Porth's Essentials of Pathophysiology, 4e

Disorders of the Skeletal System: Trauma, Infections, Neoplasms, and Childhood Disorders 1097

C h a p t e r 4 3

Ewing sarcoma is primarily a disease of children and young adults and is rarely seen in older adults. 34,48,49 Males are affected slightly more frequently than females, and white children have an approximately ninefold higher incidence rate than black children. The most frequent site of Ewing sarcoma is the femur, usually in the diaph- ysis (see Fig. 43-10). The pelvis represents the second most common site; other sites include the pubis, sacrum, humerus, vertebrae, ribs, skull, and other flat bones. Manifestations of Ewing tumor include bone pain, limi- tation of movement, and tenderness over the involved bone or soft tissue. It often is accompanied by systemic manifestations such as fever or weight loss, which may serve to confuse the diagnosis. There may be a delay in diagnosis when the pain and swelling associated with the tumor are attributed to a sports injury, or when the tumor is located in the pelvis and the pain is not localized and the mass is not apparent. Pathologic fractures are common because of bone destruction. The most common sites of metastasis are the lungs, bone marrow, and other bones. Because Ewing sarcoma is a difficult diagnosis to establish, the diagnostic biopsy is very important. Treatment methods incorporate a combination of multiagent chemotherapy, surgery, and radiation ther- apy. 34,48,49 Multiagent chemotherapy can shrink the tumor rapidly, and is generally given before local con- trol measures are initiated. Ewing sarcoma is considered to be a radiosensitive tumor, and local control may be achieved through radiation or surgery. Patients with small, nonmetastatic, distally located tumors generally have the best prognosis. Metastatic Bone Disease Skeletal metastases are the most common malignancy of osseous tissue. 50,51 Approximately half of all people with cancer have bone metastasis at some point in their disease. Metastatic lesions are seen most often in the spine, femur, pelvis, ribs, sternum, proximal humerus, and skull, and are less common in anatomic sites more distant from the trunk of the body. Tumors that fre- quently spread to the skeletal system are those of the breast, lung, prostate, kidney, and thyroid, although any cancer can ultimately involve the skeleton. The major symptom of bone metastasis is pain with evidence of an impending pathologic fracture. It usu- ally develops gradually, over weeks, and is more severe at night. Pain is caused by stretching of the periosteum of the involved bone or by nerve entrapment, as when the nerve roots of the spinal cord are compressed by the vertebral body. Symptoms of hypercalcemia may occur in cases of bony destruction. Radiographic examinations are used along with CT or bone scans to detect, diagnose, and localize meta- static bone lesions. A bone biopsy usually is done when there is a question regarding the diagnosis or treatment. Serum levels of alkaline phosphatase and calcium often are elevated in persons with metastatic bone disease. The primary goals in treatment of metastatic bone disease are to prevent pathologic fractures and promote

survival with maximum functioning, allowing the person to maintain as much mobility and pain control as pos- sible. Standard treatment methods include chemother- apy, irradiation, and surgical stabilization. Radiation therapy is primarily used as a palliative treatment to alleviate pain and prevent pathologic fractures. After a pathologic fracture has occurred, bracing, intramedul- lary nailing of the femur, or spine stabilization may be done. Because adequate fixation often is difficult, bone cement often is used with internal fixation devices to stabilize the bone. Recent research has focused on the role of osteo- clastic and osteoblastic activity in the pathogenesis of metastatic bone disease and on the use of the bisphos- phonates (e.g., pamidronate disodium, zoledronic acid) for its treatment. 52 The bisphosphonates, which are now well-established agents for the prevention and treatment of osteoporosis, have recently been shown to decrease symptoms associated with bone metastasis secondary to breast and prostate cancer. These agents bind prefer- entially to bone at sites of active bone metabolism, are released from the bone matrix during bone resorption, and potentially inhibit osteoclast activity and survival, thereby reducing osteoclast-mediated bone resorption. Recent studies suggest that besides their strong anti- osteoclastic activity, these agents may also have some direct antitumor effects. 41 ■■ Both benign and malignant tumors can develop from the cartilage (chondrogenic), bone (osteogenic), and supporting (fibrogenic) elements of bone, and bone tumors are generally classified according to their tissue counterpart. ■■ Benign bone tumors grow slowly and usually do not destroy the surrounding tissues. Malignant tumors can be primary or metastatic. Primary bone tumors are rare, grow rapidly, metastasize to the lungs and other parts of the body through the bloodstream. They include osteosarcoma, which begins in osteogenic cells of the bone and is the most common type of bone cancer; chondrosarcoma, which has its origin in the cartilaginous elements of bone; and Ewing sarcoma, which is characterized by small round cell tumors of bone and soft tissue origin. ■■ Metastatic bone tumors usually are multiple in occurence, originating primarily from cancers of the breast, lung, and prostate. A primary goal in metastatic bone disease is the prevention of pathologic fractures. SUMMARY CONCEPTS