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 and is the 8th most common malignancy of childhood.
• 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.
• 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.

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.
• Most cases of pediatric osteosarcoma are high-grade cancers, although lower grade variants are seen.
• No classic genetic change, although karyotypes are typically highly abnormal
• Major subtypes of osteosarcoma include osteoblastic, chondroblastic, fibroblastic, telangiectatic, and small cell.
• 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. In 20% of tumors, other sites of involvement will include the pelvis, facial bones, and shoulder blade.
• The most common sites of metastatic disease are lungs and bone. Involvement of regional lymph nodes is rare.

Etiology

• The etiology of most cases is unknown.
• Abnormal TP53 and/or Rb function implicated in laboratory studies of osteosarcoma
• Radiation exposure is a known cause of osteosarcoma and usually presents 10–20 years after exposure.