Porth's Essentials of Pathophysiology, 4e

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Musculoskeletal Function

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Osteosarcoma Osteosarcoma is an aggressive and highly malignant bone tumor. 18,19,44–46 It is the most common malignant bone tumor, representing one fifth of all primary bone tumors. 19 The tumor has a bimodal distribution, with 75% occurring in persons younger than 20 years of age. 19 A second peak occurs in the elderly with pre- disposing factors such as Paget disease, bone infarcts, or prior irradiation. Overall, men are more commonly affected than women. The cause of osteosarcoma is unknown. The correla- tion of age and location of most of the tumors with the period of maximum growth suggests some relation to increased osteoblastic activity. In younger persons, the primary tumor most often is located at the anatomic sites associated with maximum growth velocity—the distal femur, proximal tibia, and proximal humerus. Bone tumors in the elderly are more common in the humerus, pelvis, and proximal femur. There are known genetic factors associated with osteosarcoma. Mutations in two genes are reported to increase susceptibility: the retinoblastoma gene ( RB ), a critical cell cycle genera- tor; and the p53 gene, which regulates deoxyribonucleic acid (DNA) repair and certain aspects of cellular metab- olism 19 (see Chapter 7). Osteosarcomas are aggressive tumors that grow rap- idly in a circular, ball-like mass in the bone tissue. They often are eccentrically placed in the bone and move from the metaphysis of the bone out into the periosteal surface, with subsequent spread to adjacent soft tissues (Fig. 43-11). These tumors spread through the blood- stream; most often, the tumor cells exit the primary tumor through the venous end of the capillary, and early

metastasis to the lung is common. Lung metastases, even if massive, usually are relatively asymptomatic. The prognosis for a person with osteosarcoma depends on the aggressiveness of the disease, presence or absence of pathologic fractures, size of the tumor, and rapidity of tumor growth. The primary clinical feature of osteosarcoma is deep, localized pain with nighttime awakening and swelling in the affected bone. Because the pain is often of sud- den onset, patients and their families often associate the symptoms with recent trauma. The skin overlying the tumor may be warm, shiny, and stretched, with promi- nent superficial veins. The range of motion of the adja- cent joint may be restricted. The treatment of osteosarcoma is surgery in combi- nation with multiagent chemotherapy, both before and after surgery. 45,46 In the past, treatment usually entailed amputation above the level of the tumor. Limb salvage surgical procedures, using a metal prosthesis or cadaver allograft, are now a standard alternative. In younger children who undergo arthroplasty, an expandable internal prosthesis is used to allow for bone growth. Amputation is another surgical option. It involves either the removal of expendable bones such as the fibula, toes, or ulna, or the complete removal of the tumor and the affected limb. Chondrosarcoma Chondrosarcoma consists of malignant tumors of cartilag- inous lineage and is commonly subclassified according to site of origin as central (intramedullary) or peripheral (jux- tacortical and surface). 18,19 Chondrosarcomas can arise as a primary tumor from preexisting benign cartilage tumors such as osteochondroma or chondroblastoma. 47 They commonly arise in the central portions of the skeleton, including the pelvis, shoulder, and ribs (see Fig. 43-10). Chondrosarcomas develop about half as frequently as osteosarcomas. They occur primarily in middle or later life; however, there are chondromas that occur in younger persons. Chondrosarcomas are slow growing and metastasize late, and often are painless. They can remain hidden in an area such as the pelvis for a long period of time. This type of tumor, like many primary malignancies, tends to destroy bone and extend into the soft tissues beyond the confines of the bone of origin. Early diagnosis is important because chondrosar- comas respond well to early radical surgical excision. It usually is resistant to radiation therapy and avail- able chemotherapeutic agents. Not infrequently, these tumors transform into a highly malignant tumor, mesen- chymal chondrosarcoma, which requires a more aggres- sive treatment, including combination chemotherapy. Ewing Sarcoma Ewing sarcoma is a member of a family of tumors that includes primitive neuroectodermal tumor (PNET). Both tumors are characterized by densely packed, regu- larly shaped, small cells with round or oval nuclei; and both share a specific reciprocal translocation of chromo- somes 11 and 31, or variants thereof. 19,42,48,49

FIGURE 43-11. Osteosarcoma.The distal femur contains a dense osteoblastic malignant tumor that extends through the center in the soft tissue and epiphysis. (From Garcia RA, Klein MJ, Schiller AL. Bones and joints. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &Wilkins; 2012:1244.)