We report for the first time the presence of focal Hep Par 1 reactivity, a marker of the hepatocellular phenotype, in 6 of 7 hepatoid adenocarcinomas, including 1 from the gallbladder. Hence, demonstration of Hep Par 1 in adenocarcinomas outside the liver strongly supports the previously held view that these hepatoid foci represent true hepatocellular differentiation. This finding is not surprising in the stomach and gallbladder, because both organs are foregut derivatives and probably harbor stem cells. It would be interesting to study Hep Par 1 reactivity in hepatoid neoplasms from embryologically disparate sites such as the urinary bladder or gonads. Aside from the ontogenetic value of demonstrating Hep Par 1 reactivity in hepatoid adenocarcinomas, this finding may have diagnostic importance for the pathologist.
Hepatoid adenocarcinomas have a tendency to metastasize to the liver.
When metastatic to the liver, hepatoid adenocarcinomas would generally be multiple and show characteristic central umbilication. In such cases, demonstration of Hep Par 1 immunoreactivity would be invaluable for characterizing the tumor as a hepatoid adenocarcinoma and alerting the clinician to the substantially worse prognosis associated with these tumors. We studied Hep Par 1 expression in 7 hepatoid adenocarcinomas of the gastrointestinal tract and demonstrated focal immunoreactivity in 6 cases. Our results underscore the fact that Hep Par 1 expression is not unique to primary hepatocellular neoplasms, and, therefore, adenocarcinomas with hepatoid features must be considered in the differential diagnosis of Hep Par 1 positive lesions. Am J Pathol .