74 SARCOMAS OF BONE AND SOFT TISSUES
Harrison’s Manual of Medicine
SARCOMAS OF BONE AND SOFT TISSUES
Soft Tissue Sarcomas
SOFT TISSUE SARCOMAS
INCIDENCE AND ETIOLOGY About 6400 cases are diagnosed each year in the U.S. 60% arise in extremities, lower:upper = 3:1; 30% on the the trunk, often the retroperitoneum; 10% in the head and neck region. Although malignant nerve sheath tumors may develop from neurofibromas, nearly all other sarcomas arise de novo and are not malignant transformations of benign tumors. Sarcomas occur with increased frequency in persons who have undergone radiation therapy (usually within the treatment port), who are immunosuppressed (congenital or acquired), or who have been exposed to chemical carcinogens such as polycyclic hydrocarbons, asbestos, and dioxin. Sarcomas may rarely develop within a scar from a prior operation, burn, injury, or foreign body implantation. Kaposi’s sarcoma is associated with human herpes virus 8 infection. Individuals with germline mutations in the p53 gene (Li-Fraumeni syndrome) are at increased risk for these and other malignancies. Those who have survived congenital retinoblastoma (germline mutations in the Rb gene) are at risk of developing sarcomas.
PATHOLOGY AND CLINICAL FEATURES A common presentation is with an asymptomatic mass. Local symptoms may be related to pressure, traction, or entrapment of nerves. The tumor spreads hematogenously; lung is the most common site. About 20 different types of sarcomas are recognized, based upon the normal tissue from which they derive (e.g., fibrous tissue, skeletal muscle, smooth muscle, blood vessels, fat). Diagnosis is based upon an incisional biopsy placed so that it can be encompassed by a subsequent definitive surgical procedure. Imaging of the primary tumor is best with plain radiographs and MRI for extremity or head and neck lesions and by CT for truncal primaries.
STAGING The only routine staging test is the CXR. Other tests should be done only when indicated by signs and symptoms. Two staging systems exist: American Joint Commission on Cancer (AJCC) and Musculoskeletal Tumor Society. Both are predominantly based upon the histologic grade of the tumor. The AJCC system classifies grade 1 (well differentiated) tumors as stage I, grade 2 (intermediate differentiation) as stage II, and grade 3 (poorly differentiated) as stage III. Tumors are also classified on the basis of size: A, <5cm; B, ³5cm. Pts with metastatic disease are stage IV. Prognosis is related to stage: 75% 5-year survival for stage I; 55% for stage II; 29% for stage III; <20% for stage IV.
Radical excision with documented histologic negative margins is the treatment of choice. Although some histologies behave differently (e.g., chondrosarcoma and GI leiomyosarcomas are refractory to chemotherapy), soft tissue sarcomas are generally lumped together for treatment. Adjuvant radiation therapy and/or chemotherapy improve local control and permit the use of a limb-sparing surgical procedure. Several doxorubicin-based combination chemotherapy programs are similar in efficacy and improve disease-free survival. Impact on overall survival is less consistent. Combination chemotherapy with doxorubicin and ifosfamide is used in the setting of metastatic disease and may cure 10–15% of pts.
INCIDENCE AND ETIOLOGY Multiple myeloma is the most common neoplasm of bone (Chap 64). Osteosarcoma, chondrosarcoma, Ewing’s sarcoma, and malignant fibrous histiocytoma are the major sarcomas involving bone. About 2500 new cases occur each year. Benign bone tumors such as enchondromas and osteochondromas may transform into chondrosarcoma, and fibrous dysplasia and Paget’s disease of bone may transform into osteosarcoma or malignant fibrous histiocytoma.
Osteosarcoma accounts for ~45% of bone sarcomas; 60% of osteosarcomas occur in children and adolescents. Males are affected 1.5–2 times more frequently than females. Osteosarcoma has a predilection for the metaphyses of long bones, epecially the distal femur and proximal tibia and humerus. Malignant fibrous histiocytoma is considered part of the spectrum of osteosarcoma. Pts present with pain and swelling of the affected area. Plain radiograph reveals a destructive lesion with a moth-eaten appearance, a spiculated periosteal reaction (sunburst appearance), and a cuff of periosteal new bone formation at the margin of the soft tissue mass (known as Codman’s triangle). It spreads hematogenously to the lungs. The most important prognostic factor is response to chemotherapy. Preoperative chemotherapy with doxorubicin, ifosfamide, cisplatin, and high-dose methotrexate followed by limb-sparing surgery and postoperative chemotherapy is the standard treatment approach. The disease is radioresistant. Long-term survival of extremity primaries is 60–70%. Resection of pulmonary metastases may lead to long-term survival in pts with metastatic disease.
Chondrosarcoma accounts for ~25% of bone sarcomas; peak incidence is in the fourth to sixth decades of life. It has a predilection for flat bones, especially the shoulder and pelvis. The disease has an indolent natural history, presenting with pain and swelling. On radiography, lesions may appear lobular with mottled, punctate, or annular calcification. Chondrosarcomas are difficult to distinguish from benign cartilage tumors radiographically; clinical signs of progressive tumor growth and inflammation favor the malignant diagnosis. This neoplasm is resistant to chemotherapy. Surgery is the treatment of choice.
Ewing’s sarcoma comprises 10–15% of bone sarcomas; peak incidence is in teenagers. It has a predilection for the diaphyses of long bones and for flat bones. Radiographs show a characteristic onion peel periosteal reaction with a soft tissue mass. The tumor consists of sheets of small, round, blue-staining cells that may be confused with lymphoma, small cell lung cancer, or embryonal rhabdomyosarcoma. The diagnosis is confirmed by detecting p30/32, the product of the mic-2 gene on the cell surface. Ewing’s sarcoma is a member of a family of tumors called peripheral primitive neuroectodermal tumors (PNETs), most of which occur in soft tissues. The characteristic chromosomal translocation associated with PNETs including Ewing’s sarcoma is t(11;22), which creates a chimeric gene product with components from the fli-1 gene on chromosome 11 and ews on 22. The disease commonly spreads to lungs, other bones, and bone marrow. Systemic chemotherapy with doxorubicin, ifosfamide, etoposide, and vincristine is effective treatment and usually employed before limb- sparing surgery. Peripheral primary lesions (below the elbow and mid-calf) have a 5-year survival of 80%. Even with metastatic disease, 25–40% are curable with high-dose therapy and stem cell transplantation.
For a more detailed discussion, see Patel SR, Benjamin RS: Soft Tissue and Bone Sarcomas and Bone Metastases, Chap. 98, p. 625, in HPIM-15.