Osteosarcoma (OS) is the most common primary bone tumour in dogs accounting for up to 85% of malignancies originating in the skeleton. OS is largely a disease of middle-aged to older dogs, with a median age of 7 years; however, there is also a small early peak in age incidence at 18-24 months. Primary rib OS tends to occur in younger adult dogs with a mean age of 5 years. Only 5% of OS occur in dogs weighing less than 15 kg.

Location

Approximately 75% of OS occur in the appendicular skeleton, with the remainder occurring in the axial skeleton. The metaphyseal region of long bones is the most common site with front limbs affected twice as often as rear limbs and the distal radius and proximal humerus being the two most common locations. In the rear limbs, tumours are fairly evenly distributed between the distal femur, distal tibia and proximal tibia, with the proximal femur a slightly less common site. In the axial skeleton, OS can occur, in decreasing order of frequency, in the mandible, maxilla, spine, cranium, ribs, nasal cavity or paranasal sinuses and the pelvis.

Clinically documentable multicentric OS at the time of initial diagnosis occurs in less than 10% of all cases. Osteosarcoma of extraskeletal sites is rare, but has been reported in mammary tissue, subcutaneous tissue, spleen, bowel, liver, kidney, testicle, vagina, eye, gastric ligament, synovium, meninges and adrenal gland.

Aetiology

Aetiology of canine OS is generally unknown.

Physical Factors

Since OS tends to occur in major weightbearing bones adjacent to late-closing physes and heavy dogs are predisposed, multiple minor trauma and subsequent injury to sensitive cells in the physeal region may occur. OS has been associated with metallic implants used for fracture repair, chronic osteomyelitis and with fractures in which no internal repair was used. Exposure to ionising radiation can induce OS. Osteosarcomas have been concurrently seen in dogs with bone infarcts, but it is not clear whether there is any causal relationship.

Molecular and Genetic Factors

There is a growing body of experimental and clinical data to support molecular and genetic factors by which OS may develop and progress. These include the p53 suppressor gene as well as alterations in several growth factors, cytokines or hormone signaling systems.

History and Clinical Signs

Dogs with OS of appendicular sites generally present with a lameness and swelling at the primary site. There may be a history of mild trauma just prior to the onset of lameness. This history can often lead to misdiagnosis as another orthopaedic or soft tissue injury. The lameness worsens and a moderately firm to soft, variably painful swelling arises at the primary site. Dogs may present with acute, severe lameness associated with pathological fractures, although they account for less than 3% of all fractures seen. Large and giant-breed dogs that present with lameness or localised swelling at metaphyseal sites should be evaluated with OS as a likely diagnosis.

The signs associated with axial skeletal OS are site dependent. Signs vary from localised swelling with or without lameness to dysphagia (oral sites), exophthalmos and pain on opening the mouth (caudal mandibular or orbital sites), facial deformity and nasal discharge (sinus and nasal cavity sites) and hyperaesthesia with or without neurological signs (spinal sites). Dogs with tumours arising from ribs usually present because of a palpable, variably painful mass.

Dogs rarely have respiratory signs as the first clinical evidence of pulmonary metastasis; rather, their first signs are usually vague. With radiographically detectable pulmonary metastasis dogs may remain asymptomatic for many months, but most dogs develop decreased appetites and non-specific signs such as malaise within 1 month. Hypertrophic osteopathy may develop in dogs with pulmonary metastasis.

Diagnostics

Radiology

Initial evaluation of the primary site involves interpretation of good-quality radiographs taken in lateral and craniocaudal projections. The overall radiographic abnormality of bone varies from mostly bone lysis to almost entirely osteoblastic or osteogenic changes. There is an entire spectrum of changes between these two extremes and the appearance of OS can be quite variable. There are some features, however, that are commonly seen. Cortical lysis is a feature of OS along with a soft tissue extension with an obvious soft tissue swelling. New bone (tumour bone) may form in these areas in a palisading pattern perpendicular to or radiating from the axis of the cortex (i.e., 'sun-burst'). As tumour invades the cortex the periosteum is elevated and new bone is laid down providing a triangular-appearing deposition of dense new bone on the cortex at the periphery of the lesion ('Codman's triangle'). Osteosarcoma does not directly cross articular cartilage and primary lesions usually remain monostotic. Differential diagnoses of lytic, proliferative or mixed pattern aggressive bone lesions identified on radiographs include: other primary bone tumours (chondrosarcoma, fibrosarcoma, haemangiosarcoma); metastatic bone cancer; multiple myeloma or lymphoma of bone; systemic mycosis with bony localisation; bacterial osteomyelitis; and, albeit rare, bone cysts. Metastatic cancer can spread to bone from almost any malignancy.

Tissue Biopsy

A diagnosis is suggested by signalment, history, physical examination and radiographic findings. Cytology may support the tentative diagnosis, and, combined with clinical features and radiographic appearance, enough confidence in the diagnosis to move forward with discussion of treatment options may exist. However, in most cases, a definitive diagnosis lies in procurement and interpretation of tissue for histopathology. With new treatments such as limb-sparing, it is crucial that the biopsy procedure is planned and performed carefully. Bone biopsy may be performed as an open incisional, closed needle or trephine biopsy.

Staging

Examination for evidence of apparent spread of the disease is important. Regional lymph nodes, although rarely involved should be palpated and fine needle cytology performed on any enlarged node. Sites of bone metastasis may be detected by a careful orthopaedic examination with palpation of long bones and the accessible axial skeleton. High-detail thoracic radiographs should be taken during inspiration with the patient awake. It is uncommon to detect pulmonary metastatic disease at the time of diagnosis (less than 10% of dogs). Advanced imaging (e.g., computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) /CT) may play a more important role in patient staging in the future. Bone survey radiography has been useful in detecting dogs with second skeletal sites of osteosarcoma. There are conflicting reports on the usefulness of nuclear scintigraphy (bone scan) for clinical staging of dogs with osteosarcomas.

Prognostic Factors

The biological behaviour for non-appendicular sites of OS appears to be similar (aggressive) with the exception of the mandible and possibly the rest of the calvarium. Elevated alkaline phosphatase has been clearly associated with a poorer prognosis for dogs with appendicular OS.

Therapy

Amputation

Amputation of the affected limb is the standard local treatment for appendicular osteosarcoma. Even large and giant-breed dogs will usually function well after limb amputation and most owners are pleased with their pet's mobility and quality of life.

Limb-Sparing Surgery

Although most dogs function well with amputation, there are some dogs where limb-sparing would be preferred over amputation, such as dogs with severe pre-existing orthopaedic or neurological disease or dogs with owners who absolutely refuse amputation. To date, more than 500 limb-sparing procedures have been performed at Colorado State University. Limb function has generally been good to excellent in most dogs and survival has not been adversely affected. Limb-sparing in dogs with tumours in the distal radius or distal tibia usually results in good function.

Adjuvant Systemic Treatment

In general, dogs with OS ultimately die of metastatic disease distant to the site of their primary tumour. Several protocols are under review; however, most involve either a platinum agent (i.e., carboplatin or cisplatin) alone or in combination with doxorubicin. Median survivals of approximately 1 year can be expected with these protocols and approximately 25% of dogs will survive 2 years or longer. While the platinum chemotherapeutics have quadrupled medium survival times, approximately 80% of dogs still eventually die of distant disease. Much remains to be achieved regarding the prolongation of disease-free survival in dogs with OS and novel chemotherapeutics, drug delivery techniques, targeted molecular and immunomodulatory therapies are the subject of intense research in the medical community.

Palliative Therapy

Radiation therapy to palliate bone pain has been investigated and extensively applied in veterinary oncology. Using protocols ranging from two to four 8 Gy fractions, pain management is palliated in 74-92% of dogs for medians ranging from 2-4 months. For short-term pain control, a non-steroidal anti-inflammatory drug (e.g., piroxicam, carprofen, meloxicam, etc.) may be given, dependent on control of clinical signs. This appears to give temporary pain relief to most dogs with OS lesions. Other choices include acetaminophen/ codeine combinations and other opiates. The bisphosphonates (e.g., pamidronate, zoledronate) have been used in people to control bone loss and subsequent pain due to metastatic lesions.

References

1.  Dernell WS, Ehrhart NP, et al. Tumors of the skeletal system. In: Withrow, SW; Vail, DM. eds. Small animal clinical oncology (fourth edition). St. Louis: Saunders/ Elsevier, 2007; 540-582.