Endometrial Endometrioid Carcinomas With Signet Ring Cells: Report of a Case Series With Detailed Clinical,...

Signet ring cells are extremely rare in primary endometrial carcinomas with a limited number of reported cases. We report a series of 5 endometrioid-type endometrial carcinomas with signet ring cells, the largest reported series in the literature to date. The patients ranged in age from 53 to 89 yr (mean: 72), and all presented with postmenopausal bleeding. Four of the tumors were FIGO grade 3, and 1 FIGO grade 2, and the FIGO stages were IA, IB, IIIA, IIIB, and IIIC1. The percentage of signet ring cells ranged from 10% to 30% of the tumor, and the signet ring cells were confined to solid areas of the neoplasm. All tumors were positive with estrogen receptor (ER) (4 diffuse, 1 focal); p53 immunohistochemistry was wild-type in 4 and diffuse mutation-type in 1. Three neoplasms were mismatch repair (MMR) deficient (loss of MLH1/PMS2) on immunohistochemistry. Molecular testing revealed a POLE pathogenic variant with an associated ultramutated phenotype in one of the MMR-proficient tumors and a TP53 mutation in the tumor exhibiting mutation-type p53 staining (this was also MMR proficient on immunohistochemistry). Using The Cancer Genome Atlas (TCGA) molecular classification, tumors were POLE mutated (n=1), MMR deficient (n=3), and p53 abnormal (n=1). On follow-up, 4 patients were alive with no evidence of disease (4-24 mo follow-up), and 1 patient died 7 mo after diagnosis from an unrelated cause. In reporting these neoplasms, we highlight that signet ring cells occasionally occur in primary endometrial carcinomas of endometrioid-type and, although numbers are small, there appears to be an association with MMR deficiency. These tumors have a propensity for high-stage at presentation.