Abstract
The development of hepatocellular carcinoma (HCC) is probably related to infection with hepatitis B virus (HBV). Hepatocytes in livers of patients with HCC have been reported to show putative preneoplastic changes such as hyperplasia, dysplasia, or adenomatous regeneration. To determine quantitatively whether these morphologic changes are associated with HBV-infected cells, the authors performed morphometry of hepatitis B surface antigen (HBsAg)-positive hepatocytes in the nontumorous portion of 10 livers with HCC and in 10 livers without HCC. The diameter of nuclei and cytoplasm of HBsAg-positive hepatocytes was measured after demonstration of HBsAg by the peroxidase-antiperoxidase method. As controls, HBsAg-negative hepatocytes in the same liver sections were measured as well as hepatocytes of 20 age-matched HBsAg-negative patients with normal liver or alcoholic cirrhosis. HBsAg-positive hepatocytes exhibited significantly larger nuclei and a higher nucleocytoplasmic ratio than control hepatocytes. In addition, HBsAg-positive cells were often arranged in foci that consisted of two cell populations: hypertrophic (enlarged nuclei and nucleocytoplasmic ratio) and hyperplastic (two-cell-thick plates of small cells with a high nucleocytoplasmic ratio). While precancerous cells have been difficult to identify, these morphologic changes are frequently associated with the development of malignant neoplasia.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anthony P. P. Precursor lesions for liver cancer in humans. Cancer Res. 1976 Jul;36(7 Pt 2):2579–2583. [PubMed] [Google Scholar]
- Anthony P. P., Vogel C. L., Barker L. F. Liver cell dysplasia: a premalignant condition. J Clin Pathol. 1973 Mar;26(3):217–223. [PMC free article] [PubMed] [Google Scholar]
- Blendis L. M., Orrego H., Crossley I. R., Blake J. E., Medline A., Isreal Y. The role of hepatocyte enlargement in hepatic pressure in cirrhotic and noncirrhotic alcoholic liver disease. Hepatology. 1982 Sep-Oct;2(5):539–546. doi: 10.1002/hep.1840020505. [DOI] [PubMed] [Google Scholar]
- Cohen C., Berson S. D., Geddes E. W. Liver cell dysplasia: association with hepatocellular carcinoma, cirrhosis and hepatitis B antigen carrier status. Cancer. 1979 Nov;44(5):1671–1676. doi: 10.1002/1097-0142(197911)44:5<1671::aid-cncr2820440521>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
- Farber E. Chemical carcinogenesis: a biologic perspective. Am J Pathol. 1982 Feb;106(2):271–296. [PMC free article] [PubMed] [Google Scholar]
- Gerber M. A., Hadziyannis S., Vissoulis C., Schaffner F., Paronetto F., Popper H. Electron microscopy and immunoelectronmicroscopy of cytoplasmic hepatitis B antigen in hepatocytes. Am J Pathol. 1974 Jun;75(3):489–502. [PMC free article] [PubMed] [Google Scholar]
- Gerber M. A., Thung S. N. The localization of hepatitis viruses in tissues. Int Rev Exp Pathol. 1979;20:49–76. [PubMed] [Google Scholar]
- Ho J. C., Wu P. C., Mak T. K. Liver cell dysplasia in association with hepatocellular carcinoma, cirrhosis and hepatitis B surface antigen in Hong Kong. Int J Cancer. 1981 Nov 15;28(5):571–574. doi: 10.1002/ijc.2910280507. [DOI] [PubMed] [Google Scholar]
- Israel Y., Orrego H., Colman J. C., Britton R. S. Alcohol-induced hepatomegaly: pathogenesis and role in the production of portal hypertension. Fed Proc. 1982 Jun;41(8):2472–2477. [PubMed] [Google Scholar]
- Jagoe R., Sowter C., Dandy S., Slavin G. Morphometric study of liver cell nuclei in hepatomas using an interactive computer technique: (i) nuclear size and shape. J Clin Pathol. 1982 Oct;35(10):1057–1062. doi: 10.1136/jcp.35.10.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kam W., Rall L. B., Smuckler E. A., Schmid R., Rutter W. J. Hepatitis B viral DNA in liver and serum of asymptomatic carriers. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7522–7526. doi: 10.1073/pnas.79.23.7522. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakashima T., Okuda K., Kojiro M., Jimi A., Yamaguchi R., Sakamoto K., Ikari T. Pathology of hepatocellular carcinoma in Japan. 232 Consecutive cases autopsied in ten years. Cancer. 1983 Mar 1;51(5):863–877. doi: 10.1002/1097-0142(19830301)51:5<863::aid-cncr2820510520>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
- Orrego H., Blendis L. M., Crossley I. R., Medline A., Macdonald A., Ritchie S., Israel Y. Correlation of intrahepatic pressure with collagen in the Disse space and hepatomegaly in humans and in the rat. Gastroenterology. 1981 Mar;80(3):546–556. [PubMed] [Google Scholar]
- Ranek L., Keiding N., Jensen S. T. A morphometric study of normal human liver cell nuclei. Acta Pathol Microbiol Scand A. 1975 Sep;83(5):467–476. doi: 10.1111/j.1699-0463.1975.tb00157.x. [DOI] [PubMed] [Google Scholar]
- Sell S., Leffert H. L. An evaluation of cellular lineages in the pathogenesis of experimental hepatocellular carcinoma. Hepatology. 1982 Jan-Feb;2(1):77–86. doi: 10.1002/hep.1840020113. [DOI] [PubMed] [Google Scholar]
- Szmuness W. Hepatocellular carcinoma and the hepatitis B virus: evidence for a causal association. Prog Med Virol. 1978;24:40–69. [PubMed] [Google Scholar]
- Thung S. N., Gerber M. A., Sarno E., Popper H. Distribution of five antigens in hepatocellular carcinoma. Lab Invest. 1979 Aug;41(2):101–105. [PubMed] [Google Scholar]
- Watanabe S., Okita K., Harada T., Kodama T., Numa Y., Takemoto T., Takahashi T. Morphologic studies of the liver cell dysplasia. Cancer. 1983 Jun 15;51(12):2197–2205. doi: 10.1002/1097-0142(19830615)51:12<2197::aid-cncr2820511208>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
- Watanabe T., Tanaka Y. Age-related alterations in the size of human hepatocytes. A study of mononuclear and binucleate cells. Virchows Arch B Cell Pathol Incl Mol Pathol. 1982;39(1):9–20. doi: 10.1007/BF02892832. [DOI] [PubMed] [Google Scholar]