Significantly Decreased Progesterone Receptor Expression in Corded and Hyalinized Variant of Endometrioid Adenocarcinoma: A Potential Cause of Resistance to Progestin Treatment

INTRODUCTION: The corded and hyalinized variant of endometrioid adenocarcinoma (CHEC) is a biphasic tumor composed of cords of epithelioid and/or spindle cells (CoES) within hyalinized or chondroid stroma, which is often misdiagnosed as carcinosarcoma. CHEC predominantly occurs in younger women, and it has a favorable clinical outcome. Thus, many patients wish to preserve their fertility and undergo conservative treatment. This study investigated a selective loss of progesterone receptor (PR) in the CoES component and reported clinical, histopathological, and immunohistochemical features of CHEC. METHODS: A total 6 patients with CHEC between 2004 and 2021 were searched. We performed immunohistochemistry for estrogen receptor (ER), PR, β-catenin, E-cadherin, cytokeratin, p53, and Ki-67. RESULTS: The patients were 21-40 years old. All of the tumors were FIGO grade 1 endometrioid adenocarcinoma (EAC) intermingled with CoES component. Notably, PR expression was completely lost in the CoES component in contrast to the EAC component, with a significantly different expression pattern of cytokeratin, ER, β-catenin, and E-cadherin from the areas of typical EAC. Four of the 6 patients initially received exogenous progestin treatment, and two of them ultimately had a hysterectomy after progestin treatment. All 4 patients treated with progestin had persistent tumors at the last follow-up curettage or hysterectomy. CONCLUSION: Considering the usual high rate of complete remission with progestin treatment in patients with EAC, the high rate of persistent tumors in our case series suggests that CHEC may be intrinsically resistant to progestin treatment due to the lack of expression of PR in the CoES component.