Endometrial endometrioid adenocarcinoma: Histology, precursors and molecular alterations

Endometrioid adenocarcinoma is the most common endometrial cancer. It is highly associated with excess estrogen, whether endogenous or exogenous, and tends to be more common in post-menopausal women. Hyperplasia, with and without atypia, is considered a non-obligate precursor. In this review, we summarize the histologic features of endometrial hyperplasia and progestin therapy and review different classification systems for endometrioid adenocarcinoma precursors, including endometrial intraepithelial neoplasia. The histology, variants, and staging of endometrioid adenocarcinoma are also reviewed, with an emphasis on problematic areas in diagnosis, including assessment of myometrial and cervical stromal invasion, atypical hyperplasia versus adenocarcinoma, endometrial versus cervical primary, and endometrial versus ovarian primary versus synchronous primaries, and the application of immunohistochemical stains in diagnosis. In addition, pitfalls in diagnosis are discussed, such as endometrioid versus serous carcinoma and lymph node metastasis versus benign glandular inclusions. Lastly, molecular changes in endometrioid adenocarcinoma are explored.