Utility of AMACR immunohistochemical staining in differentiating Arias-Stella reaction from clear cell carcinoma of ovary and endometrium

BACKGROUND: The Arias-Stella reaction is a hormone-related atypical endometrial change characterized by cytomegaly, nuclear enlargement, and hyperchromasia of endometrial glands; typically associated with intrauterine or extrauterine pregnancies or with gestational trophoblastic disease. Although differentiating the Arias-Stella reaction (ASR) from clear cell carcinoma (CCC) of the endometrium is usually straightforward, but differentiating ASR might be difficult if it occurs outside the setting of pregnancy, in extra-uterine sites or in older patients. The aim of this study was to determine whether P504S/Alpha Methyacyl CoA racemase (AMACR) immunohistochemical (IHC) staining can be used to differentiate ASR from CCC. METHODS: Fifty endometrial ASR and 57 CCC samples were assessed by IHC staining with antibody for AMACR. The immunoreactive score (IRS) was based on total intensity score (no staining to strong scored as 0–3) + percentage score (0-100% categorized as 0–3) ranged from 0 to 6. Positive expression was considered as a total IRS exceeding 2. RESULTS: The mean age of the patients in the ASR was significantly lower than that of CCC (33.34 ± 6.36 and 57.81 ± 11.64 years old, respectively, p < 0.001). The overall AMACR staining score was significantly higher among CCC compared to ASR groups (p = 0.003). The positive and negative predictive values for AMACR expression in detecting CCC from ASR were 81.1% and 57%, respectively. CONCLUSION: IHC staining for AMACR can be helpful and a member of discriminatory IHC panel when clinical or histologic features cannot facilitate the differential diagnosis between ASR versus CCC.