Immunohistochemical expression of napsin A and hepatocyte nuclear factor-1-beta in Arias-Stella reaction

Abstract

Background: Arias-Stella reaction is a spectrum of benign cellular changes which is associated with exogenous progestogens or pregnancy. Histologically, this reaction is characterized by striking nuclear atypia with or without clear cytoplasm and can potentially mimic clear cell carcinoma. The diagnostic difficulty may be encountered in small biopsy samples containing atypical clear cells and in which the drug history or pregnancy status is unknown. In order to exclude a diagnosis of clear cell carcinoma, immunohistochemistry is often used. Recently, two immunohistochemical markers, napsin A and hepatocyte nuclear factor-1-beta (HNF-1β) have been proposed to be useful in the diagnosis of endometrial clear cell carcinomas as other tumors containing clear cells, such as endometrioid carcinomas, are often negative. However, the expression of these markers in Arias-Stella reaction has not been fully evaluated. Aim: To study the frequency and extent of napsin A and HNF-1β expression in cases of Arias-Stella reaction in small biopsy samples. Design: Immunohistochemistry was performed on 41 endometrial and cervical biopsies. The extent of staining for each marker was assessed and classified as negative, <5%, 6-33%, 34-66% and >66%. Results: Thirty-nine cases were gestational and two were on oral progestogen. Six cases were endocervical polyps and one was an endometrial polyp, and the rest were endometrial biopsies. In each case, the Arias-Stella reaction was either of the secretory/hypersecretory type or monstrous cell type with various degrees of atypia. Stromal decidual change was found in 31 cases (75.6%). All 41 cases (100%) were positive for napsin A and HNF-1β. For napsin A, positive staining involving <33%, 34-66% and >66% of glands were found in 28 (68.3%), 13 (31.7%) and 1 (2.4%) cases, respectively. For HNF-1β, positive staining involving 34-66% and >66% of glands were found in 6 (14.6%) and 35 (85.4%) of cases, respectively. In 6 cases in which the Arias-Stella reaction was focal (<50%) and unaccompanied by any stromal decidual change, both markers were also positive. Conclusion: In our series, both naspin A and HNF-1β were positive in gestational and progestogen-induced Arias-Stella reaction. These markers may stain atypical cells with or without clear cytoplasm. Despite their usefulness in the histologic subtyping of an established carcinoma, both naspin A and HNF-1β are not useful for distinguishing carcinomas from Arias-Stella reaction. The interpretation of their staining in limited samples containing atypical glands should be made with caution.