Primary Endometrial Carcinoma with Signet Ring Cells: A Rare and Unusual Entity

Abstract

Abstract Introduction/Objective The presence of signet ring cells in an endometrial tumor is suggestive of metastasis, as primary tumors with this morphology are extremely rare. As a result, primary tumors are a diagnosis of exclusion, defined by the presence of signet-ring cells usually associated with mucinous endometrioid carcinoma without clinical or radiographic evidence of metastases from breast, stomach, or colon. Methods/Case Report A 64-year-old woman presented with vaginal bleeding. Ultrasound showed a large, heterogenous uterine mass that was diagnosed as poorly differentiated carcinoma on biopsy. Serum CEA was elevated, and CA-125 was normal. Hysterectomy with salpingo-oophorectomy showed a minor endometrial component of grade 3 endometrioid carcinoma and a predominant component of poorly differentiated carcinoma with signet ring cells. The myoinvasive component consisted of the signet ring cells with pools of acellular mucin. Extensive lymphovascular invasion was noted. Cervix, adnexa, and lymph nodes were free of disease. The signet ring cells were positive for CK7, CK20, and CDX2, and negative for ER and Pax-8. The endometrioid component was positive for ER, Pax-8, and CK7, and negative for CK20 and CDX2. E-cadherin staining was lost in the myoinvasive component of the tumor. Loss of MLH1 and PMS2 nuclear expression was seen, and MLH1 promoter methylation was detected in both components of the tumor. Subsequent colonoscopy and imaging did not reveal any other disease sites. Based on histology, pattern of uterine involvement, and lack of extrauterine disease, a diagnosis of primary poorly-differentiated endometrial adenocarcinoma with signet ring cell features was made. The patient was treated with adjuvant chemotherapy and is currently being followed. Results (if a Case Study enter NA) NA Conclusion We present a rare case of primary signet ring carcinoma of the uterus, a challenging diagnosis made after extensive work-up to rule out metastases. Of the previous 9 reported cases, only one was similar to our tumor with distinct endometrioid and signet ring components. Although these primary endometrial tumors are unified by the presence of signet ring cells, there is considerable immunohistochemical heterogeneity. Some reports suggest the signet ring cells have a Mullerian phenotype, while others, including our case, suggest a gastrointestinal phenotype. In presenting this case, we hope to contribute to this entity’s characterization and bring further awareness that the presence of signet ring cells does not exclude a uterine primary.