Mimics of Hepatocellular Carcinoma: A Review and An Approach to Avoiding Histopathological Diagnostic Missteps

Abstract Hepatocellular carcinoma (HCC) is one of the commonest carcinomas and leading causes of cancer-related death. Although in cirrhotic patients, radiologic diagnosis has improved significantly over the years, needle biopsy and histopathological assessment remains an important diagnostic modality. Most importantly histopathological diagnosis is essential in patients with contending extrahepatic primaries, those with no known HCC risk factors, patients with ambiguous radiological features, and many other clinical contexts. Helpful features such as high serum alpha-fetoprotein (AFP) serologies, are known to be present in many other tumor (including but not only HCC) and non-tumor contexts, and therefore not only lack sufficient diagnostic specificity for HCC, but also create the potential to overlook non-HCC AFP-producing tumors, of which there are many. Therefore, using clinical examples and other examples from the medical literature, this review discusses several clinical and histological mimics of HCC and proffers an approach for practicing pathologists geared towards avoiding missteps.