Sarcomas are an extremely rare and heterogeneous group of tumors that arise from mesenchymal tissues. According to the estimates of the American Cancer Society, approximately 1.4 million people were estimated to be diagnosed with cancer in the year 2009, with only 13,230 cases representing sarcomas (1); 10,660 of these represented new soft tissue sarcomas and 2570 bone sarcomas diagnosed in 2009, with 3820 and 1470 deaths, respectively, resulting from these tumors (1).
The etiology and pathogenesis of sarcomas, like most cancers, is not well understood. Multiple environmental factors have been associated with the development of soft tissue and bone sarcomas. Many studies have shown that patients who have received radiation therapy for prior cancers have an increased risk of developing soft tissue sarcomas near or within the field of radiation (2-7). In one series, patients developed sarcoma between 3 and 23 years after radiation therapy (5). The average time for development is between 10 and 13 years (2, 4-6). Postirradiation sarcomas have been reported to occur most commonly in patients who received radiation for breast cancer, Hodgkin and non-Hodgkin lymphoma, and cervical cancer. These have also been reported in patients who received radiation for other benign and malignant conditions (2,3). Postirradiation sarcomas comprise a variety of histologic types, including malignant fibrous histiocytoma, osteosarcoma, fibrosarcoma, malignant peripheral nerve sheath tumor, and angiosarcoma (3,5,6). Most postirradiation sarcomas are high-grade lesions, which may be less responsive to chemotherapy than their de novo counterparts and are associated with a poorer prognosis (2-7).
Exposure to various chemicals and environmental toxins—such as asbestos, phenyl herbicides, chlorophenols (wood preservatives), dioxins (Agent Orange), and hexachlorobenzene (pesticide)—has been linked to the development of sarcoma (8-15). Arsenic, vinyl chloride, and Thorotrast have also been associated with the occurrence of sarcomas (15-18). Tamoxifen, which is used to treat and to prevent breast cancer, has been implicated in the etiology uterine sarcomas (19).
Trauma and foreign bodies have also been associated with sarcoma development. There are reports of sarcomas developing after recent trauma (20,21), although a causal relationship is unclear; the trauma is likely responsible for bringing the tumor to medical attention. Chronic inflammation has been associated with sarcoma development and may be a risk factor (15). Lymphangiosarcoma can occur in the setting of chronic lymphedema and is known as Stewart-Treves syndrome (22). Sarcomas have also been associated with viral infections; the best-known examples are herpesvirus 8 (HHV-8), HIV-1, and Kaposi sarcoma (15,16). Other viral infections have been suggested, but no epidemiologic data have been found to establish a true causal relationship (15).
Molecular and genetic alterations have been shown to be responsible for the development of soft tissue sarcomas and bone sarcomas. Though most of these genetic aberrations are sporadic in origin, some of ...