Cancers of the uterine corpus are predominantly derived from endometrial glandular epithelial cells (endometrial adenocarcinoma), with small number of cases derived from either endometrial stromal cells (endometrial stromal sarcomas) or smooth muscle cells (leiomyosarcomas). In the past, carcinosarcomas, high-grade biphasic tumors of endometrium showing both epithelial and stromal differentiation, were classified with the sarcomas, but based on molecular evidence they are best considered to be endometrial carcinomas with metaplastic (sarcomatous) growth [11].

Endometrial carcinomas arise through two different pathways, and these are referred to as Type 1 and Type 2 carcinomas [12]. The Type 1 carcinomas account for approximately 90 % of cases and are associated with estrogen excess (obesity, infertility, estrogen producing tumors such as granulosa cell tumor, exogenous hormonal therapy) and the precursor lesion is atypical hyperplasia of the endometrium. Most Type 1 tumors are low-grade (grade 1 or 2) endometrioid carcinomas. Type 2 carcinomas arise in an estrogen independent fashion and the patients tend to be older and not obese, the precursor lesion is endometrial intraepithelial carcinoma, and the prototypical Type 2 tumor is serous carcinoma of the endometrium. It is now clear that these Type 1 and Type 2 designations, which were derived based on consideration of epidemiological data, refer to loose clinicopathological clusters and do not correspond to specific histopathological tumor types. As can be seen from Fig. 25.2, some serous carcinomas arise from low-grade endometrioid carcinomas, in patients with increased estrogenic stimulation of the endometrium, as a result of acquired mutations during tumor progression, while some arise de novo, from endometrial intraepithelial carcinoma, in a background of atrophic endometrium [13]. Gross Findings: Endometrial carcinomas present as exophytic masses projecting into the endometrial cavity. When large, they may prolapse through the cervical os. The tumor is typically friable and soft, and there may be extensive necrosis. Myometrial invasion, cervical involvement, serosal implants or extrauterine spread may be seen, and are more common in high-grade endometrial carcinomas. Microscopic Findings: Endometrial carcinomas, like other ovarian carcinomas, are subclassified based on cell type. Endometrioid, serous, and clear cell subtypes, and carcinosarcomas together account for almost all cases of endometrial carcinoma. Endometrioid carcinomas are composed of glandular epithelial cells resembling normal endometrial epithelium, but with significant nuclear atypia and increased mitotic activity. Squamous differentiation and mucinous metaplasia are common. Endometrioid carcinomas are graded based on the percent solid non-squamous growth as grade 1 (<5 % solid), grade 2 (6–50 % solid), or grade 3 (>50 % solid) [14]. Grade 1 and 2 tumors are considered low grade, account for most endometrioid carcinomas, and a majority are stage Ia at presentation. All serous carcinomas, clear cell carcinomas, and carcinosarcomas of the endometrium are considered high-grade [1]. Serous and clear cell carcinomas resemble their counterparts in the ovary, and most commonly show papillary or solid architecture, although glandular architecture is also commonly encountered. The tumor cell nuclei show high-grade features and there is a brisk mitotic rate. Carcinosarcomas have both a high-grade carcinoma and high-grade sarcoma component; the sarcoma can be homologous (i.e. composed of cell types normally found in the uterus, such as smooth muscle or endometrial stromal cells) or heterologous (e.g. malignant cartilage, skeletal muscle, adipose tissue etc.).

Within the category of uterine sarcoma, there are (1) leiomyosarcomas, of smooth muscle origin, (2) endometrial stromal sarcomas, of endometrial stromal cell origin, and (3) high-grade undifferentiated sarcomas, which probably are a mixed group of cases, including poorly differentiated leiomyosarcomas and endometrial stromal sarcomas, in which morphological features of smooth muscle or endometrial stromal cell origin, respectively, have been lost, and poorly differentiated carcinosarcomas in which the carcinomatous component has been overgrown. Leiomyo-sarcomas show complex genetic abnormalities, and once cases of benign mimics of leiomyosarcoma are excluded (e.g. mitotically active leiomyoma, leiomyoma with bizarre nuclei, etc.) are aggressive neoplasms [15]. They consist of fascicles or bundles of spindle cells with markedly atypical nuclei and eosinophilic cytoplasm, that stain positively for markers of smooth muscle differentiation, such as desmin and h-caldesmon. There is no one feature that allows distinction between leiomyomas and leiomyosarcomas, apart from metastasis, and a combination of infiltrative margin, mitotic activity, cytological atypia, and coagulative tumor cell necrosis are used in the diagnosis of leiomyosarcoma [16]. Rare tumors have morphological features intermediate between leiomyoma and leiomyosarcoma, and a designation of “smooth muscle tumor of uncertain malignant potential” (STUMP) can be used for those cases. Endometrial stromal sarcomas, unlike leiomyosarcomas, are characterized genetically by recurrent translocations. In low-grade endometrial stromal sarcomas the chromosomal translocation t7:17, bringing together the JAZF1 and SUZ12 genes, is the most common genetic abnormality in low-grade endometrial stromal sarcoma [17], while high-grade stromal sarcomas are characterized by t10:17 translocations [18]. Endometrial stromal sarcomas are characterized by cells with scant cytoplasm, and prominent small blood vessels, resembling the spiral arterioles of the normal endometrium. Mitotic figures are present, being more common in the high-grade endometrial stromal sarcomas. The high-grade undifferentiated sarcomas consist of pleomorphic cells which often show differentiation along heterologous lineages, such as cartilage or skeletal muscle. Mitotic rates are high, and abnormal mitotic figures common.