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Tumors of the musculoskeletal system are an extremely heterogeneous group of neoplasms consisting of well over 200 benign types of neoplasms and approximately 90 malignant conditions. The relative incidence of benign to malignant disease is 200:1. The tumors uniformly arise from embryonic mesoderm and are categorized according to their differentiated or adult histology. Current classification schemes are essentially descriptive. Each histologic type of tumor expresses individual, distinct behaviors with great variation between tumor types. Benign disease, by definition, behaves in a nonaggressive fashion with little tendency to recur locally or to metastasize. Malignant tumors or sarcomas, such as osteosarcoma and synovial cell sarcoma, are capable of invasive, locally destructive growth with a tendency to recur and to metastasize.

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Neoplastic processes arise in tissues of mesenchymal origin far less frequently than those of ectodermal and endodermal origin. In 2004, soft-tissue and bone sarcomas had an annual incidence in the United States of 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 a relatively uncommon form of cancer, these mesenchymal tumors behave in an aggressive fashion with reported current mortality rates in some series 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 are more common in older patients, with 15% percent affecting patients younger than 15 years and 40% percent affecting persons older than 55 years. Accordingly, as the population ages, as it is doing at a rapid rate, the incidence of these tumors will increase.

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Tumorigenesis is a complex multiple-step process by which healthy tissue progressively transforms from a normal phenotype into an abnormal colony of proliferating cells. During this process, cells acquire genetic abnormalities in oncogenes, tumor suppressor genes, and other genes that directly or indirectly control proliferation. Such a process may progress beyond the controlled state of benign disease to become a dedifferentiated, aggressive, and immortal phenotype by genomic instability. It is this instability that allows the cell to progress to fulminant malignancy. DNA regulation and, correspondingly, integrity is ultimately lost and a cancer is born.

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To appreciate how bone or soft-tissue tumors develop, one must have a basic understanding of the cell cycle during which cell division occurs. The cell cycle is divided into four distinct phases: G1 (gap 1), S (DNA synthesis), G2 (gap 2), and M (mitosis). DNA synthesis occurs during the S phase, with chromosomal separation and cell division occurring in the M phase. The majority of cell growth takes place during G1. The mature state for mesenchymal tissues is normally in a resting, nonproliferative phase designated G0. It is the factors that ...

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