Early Hepatocellular Carcinoma: Definition and Diagnosis

Early hepatocellular carcinoma (HCC) can be described as “early” according to its pathological characteristics as well as its clinical characteristics. Taking the pathological approach first, the term “early” implies that a lesion is at a relatively early stage of carcinogenesis and prognosis is still good. Well-differentiated HCC is not necessarily early HCC. According to the clinical approach, the term “early” is used to differentiate HCC diagnosed in its early developmental stage from that diagnosed at more advanced stages. The clinical approach to diagnosing early HCC is used preferentially in the United States and Europe and, in general, this conceptualization of early HCC refers to tumors smaller than 3 cm and three or fewer in number at stage A (early stage) with respect to Barcelona Clinic Liver Cancer staging, although it sometimes includes solitary tumors up to 5 cm in size, as defined in the Milan criteria. Both very early and early stage tumors are relatively small, but both are hypervascular in the arterial phase and are regarded as classic HCC. The pathological approach, however, defines early HCC as HCC in the early stage of carcinogenesis (generally ≤2 cm) that is often hypovascular with irregular boundaries on diagnostic imaging and contains portal elements without significantly affecting the original structure of the liver. The pathological characteristics of HCC include its multistep progression from a low-grade to a high-grade dysplastic nodule, to early HCC, and eventually to classic hypervascular HCC [1](fig.1). Accordingly, the accurate diagnosis and proper treatment of early HCC, a precursor of classic (typical) HCC, is extremely important. Therefore, I will discuss here the pathological aspects of early HCC. According to the General Rules for the Clinical and Pathological Study of Primary Liver Cancer developed by the Liver Cancer Study Group of Japan [2], early HCC is defined as follows. Early HCC exhibits focal structural abnormalities such as acinar or pseudoglandular structures, broken or irregular trabecular alignment, and/or obvious invasion of the stromal tissue. Cellular atypia is usually unremarkable, but the nuclear–cytoplasmic ratio is increased due to decreased amounts of cytoplasm. The cytoplasm also shows eosinophilia or basophilia. The cell density may be more than twice that of the surrounding non-cancerous liver tissue. In addition, lesions often exhibit fatty changes or clear cell changes. Because the cancer cells of early HCCs do not grow expansively, they instead proliferate by replacing ad© 2013 S. Karger AG, Basel 2235-1795/13/0022-0069$38.00/0 www.karger.com/lic Liver Cancer 2013;2:69–72