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Arch Pathol Lab Med. 2011 Jun;135(6):704-15. doi: 10.1043/2010-0524-RA.1.

Update on precursor and early lesions of hepatocellular carcinomas.

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  • 1Department of Pathology, Brain Korea 21 Project for Medical Science, Center for Chronic Metabolic Disease, Yonsei University Health System, Seoul, South Korea.



There is increasing evidence to support a multistep model of the process of human hepatocarcinogenesis. Precursor lesions are characterized by the appearance of dysplastic lesions in the form of microscopic dysplastic foci and macroscopic dysplastic nodules. There are 2 types of small hepatocellular carcinoma (HCC) (≤2 cm in diameter): (1) early HCC with an indistinct margin and (2) progressed HCC with a distinct margin. Pathologic diagnostic criteria for early HCC have recently been set up based on a consensus between Eastern and Western pathologists.


To review the nomenclature, pathology, and biomarkers of precursor and early lesions of HCC.


Literature review and illustrations from case materials were used.


Dysplastic foci are composed of large and small cell changes. Small cell change is considered to be a more advanced precursor lesion than large cell change, and large cell change is a rather heterogeneous lesion that may represent both reactive change and true dysplasia. Dysplastic nodules can be categorized as low or high grade according to the degree of atypia. High-grade dysplastic nodules have been reported to show molecular changes similar to HCC and have a high risk of malignant transformation. Early HCC, which may correspond to microinvasive carcinomas of other organs, is a well-differentiated HCC, and differential diagnosis between early HCC and high-grade dysplastic nodule is difficult. Identification of stromal invasion and application of a panel of markers (glypican-3, heat shock protein 70, and glutamine synthetase) is helpful for diagnosis of early HCC. Detection of precursor lesions of HCC is important in recognizing patients with higher risk of developing HCC, and diagnosis of early HCC can improve patient survival by allowing for early and adequate treatment.

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