Combining a Unique Biomarker Profile with Morphology To Differentiate Benign Reactive Epithelial Change from Adenomas and Adenocarcinomas in Ampullary Biopsies: A Large Cohort Study
Amy A Lo, Wendy Cao, Jie Liao, Haonan Li, Wanying Zhang, M Sambasiva Rao, Guang-Yu Yang. Northwestern University, Chicago, IL
Background: Morphologic differentiation of benign reactive epithelial change, adenoma and adenocarcinoma in ampullary biopsy is challenging, particularly in the background of both duodenal and pancreaticobilliary epithelium, inflammation and fibrosis. Combining morphologic features with a panel of biomarkers would allow for straightforward and accurate diagnosis. We therefore identified 349 ampullary biopsies, analyzed their morphologic features and determined the usefulness of a biomarker panel including HMGA2, p53, β-catenin and Ki-67 in differentiating benign reactive epithelial change from adenoma and adenocarcinoma.
Design: Ampullary biopsies from 2003-2012 were identified in patients between 18 and 80 years old (n=349). All cases were separated into marked reactive change, adenoma and adenocarcinoma categories based on morphology. Immunohistochemistry (IHC) for HMGA2, p53, Ki-67 and β-catenin were performed on randomly selected slides from each category with appropriate controls. Nuclear positivity in epithelial cells from 5 high power fields was calculated for each marker and 5% positivity was considered a positive result in all cases.
Results: Morphologically, 22% of cases (n=76) demonstrated normal ampullary mucosa, 46% demonstrated benign reactive epithelial change (n=162), 19% were adenomas (n=68), 12% were adenocarcinomas (n=40) and 1% were others (n=3). Cases of benign reactive epithelial change demonstrated inflammation and/or fibrosis (n=105), pseudostratefication and hyperchromasia (n=39) similar to adenomas, or cytological atypia or mitosis (n=18) suspicious for adenocarcinoma. IHC revealed that HMGA2 was positive in 80% of the adenocarcinomas (16/20), 8% of those with benign reactive epithelial change (n=15) and none of the adenomas (n=15). p53 demonstrated 75% positivity in adenocarcinoma cases, but was negative in adenomas and reactive epithelial change. Ki-67 and β-catenin were diffusely positive in the proliferative zone, extending to the luminal surface in all adenoma cases (top-down pattern, n=15). In contrast, Ki-67 positive cells were limited to the epithelial proliferative zone in reactive epithelium with occasional cells positive for β-catenin.
Conclusions: The top-down growth pattern in ampullary adenomas is a unique morphologic feature that can differentiate adenomas from benign reactive epithelial change when combined with IHC for Ki-67 and β-catenin. Combining morphology with IHC for malignant biomarkers HMGA2 and p53 can also assist in the diagnosis of ampullary adenocarcinoma.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 271, Monday Morning