Bone sarcomas are extremely rare neoplasms, which precludes determination of their true incidence. It is estimated that in 2015, approximately 2,970 new cases of cancer of the bones and joints were diagnosed in the United States, and some 1,490 patients died of the disease. Population-based tumor registries seldom separate bone sarcomas into various histologic types.
Osteosarcoma is the most common malignant primary bone tumor (excluding multiple myeloma), accounting for 30% of all such malignancies. The annual incidence of osteosarcoma is approximately 800 cases per year in the United States. Chondrosarcoma is the second most common malignant primary tumor of bone; its annual incidence is approximately half that of osteosarcoma. Ewing sarcoma represents approximately 6% of all primary malignant bone tumors, with an annual incidence of 200 cases. Malignant fibrous histiocytoma (MFH) accounts for less than 1% of primary bone sarcomas.
The incidence of primary bone sarcomas is higher in males than in females, regardless of histologic type. A low-grade variant of osteosarcoma (parosteal osteosarcoma) is observed more frequently in females.
Osteosarcoma and Ewing sarcoma develop primarily in children and adolescents. A biphasic pattern of incidence of osteosarcoma has been observed; peaks have been noted among adolescents (rapid growth of long bones) and in patients over 60 years of age (secondary tumors arising in association with Paget disease or within previously irradiated tissue). Chondrosarcomas are rarely seen in skeletally immature patients. They usually develop in middle-aged and older adults. MFH is observed in adults.
No predilection has been noted in any particular race. However, Ewing sarcoma is extremely rare in American and African blacks. Recent evidence suggests that polymorphisms in EWS/FLI1-responsive microsatellites correlate with these racial disparities.
Any bone and any site within a given bone may be affected. Most osteosarcomas occur in the metaphyseal region of skeletally immature long bones (ie, distal femur, proximal tibia, and proximal humerus), which have the greatest growth potential. Ewing sarcoma is classically described as a diaphyseal (main or midsection of a long bone) lesion, but it may arise in any region within an involved long bone. It commonly arises in the flat bones of the pelvis and scapula. Primary bone tumors of any histologic type are extremely rare in the spine and sacrum.
Low-grade sarcomas are associated with the most favorable survival, which approaches and may even exceed 90% in patients with adequately treated tumors. With regard to high-grade sarcomas, survival has improved dramatically in patients with osteosarcoma or Ewing sarcoma because of the advent of effective multiagent chemotherapy regimens. Survival has improved with multimodality therapy, from historic rates of less than 20% to current rates of 60% to 75%, but it has plateaued at this level for well over a decade. Novel agents are certainly necessary for refractory cases.
For the majority of bone sarcomas, no specific etiology has been established. A few predisposing factors have been identified, including genetics, radiation therapy, chemotherapy, preexisting benign tumors and conditions, trauma, and orthopedic implants.
Children with familial retinoblastoma have a 13q chromosome deletion and an increased incidence of osteosarcoma. Li-Fraumeni syndrome is also associated with an increased risk of bone sarcomas as well as other cancers, such as breast cancer, leukemia, soft-tissue sarcoma, and brain and adrenal cortical tumors. Li-Fraumeni syndrome results from a genetic loss of TP53. A maternal history of breast cancer or melanoma has been suggested as a risk factor in at least one study. Screening of at-risk families and surveillance of affected individuals for these syndromes may permit earlier diagnosis and more effective treatment in these populations. There is some preliminary evidence that pleomorphisms in the microsatellite region of the promoters for downstream targets of EWS/Fli1 may make certain populations at increased risk for developing Ewing sarcoma.
Bone sarcomas constitute a rare, but devastating, consequence of therapeutic irradiation. Radiation-associated sarcomas develop within the radiation field, usually after a latent period of at least 3 years, occurring anytime thereafter. The majority of these tumors are osteosarcomas. MFH and other histologies also can arise within a radiation field.
Alkylating agents and anthracyclines administered for unrelated cancers have been implicated as etiologic factors in the development of second malignant neoplasms, particularly osteosarcoma.
Preexisting Benign Tumors/Conditions
Osteosarcomas can arise in association with Paget disease and rarely in association with benign bone tumors (ie, fibrous dysplasia). Chondrosarcomas can develop in the cartilaginous component of osteochondromas (solitary and multiple hereditary exostosis) and in patients with enchondromatosis (Ollier disease and Maffucci syndrome). MFH can arise in association with bone infarcts.
A traumatic event often prompts medical intervention, at which time the bone sarcoma is detected. Interestingly, experimental inflammation via wounding in animal models infected with the Rous sarcoma virus led to sarcomagenesis. Such a finding is truly intriguing. Nonetheless, the incidence of trauma relative to that of sarcomas certainly implies inflammation alone is not causative.
Case reports of bone sarcomas arising in the region in which a metallic prosthetic device has been implanted have been published. The rarity of these clinical situations relative to the vast number of devices implanted makes a causal relationship unlikely.
Localized pain and swelling are the hallmark clinical features of bone sarcomas. The pain, which initially is insidious and transient, becomes progressively more severe and unremitting. Localized soft-tissue swelling, with or without associated warmth and erythema, may be present. A joint effusion may be observed, and range of motion of the adjacent joint may be limited and painful. Movement or weight bearing of the involved extremity may exacerbate local symptoms.
Patients with tumors that arise in the lower extremities can present with a painful limp. The neurovascular examination of the affected extremity is usually normal. Regional lymph nodes are rarely involved.
Pathologic fracture may also be a presenting sign, although a history of pain before fracture usually can be elicited.
These are rare in patients with bone sarcoma, but such symptoms as fever, malaise, and weight loss can be observed in those with Ewing sarcoma.