High-grade endometrial carcinomas - strategies for typing

High-grade endometrial carcinomas are subject to low rates of interobserver diagnostic agreement; this may be a result of the existence of morphologically ambiguous carcinomas, many of which are microsatellite instability-high. High-grade endometrial carcinomas with prototypic morphology have characteristic genotypes and immunohistochemical profiles. Assays accounting for these features may be applied to morphologically ambiguous carcinomas in the hope that the results will provide some clarity about a tumour's origin and expected clinical outcome, and even whether tumour progression has occurred. It is important to be able to demonstrate that morphologically based diagnoses are strongly linked not only to clinical outcomes, but also to genetic signatures and expression profiles. There are still numerous persistent problems in tumour classification that will require a critical evaluation of the type and strength of evidence needed to refine diagnostic algorithms.