Malignant tumors of the uterine corpus are broadly divided into three main types: carcinomas (Chap. 33), 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 are mainly characterized by differentiation toward smooth muscle (leiomyosarcoma) or stromal tissue within the endometrium (endometrial stromal tumors). Carcinosarcomas are mixed tumors demonstrating both epithelial and stromal components and 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.
Sarcomas account for approximately 3 to 8 percent of all malignancies of the uterine corpus (Brooks, 2004; Major, 1993). Historically, uterine sarcomas included carcinosarcomas, comprising 40 percent of cases; leiomyosarcomas, 40 percent; endometrial stromal sarcomas, 10 to 15 percent; and undifferentiated sarcomas, 5 to 10 percent. Recently, carcinosarcomas have been reclassified as a metaplastic form of endometrial carcinoma. Despite this, carcinosarcomas are still commonly included in most retrospective studies of uterine sarcomas as well as in the 2003 World Health Organization (WHO) classification (Greer, 2011; McCluggage, 2002; Tavassoli, 2003). After excluding carcinosarcomas, leiomyosarcomas have become the most common subtype of true uterine sarcomas (D'Angelo, 2010).
Because of their relative infrequency, the epidemiology of uterine sarcomas and carcinosarcomas has not been extensively studied. As a result, relatively few risk factors have been identified, but they 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.
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). They are, however, often found in proximity to leiomyomas. Supporting this theory, leiomyosarcomas have molecular pathways that have been shown to be distinct from those of leiomyomas or normal myometrium (Quade, 2004; Skubitz, 2003).
Endometrial stromal tumors have heterogeneous chromosomal aberrations (Halbwedl, 2005). However, the pattern of rearrangements is clearly nonrandom, with chromosomal arms 6p and 7p frequently involved (Micci, 2006). A loss of tumor suppressor gene function(s) is suspected. However, too few cases have been studied to generate a working hypothesis (Moinfar, 2004).
Uterine carcinosarcomas are monoclonal, biphasic neoplasms composed of distinctive and separate, but admixed, malignant epithelial and malignant stromal elements (D'Angelo, 2010; Wada, 1997). The sarcomatous component is derived from the carcinomatous element, which is the driving force (McCluggage, 2002). Several identifiable risk factors parallel those observed in endometrial carcinoma, thus it would seem plausible that these tumors have ...