388 The Korean Journal of Hepatology : Vol. 6. No COMMENT 1. (dysplastic nodule) (adenomatous hyperplasia, AH), (macroregenerative nodule, MR

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6 3 2000 ; 387-392 (3) Dysplastic Nodule Young Nyun Park, M.D., Chanil Park, M.D. Department of Pathology, Yonsei University College of Medicine BRIEF HISTORY 56. AST/ALT 72/73 IU/L, total bilirubin 0.7 mg/dl, HBsAg(+), HBeAg(+), HBcAb IgG(+)/IgM(+).. GROSS FINDING 4.5 3 2cm, 2cm,.,.,.. MICROSCOPIC FINDING,. (small liver cell dysplasia),. Mallory.., 1 normotrabecular pattern. well differentiated hepatocelllular carcinoma (HCC) (Edmondson- Steiner grade I), cell proliferating nuclear antigen. well differentiated HCC. - smooth muscle actin (unpaired artery) CD34. - fetoprotein. DIAGNOSIS Dysplastic nodule, high grade with microscopic foci of well differentiated HCC Chronic hepatitis, B viral, moderate lobular activity, severe portoperiportal activity with fibrous septa formation (transition to cirrhosis)

388 The Korean Journal of Hepatology : Vol. 6. No. 3. 2000 COMMENT 1. (dysplastic nodule) (adenomatous hyperplasia, AH), (macroregenerative nodule, MRN), 1994 working international party HCC.1 2. 1mm.,. (portal tract). (low grade) (high Figure 1. A proposed model of early hepatocarcinogenesis. grade)., HCC..2-4 T ype I MRN - ordinary AH - dysplastic nodule, low grade T ype II MRN - atypical AH - dysplastic nodule, high grade,,, HCC,, muscular artery (unpaired artery),,, factor VIII CD34.5-6 3. (Early HCC)., microscopic HCC Figure 2. Gross feature of high grade dysplastic nodule with microscopic foci of hepatocellular carcinoma. T he nodule showing yellowish tan and bulging surface with indistinct margin (arrow s) and the surrounding liver showing chronic hepatitis with irregular surface.

Young Nyun Park. et al. Dysplastic Nodule 389 Figure 3. Microscopic feature of high grade dysplastic nodule. Low power view of the nodule showing fatty change and indistinct margin (arrows) (A). T he hepatocytes of the nodule showing small liver cell dysplasia (B) and Mallory bodies (C). Portal tract (D) found in the nodule (H&E)., HCC ( 1). REFERENCE 1. International Working Party. T erminology of nodular hepatocellular lesion. Hepatology 1995; 22: 983-993. 2.. ( ) - ). Med Postgraduate 1998; 6:358-364. 3. T heise ND. Macroregenerative (dysplastic)

390 6 3 2000 Figure 4. Microscopic feature of well differentiated hepatocellular carcinoma (HCC) in dysplastic nodule. A. Low power view show ing subnodule of increased cell density (arrows). B. Well differentiated HCC showing normotrabecular pattern. Immunohistochemical stain for cell proliferating nuclear antigen showing high activity in well differentiated HCC (arrow s) (C), comparing with low activitiy of surrounding non- neoplastic liver (D).

1. 391 Figure 5. Neoangiogenesis in high grade dysplastic nodule showing unpaired arteries (arrows), not accompanied by bile ducts (A) and highlighted by - smooth muscle actin (B). Immunohistochemical stain for CD34 showing diffuse sinusoidal capillarization in high grade dysplastic nodule (C) in comparison with focal peripheral pattern of surrounding non- neoplastic liver (D).

392 The Korean Journal of Hepatology : Vol. 6. No. 3. 2000 nodules and hepatocarcinogenesis: theoretical and clinical considerations. Seminars in Liver Dis 1995; 15: 360-371. 4. Nakanuma Y, Terada T, Ueda K, T erasaki S, Nonomura A, Matsui O. Adenomatous hyperplasia of the liver as a precancerous lesion. Liver 1993;13:1-9. 5. Park YN, Yang C- P, Cubukcu O, T hung S N, T heise ND. Neoangiogenesis and sinusoidal "capillarization" in dysplastic (macroregenerative) nodules. Am J Surg Pathol 1997;22:656-662. 6. Park YN, Kim YB, Yang KM, Park C. Increased expression of vascular endothelial growth factor and angiogenesis in the early stage of multistep hepatocarcinogenesis. Arch Pathol Lab Med 2000;124:1061-1065. 7. Sakamoto M, Hirohashi S, Shimosato Y. Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma. Hum Pathol 1991; 22:172-178. 8 Nakashima O, Sugihara S, Kage M, Kojiro M. Pathomorphologic characteristics of small hepatocellular carcinoma: A special reference to small hepatocellular carcinoma with indistinct margins. Hepatology 1995;22:101-105.