Osteosarcoma of the tibiotarsus with possible pulmonary metastasis in a ring-necked dove (Streptopelia risoria).
Key words: osteosarcoma, tibiotarsus, pulmonary metastasis, avian, ring-necked dove, Streptopelia risoria
An adult intact female ring-necked dove (Streptopelia risoria) of unknown age was presented for non-weight-bearing lameness and picking at the right leg for 1 week. Physical examination revealed the dove was 5% dehydrated with an approximately 3.0- x 1.5- x 1.0-cm mass present on the medial right tibiotarsus, encircling to the lateral side. The medial surface of the mass appeared ulcerated with a moderate amount of dried blood. Although the dove often rested on its sternum instead of standing to support its weight, the remaining findings of the physical examination appeared normal.
The dove was admitted to the hospital for diagnostic testing. A complete blood cell count was performed, and results revealed severe anemia (packed cell volume of 15%; reference interval, 39%-59%) with slight polychromasia. (1) The white blood cell count was within reference intervals. A VetScan VS2 (Abaxis, Union City, CA, USA) was used for plasma biochemical results. The creatine kinase concentration was high (2655 U/L; in-house analyzer reference interval, 69-524 U/L) and blood glucose concentration was mildly elevated (394 mg/ dL; in-house analyzer reference interval, 223-390 mg/dL). The globulin level was decreased (0.3 g/ dL; in-house analyzer reference interval, 2-4 g/dL).
Radiographs were performed while the bird was anesthetized to allow for optimum patient positioning. Anesthesia was induced by mask induction with isoflurane at 5%, then maintained with isoflurane mask at 1.5%. Ventrodorsal and right lateral whole body views were obtained. Results showed severe boney lysis of the right tibiotarsus with a proliferative periosteal reaction. Medially, a soft tissue mass was present (Fig 1).
A fine-needle aspirate of the mass revealed debris, unidentifiable broken cells, and a moderate amount of blood contamination. There were increased numbers of large mononuclear cells having abundant and variably staining cytoplasm, small vacuoles, and an eccentrically located oval cell nucleus, with lower numbers of small lymphocytes and heterophils. A few multinucleated cells were identified that were thought to be either multinucleated macrophages or normal osteoclasts. These cells were characterized by abundant cytoplasm, small cytoplasmic vacuoles, and multiple round to oval cell nuclei. No microorganisms or evidence of neoplasia was seen. This result was considered inconclusive.
After evaluating these results, the limb was determined to be nonsalvageable and surgical amputation of the right tibiotarsus was elected. The dove was admitted to the hospital and a bandage was placed around the mass. Initial treatments were meloxicam (0.3 mg/kg PO q12h; Metacam, Boehringer Ingelheim, St Joseph. MO, USA); enrofloxacin (15 mg/kg PO q12h; Baytril, Bayer, Shawnee Mission, KS, USA); subcutaneous fluids (25 mL/kg SC q12h, lactated Ringer's solution); calcium glubionate (25 mg/kg PO q24h; calcionate syrup, Rugby, Duluth, GA, USA); a commercial pet multivitamin supplement that contained iron (0.7 mL/kg PO q24h; Pet-tinic, Pfizer, New York, NY, USA); a vitamin A, E, and D3 supplement (6600 IU/kg; Injacom ADE, Wedgewood Compounding Pharmacy, Swedesboro, NJ, USA); and calcium gluconate (100 mg/ kg SC once).
Two days after admission, a blood transfusion was performed. The patient was again anesthetized as previously described and a 25-gauge needle was introduced into the left tibiotarsal medullary cavity to act as an indwelling intraosseous catheter. A healthy male pigeon (Columba livid), was selected as a donor for the transfusion. An appropriate transfusion amount was calculated as 1.3 mL of whole blood. This was collected and mixed with the anticoagulant acid citrate dextrose (ACD solution, The Metric Company, Dubuque, IA, USA). (2,3) Once collection was complete, the blood was administered to the recipient slowly over 5 minutes via the previously placed intraosseous catheter. No reactions were noted and both birds remained stable after transfusion.
Six days after presentation, the bird was discharged from the hospital on meloxicam (0.3 mg/kg PO q12h), enrofloxacin (15 mg/kg PO q12h), calcium glubionate (25 mg/kg PO q24h) and Pet-tinic (0.7 mL/kg PO q24h) until recheck. A bandage was left over the mass on the affected leg to prevent further self-trauma and resultant blood loss. Two weeks later, the patient returned for reevaluation. A blood sample was collected and revealed the anemia had resolved (packed cell volume 42%). The mass remained unchanged. The dove was deemed stable for surgery and admitted to the hospital. Previously administered medications were continued.
Two days later, the bird was premedicated for surgery with butorphanol (1 mg/kg IM; Dolorex, Intervet, Milsoboro, DE, USA), ketamine (10 mg/ kg IM; Putney, Portland, ME, USA), and dexmedetomidine (0.09 mg/kg IM; Dexdomitor, Pfizer). Subcutaneous fluids (25 mL/kg SC, lactated Ringer's solution) were administered. Once sedate, isoflurane anesthesia was administered via face mask, inducing the patient at 5% with oxygen at 1 L/min. A surgical plane of anesthesia was reached and the patient was maintained between 1% and 2% isoflurane by face mask. The surgical site was aseptically prepared.
A lateral approach to the femur was made according to published protocols. (4) Muscle bellies, ligaments and vessels were incised and ligated accordingly to separate the tibiotarsus from the body. Ronguers were used to remove approximately 5 mm of the distal femur. Muscle bellies were then sutured over the femoral stump in a simple continuous pattern with 5-0 polydioxanone (PDS II, Ethicon, Guaynabo, Puerto Rico). The skin was sutured in a simple continuous pattern with 5-0 polydioxanone.
After surgery, dexmedetomidine was reversed with atipamezole (0.75 mg/kg IM; Antisedan, Pfizer) and recovery was uneventful. Postoperative pain management consisted of butorphanol (1 mg/ kg IM q12h) for the next 2 days. The day after surgery, the dove appeared bright and alert, and was eating well and standing on the left leg as opposed to sitting as it had done previously. Pettinic and calcium glubionate were discontinued. Meloxicam (0.3 mg/kg PO q12h) and enrofloxacin (15 mg/kg PO q12h) were continued for 7 days after surgery. The dove was discharged 2 days after the surgery.
The leg was examined histologically, from the tibiotarsus distally. Histopathologic examination revealed an infiltrative, unencapsulated neoplasm with streaming irregular bundles of cells that were elongate to polygonal with small-to-moderate amounts of a fine, granular, eosinophilic cytoplasm. The cell nuclei were oval with a lightly stippled chromatin and 1 to 2 variably prominent amphophilic nucleoli. The cells were associated with osteoid deposition that was mineralizing (Fig 2). The mitotic index was low at 0-1 per high-power field (x400). The tumor effaced the soft tissues of the leg and bone extending to the dermalepidermal junction. A granuloma, with numerous bacterial cocci surrounded by multinucleated giant cells and epithelioid macrophages, was present and abutting the neoplasm. A diagnosis of osteosarcoma with a focally extensive bacterial granuloma was made.
At the 2-week recheck, the dove was reported to be doing very well at home. The amputation site healed well, and sutures were removed. Further recommendations of chemotherapy were declined by the owners.
At the 6-month recheck, the dove was in good body condition, and all vital parameters were normal. Radiographs were performed under sedation with midazolam (1 mg/kg IM once). The amputation site revealed no honey lesions and the lungs and air sacs appeared clear. A complete blood count was rechecked and results were within reference intervals. The biochemical results, performed as previously described, revealed a high creatine kinase level (3404 U/L) and a low globulin level (0.2 g/dL). (1)
Eight months after surgery, the dove was found dead after a 4-day history of lethargy. The carcass was presented for necropsy 3 days after death and had been frozen. After thawing, it was found to be in a cachexic body condition. A large, multi-lobulated red mass was found on the left side of the coelomic cavity extending from the cranial portion of the left lung to the cranial pole of the left kidney. The mass invaded the left pulmonary tissue but not the kidney. The gastrointestinal tract and liver were displaced to the right side of the body. The caudal third of the mass was necrotic. The spleen, ovary, and oviduct could not be identified. The previous amputation site and remaining organs appeared normal.
On histopathologic examination, the coelomic mass was infiltrative, unencapsulated, and comprised of proliferative neoplastic spindle to polyhedral cells (Fig 3). Cytoplasmic borders were indistinct with moderate amounts of fine granular eosinophilic cytoplasm. Mitotic index was low at 0-1 per high-power field (X400). There were also focally extensive regions of necrosis and hemorrhage within the mass. The mass was effacing sections of the left lung with necrosis and hemorrhage present in the remaining viable tissue. The right lung was congested and moderately autolyzed. The proventriculus, ventriculus, intestines, pancreas, adrenal gland, and liver were mild to moderately autolyzed. Freeze-fracture artifact was present in the liver and heart. The kidneys also had focal luminal collecting duct microliths and urate deposition. The previous surgery site and left limb did not have any evidence of a neoplastic process. The diagnosis for the coelomic mass was spindle cell sarcoma.
In an attempt to further characterize the spindle cell sarcoma mass, immunohistochemical analysis was performed for osteocalcin and osteonectin. Both the surgically amputated tibiotarsus and the coelomic mass were stained and positive and negative controls were examined. Within the spindle cell sarcoma, positive immunoreactivity of the cytoplasm was rare. However, immunoreactivity of the tibiotarsus appeared more intensely positive in multiple cells for osteocalcin and osteonectin (Fig 4). Although this test has not been utilized before in avian species, the osteosarcoma of the tibiotarsus was considered positive, while results for the spindle cell sarcoma were inconclusive as there was only rare positive immunoreactivity.
In this case report, we identified osteosarcoma in a ring-necked dove, a species in which it has not been previously reported. A potential pulmonary metastasis was recognized and a novel diagnostic test was used to further confirm this suspicion. This is the first time osteocalcin and osteonectin immunohistochemical staining has been described in avian tissues, to our knowledge.
Osteosarcoma is a rare tumor in avian species. Little information is available on the most common locations, rate of metastasis, radiographic appearance, and biochemical changes in birds. In other species, such as dogs, it can be found most frequently in the metaphyseal region of the appendicular skeleton but has also been reported in ribs, vertebrae, bones of the head, and rarely, in soft tissues. It has a predilection for the distal radius, distal tibia, and proximal humerus. (5,6)
Though few reports of osteosarcoma are available for birds, it appears to occur more frequently in the appendicular skeleton. Previous reports have described it to occur in long bones such as the radius, humerus, femur, tibiotarsus, and tarsometatarsus, localizing to the proximal and distal portions of the bone. Other locations where osteosarcoma has been identified in birds are the mandible, orbit, and intraocular region. (7-13) In this dove, the tibiotarsus was the affected bone.
The biologic behavior of this neoplasm in dogs has been well described. It is locally invasive with most patients exhibiting significant cortical bone destruction early in the course of disease. Pulmonary tissue is the most common site of metastasis, though additional sites include other bones, skin, and other soft tissue. Although early pulmonary metastasis is common, at the onset of clinical signs, less than 10% of canines have radiographic evidence of metastasis. (6,14)
Little is known of the biologic behavior of osteosarcoma in birds. It has been described as having a low metastatic rate and evidence exists to support this. (9,15) In reports where patients survived and were available for follow-up, there was no evidence of metastasis up to 20 months after successful treatment. (15,16,17) One report of a Panama boat-billed heron (Cochlearius cochlearius panamensis) did, however, describe metastases in the lungs, liver, kidneys, mesentery, and ovary. (15) Other sources have reported osteosarcoma in the lungs of birds. (15) The dove in this report had a spindle cell sarcoma mass identified 8 months after the initial diagnosis of osteosarcoma. Immunohistochemical staining for osteocalcin and osteonectin was performed on this mass in an attempt to further classify its origin. Conclusive results could not be determined because of minimal immunoreactivity (less than 1% of the cells). Although there is no standard for the percentage of tumor cells that should be positive, reports have used a 10% cutoff for membranous and cytoplasmic immunoreactive staining. (19-20) It is likely that this coelomic mass is a metastatic osteosarcoma to the pulmonary tissue based on the clinical history and common location for bone tumor metastasis. If this is true, then this represents another case of osteosarcoma metastasis.
Radiographic changes that are consistent with osteosarcoma in avian species are also not known. (21) In this case, lytic lesions were seen with proliferative periosteal reaction. Lesions that have been described in other cases range from no radiographic lesions to mild periosteal reaction, boney proliferation, and lysis. (9,11,16,17) In cases of canine osteosarcoma, radiographic changes are variable, although cortical lysis is a common feature. (6,14)
Clinical pathologic changes seen in this dove were an increased creatine kinase concentration, mild hyperglycemia, hypoglobulinemia, and anemia. An elevated creatine kinase concentration has been reported in other birds with osteosarcoma. (9,16) The mild hyperglycemia was likely a result of stress from handling and has not been reported in other cases. (22) Hypoglobulinemia that was identified is likely unreliable, as this was not from a protein electrophoresis, which is widely accepted as the most accurate way to measure avian protein levels. (23) Hypoglobulinemia has not been reported in other cases. Anemia was reported in one case in an umbrella cockatoo (Cacatua alba) with osteosarcoma. (9) Though not appreciated in this case, other reports of osteosarcoma have described patients experiencing a leukocytosis. (9,11)
There are several options for treatment of canine osteosarcoma. Currently, amputation followed by chemotherapy is the preferred method because it has been shown to increase mean survival time compared with amputation alone. Common chemotherapeutics are cisplatin and doxorubicin, though carboplatin and others have been used. (6,24) Palliative intent radiation therapy and limb-sparing procedures have also been described as treatment modalities. (6,14)
Current recommendations for treatment of osteosarcoma in avian species are amputation of the affected area followed by chemotherapy. This protocol has been extrapolated from canine medicine. (21) Chemotherapeutics that have been used include doxorubicin, carboplatin, and pamidronate. (8,13,16,17) In a blue-fronted Amazon (Amazona aestiva aestiva), surgical debulking and radiosurgical coagulation was performed and followed by the administration of doxorubicin 4 times at once-monthly intervals. Complete remission was achieved. (16) A Toulouse grey goose (Anser anser domesticus) was treated with carboplatin and pamidronate after unsuccessful treatment with radiation therapy. Both were administered once every 3 weeks and resulted in the goose doing well 12 months after the initial diagnosis. (17) Although the affected limb was surgically amputated in the dove we describe, further treatment with chemotherapy was declined. Had this dove received chemotherapy, the question arises as to whether or not the final outcome would have been different.
Radiation therapy is another treatment option that has been explored. This treatment modality was used in a Toulouse grey goose; however, it failed to improve the goose's condition and management was switched to the use of chemotherapy. (17) In a report of osteosarcoma in the orbit of an umbrella cockatoo, 17 treatments of radiation therapy were performed. Two months after radiation therapy, the cockatoo was doing well; however, at 3 months, the bird exhibited neurologic signs and died. A necropsy was declined; therefore, it is not known if osteosarcoma was the cause of death in this bird. (9) With the small number of avian patients that have been treated with radiation therapy for osteosarcoma, the efficacy of this treatment modality is not known. Historically, mesenchymal tumors are less responsive than carcinomas to radiation therapy. (8)
Prognosis for long-term survival from osteosarcoma is variable in dogs. Younger age, larger breeds, distant metastasis at diagnosis, and increase in serum alkaline phosphatase concentration are all negative prognostic indicators. When amputation is used as the sole treatment for appendicular osteosarcoma, 90% of dogs die from pulmonary metastases within 1 year. Chemotherapy has been shown to improve survival time after amputation and, depending on the agent used, mean survival time can be increased to greater than 1 year. (6-14,24)
No studies have been performed in birds to identify the prognosis and survival times from osteosarcoma. Survival time has been reported to be as little as 3 weeks but up to 20 months after diagnosis. (9,11,13,16,17) Treatment is likely a contributing factor in the survival times for the different cases. The dove we describe died 8 months after surgical amputation, but whether death of this bird was caused by osteosarcoma metastasis or sarcoma of a different cell origin is uncertain.
Immunohistochemical staining for osteocalcin and osteonectin was performed in this case in an attempt to further classify the identified spindle cell sarcoma. Osteocalcin is one of the most prevalent noncollagenous intraosseous proteins, and it is predominantly localized to osteoblasts, and thus virtually completely specific for boneforming cells. Osteonectin is a protein that is concerned with regulating the adhesion of osteoblasts and platelets to their extracellular matrix, as well as early stromal mineralization. (23) Although this test has not been used previously in birds, osteocalcin and osteonectin immunostaining has proven to be helpful in the diagnosis of osteosarcoma in other species. (26-28) The findings in this case indicate that the tibiotarsal osteosarcoma stained positive for osteocalcin and osteonectin. The spindle cell sarcoma, on the other hand, was only mildly positive for osteocalcin and osteonectin immunoreactivity, therefore precluding a firm diagnosis of osteosarcoma metastasis. Many factors, such as freezing of the tissues, the delay in collecting the tissue for formalin fixation, and the tissue necrosis can affect immunostaining and these may have contributed to poor immunoreactivity. (19) Interpreting these results is difficult because no reports exist on the use of this immunohistochemical stain in avian species; however, it is promising to see positive staining results in confirmed osteosarcoma tissue, because this indicates that this diagnostic test may become useful in future cases.
Reports of avian species with osteosarcoma include budgerigars (.Melopsittacus undulatus), an umbrella cockatoo, a rose-breasted cockatoo (Eolophus roseicapilla), a blue-and-gold macaw (Ara ararauna), an American robin (Turdus migratorius), a blue-fronted Amazon, a Toulouse grey goose, and a Panama boat-billed heron (8,9,11,13,15-17,29) To our knowledge, this is the first report of appendicular osteosarcoma in a ring-necked dove. Because of the scarcity of reports in avian species, many questions need to be answered and further research is needed to advance our understanding of this neoplasm in avian patients.
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Stephanie Lamb, DVM, Drury Reavill, DVM, Dipl ABVP (Avian), Dipl ACVP, John Wojcieszyn, PhD, and Nicholas Sitinas, VMD, Dipl ABVP (Avian)
From the South Wilton Veterinary Group. 51 Danbury Rd. Wilton, CT 06897, USA (Lamb, Sitinas); the Zoo/Exotic Pathology Service, 2825 KOVR Dr, West Sacramento, CA 95605, USA (Reavill); and the IHC Services, 185 Mountain Valley Dr, Smithville, TX 78957, USA (Wojcieszyn).
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|Title Annotation:||Clinical Reports|
|Author:||Lamb, Stephanie; Reavill, Drury; Wojcieszyn, John; Sitinas, Nicholas|
|Publication:||Journal of Avian Medicine and Surgery|
|Date:||Mar 1, 2014|
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