Hepatocellular carcinoma in the early stage

  • Setsuo Hirohashi
  • Michiie Sakamoto


Progress in imaging diagnosis has made it possible to detect an increasing number of minute hepatocellular carcinomas (HCCs), some of which can be removed successfully by surgery. In addition, lesions intermediate between regenerative nodules and minute HCCs, i.e. borderline lesions, can also be detected. Through analysis of these lesions, we have learned the natural course of human hepatocarcinogenesis. Long after infection with hepatitis viruses, small nodular lesions (adenomatous hyperplasia), which do not destroy substantially the underlying liver structure, develop in liver showing chronic hepatitis or cirrhosis. Some of these nodules show structural abnormalities and are diagnosed as well-differentiated HCC (early HCC). Nodule-in-nodule lesions composed of a peripheral area of early HCC and a central area of less well differentiated HCC are also observed. Clinicopathologically, it is very important to establish criteria for differentiating between adenomatous hyperplasia and early HCC.


Portal Vein Tumor Thrombus Small Hepatocellular Carcinoma Adenomatous Hyperplasia Atypical Adenomatous Hyperplasia Borderline Lesion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Sakamoto M, Hirohashi S, Shimosato Y (1991) Early stages of multistep hepatocarcinogenesis: Adenomatous hyperplasia and early hepatocellular carcinoma. Hum Pathol 22: 172–178PubMedCrossRefGoogle Scholar
  2. 2.
    Watanabe H, Hirohashi S, Sakamoto M, Hasegawa H, Yamazaki S, Makuuchi M, Moriyama N, Takayasu K (1990) New macroscopic subtype of small hepatocellular carcinoma—common type in early type—and histological consideration of the multistep progression of HCC (in Japanese). Acta Hepatol Jpn 31: 1267–1273CrossRefGoogle Scholar
  3. 3.
    Sakamoto M, Hirohashi S, Tsuda H, Shimosato Y, Makuuchi M, Hosoda Y (1989) Multicentric independent development of hepatocellular carcinoma revealed by analysis of hepatitis B virus integration pattern. Am J Surg Pathol 13: 1064–1067PubMedCrossRefGoogle Scholar
  4. 4.
    Tsuda H, Hirohashi S, Shimosato Y, Terada M, Hasegawa H (1988) Clonal origin of atypical adenomatous hyperplasia of the liver and clonal identity with hepatocellular carcinoma. Astroenterology 95: 1664–1666Google Scholar
  5. 5.
    Kanai T, Hirohashi S, Upton M, Noguchi M, Kishi K, Makuuchi M, Yamasaki S, Hasegawa H, Takayasu K, Moriyama N, Shimosato Y (1987) Pathology of small hepatocellular carcinoma: a proposal for a new gross classification. Cancer 60: 810–819PubMedCrossRefGoogle Scholar
  6. 6.
    Yuki K, Hirohashi S, Sakamoto M, Kanai T, Shimosato Y (1990) Growth and spread of hepatocellular carcinoma: A review of 240 consecutive autopsy cases. Cancer 66: 2174–2179PubMedCrossRefGoogle Scholar
  7. 7.
    Sakamoto M, Hirohashi S, Tsuda H, Ino Y, Shimosato Y, Yamasaki S, Makuuchi M, Hasegawa H, Terada M, Hosoda Y (1988) Increasing incidence of hepatocellular carcinoma possibly associated with non-A, non-B hepatitis in Japan, disclosed by hepatitis B virus DNA analysis of surgically resected cases. Cancer Res 48: 7294–7297PubMedGoogle Scholar
  8. 8.
    Tsuda H, Zhang W, Shimosato Y, Yokota J, Terada M, Sugimura T, Miyamura T, Hirohashi S (1990) Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proc Natl Acad Sci USA 87: 6791–6794PubMedCrossRefGoogle Scholar
  9. 9.
    Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Okazaki N, Takayasu K, Kosuge T, Motoo Y, Yamazaki S, Hasegawa H (1990) Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma. Lancet 336: 1150–1153PubMedCrossRefGoogle Scholar
  10. 10.
    Edmondson H, Steiner P (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7: 462–503PubMedCrossRefGoogle Scholar
  11. 11.
    Anthony P, Vogel C, Barker L (1973) Liver cell dysplasia: a pre-malignant condition. J Clin Pathol 26: 217–223PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1992

Authors and Affiliations

  • Setsuo Hirohashi
    • 1
  • Michiie Sakamoto
    • 1
  1. 1.Pathology DivisionNational Cancer Center Research, InstituteTsukiji, Chuo-ku, TokyoJapan

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