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Musculoskeletal oncology is a field of medicine that involves the diagnosis and management of neoplastic conditions affecting the musculoskeletal system. This not only entails neoplasia of mesenchymal origin (derived from embryonic mesoderm), but also metastatic carcinoma and a variety of pseudotumorous conditions. Mesenchymal tumors are an extremely heterogeneous group of neoplasms including over 200 benign conditions and 90 types of sarcoma, and so the majority of this chapter is dedicated to them. The relative incidence of benign to malignant disease is 200:1. These tumors are classified histomorphologically based on features of differentiation, but there is considerable overlap. It is favorable to consider these separate conditions as points on a continuum, rather than entirely distinct entities. Classification, nevertheless, is important because it may yield insight to the behavior, treatment response, and overall prognosis. Benign disease, by definition, behaves in a nonaggressive fashion and exhibits little tendency to locally recur or metastasize. Sarcomas (malignant tumors of mesenchymal origin), however, can be rapidly destructive, have metastatic potential, and have a tendency to locally recur.

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Neoplastic processes arise in tissues of mesenchymal origin far less frequently than those of ectodermal or endodermal origin. In 2004, soft-tissue and bone sarcomas had an annual incidence in the United States of just more than 8600 and 2400 new cases, respectively. When compared with the overall cancer mortality of 563,000 cases per year in 2004, sarcomas are a small fraction of the problem. However, although they are a relatively uncommon form of cancer, these tumors behave in an aggressive fashion, with currently reported mortality rates in some series of greater than 50%. According to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, approximately 8600 new soft-tissue sarcomas developed in the United States in 2004 with over 3600 sarcoma-related deaths. The associated morbidity is much higher. These tumors inflict a tremendous emotional and financial toll on individuals and society alike. Furthermore, sarcomas preferentially affect older patients, with only 15% occurring in patients younger than 15 years and 40% in patients older than 55 years. Accordingly, as the population ages, the incidence of these conditions will increase.

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Tumorigenesis is a multifactorial process, which, despite considerable fiscal and intellectual interest, is still poorly understood. There is commonality in genetic mutation that confers to cells the ability to replicate in an unregulated fashion. The development of a colony of abnormally proliferating cells out of normal tissue is referred to as transformation. This process involves acquired mutations in oncogenes, tumor suppressor genes, and other genes that directly or indirectly control proliferation, cell motility, and properties of invasiveness. Such a process may progress beyond the state of benign disease to an aggressive, dedifferentiated state with considerable genomic instability.

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To appreciate how bone or soft-tissue tumors develop, one must have a basic understanding of the cell cycle and the regulation thereof. The cell cycle is divided into four distinct phases: G1 (gap 1), S (DNA synthesis), G2 (gap 2), and ...

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