Undifferentiated Carcinoma of the Endometrium: Morphology, Immunophenotype, and Differential Diagnoses to Avoid...

More than 20 years have passed since the distinct definition of undifferentiated endometrial carcinoma (UEC) was proposed in 2005. Based on its distinguishing clinicopathological features, the fourth and fifth editions of the World Health Organization classification of gynecological tumors recognized UEC as a distinct subtype of endometrial carcinoma. An accurate diagnosis of UEC is crucial due to its aggressive clinical behavior and for ensuring appropriate patient management. Many investigators have elucidated clinicopathological and molecular characteristics that are useful for its diagnosis; however, a number of differential diagnoses need to be considered before the final pathological diagnosis. This review summarizes the pathological characteristics of UEC, with a focus on its histological, molecular, and immunophenotypic features, as well as key points for a differential diagnosis. UEC shows diverse immunophenotypes. In addition to the loss of or a marked reduction in epithelial and gynecological markers, UEC frequently expresses ZEB1 and cyclin D1, and occasionally expresses neuroendocrine and germ cell tumor markers. Approximately 60% of UECs show the loss of SMARCA4, SMARCB1, or ARID1A/1B, which may contribute to tumor pathogenesis. These immunophenotypes are not specific because other epithelial and non-epithelial uterine tumors may exhibit overlapping features. Therefore, a comprehensive pathological understanding of UEC is essential for avoiding diagnostic pitfalls and improving diagnostic accuracy.