Practical issues in the diagnosis of serous carcinoma of the endometrium

Serous carcinoma (SC) represents ~10% of endometrial carcinomas, but is responsible for almost 40% of cancer deaths. This article reviews the main pathological features, differential diagnosis, and the usefulness of molecular pathology and immunohistochemistry in its diagnosis. Most helpful features for the diagnosis include: irregularly shaped and sized papillae, slit-like spaces, cell stratification and budding, highly atypical cells, architectural and cytological discordance in pseudoglandular tumors, as well as lack of endometrioid features. SC shows typically a predominant papillary growth, which is also found in some subtypes of endometrioid carcinoma of the endometrium (EEC). Distinction is easy when attention is paid to the presence of diffuse marked nuclear pleomorphism, but also to the complex papillary architecture. SC may also show a solid or pseudoglandular patterns, and in these cases differential diagnosis may be difficult with EEC grade 3. Moreover, a high proportion of SC may exhibit clear cells, and, thus, may be confused with clear cell carcinoma. Finally, it is sometimes difficult to distinguish mixed SC-EEC, from SC that combines papillary and pseudoglandular growths. Although there is not a single immunohistochemical marker for distinguishing SC from its mimickers, some antibodies are useful (p53, p16, IMP2, and IMP3), particularly when used in combination. Diagnosis of SC may be even more problematic in small biopsies; a diagnosis of high-grade endometrial carcinoma, SC component can not be excluded, is acceptable as a managerial approach, so it could be taken into account at the time of final surgery.