Overview of Tumors. Section I: Clinical Avian Neoplasia and Oncology

Table of Contents

• Section I: Clinical Avian Neoplasia and Oncology
• Cutaneous Masses

• Xanthomas
• Lipomas
• Mucoepidermoid Carcinomas
• Fibrosarcomas
• Squamous Cell Carcinomas

• Neoplasia Occurring in the Musculoskeletal System

• Chondromas
• Osteosarcoma

• Internal Neoplasia

• Hemangiomas
• Internal Carcinomas
• Endocrine Neoplasia
• Respiratory Neoplasia
• Lymphoma/Lymphosarcoma

• Chemotherapeutic Agents
• Section II: A Retrospective Study of Case Submissions to a Specialty Diagnostic Service

Avian neoplasias encountered in practice include cancer of the skin, oral cavity, sinuses, liver, kidney, reproductive organs, bones, brain, vascular structures and connective tissue. External tumors may be detected by physical examination and can often be diagnosed by needle aspiration, wedge, punch or surgical biopsy. Internal neoplasias often require radiographs, ultrasound, endoscopy, and biopsy or exploratory surgery to identify, diagnose and determine the extent of the neoplastic processes.

Treatment of neoplastic processes in birds is poorly documented. Most reports of treatment protocols are either anecdotal or involve a single patient. Many reports are not published, but are to be found in avian veterinary discussion groups on the Internet [35-37].

The presentation in this text of these anecdotal treatments is problematic. Failure to include preliminary information regarding efficacy and/or clinical response may reduce the practitioner’s willingness and ability to recommend treatment. However, future studies may either reinforce these experimental protocols or they may demonstrate a lack of efficacy or serious side effects of these regimes. The ultimate decision will lie with the knowledgeable practitioner and the well-informed client.

To date, the treatment of avian neoplasia has mirrored treatment in other domestic species. Generally, solid tumors are best treated with surgical excision, while systemic neoplastic processes (i.e., systemic lymphoma, metastatic conditions) are most effectively managed with use of systemic chemotherapy. Cases in which surgical excision is incomplete or impossible may benefit from alternative forms of local therapy, including external beam radiation (Cobalt 60 or linear accelerator), cryotherapy, photodynamic therapy or hand-held radiation applicators.

Cutaneous Masses

These may be pseudo-neoplastic conditions such as xanthomas and lipomas, or neoplastic lesions.

Xanthomas

These are generally friable, yellow-colored, fatty-appearing masses that may be located anywhere on the body, but are often seen on the distal wing, in the sternopubic area and on the keel (see Chapter 13, Integument). The origin of xanthomas is unknown, however, dietary improvement, including sufficient vitamin A or vitamin A precursors, has been noted to be curative in less advanced cases. Xanthomas tend to be very vascular and surgical excision, when necessary, should be undertaken with due attention to hemostasis. Diffuse xanthomas may be amenable to cryotherapy, but attention must be paid to maintenance of the vascular supply [35].

Lipomas

These occur most frequently in budgerigars and are usually located on the keel or in the sterno pubic area. Most early lipomas respond to modified diet therapy. Lipomas that cause clinical signs can be addressed via surgical excision. Malignant liposarcomas are rare in psittacines [33].

Mucoepidermoid Carcinomas

Mucoepidermoid carcinomas are rarely reported in birds. In humans, these tumors demonstrate variable degrees of malignancy and surgical resection is often curative. Comparable grading of this type of neoplasia has not been established in the avian patient (Fig. 20.1, Fig. 20.2).

Figure 20.1. Mucoepidermoid carcinoma. (Lucy Bartlett).

Figure 20.2. Mucoepidermoid carcinoma after resection. (Lucy Bartlett).

Fibrosarcomas

These can occur anywhere on the body, but are most commonly seen in the oral cavity, associated with long bones, or in the abdominal cavity (Fig. 20.3, Fig. 20.4).

Figure 20.3. Fibrosarcoma on the face of a budgerigar.

Figure 20.4. Fibrosarcoma on the wing of a lovebird.  

Fibrosarcomas may be subcutaneous or more deeply located in underlying tissue, and often appear fixed and proliferative with a nodular, red surface. They tend to be locally invasive and often recur with conservative surgical excision. Therefore, additional local treatment in the form of radiation therapy is often indicated for providing long-term local control. As the metastatic rate in other domestic species ranges from 5 to 15%, local disease management is paramount, with metastatic control as a secondary concern. Surgical excision followed by both radiation and chemotherapy has been reported with some success in a few publications [14]. Strontium radiation therapy, although limited by depth of penetration, has been anecdotally reported as efficacious in several instances [35].

Squamous Cell Carcinomas

These also may occur anywhere on the body, being most prevalent at mucocutaneous junctions of the head (Fig. 20.5), on the distal wing and on the phalanges. The uropygial (preen) gland also may develop either adenocarcinoma or squamous cell carcinoma. (Note that Amazona spp. do not possess a preen gland). Squamous cell carcinomas tend to be extremely locally invasive and complete excision is rarely accomplished. Radiation therapy has been attempted with some success, however, squamous cell carcinoma appears to be an exceptionally radioresistant tumor and long-term control is rare. Anecdotal reports indicate that radioresistance may be even greater in birds than in mammals [19, 35]. Strontium therapy when tumor depth is not a limiting factor has shown some promise in selected psittacine cases [35]. Distant metastasis is rare, therefore chemotherapy is not commonly utilized. Photodynamic therapy (PDT) has been attempted in two reported cases. One case of a squamous cell carcinoma in the beak of a hornbill showed a positive result in decreasing tumor size, but failure to eliminate the neoplasia [31]. The second case demonstrated a positive response to PDT after each treatment, but treatments were not able to be administered at regular intervals [28].

Figure 20.5. Squamous cell carcinoma of the rhamphotheca, and papillomatosis in an older Timneh grey parrot.  

Neoplasia Occurring in the Musculoskeletal System

Theoretically these include the benign lesions such as chondroma and hemangioma, and malignant tumors including osteosarcoma, chondrosarcoma and leiomyosarcoma. Wide surgical resection or amputation are generally the suggested methods of treatment, as benign lesions are often cured with complete excision and a decrease in tumor burden can be accomplished in malignant lesions. As tumors such as osteosarcoma carry high metastatic rates, additional therapies may be indicated. Extrapolation from canine and feline oncology may suggest other modalities such as radiation therapy for additional local treatment and chemotherapy for systemic control.

Chondromas

Therapy for chondromas generally involves aggressive surgical excision of the affected area (Fig. 20.6). Radiation and chemotherapy may be considered.

Figure 20.6. Chondroma on the leg of a budgerigar.  

Osteosarcoma

Confirmation of osteosarcoma has rarely been reported in psittacines. Species and anatomic location predilections have not been noted in psittacines. Documentation of classifiable radiographic changes consistent with osteosarcoma is not available for birds.

A biopsy should be obtained from patients where radiographic bony lesions are present. Under inhalant anesthesia, a 22- to 20-gauge needle can be surgically introduced into the bone. A sufficient sample is usually obtained and subsequently retained in the hub of the needle. The sample can then be dislodged with smaller gauge wire and submitted. If a diagnosis of osteosarcoma is received, amputation with follow-up chemotherapy is the current recommended protocol extrapolated from canine medicine.

Internal Neoplasia

Hemangiomas

These seem to occur more commonly than hemangiosarcomas in birds. Hemangioma may be internal or external and commonly appears as a red-purple, flat, firm lesion (see Chapter 13, Integument). Although histopathologically benign, in at least one case in this author’s experience, hemangioma occurred in a juvenile African grey (Psittacus erithacus) and involved the coelomic cavity, small intestine, liver, lung, air sacs and pericardium. Complete surgical excision could not be accomplished and euthanasia was eventually required (Fig. 20.7and Fig. 20.8). Treatment of a hemangiosarcoma with radiation therapy has been reported in one case [9].

Figure 20.7. Gross appearance of the abdomen in a 9-month-old African grey parrot with diffuse coelomic hemangioma.  

Figure 20.8. The bird in Fig. 20.11, showing hemangioma encompassing most abdominal viscera.  

Internal Carcinomas

These are commonly reported in birds and include ovarian neoplasias (of various cell origins), renal carcinomas, hepatic adenocarcinoma, hepatobiliary and pancreatic adenocarcinoma (related to papillomas in Amazons), splenic and gastric carcinomas. Papillary carcinomas of air sac origin are locally invasive and may present as external masses. Anecdotal reports exist indicating intralesional carboplatin therapy may be useful in ovarian and renal adenocarcinoma, generally following surgical debulking and confirmation of the neoplasia on histopathology [18,34]. Bile duct carcinoma also has been treated with carboplatin successfully in one report [38]. Toxicity studies with cisplatin in cockatoos indicate that psittacine tolerance for this drug may be greater than that of mammals [8].

Tamoxifen administration has not been evaluated for efficacy in cases of avian ovarian carcinoma, but anti-estrogenic activity was suggested and side effects were minimal in one drug trial [17]. GnRH agonists [a] have been effective empirically (dosed at 200 - 800 µg/kg), however, confirmation of neoplasia (as opposed to cystic ovarian disease) has not often been confirmed prior to therapy [16,20].

Doxorubicin (adriamycin) is commonly employed in the treatment of carcinomas in human and canine patients. The limiting toxic effects of doxorubicin include myelosuppression and cardiac toxicity. To date, the degree to which these concerns will apply to avian cancer patients has not been determined. Anecdotal reports of both toxicity and efficacy of doxorubicin in avian patients are currently inconclusive [34]. Dosages of 50 - 60 mg/m2 have been used with no adverse reactions. In several cases there has been significant tumor regression (Goldsmith, Lightfoot, unpublished data, 2004).

Carcinomas, generally diagnosed at necropsy, are often found at the proventricular-ventricular junction. Death from this neoplasia may be due to hemorrhage, perforation and sepsis or endotoxic shock, or inanition and subsequent wasting. Metastasis to the lungs has been confirmed in one case report [4].

Biliary and pancreatic carcinomas are frequently diagnosed in the genus Amazona and to a lesser degree, Ara, in conjunction with internal papillomatosis [11,13]. A recent connection to a herpesvirus has been identified (see Chapter 32, Implications of Viruses in Clinical Disorders). Carboplatin has been used in several cases with equivocal results, but with no apparent toxicity [7,35,38].

Surgical excision is the treatment of choice with solitary lesions of hepatic cell carcinoma in other species, and is the only documented curative treatment in human medicine. Combinations of chemotherapy and radiation therapy have been used with equivocal results in people in an attempt to prevent or limit metastatic disease. In widely disseminated hepatic carcinoma, palliative chemotherapy is often employed. However, extrapolation from people would indicate that this type of cancer is highly resistant to chemotherapy. The most commonly employed chemotherapeutic agents in human medicine appear to be doxorubicin and 5-fluorouracil (5-FU), however, mean survival times do not appear to be statistically improved in patients with widely disseminated disease. The use of immunotherapy - including interferon, in conjunction with cisplatin, doxorubicin and 5-FU - has shown the most promise to date in human patients. Unfortunately, interferon is limited in its usefulness by cost and availability in veterinary medicine. The efficiency of radiation therapy for carcinomas and other neoplasias is largely unknown. However, tolerance of radiation therapy has been anecdotally reported as greater than anticipated.

Endocrine Neoplasia

Neoplasia of endocrine origin is not frequently reported in birds.

Pituitary Adenomas

These have been documented in multiple avian species, but are most prevalent in budgerigars and cockatiels. Affected animals may present with acute neurologic conditions (seizures/opisthotonos). They also may present with conditions related to the pituitary hormone(s) that are affected. Usually, this will be pronounced polydypsia and polyuria. Occasional presentations will be that of a retrobulbar mass and subsequent exophthalmia [27]. In human medicine, surgical resection and radiation therapy (if needed) are utilized for treatment. Size and monetary constraints make routine treatment by these methods unlikely in our small psittacine patients.

Thyroid

Budgerigars that are iodine deficient may develop nonneoplastic thyroid hyperplasia that presents as a thyroid mass, often causing a change in the voice or a respiratory squeak.

Thyroid Tumors

These are not as common in birds as they are in domestic rabbits, but do occur (Fig. 20.9). They may be intrathoracic or located in the area of the neck. In humans, classification according to cell type (medullary, cortical and mixed) is a prognostic indicator, with cortical tumors having the highest incidence of recurrence and malignancy. Thymoma and thyroid adenocarcinoma have been reported in several psittacine species. Surgical excision is the primary treatment recommendation. Adjuvant radiation and chemotherapy protocols are being utilized in human medicine. Cisplatin is used in many human chemotherapy protocols for thymomas and thymic carcinomas. Limited studies have shown that psittacines may be tolerant of the common side effects induced by cisplatin, and this agent may be useful in the treatment of these neoplasias.

Figure 20.9. Thymoma in a lovebird, intraoperatively. (Lucy Bartlett).

Pancreatic Neoplasias

Infrequent accounts of primary pancreatic neoplasia of variable cell origin, not associated with internal papillomatosis, have been reported [23].

Respiratory Neoplasia

Primary respiratory neoplasia is uncommon in psittacines [12]. An exception seems to be an intrathoracic neoplasia reported in cockatiels. It is characterized by the inclusion of two cell types, having both mesenchymal and epithelial cell components (see Section II of this chapter). Few other primary pulmonary neoplasias have been reported in the literature [2]. Metastatic pulmonary neoplasia may occur, but it is not noted with the same frequency as is documented in dogs [4].

Lymphoma/Lymphosarcoma

Numerous reports of exophthalmos in psittacines, particularly young African greys, have been diagnosed as retrobulbar lymphoma (Fig. 20.10). Differential diagnoses for this condition are pituitary adenoma and hyperplasia or adenoma of the Harderian gland. Lymphoma may have many presentations in pet birds, much as it does in other companion animals (Fig. 20.11). Chemotherapy is the treatment of choice for systemic disease, and surgery and radiation therapies have been successfully employed in cases of solitary lymphoma [6,35]. To date, no evidence of retroviral activity has been associated with psittacine lymphoma.

Figure 20.10. Retrobulbar lymphoma in a young African grey. (Lori Harrison).

Figure 20.11. Gross necropsy photo of the liver from the African grey in Fig. 20.10. A fine-needle aspirate of the liver demonstrated that the lymphoma had spread to involve the hepatic parenchyma. (Lori Harrison).

The clinician may find it useful to have access to current protocols for lymphoma that are utilized in canine medicine. Tracy LaDue, Diplomate ACVIM-Oncology and ACVR-Radiation Oncology, of Florida Veterinary Specialists in Tampa, Florida, USA, has generously provided the following abbreviated outline of therapeutic options and chemotherapeutic agents. These protocols are NOT established for avian patients, but are provided to give the practitioner a point of reference when attempting to design potential therapeutic regimes for birds with lymphoma. Again, species differences in response may well exist. Some of the chemotherapeutic agents listed may be determined to be either ineffectual or contraindicated in birds. As documentation of these variables occurs, it is hoped that protocols can be developed that will produce more predictable results in the avian patient.

Chemotherapy Protocols for Canine Lymphoma*

(Current recommended canine dosages can be found in Plumb’s Veterinary Handbook).

1. Oral Therapies

1. Prednisolone and cyclophosphamide
2. Lomustine (CCNU)

2. Injectable Therapy

1. COP-L Protocol

1. L-asparaginase injection
2. Oral prednisolone (tapering dose)
3. Oral weekly cyclophosphamide
4. Vincristine injections weekly IV

2. Single-agent adriamycin injections q 3 weeks IV
3. UW-Madison Cyclic Combination

1. L-asparaginase
2. Vincristine
3. Cyclophosphamide
4. Adriamycin
5. Prednisolone

Applicable testing (CBC, biochemistries, cardiac evaluation) should be performed to assess the initial and intratherapeutic health of the patient.

*It must be emphasized again that these protocols are designed for canine patients. Extrapolation to avian patients must be undertaken with the knowledge that efficacy and potential side effects have not been documented.

Chemotherapeutic Agents

Anticancer agents are typically broken into six categories based on their mechanism of action.

1. Alkylating agents such as cyclophosphamide and lomustine prevent cell replication by covalently binding to the nucleotide bases of the DNA molecule.
2. Antimetabolites will mimic purine, pyrimidine or metabolite precursors of the nucleotide bases, resulting in non-functional DNA.
3. Steroids such as prednisone and prednisolone cause lympholysis and suppress neutrophil function and antibody production.
4. Plant alkaloids such as vincristine bind to microtubules to prevent normal formation and function of the mitotic spindle. The antibiotics such as adriamycin intercalate between DNA base pairs to disrupt transcription and also cause oxygen free radical damage.
5. Miscellaneous drugs such as the Platinol compounds (cisplatin and carboplatin) also bind to bases of the DNA preventing replication, but have a bifunctional ability with double attachment to DNA strands.
6. L-asparaginase hydrolyzes asparagine to aspartic acid and ammonia, resulting in loss of an essential amino acid for cell function.

Most anticancer agents have associated vomiting, diarrhea and bone marrow suppression as sequelae. It is important to monitor patients for signs of dehydration or secondary infection as a result of chemotherapy administration. Some anticancer agents have particular toxicities known to that drug alone, such as sterile hemorrhagic cystitis due to cyclophosphamide metabolites in dogs and people. Such toxicities are not well reported in avian species and should be monitored for accordingly.

When confronted with a confirmed diagnosis of neoplasia, a current literature search is warranted due to the rapid advances and changes in treatment recommendations. Consultation with a veterinary oncologist will increase the likelihood of selecting an appropriate treatment regime and properly administering the chosen therapy.

Products Mentioned in the Text

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