Original ArticlesCorded and Hyalinized and Spindled Endometrioid Endometrial Carcinoma A Clinicopathologic and Molecular Analysis of 9 Tumors Based on the TCGA ClassifierSafdar, Nida S. MD*; Thompson, Emily F. MBChB†; Gilks, C. Blake MD†; Isacson, Christina MD‡; Bennett, Jennifer A. MD§; Clarke, Blaise MD∥; Young, Robert H. MD*; Oliva, Esther MD* Author Information *James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA †University of British Columbia, Vancouver, BC ∥University Health Network, University of Toronto, Toronto, ON, Canada ‡CellNetix Pathology and Laboratories, Seattle, WA §University of Chicago, Chicago, IL Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Nida S. Safdar, MD, James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Warren Building, 2nd Floor, Boston, MA 02114 (e-mail: [email protected]). The American Journal of Surgical Pathology: August 2021 - Volume 45 - Issue 8 - p 1038-1046 doi: 10.1097/PAS.0000000000001737 Buy Metrics Abstract Corded and hyalinized and spindled carcinomas are rare variants of endometrioid carcinoma (EC) characterized by cords of low-grade epithelial cells (±spindle cells) within a hyalinized stroma or spindled epithelial cells, respectively, that merge with conventional low-grade EC. Due to their “biphasic” morphology, these tumors are often misdiagnosed as carcinosarcoma. The clinicopathologic features including mismatch repair protein (PMS2 and MSH6) and p53 immunohistochemical expression and POLE mutational status of 9 corded and hyalinized and spindled endometrial ECs were evaluated and classified into The Cancer Genome Atlas (TCGA) based molecular subgroups. Beta-catenin immunohistochemistry was performed as a surrogate for CTNNB1 mutational status. The mean age at diagnosis was 49 years (range: 34 to 68 y) with staging information available for 6 patients: stage IA (n=1), stage IB (n=1), stage II (n=2), stage IIIA (n=1), stage IIIC1 (n=1). A prominent corded and hyalinized component was present in 7 ECs comprising 15% to 80% of the tumor with a minor (5% to 15%) spindled morphology in 5. Two additional tumors were composed of a low-grade spindled component comprising 25% to 30% of the neoplasm. Tumors were grade 1 (n=3), grade 2 (n=5), and grade 2 to 3 (n=1) and squamous differentiation was identified in 8/9. All tumors had preserved expression of mismatch repair proteins with 8 showing a p53 wild-type phenotype including the grade 2 to 3 EC; 1 grade 2, stage IB tumor exhibited a mutant pattern of expression. All (n=7) but 1 tumor demonstrated nuclear beta-catenin expression in the glandular, squamous, and corded or spindled components. POLE exonuclease domain mutations were absent in all tumors. Based on our findings, corded and hyalinized EC and EC with spindle cells are usually low grade, low stage, and present at a younger age and exhibit squamous differentiation at an increased frequency compared to typical EC. Unlike carcinosarcomas, which frequently harbor TP53 mutations, these tumors usually exhibit wild-type p53 and nuclear beta-catenin expression, indicative of underlying CTNNB1 mutations. According to the TCGA subgroups of endometrial carcinoma, the majority of corded and hyalinized and spindled EC appear to fall into the copy number low (“no specific molecular profile”) subgroup. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.