Diagnostic histopathology of hepatocellular carcinoma: A case-based review

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignant neoplasm in adults. Clinically, it tends to present late, and its prognosis historically has been poor, due to limited treatment options at the more advanced stage. A multidisciplinary approach for surveillance and early diagnosis of hepatocellular carcinoma in high-risk populations, combined with advances in surgical and other forms of ablative or chemotherapy, has greatly improved outcomes for patients with this tumor. Liver biopsies for HCC are becoming rare, being performed only for lesions that are atypical on imaging, to avoid the risk of bleeding or of inadvertently seeding the needle tract with HCC. HCC, a tumor of varied appearance, can be diagnostically challenging, particularly on a liver biopsy, due to sampling errors. Although HCC typically occurs on a background of cirrhosis, or advanced fibrosis, it may also arise in the noncirrhotic liver. Well-differentiated HCC may be hard to distinguish from benign lesions in the noncirrhotic liver and premalignant lesions in the cirrhotic liver, whereas a poorly-differentiated neoplasm may be difficult to tell apart from metastases or primary intrahepatic cholangiocarcinoma. Additionally, variant forms of HCC may mimic other neoplasms. This case-based review discusses typical HCC, the increasingly recognized steatohepatitic variant of HCC, the rare scirrhous variant of HCC and the extremely rare and clinically challenging cirrhotomimetic HCC.