Original ArticlesMismatch Repair Deficiency in Uterine Carcinosarcoma A Multi-institution Retrospective ReviewJenkins, Taylor M. MD*; Hanley, Krisztina Z. MD†; Schwartz, Lauren E. MD‡; Cantrell, Leigh A. MD§; Stoler, Mark H. MD*; Mills, Anne M. MD*Author Information Departments of *Pathology §Obstetrics and Gynecology, University of Virginia Health System, Charlottesville, VA †Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA ‡Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 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: Anne M. Mills, MD, Department of Pathology, University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22903 (e-mail: [email protected]). The American Journal of Surgical Pathology: June 2020 - Volume 44 - Issue 6 - p 782-792 doi: 10.1097/PAS.0000000000001434 Buy Metrics Abstract Immunohistochemistry (IHC) for mismatch repair (MMR) proteins is recommended in endometrial carcinomas as a screening test for Lynch syndrome, and mismatch repair deficiency (MMRd) is reported in ∼30% of cases. However, few studies have evaluated the rate of MMR loss in uterine carcinosarcomas. A 5-year retrospective database search of uterine carcinosarcomas was performed at 3 academic institutions. The histologic diagnoses, type of carcinoma present, and MMR IHC interpretations were confirmed by a gynecologic pathologist. One hundred three cases of uterine carcinosarcomas with available MMR IHC results were identified. Ninety-nine cases (96%) showed intact expression and 4 cases (4%) showed loss of MLH1/PMS2. All MMRd carcinosarcomas identified in this series had an endometrioid carcinomatous component and wild-type p53 expression. In contrast, the majority of MMR intact carcinosarcomas had a serous morphology and aberrant p53 expression. Three additional cases initially diagnosed as carcinosarcoma also revealed MMRd; however, given the lack of clear mesenchymal differentiation, these cases were reclassified as dedifferentiated endometrial carcinomas and were subsequently excluded from the carcinosarcoma category. No cases of Lynch syndrome were identified among carcinosarcoma patients, as all 4 MMRd cases were due to somatic MLH1 hypermethylation. In summary, we found that the rate of MMRd is markedly lower in uterine carcinosarcoma when compared with endometrial carcinoma. In the setting of MMR loss, a diagnosis of dedifferentiated carcinoma should be considered as almost half of the MMRd tumors which were called carcinosarcomas initially were reclassified as dedifferentiated on review. However, given the interobserver variability in the classification of carcinosarcoma versus dedifferentiated carcinoma a universal screening approach that includes uterine carcinosarcoma is still recommended. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.