Bone sarcomas are extremely rare neoplasms, which precludes determination of their true incidence. Approximately 2,400 new cases are identified annually in the United States. Population-based tumor registries seldom separate bone sarcomas into various histologic types.

Osteosarcoma is the most common malignant primary bone tumor (excluding multiple myeloma), comprising 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’s sarcoma represents approximately 6% of all primary malignant bone tumors, with an annual incidence of 200 cases. Malignant fibrous histiocytoma (MFH) comprises < 1% of primary bone sarcomas.

Epidemiology

Gender 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.

Age Osteosarcoma and Ewing’s sarcoma develop primarily in children and adolescents. A biphasic pattern of incidence of osteosarcoma has been observed; peaks in adolescents (rapid growth of long bones) and in the elderly (secondary tumors arising in association with Paget’s 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.

Race No predilection has been noted in any particular race. However, Ewing’s sarcoma is extremely rare in American and African blacks.

Disease site 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’s sarcoma is classically described as a diaphyseal lesion but 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.

Survival Low-grade sarcomas are associated with the most favorable survival, which approaches 90% in patients with adequately treated tumors. With regard to high-grade sarcomas, survival has improved dramatically in patients with osteosarcoma or Ewing’s sarcoma due to the advent of effective multiagent chemotherapy regimens. Survival has improved with multimodality therapy from historic rates of < 20% to current rates of 50% to 75%.

Etiology and risk factors

For the majority of bone sarcomas, no specific etiology has been established. A few predisposing factors have been identified.

Genetic factors 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, leukemia, soft-tissue sarcoma, brain, and adrenal cortical tumors. Li-Fraumeni syndrome results from a genetic loss of p53.

Radiation therapy 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. The majority of these tumors are osteosarcomas. MFH and other histologies also can arise within a radiation field.

Chemotherapy 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’s 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’s disease and Maffucci’s syndrome). MFH can arise in association with bone infarcts.

Trauma A traumatic event often prompts medical intervention, at which time the bone sarcoma is detected. The short temporal relationship between the traumatic event and the diagnosis of the tumor usually rules out a causal relationship.

Orthopedic implants 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.

Signs and symptoms

Local symptoms 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 arising 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 prior to fracture usually can be elicited.

Constitutional symptoms are rare in patients with bone sarcoma, but such symptoms as fever, malaise, and weight loss can be observed in those with Ewing’s sarcoma.

Screening and diagnosis

Currently, there is no screening test for primary bone sarcomas. The diagnosis must be made by clinical and radiographic evaluations and confirmed by histopathologic analysis of biopsy-obtained tissue.

Physical examination should include an assessment of the local extent of the soft-tissue mass, if present, and its relationship to the adjacent joint.

Laboratory studies A CBC may demonstrate anemia and/or leukocytosis associated with Ewing’s sarcoma, but, in general, results of these studies fall within the normal range. Alkaline phosphatase and lactic dehydrogenase (LDH) levels may be elevated in patients with osteosarcoma or Ewing’s sarcoma. An abnormal glucose tolerance test may be observed in patients with chondrosarcomas.

X-rays Biplanar (AP and lateral) plain radiographs of the affected extremity provide critical information on the nature of the bone lesion. The specific site of involvement within the bone, pattern and extent of bone destruction, type of periosteal changes, presence of matrix mineralization within the tumor, and presence of soft-tissue extension may be gleaned from plain films.

CT Standard CT scans provide further delineation of many of these changes.

MRI is the imaging study of choice for the evaluation of the extent of an associated soft-tissue mass and the relationship of the tumor to the neurovascular structures, surrounding soft tissues, and the adjacent joint. The intramedullary extent of the tumor and presence of skip metastases within the bone are best demonstrated by MRI.

Bone scan A bone scan is performed to screen for distant osseous metastases.