DESCRIPTION

Osteosarcoma is a malignant tumor of the bone and arises from mesenchymal cells. The malignant cells are usually pleomorphic spindle cells that lay down abnormal bone (osteoid formation).

EPIDEMIOLOGY

• Osteosarcoma is the most common pediatric primary bone cancer.
• In the United States, there are about 4.4 cases per million children and adolescents.
• Approximately 400 new pediatric cases of osteosarcoma are diagnosed each year in the United States, which is about 2% of all childhood cancers.
• A bimodal distribution is noted with the first peak in adolescence (median, age 16 years) and second peak during the 7th and 8th decade of life.
• Incidence of osteosarcoma parallels skeletal growth and is more frequently noted in tall individuals.
• Males are more commonly affected than females.

RISK-FACTORS

• Radiation exposure
• Hereditary retinoblastoma, in which patients with germline Rb gene mutation have increased risk of osteosarcoma with or without radiation exposure
• Li-Fraumeni syndrome, in which patients have germline TP53 gene mutation and increased risk of a range of sarcomas, among other malignancies
• Rothmund-Thomson syndrome
• Bloom syndrome
• Enchondromatosis
• Hereditary multiple exostoses
• Fibrous dysplasia
• Paget disease of the bone, although less relevant to pediatric populations

PATHOPHYSIOLOGY

• The histologic hallmark of osteosarcoma is the presence of osteoid formation.
• Most cases of pediatric osteosarcoma are high-grade cancers, although lower grade variants are seen.
• No single genetic change, although karyotypes are typically highly abnormal
• At diagnosis, 80% of patients will have localized disease and 20% will have metastatic disease.
• In >80% of tumors, the metaphysis of long bones will be involved, such as the femur, tibia, and humerus, with distal femur the most common primary site. Less common primary sites include the pelvis, facial bones, and scapula.
• The most common sites of metastatic disease are lungs and bone. Regional lymph node or extraosseous involvement is rare.

ETIOLOGY

• The etiology of most cases is unknown.
• Abnormal p53 and/or Rb function implicated in laboratory studies of osteosarcoma
• Radiation exposure is a known cause of osteosarcoma and usually presents 10 to 20 years after exposure.