Malignant Bone Tumors, Sarcomas, and Other Soft Tissue Neoplasms

Bone Tumors

Primary bone tumors include osteosarcomas, chondrosarcomas, and Ewing sarcoma. These rare tumors, which arise from the normal cellular components of bone and can potentially metastasize, have an incidence of 1.8 new cases per 100,000 population per year and account for only 0.2% of all cancers. Tumors that originate in other organs can metastasize to bone and represent the vast majority of bone cancers in adults.

Clinical Manifestations and Diagnosis

Patients who have either primary malignant or benign bone tumors can present with pain, swelling, and sometimes pathologic fracture of the involved bone. Metastatic tumors to bone also can be similarly symptomatic but are often first suspected based on imaging tests that are obtained to stage the tumor. Imaging of a primary bone tumor includes plain radiographs, magnetic resonance imaging (MRI), and computed tomography (CT). On imaging, malignant tumors generally have irregular, poorly defined borders, a wide area of transition, evidence of cortical bone destruction, periosteal reaction, and soft tissue extension.

When imaging suggests a malignant primary bone tumor, the patient should be referred to an orthopedic oncologist to perform a diagnostic biopsy. An improperly performed biopsy can potentially change a tumor that is resectable by limb salvage to a tumor that requires amputation. Staging evaluation should include both a CT scan and a bone scan.

Major Primary Malignant Bone Tumors

Osteosarcoma

Osteosarcoma, which is the most common bone sarcoma, accounts for approximately 35% of all primary bone tumors. Osteosarcomas have a bimodal age distribution, with the highest incidence before age 20 years and a second peak after age 60 years. About 60% of cases occur in males. The most common primary sites in the younger age group are the metaphyses of long bones and the extremities, especially the distal femur, proximal tibia, and proximal humerus. In older adults, the primary anatomic sites are more varied.

Most osteosarcomas are sporadic, but the incidence is higher among families with germline gene mutations or deletions, such as retinoblastoma (about 60% of familial cases), TP53 (Li-Fraumeni syndrome, about 40% of familial cases), or rarely the RecQ DNA helicase genes (Rothman-Thompson, Werner, or Bloom syndrome). Prior radiation and Paget disease ( Chapter 228 ) are also risk factors, particularly for older individuals.

On histologic examination, osteosarcomas contain varying amounts of osteoid as well as cartilage and fibrous tissue. The typical radiologic appearance consists of a mixture of osteoblastic and osteolytic features with periosteal elevation.

Treatment

Management generally consists of neoadjuvant chemotherapy followed by surgical resection and then adjuvant chemotherapy. Most patients can undergo limb salvage surgery rather than amputation. For patients under age 40 years, the most widely used chemotherapy schedule consists of methotrexate, doxorubicin, and cisplatin under expert supervision. Some patients with solitary or oligometastatic disease can undergo surgery with curative intent, but the evidence base is limited. A number of salvage chemotherapy schedules can be considered, including gemcitabine/docetaxel and ifosfamide/etoposide.

Prognosis

With current multidisciplinary management, including complete surgical resection and multiagent chemotherapy, the overall survival of patients with osteosarcoma is on the order of 65%. A higher percentage of tumor necrosis (>90%) following neoadjuvant chemotherapy portends a better prognosis. However, the outcome for patients with metastatic osteosarcoma is poor.

Chondrosarcoma

Chondrosarcomas, which are the second most common bone sarcoma (25% of cases), are characterized by malignant differentiation of hyaline cartilage. The peak incidence is in the fifth to seventh decades. The pelvis, proximal femur, and proximal humerus are the most common primary sites, and patients can present with long-standing swelling and/or pain. Approximately 15% of chondrosarcomas arise from preexisting peripheral osteochondromas and harbor mutations in the exostosin ( EXT1 or EXT2 ) gene. The other 85% arise in a central location, some in preexisting enchondromas. The majority of chondrosarcomas (90%) are low or intermediate grade, but the 10% of chondrosarcomas that are high-grade exhibit much more metastatic potential.

The pathologic distinction between low-grade chondrosarcoma and benign central enchondromas can be challenging, but size greater than 5 cm and axial location are very suggestive of malignancy. On imaging, chondrosarcomas often have a mixed sclerotic and lytic appearance.

Treatment and Prognosis

Complete surgical resection with clear margins is the mainstay of management for all grades of chondrosarcoma. The overall 5-year survival rate is about 75%, and most patients who survive for 4 years also survive for 10 years or longer. Unfortunately, these tumors are relatively insensitive to radiation and chemotherapy, although these modalities may be considered in the palliative setting.

Ewing Sarcoma

Ewing sarcoma, which accounts for approximately 15% of bone sarcomas, commonly has a characteristic translocation between EWS and ETS family transcription factors. The most common translocation [t(11;22)(q24;q12)] between EWSR1 and FLI1 occurs in approximately 85% of cases, but other fusion genes are also found. Although Ewing sarcoma most commonly presents in bone, it can also arise in soft tissue, in which case it is called extraosseous Ewing sarcoma.

The peak incidence for Ewing sarcoma is in the second decade, but about 20% of cases occur in older patients. This disease mainly occurs in Whites of European origin. Patients can present with a systemic illness, characterized by intermittent low-grade fever, leukocytosis, and anemia. Ewing sarcoma has a predilection for the diaphyseal region of long bones, pelvis, and ribs.

On imaging, these tumors frequently have associated soft tissue involvement and can also have a permeative or “moth-eaten” appearance and a multilayered “onion-skin” periosteal reaction. Special pathologic input is critical in establishing the diagnosis, particularly in distinguishing Ewing sarcoma from other small, round, blue cell tumors.

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