Expression of Calretinin, Marker of Mesothelial Differentiation, in Pancreatic Ductal Adenocarcinoma: A Potential Diagnostic Pitfall

Objective: Pancreatic ductal adenocarcinoma is one of the most common causes of “peritoneal carcinomatosis” and has an insidious growth pattern. Thus, it falls into the differential diagnosis of other peritoneal malignancies including malignant mesothelioma. Recently, we have encountered an undifferentiated pancreatic carcinoma presenting with peritoneal disease and exhibiting immunoreactivity to calretinin, mimicking mesothelioma. In this study, we explored the incidence of calretinin expression in pancreatic ductal adenocarcinoma. Materials and Methods: Calretinin immunohistochemical staining was performed on the tissue microarrays (TMAs), which were created using three 0.6 mm diameter punches per tumor (n=113). Distribution and intensity of expression were evaluated. Results: The TMAs contained 86 well/moderately differentiated and 27 poorly differentiated/undifferentiated carcinomas. Calretinin was positive in nine tumors (8%); six with diffuse and strong staining, three with focal and/or weak staining. The incidence of calretinin expression was 15% in poorly differentiated/undifferentiated carcinomas (vs. 6% in well/moderately differentiated carcinomas, p=0.03). Conclusions: Pancreatic ductal adenocarcinomas, especially when poorly differentiated/undifferentiated, may be diffusely and strongly positive for calretinin creating a potential diagnostic challenge with malignant mesothelioma. Therefore, caution should be exercised when using this marker to explore a diagnosis of malignant mesothelioma. Tumors expressing calretinin without other mesothelial markers should prompt a careful evaluation of the morphologic and immunohistochemical features to exclude other malignancies. If the diagnosis of pancreatic ductal adenocarcinoma is considered, ductal differentiation can be demonstrated by using additional immunohistochemical markers such as mucin-related glycoproteins (MUC1, MUC5AC) and/or oncoproteins (CEA, B72.3, CA125).