Endometrial carcinomas with ambiguous features

Endometrial carcinomas are a heterogenous group of tumors that show variable histologies, molecular abnormalities and clinical outcomes. The idea of rigid distinctions between tumor types is appealing to pathologists, gynecologists, researchers and patients, but in a recent study where high grade endometrial carcinomas were reviewed by three experienced gynecologic pathologists, diagnostic agreement about tumor type was reached in only approximately one half of cases. In general, biologically and clinically validated diagnostic criteria are lacking for high grade endometrial carcinomas and for those that appear mixed epithelial. Until such criteria are developed, it remains important to define which morphologic patterns convey accurate clinical and biological information and which do not or might not. "Endometrial carcinomas with ambiguous features," the focus of this review, are tumors with comparatively uninformative morphologic features. Some publications indicate that gland forming and papillary endometrial carcinomas that appear morphologically low grade or ambiguous are really high grade. There are also indications that high grade endometrial carcinomas are biologically heterogeneous and that the morphologic clues we currently use to distinguish one subtype from another fail to correlate with biological data. Many tumors that appear morphologically mixed are, in fact, not biologically or clinically confused: most represent biologically "pure" tumors with variant morphology. Interesting associations between the presence of Lynch Syndrome (hereditary nonpolyposis colorectal carcinoma syndrome) and ambiguous morphology have been discussed in the literature. An apparent relationship between morphologic ambiguity and malignant mixed Müllerian tumor (MMMT) also exists. The identity of some morphologically ambiguous endometrial carcinoma can be elucidated with immunohistochemistry or other ancillary techniques at present, but the nature of many still remains undefined. This review presents the concept of morphologically ambiguous endometrial carcinomas, proposes morphological gold standard diagnostic criteria for tumors that are not ambiguous (an effort that helps define tumors that are ambiguous), provides a relevant literature review and offers practical guidance for sorting through diagnostically challenging cases.