Surgical Treatment of Appendicular Bone Tumours in the Dog and Cat

Introduction

Osteosarcoma (OS) is the most common bone tumour in the canine patient; it accounts for more than 85% of the malignancies originating in the skeleton. It is a disease of the middle-aged large and giant breed dog and older cat. Predictive factors are increasing weight and more specifically increasing height in dogs. The breeds more at risk are St. Bernard, Great Dane, Irish Setter, Doberman Pincher, Rottweiler, German Shepherd, and Golden Retrievers. No specific breed information is available for cats.

Canine Bone Tumours

Seventy-five (75%) of the OS occurs at the appendicular skeleton. The most common primary site is the metaphyseal region of the long bones. The predilection sites are “far from the elbow” and “near the knee joint,” (i.e., proximal humerus and distal radius, and distal femur and proximal tibia, respectively. The remaining 25% of the OS occurs at the axial skeleton. The most common primary sites are: 27% mandible, 22% maxilla, 15% spine, 14% cranium, 10% ribs, 9% nasal cavity or sinuses, and 6% pelvis. Extra­skeletal OS is rare.

The aetiology of OS is largely unknown. Suspected physical factors include repetitive micro-trauma, metallic implants used for fracture repair, and radiation therapy. There is growing evidence that there may be molecular and genetic factors implicated in OS tumorigenesis. Gene mutations of retinoblastoma (Rb), p53, and c-Met have been suggested to increase the susceptibility to develop OS. Furthermore, growth factors, including growth hormone, insulin like growth factor 1, hepatocyte growth factor, and angiogenic factors have also been suggested to contribute to the malignancy of OS.

The clinical presentation of appendicular OS is a history of lameness and swelling at the primary site. There may be history of mild trauma prior to the onset of lameness. Acute and severe lameness is seen in case of a pathologic fracture. The clinical presentation of axial OS is dependent upon the location of OS. Respiratory signs associated with clinical evidence of pulmonary metastasis are rare; additionally, less than 15% of the dogs will have radiographic visible pulmonary metastasis. Metastasis commonly occurs, although at presentation it is often sub-clinical. Metastasis occurs through the haematogenous route. Metastasis may also be encountered in the regional lymph nodes, however. A more sensitive detection technique than radiographs of pulmonary metastases is computer tomography.

Diagnosis is based upon

a.  Full clinical, orthopaedic and neurological examination.

b.  Radiography: evaluation of the primary site and the thorax. Common radiographic findings are: lysis of the cortex, soft tissue swelling, and new bone formation. The tumour invades the periosteum, lifts it up and new bone is laid down. The latter results in a triangular appearing deposition of bone on the cortex at the periphery of the lesion, the Codman’s triangle.

c.  Computer tomography of the thorax for the evaluation of pulmonary metastasis.

d.  Cytology of the primary site and of enlarged lymph nodes. Typically osteoblasts are encountered in the case of OS.

e.  Tissue biopsy. OS is a malignant mesenchymal tumour; the tumour cells are primitive osteoblasts and produce osteoid. The latter is used as criteria for the histological diagnosis of OS. A small biopsy sample before surgery may help to confirm a preliminary diagnosis. Misdiagnosis, however, including chondrosarcoma, fibrosarcoma, hemangiosarcoma or reactive bone, is relatively common due to the mixed histologic appearance of the tumour. Therefore, it is essential that the diagnosis OS is confirmed with histologic evaluation of the entire tumour after definitive excision.

f.  Blood examination for the general clinical work up of the patient. Elevated bone alkaline phosphatase has been correlated with a poorer prognosis of appendicular OS.

Surgical Treatment of OS

Amputation is the standard local treatment for appendicular OS. It is performed as a forequarter amputation for the front leg, as an amputation at the diaphysis of the femur or at the coxofemoral joint depending on the location and extent of the tumour for the hind leg. Even large and giant breed dogs function well after amputation and their owners are pleased with the mobility and quality of life of their pets. Amputation alone is considered a palliative treatment.

Another option, that is increasingly applied, is limb-sparing surgery. Limb sparing is a complicated and long process that requires efforts from the owner, surgeon, oncologist, and radiologist. There are certain prerequisites, for the selection of suitable candidates for a limb sparing procedure. These include dogs with OS clinically and radiographically confined to the leg, the primary tumour does not affect more than 50% of the bone, and the patient should be in an otherwise good health. Other criteria for consideration are the absence of pathological fracture and less than 360° involvement of soft tissues.

These patients can receive a pre-operative treatment: intra-arterial cisplatin, intra-venous cisplatin, radiotherapy of the bone, or combination of the above. Pre-operative treatment with cisplatin has no additional advantage on survival time over post-operative treatment. So far, pretreatment with radiation has revealed to be unsatisfactory for the preservation of the limb and even of life but can be used successfully for palliation.

The most suitable cases for limb sparing are those with a confined tumour in the distal radius or ulna, the distal fibula, and scapula. The carpal joint is suitable for arthrodesis in these cases. In all other cases, where arthrodesis of the scapulohumeral, coxofemoral, stifle, or tarsal joints is performed, a limb sparing procedure has given so far only fair to poor function of the patient. The latter in combination with the high complication rate of limb sparring procedures leads surgeons away from recommending limb sparing near these joints.

There are several limb spearing procedures described. Their advantages and disadvantages are described in the following Table.

On the overall, 80% of the limb spared OS-patients experience a good to excellent limb function. For a successful limb sparing process, a dedicated owner and veterinary expert team are essential. There is, on the overall, no significant difference in the survival rate for dogs treated with limb sparring and cisplatin compared to dogs treated with amputation and cisplatin.

Canine limb spare patients have a high infection rate of 31–68%. Once there is an infection it can be controlled with long-term antibiotic therapy based on an antibiogram. However, the infection rarely, if ever, resolves. These infections can result in draining tracts, exposure of the fixation material or the graft, and can result into loosening of the implanted material. Revision surgery is common practice is such cases. In case there is a catastrophic implant failure amputation of the limb is required. Unexpectedly, allograft infection is related to a significantly longer survival time compared to dogs with no allograft infection. It is unclear how this can be explained, but it is speculated that the immune system is activated by humeral factors and plays a role in the elimination of the cancer cells.

The surgical treatment (amputation or limb-sparing), if used alone, is considered a palliative treatment and does not change the prognosis of the OS patient. The latter is attributed to poor medical control of the (micro-) metastasis. Therefore, surgical treatment is combined with one or more of the following adjuvant therapies:

1.  Chemotherapy: systemic cisplatin, carboplatin, doxorubicin, or combination therapy after the surgical treatment.

2.  Several other adjuvant drug delivery systems that are under current investigation. Examples are: (a) the implantation of a platinum polymer (OPLA-Pt) that releases slowly relatively low concentrations of platinum into the circulation but reaches up to 30-fold high concentrations locally and (b) the combination of immune stimulant lipospheres with chemotherapeutics.

3.  Resection of solitary metastatic pulmonary nodes (metastasectomy). This is performed either with nodulectomy or complete or partial lobectomy. The criteria that increase the probability of a longer survival period include

a.  Complete remission of the primary tumour, preferentially >300 days

b.  One or two metastatic nodules visible on radiographic examination

c.  No other signs for metastatic disease elsewhere

4.  Pre-operative radiation of the tumour. Radiation therapy can cause considerable necrosis of the OS and is used in an effort to downstage the tumour and improve local disease control following surgical removal of the tumour.

OS needs to be differentially diagnosed from other canine primary bone tumours.

Chondrosarcoma is considered to have a low metastatic potential but up to 25% metastatic rates are reported. Chondrosarcoma develops most commonly in large- and medium-breed dogs. Aggressive surgical resection often results in very long surgical tumour control with low- and intermediate-grade tumours, i.e., 2.7 and 6 years, respectively. High-grade chondrosarcoma carries a poorer prognosis with 0.9-year survival time. There is no reliable adjuvant chemotherapeutic agent. Differential diagnosis is based on the location of the tumour: the proximal tibia is the most common localization for chondrosarcoma, whereas the distal radius is the most common one for OS and on histological examination of the entire tumour after complete surgical excision.

Primary hemangiosarcoma is a rare bone tumour. It is highly metastatic and virtually all dogs will develop metastasis within 6 months of diagnosis. The metastasis is wide spread and makes it difficult to determine which the primary tumour is. The predominant radiographic sign of hemangiosarcoma is lysis of the bone. It has a very poor prognosis, i.e., less than 10% 1-year survival if the tumour can be completely excised.

Fibrosarcoma is a rare primary bone tumour with low metastatic potential in low and intermediate-grade tumours and up to 50% metastatic rate in high-grade tumours. Complete resection of the tumour that is clinically confined to the primary site can be curable. On a histological level, it is very difficult to differentially diagnose fibrosarcoma and fibroblastic osteosarcoma, especially from relatively small tissue samples. It is therefore, crucial to re-evaluate the tumour histopathologically after complete surgical resection.

Osteomas are benign tumours of the bone. The differential diagnosis is based on the fact that (a) the tumours are radiographically well defined and radiodense and (b) the tumour location is not painful on palpation. Surgical excision of the tumour is curable.

Multiple cartilaginous exostosis is considered a developmental hereditable disorder of growing dogs. They stop growing as soon as dogs reach skeletal maturity. Occasionally, malignant transformations occur. The differential diagnosis is based on (a) the age of the patient, (b) the non- or moderate painful palpable mass at the metaphyseal are of the long bones, (c) the benign radiographic appearance with a trabecular pattern. Surgical excision is advised only when clinical signs do not decline after skeletal maturity.

Bone cysts are benign lesions of the bone. The differential diagnosis is based on (a) the young age of the animal, (b) the radiographically multilobular, sharply defined radiolucent defects in the medullary canal of the long bones. It needs to be confirmed with histological examination since it may resemble radiographically a highly resorptive OS.

Bacterial and fungal osteomyelitis. Bacterial osteomyelitis is usually associated with a history of a penetrating trauma, like dog bites and open fractures. Fungal osteomyelitis is related to geographic location or history of travel to endemic fungal areas. Particularly fungal osteomyelitis should be considered due to the fact that it is preferably monostotic and located in the metaphyseal are of long bones. The most common fungal organisms affecting bone are Coccidioides immitis and Blastomyces dermatitis. Differential diagnosis is based upon (a) the history and signalment of the patient, (b) clinical presentation (febrile, general illness, possible lung infiltrates due to pulmonary infection), (c) serology, and (d) histologic examination and (fungal) culture.

*Manuscript is adapted from previous version written by Marianna Tryfonidou-van Megen, DECVS.