Epidemiology and Pathogenesis

OS is the most common malignancy of bone in childhood, representing 15% of all primary bone tumors. The disease is somewhat more common in boys than girls (1.5 : 1), and the incidence is slightly higher in African Americans than in whites. The incidence is highest in patients between 10 and 20 years of age. OS is extremely rare in children younger than 5 years of age. Three percent of patients with OS have a germ line mutation in p53; many of these patients’ families are affected by Li-Fraumeni syndrome. This is a familial cancer syndrome in which affected individuals have a risk of developing sarcomas, brain tumors, leukemia, breast cancer, and adrenal cortical carcinoma at a young age; this risk persists throughout patients’ lifetimes. Patients who have had hereditary retinoblastoma are also at higher risk for the development of OS. OS is also associated with Rothmund-Thomson syndrome (skin rash, short stature, and skeletal abnormalities) and Paget’s disease in patients older than 40 years of age.

The etiology of OS is unknown. Exposure to ionizing radiation, such as that used for treatment of previous malignancies, has been linked to secondary OS. There are no convincing data to support a link between other environmental or infectious exposures and OS.

Clinical Presentation

The most common clinical symptom at presentation is pain, often described as dull and aching, and typically of several months’ duration. Other complaints include a palpable mass with or without swelling. Systemic complaints such as fevers, weight loss, and decreased appetite are rare. Eighty percent of OS occur in the extremities, and on examination, a mass (tender or nontender) may be noted (Figure 60-1). The examination may also reveal decreased range of motion or muscle atrophy. Regional lymphadenopathy is rare. The most common sites of disease include the distal femur, proximal tibia, and proximal humerus, although OS may occur in any bone. Involvement of the axial skeleton can occur but is less common. Eighty percent of patients with OS have localized disease at the time of diagnosis. The lung is the most common site of detectable metastatic disease at diagnosis, although patients may present with multifocal bone disease without pulmonary involvement.

Figure 60-1 Osteosarcoma.

The differential diagnosis includes benign bone tumors, infections, and other malignant disorders. Benign tumors to be considered in the differential diagnosis include unicameral bone cysts, osteoblastomas, eosinophilic granulomas, giant cell tumors, aneurysmal bone cysts, osteochondromas, and fibrous dysplasia. Infections that may present in similar manner to OS include osteomyelitis and septic arthritis. Other malignancies must also be considered, including ESFT, chondrosarcoma, fibrosarcoma, leukemia, and metastatic lesions of other solid tumors.

Evaluation

Imaging studies are more helpful in making the diagnosis of OS than are laboratory tests. A plain radiograph will often reveal a lytic or blastic lesion of the bone with poorly defined borders (see Figure 60-1). Other findings include periosteal elevation adjacent to the primary lesion, a sunburst appearance, or a pathologic fracture. If OS is suspected, chest computed tomography (CT) and bone scan can be used to assess for pulmonary and bone metastases. Magnetic resonance imaging (MRI) should be performed to better evaluate the extent of the tumor and should include the joint above and below the involved area so that skip lesions are not missed (see Figure 60-1). In addition to delineating the intra- and extraosseous extent of the tumor, the MRI may provide information regarding tumor effects on critical neurovascular structures.

The diagnosis of OS can only be made by biopsy. Biopsies should be performed by an experienced orthopedic oncologist. The surgical approach at the time of biopsy may have an impact on the feasibility of future limb-sparing surgeries, which are necessary for local control of the tumor. In some situations, interventional radiologists are able to obtain the necessary biopsies with active participation by orthopedic oncologists. Involvement of the surgeon who will eventually perform the definitive surgical resection is preferable.

Under the microscope, OS classically appears to be composed of spindle cells associated with malignant osteoid (see Figure 60-1). The extent of osteoid production may vary among the osteoblastic, chondroblastic, fibroblastic, telangiectatic, and small cell subtypes; however, the presence of tumor osteoid is the key pathologic feature of this disease.

Management

Advances in chemotherapy over the past 30 years have resulted in higher overall survival rates and improved rates of limb salvage for patients with OS. Chemotherapy is used initially both to treat pulmonary micrometastases and to decrease the size of the primary tumor mass to facilitate surgical resection. Current treatment protocols for OS typically include preoperative (induction) and postoperative (adjuvant) chemotherapy. The total duration of treatment is approximately 8 to 12 months. Drugs that have been shown to be effective against OS include cisplatin, doxorubicin, and high-dose methotrexate. North American and European investigators are currently evaluating the role of ifosfamide and etoposide in OS therapy through an international clinical trial.

Complete surgical resection with wide margins is necessary for cure. Modern approaches to limb salvage surgery have resulted in local recurrence rates that are similar to those achieved with amputation. Limb salvage has therefore become the standard of care except when limb preservation would compromise disease control. Decision making with regard to approach to limb reconstruction is complex, particularly in patients who have not reached skeletal maturity. OS is not considered a radiosensitive tumor, although high-dose radiation may be considered for local control in rare cases in which tumor location precludes surgical resection. Surgery also remains the key therapeutic modality for macroscopic pulmonary metastases.