Fibrolamellar Carcinoma: What Is New and Why It Matters

Fibrolamellar carcinoma is distinctive at clinical and histologic levels. A novel DNAJB1-PRKACA fusion gene characterizes almost all cases, distinguishes it from other hepatocellular neoplasms, and drives the pathogenesis of this unique tumor. A subset of cases of fibrolamellar carcinoma is associated with alternate mechanisms of protein kinase A activation. This review article discusses common and unusual histologic features of fibrolamellar carcinoma, its differential diagnoses, and how to make the diagnosis while avoiding key pitfalls. The impact of the discovery of the fusion gene on the understanding of the tumor and the prognosis of fibrolamellar carcinoma are also discussed.