Endometrial cancer is undoubtedly the most prevalent gynecologic cancer in the United States of America. Yet metastasis to the brain is uncommon and the diagnosis can be quite onerous. Immunohistochemistry, pan-imaging, and histopathologic studies were some of the long-established tools used to determine whether a tumor happens to be a primary or metastatic lesion. In order to increase these tests, molecular testing with next-generation sequencing (NGS) or high-throughput sequencing has been progressively used. The researchers put forward the case of a patient with a brain lesion who was at first diagnosed with glioblastoma on immunohistochemistry and histology. The diagnosis, however, was later altered to metastasis from an endometrial primary on the basis of molecular findings. About 51 DNA variants, containing oncogenic driver mutations PTEN p.I135V, PIK3CA p.E545A, p.K267Rfs*9, and KRAS p.G13D as well as a mutual microsatellite instability signature was shared by the two tumors. This calls attention to the power of molecular investigation in making the diagnosis in the cases of rare metastases.

As such, the study brings two vital points into the limelight. Firstly, brain metastasis is uncommon from the endometrial primary, and histopathological aspects might be increased with the molecular investigation to support the diagnosis in such cases. Secondly, the comparison of the metastatic lesion with the molecular arrangement of the primary endometrial lesion may uncover high-risk molecular features that may be demonstrative of metastatic potential.