Intestinal type mucinous adenocarcinoma of the endometrium with signet ring cells (179)

Abstract

<b>Objectives:</b> Endometrial cancer is the most common gynecological malignancy in the United States. In the 66,000 new cases reported annually, only 1-9% are reported to be mucinous adenocarcinomas of the endometrium (MACE). Intestinal type mucinous adenocarcinoma (iMACE) is a rare variant of mucinous carcinoma of the endometrium that may show focal features of very poorly differentiated adenocarcinomas of gastric, pancreatic, or intestinal origin by producing signet ring cells (SRC). To date, only two reported cases of SRC as a morphological feature of iMACE have been reported. The presence of SRC morphology in carcinomas of non-endometrial primary sites has been found to portend a worse prognosis. Alterations in E-cadherin expression have been linked to decreased cell-to-cell adhesion, increased metastatic potential, tumor de-differentiation, and deep myometrial invasion in endometrial carcinomas. The presence or absence of E-cadherin in iMACE with SRC has not been studied. Thus, we sought to analyze E-cadherin expression in this aggressive variant of endometrial carcinoma. <b>Methods:</b> After informed consent was obtained, we analyzed three cases of iMACE with SRC. Demographics and clinical outcomes were obtained for the three cases from the chart review. Immunohistochemical staining was performed for E-cadherin, CX20, CDX2, CK7, PAX-8, and ER expression on formalin-fixed paraffin-embedded tumor tissue. <b>Results:</b> Diagnosis of iMACE with SRC was rendered with the aid of immunohistochemical staining (Table 1) and histological analysis. The average age of diagnosis was 72 years, with all three women presenting with the complaint of post-menopausal bleeding. All three cases presented with late-stage disease, and two patients died of disease, with the third disease-free at three years post-therapy. Focal loss or weakly positive E-cadherin expression was seen in areas of SRC morphology in all three cases. No changes in E-cadherin expression were seen within the rest of the tumor (Table 1). <b>Conclusions:</b> A potential mechanism of action for the aggressive nature of iMACE with SRC morphology is the focal downregulation of E-cadherin expression. However, additional data is needed to corroborate these findings. Our data add to the current literature that supports the concept of divergent molecular profiles, including cell adhesion molecule expression, in different types of endometrial carcinoma.