Comprehensive Genomic Profiling for Therapeutic Decision and Identification of Gene Mutation in Uterine Endometrial Dedifferentiated Carcinoma.

Endometrial dedifferentiated carcinoma is a new concept among endometrial malignancies, is rare, and has a poor prognosis as it is discovered in advanced stages and has no established treatment. It has higher rates of gene mutations, such as mismatch repair, than general endometrial cancer and has been associated with Lynch syndrome. However, due to its heterogeneity, case-by-case searches are needed. Comprehensive genomic profiling by Foundation One® CDx can comprehensively identify over 300 gene mutations via a next-generation sequencer and can evaluate biomarkers, such as the microsatellite status and tumor mutation burden. Therefore, it may be beneficial in identifying therapeutic targets and drugs for diseases whose treatment has not been established. In this case, 13 therapies, including immune checkpoint inhibitor therapy for microsatellite instability-High and 40 clinical trials for several gene mutations might be beneficial. We report a case of endometrial dedifferentiated carcinoma for which Foundation One® CDx gene profiling was used to propose treatment.

A novel case of endometrial dedifferentiated adenocarcinoma associated with MLH1 promotor hypermethylation and microsatellite instability.

Endometrial dedifferentiated carcinoma is a rare, malignant tumor whose molecular alterations have not been clarified yet. We report a novel case of a 61-year old woman who presented with irregular vaginal bleeding after menopause and a 3 cm uterus mass. Histology revealed endometrial dedifferentiated adenocarcinoma, a rare subtype comprised of undifferentiated adenocarcinoma. The patient still survived 1 year after surgery without chemotherapy and radiotherapy. Immunohistochemistry revealed loss of MLH1/PMS2 expression and retained MSH2/MSH6 expression. Consistently, microsatellite instability was detected indicative of high microsatellite instability (MSI-H). No BRAF V600E, KRAS and POLE mutations were identified. Remarkably, the promoter regions of mutL homolog 1(MLH1) were methylated. Furthermore, several tumor cells were PD-L1 positive in this case with a concentration at the infiltrating tumor edge indicating MSI-H in endometrial dedifferentiated adenocarcinoma is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1.

Dedifferentiated carcinoma with clear cell carcinoma of the endometrium: A case report.

Endometrial dedifferentiated carcinoma consists of a combination of undifferentiated and differentiated carcinomas. To date, clear cell carcinoma components in endometrial dedifferentiated carcinoma have not been reported. We report the first case of endometrial dedifferentiated carcinoma with clear cell carcinoma in a 58-year-old woman. The uterine corpus was completely replaced and enlarged by a heterogeneous mass. The endometrial cut surface showed a yellowish papillary growing mass involving endometrium and deeper myometrium. Microscopically, the three components (endometrioid carcinoma, FIGO grade 1, clear cell carcinoma and undifferentiated carcinoma) were noted with differentiated carcinoma components lining the endometrial cavity, while undifferentiated carcinoma components were identified in deeper endometrium and myometrium. Our histologic diagnosis was supported by the pattern of immunoreactivity. Tumor cells showed loss of expression of MLH1/PMS2 protein and displayed high microsatellite-instability in all three components. Furthermore, all three components including clear cell carcinoma had loss of PTEN and ARID1A expression. Our observations suggest that the three components derived from a monoclonal origin, as the three components had in common specific genetic alterations.