Uterine Cancer: Pathology

Endometrioid adenocarcinoma is the most common type of endometrial carcinoma (approximately 85 %). By definition, it should resemble, at least focally, proliferative-type endometrium with tubular glands lined by mitotically active columnar cells. Common problems in diagnosis involve its distinction from complex atypical hyperplasia, endocervical adenocarcinoma, serous carcinoma, clear cell carcinoma, and carcinosarcoma. Pure serous carcinomas comprise about 10 % of endometrial cancers. The term “serous” refers to shared characteristics with cells lining the fallopian tube, particularly the tumor cells’ columnar shape, eosinophilic cytoplasm, and tendency to form papillae. However, some serous carcinomas are not papillary but glandular. Importantly, all serous carcinomas exhibit marked nuclear pleomorphism and most demonstrate discrepancies between architectural differentiation and cytologic features. Clear cell carcinoma is the third most common endometrial carcinoma subtype, even though it represents <5 % of all endometrial cancers. Epidemiologic characteristics of patients with clear cell carcinoma are obscure because of this tumor’s rarity, difficulties in diagnostic reproducibility, and accumulating evidence that there are perhaps several subtypes of clear cell carcinoma. Most clear cell carcinomas are composed of cells with clear cytoplasm, but this feature is not restricted to clear cell carcinoma and some clear cell carcinomas contain cells with eosinophilic cytoplasm. Other subtypes of endometrial carcinoma are rare and include squamous, transitional, small cell, undifferentiated/dedifferentiated, and mixed cell types. Among pure mesenchymal tumors of the uterus, leiomyosarcoma is the most common. Microscopic criteria to establish the diagnosis of leiomyosarcoma include the combination of two of the following: cytologic atypia, mitotic activity, and tumor cell necrosis. The threshold for mitotic activity varies for spindled, epithelioid, and myxoid subtypes and a variety of uterine tumors enter in the differential diagnosis, including several variants of leiomyoma (mitotically active, apoplectic, with bizarre nuclei, highly cellular, and hydropic). Low-grade endometrial stromal sarcomas are composed of a homogenous population of small cells with scant cytoplasm resembling proliferative-type endometrial stroma. They show a diffuse growth and infiltrate the uterine wall in a permeative (not destructive) fashion and may have prominent intravascular growth. High-grade endometrial stromal sarcomas do not resemble proliferative stroma, are composed of small rounds cells with brisk mitotic activity and are more aggressive than low-grade tumors. Undifferentiated uterine sarcoma is a very poorly differentiated sarcoma and a diagnosis of exclusion. Carcinosarcomas (malignant mixed mullerian tumors) are biphasic tumors typically composed of highly malignant epithelial and stromal/mesenchymal elements. The histogenesis of these tumors has evolved in recent years and it is now accepted that they either arise from a common pluripotential cell with divergent differentiation or that the sarcomatous component develops from the carcinomatous component by a metaplastic process. Other rare low-grade or clinically aggressive mesenchymal tumors include: (1) low-grade mullerian adenosarcoma (composed of benign-appearing glands and malignant stroma); (2) PEComa, which is composed of epithelioid cells that are typically positive for HMB-45 and may be associated with tuberous sclerosis; and (3) intravenous leiomyomatosis which shows a proliferation of smooth muscle cells within vascular spaces. Even though the latter smooth muscle proliferation is considered benign it can behave aggressively from the clinical point of view.