When you feel life at crossroads, you need higher perspective view.

—Toba Beta in My Ancestor Was an Ancient Astronaut

After the publication of the integrated genomic characterization of endometrial carcinoma by The Cancer Genome Atlas project in 2013, the subclassification of endometrial carcinoma has gained much more attention than previously. Like in many other areas in our profession, we are at a crossroad where molecular information is changing diagnostic practice. In this issue of AJSP: Reviews & Reports, Drs Bosse and Köbel share their thoughts in 2 separate articles on how they envision the future with the added complexity of molecular information on top of standard anatomical pathology. Both agree on the value of molecular information and certain basic principles (eg, the defining nature of key oncogenic alterations such as POLE mutations or mismatch repair deficiency). However, they have different views of how to integrate molecular subtype information with standard histomorphology: with one approach being more integrated versus more stand-alone. Although standard histomorphology and molecular subtype strongly correlate, sometimes they contradict each other. At this point, someone, either the pathologist or the oncologist, has to adjudicate. This decision is not generalizable and is dependent on the context of the specific histomorphology and the specific molecular result, and who would be better posed to make that decision than a pathologist? Designation of an endometrial carcinoma to a specific category increasingly conveys prognostic, predictive, and germline information; accurate and reproducible diagnosis is mandatory. Integration of the traditional and molecular parameters is critical to ensure a relevant taxonomy of endometrial pathology with the ultimate goal of improving the outcomes in women's health.

Drs Chapel and Park next provide a comprehensive contemporary review on mesonephric-like adenocarcinomas. Although various explanations of the etiology of this tumor type have been discussed, the authors state that endometrial mesonephric-like adenocarcinomas likely arise through mesonephric-type transdifferentiation from endometrioid carcinomas. They describe the morphological, immunohistochemical, and molecular features of this tumor type and give recommendations for the diagnostic approach. They provide cogent clinical reasons to warrant distinguishing this tumor type from endometrioid carcinomas.

The entity of undifferentiated endometrial carcinoma and its related dedifferentiated carcinoma has gained substantial interest over the last years. Drs Y.-S. Lee and C.-H. Lee take us a step further by emphasizing the importance of key molecular alterations in the SWI/SNF (SWItch/sucrose non-fermentable) pathway as a defining feature for cases that are associated with a devastating clinical outcome. Again, ancillary molecular testing enables a more homogeneous diagnosis, which clarifies the poor response to standard therapy and calls for more research in experimental models to find new ways to treat patients with this molecularly defined entity.

The synchronous involvement of the endometrium and ovary/fallopian tube by carcinoma is a regular diagnostic challenge. Drs Singh et al provide a new perspective by separately discussing this issue for serous and endometrioid histotypes. Although questions remain, systematically the authors list criteria and provide reporting strategies for different scenarios based on current understanding. Perhaps, the integration of molecular subtypes particularly for endometrioid histotypes can further aid in risk stratification of these patients.

We are increasingly receiving requests from obstetrician-gynecologist for CD138 immunohistochemistry in the context of infertility. Dr S. Lee reviews the current data: although there is some indication that diagnosis and successful treatment of chronic endometritis may positively affect pregnancy outcome, a single randomized clinical trial did not confirm this. Yet, another trial is ongoing, which uses ≥5 CD138+ plasma cells per 10 mm2 as cutoff for chronic endometritis. But the results are pending. Until then, there is no indication for routine use of CD138 or other immunohistochemistry to detect plasma cells in the context of infertility and certainly not in others.