Aberrant CDX2 expression in hepatocellular carcinomas: an important diagnostic pitfall

CDX2 is a sensitive and specific marker of intestinal differentiation. It is routinely used in surgical pathology, as its expression within a tumor favors an origin within the gastrointestinal tract. We had anecdotally encountered occasional hepatocellular carcinomas (HCCs) that were CDX2 positive. CDX2 expression in HCC has not yet been reported, but it has also not been examined in detail. Therefore, we evaluated CDX2 expression in a large number of resected HCCs. Full tumor sections from 172 resected HCCs and 6 resected fibrolamellar carcinomas (FLCs) were stained for CDX2. Nine (5.2%) of 172 HCCs were positive for CDX2, whereas all 6 FLCs were negative. CDX2 expression in HCCs was more commonly seen in poorly differentiated tumors (5 of 16 cases, 31%) than well and moderately differentiated tumors (4 of 156 cases, 2.5%), P = .0004. No other statistically significant correlations were observed (P>.05). Results of our study show that a small subset (5%) of HCCs can be CDX2 positive. Awareness of this phenomenon is important because CDX2 expression in a liver tumor does not completely exclude a diagnosis of HCC.