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Chondrosarcoma Associated With the Appendicular Skeleton of 2 Domestic Ferrets
AEMV FORUM CHONDROSARCOMA ASSOCIATED WITH THE APPENDICULAR SKELETON OF 2 DOMESTIC FERRETS Rina Maguire, BVSc, Drury R. Reavill, DVM, Dip. ABVP (Avian), Dip. ACVP, Patrick Maguire, BVSc, and Jeffrey R. Jenkins, DVM, Dip. ABVP (Avian)
Abstract A 5-year-old male neutered ferret (Mustela putorius) and a 2-year-old male neutered ferret were evaluated for fast growing immobile swellings involving the left hock and the right scapula, respectively. In both cases, serum chemistry was unremarkable and a complete blood count demonstrated mild anemia. In case 1, radiographic evaluation demonstrated increased soft tissue density in the region of the distal tibia and fibular tarsal bone. A fine-needle aspirate demonstrated atypical mesenchymal cells, and an incisional biopsy revealed irregular partly mineralized proliferations of cartilage consistent with chondrosarcoma. Computed tomography was performed, demonstrating attachment of the mass to the distolateral tibial epiphysis. A limb-sparing surgery was performed; however, 5 months following resection local reoccurrence was noted. At 18 months, the ferret underwent a left hind limb amputation. No sign of metastatic disease was reported at 27 months. In case 2, radiographic evaluation demonstrated a poorly organized mineralized soft tissue mass extending from the right acromion to the area surrounding the neck of the scapula. Microscopic evaluation of an incisional biopsy revealed a chondrosarcoma. A forequarter amputation was performed. The ferret died 4 years later with no evidence of local recurrence or the development of metastatic disease. These 2 cases represent the first reports of chondrosarcoma in the appendicular skeleton of 2 ferrets. Based on these 2 cases, local recurrence may be expected unless adequate surgical margins are achieved. The metastatic potential of chondrosarcoma in this species appears to be low. Copyright 2014 Elsevier Inc. All rights reserved. Key words: chondrosarcoma; ferret; neoplasm; treatment; tumor
T
he incidence of neoplasia and associated paraneoplastic syndromes is high in ferrets (Mustela putorius). Although adrenocortical tumors, insulinoma, and malignant lymphoma represent the most common diagnoses, a host of other neoplasms have been reported.1 Although chordomas are recognized as the most common musculoskeletal tumor, they arise from remnants of embryonic notochord and not from the appendicular skeleton. Primary appendicular neoplasms include both osteosarcoma and rhabdomyosarcoma; these tumors are locally invasive, result in significant patient morbidity, and generally necessitate either palliative or curative intent surgical procedures. The following report describes 2 cases of appendicular chondrosarcoma; to the authors' knowledge, this tumor type has not been previously described in ferrets.
CASE 1 _______________________________________ A 5-year-old, 1.25-kg, male neutered ferret was evaluated at the Center for Avian and Exotic
Medicine (New York, NY USA) for left tarsal swelling of 1-week duration. The exclusively indoor ferret was the only pet in the house and fed a commercial ferret kibble diet. The owner described
From the Center for Avian and Exotic Medicine, New York, NY USA; the Zoo/exotic Pathology Service, West Sacramento, CA USA; the New York, Veterinary Specialty and Emergency Center, Farmingdale, NY USA; and the Avian and Exotic Animal Hospital, San Diego, CA USA. Address correspondence to: Rina Maguire, BVSc, Island Exotic Veterinary Care, 591 East Jericho Turnpike, Huntington Station, NY 11746. E-mail: [email protected]. Ó 2014 Elsevier Inc. All rights reserved. 1557-5063/14/2101-$30.00 http://dx.doi.org/10.1053/j.jepm.2014.02.011
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no changes in general activity, appetite, or water consumption. On physical examination, a firm, immobile, nonalopecic swelling measuring 2.5 cm 5 cm was identified on the left tarsus. No clinical lameness was observed, and no crepitus or pain could be elicited when the hock was moved through its range of motion. The findings of the remainder of the physical examination were unremarkable. The ferret was anesthetized for diagnostic testing. The ferret was induced and maintained by face mask using isoflurane (Primal Healthcare Limited, Bethlehem, PA USA) gas anesthesia (2% to 3%) and oxygen (2 L/min) throughout the procedure. Venipuncture of the cranial vena cava was performed and a blood sample was collected. The results of the serum biochemistry panel and complete blood count were unremarkable except for a mild anemia (packed cell volume ¼ 36.5%, reference range: 43% to 55%).2 Ventrodorsal and lateral radiographic images of the left rear limb were obtained, which revealed a large soft tissue density associated with the left tibia and tarsal joint. Irregular opacity within the mass appeared consistent with partial mineralization. It was determined that there was a radiographic union of the cortex of the distal tibia and the region of apparent mineralization. An area of lucency consistent with bone lysis was evident within the left tibia. There was also a marked distortion and caudal deviation of the left gastrocnemius tendon. A fine-needle aspirate using a 19-gauge needle and a 5-mL syringe was taken from the center of the mass. Microscopic evaluation of the sample revealed a proliferation of atypical mesenchymal
cells. Osteosarcoma was considered the provisional diagnosis; however, other forms of neoplasia could not be completely ruled out. An incisional biopsy of the mass was performed 5 days following the fine-needle aspirate. The ferret was premedicated with buprenorphine (0.03 mg/kg subcutaneously, Buprenex; Reckitt Benckiser Pharmaceuticals Inc, Richmond, VA USA) and midazolam (0.5 mg/kg, intramuscularly, Versed; Roche Laboratories, Nutley, NJ USA), and anesthesia was induced with isoflurane and oxygen as previously described. Three radiographic views of the thorax and abdomen were taken as part of metastatic screening and no abnormalities were detected. A wedge biopsy was collected from the mass using a number 15 scalpel blade. A fine-needle aspirate was procured from the left popliteal lymph node. The biopsy tissue sample was decalcified, processed, and stained with hematoxylin and eosin. Microscopic evaluation of the sample revealed multiple variably sized lacunae within a homogenous hyaline cartilage matrix. The lacunae supported single to occasional, multiple neoplastic chondrocytes that were pleomorphic to oval and occasionally stellate with 1 to 3 indistinct nucleoli. The mitotic index was low at less than 1 per highpower field. Interspersed within the sample were focal areas of mineralization. These findings were supportive of a diagnosis of chondrosarcoma. The sample taken from the left popliteal lymph node did not reveal any neoplastic cells. Computed tomography was utilized to determine the margins of the neoplasm (Fig. 1). Anesthesia was administered as described
FIGURE 1. Case 1. A CT image (A) and 3-dimensional reconstruction (B) of a 5-year-old male neutered ferret with a growth associated with the left tibia. CT, computed tomography.
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previously, and transverse images of 2-mm thickness were obtained. The mass was measured and found to be 2.5 cm 1.5 cm 1.1 cm. The mass appeared to be cavitated and demonstrated areas of apparent mineralization. The mass appeared confluent with the articular surface of the distolateral tibial epiphysis, closely associated with the distal fibular epiphysis and expanded into surrounding tissues in a caudolateral fashion. The popliteal lymph node was markedly enlarged compared with the contralateral node, whereas the iliac lymph nodes were within normal limits. Involvement of the tibiotarsal and intertarsal joints was suspected owing to the close proximity of the mass to these structures. Complete local resection did not appear possible and amputation proximal to the midshaft of the left tibia was recommended. However, the owners opted not to amputate and instead elected a limb salvage procedure. Risk factors for this procedure included local tumor reoccurrence and pathological fracture of the tibia. The ferret was premedicated with midazolam (0.5 mg/kg) and hydromorphone (0.2 mg/kg, intramuscularly, Dilaudid-HP; Abbott Laboratories, North Chicago, IL USA). A 22-gauge intravenous catheter was placed in the left cephalic vein to facilitate intraoperative administration of 10 mL/kg/h of the lactated Ringer solution. Intravenous boluses of 5-mL/kg lactated Ringer solution were administered as needed to offset intraoperative bleeding. Anesthesia was induced with 2% isoflurane in 2 L/min of oxygen using a face mask. The ferret was then intubated with a 2.5mm uncuffed endotracheal tube. A Doppler probe was placed over the left palmar metatarsal artery to monitor heart rate and rhythm. Pulse oximetry was also utilized to monitor oxygen saturation with the probe placed over the front left foot pad. A forced warm air blanket was used to maintain normothermia, and temperature was monitored using a manual thermometer every 10 minutes. A 3-cm incision was made on the lateral aspect of the distal tibia to the level of the tarsal joint. Blunt dissection was used to elevate the soft tissue capsule and attachments of the tumor to the surrounding muscle. A periosteal elevator was used to separate the bulk of the tumor from the tibia. The tumor was then removed with bone rongeurs and an osteotome. Portions of adjacent tibial cortex were also removed. The superficial digital flexor was displaced laterally by the growth, and this was replaced into its normal anatomical position and maintained in this position by suturing a soft tissue envelope around the tendon. Samples from the bulk of the tumor and the deeper segment attached
to the tibia were submitted for histopathology. The surgery site was copiously flushed with sterile saline. Instruments and gloves were changed, and the site was closed in 3 layers with 5-0 polydioxanone (Ethicon Inc, Somerville, NJ USA). Gentle manual flexion and extension of the limb was performed and the tarsal joint was deemed stable. The ferret recovered uneventfully from anesthesia. Postoperative pain management included meloxicam (0.5 mg/kg, subcutaneously twice daily, Metacam; Boehringer-Ingelheim Pharmaceuticals, Inc, Ridgefield, CT USA) and hydromorphone (0.1 mg/kg, intramuscularly every 12 hours) for the next 24 hours. The ferret was maintained on the intravenous lactated Ringer solution at 2.5 mL/kg/h for 12 hours. Two doses of perioperative ampicillin were administered (30 mg/kg, intravenously every 8 hours, Ampicillin; Sandoz Inc, Broomfield, CO USA). Twenty-four hours after completion of the procedure, the ferret was switched to amoxicillin/ clavulanate (14 mg/kg orally every 12 hours, Clavamox; Pfizer Animal Health, Exton, PA USA) for 7 days and continued on meloxicam (0.5 mg/ kg, orally every 12 hours) for 5 days. The ferret was restricted to a cage for the next 2 weeks to reduce the risk of tibial fracture at the surgical site. Histologically prepared sections of the tumor were found to be consistent with a chondrosarcoma. The deeper section of the resected tissue sample demonstrated tumor invasion into the cortex of the tibia with fragmented and irregular trabecular structures and marrow elements (Fig. 2). The outer portion of the resected tissue sample was comprised of irregularly shaped, sized, and haphazardly arranged lacunae within a hyaline cartilage matrix. Within these lacunae were nests of pleomorphic chondrocytes. Several binucleate cells were observed and rare mitotic figures were identified at a rate of 0-1 per high-power field. Portions of the matrix were mineralized, consistent with endochondral ossification. Bone trabeculae in this section were fragmented and widely separated by lacy connective tissue. In some areas, neutrophilic infiltrates were appreciated. Despite the hisopathological findings, the owners declined amputation or adjunctive radiation therapy. At a recheck examination 2 weeks following surgery, no lameness was noted and the left tibiotarsal joint demonstrated normal range of motion. Follow-up radiographic images were declined by the owners. Five months following the initial limb-sparing procedure, reevaluation of the ferret was performed owing to local recurrence of
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FIGURE 2. Case 1. Islands of neoplastic chondrocytes invade normal bone (B). Bar ¼ 0.1 mm. H&E stain. H&E, hematoxylin and eosin.
the swelling on the distal tibia and tarsal joint. Further testing and therapy was declined by the owner. The tumor continued to grow over the following months, and its large size eventually affected the ferret's ability to ambulate. Thirteen months following the initial surgery, a left rear limb amputation was performed at another facility. The surgery was considered a success and on recheck examination, 2 years following the initial diagnosis, there was no evidence of local recurrence. CASE 2 _______________________________________ A 2-year-old, 956-g, male neutered ferret was evaluated at the Avian and Exotic Animal Hospital (San Diego, CA USA) for a rapidly growing swelling associated with the right shoulder. The client reported rapid growth of the mass over the previous 2 weeks. The ferret was maintained exclusively indoors and was from a single pet household. The ferret was fed a commercial ferret kibble diet and had no previous vaccination or medical history. The findings of the external physical examination were unremarkable except for a firm, immobile, and nonalopecic swelling that appeared to be attached to the right scapula. No lameness was detected and no pain was elicited when the lesion was manipulated. Normal range of motion was present in the affected limb. The ferret was anesthetized using isoflurane gas (2% to 4%) administered in 1.5-L/min oxygen via 1 6 8
a face mask to facilitate collection of samples for diagnostic testing and radiographic evaluation. Venipuncture of the caudal vena cava was performed and results of the complete blood count and serum biochemistry were normal, except for anemia (packed cell volume ¼ 33%, reference range: 43% to 55%).2 Radiographs of the right front limb were taken and revealed a round proliferative partially mineralized lesion extending from the acromion to the neck of the scapula (Fig. 3). Owing to the suspicion of a bony neoplasm, an incisional biopsy was performed. The next day, the ferret was premedicated with buprenorphine (0.03 mg/kg subcutaneously), and anesthesia was induced with isoflurane and oxygen as previously described. The patient was intubated with a 2.5-mm uncuffed endotracheal tube and maintained on 2% isoflurane and 1.5-L/min oxygen. A 4-mm dermal punch biopsy was used to obtain samples in 3 separate areas of the tumor. The tumor samples were prepared with hematoxylin and eosin stain, and histopatholgical evaluation of the tissue revealed variable amounts of hyaline cartilage matrix. There were multiple variably sized clustered lacunae containing individual to occasionally multiple chondrocytes that were pleomorphic, oval to stellate, and occasionally contained multiple nucleoli. The mitotic index was low at 0-1 per high-power field. Fragments of bone trabeculae were also identified in the sample. Based on the cartilaginous differentiation of tumor cells and matrix, the lesion was considered consistent with a chondrosarcoma. The ferret was returned 7 days later for foreleg amputation. A 22-gauge intravenous catheter was placed in the left cephalic vein, and the ferret was maintained on 10 mL/kg/h of the lactated Ringer solution throughout surgery. After premedication with buprenorphine (0.03 mg/kg subcutaneously), the ferret was anesthetized with isoflurane and oxygen as described previously. A skin incision was made from the dorsal border of the scapula, over the scapular spine, to the proximal third of the humerus, and then circumferentially around the limb at this level. The muscular attachments of the scapula were transected, and the scapula was retracted laterally to reveal the medial surface. The axillary artery and vein were ligated with hemoclips. The brachial plexus was transected. The forelimb was then removed by excising the remaining muscular attachments. The muscle and subcutaneous tissues were closed with 5-0 polyglyconate monofilament (Maxon, Covidien Inc, Mansfield, MA USA) over the brachial plexus and vessels using a simple interrupted pattern. The
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FIGURE 3. Case 2. Lateral (A) and ventrodorsal (B) radiographic images of a 2-year-old male neutered ferret with a rapidly growing mass associated with the scapula. A partially mineralized lesion extending from the acromion to the neck of the right scapula was seen on radiographs.
skin layer was closed with surgical staples. The tumor was submitted for histopathologic evaluation, and a diagnosis of chondrosarcoma was confirmed. Histopathologic examination revealed an unencapsulated, discrete neoplasm comprised of variable amounts of hyaline cartilage matrix. Inconsistently sized lacunae within this matrix supported nests of pleomorphic chondrocytes with indistinct nucleoli. Clusters of chondrocytes were seen to invade normal bone. The mitotic index was low at 0-1 per high-power field. The ferret recovered very well and buprenorphine (0.03 mg/kg subcutaneously) was continued for the next 12 hours. After 24 hours, the patient was discharged on amoxicillin (25 mg/ kg orally twice daily) for 7 days and meloxicam (0.5 mg/kg orally twice daily) for 5 days. On a recheck physical examination 10 days following surgery, the incision had healed and the staples were removed. The owner reported that the patient was doing well and was able to ambulate on 3 limbs. Follow-up thoracic radiographs performed 1 month following amputation were considered unremarkable. The ferret survived for 4 years with no recurrence of the tumor and was euthanized for unrelated health issues at 6 years of age. DISCUSSION _________________________________ To the authors' knowledge, this is the first report describing the diagnosis, treatment, and outcome of chondrosarcoma of the appendicular skeleton in the ferret. Although a report exists describing a chondrosarcoma of the axial skeleton, it is possible that this early report may have mischaracterized a caudal vertebrae chordoma as a chondrosarcoma
because insufficient histopathologic evidence was present to support the diagnosis.1,3 Histologically, chordomas and chondrosarcomas may appear similar, although the location and presence of physaliferous cells helps to differentiate the 2 tumor types. In diagnostically challenging cases, additional immunohistochemical staining can help differentiate the tumor types, especially in suspected metastatic foci.4-7 Positive uptake of intermediate filaments cytokeratin, vimentin, and S-100 protein occurs in chordomas but not chondrosarcomas.6,7 Immunohistochemical staining was not used in these 2 cases as the histopathological detail, revealed by conventional staining techniques, was considered sufficient. Additionally, chordromas were not considered a differential diagnosis based on the lesions' remote location from the notocord, and as such, the additional expense of immunohistochemical staining could not be justified. Both ferrets were noted to be anemic at the time of initial diagnostic evaluation. A transient reduction in hematocrit has been previously reported in ferrets anesthetized with isoflurane at the time of venipuncture and could be responsible for the changes seen in these cases.8 To more accurately evaluate hematologic variables, venipuncture could have been performed before anesthesia was induced or reevaluated at a later time. Primary tumors of the skeletal system in ferrets that have been described in the peer-reviewed literature include chordomas, osteomas, multilobular tumor of bone, and osteosarcomas.1 Chordomas are considered the most frequently encountered neoplasm of the musculoskeletal system in the ferret, comprising 79% of
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musculoskeletal neoplasms reviewed.1 Chordomas are locally aggressive primary malignant bone neoplasms that develop from remnants of embryonic notochord in the skull base and spine. Chordomas may arise from the vertebrae in any region of the spinal column but are most commonly seen at the tail tip involving the last caudal vertebrae.6 Macroscopically, chordomas appear as lobulated, firm, nonencapsulated ulcerated masses.7 Microscopically, these tumors consist of lobules of physaliphorous cells with welldifferentiated bone or cartilage throughout.6,9 Ferrets with lytic lesions affecting cervical and thoracic vertebrae can present with signs of tetraparesis or paraparesis, respectively.9 Debulking of a cervical or thoracic chordoma, although not necessarily curative, may provide the ferret with relief from neurologic signs and pain for a period of time.9 Chordomas affecting the tail are easily treated by amputation, but late excision may predispose to metastasis.4 Metastasis of a chordoma from the cervical region has also been described.9 Osteomas are benign, dense bony masses in ferrets that arise from flat bones; most commonly the bones of the skull and sometimes ribs.6 Histopathology usually reveals compact lamellar bone, bony trabeculae, and mild-to-moderate osteoblastic and hematologic activity.7,10,11 Complete surgical excision of osteomas is considered curative. In ferrets, there is a report of a multilobular tumor of the bone originating from the neck causing extradural compression of the spinal cord.12 Osteomas have a characteristic pattern of numerous contiguous lobules that vary in their composition of cartilage and bone matrix.12 Osteosarcomas are rarely reported tumors in the flat or long bones of ferrets.1 Osteosarcomas appear locally destructive as described in other domestic species and are best treated by amputation.1 The metastatic potential of osteosarcoma in the ferret is not well described, but in other species, this tumor type carries a poor prognosis owing to the high rate of malignancy. Chondrosarcoma is a malignant bone tumor that produces a cartilaginous matrix. There is a lack of direct bone formation by the tumor cells, although new bone formation may be present owing to endochondral ossification of tumor cartilage. In domestic animals, most chondrosarcomas are primary bone tumors arising from within the medullary cavity.13 Secondary chondrosarcomas have been described in humans arising from pre-existing benign cartilaginous lesions, but this has not been identified in other species.13 Chondrosarcomas are typically slow to 1 7 0
metastasize and considered less malignant than osteosarcoma.13,14 Without treatment, chondrosarcomas grow slowly to large sizes and have a longer clinical course before metastasizing. Sites of metastasis typically include the lungs, but other organ involvement is possible.13 In domestic species, chondrosarcomas are most frequently described in middle-aged medium to large breed dogs.13 The prevalence of chondrosarcoma as a primary skeletal tumor is second to osteosarcoma in dogs and accounts for about 10% of primary canine bone tumors. In dogs, chondrosarcomas more commonly affect the flat bones, and lesions in limbs are typically painful and cause lameness in affected limbs.13 In cats, chondrosarcomas are uncommon but can occur in the skeleton (70%) or subcutaneous tissue (30%).15 Overall, 63% of feline skeletal chondrosarcomas occur in the long bones.15 In cattle and goats, chondrosarcomas appear to be aggressive bony tumors that cause lameness, and lymphatic metastasis to the lungs is often identified at necropsy.16,17 Chondrosarcomas, like other bony neoplasms, are diagnosed using radiographic imaging and histopathological evaluation of affected tissue. Computed tomography can be utilized to locate the borders of the neoplasia, provide prognostic information, and assist in surgical planning. Radiographic features of chondrosarcomas can include osteolysis, but when compared with osteosarcomas the areas of bone loss are substantially smaller. Chondrosacromas also do not evoke the same periosteal response as osteosarcoma lesions.13 Diagnosing chondrosarcomas using a fine-needle aspirate can be difficult, and an incorrect diagnosis of osteosarcoma was made initially in case 1. Using this sampling technique, tumor cells from a chondrosarcoma appear cytologically similar to those from an osteosarcoma.13 In making a microscopic diagnosis of chondrosarcomas, clinical findings, histopathology, and radiographic presentation must always be considered to ensure compatibility. Other differentials should include chondroblastic osteosarcomas, actively growing or traumatized osteochondromas, and nonmalignant responses (e.g., injury to ligament insertions, periosteum, or synovium).13 In human and canine patients, chondrosarcomas are classified into grade I, II, or III in order of ascending malignancy. In humans, this grading system is used to guide the aggressiveness of the therapy with only some success.18 The grading is based upon nuclear size, staining pattern (hyperchromasia), mitotic activity, and degree of cellularity.13 The amount or nature of the matrix in chondrosarcomas
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has no prognostic value.13 However, when the matrix becomes fibrillar, hyalinized, or ossified, it may make differentiation between chondrosarcomas and other sarcomas more difficult.13 The therapy recommended for chondrosarcomas in companion animals is wide surgical excision, as complete resection can be curative.13-15 Chemotherapy for grade III chondrosarcomas in canine patients is advised in addition to surgical excision.13,19 Radiation therapy has also been described as an adjunct to surgical therapy, or in cases where complete excision is not possible.19 However, radiation therapy has not been proven to be effective without prior surgical debulking.19 Lowgrade chondrosarcomas in humans have been treated successfully with limb-sparing surgical procedures and intralesional curette.20 In domestic animals, such success has not been reported. Boudrieau et al21 described chondrosarcoma of the canine radius. A limb-sparing technique was performed; however, the tumor reoccurred locally and thoracic metastasis developed. The limb-sparing technique failed in the ferret in case 1 likely owing to the inability to achieve complete surgical excision. Radiation therapy may have prevented recurrence of the tumor but could have increased the likelihood of a pathological fracture. The noncompliance of ferrets with Elizabethan collars also makes radiation therapy less viable as there is concern for self-trauma of the surgical site after the treatment procedures. Chondrosarcoma should be considered a differential diagnosis for any firm nodular mass associated with the skeletal system in ferrets. A lack of previous reports suggests that this tumor type is uncommon in ferrets; however, the outcome of these 2 cases implies that chondrosarcomas have a low metastatic potential and may be amenable to local resection. Although additional studies are required to define the true malignant capacity of this tumor, differentiation of a chondrosarcoma from osteosarcoma appears to suggest a relatively better prognosis and should encourage the clinician and client to pursue biopsy and appropriate surgical therapy.
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ACKNOWLEDGMENTS The authors thank Dr Sam Silverman and Dr Alix Wilson for assistance in case management and Dr Heidi Hoefer for reviewing the manuscript. REFERENCES 1. Williams BH, Weiss CA: Neoplasia, in Quesenberry KE, Carpenter JW (eds): Ferrets, Rabbits and Rodents Clinical
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Medicine and Surgery (ed 2). Philadelphia, PA, WB Saunders, pp 91-106, 2004 Quesenberry KE, Orcutt C: Basic approach to veterinary care, in Quesenberry KE, Carpenter JW (eds): Ferrets, Rabbits and Rodents Clinical Medicine and Surgery (ed 3). Philadelphia, PA, WB Saunders, pp 132-140, 2012 Hendrick MJ, Goldschmidt MH: Chondrosarcoma of the tail of ferrets (Mustela putorius furo). Vet Pathol 24:272-273, 1987 Munday JS, Brown CA, Richey LJ: Suspected metastatic coccygeal chordoma in a ferret (Mustela putorius furo). J Vet Diagn Invest 16:454-458, 2004 Cho HY, Lee M, Takei H, et al: Immunohistochemical comparison of chordoma with chondrosarcoma, myxopapillary ependymoma, and chordoid meningioma. Appl Immunohistochem Mol Morphol 17:131-138, 2009 Dunn DG, Harris RK, Meis JM, et al: A histomorphologic and immunohistochemical study of chordoma in twenty ferrets (Mustela putorius furo). Vet Pathol 28:467-473, 1991 Antinoff N, Giovanella CJ: Musculoskeletal and neurologic diseases, in Quesenberry KE, Carpenter JW (eds): Ferrets, Rabbits and Rodents Clinical Medicine and Surgery (ed 3). Philadelphia, PA, WB Saunders, pp 132-140, 2012 Marini RP, Jackson LR, Esteves MI, et al: Effect of isoflurane on hematologic variables in ferrets. Am J Vet Res 55(10):1479-1483, 1994 Williams BH, Eighmy JE, Dunn DG: Cervical chordomas in two ferrets. Vet Pathol 30(2):204-206, 1994 Jensen WA, Myers RK, Liu CH: Osteoma in a ferret. J Am Vet Med Assoc 187(12):1375-1376, 1985 Ryland LM: What is your diagnosis? Focal, ovoid, smoothbordered, osseous proliferation compatible with an osteoma of the parietal bone. J Am Vet Med Assoc 197(8): 1065-1066, 1990 Hanley CS, Geiger T, Frank P: What is your diagnosis? Multilobular osteoma (MLO) in a ferret. J Am Vet Med Assoc 225:1665-1666, 2004 Woodant JC: Skeletal system, in Jones TC, Hunt RD, King NW (eds): Veterinary Pathology (ed 6). Hoboken, NJ, Wiley-Blackwell, pp 940-945, 1997 Farese JP, Kirpensteijn J, Kik M, et al: Biologic behavior and clinical outcome of 25 dogs with canine appendicular chondrosarcoma treated by amputation: a Veterinary Society of Surgical Oncology retrospective study. Vet Surg 38(8):914-919, 2009 Durham AC, Popovitch CA, Goldschmidt MH: Feline chondrosarcoma: a retrospective study of 67 cats (19872005). J Am Anim Hosp Assoc 44:124-130, 2008 Acland HM: Chondrosarcoma in a cow. Comp Pathol 93 (4):585-589, 1983 Schmid T, Hilbe M, Ohlert S, et al: Chondrosarcoma on the humerus of a goat. Vet Comp Orthop Traumatol 23: 273-276, 2010 Skeletal lesions interobserver correlation among expert diagnosticians (SLICED) study group. Reliability of histopathologic and radiologic grading of cartilaginous neoplasms in long bones. J Bone Joint Surg Am 89:2113-2123, 2007 Veterinary society of surgical oncology website. Chondrosarcoma. Available at: http://www.vsso.org/Bone_CSA. html. Accessed May 2, 2012 Aarons C, Potter BK, Adams SC, et al: Extended intralesional treatment versus resection of low-grade chondrosarcomas. Clin Orthop Relat Res 467:2105-2111, 2009 Boudrieau RJ, Schelling SH, Pisanelli ER: Chondrosarcoma of the radius with distant metastasis in a dog. J Am Vet Med Assoc 205:580-583, 1994
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Abstract A 5-year-old male neutered ferret (Mustela putorius) and a 2-year-old male neutered ferret were evaluated for fast growing immobile swellings involving the left hock and the right scapula, respectively. In both cases, serum chemistry was unremarkable and a complete blood count demonstrated mild anemia. In case 1, radiographic evaluation demonstrated increased soft tissue density in the region of the distal tibia and fibular tarsal bone. A fine-needle aspirate demonstrated atypical mesenchymal cells, and an incisional biopsy revealed irregular partly mineralized proliferations of cartilage consistent with chondrosarcoma. Computed tomography was performed, demonstrating attachment of the mass to the distolateral tibial epiphysis. A limb-sparing surgery was performed; however, 5 months following resection local reoccurrence was noted. At 18 months, the ferret underwent a left hind limb amputation. No sign of metastatic disease was reported at 27 months. In case 2, radiographic evaluation demonstrated a poorly organized mineralized soft tissue mass extending from the right acromion to the area surrounding the neck of the scapula. Microscopic evaluation of an incisional biopsy revealed a chondrosarcoma. A forequarter amputation was performed. The ferret died 4 years later with no evidence of local recurrence or the development of metastatic disease. These 2 cases represent the first reports of chondrosarcoma in the appendicular skeleton of 2 ferrets. Based on these 2 cases, local recurrence may be expected unless adequate surgical margins are achieved. The metastatic potential of chondrosarcoma in this species appears to be low. Copyright 2014 Elsevier Inc. All rights reserved. Key words: chondrosarcoma; ferret; neoplasm; treatment; tumor
T
he incidence of neoplasia and associated paraneoplastic syndromes is high in ferrets (Mustela putorius). Although adrenocortical tumors, insulinoma, and malignant lymphoma represent the most common diagnoses, a host of other neoplasms have been reported.1 Although chordomas are recognized as the most common musculoskeletal tumor, they arise from remnants of embryonic notochord and not from the appendicular skeleton. Primary appendicular neoplasms include both osteosarcoma and rhabdomyosarcoma; these tumors are locally invasive, result in significant patient morbidity, and generally necessitate either palliative or curative intent surgical procedures. The following report describes 2 cases of appendicular chondrosarcoma; to the authors' knowledge, this tumor type has not been previously described in ferrets.
CASE 1 _______________________________________ A 5-year-old, 1.25-kg, male neutered ferret was evaluated at the Center for Avian and Exotic
Medicine (New York, NY USA) for left tarsal swelling of 1-week duration. The exclusively indoor ferret was the only pet in the house and fed a commercial ferret kibble diet. The owner described
From the Center for Avian and Exotic Medicine, New York, NY USA; the Zoo/exotic Pathology Service, West Sacramento, CA USA; the New York, Veterinary Specialty and Emergency Center, Farmingdale, NY USA; and the Avian and Exotic Animal Hospital, San Diego, CA USA. Address correspondence to: Rina Maguire, BVSc, Island Exotic Veterinary Care, 591 East Jericho Turnpike, Huntington Station, NY 11746. E-mail: [email protected]. Ó 2014 Elsevier Inc. All rights reserved. 1557-5063/14/2101-$30.00 http://dx.doi.org/10.1053/j.jepm.2014.02.011
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no changes in general activity, appetite, or water consumption. On physical examination, a firm, immobile, nonalopecic swelling measuring 2.5 cm 5 cm was identified on the left tarsus. No clinical lameness was observed, and no crepitus or pain could be elicited when the hock was moved through its range of motion. The findings of the remainder of the physical examination were unremarkable. The ferret was anesthetized for diagnostic testing. The ferret was induced and maintained by face mask using isoflurane (Primal Healthcare Limited, Bethlehem, PA USA) gas anesthesia (2% to 3%) and oxygen (2 L/min) throughout the procedure. Venipuncture of the cranial vena cava was performed and a blood sample was collected. The results of the serum biochemistry panel and complete blood count were unremarkable except for a mild anemia (packed cell volume ¼ 36.5%, reference range: 43% to 55%).2 Ventrodorsal and lateral radiographic images of the left rear limb were obtained, which revealed a large soft tissue density associated with the left tibia and tarsal joint. Irregular opacity within the mass appeared consistent with partial mineralization. It was determined that there was a radiographic union of the cortex of the distal tibia and the region of apparent mineralization. An area of lucency consistent with bone lysis was evident within the left tibia. There was also a marked distortion and caudal deviation of the left gastrocnemius tendon. A fine-needle aspirate using a 19-gauge needle and a 5-mL syringe was taken from the center of the mass. Microscopic evaluation of the sample revealed a proliferation of atypical mesenchymal
cells. Osteosarcoma was considered the provisional diagnosis; however, other forms of neoplasia could not be completely ruled out. An incisional biopsy of the mass was performed 5 days following the fine-needle aspirate. The ferret was premedicated with buprenorphine (0.03 mg/kg subcutaneously, Buprenex; Reckitt Benckiser Pharmaceuticals Inc, Richmond, VA USA) and midazolam (0.5 mg/kg, intramuscularly, Versed; Roche Laboratories, Nutley, NJ USA), and anesthesia was induced with isoflurane and oxygen as previously described. Three radiographic views of the thorax and abdomen were taken as part of metastatic screening and no abnormalities were detected. A wedge biopsy was collected from the mass using a number 15 scalpel blade. A fine-needle aspirate was procured from the left popliteal lymph node. The biopsy tissue sample was decalcified, processed, and stained with hematoxylin and eosin. Microscopic evaluation of the sample revealed multiple variably sized lacunae within a homogenous hyaline cartilage matrix. The lacunae supported single to occasional, multiple neoplastic chondrocytes that were pleomorphic to oval and occasionally stellate with 1 to 3 indistinct nucleoli. The mitotic index was low at less than 1 per highpower field. Interspersed within the sample were focal areas of mineralization. These findings were supportive of a diagnosis of chondrosarcoma. The sample taken from the left popliteal lymph node did not reveal any neoplastic cells. Computed tomography was utilized to determine the margins of the neoplasm (Fig. 1). Anesthesia was administered as described
FIGURE 1. Case 1. A CT image (A) and 3-dimensional reconstruction (B) of a 5-year-old male neutered ferret with a growth associated with the left tibia. CT, computed tomography.
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previously, and transverse images of 2-mm thickness were obtained. The mass was measured and found to be 2.5 cm 1.5 cm 1.1 cm. The mass appeared to be cavitated and demonstrated areas of apparent mineralization. The mass appeared confluent with the articular surface of the distolateral tibial epiphysis, closely associated with the distal fibular epiphysis and expanded into surrounding tissues in a caudolateral fashion. The popliteal lymph node was markedly enlarged compared with the contralateral node, whereas the iliac lymph nodes were within normal limits. Involvement of the tibiotarsal and intertarsal joints was suspected owing to the close proximity of the mass to these structures. Complete local resection did not appear possible and amputation proximal to the midshaft of the left tibia was recommended. However, the owners opted not to amputate and instead elected a limb salvage procedure. Risk factors for this procedure included local tumor reoccurrence and pathological fracture of the tibia. The ferret was premedicated with midazolam (0.5 mg/kg) and hydromorphone (0.2 mg/kg, intramuscularly, Dilaudid-HP; Abbott Laboratories, North Chicago, IL USA). A 22-gauge intravenous catheter was placed in the left cephalic vein to facilitate intraoperative administration of 10 mL/kg/h of the lactated Ringer solution. Intravenous boluses of 5-mL/kg lactated Ringer solution were administered as needed to offset intraoperative bleeding. Anesthesia was induced with 2% isoflurane in 2 L/min of oxygen using a face mask. The ferret was then intubated with a 2.5mm uncuffed endotracheal tube. A Doppler probe was placed over the left palmar metatarsal artery to monitor heart rate and rhythm. Pulse oximetry was also utilized to monitor oxygen saturation with the probe placed over the front left foot pad. A forced warm air blanket was used to maintain normothermia, and temperature was monitored using a manual thermometer every 10 minutes. A 3-cm incision was made on the lateral aspect of the distal tibia to the level of the tarsal joint. Blunt dissection was used to elevate the soft tissue capsule and attachments of the tumor to the surrounding muscle. A periosteal elevator was used to separate the bulk of the tumor from the tibia. The tumor was then removed with bone rongeurs and an osteotome. Portions of adjacent tibial cortex were also removed. The superficial digital flexor was displaced laterally by the growth, and this was replaced into its normal anatomical position and maintained in this position by suturing a soft tissue envelope around the tendon. Samples from the bulk of the tumor and the deeper segment attached
to the tibia were submitted for histopathology. The surgery site was copiously flushed with sterile saline. Instruments and gloves were changed, and the site was closed in 3 layers with 5-0 polydioxanone (Ethicon Inc, Somerville, NJ USA). Gentle manual flexion and extension of the limb was performed and the tarsal joint was deemed stable. The ferret recovered uneventfully from anesthesia. Postoperative pain management included meloxicam (0.5 mg/kg, subcutaneously twice daily, Metacam; Boehringer-Ingelheim Pharmaceuticals, Inc, Ridgefield, CT USA) and hydromorphone (0.1 mg/kg, intramuscularly every 12 hours) for the next 24 hours. The ferret was maintained on the intravenous lactated Ringer solution at 2.5 mL/kg/h for 12 hours. Two doses of perioperative ampicillin were administered (30 mg/kg, intravenously every 8 hours, Ampicillin; Sandoz Inc, Broomfield, CO USA). Twenty-four hours after completion of the procedure, the ferret was switched to amoxicillin/ clavulanate (14 mg/kg orally every 12 hours, Clavamox; Pfizer Animal Health, Exton, PA USA) for 7 days and continued on meloxicam (0.5 mg/ kg, orally every 12 hours) for 5 days. The ferret was restricted to a cage for the next 2 weeks to reduce the risk of tibial fracture at the surgical site. Histologically prepared sections of the tumor were found to be consistent with a chondrosarcoma. The deeper section of the resected tissue sample demonstrated tumor invasion into the cortex of the tibia with fragmented and irregular trabecular structures and marrow elements (Fig. 2). The outer portion of the resected tissue sample was comprised of irregularly shaped, sized, and haphazardly arranged lacunae within a hyaline cartilage matrix. Within these lacunae were nests of pleomorphic chondrocytes. Several binucleate cells were observed and rare mitotic figures were identified at a rate of 0-1 per high-power field. Portions of the matrix were mineralized, consistent with endochondral ossification. Bone trabeculae in this section were fragmented and widely separated by lacy connective tissue. In some areas, neutrophilic infiltrates were appreciated. Despite the hisopathological findings, the owners declined amputation or adjunctive radiation therapy. At a recheck examination 2 weeks following surgery, no lameness was noted and the left tibiotarsal joint demonstrated normal range of motion. Follow-up radiographic images were declined by the owners. Five months following the initial limb-sparing procedure, reevaluation of the ferret was performed owing to local recurrence of
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FIGURE 2. Case 1. Islands of neoplastic chondrocytes invade normal bone (B). Bar ¼ 0.1 mm. H&E stain. H&E, hematoxylin and eosin.
the swelling on the distal tibia and tarsal joint. Further testing and therapy was declined by the owner. The tumor continued to grow over the following months, and its large size eventually affected the ferret's ability to ambulate. Thirteen months following the initial surgery, a left rear limb amputation was performed at another facility. The surgery was considered a success and on recheck examination, 2 years following the initial diagnosis, there was no evidence of local recurrence. CASE 2 _______________________________________ A 2-year-old, 956-g, male neutered ferret was evaluated at the Avian and Exotic Animal Hospital (San Diego, CA USA) for a rapidly growing swelling associated with the right shoulder. The client reported rapid growth of the mass over the previous 2 weeks. The ferret was maintained exclusively indoors and was from a single pet household. The ferret was fed a commercial ferret kibble diet and had no previous vaccination or medical history. The findings of the external physical examination were unremarkable except for a firm, immobile, and nonalopecic swelling that appeared to be attached to the right scapula. No lameness was detected and no pain was elicited when the lesion was manipulated. Normal range of motion was present in the affected limb. The ferret was anesthetized using isoflurane gas (2% to 4%) administered in 1.5-L/min oxygen via 1 6 8
a face mask to facilitate collection of samples for diagnostic testing and radiographic evaluation. Venipuncture of the caudal vena cava was performed and results of the complete blood count and serum biochemistry were normal, except for anemia (packed cell volume ¼ 33%, reference range: 43% to 55%).2 Radiographs of the right front limb were taken and revealed a round proliferative partially mineralized lesion extending from the acromion to the neck of the scapula (Fig. 3). Owing to the suspicion of a bony neoplasm, an incisional biopsy was performed. The next day, the ferret was premedicated with buprenorphine (0.03 mg/kg subcutaneously), and anesthesia was induced with isoflurane and oxygen as previously described. The patient was intubated with a 2.5-mm uncuffed endotracheal tube and maintained on 2% isoflurane and 1.5-L/min oxygen. A 4-mm dermal punch biopsy was used to obtain samples in 3 separate areas of the tumor. The tumor samples were prepared with hematoxylin and eosin stain, and histopatholgical evaluation of the tissue revealed variable amounts of hyaline cartilage matrix. There were multiple variably sized clustered lacunae containing individual to occasionally multiple chondrocytes that were pleomorphic, oval to stellate, and occasionally contained multiple nucleoli. The mitotic index was low at 0-1 per high-power field. Fragments of bone trabeculae were also identified in the sample. Based on the cartilaginous differentiation of tumor cells and matrix, the lesion was considered consistent with a chondrosarcoma. The ferret was returned 7 days later for foreleg amputation. A 22-gauge intravenous catheter was placed in the left cephalic vein, and the ferret was maintained on 10 mL/kg/h of the lactated Ringer solution throughout surgery. After premedication with buprenorphine (0.03 mg/kg subcutaneously), the ferret was anesthetized with isoflurane and oxygen as described previously. A skin incision was made from the dorsal border of the scapula, over the scapular spine, to the proximal third of the humerus, and then circumferentially around the limb at this level. The muscular attachments of the scapula were transected, and the scapula was retracted laterally to reveal the medial surface. The axillary artery and vein were ligated with hemoclips. The brachial plexus was transected. The forelimb was then removed by excising the remaining muscular attachments. The muscle and subcutaneous tissues were closed with 5-0 polyglyconate monofilament (Maxon, Covidien Inc, Mansfield, MA USA) over the brachial plexus and vessels using a simple interrupted pattern. The
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FIGURE 3. Case 2. Lateral (A) and ventrodorsal (B) radiographic images of a 2-year-old male neutered ferret with a rapidly growing mass associated with the scapula. A partially mineralized lesion extending from the acromion to the neck of the right scapula was seen on radiographs.
skin layer was closed with surgical staples. The tumor was submitted for histopathologic evaluation, and a diagnosis of chondrosarcoma was confirmed. Histopathologic examination revealed an unencapsulated, discrete neoplasm comprised of variable amounts of hyaline cartilage matrix. Inconsistently sized lacunae within this matrix supported nests of pleomorphic chondrocytes with indistinct nucleoli. Clusters of chondrocytes were seen to invade normal bone. The mitotic index was low at 0-1 per high-power field. The ferret recovered very well and buprenorphine (0.03 mg/kg subcutaneously) was continued for the next 12 hours. After 24 hours, the patient was discharged on amoxicillin (25 mg/ kg orally twice daily) for 7 days and meloxicam (0.5 mg/kg orally twice daily) for 5 days. On a recheck physical examination 10 days following surgery, the incision had healed and the staples were removed. The owner reported that the patient was doing well and was able to ambulate on 3 limbs. Follow-up thoracic radiographs performed 1 month following amputation were considered unremarkable. The ferret survived for 4 years with no recurrence of the tumor and was euthanized for unrelated health issues at 6 years of age. DISCUSSION _________________________________ To the authors' knowledge, this is the first report describing the diagnosis, treatment, and outcome of chondrosarcoma of the appendicular skeleton in the ferret. Although a report exists describing a chondrosarcoma of the axial skeleton, it is possible that this early report may have mischaracterized a caudal vertebrae chordoma as a chondrosarcoma
because insufficient histopathologic evidence was present to support the diagnosis.1,3 Histologically, chordomas and chondrosarcomas may appear similar, although the location and presence of physaliferous cells helps to differentiate the 2 tumor types. In diagnostically challenging cases, additional immunohistochemical staining can help differentiate the tumor types, especially in suspected metastatic foci.4-7 Positive uptake of intermediate filaments cytokeratin, vimentin, and S-100 protein occurs in chordomas but not chondrosarcomas.6,7 Immunohistochemical staining was not used in these 2 cases as the histopathological detail, revealed by conventional staining techniques, was considered sufficient. Additionally, chordromas were not considered a differential diagnosis based on the lesions' remote location from the notocord, and as such, the additional expense of immunohistochemical staining could not be justified. Both ferrets were noted to be anemic at the time of initial diagnostic evaluation. A transient reduction in hematocrit has been previously reported in ferrets anesthetized with isoflurane at the time of venipuncture and could be responsible for the changes seen in these cases.8 To more accurately evaluate hematologic variables, venipuncture could have been performed before anesthesia was induced or reevaluated at a later time. Primary tumors of the skeletal system in ferrets that have been described in the peer-reviewed literature include chordomas, osteomas, multilobular tumor of bone, and osteosarcomas.1 Chordomas are considered the most frequently encountered neoplasm of the musculoskeletal system in the ferret, comprising 79% of
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musculoskeletal neoplasms reviewed.1 Chordomas are locally aggressive primary malignant bone neoplasms that develop from remnants of embryonic notochord in the skull base and spine. Chordomas may arise from the vertebrae in any region of the spinal column but are most commonly seen at the tail tip involving the last caudal vertebrae.6 Macroscopically, chordomas appear as lobulated, firm, nonencapsulated ulcerated masses.7 Microscopically, these tumors consist of lobules of physaliphorous cells with welldifferentiated bone or cartilage throughout.6,9 Ferrets with lytic lesions affecting cervical and thoracic vertebrae can present with signs of tetraparesis or paraparesis, respectively.9 Debulking of a cervical or thoracic chordoma, although not necessarily curative, may provide the ferret with relief from neurologic signs and pain for a period of time.9 Chordomas affecting the tail are easily treated by amputation, but late excision may predispose to metastasis.4 Metastasis of a chordoma from the cervical region has also been described.9 Osteomas are benign, dense bony masses in ferrets that arise from flat bones; most commonly the bones of the skull and sometimes ribs.6 Histopathology usually reveals compact lamellar bone, bony trabeculae, and mild-to-moderate osteoblastic and hematologic activity.7,10,11 Complete surgical excision of osteomas is considered curative. In ferrets, there is a report of a multilobular tumor of the bone originating from the neck causing extradural compression of the spinal cord.12 Osteomas have a characteristic pattern of numerous contiguous lobules that vary in their composition of cartilage and bone matrix.12 Osteosarcomas are rarely reported tumors in the flat or long bones of ferrets.1 Osteosarcomas appear locally destructive as described in other domestic species and are best treated by amputation.1 The metastatic potential of osteosarcoma in the ferret is not well described, but in other species, this tumor type carries a poor prognosis owing to the high rate of malignancy. Chondrosarcoma is a malignant bone tumor that produces a cartilaginous matrix. There is a lack of direct bone formation by the tumor cells, although new bone formation may be present owing to endochondral ossification of tumor cartilage. In domestic animals, most chondrosarcomas are primary bone tumors arising from within the medullary cavity.13 Secondary chondrosarcomas have been described in humans arising from pre-existing benign cartilaginous lesions, but this has not been identified in other species.13 Chondrosarcomas are typically slow to 1 7 0
metastasize and considered less malignant than osteosarcoma.13,14 Without treatment, chondrosarcomas grow slowly to large sizes and have a longer clinical course before metastasizing. Sites of metastasis typically include the lungs, but other organ involvement is possible.13 In domestic species, chondrosarcomas are most frequently described in middle-aged medium to large breed dogs.13 The prevalence of chondrosarcoma as a primary skeletal tumor is second to osteosarcoma in dogs and accounts for about 10% of primary canine bone tumors. In dogs, chondrosarcomas more commonly affect the flat bones, and lesions in limbs are typically painful and cause lameness in affected limbs.13 In cats, chondrosarcomas are uncommon but can occur in the skeleton (70%) or subcutaneous tissue (30%).15 Overall, 63% of feline skeletal chondrosarcomas occur in the long bones.15 In cattle and goats, chondrosarcomas appear to be aggressive bony tumors that cause lameness, and lymphatic metastasis to the lungs is often identified at necropsy.16,17 Chondrosarcomas, like other bony neoplasms, are diagnosed using radiographic imaging and histopathological evaluation of affected tissue. Computed tomography can be utilized to locate the borders of the neoplasia, provide prognostic information, and assist in surgical planning. Radiographic features of chondrosarcomas can include osteolysis, but when compared with osteosarcomas the areas of bone loss are substantially smaller. Chondrosacromas also do not evoke the same periosteal response as osteosarcoma lesions.13 Diagnosing chondrosarcomas using a fine-needle aspirate can be difficult, and an incorrect diagnosis of osteosarcoma was made initially in case 1. Using this sampling technique, tumor cells from a chondrosarcoma appear cytologically similar to those from an osteosarcoma.13 In making a microscopic diagnosis of chondrosarcomas, clinical findings, histopathology, and radiographic presentation must always be considered to ensure compatibility. Other differentials should include chondroblastic osteosarcomas, actively growing or traumatized osteochondromas, and nonmalignant responses (e.g., injury to ligament insertions, periosteum, or synovium).13 In human and canine patients, chondrosarcomas are classified into grade I, II, or III in order of ascending malignancy. In humans, this grading system is used to guide the aggressiveness of the therapy with only some success.18 The grading is based upon nuclear size, staining pattern (hyperchromasia), mitotic activity, and degree of cellularity.13 The amount or nature of the matrix in chondrosarcomas
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has no prognostic value.13 However, when the matrix becomes fibrillar, hyalinized, or ossified, it may make differentiation between chondrosarcomas and other sarcomas more difficult.13 The therapy recommended for chondrosarcomas in companion animals is wide surgical excision, as complete resection can be curative.13-15 Chemotherapy for grade III chondrosarcomas in canine patients is advised in addition to surgical excision.13,19 Radiation therapy has also been described as an adjunct to surgical therapy, or in cases where complete excision is not possible.19 However, radiation therapy has not been proven to be effective without prior surgical debulking.19 Lowgrade chondrosarcomas in humans have been treated successfully with limb-sparing surgical procedures and intralesional curette.20 In domestic animals, such success has not been reported. Boudrieau et al21 described chondrosarcoma of the canine radius. A limb-sparing technique was performed; however, the tumor reoccurred locally and thoracic metastasis developed. The limb-sparing technique failed in the ferret in case 1 likely owing to the inability to achieve complete surgical excision. Radiation therapy may have prevented recurrence of the tumor but could have increased the likelihood of a pathological fracture. The noncompliance of ferrets with Elizabethan collars also makes radiation therapy less viable as there is concern for self-trauma of the surgical site after the treatment procedures. Chondrosarcoma should be considered a differential diagnosis for any firm nodular mass associated with the skeletal system in ferrets. A lack of previous reports suggests that this tumor type is uncommon in ferrets; however, the outcome of these 2 cases implies that chondrosarcomas have a low metastatic potential and may be amenable to local resection. Although additional studies are required to define the true malignant capacity of this tumor, differentiation of a chondrosarcoma from osteosarcoma appears to suggest a relatively better prognosis and should encourage the clinician and client to pursue biopsy and appropriate surgical therapy.
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ACKNOWLEDGMENTS The authors thank Dr Sam Silverman and Dr Alix Wilson for assistance in case management and Dr Heidi Hoefer for reviewing the manuscript. REFERENCES 1. Williams BH, Weiss CA: Neoplasia, in Quesenberry KE, Carpenter JW (eds): Ferrets, Rabbits and Rodents Clinical
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