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Malignant tumors of the uterine corpus are broadly divided into three main types: carcinomas, sarcomas, and carcinosarcomas. Although the latter two categories are rarely encountered, they tend to behave more aggressively and contribute to a disproportionately higher number of uterine cancer deaths. Pure sarcomas differentiate toward smooth muscle (leiomyosarcoma) or toward endometrial stroma (endometrial stromal tumors). Carcinosarcomas are mixed tumors demonstrating both epithelial and stromal components. These have also been known as malignant mixed müllerian tumor (MMMT). In general, uterine sarcomas and carcinosarcomas grow quickly, lymphatic or hematogenous spread occurs early, and the overall prognosis is poor. However, there are several notable exceptions among these tumors.
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EPIDEMIOLOGY AND RISK FACTORS
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Sarcomas account for approximately 3 to 8 percent of all malignancies of the uterine corpus (Brooks, 2004; D’Angelo, 2010; Major, 1993). Historically, uterine sarcomas included carcinosarcomas, accounting for 40 percent of cases; leiomyosarcomas, 40 percent; endometrial stromal sarcomas, 10 to 15 percent; and undifferentiated sarcomas, 5 to 10 percent. In 2009, the International Federation of Gynecology and Obstetrics (FIGO) reclassified carcinosarcomas as a metaplastic form of endometrial carcinoma. Despite this, carcinosarcomas are still commonly included in most retrospective studies of uterine sarcomas and in the 2014 World Health Organization (WHO) classification (Greer, 2015; Kurman, 2014; McCluggage, 2002).
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Because of their infrequency, uterine sarcomas and carcinosarcomas have few identified risk factors. These include chronic excess estrogen exposure, tamoxifen use, African American race, and prior pelvic radiation. In contrast, combination oral contraceptive pill use and smoking appear to lower risks for some of these tumors (Felix, 2013).
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Leiomyosarcomas have a monoclonal origin, and although commonly believed to arise from benign leiomyomas, for the most part they do not. Instead, they appear to develop de novo as solitary lesions (Zhang, 2006). Supporting this theory, leiomyosarcomas have molecular pathways distinct from those of leiomyomas or normal myometrium (Quade, 2004; Skubitz, 2003). They are, however, often found in proximity to leiomyomas.
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Endometrial stromal tumors (ESS) have heterogeneous chromosomal aberrations (Halbwedl, 2005). However, the pattern of rearrangements is clearly nonrandom, and chromosomal arms 6p and 7p are frequently involved (Micci, 2006). Translocations involving several chromosomes and the resultant fusion proteins are thought to be involved in ESS pathogenesis (Lee, 2012; Panagopoulos, 2012).
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Uterine carcinosarcomas are monoclonal, biphasic neoplasms. Namely, they are composed of separate but admixed malignant epithelial and malignant stromal elements (D’Angelo, 2010; Wada, 1997). Both the carcinoma and sarcoma components are thought to arise from a common epithelial progenitor cell. Acquisition of any number of genetic mutations, including defects in p53 and DNA mismatch repair genes, may be sufficient to trigger tumorigenesis (Liu, 1994). These early molecular defects will be shared by both components as ...