Osteosarcoma (OS) and Ewing’s sarcoma, which together account for approximately 6% of all pediatric malignancies,1,106 are the most common primary malignant tumors of bone in the pediatric and adolescent population. Although the biologic properties of these tumors are distinct, their treatment principles are quite similar.107 A comprehensive discussion of osteosarcoma is provided in Chapter 116. The main features of OS in the pediatric population, including its unique molecular genetic and cytogenetic features, will be discussed in this section.

OS, the most common primary bone tumor in children and adolescents, accounts for 4% of all childhood cancers.1 The majority of cases occur in the second decade of life, with a peak age of incidence of 16 years in males and 12 years in females.108 OS occurs more frequently in boys than in girls, and the incidence in black children is slightly higher than in white children.108

The majority of osteosarcomas are sporadic. However, certain conditions are known to predispose to the development of OS, such as previous exposure to ionizing radiation109 and alkylating agents.110 Approximately 3% of cases are attributable to prior irradiation. OS in patients older than 40 years are almost always attributable to Paget disease.111

OS is associated with several cancer predisposition syndromes, including hereditary retinoblastoma, Li-Fraumeni syndrome (LFS), and Rothmund-Thomson syndrome (RTS). Patients with hereditary retinoblastoma have germline mutations in the RB1 ...