amazon parrots, pancreaticadenomas may be associated with internal papil-lomas or may be observed as incidental findings atnecropsy.56

On gross inspection, multifocal pancreatic adenomasusually are observed associated with ductular struc-

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tures. Intraductal neoplasms may cause local disten-tion of affected ducts with concurrent compressionatrophy of the adjacent pancreatic parenchyma.56

Histologically, these neoplasms are composed of pro-liferating columnar epithelial cells arranged in cordsor papillary projections. Epithelial cell proliferationmay be accompanied by fibroplasia.56

Pancreatic Adenocarcinoma: Pancreatic adenocar-cinoma may be observed in various species of birdsincluding psittacines, doves, Anseriformes and rat-ites.49,56,72,108,137 These neoplasms occasionally may bequite large, envelop bowel loops and result in abdomi-nal effusion.137 They are not amenable to treatment(Figure 25.16).

Histologically, adenocarcinomas are composed of apleomorphic population of epithelial cells that infil-trate or dissect local tissues. Metastasis may occur,usually by serosal seeding.56 Pancreatic adenocarci-noma should be a diagnostic consideration when car-cinomatosis is observed (Color 25.6).

Endocrine System

The endocrine system is composed of widely distrib-uted tissues, glands and organs. The endocrine sys-tem, in conjunction with the nervous system, main-tains homeostasis by the ability to synthesize, storeand release various hormones. These hormones aredistributed via the blood to effector cells, tissues ororgans where their biological effect is mediated. Neo-plasms usually affect only one endocrine cell type.

Rarely, neoplasia will involve two or more differentendocrine cell lines, a condition called multiple endo-crine neoplasia. Evidence suggests that multiple endo-crine neoplasia occurs in birds as well as in mammals.49

Pituitary GlandPituitary neoplasms are the most frequently re-ported endocrine neoplasm in birds and there is noeffective treatment for them.10,12,102,121

Pituitary Adenoma: Pituitary adenoma is the mostfrequently reported endocrine neoplasm of birds, es-pecially budgerigars.10,12,15,39,49,102,108,121 These neo-plasms often originate from proliferation of chromo-phobe cells in the anterior lobe. Because of theanatomic location of the pituitary gland, expansiveneoplasms follow the path of least resistance, com-pressing the hypothalamus and optic chiasm.Neurologic signs resulting from compression includeincoordination, poor perching or posture, somno-lence, seizures and convulsions, and visual impair-ment including blindness associated with dilated,fixed pupils.10,12,39,102,108,121 Unilateral or bilateral exo-phthalmos may result from neoplastic cell infiltra-tion along the optic nerve(s).121

Pituitary adenomas also may be associated withpolydypsia and polyuria.10,12,39,102 The mechanisms ofpolydypsia and polyuria have not been investigatedin birds, but may be caused by decreased antidiuretichormone (ADH) concentrations or by over-productionof adrenocorticotrophic hormone (ACTH). Compres-sion of the posterior lobe of the pituitary decreasesADH transport and storage with subsequent diure-sis. Excessive production of ACTH might cause adre-nal cortical hyperplasia with excess corticosteronesecretion and steroid-induced diuresis.

Pigment changes such as alterations in feather col-oration pattern and cere color have been reported ina cockatiel and budgerigar; however, hormonalchanges were not investigated.10,39

Necropsy usually reveals a mass in the location of thepituitary that compresses the overlying hypothala-mus. Microscopically, these neoplasms are composedof round-to-cuboidal cells arranged in sheets orsinusoidal patterns containing a delicate fibrovascu-lar stroma. Cells have round nuclei, stippled chroma-tin and variable quantities of cytoplasm. In chromo-phobe adenomas, the cytoplasm stains poorly.Mitoses are infrequent and a remnant of the parsdistalis may be apparent.88

FIG 25.16 Pancreatic carcinoma with involvement of the serosalsurface of the intestines in a cockatiel (see Color 25.6) (courtesy ofCheryl Greenacre).

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Pituitary Carcinoma: Pituitary carcinomas are rareneoplasms in birds, but have been reported and char-acterized in two budgerigars.121 Neoplastic cell inva-sion of the brain and formation of retrobulbar masseshave been observed, along with distant metastasis tothe liver and kidney. Histologically, these neoplasmsare highly cellular and may contain foci of necrosisand hemorrhage. Confirmation of metastasis sup-ports the presumptive diagnosis.

Pineal GlandNeoplasms of the pineal gland are rare. These expan-sive neoplasms may displace or compress adjacentneural tissue resulting in neurologic deficits. Be-cause of their anatomic location, surgical excision ofpineal gland neoplasms is virtually impossible.

Pineoblastoma: A pineoblastoma has been describedin a cockatiel.151 Clinical signs included polydypsia,depression, right-sided head tilt and inability tograsp objects with the right foot.

Necropsy examination disclosed a grey suprathal-amic mass extending into the right ventricle andcompressing the right occipital lobe and thalamus.Microscopically, the mass consisted of sheets, cordsand fewer palisades of round cells with round-to-ovalnuclei, stippled chromatin and lightly basophilic cy-toplasm. A delicate fibrovascular stroma was pre-sent. Occasional mitotic figures were observedthroughout the mass.

Pinealoma: Pinealoma has been reported in twochickens and a dove.22,108,138 The neoplasm apparentlywas an incidental finding in one chicken from a flockexhibiting increased mortality and trembling.138 Theneoplasm in the dove was a serendipitous discoveryduring postmortem assessment of cranial trauma.108

On microscopic examination, the mass was encapsu-lated, cellular and displaced cerebellar folia and ex-tended deeply between them. The mass had a lobulararchitecture, with some lobules containing singlelayers of ciliated columnar-to-pseudostratified-co-lumnar epithelium. Neoplastic cells containedround-to-oval nuclei exhibiting mild anisokaryosis.Mitotic figures were observed occasionally.

Thyroid GlandEnlargement of the thyroid glands may be observedwith hyperplasia or neoplasia. Signs of thyroid glandenlargement may include dyspnea and a distinctivesquawk on vocalization.6,12,118 Their anatomic locationnear the thoracic inlet precludes palpation of massesunless glandular enlargements are extreme.6 Thy-

roid hyperplasia can be managed medically. Theo-retically, thyroid neoplasia can be managed surgi-cally, but diagnosis and extirpation of intrathoraciclesions are difficult.

Thyroid Hyperplasia: Thyroid hyperplasia (goiter)may be associated with iodine-deficient diets, inges-tion of goitrogenic plants such as Brassica species,exposure to iodine-containing disinfectants or exces-sive dietary iodine.88,115 Thyroid hyperplasia is mani-fested by bilateral glandular enlargement. Colloid-distended follicles may result in glandularenlargements reaching 20 mm in diameter.12 Becauseof improved diets for companion birds, thyroid hyper-plasia is reported less frequently than three decadesago.6,12,15,118

On gross necropsy examination, the thyroid glandsare bilaterally enlarged and may appear cystic. His-tologic sections of thyroid gland contain large, irregu-lar follicles that are lined by columnar epitheliumand distended with light-pink colloid. Papillary pro-jections of epithelium may protrude into the lumenof some follicles (see Chapter 23).

Thyroid Adenoma: Thyroid adenomas are usuallyunilateral but may occasionally cause bilateral glan-dular enlargement. These neoplasms usually repre-sent incidental necropsy findings in birds.12,15,49,108

Histologically, thyroid adenomas are poorly charac-terized in birds. Most thyroid adenomas appear asnodules of encapsulated glandular tissue.

Thyroid Carcinoma: Thyroid carcinomas are rareand poorly characterized in birds.12,49,102 Thyroidgland enlargement may be unilateral or bilateral.Dyspnea may be a presenting complaint.102 Histologi-cally, thyroid carcinomas may appear nodular, poorlyencapsulated and invasive. These neoplasms arehighly vascular.

Adrenal GlandIn contrast to mammals, avian adrenal glands haveno distinct cortex or medulla. Both interrenal (corti-cal) and enterochromaffin (medullary) cells are inter-mingled throughout the gland.109 Adrenal neoplasmsare rare in captive and free-ranging birds and havenot been studied in detail. When enlargement of theadrenal glands is observed at necropsy, a primaryconsideration is adrenal gland hyperplasia.

Adrenal Adenoma: Adrenal adenomas arise from in-terrenal (cortical) cells and have rarely been re-

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ported in birds and generally are not associated withclinical signs of disease.15,49,108

Histologically, affected adrenal glands are replacedby a lobulated mass of tubuloacinar tissue. Epithelialcells appear pale with foamy cytoplasm and centrallylocated nuclei. Mitotic figures are uncommon.108

Adrenal Carcinoma: Adrenal carcinoma was de-scribed in a Mountain Duck that was depressed andhad leg paralysis.43

The adrenal gland neoplasm was unilateral and com-posed of a pleomorphic population of polyhedral-to-elongated cells arranged in a frond-like pattern.Marked anisocytosis and anisokaryosis was appar-ent, including the presence of tumor giant cells. Mi-toses were observed infrequently. Neoplastic cellsinfiltrated adjacent nerves.43

Pheochromocytoma: A single pheochromocytomahas been reported in a Mouflon, but clinical, necropsyand histologic findings were not discussed.49

Endocrine PancreasIslet Cell Carcinoma: The islets of Langerhans con-stitute the endocrine portion of the pancreas. Thesescattered islets are composed of a diverse aggregationof alpha, beta and delta cells that secrete glucagon,insulin and gastrin, respectively. Islet cell neoplasmsmay be secretory or non-secretory. Secretory islet cellneoplasms may have diverse clinical presentations.

An islet cell carcinoma has been reported in a budg-erigar with hyperglycemia.116 The neoplasm was pre-sumed to be of alpha cell origin and associated withglucagon hypersecretion and diabetes mellitus, butthis assumption was not proven. It must be notedthat in health, birds have higher glucose values thanmammals. In stressful situations, avian blood glu-cose values may temporarily approach or exceed 700to 800 mg/dl. Therefore, persistent and dramatichyperglycemia must be present to confirm a diagno-sis of avian diabetes mellitus.

Histologically, this islet cell carcinoma consisted ofnests and lobules of pleomorphic, pale-staining cellswith vesicular nuclei and a moderate mitotic index.The neoplasm was poorly circumscribed and con-tained a delicate fibrovascular stroma. Both com-pression and invasion of the adjacent exocrine pan-creas were observed.116

Chemoreceptor NeoplasmsChemoreceptors, in concert with the parasympa-thetic and sympathetic nervous systems, regulateblood pH, pCO2 and pO2. These neoplasms are veryrare in birds. A carotid body tumor has been reportedin a parakeet, but no details of the neoplasm werepresented.15

Nervous System and Eye

Nervous system and ocular neoplasms apparentlyare infrequent in birds with the exception of pituitaryadenomas in budgerigars and malignant lymphoma(leukosis) in chickens.48,49,121

Central Nervous SystemNeoplasms of the central nervous system may repre-sent an interesting incidental finding at necropsy ormay be related to profound neurologic deficits fromcompression and infiltration of neural tissue, ob-struction of cerebrospinal flow, or secondary edema,hemorrhage or necrosis. These neoplasms have apoor prognosis, and effective treatment regimenshave yet to be developed (Color 25.14). The discus-sion below is confined to those neoplasms recentlyreported in birds.

Astrocytoma: An astrocytoma is a differentiated neo-plasm of astrocytes that exhibits slow but progressivegrowth. These neoplasms usually arise in the cere-bral hemispheres, thalamus, brainstem, cerebellumor spinal cord.88 A single astrocytoma has been re-ported in a duck with neurologic signs (especiallycircling).108 At necropsy, a lobulated mass was iden-tified in the base of the cerebellum. Histologically, theneoplasm was lobulated and unencapsulated withlarge globular cells in a fibrillar network.108 The tu-mor description suggests a gemistocytic astrocytoma.

Glioblastoma: A glioblastoma is an undifferentiatedneoplasm of astrocyte origin. These neoplasms growrapidly, infiltrate surrounding neural tissue, and arevery destructive. A glioblastoma has been describedin a budgerigar with weakness, incoordination, in-ability to perch properly, tremors of the wings andrigidity of the legs.106 Gross brain lesions were notobserved at necropsy. Microscopically, a circum-scribed mass occupied a large area of the diencepha-lon and mesencephalon. Neoplastic cells were pleo-

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Oncology

Color 25.1A ten-year-old Amazon parrot was pre-sented with a one-year history of progres-sive swelling of the head and face. Numer-ous masses were palpable throughout thebody, and their occurrence was confirmedby radiographs (see Figure 25.2). His-topathology indicated an invasive fibrosar-coma involving the soft tissues and bones ofthe head (courtesy of Jane Turrel).

Color 25.2A six-year-old budgerigar was presentedwith a large, featherless mass involving theventral abdomen. The mass interfered withthe bird’s ability to fly and perch. Cytologyindicated a lipoma with xanthomatosis ofthe skin overlying the mass (note the yel-lowish, thickened skin). The tumor and as-sociated xanthoma were surgically excised(courtesy of Jane Turrel).

Color 25.3A four-year-old African Grey Parrot waspresented with a history of anorexia,weight loss and depression. The bird did notrespond to supportive care. Hepatomegalyand splenomegaly with raised white nod-ules in the liver were noted at necropsy.Histopathology revealed an accumulationof lymphoid cells in the nodules, consistentwith a diagnosis of lymphosarcoma (cour-tesy of Jane Turrel).

Color 25.4A five-year-old male budgerigar was pre-sented for abdominal distention and leftlimb paresis. The bird did not respond tosupportive care. Necropsy findings in-cluded seasonal testicular (t) hypertrophy(which should not be confused with neo-plasm) and a renal mass (arrow). The renalmass was histologically identified as a re-nal carcinoma (courtesy of Jane Turrel).

Color 25.5A five-year-old budgerigar was presentedwith a rapidly growing firm mass on thedorsal surface of the wing. Cytology indi-cated a pleomorphic population of spindlecells suggestive of fibrosarcoma. The masswas limited to the soft tissue of the wingand did not involve the underlying bones.The case was managed by amputating theaffected wing (courtesy of Jane Turrel).

Color 25.6An adult female cockatiel was presented forweight loss and a distended abdomen. Onphysical examination, the bird was bright,

alert and responsive, and weighed 91 g butwas severely emaciated as detected by pec-toral muscle atrophy. The abdomen wasseverely dilated and had a fluid consis-tency. Abdominocentesis was used to col-lect 10 mls of fluid that was used for cy-tologic evaluation. The fluid had thecharacteristics of a modified transudateand contained cells suggestive of neoplasm.The bird did not respond to supportive care.At necropsy, 20 mls of fluid were removedfrom the distended abdomen. A large masswas filling the space between the descend-ing and ascending duodenum that is nor-mally occupied by the pancreas. The his-tologic diagnosis was multicentric,anaplastic pancreatic carcinoma with car-cinomatosis of the serosal surfaces of theabdomen and the tunica muscularis of theintestines (courtesy of Cheryl Greenacre).

Color 25.7A captive Blue Jay was presented with acrusty, hemorrhagic, poorly defined masson the wing. The lesion first appeared as anon-healing wound that progressively en-larged over a period of several months. Bi-opsy of the lesion revealed a squamous cellcarcinoma (courtesy of Jane Turrel).

Color 25.8A 50-year-old Amazon parrot was pre-sented with a history of dysphagia, regur-gitation and weight loss of several months’duration. Histopathology of the mass con-firmed a squamous cell carcinoma (see Fig-ure 25.14) (courtesy of Jane Turrel).

Color 25.9A two-year-old Umbrella Cockatoo was pre-sented with epiphora and an ocular mass.The mass was debulked and the histologicdiagnosis was squamous cell carcinoma.The tumor margin was irradiated with astrontium-90 ophthalmic probe (courtesy ofJane Turrel).

Color 25.10A three-year-old cockatoo was presentedwith bilateral foot lesions characterized bydepigmented, scaly, hard, thickened skin.The lesions were suggestive of a viral-in-duced papilloma. If not associated with anyspecific dysfunction, lesions such as thesecan remain untreated (courtesy of JaneTurrel).

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Oncology

Color 25.11A mature, male cockatiel was presentedwith a several-month history of poor gener-alized feather condition and feather lossaround the uropygial gland. A raised, firm,uropygial gland mass was evident. Cytol-ogy of the mass revealed multiple mitoticfigures. The mass was surgically removedand the histopathologic diagnosis was ade-nocarcinoma.

Color 25.12A four-year-old female cockatiel on an all-seed diet was presented with a three-monthhistory of a progressively enlarging ab-dominal mass. On presentation, the ventralsurface of the mass was dragging on theground and the bird was having troubleambulating. The bird weighed 128 g. Notethe rotund appearance of the pelvic muscu-lature. This bird responded to a change indiet and increased exercise over a three-month period, followed by surgical excisionof the mass that was half its original size atthe time of surgery.

Color 25.13A four-year-old female African Grey Parrotwas presented for removal of a fibrosar-coma from the left dorsal humerus. Surgerywas complete and uneventful. The bird waspresented one year later with lethargy,anorexia, ataxia and severe dyspnea. Ra-diographs indicated a large, soft tissuemass in the cranial thorax. Cytology of afine-needle aspirate indicated ovoid cellswith large, eccentric nuclei suggestive of aneoplasm. The bird did not respond to sup-portive care. Histopathology revealed a re-nal tubular adenocarcinoma with metasta-sis to the lung, liver and myocardium.Interestingly, the bird’s mate died fromadenocarcinoma two years earlier.

Color 25.14A four-year-old Blue-fronted Amazon Par-rot was presented for an acute onset ofdepression and apparent blindness. Theonly abnormal physical examination find-ing was mild ataxia. Radiographs of theabdomen were unremarkable. Blood leadand zinc levels were normal. A mild hetero-philia (19,000 cells/µl) was the only abnor-mal clinicopathologic finding. EEGs indi-cated diffuse cerebral inflammation. Thebird would maintain weight and conditionwith supportive care but would deterioratewhen the supportive care was stopped. Af-ter two months the bird was euthanatized.The ventral surface of the brain was nodu-lar in appearance. The histopathologic di-agnosis was meningioma.

Color 25.15A two-year-old female cockatiel was pre-sented for feather picking associated with

the right carpus. A diffuse, firm, yellowmass was noted in the carpal region onphysical examination. The appearance ofthe lesion was suggestive of xanthoma, andthe demonstration of vacuolated macro-phages, lipids and cholesterol crystals in afine-needle aspirate from the mass wasconfirmatory. The xanthoma was surgi-cally excised.

Color 25.16 A mature Amazon parrot was presentedwith a non-weight-bearing lameness of oneweek’s duration. Radiographs indicated afracture of the mid-diaphyseal tibiotarsalbone. During surgery for placement of anIM pin, it was noted that the bone did notappear normal and a biopsy was per-formed. Surgical recovery was unremark-able. The biopsy report indicated osteosar-coma, and the client chose to have the birdeuthanatized. Inset shows the dissectedbone, which had healed from the pathologicfracture, with the pin in place.

Color 25.17An adult Indian Ring-necked Parakeet waspresented with a three-month history of aproliferating mass involving the cere andleft periocular area. Note the defect in therhamphotheca, indicating inflammation ofthe germinative layers of the beak. Themasses were surgically removed. His-topathology was suggestive of a papilloma.

Color 25.18 A mature budgerigar was presented withprogressive dysphagia, and a disfiguringoral lesion was noted on physical examina-tion. Histologic lesions were consistentwith adenocarcinoma.

Color 25.19A four-year-old budgerigar was presentedwith a rapidly growing, necrotic mass of theupper beak. The mass was interfering withthe bird’s ability to eat, and the ownerschose euthanasia. Histologic evaluation in-dicated the mass was a fibrosarcoma (cour-tesy of Jane Turrel).

Color 25.20A ten-year-old Umbrella Cockatoo was pre-sented for dysphagia, weight loss and poorfeather formation. On physical examina-tion, a large, pendulated, ulcerative sublin-gual mass was identified. The bird haddystrophic feathers and was positive forPBFD virus by DNA probe testing of wholeblood. Cytology of a fine-needle aspirate ofthe oral mass was suggestive of a giant cellgranuloma. Radiographs of the head indi-cated the extent of the sublingual mass (seeFigure 25.13).

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morphic and numerous multinucleated giant cellswere observed.

Oligodendroglioma: This neoplasm originates fromoligodendroglial cells. These neoplasms usually arisein the cerebral hemispheres. Microscopically, theyare composed of small cells with round, hyperchro-matic nuclei arranged in a honeycomb pattern.88 Asingle “glioma” has been reported in the left cerebralhemisphere of a budgerigar, but microscopic charac-teristics of the neoplasm were not reported.6

Choroid Plexus Papilloma: These benign neoplasmsoriginate from the choroid plexus epithelium, usuallyin the fourth ventricle at the cerebropontine angle.88

A choroid plexus papilloma has been observed in abudgerigar with blindness, exophthalmos and sei-zures.102 A visible mass was not observed at necropsy;however, the tumor was apparent in tissue section.This neoplasm arose from the choroid plexus of thefourth ventricle. Rows of columnar cells were ar-ranged in irregular papillary projections, small ro-settes and contorted cysts. Neoplastic cells were co-lumnar with round-to-oval, basal nuclei.

Neuroblastoma and Ganglioneuroma: These neo-plasms are derived from primitive neuroepithelialcells that differentiate toward neuroblasts(neuroblastoma) or neurons (ganglio-neuroma).88

Ganglioneuromas have been reported in chickenswhere they may arise in the nervous system, gastro-intestinal tract, ovary, muscle or heart.23 These neo-plasms are composed of ovoid, pyramidal or irregularneurons scattered among Schwann cells and fibrousstroma. Ganglioneuromas are usually benign, butmay be malignant.

Vascular Neoplasms: The most common vascularneoplasms observed in the central nervous systemare hemangiosarcoma and hamartoma. A hamar-toma is a benign tumor-like nodule composed of anovergrowth of mature cells. A hamartoma-like lesionhas been reported in the brain of an 11-week-oldbudgerigar. Microscopically, the lesion was composedof blood-filled spaces within the neuropil that com-pressed adjacent tissue.12 Vasoformative neoplasmsare frequently observed in chickens; however, braininvolvement has not been reported.74,129

Teratoma: Grossly, these primordial germ cell neo-plasms, which may be large and cystic, have beenobserved in chickens and ducks.21,23,38,58,61,63,68,76,112

Teratomas have diverse sites of origin including thebrain, pineal gland, testis, ovary, kidney, orbit, cra-nium, thoracoabdominal cavity and retroperitoneal

space. Teratomas arising within the cranial vaultmay cause neurologic deficits such as head tilt, cir-cling and facial nerve paralysis.68,76

The microscopic appearance of these neoplasms isquite striking, containing a mixture of tissue typesderived from two or three germ cell layers. The dif-ferentiated tissues may include cartilage, bone, fat,keratin cysts, smooth muscle, epithelium, neuralcells and melanocytes.

Lymphosarcoma: Lymphosarcoma of the centralnervous system may be classified as a primary orsecondary disease. Primary lymphosarcoma origi-nates in the CNS, while secondary lymphosarcomarepresents a metastatic event. Evidence exists forboth of these presentations of lymphoid neoplasia inbirds, although metastatic neoplasia is more com-mon.9,49 Most instances of CNS lymphosarcoma occurin poultry and are viral-induced.20,101 Lymphosar-coma is discussed in detail under the hemolymphaticsystem.

Meningioma: Meningiomas originate from neuralcrest cells or mesenchymal cells in contact with neu-ral crest cells. Microscopically, meningiomas areoften characterized by whorls of crescent-shapedcells.88 Meningiomas have been reported in chickens,but have not been characterized in detail.23

Peripheral Nervous SystemPeripheral nervous system neoplasms arise in nerv-ous tissues other than the brain and spinal cord.Localized neoplasms may be amenable to surgicalexcision based upon their location, size and proxim-ity to vital structures.

Schwannoma: These neoplasms previously havebeen reported as neurolemmomas or neurofibroma,the latter term being a misnomer.88 Schwannomasmay arise from Schwann cells or perineural cells ofthe peripheral nerve sheaths in any location includ-ing unspecified peripheral nerves, cranial nerves,sciatic plexus, gastrointestinal tract, testis, pinealgland, kidney, skin, muscle and spleen.17,23,85,108

Grossly, these neoplasms appear as single-to-multi-ple nodular masses or varicose thickenings of thenerve sheath. Histologically, fusiform cells are ar-ranged in interwoven bundles, whorls or palisadearrangements. Specific diagnosis relies upon obser-vation of the associated nerve of origin.17,88

Malignant Schwannoma: Malignant schwannomas(neurofibrosarcoma is a misnomer) also originate

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from Schwann cells or perineural cells. These neo-plasms have greater cellularity, marked anaplasia,an increased mitotic rate and may metastasize. Ma-lignant schwannomas have been reported to occur inCanada Geese, but histologic studies have failed todemonstrate a neural origin.82,127 Therefore, thoseneoplasms should be classified as fibrosarcomas in-stead of malignant schwannomas.

Lymphoid Neoplasia (Lymphosarcoma): M a r e k ’ sdisease in chickens is often associated with leg pa-ralysis secondary to ischiatic nerve infiltration byneoplastic lymphocytes. Affected nerves appearthickened. Microscopically, the lymphoid infiltratesmay vary from small lymphocytes and plasma cellsto lymphoblasts.20 The former infiltrates appear in-flammatory, while the latter infiltrates clearly areneoplastic.

Ocular NeoplasmsThe following discussion is concerned with primaryand metastatic intraocular neoplasms of birds. Neo-plasms involving the eyelids, conjunctiva and orbitare discussed under appropriate organ systems andwill not be considered here (Figure 25.17).

Intraocular neoplasms in birds may be associatedwith blindness, hyphema or aqueous flare. Some neo-plasms, such as malignant lymphoma, may be visu-alized occasionally by ophthalmoscopy. Because theavian eye is reinforced by scleral ossicles, buphthal-mos is not expected. In contrast, exophthalmos oc-curs with some frequency and usually indicates aretrobulbar space-occupying lesion or extension ofmalignant ocular neoplasia into the retrobulbararea. In birds, exophthalmos has been associatedwith various retrobulbar neoplasms including malig-nant lymphoma, pituitary adenoma and adenocarci-noma, malignant intraocular medulloepithelioma,intraocular rhabdomyosarcoma, undifferentiatedcarcinoma, teratoma, and glioma.15,23,48,51,100,105,121,122

Lymphosarcoma: Lymphosarcoma (malignant lym-phoma) involving the iris, ciliary body and choroid isobserved most frequently in chickens with Marek’sdisease.48 When visualized, these neoplasms may ap-pear as yellow-to-white proliferative masses. Mostoccurences of ocular lymphoid neoplasia representmetastatic lesions.

Rhabdomyosarcoma: Intraocular rhabdomyosarco-mas have been reported in two chickens.48 Theseneoplasms may have arisen from the ciliary muscles,which are striated in birds. One neoplasm extended

into the retrobulbar space. The other neoplasm re-placed the iris, ciliary body and choroid.

Malignant Medulloepithelioma: Intraocular medul-loepitheliomas are primitive neoplasms that origi-nate from the optic cup epithelium88 and have beendescribed in two cockatiels.122 The neoplasms werecomposed of tall columnar neuroepithelial cells withwell defined limiting membranes. These cells werearranged in nests, sheets and rosettes. Foci of ne-crosis also were observed. Neoplastic cells extendedinto the retrobulbar spaces, infiltrating the opticnerve and adjacent skeletal muscle.

Malignant Melanoma: Metastatic ocular malignantmelanoma has been reported in a Pintail Duck inassociation with multiple neoplasms involving adre-nal gland, skin, liver, skeletal muscle, heart, lung,kidney, brain and bone.72

Hemolymphatic System

The hemolymphatic system encompasses those tis-sues and organs that are involved in leukocyte,erythrocyte and thrombocyte production. The bonemarrow produces thrombocytes, erythrocytes and most of

FIG 25.17 A mature African Grey Parrot was presented with aspace-occupying mass involving the right periorbital area andglobe. The mass was surgically removed in conjunction with enu-cleation. The mass reappeared two years later and the bird waseuthanatized.

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the leukocytes with the exception of lymphocytes.Lymphocyte production occurs within lymphoid tis-sues, which can be divided into primary and secon-dary lymphoid tissues. The thymus and bursa ofFabricius are the primary lymphoid tissues. The sec-ondary lymphoid tissues are more diverse and, de-pending upon the species of bird, include the spleen;conjunctival, nasal and bronchial-associated lym-phoid tissues; cecal tonsils, Peyer’s patches, Meckel’sdiverticulum and other gut-associated lymphoid tis-sues; lymph nodes and lymphoid aggregates distrib-uted throughout the body.109 The majority of the lym-phocytes are produced in the secondary lymphoidtissues.

Clinical signs related to hemolymphatic neoplasiaare variable and vague including lethargy, anorexia,weight loss, lameness, swellings, dyspnea, loosedroppings and petechial-to-ecchymotic hemorrhages.Death often occurs from organ dysfunction secondaryto infiltrative disease.

Lymphoid NeoplasiaLymphoid neoplasia is the most common form ofhemolymphatic neoplasia occurring in domestic, cap-tive, and free-ranging birds.9,20,49,70,72,97,108,146 This formof neoplasia may originate from the peripheral lym-phoid tissues as lymphosarcoma (malignant lym-phoma) or in the bone marrow as leukemia.

Lymphoid neoplasia of poultry has been studied ex-tensively. In chickens, lymphoid neoplasms may beinduced by herpesvirus or retrovirus infections. Her-pesvirus infection causes Marek’s disease. In thisdisease, early lymphoid infiltrates may appear in-flammatory and consist of a mixture of small lympho-cytes, plasma cells and lymphoblasts. Following neo-plastic transformation, lymphoid neoplasms appearmore progressive and are composed of lymphoblasts.In contrast, lymphoid leukosis is caused by retrovi-ral-induced neoplastic transformation of B-lympho-cytes. The presentations of Marek’s disease and lym-phoid leukosis may differ considerably.20

Lymphoid neoplasia of free-ranging and captive birdshas not been studied in detail. A recent pathologicsurvey subclassified avian lymphoid neoplasia asplasmacytoma or fibrifying, lymphoblastic, lympho-cytic or mixed-cell lymphosarcoma.108 However, theprognostic importance of these subclassifications hasnot been demonstrated and requires further clinico-pathologic study.

Currently, there is no effective treatment for avianlymphoid neoplasia. Radiation therapy may be pal-

liative.100 Combination chemotherapy with vincristinesulfate, prednisone and chlorambucil appears prom-ising but requires more clinical research.93

Lymphosarcoma: Lymphosarcoma (malignant lym-phoma) is defined as any lymphoid neoplasm thatoriginates in the peripheral lymphoid tissues. Thisform of lymphoid neoplasia is commonly observed inbirds and is characterized by the formation of white-to-yellow tissue discolorations or sarcomatousmasses.

Lymphosarcoma usually presents as a disseminatedmultisystemic disease that can involve all tissues ofthe body, including bone marrow.9,20,97,108,146 The ab-dominal viscera often are involved (visceral leuk-osis), especially the liver, spleen and kidney (Color25.3). Occasionally, lymphosarcoma may show tissuetropism with multiple neoplasms being observed inone tissue such as skin.9 The rarest presentation oflymphosarcoma is the presence of a single, localizedneoplasm. This presentation was documented as asingle neoplasm at the optic chiasm of a cockatiel.9

A presumptive diagnosis of neoplasia may be appar-ent after physical examination by observing swel-lings of the skin or retrobulbar masses.9,100,105 Ab-dominal enlargement and hepatomegaly also may bepresent. In addition, soft tissue masses, hepa-tomegaly or osteolysis may be detected or confirmedradiographically.100,105 A complete blood count may bebeneficial in diagnosing lymphoid neoplasia by de-tecting lymphocytosis and demonstrating variablenumbers of immature (neoplastic) lymphocytes inthe blood film.9 The latter finding is termed a“leukemic blood picture” and indicates hemato-genous dissemination of the neoplasm.

Lymphoid Leukemia: Lymphoid leukemia origi-nates in the bone marrow and disseminates to vari-ous body tissues. This presentation of lymphoid neo-plasia is rare compared to lymphosarcoma.93 Birdswith lymphocytic leukemia may have anemia, throm-bocytopenia and marked lymphocytosis. Lympho-cytes in blood smears may be well differentiated orblastic. Bone marrow aspirates contain innumerablelymphocytes. Sarcomatous masses are not observedin tissues at necropsy; however, hepatosplenomegalymay be prominent. Infiltration of various tissues byneoplastic lymphocytes is observed microscopically.

Thymoma: Thymoma is a localized form of lymphoidneoplasia that is confined to one or more thymic lobes.Histologically, thymomas may present as lympho-cytic or epithelial masses.

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Thymoma has been observed in two budgerigars.15,152

Only one neoplasm has been described in detail andpresented as a palpable mass on the right side of thebase of the neck.152 Histologically, the neoplasm wasan epithelial-type thymoma, consisting of aggregatesof small lymphocytes and epithelial cells encased ina dense fibrous stroma. The epithelial cells had a“clear cell” morphology.

Nonlymphoid NeoplasiaNonlymphoid hematologic neoplasia is observedmost frequently in chickens infected with certainstrains of leukosis (sarcoma) retroviruses.101 Somestrains of virus are associated with the developmentof granulocytic leukemia (myelocytomatosis) orerythremic myelosis (erythroblastosis).

Granulocytic Leukemia: Granulocytic leukemia isthe unregulated proliferation of granulocytes. Inchickens, this disease (myeloblastosis) is caused byretrovirus infection; the etiology in captive and free-ranging birds has not been identified.101

Granulocytic leukemia in birds is sometimes associ-ated with the formation of sarcomatous massescalled myelocytomas. These lesions are analogous tochloromas in mammals. More commonly, tissue infil-tration by neoplastic granulocytes results in hepa-tosplenomegaly. Microscopically, the neoplastic cells

appear either blastic (myeloblastosis) or exhibit het-erophilic (myelocytic) differentiation.108 Differentia-tion is appreciated more readily, however, in blood andbone marrow smears as opposed to histologic sections.

Erythremic Myelosis: Erythremic myelosis is the un-regulated production of erythrocyte precursors. Thisform of leukemia is caused by retrovirus infection inchickens and has been called erythroblastosis.101

An erythremic myelosis-like syndrome has been de-scribed in conures.114 Most of these birds appearweak and have a history of spontaneous hemorrhage.Histopathology has documented acute and chronichemorrhages within various tissues in conjunctionwith erythrocyte proliferation in the bone marrow,hepatic sinusoids and splenic red pulp.114 Althoughthe evidence occasionally appears supportive oferythremic myelosis, marked extramedullaryerythropoiesis cannot be excluded. In comparison tomammalian erythrocytes, avian erythrocytes have avery short life span (20 to 25 days). Following acuteand ongoing hemorrhage, intense extramedullaryerythropoiesis could occur, especially with concur-rent recycling of iron from internal hemorrhage.Therefore, the conure bleeding syndrome will requirefurther hematologic characterization before it can beclassified absolutely as erythremic myelosis.

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TABLE 25.2 Cytologic and Histologic Differentiation of Integumentary and Connective Tissue Neoplasms and Masses

Mass Cytology Histopathology

Lipoma Abundant free lipid, some intact adipocytes See text

Myelolipoma Hematopoietic precursors, differentiatedhematopoietic cells, free lipid and intact adipocytes

Hematopoiesis (particularly heterophils) mixed withmature adipose tissue

Liposarcoma Free lipid, scattered polyhedral cells with cytoplasmicvacuoles similar to xanthomas

See text

Xanthoma Vacuolated macrophages, multinucleated giant cells,lipids, cholesterol clefts (appear as parallelogramswith notched corners), rarely fibroblasts

Lipid-laden macrophages, multinucleated giant cells,cholesterol clefts, varying fibroplasia117

Fibrosarcoma Pleomorphic spindle cells, multinucleated tumor giantcells, similar to reactive fibroplasia

Pleomorphic to spindle-shaped cells, plump nuclei,eosinophilic fibrillar cytoplasm, cells in bundles,sheets, whorls, mitotic figures may be numerous

Fibromas Sparsely cellular, similar to fibrosarcomas, reactivefibroplasia

Compressed fibroblasts, dense collagenous stromacells in sheets, swirls, or interlacing bundles

Myxoma/sarcoma Viscous aspirate, free nuclei, spindle cells (singular orclusters)

Spindle cells in loose collagen matrix, alcian blue-positive mucinous ground substance, rare mitotic figures

Papilloma See text See text

Squamous cell carcinoma See text See text

Basal cell tumors See text See text

Cutaneous lymphosarcoma See text Neoplastic lymphocytes in the dermis or pulp cavity

Mast cell tumors Round cell population with fine, purple cytoplasmicgranules that may obscure nuclear detail(Romanowsky stain)

Uniform population of round cells, central round-to-oval nuclei and abundant eosinophilic cytoplasm,metachromatic granules (Giemsa stain)

Cytology based on fine-needle aspirates unless otherwise noted. The presence of lipid in cells and the background of the smears may be indirectly demonstrated bynew methylene blue staining (fat- and aqueous-based stains do not mix). Histopathology is usually necessary to definitively diagnose the type of tumor.

TABLE 25.1 Specific Treatment Concerns of Neoplasms*

Lipomas Frequently recur following excision

Liposarcomas Locally invasive and metastatic

Xanthomas Excise localized masses, amputatelimb if deeper tissues involved,irradiation (see text)

Fibrosarcomas Generally unrewarding, locally invasive,if in extremeties amputate ASAP

Hemangioma Highly vascularized and must beexcised with great care

Hemangiosarcomas Frequently recur after surgical excision,amputate affected limb

Leiomyosarcoma Must excise before metastasis occurs

Rhabdomyomas Radical excisions necessary, marginsdifficult to define

Rhabdomyosarcomas Radical excision before metastasis,bleed extensively

Chondromas/sarcomas Difficult to remove without extensivedamage to surrounding tissues

Osteosarcomas Remove affected bone or limb;endoscopy, radiology and biopsy tocheck for metastasis

Renal adenocarcinomas Generally considered untreatable,radioisotopes hold some promise

Embryonal nephroma** Non-reported, difficult to removebecause of underlying sacral plexus

*Surgical excision is the treatment of choice for all tumors that are not listed.**All renal tumors are difficult to excise because of potential damage to sacralplexus.

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