Stromal p16 Expression Helps Distinguish Atypical Polypoid Adenomyoma From Myoinvasive Endometrioid Carcinoma of the Uterus

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.

Atypical polypoid adenomyoma of the endometrium: diagnosis and treatment. A case report

“…In previous studies, some molecular alterations were described in APA cases such as mutations in K-RAS and CTNNB1, deletions of PTEN and MLH-1 promoter methylation. However, these alterations do not distinguish APA from endometrial carcinoma because they can be found in both lesions 3 , 4 .…”

“…Unfortunately, the absence of CD10 “fringe-like staining pattern” does not exclude myoinvasive carcinoma; therefore further markers are needed 4 .…”

“…The p16 protein can be variously expressed in different gynecological lesions. It is usually absent in endometrial carcinoma, while it is usually present in the stromal component of APA 4 . Moreover, typical and constant immunohistochemical findings of APA are the intense nuclear beta-catenin positivity of morules and their negativity for estrogen and progesterone receptors.…”

Lesion‐targeted cytology to improve cytological sampling for atypical polypoid adenomyomas of the uterus: A case series and review of the literature

“…Histologically, the differential diagnoses of APAs and endometrioid carcinomas with muscular invasion are often problematic 8,10,11,15 . Recently, Kihara et al reported that stromal p16 expression is more suggestive of APAs than of myoinvasive endometrioid carcinomas 27 …”

Patterns of SATB2 and p16 reactivity aid in the distinction of atypical polypoid adenomyoma from myoinvasive endometrioid carcinoma and benign adenomyomatous polyp on endometrial sampling

“…Kihara et al . demonstrated increased stromal p16 reactivity in APAM as compared with myoinvasive endometrioid carcinoma 11 . The immunohistochemical features of each component of APAM have recently been documented in a review article by Travaglino et al 12 …”