Original ArticlesStromal p16 Expression Helps Distinguish Atypical Polypoid Adenomyoma From Myoinvasive Endometrioid Carcinoma of the UterusKihara, Atsushi MD*; Amano, Yusuke DDS, PhD*; Yoshimoto, Taichiro MD, PhD*; Matsubara, Daisuke MD, PhD*; Fukushima, Noriyoshi MD, PhD*; Fujiwara, Hiroyuki MD, PhD†; Niki, Toshiro MD, PhD* Author Information Departments of *Pathology †Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan All the authors contributed considerably to this manuscript. A.K.: conceived and designed the study. A.K. and T.N.: performed experiments and analyzed data. A.K., Y.A., T.Y., and D.M.: performed pathological and statistical analyses. H.F.: provided clinical information. A.K. and T.N.: wrote the manuscript with contributions from all the other authors. T.N. and N.F.: supervised all the procedures of this study. All authors approved the submitted manuscript. 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: Atsushi Kihara, MD, Department of Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke city, Tochigi 329-0498, Japan (e-mail: [email protected]). The American Journal of Surgical Pathology 43(11):p 1526-1535, November 2019. | DOI: 10.1097/PAS.0000000000001320 Buy SDC Metrics Abstract Atypical polypoid adenomyoma (APA) is a polypoid lesion that is comprised of atypical endometrial glands and fibromuscular stroma, which pathologists often confuse with myoinvasive endometrioid carcinoma. Here, we characterized the immunohistochemical and molecular features of the stromal components of APA to find distinct markers between APA and myoinvasive endometrioid carcinoma. First, we examined the immunohistochemical expression and gene mutations that were previously investigated in uterine and breast fibroepithelial lesions using 12 cases of APA. α-smooth muscle actin was diffusely positive in the stromal component in all cases, whereas desmin and h-caldesmon were focally expressed in 8 cases. Positive expression was also observed in 9 cases for CD10, 12 cases for estrogen receptor, 3 cases for HMGA2, and 3 cases for MDM2. All cases showed normal p53 expression and negative staining of HMGA1 and nuclear β-catenin. No mutations in MED12 exon 2 and the TERT promoter were found in any cases. p16 was positive in all cases and showed diffuse expression in 10 cases. We assessed stromal p16 expression in 84 cases of myoinvasive endometrioid carcinoma. The stromal p16 status was negative in all myoinvasive carcinomas, but there was 1 case with focal staining. There was a significant difference in stromal p16 expression between APA and myoinvasive endometrioid carcinoma (P<0.001). Stromal p16 expression was more suggestive of APA than myoinvasive endometrioid carcinoma among endometrial fibroepithelial lesions. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.