Atypical Polypoid Adenomyoma of the Uterus

Abstract

Atypical polypoid adenomyoma (APA) is an uncommon uterine lesion that commonly recurs after local excision and is occasionally associated with or precedes the development of atypical hyperplasia or endometrioid adenocarcinoma. Despite the fact that about 230 cases have been reported in the literature, only 2 studies of 6 and of 7 cases have investigated the molecular aspects; as such, molecular alterations that occur in APA remain largely unknown. We undertook a comprehensive immunohistochemical and molecular analysis of 21 cases of APA in 17 patients (including 4 recurrent/persistent lesions). The analyzed genes were PTEN and TP53 (by fluorescence in situ hybridization) and KRAS, BRAF, EGFR, and NRAS (all by polymerase chain reaction). Immunohistochemical staining was performed for PTEN, p53, mTOR, β-catenin, HNF-1β, and GLUT1 and for the mismatch-repair proteins MLH-1, MSH-2, MSH-6, and PMS-2. In most cases, there was nuclear expression of β-catenin in squamous morules and expression of HNF-1β, mTOR, and GLUT1 in the glandular component. All cases exhibited "wild-type" expression of p53. A common finding was loss of PTEN expression (6/19 cases). In 1 of these cases, loss of PTEN expression was accompanied by PTEN deletion. Mutation of the KRAS gene was found in 5/19 cases. Intact mismatch-repair protein expression was present in all cases, and TP53 abnormalities or mutations of EGFR, NRAS, or BRAF genes were not found. Given the association with atypical hyperplasia and endometrioid adenocarcinoma and the shared immunohistochemical and molecular features, we feel that, conceptually, APA is best regarded as analogous to a localized form of atypical hyperplasia.

Mutations of RAS genes in endometrial polyps

“…Previous small-scale studies have shown that APAM is associated with MLH1 hypermethylation, and microdissected glandular components were shown to contain CTNNB1 mutations (31,32). In addition, KRAS mutation was found in 4/16 cases (25%) without BRAF mutation (33), in contrast with the absence of RAS mutations in our APAM samples (0/12). Larger studies employing laser-microdissection followed by RAS mutation analysis in individual APAM components, will be necessary to draw final conclusions on this issue.…”

Mesenchymale und gemischte Uterustumoren

“…Das Stroma ist immunhistochemisch positiv für SMA, aber negativ für Desmin und Caldesmon, wodurch der Name Adenomyofibrom besser passen würde [35]. Der häufige Verlust von PTEN und häufige andere molekulare Veränderungen wie Mikrosatelliteninstabilität und KRAS-Mutationen legen die neoplastische Natur und die Verwandtschaft mit der atypischen Endometriumhyperplasie nahe [36]. Ein myoinvasives Wachstum fehlt.…”

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

“…APA is a biphasic lesion that is composed of atypical endometrial glands and fibromuscular stroma. Because the glandular component shows endometrioid features with irregular architecture and cytologic atypia, pathologists sometimes have difficulties in differentiating APA from myoinvasive adenocarcinoma 3 . This distinction is crucial and influences the clinical management of patients, allowing fertility preservation for patients with APA 1-6 .…”

“…To discriminate between these cases, some immunoistochemical markers are needed. Previous studies investigated the expression of muscular and endometrial stromal markers in APA 3 , 7-12 .…”