What's new in canine osteosarcoma – the CSU experience (Proceedings)


What's new in canine osteosarcoma – the CSU experience (Proceedings)

Osteosarcoma (OSA) represents the most common bony tumor of dogs and cats. Although information regarding etiopathogenesis is lacking, OSA of the long bones (appendicular OSA) is far more common in large and giant breed dogs than in smaller dogs. Rare causes of OSA include those associated with metallic implants, those formed after radiation therapy, and some feline vaccine-associated sarcomas. OSA of the axial skeleton has a more even distribution between breeds. The most common age of incidence is between 6 and 8 years, however there is another small group of dogs that can develop OSA at 18 to 24 months. Overall, axial skeletal OSA occurs at an earlier age than appendicular OSA. OSA is a clinical problem not only due to its aggressive destruction of bone and the attendant pain and structural damage caused, but also due to its high potential for metastasis.

History – physical examination

Most dogs with appendicular OSA will present with a history of lameness. This may be acute in onset, or may have been chronic and progressive. It is common for owners to attribute some trauma to the development of lameness, and it is common for lameness to initially respond to nonsteroidal anti-inflammatory drugs or other analgesics. Owners may notice a firm swelling of the limb as well.

Physical examination will usually reveal lameness. Careful palpation and manipulation of the affected limb should be undertaken to determine the area of interest and detect any subtle swellings or asymmetries between limbs. Although lymph node involvement is uncommon, palpation of the regional lymph node should be undertaken as well. Orthopedic and neurologic examination is reasonable if amputation is to be considered.

Diagnosis, staging, prognosis

At least two radiographic views of the affected area of the limb should be obtained. The classic radiographic appearance of OSA is a mixed lytic and proliferative lesion of the metaphysis of the long bone. OSA will typically not cross a joint space. OSA is most common in the proximal humerus and distal radius of the thoracic limb (away from the elbow), and in the proximal tibia and distal femur of the pelvic limb (toward the knee).

Important differential diagnoses for bony lysis include: (1) Other primary bone tumors (chondrosarcoma, fibrosarcoma, hemangiosarcoma, synovial cell sarcoma); (2) Bone metastasis (most commonly from carcinomas of the lung, mammary gland, or prostate); (3) Bony involvement from systemic neoplasia such as lymphoma or multiple myeloma; (4) Osteomyelitis (fungal or bacterial); (5) Other diseases, such as Legg-Calve-Perthes disease, traumatic osteonecrosis, or aneurysmal bone cyst. It is also important to obtain thoracic radiographs (3 views) at the time of limb radiographs if neoplasia is a differential. Although 90% of dogs with OSA have microscopic metastasis at the time of presentation, only approximately 7% have macroscopic evidence of metastasis at diagnosis.

Following radiographs, a biopsy of the affected area is indicated. This can be obtained by several means, including: (1) Jamshidi bone core biopsy; (2) Michele trephine; or (3) Open, surgical biopsy. Unlike with most soft-tissue tumors, biopsies of bony tumors should be obtained from the center of the radiographic lesion. Biopsies of the periphery of the lesion or the apparent tumor:normal tissue interface will often yield diagnoses of "reactive bone". A fourth method which some clinicians find effective is fine needle aspiration cytology, using either the radiographs or ultrasound as a guide. Approximately 10% of bone biopsies will be nondiagnostic, irrespective of the method used. Some clinicians are comfortable proceeding to definitive surgery without a biopsy if the presentation is "classic" (e.g. correct age, breed, location, radiographic appearance).

Standard presurgical screening (complete blood count, serum chemistry profile, urinalysis) should be obtained as with any patient that may undergo general anesthesia. One important parameter to evaluate is serum alkaline phosphatase (SAP). High SAP has been shown in humans, and recently in 2 separate papers in dogs, to be a poor prognostic indicator for dogs with appendicular OSA. In the more recent study, dogs treated with amputation and chemotherapy that had normal SAP had a median survival time of 12.5 months whereas dogs with increased SAP had a median survival time of 5.5 months. A second laboratory factor recently shown to correlate with outcome is monocyte count. Dogswith monocyte counts less than 400/uL had disease-free intervals twice as long as those with monocyte counts greater than 400/uL. Dogs with overt monocytosis (>1,000/uL) had extremely poor prognoses.

At CSU, a bone scan (99M-Tc nuclear scintigraphy) is always offered as part of the staging process in dogs with OSA. This noninvasive and nontoxic screening test for bone metastasis will reveal additional sites of uptake in approximately 7% of dogs, half of which may be areas of bone metastasis from OSA.

Two recent retrospective studies from CSU determined the outcome in dogs with OSA presenting with metastasis. The first study compared dogs without metastasis to those with metastasis to the regional lymph node only. Median disease free intervals and survival times were significantly shorter in those dogs presenting with lymph node metastasis (DFI 48 vs 238 days, ST 59 vs 318 days). Thus, although the incidence of lymph node metastasis is only approximately 5%, it is recommended that the lymph nodes be removed separately and submitted for evaluation in dogs undergoing surgical management for OSA. A second study evaluated the outcomes in dogs presenting initially with distant metastasis. The median survival time was 78 days. Dogs treated with multi-modality therapy fared better than dogs treated with only surgery, and dogs with bone metastasis fared better than dogs with soft-tissue metastasis. These results underscore the importance of complete staging prior to pursuing definitive therapy.

A small percentage of dogs with OSA will present with a pathologic fracture. In humans, it is controversial as to whether this type of presentation adversely affects outcome. A recent in-press retrospective study using the CSU OSA population evaluated whether this presentation impacted outcome. There were no significant differences in disease-free or overall survival between dogs presenting with pathologic fracture and location- and treatment-matched control dogs presenting without fracture.