Long-term management of thymic lymphoma in a java sparrow (Lonchura oryzivova).
Key words: lymphoid tumor, chlorambucil, prednisolone, avian, Java sparrow, Lonchura oryzivora
A 25-g, 4-year-old Java sparrow (Lonchura oryzivora) was presented for examination of a cervical mass. The mass was first noticed by the owner approximately 1 month before presentation, and it had gradually enlarged during the previous 2 weeks. The bird's appetite and overall condition were not affected by the mass. On presentation, the bird was alert and well hydrated. The physical examination revealed a solid, featherless mass approximately 1.5 [cm.sup.3] in size with a stalk connected to the deep cervical region. The epithelium covering the mass was not damaged, and no discharge from the mass was observed. The remainder of the physical examination was unremarkable. The bird was free to roam the owner's home, and it was housed in 20 x 30 x 50-cm cage during the evening and nighttime hours. The bird was primarily fed a seed diet, with food available ad libitum.
At the owner's request, blood tests were not performed because of the risk of blood loss due to the bird's size. Direct examination and a Gram's stain of the fecal material revealed no abnormalities, and results of the whole body radiograph were unremarkable. General anesthesia was induced with 5% isoflurane and oxygen. The bird was then intubated with an 18-gauge intravenous catheter, and anesthesia was maintained with 2% to 3% isoflurane in oxygen via the catheter by intermittent positive-pressure ventilation. The heart rate and oxygen saturation were monitored by pulse oximeter throughout the biopsy procedure.
The owner declined surgical excision because of concerns about age of the patient, and the infiltrative nature of the mass made complete excision unlikely. Therefore, a Tru-cut biopsy was performed using a Temno 16-gauge X 9-cm biopsy needle (CareFusion, San Diego, CA, USA). Recovery was uneventful but the owner reported transient lameness, which resolved with cage rest. The biopsy sample was fixed in 10% neutral buffered formalin and submitted for histopathologic evaluation. The observed cells were arranged in a sheet with a strip of eosinophilic connective tissue. The predominant cell type was round cells with a distinct cellular border and basophilic cytoplasm and exhibiting a high nuclear: cytoplasm ratio. The anisokaryotic, round nuclei were centrally located and contained highly condensed chromatin; mitotic events were rare. Genomic DNA was extracted from the formalin-fixed, paraffin-embedded biopsy tissues by using the Qproteome FFPE Tissue Kit (Qiagen, Chatsworth, CA, USA). The genomic DNA was analyzed by polymerase chain reaction for the presence of Marek's disease virus, lymphoid leukosis virus, and reticuloendothelial viruses, but none were detected. Immunohistochemical staining was performed by using anti-CD3 (CD3, Dako, Glostrup, Denmark), anti-CD79a rabbit polyclonal antibodies (CD79a, Dako) and anti-CK mouse monoclonal antibody (Cytokeratin clone AE1/AE3, Dako). The neoplastic cells exhibited only CD3 reactivity, indicating a T-lymphocyte origin (Fig 1), while CK-positive cells were organized as normal thymic epithelial networks (Fig 2). (1) The diagnosis of thymic lymphoma was made.
Choices of chemotherapy regimens were limited because of the small size of the bird and the difficulty associated with intravenous administration. (2-5) 5 Chlorambucil (2 mg/kg PO twice weekly) was selected because it can be administered orally at a relatively low frequency. During treatment, the bird's activity level, appetite, and fecal output were monitored by the owner. The size of the mass, the bird's body weight, and the fecal Gram's-staining status were monitored at weekly clinical examinations. Vitamin B complex (dosed based on thiamine 1 mg/kg PO q24h), ursodeoxycholic acid (10 mg/kg PO q24h), silimarin (100 mg/kg PO q12h), and sucralfate (25 mg/kg PO q12h) were prescribed to reduce side effects of chemotherapy. Soft stools were observed occasionally. After 3 weeks of chemotherapy, the size of the mass was reduced by approximately 66%.
At week 19, the bird became acutely ill and anorexic. The chlorambucil treatment was withheld by the owner from weeks 20 to 22, and the bird's condition recovered remarkably. Although the neoplasm began to grow gradually, the patient thrived during this period. At week 23, the chlorambucil regimen was resumed. At week 28, although the bird's level of activity remained high, the size of the neoplasm remained at 1.5 X 1.5 cm, and the chlorambucil treatment was discontinued. From weeks 29 to 60, prednisolone (2.2 mg/kg PO q12h) was administered as a palliative treatment. (5) During weeks 53 to 61, although the size of the tumor had not changed significantly, three episodes of depressed physical activity and anorexia occurred. The bird became acutely ill at week 61, and treatment was discontinued. The owner elected to euthanatize the bird, and necropsy was declined.
In this clinical report, we describe the treatment and long-term management of thymic lymphoma in a Java sparrow. Lymphoma has been described in birds in the orders Anseriformes, Charadriiformes, Columbiformes, Ciconiiformes, Galliformes, Passeriformes, Psittaciformes, Strigiformes, Sphenisciformes, Pelecaniformes, and Struthioniformes. (6-15) Thymomas, classified histologically as either epithelial or lymphocytic, are rarely reported in avian species and have only been documented in an African grey parrot (Psittacus erithacus), a finch (unspecified species), domestic chickens, budgerigars (Melopsittacus undulatus), Java sparrow, (16) and a red-tail common mynah bird (Acridotheres tristis). (17) Thymoma is the main differential diagnosis for thymic lymphoma and can be easily confused because they are sometimes accompanied to a greater or lesser degree by small lymphocytes. (16)
In this Java sparrow, the diagnosis of lymphoproliferative diseases was straightforward, but further investigation into the type of lymphocyte malignancy and to differentiate thymoma from thymic lymphoma requires special staining techniques. Immunocytochemistry using monoclonal antibodies against cell-surface glycoproteins is frequently used to differentiate between B- and T-lymphocyte malignancies in dogs, (18) and similar assessments can be used in birds. (3,14,15,19,20) Also, a cervical type AB thymoma (mixed) tumor was diagnosed in a mynah with the help of clinicohistologic, immunohistochemical, and cytohistopathologic study. (17) In humans, cytokeratin profiles are used to differentiate thymic lymphoma from thymoma. (1) A positive treatment response was reported in an umbrella cockatoo (Cacatua alba) with B-cell lymphoma, (3) and chlorambucil treatment failed in a great horned owl (Bubo virginianus) with disseminated T-cell lymphoma. (15) These findings in birds are consistent with the current concept that B-cell tumors in dogs respond more favorably to treatment than T-cell tumors. (3) In the Java sparrow that we treated, the owner decided against blood testing because of the volume required for diagnostic tests and the risks of blood loss due to the bird's size. However, an immunocytochemical analysis of a biopsy sample provided sufficient evidence for a final diagnosis of thymic lymphoma. Reports of favorable responses to treatment in animals with T-cell lymphoid tumor are scant. (3)
Although lymphoid neoplasias in psittacine and passerine pet species are commonly believed to be caused by viral infections, limited data have been reported in support of this. Molecular investigations of multicentric lymphoma in starlings (Sturnus vulgaris) have suggested a retroviral etiology. (11) Retrovirally induced lymphoma has also been suspected in other passerine birds. In our clinical report, an analysis of the genomic DNA from the biopsy tissue revealed that neither the Marek's disease virus, nor the lymphoid leukosis virus, nor a reticuloendothelial virus was present. Thus, the PCR results suggested primary lymphoma.
The treatment of lymphoma in avian species is challenging. Currently, no standard protocols have demonstrated a high level of success in the longterm management of lymphoma in birds. (2,3) Among various therapeutic agents, only chlorambucil, prednisolone, and cyclophosphamide can be administered orally. However, prednisolone and cyclophosphamide combination therapy is most often excluded in the treatment of birds because of its adverse effects in avian species. (21,22) In addition, chlorambucil is the only agent that has demonstrated successful treatment when used alone. (4) In this sparrow, chlorambucil was replaced with prednisolone at week 29 because of a failure to reduce the tumor size during weeks 23 to 28, which indicated an ineffective response to the second round of chlorambucil treatment. Although lymphoma has demonstrated responsiveness to the initial treatment, the development of resistance to the drugs used in the initial protocol has been reported. (23) Lymphoid neoplasms in humans have also demonstrated resistance to chlorambucil. (24) Thus, the prednisolone treatment was introduced in the treatment of the Java sparrow as a rescue protocol.
Monitoring side effects of chemotherapy in small animals is challenging. Invasive procedures are not used routinely. Thus, the medication was adjusted based on the bird's clinical status and the diagnostic test results. The most common adverse effects associated with chlorambucil therapy are myelosuppression and gastrointestinal toxicosis. Neutropenia is the most common cytopenia associated with chemotherapy-induced myelosuppression, and sepsis is the most common complication associated with neutropenia. (3) We used vitamin-B complex, ursodeoxycholic acid, silymarin, and sucralfate as prophylactic agents to mitigate the side effects of chemotherapy in the Java sparrow, and antibiotics were prescribed only when necessary. Chlorambucil and prednisolone were used separately for 18 and 25 weeks, respectively. Although the dosages of these drugs were comparable to those investigated in various clinical trials, combination chemotherapy protocols are often preferred in cancer treatment to target multiple aspects of the pathologic mechanisms of the cancer and delay the onset of drug resistance. (23) In addition, chlorambucil is a potent steroid-sparing agent, thereby reducing the required dose and toxic effects of steroids. (25)
The field of avian oncology remains in its infancy. Data regarding the effectiveness of the various treatments available are needed to aid clinicians in choosing optimal regimens. Although thymic pathology has been reported in Java sparrows, (19,26) we describe the long-term management of thymic lymphoma of a clinical case. Our description of the therapeutic limitations, tumor drug-resistance, and modifications to treatment may aid the efforts of other clinicians in the treatment of lymphoid tumors in other passerine birds.
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Pin Huan Yu, DVM, MS, and Chau Hwa Chi, DVM, PhD
From the Veterinary Teaching Hospital, Section of Large and Wild Animal Medicine, School of Veterinary Medicine, National Taiwan University, No 153, Sec 3, Keelung Rd, Da'an District, Taipei City 10672, Taiwan.
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|Author:||Yu, Pin Huan; Chi, Chau Hwa|
|Publication:||Journal of Avian Medicine and Surgery|
|Article Type:||Clinical report|
|Date:||Mar 1, 2015|
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