Oncologia Aves
Oncologia Aves
Oncologia Aves
KEYWORDS
Neoplasia Tumor Neoplastic Bird Psittacine Cancer
KEY POINTS
Cytologic examination of fine-needle aspirates of neoplastic lesions should be performed
whenever feasible, because it has a potential to provide a rapid diagnosis with low
morbidity and costs associated.
Surgical excision of a neoplastic lesion should only be formed after staging to evaluate
extend of disease and optimize the surgical planning.
Safe and effective chemotherapy dosages and frequency of administration in companion
birds are yet to be established and although many published drug protocols seem safe,
they are also largely ineffective, likely due to subtherapeutic drug concentrations reached.
Radiation therapy seems to be well tolerated in birds; however, the need for general anes-
thesia and lack of established radiation protocols limit its use in companion birds.
INTRODUCTION
Birds kept as companion animals are increasingly living longer due to improved
husbandry, nutrition, and veterinary care provided. As a consequence, a growing
number of geriatric disease conditions, such as degenerative and neoplastic diseases,
are diagnosed and managed by veterinarians. The increasing awareness of bird
owners of diagnostic and treatment options for neoplastic diseases in humans and
domestic animals has led to an increasing demand to provide advanced diagnostic
and treatment modalities for companion birds diagnosed with neoplasia.
Among companion birds, Psittaciformes are most frequently diagnosed with
neoplasia, with budgerigars the most commonly affected species (17%–24% overall
incidence).1 Passeriformes have the lowest reported incidence of neoplasia among
DIAGNOSIS
BODY MAP
A body map, which documents the location and size of the neoplastic masses, should
be performed anytime a new mass is found in a patient (Fig. 1). Calipers should be
used to measure the longest diameter of a mass, and this value should be recorded
on the body map form, with the visit date. This allows for close monitoring of the
changes in mass size. If owners have declined further diagnostics, or if the mass
was diagnosed as benign but is growing, repeated discussion with the clients about
benefits of therapeutic intervention could be pursued.
BLOOD WORK
Blood work should be performed to assess overall health as well as to look for
abnormal blood counts, which could be linked to the presence of neoplasia. A com-
plete blood cell count may reveal cytopenias, which may result from the presence
of hematopoietic malignancies in which the neoplastic cells may crowd the bone
marrow (myelophthisis). Anemia may occur in patients with cancer for a variety of rea-
sons, including bleeding from a tumor or bone marrow infiltration by hematopoietic tu-
mors. Leukocytosis, consisting of a mature lymphocytosis (chronic lymphocytic
leukemia)2,3 or a population of large immature blasts (acute leukemia), may be seen
in patients with leukemia.
An abnormal biochemistry profile may be the sign of organ involvement by the tumor
or organ dysfunction related to age or other diseases and may preclude the use of
certain therapies. Paraneoplastic syndromes, such as hypercalcemia and hyperglobu-
linemia, are commonly described in canine patients with hematopoietic malignancies.
Hypercalcemia was present in 2 Amazon parrots with malignant lymphoma and
believed to be paraneoplastic.4 Ionized calcium should be determined if hypercalce-
mia of malignancy is suspected.
Diagnostic Imaging
Many malignant tumors have the propensity to spread to other organs, commonly to
lungs but also to coelomic organs or bones.5–8 Radiographs allow for visualization of
bone lesions (Fig. 2) and soft tissue masses; however, whole-body CT, preferably
contrast enhanced, is becoming the mainstay in diagnostic imaging of avian patients,
Avian Oncology 59
Fig. 1. Avian body map. (Courtesy of Ruth Houseright, DVM, DACVP, Madison, WI.)
because it allows for 3-D visualization and better assessment of internal organs for
the presence of primary or metastatic lesions (Fig. 3A, B). CT images also allow for
better surgical planning. CT can be performed in sedated avian patients in most in-
stances, therefore eliminating anesthetic risks (Fig. 4) Noniodinated contrast material
(eg, iohexol) can be administered either intravenously (IV) or intraosseously (IO) after
catheter placement.
Ultrasound is a valuable diagnostic tool in avian patients, in particular for large
coelomic masses; however, the presence of air sacs may reduce its suitability in
some instances. Ultrasound-guided fine-needle aspirates should be performed when-
ever possible to increase the chance of obtaining a diagnostic sample and to reduce
60 Robat et al
Fig. 2. Ventrodoral (A) and lateral radiographs of a 33-year-old blue-fronted Amazon parrot
(Amazona aestiva), which presented with left leg lameness. Radiographs show expansion of
left distal tibiotarsus and tarsometatarsus and abnormal angulation, consistent with chronic
osteomyelitis or neoplasia. Fine-needle aspiration did not reveal a diagnostic sample. Post-
mortem diagnosis was a well-differentiated chondrosarcoma affecting the left tibiotarsus
and metatarsus. (Courtesy of Christoph Mans, Madison, WI.)
Fig. 3. CT and laparoscopy in a 35-year-old Congo African gray parrot (P erithacus) diagnosed
with primary lung neoplasia. (A) Cross-sectional and (B) sagittal CT views. Note the bilateral
asymmetric soft tissue attenuation in the lungs. (C) Laparoscopic examination of the lung
was performed and (D) biopsies for histopathologic examination collected using 5F biopsy for-
ceps. The biopsy samples did not reveal a neoplastic or infectious underlying cause. Necropsy
revealed a primary pulmonary carcinoma. (Courtesy of Christoph Mans, Madison, WI.)
Avian Oncology 61
Fig. 4. CT in sedated avian patients. (A) Cockatiel (N hollandicus); note the supplemental
oxygen provided and the cardboard cone, which facilitates to keep the patient in a sternal
body position without restraint. (B) Bald eagle (Haliaeetus leucocephalus) hooded
and sedated for whole-body CT scan in dorsal recumbence. (Courtesy of Christoph Mans,
Madison, WI.)
associated morbidity. A 3-D ultrasound has been successfully used to identify the
origin of a coelomic mass in a mynah, by providing better spatial perspective of the
internal organs.9
Cytology
Cytology is a readily available tool, which is inexpensive and associated with low
patient morbidity. The turnaround time for results is also faster than for histopathol-
ogy. Cytology can often be used to differentiate between an inflammatory process
(eg, septic heterophilic inflammation, or granuloma) and neoplasia and, depending
on the type of tumor, can lead to the differentiation between a benign and malign tu-
mor. Most masses can be sampled with little concern for complications. Patients
may need to be sedated for a fine-needle aspirate. If deeper-seated tumors are to
be sampled, ultrasound guidance may be helpful.
Fluid aspirates (effusions) can also be evaluated, either as a direct smear (if cell
count is high) or after cytocentrifugation (if low cellularity). Some neoplasias tend to
exfoliate well, such as hematopoietic tumors (eg, lymphoma) and carcinomas. Many
sarcomas exfoliate poorly, however, because they contain more connective tissue,
which holds cells together. Bone lesions and bone marrow can readily be sampled
although patients need to be under a short general anesthesia.
When sampling a mass, a small-gauge needle should be used first (eg, 25G or 23G).
Larger needles are rarely helpful, because blood contamination is a common compli-
cation. Nonaspiration techniques are preferred for cytologic sample collection,
because blood contamination and cell lysis are common with the aspiration tech-
niques. If the nonaspiration technique does not yield an adequately cellular sample,
the aspiration technique can be attempted. This technique uses a syringe attached
to the needle. Once a needle has been introduced into the mass, negative pressure
is applied by quickly pulling on the plunger and releasing. This increases the chance
62 Robat et al
Fig. 5. (A) Fine-needle aspiration technique using a 25-G needle. (B) Occlusion of the needle
hub should using the index finger reduces the risk of blood contamination of the sample.
(Courtesy of Christoph Mans, Madison, WI.)
Avian Oncology 63
Fig. 6. Cytologic artifacts. (A) Most of the nucleated cells are lysed. Bare nuclei are present
and nuclear streaming (spread chromatin) is evident. Cell lysis can occur after excessive suc-
tion during sample collection, use of a needle that is too small, or excessive pressure during
spreading of the sample with a glass slide. (B) This sample is poorly spread therefore individ-
ual cell morphology cannot be assessed. Cytology samples that are too thick are also often
poorly stained unless stained more than once. (C) Edge of the sample shows poor cell spread
and cell lysis. (Courtesy of Melanie Ammersbach, Guelph, Ontario.)
STAGING
Treatment
Surgery
When possible, surgical excision of a tumor, with adequate margins, will always result
in a better outcome. Prior to any surgical intervention, careful planning should be per-
formed to increase chances of the first surgery being successful. This includes making
every effort to obtain a presurgical diagnosis with cytology or histopathology as well
as, if necessary, using imaging techniques to assess the extent of disease and help
plan the optimal approach. Full staging should be performed, and benefits and risks
of surgical intervention discussed with the owners. The goal is to remove the tumor
with adequate margins to avoid recurrence. Recurrent tumors are harder to manage
surgically, because tissues have been disrupted and the resulting surgical field is
much larger, making a second excision exceedingly difficult. Recurrent tumors carry
a poorer prognosis, and many avian patients are euthanized due to local tumor pro-
gression.16,17 Surgery can sometimes be performed in a purely palliative setting, to
relieve discomfort associated with the size and/or location of the tumor. If margins
are incomplete, adjuvant treatment options should be discussed with the owners,
such as a second surgery, radiation therapy, or chemotherapy. Most benign tumors
are cured with adequate surgical excision. Recurrence is still possible, however,
and has been reported in cases of a surgically removed lipoma in an orange-winged
Amazon parrot (Amazona amazonica).18
Radiation therapy
Radiation therapy is a form of local therapy, used either in a gross disease setting
to provide palliation of clinical signs and attempt to shrink the tumor (palliative,
coarse-fractionation radiation therapy) or in a microscopic disease setting to kill cells
remaining after surgical excision and extend survival time (curative/definitive radiation
therapy). The tumor is irradiated as well as a margin of normal surrounding tissue to
account for microscopic tumor extension.
Several reports of radiation therapy in birds exist and show mixed results in terms
of success and side effects. Major problems include the lack of information on
adequate fractionation and schedule in avian patients, knowledge of radiosensitivity
of avian tumors, and tolerance of normal tissues. Some of this information can be
extrapolated from other species, in which hematopoietic tumors are exquisitely sen-
sitive to radiation therapy, whereas carcinomas are moderately sensitive and sar-
comas much less so.19
The tolerance of skin and mucosal tissues to radiation therapy has been evaluated in
ring-necked parakeets.20 Each bird was treated with cobalt-60 teletherapy and
received 4-Gy fractions to a total of 48 Gy, 60 Gy, or 72 Gy. Minimal epidermal
changes were noted in all birds, including in the high-dose group, and no chronic
side effects were present 9 months post-therapy. This suggests that birds may
have higher tissue tolerance to radiation and may require higher radiation dosages
to treat sensitive tumors.
Radiotherapy has been used after surgery to treat a squamous cell carcinoma (SCC)
of the mandibular beak in a Buffon macaw (Ara ambigua).21 The bird was treated on a
Monday-Wednesday-Friday schedule with 5.6 Gy per fraction to a total of 48 Gy and
an additional 8-Gy boost, with cobalt-60, with no effect on the tumor and no side ef-
fects. Possible explanations for lack of response include a high number of hypoxic
cells (presence of infection/necrosis), lack of radiosensitivity of the tumor (as in other
species, such as felines, where best responses are mostly stable or partial, with only
modest improvements in survival time compared with untreated patients22), or inade-
quate radiation dose.
Avian Oncology 65
Partial response to radiation therapy has been reported in a few cases. A stage
4 mandibular beak melanoma in a thick-billed parrot was treated with 20 daily frac-
tions (Monday through Friday) of 2.5 Gy (total 50 Gy), using a linear accelerator,
yielding a partial response at the primary tumor site; however, the bird died of meta-
static disease 11.5 weeks postdiagnosis.23 A hemangiosarcoma on the wing of a
budgerigar resolved without complications after radiotherapy with 137cesium telether-
apy (10 fractions of 4 Gy, Monday-Wednesday-Friday) but recurred 1 month later, and
the bird was subsequently euthanized 2 months postdiagnosis due to disseminated
hemangiosarcoma.24
Orthovoltage was used to treat an intraocular osteosarcoma after exenteration and
mass removal in an umbrella cockatoo (Cacatua alba) using a Monday-Wednesday-
Friday schedule to a total dose of 68 Gy over 6 weeks.25 The bird died of neurologic
signs 3 months later and no necropsy was performed. Although the treatment was
administered without complications, response could not be evaluated due to the rapid
death of the bird.26 A malignant lymphoma involving the periorbital area in an African
gray parrot (Psittacus erithacus) was treated with orthovoltage teletherapy for 10 frac-
tions of 4 Gy on a Monday-Wednesday-Friday schedule. By the third treatment, the
mass had markedly shrunk but at a 2-month recheck had grown back to at least
50% of its original size.27
Combination therapies have been evaluated using intralesional chemotherapy and
radiation. A fibrosarcoma of the wing in a blue-and-yellow macaw (Ara ararauna) was
treated with 4 Gy per fraction on a Monday-Wednesday-Friday schedule to a total of
40 Gy with a cobalt-60 unit, with concurrent administration of intratumoral cisplatin.
Complete tumor response was noted 2 months postcompletion of therapy.28 There
was no evidence of reoccurrence 15 months post-treatment. Intralesional cisplatin
was also used in a treatment protocol using surgery and orthovoltage radiation
(before the 8th and 11th radiation treatments) to treat a fibrosarcoma on the face of
a blue-and-yellow macaw.29 The tumor had been increasing in size at the 6th radiation
treatment, so intralesional cisplatin was added. The patient remained in remission for
29 months.
In general, avian patients seem to tolerate radiation better than other species. Pro-
tocols using 4-Gy fractions, administered 3 times a week (10–12 total fractions), for a
cumulative dose of 40 Gy to 48 Gy seem most commonly reported. Side effects are
either absent or mild and include erythema, feather loss in the radiation field, pigmen-
tary changes, and, rarely, necrosis, fibrosis, and leukopenia. A recent study of radia-
tion of the head in birds concluded that the unique anatomy of this species, with the
presence of an elaborate set of sinuses, resulted in inhomogeneity of dose distribution
and that the intended amount of radiation delivered did not reach intended levels.30
Chemotherapy
When considering the use of chemotherapy in companion birds, several precautions
must be taken. Every effort should be made to include a board-certified oncologist in
the decision-making process. There is no established standard of care for the
treatment of avian cancer; dosages are mostly unknown and side effects difficult to
predict. This should be discussed with clients so that expectations are realistic.
Reports of avian species with various neoplasms treated with chemotherapy
(mostly hematopoietic diseases) have been published2,3,13,15,28,31–36; however, re-
sponses and outcome remain anecdotal.
Dosages of chemotherapy are extrapolated from those used in canine and feline
species; however, they may not be appropriate for use in avian patients. Most chemo-
therapy agents are dosed based on body surface area (BSA); however, concerns have
66 Robat et al
been raised that BSA does not adequately correlate with the physiologic/pharmaco-
logic factors that influence drug exposure.37 Another commonly used formula is based
on weight (milligrams per kilogram). Pharmacokinetics of several chemotherapy
agents have been studied in healthy sulphur-crested cockatoos and other avian spe-
cies in an attempt to improve dosage of chemotherapy agents in birds.38–42
Chemotherapy kills rapidly dividing cells (neoplastic cells) but may cause collateral
damage on normal rapidly dividing cells, such as cells in the hair follicles, gastrointes-
tinal tract, and bone marrow. Gastrointestinal side effects usually occur 3 to 5 days
post-therapy and are readily managed with supportive medications. Bone marrow
suppression and resulting heteropenia happen most commonly at approximately
1 week after chemotherapy and close monitoring of blood cell counts is, therefore,
necessary. In canine and feline patients, treatment is administered if the neutrophil
count is greater than 1500/mL. Antibiotic therapy is initiated if the neutrophil count is
less than 1000/mL, and a febrile and neutropenic patient is considered a medical emer-
gency and should be hospitalized on IV antibiotics.
Side effects of chemotherapy in avian species have been reported (Table 1).
Cisplatin, if given at the dog dosage, can cause severe nephrotoxicity, but it seems
safe at a dose of 1 mg/kg IV.25 Carboplatin has been used at 5 mg to 27 mg/kg IV
or IO, every 3 to 4 weeks with minimal toxicity.35,36,43 Both carboplatin and cisplatin
have been used intralesionally, in an oil-based emulsion.21,28,29,34,44 Cyclophospha-
mide causes marked heteropenia in birds, in experimental settings45,46 and causes
feather lesions in chicken.47 Lomustine (CCNU) causes hepatotoxicity in humans
and dogs but this has not yet been reported in birds. Topical 5-fluorouracil has suc-
cessfully been used for the treatment of cutaneous SCC.1 Vincristine and doxorubicin
are vesicants in humans, dogs, and cats. Doxorubicin has been used at 2 times the
typical dog dose with no side effects observed.48 L-Asparaginase has been used by
the authors at both the canine/feline dosage (400 U/kg) and 4 times that dose, with
no effect and no toxicity in a finch with lymphoma. Metronomic chemotherapy
(low dose, daily oral chemotherapy, and using cyclophosphamide and meloxicam)
has been used successfully to delay recurrence in a kori bustard (Ardeotis kori) with
an incompletely excised myxosarcoma.31 No side effects were reported. In dogs,
metronomic chemotherapy has also been shown to slow down recurrence of soft tis-
sue sarcomas.49 Although maximum tolerated dose chemotherapy targets the DNA of
rapidly dividing cancer cells, the purpose of metronomic chemotherapy is to inhibit
angiogenesis by damaging endothelial cells and possibly to modulate the immune
system by decreasing levels of regulatory T cells.49
Chemotherapy administration may be oral, IV, intramuscular, subcutaneous. Birds
have thin and delicate skin, which makes the placement of vascular access ports diffi-
cult. A recent report of a vascular access port placement in a chicken suggests, how-
ever, that this may be feasible in select cases, making IV chemotherapy administration
much more feasible.50 When administering chemotherapy, personal protective equip-
ment should always be worn, any spills cleaned thoroughly with bleach, and the
contaminated materials disposed of appropriately. Closed system devices are
now readily available and relatively cheap (eg, Tevadaptor, Equashield, and PhaSeal)
and should be used when administering chemotherapy to decrease risk of exposure to
hazardous drugs. Sending clients home with oral (liquid or pill/capsule) chemotherapy
is not encouraged, because administration can be challenging, and environmental and
user contaminations are common. In addition, chemotherapy may be administered
directly into a solid tumor (intralesional chemotherapy). The goal of intralesional
chemotherapy is to achieve a high concentration of chemotherapy at the tumor site
while minimizing systemic uptake and therefore side effects. Although this seems
Table 1
Selected chemotherapy protocols used in birds
Avian Oncology
Amazon parrot (Amazona lymphocytic euthanasia
ochrocephala oratrix) leukemia
67
68
Robat et al
Table 1
(continued )
Drug Species Tumor Protocol Response/Duration/Survival Side Effects Ref
15
Chlorambucil Umbrella cockatoo (Cacatua Nonepitheliotropic Chlorambucil (2 mg/kg po Partial remission week 9 Myelosuppression
1 vincristine alba) B-cell cutaneous twice weekly) 1 (treatment d/c at week 17
lymphoma and Vincristine (0.1 mg/kg IV q due to anemia) —complete
leukemia 1–3 wk) response at week 29 and
ongoing (>8 y)
33
Multiple Green-winged macaw (Ara Chronic lymphocytic Chlorambucil 1 mg/kg po Unknown to chlorambucil Thrombocytopenia
protocols chloropterus) leukemia twice weekly (6 wk d/c due Stable disease on (chlorambucil)
to thrombocytopenia) 1 cyclophosphamide
prednisone 1 mg/kg po q 24
h
THEN Cyclophosphamide
5 mg/kg po 4 d q 21 d
(week 8.5)
2
Multiple Black swan (Cygnus atratus) Chronic T-cell Chlorambucil 2 mg po q 48 h No response to chlorambucil None
protocols lymphocytic (until day 150), then L-Spar L-Spar/CCNU/prednisone.
leukemia 400 IU/kg SQ 1 CCNU Partial response to whole-
with coelomic 60 mg/m2 po q 3 wk, then body radiation. Died at day
organ involvement prednisone added 450.
0.5 mg/kg po q 24 h, then
whole-body radiation
Photodynamic therapy
Photodynamic therapy (PDT) uses an IV or intratumoral photosensitizing agent, acti-
vated by a light source. Once activated, oxygen radicals are produced and destroy
the neoplastic cells. This technique has most commonly been used for the treatment
of cutaneous SCC in cats and equine periocular SCC.52–55 In birds, use of PDT has
been reported for treatment of SCC.56,57 In a 5-year-old ringed-necked parakeet
(Psittacula krameri), an ulcerated SCC on the medial aspect of the postpatagial
area of the right wing was treated with PDT.57 This resulted in necrosis of the tumor
and reduction in tumor burden but not complete resolution. In a 33-year-old great
hornbill (Buceros bicornis), PDT was used to treat SCC of the rostral casque. A partial
response was noted, but the tumor then progressed and the bird was euthanized.56
These 2 reports suggest that PDT may be a useful tool to treat sold tumors in birds;
however, further studies are necessary to determine optimal technique and
indications.
Cryotherapy
Cryotherapy used extremely cold temperatures to achieve destruction of tissues.
There are many different techniques described (open-spray, closed-spray, and cryo-
probe) using single or multiple freeze-thaw cycles and most commonly using liquid
nitrogen. Cryotherapy is commonly used for the treatment of superficial small lesions,
most commonly on the head/face area in dogs and cats.58 In birds, cryotherapy has
been used successfully after treatment with intralesional cisplatin in an African
penguin (Spheniscus demersus) with choanal SCC.34 Advantages of cryotherapy
are the ease of treatment and low morbidity associated with it and the possibility of
performing repeat treatments if necessary. The disadvantage is that it is only suitable
for superficial lesions of small diameter.
Antihormonal therapy
The administration of long-acting synthetic gonadotropin-releasing hormone (GnRH)
supra-agonists (eg, leuprolide acetate and deslorelin acetate) leads to a reduction
70 Robat et al
COMMON NEOPLASMS
Integumentary and Soft Tissue Tumors
SCCs are a malignant tumor of the epithelial cells lining certain tissues or organs.
These can occur anywhere on the body and are commonly seen on the feathered
skin,44,57 beak,21 uropygial gland,64 and phalanges and in the upper gastrointestinal
tract (in particular affecting the crop).65–67 Cockatiels, Amazon parrots, and conures
are commonly affected.68 SCCs present as pink, raised, infiltrative, and proliferative
masses. They are usually ill defined and can be ulcerated. Diagnosis can be obtained
by cytology (SCCs exfoliate well) or histopathology. They behave in a locally invasive
fashion and have a low metastatic rate. They are best treated surgically, with the goal
of achieving a complete surgical excision.68 Local radiation therapy using a single
treatment with a strontium probe has been used successfully as the sole treatment
in 2 budgerigars (M undulatus) with uropygial gland carcinoma and in a cockatiel
(Nymphicus hollandicus) with a uropygial gland adenoma.69 Complete resolution of
the neoplastic lesions occurred and all three birds were disease-free at the time of
reporting, 8 months, 9 months, and 2 months post-treatment, respectively.69 Prelim-
inary data from a multi-institutional retrospective study on outcome of SCC in 85 birds
treated with surgery, chemotherapy, or radiation therapy (orthovoltage or strontium)
indicate that complete surgical excision was associated with a more positive
outcome.68 Radiation, however, penetrates only a few millimeters with strontium ther-
apy and may not be appropriate for more invasive tumors. As in other species, SCCs
are radiation resistant, making the treatment of larger or deeper lesions difficult. Intra-
lesional chemotherapy, using carboplatin or cisplatin chemotherapy, and cryotherapy
have yielded some mixed success.
Lipomas
Lipomas are benign neoplasms of adipose tissue and are the most common skin
tumor in avian species. Lipomas are usually well circumscribed, but infiltrative
lipomas have been reported in psittacines.70,71 Lipomas occur frequently in obese
birds, specifically budgerigars, Quaker parrots, Amazon parrots, and macaws
(Fig. 7).
Lipomas are most commonly found in the subcutaneous tissues and can arise any-
where on the body, including inside the thoracic or coelomic cavity. A recent study18
reported that lipomas were the most common neoplasm referred for a surgical
procedure in birds. Most lipomas were present subcutaneously in the pericloacal
area (see Fig. 7B). Cytology can yield a population of well-differentiated adipocytes
(Fig. 8). They are prone to lysis, however, during sampling and their content dissolves
Avian Oncology 71
during the staining process. The slide, therefore, can look devoid of material despite a
seemingly copious sample visible at the time of slide preparation. Treatment depends
on tumor size and location. Dietary changes and increase in exercise are appropriate
for many obese avian patients. Lipomas can resolve once the obesity has been cor-
rected. In a pilot study, supplementation with L-carnitine (1000 mg/kg of pellets) has
been shown to reduce subcutaneous lipoma size and body weight in budgerigars
compared with the control group.72 Further research is necessary to fully understand
the possible benefits of this supplement. If the tumor is growing fast or causing
discomfort, surgical excision should be performed and the tissue submitted for histo-
pathologic analysis to obtain a definitive diagnosis. A differential diagnosis for lipomas
is a liposarcoma.73,74 These do not result from malignant transformation of a lipoma.
They are composed of immature adipocytes and are typically less well circumscribed
Fig. 8. Cytologic appearance of a lipoma. Note this sample consists of large clusters of intact
well-differentiated adipocytes, which is consistent with a lipoma. Subcutaneous fat has the
same appearance; therefore, the interpretation depends on clinician confidence that these
cells are representative of the mass sampled. (Courtesy of Cecilia Robat, Madison, WI.)
72 Robat et al
and more invasive. They act more aggressively and recurrence rates are high and
metastasis common.74
Fibrosarcomas
Fibrosarcomas are a type of soft tissue sarcoma (Fig. 9). They are a malignant tumor of
fibrous tissue. They are locally invasive, and metastasis is uncommonly reported.75,76
They are most commonly seen in the facial/oral regions and bones and can be seen in
the coelomic cavity or cloaca77 as well. They tend to have a high recurrence rate after
conservative surgery due to their invasive nature and the need for wide surgical margins.
Postoperative radiation therapy with or without intralesional chemotherapy should be
considered and has been described as effective, if radical surgery and complete excision
are not achievable.28,29
Myxosarcomas
Myxosarcomas are uncommon soft tissue sarcomas, mostly reported in chickens and
in a kori bustard.31 The authors diagnosed a metastatic myxosarcoma in a severe ma-
caw (Fig. 10). This neoplasm produces abundant mucinous stroma, which can readily
be sampled on fine-needle aspirate (see Fig. 10). They are locally invasive with a low
metastatic rate. Wide surgical margins are necessary for adequate tumor control.
Xanthomas
Xanthomas are dermal non-neoplastic masses composed of lipid-laden macrophages
and cholesterol (ie, cholesterol granuloma). Xanthomas are more common in the skin
and subcutaneous tissues of gallinaceous birds and psittacines.78 Grossly, they are
friable and well-vascularized yellow/orange masses, located on the dorsum, wings,
and thighs and, therefore, can easily be mistaken as a neoplastic mass. Cytologic ex-
amination of a fine-needle aspirate shows multinucleated giant cells and cholesterol
clefts. Xanthomas are thought to develop secondary to obesity and hyperlipidemia
with concurrent trauma.79 A diet supplemented in vitamin A or precursors may help
treat these masses; however, no treatment is necessary unless the mass in causing
functional problems or being traumatized.
Fig. 9. Cytologic appearance cells aspirated from a mass on the wing of 3-year-old budger-
igar (M undulatus). Note the large mesenchymal cells, with high nuclear:cytoplasmic ratios,
up to 5-fold anisocytosis and anisokaryosis, and prominent multiple nucleoli, consistent with
a sarcoma, most likely a soft tissue sarcoma (magnification 600). (Courtesy of Melanie Am-
mersbach, Guelph, Ontario.)
Avian Oncology 73
Fig. 10. A 36-year-old severe macaw (Ara severus) that presented with a large mass over the
right sternal area. (A, B) Cytologic aspirate of the mass revealed a pleomorphic mesen-
chymal population with moderate to high nuclear:cytoplasmic ratios, abundant pale baso-
philic cytoplasm, and (A) numerous clear punctate vacuoles and (B) fine magenta granules
consistent with a malignant mesenchymal tumor. (C) Postmortem diagnosis was a myxosar-
coma, with metastasis to the lungs. (Courtesy of Ruth Houseright, Madison, WI.)
Musculoskeletal Tumors
Musculoskeletal tumors in birds are infrequently reported in the literature. The most
common are osteosarcoma and chondrosarcoma. They most commonly arise from
long bones but are also reported in the ribs and skull bones. Clinical signs include
lameness, pain, or presence of a mass. Diagnosis is suspected based on radiographic
findings of osteolysis with or without proliferation; however, a definitive diagnosis can
only be achieved on histopathology. Although osteosarcoma commonly metastasizes
to the lungs in dogs, it seems infrequent in birds, and in 10 reported cases, 4 tumors
metastasized (only 1 to the lungs).80 As in other species, chondrosarcomas are locally
invasive with a low metastatic rate (see Fig. 2).80 A synovial cell sarcoma arising at the
site of a previous fracture, associated with an intramedullary pin,81 has recently been
described. Other nonmalignant neoplasms of bone, such as chondromas and oste-
omas, have also been reported. Leiomyosarcoma is a tumor of smooth muscle. It is
most commonly reported in intracoelomic organs, such as the spleen and gastrointes-
tinal tract. It is locally invasive and infrequently metastasizes.82 Rhabdomyosarcomas
are malignant tumors of skeletal muscle. They are most common in the muscles of the
shoulder and wing but can arise from any skeletal muscle.11,12,83 Surgery is the treat-
ment of choice although behavior of this neoplasm and expected outcome are not
described in birds.
Hematopoietic Tumors
Lymphoma is one of the most common neoplasms in companion birds and the most
frequent neoplastic condition diagnosed at the authors institution in avian patients.
Lymphoma can manifest in birds as a visceral, cutaneous, retrobulbar or periorbital,
oral, or leukemic disease (Figs. 11–13).2–4,13,27,33 Cutaneous lymphoma most
commonly occurs around the head/periocular/neck area (see Fig. 12) and may pre-
sent as diffuse swelling or as multifocal nodules.14,15 Lymphoma may either occur
in organs or tissues, solely in the blood (leukemia), or in both (leukemic lymphoma)
(see Fig. 12). Clinical signs reported are progressive weight loss and lethargy, feather
loss, self-mutilation, a distended coelomic cavity (secondary to hepatosplenomegaly)
(see Fig. 13), and diarrhea, among others. Blood work may reveal anemia, lymphocy-
tosis, or elevated liver values. These changes are nonspecific for lymphoma; however,
a severe lymphocytosis should raise suspicion for a leukemic process (see Fig. 12D).
Rarely, paraneoplastic hypercalcemia4 and monoclonal hyperglobulinemia84 have
been reported.
74 Robat et al
Fig. 11. Clinical presentation of lymphoma in companion birds. (A) Amazon parrot (Amazona
spp) with severe swelling and ulceration of the pericloacal skin and cloacal opening. (B) Red
lory (Eos bornea) with unilateral severe periocular swelling and exophthalmos. In both cases
the diagnosis of lymphoma was made by cytology. (Courtesy of Christoph Mans, Madison, WI.)
Fig. 12. A 22-year-old Congo African gray parrot (P erithacus) diagnosed with leukemic cuta-
neous lymphoma. (A) Alopecia and scabbing affecting skin of the head and (B) pericloacal
area. (C) Cytologic examination of samples collected from the skin of the head reveal an
increased number of lymphocytes, a majority of which are medium-sized with a lower number
of small and large lymphocytes (magnification 1000). (D) Blood smear showing marked
lymphocytosis. The absolute lymphocyte count was 192 103/uL (magnification 600).
(Courtesy of Christoph Mans and Ruth Houseright, Madison, WI.)
Avian Oncology 75
Fig. 13. Multicentric lymphoma in a Gouldian finch (Erythrura gouldiae). (A) Cytology of a
fine-needle aspirate of the enlarged liver, showing hepatocytes and large neoplastic lym-
phocytes, which is consistent with hepatic lymphoma (magnification 1000). Treatment
with high dose L-asparaginase (1600 U/kg intramuscularly) and prednisolone did not result
in clinical improvement. (B) Postmortem photograph showing the severely enlarged liver.
Multicentric lymphoma was the final diagnosis. Neoplastic lymphocytes were found in the
liver, spleen, lungs, intestine, bone marrow, and skeletal muscle, among many other tissues.
(Courtesy of Cecilia Robat, Madison, WI.)
Respiratory Tumors
Respiratory neoplasia is uncommon in birds (see Fig. 3). SCC of the nasal cavity and
infraorbital sinus has been reported.86,87 Air sac and bronchial adenocarcinoma and
cystadenocarcinoma have been reported in Psittaciformes. Most patients present
with advanced respiratory clinical signs, weakness, and lethargy. Air sac cystadeno-
carcinoma was reported in 6 cockatoos.88 All cases presented with severe respiratory
clinical signs, which were rapidly fatal. Extensive neoplastic invasion of the lungs, ma-
jor airways, and/or humerus was present in all cases. Respiratory tumors in birds seem
to be highly locally invasive and diffuse metastatic disease to intracavitary organs and
bones is common.8,88–94 A unique and incompletely characterized form of pulmonary
tumors seems to develop in cockatiels.95 It has been reported as pulmonary bimorphic
tumor, undifferentiated pulmonary tumor, or pulmonary sarcoma. These tumors have
a unique histologic appearance. They are very aggressive and locally invasive into sur-
rounding structures but appear less metastatic. A respiratory hamartoma was
76 Robat et al
Gastrointestinal Tumors
Adenocarcinomas
Adenocarcinomas of the proventriculus or ventriculus are described in birds, the most
common site being the isthmus.97–99 Clinical signs are associated with the presence of
tissue proliferation inhibiting the normal digestive process. Affected birds often regur-
gitate/vomit, are hyporexic and may pass undigested food and have melena. Anemia
and hypoproteinemia are common. Antemortem diagnosis is only possible is larger
species, in which endoscopic biopsies can be performed. In others, these tumors
are usually diagnosed at the time of necropsy. Distant metastases are described.97
Treatment is not described. In dogs, treatment of gastric carcinoma is not rewarding
and the prognosis is poor.
Cholangiocarcinomas
Cholangiocarcinomas have most commonly been described in Amazon par-
rots.100–103 These are aggressive tumors that are known to metastasize. One report
has suggested a link between papillomatosis and bile duct carcinoma; however, these
findings should be interpreted with caution, because numbers were low in that
study.102 Clinical signs are usually nonspecific as are biochemical changes. Ante-
mortem diagnosis is uncommon; however, lesions may be seen on ultrasound imaging
and should be sampled for cytologic diagnosis. Prognosis is poor. Carboplatin has
been used successfully in a yellow-naped Amazon parrot (Amazona ochrocephala).104
Urogenital Tumors
Ovarian and oviductal neoplasms of companion birds include adenocarcinoma, ade-
noma, carcinomas, cystadenocarcinomas, granulosa cell tumors, and hemangiosar-
coma.105–107 The most common tumor seems to be ovarian tumors of stromal cell
origin (granulosa cell tumor) and oviductal adenocarcinomas. These occur in budger-
igars at a frequency of 4% to 14%. Clinical signs include persistent breeding behavior,
egg retention, and coelomic distention secondary to ascites (Fig. 14) or organome-
galy, and sometimes no clinical signs are present at all. Polyostotic hyperostosis
has been described in patients with ovarian tumors and is thought to be associated
with secreting large amounts of estrogens108; however, the association has been
refuted in another publication.109 Diffuse coelomic metastasis is common, because
these tumors are commonly diagnosed late in the course of the disease. Diagnosis
is obtained via imaging and pathology. No effective treatment is reported for ovarian
tumors unless disease is localized and surgical excision possible, which is uncom-
mon.110 Leuprolide acetate was reported to provide a partial clinical response in 2
cockatiels with ovarian tumors.61 For oviductal tumors, surgical removal may be
attempted but carries high anesthetic and surgical risk, in particular in small patients.
Therefore, treatment with GnRH supra-agonists (eg, leuprolide acetate and deslorelin
acetate) is frequently performed to improve clinical signs (Figs. 15 and 16).106
Testicular tumors arise from Sertoli cells (Sertoli cell tumor), spermatogenic epithe-
lium (seminoma), or interstitial cells (interstitial cell tumor). They are most commonly
reported in budgerigars. Clinical signs include tachypnea, coelomic distention, and
tachypnea secondary to and enlarged testicle. Estrogen-producing Sertoli cell tumors
lead to feminization of male birds, predominately budgerigar. Affected animals often
have a change of color of the cere from blue to brown, widening of the pubic bones,
Avian Oncology 77
Fig. 14. Female budgerigar (M undulates) with severe coelomic distension. (Courtesy of
Christoph Mans, Madison, WI.)
a broad-based stance, and an enlarged cloacal opening (Fig. 17). Radiographs reveal
an increase in soft tissue opacity in the coelom and hyperostosis secondary to hyper-
estrogenism. Unilateral paresis/paralysis due to the compression of the sciatic nerve
root may occur. Seminomas have been reported to form metastases in birds.6,111
Surgical excision is the treatment of choice but is usually a high-risk procedure, in
Fig. 15. Postmortem photograph of a female cockatiel (N hollandicus) with a large coelomic
mass, diagnosed as an oviductal adenocarcinoma. (Courtesy of University of Wisconsin,
School of Veterinary Medicine, Madison, WI; with permission.)
78 Robat et al
Fig. 17. Sertoli cell tumor in a budgerigar (M undulatus). (A, B) Ventrodorsal and lateral sur-
vey radiograph showing increased soft tissue opacity in the coelom and hyperostosis of all
bones and an increased distance between the pubic bones, secondary. (C) Coelomic ultra-
sound identifying a left-sided intracoelomic mass. (D) Postmortem examination revealing
a large gonadal mass (arrow), later confirmed as a Sertoli cell tumor. Note the severely
enlarged vent opening, secondary to hyperestrogenism. (From Mans C, Pilny A. Use of
GnRH-agonists for medical management of reproductive disorders in birds. Vet Clin North
Am Exot Anim Pract 2014;17:23–33.)
Avian Oncology 79
particular in small birds. In 1 report, surgical removal of a testicular tumor was attemp-
ted in 5 budgerigars. Two died perioperatively, 2 survived and were asymptomatic
3 years later, and 1 had incomplete surgical excision followed by carboplatin chemo-
therapy but failed to respond to chemotherapy.111 Clinical signs associated with Ser-
toli cell tumors have been successfully managed in budgerigars using deslorelin
implants.62 Deslorelin acetate implants (4.7 mg) were placed subcutaneously in the
knee fold under general anesthesia.62 A response to treatment was reported in 7 of
9 budgerigars, evident by a change of cere color from brownish to blue. Further im-
provements included resolution of previously diagnosed lameness (3/3) and an
improved general condition (7/8).62 Initial clinical improvement was noted after several
days to 4 weeks. Reoccurrence of clinical signs was noted on average 19 weeks after
initial deslorelin administration. Deslorelin implants were repeatedly administered after
reoccurrence of clinical signs and the effect of deslorelin lasted on average 20 weeks.
Treatment of suspected Sertoli cell tumors in budgerigars with deslorelin implants was
found effective by temporarily treatment the clinical signs, secondary to abnormal es-
trogen production, and no significant side effects were reported.62
Renal carcinomas are the most common renal neoplasms reported. Other renal
neoplasms reported include renal adenomas, nephroblastomas and cystadenoma,
among others.112 Budgerigars are overrepresented and renal neoplasms account
for 17% to 20% of all neoplasms described in this species.113 A retroviral origin
was suggested but a recent publication refutes that theory.114 Affected birds usually
present with unilateral non–weight-bearing leg lameness, due to compression of the
lumbar or sacral nerve plexus (Fig. 18). Other clinical signs may include coelomic
distention, lethargy, regurgitation, and emaciation due to the intracoelomic mass.
Renal neoplasms rarely metastasize. Clinical signs and signalment are usually strongly
suggestive for a renal neoplasm. Diagnostic imaging can be used to attempt to diag-
nose the underlying disease, but histopathology is necessary to confirm the diagnosis.
When arising from the cranial division of the kidney, the tumor can be mistaken for a
gonadal tumor. Renal tumors can be very cystic. Metastatic rate is usually low. No
effective therapy is recognized in birds. Carboplatin resulted in a short-lived clinical
improvement in 1 patient.35
Fig. 18. (A) Budgerigar (M undulatus) with paralysis of the right leg secondary to renal
adenocarcinoma. (B) Gross image showing renal adenocarcinoma that is compressing ischi-
atic plexus. (Courtesy of D. Sanchez-Migallon Guzman and D.A. Goldsmith, Davis, CA.)
80 Robat et al
Ocular Tumors
Neoplasms involving the eyes and adjacent structures are uncommon in birds. Various
intraocular neoplasms (eg, medulloepitheliomas,115,116 lymphoreticular tumors,27 mel-
anocytic tumors,117 rhabdomyosarcomas,6 and osteosarcomas26) as well as neo-
plasms of the adnexal ocular structures (ie, conjunctiva, eyelids, and orbit), such as
periorbital liposarcoma,74 retrobulbar adenocarcinoma,118 and orbital lymphoma,119
have been reported. Retrobulbar or orbital lymphoma is among the most common
ocular neoplasms (see Fig. 11B). In a recent retrospective review of avian ocular neo-
plasms, approximately half of the cases were metastatic lesions affecting the globe
and not primary neoplasms.120 Of the primary ocular tumors in this review, none of
the observed primary ocular tumors was identified as having metastasized to regional
or distant locations.120
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