Hepatoid differentiation in renal cell carcinoma: A rare histologic pattern with clinical significance

Hepatoid adenocarcinoma is a rare extrahepatic aggressive tumor defined bymorphologic and immunohistochemical evidences of hepatoid differentiation. In this study, clinicopathologic features of 3 cases of hepatoid renal cell carcinoma (RCC) were analyzed. Case I was a 53-year-old man with stage III, with 1,460 ng/ml of serum alphafetoprotein (AFP) and a 12 cm-sized stage III RCC, which was a combined clear cell and papillary RCC type 2 with sarcomatoid dedifferentiation. Case II was a 62-year-old woman with stage IV, 6.5-cm clear cell RCC and 40,800 ng/mL of serum AFP. Case III was a 51-year-old woman with stage I, 1.6-cm Xp11 translocation RCC and 313.3 ng/mL of serumAFP. Cases I and II died of the disease at 26 and 21 months after radical nephrectomy, respectively. Case III was alive without the disease for 20months at the last follow-up. Microscopically, three cases show hepatoid carcinoma areas with eosinophilic to clear cells, arranged in trabeculae, separated by thin sinusoidal vessels, in addition to diagnostic features of corresponding RCC subtypes. The tumor cells in these hepatoid carcinoma areas as well as at least focally in RCC areas were immunopositive for AFP in all three cases, but were immunonegative for other hepatic markers (Hep Par1, polyclonal CEA, and glypican 3). This report suggests that the hepatoid features with AFP production are aberrant differentiation that can be developed in various RCC subtypes. Recognizing hepatoid RCC will help explain abnormal elevation of serum AFP levelS, which can be used as a serum surveillance marker.