Hepatocellular Carcinoma Pathology

Abstract

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Background cirrhosis is present in the majority of cases. Important clinical information needed at the time of surgery includes: (1) etiology of the underlying chronic liver disease, (2) location of tumor nodules on imaging, (3) history of neoadjuvant therapy and type of therapy, and (4) the presence or absence of a transjugular intrahepatic porto-systemic shunt (TIPS). Pathologists diagnose hepatocellular carcinoma using surgical resection specimens, core biopsies, or fine needle aspiration biopsy (FNAB). Microscopically, HCC resembles the normal liver but with important exceptions, such as the lack of portal tracts, expansion of hepatic trabeculae to three or more cells thick, loss of reticulin fibers, and cytologic atypia. HCC is the only malignancy that makes bile, a useful diagnostic clue if other malignancies are considered. There are histologic subtypes of HCC with distinct molecular alterations, and some subtypes have a better prognosis than others. Immunohistochemistry can confirm the diagnosis of HCC in difficult cases or differentiate HCC from other tumors that mimic HCC histologically. HCC has characteristic genomic mutations, and a molecular classification of HCC has been proposed with high proliferation and nonproliferation subtypes. Various histologic grading and staging systems are used to evaluate the extent of cancer, disease severity, predict survival, and ultimately drive therapy. Pathologists play a critical role in the diagnosis and staging of hepatocellular carcinoma, and with the ongoing discovery of novel prognostic biomarkers, pathologists are expanding their role into tumor prognosis and treatment optimization.