Corded and Hyalinized Endometrioid Adenocarcinoma (CHEC) of the Uterine Corpus are Characterized by CTNNB1 Mutations and Can Show Adverse Clinical Outcomes

Abstract

Corded and hyalinized endometrioid adenocarcinoma (CHEC) is a morphologic variant of endometrioid adenocarcinoma that is typically low-grade [International Federation of Gynecology and Obstetrics (FIGO) grade 1-2]. CHEC exhibits a biphasic appearance with gland forming adenocarcinoma merging with a diffuse component with corded growth often in a hyalinized matrix; squamous differentiation is frequent and osteoid production can be seen. This morphologic appearance can invoke a large differential diagnosis including carcinosarcoma. CHEC is thought to be associated with good clinical outcome although the available data is sparse. We performed detailed clinical, morphologic, immunohistochemical, and molecular analyses on a cohort of 7 CHEC. Six cases exhibited features of classic low-grade CHEC while one case showed greater cytologic atypia (high-grade CHEC). Patient age ranged from 19 to 69 yr. Four patients presented at stage I, 2 at stage II, and 1 at stage III. All tumors demonstrated nuclear staining for beta-catenin and loss of E-cadherin in the corded and hyalinized component. There was relative loss of epithelial markers. Loss of PTEN and ARID1A was seen in 4 and 3 tumors, respectively, and 1 tumor displayed loss of MLH1 and PMS2. Next-generation sequencing revealed CTNNB1 and PI3K pathway mutations in all 7 cases with TP53 and RB1 alterations in the high-grade CHEC. Clinical follow-up was available for 6 patients; 2 died of disease (48 and 50 mo), 2 are alive with disease (both recurred at 13 mo), and 2 have no evidence of disease (13 and 77 mo). Our study shows that CHEC universally harbors CTNNB1 mutations with nuclear staining for beta-catenin, can rarely show high-grade cytology, and can be associated with adverse clinical outcomes.