Dysplastic nodule (DN), which is nodular hepatocellular proliferation of at least 1mm in diameter, is detected most often through radiological and pathological observations in chronic advanced liver diseases. DNs characteristically contain portal tracts and they can be classified into low grade for mild atypia and high grade for at least moderate atypia that is insufficient for the diagnosis of malignancy. DNs are supplied portal venous blood and arterial blood supply. In unpaired arteries, new angiogenesis, shows stepwise increases in the following order of DN low grade, DN high grade, early hepatocellular carcinoma and hepatocellular carcinoma. There are convincing clinicopathological data to support the premise that DNs are considered to be precancerous lesions and early stages of multistep processes of hepatocellular carcinogenesis. Extensive clinicopathological and molecular study can provide a better understanding of the characteristics of DNs and new therapeutic approaches to DNs.
Arteries ; Carcinogenesis ; Carcinoma, Hepatocellular ; Diagnosis ; Liver Diseases ; Liver*

No abstract available.
Liver* ; Pathology*

Sclerosing hepatic carcinoma (SHC) is composed of slender cords or small nests of tumor cells with peripheral palisading, and abundant intervening sclerosis. The tumor seems to have the histologic features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma. To evaluate the phenotypic expression of SHC and to investigate its cellular origin, immunohistochemical studies on three cases of SHC were performed. In all cases, the tumor cells showed positive staining for cytokeratins AE1, AE3 and 19, carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). The expressions of cytokeratins AE1 and 19 were stronger in the palisading cells than the interior of the cords and nests. Conversely, CEA and EMA were expressed mainly in the inner portion. Alpha-fetoprotein was expressed in only one case, mainly in the palisading cells. In summary, SHC has the histological as well as the immunohistochemical profiles intermediate between HCC and cholangiocarcinoma, and the immunohistochemical profile suggests that SHC arises from primitive hepatoblast with a tendency of differentiation to the bile duct epithelium.
Carcinoma, Hepatocellular

Cases sharing features of both primary biliary cirrhosis and autoimmune hepatitis have been reported as a mixed type, overlap syndrome, immunocholangitis and autoimmune cholangiopathy. A primary biliary cirrhosis- autoimmune hepatitis overlap syndrome is unusual and characterized by overlapping features; cholestasis, high titer of alkaline phosphatase, bile duct damage and granulomas in the liver biopsy, high antinuclear antibody, increased IgG and IgM and intra-acinar hepatitis with piecemeal necrosis. Autoimmune mechanisms are thought to play a major role in the pathogenesis of the overlapping syndrome and the bases of immunosuppressive therapy. A 58-year-old female patient shows overlapping clinical and laboratory findings, chronic active hepatitis in initial liver biopsy which transits to primary biliary cirrhosis with cholangitis and granulomas. This is a case of hepatobiliary lesion showing overlapping features of both primary biliary cirrhosis and autoimmune hepatitis over 3-year period.
Alkaline Phosphatase ; Antibodies, Antinuclear ; Bile Ducts ; Biopsy ; Cholangitis ; Cholestasis ; Female ; Granuloma ; Hepatitis* ; Hepatitis, Autoimmune ; Hepatitis, Chronic ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Liver ; Liver Cirrhosis, Biliary ; Middle Aged ; Necrosis

To elucidate the effect of copper on the 3'-methyl-4-dimethylaminoazobenzene(3'-MeDAB) induced hepatic carcinogenesis, Sprague-Dawley rats were divided into 4 groups according to 3'-MeDAB and copper administration: I. noraml control, II. copper only, III. 3'-MeDAB only, IV. 3'-MeDAB plus copper. The animals of groups III and IV were fed experimental diet containing 0.06% 3'-MeDAB. Copper was administrated intraperitoneally in a dose of 0.5 mg, twice a weak. Animals were sacrificed at different intervals. Liver weight, hepatic copper content and gross and microscopical changes of the liver were examined and the cell kinetics of various lesions in the hepatic carcinogenesis was studied by applying the immunohistochemical method for bromodeoxyuridine(BrdU). The hepatic copper content was significantly increased in animals given copper but returned to the normal value after cessation of adminstration. 3'-MeDAB administration caused oval cell proliferation and produced hyperplastic nodules, cholangiofibrosis and carcinoma of the liver. Simultaneous administration of copper did not alter the incidence of 3'-MeDAB induced lesions, except for carcinoma. The liver weight and the size of hepatic nodules and masses were smaller in group IV than in group III. The liver weight as well as the nodularity and the mass formation continued to increase affect cessation of 3'-MeDAB administration. Copper did not affect the BrdU labelling indices of the hepatic lesions induced by 3'-MeDAB. The oval cell proliferation and the BrdU labelling indices of the oval cell and the hyperplastic nodule were decreased, but the incidence of cholangiofibrosis and its BrdU labelling index were still elevated after cessation of 3'MeDAB administration. These findings indicate that copper could delay the developement of 3'-MeDAB induced hepatic lesions, but not suppress, since copper does not stay long enough to accumulate in the rat liver, and that copper could not affect the proliferation of 3'-MeDAB induced hepatic lesions once developed.
Rats ; Animals ; Incidence

Adreno-hepatic fusion is rare condition defined as adhesion of the liver and right adrenal cortex with close intermingling of the respective parenchyme. It is suggested to be an aging phenomenon, because its incidence is much higher in older age group. Clinically it may pose a problem of operability of the organ involved. We report a case of incidentally found adreno-hepatic fusion in a 49 year old female patient with adenocarcinoma of the sigmoid colon. The segementectomy of VIII segement of the liver was done due to a 6 4 cm sized metastatic nodule of adenocarcioma. Pathological examination of the liver revealed an ovoid shaped, 1 0.5 cm sized adrenal cortical tissue. It was subcapsularly located and about 1cm apart from the metastatic adenocarcinoma with an intervening normal hepatic tissue. The adrenal tissue was mainly composed of zona fasciculata without medullary tissue. In the interphase, the adrenal tissue and liver tissue were admixed closely and partially septated by thin fibrous tissue. There was no inflammatory response to the heterotropically located adrenal tissue and there was no symptom related to the adrenal gland.
Adenocarcinoma ; Adrenal Cortex ; Adrenal Glands ; Aging ; Colon, Sigmoid ; Female ; Humans ; Incidence ; Interphase ; Liver ; Middle Aged ; Zona Fasciculata

It is well known that histologic grade and tumor stage are important prognostic factors, and that the monoclonal antibody to proliferating cell nuclear antigen(PCNA) can recognize S-phase cells. The PCNA index of 53 transitional cell carcinomas(TCCs) of the urinary bladder was studied to evaluate its prognostic validity. The PCNA indices of TCCs ranged from 38 to 92, whih were quite different from that of normal transitional epithelium(9.4). The PCNA indices were significantly higher in tumors of the higher histologic grade and/or tumor stage(correlation coefficient 0.64 and 0.43; P=0.00). The PCNA index was particularly valuable in discriminating the superficial TCCs from the deeply invasive TCCs(67.1+/-15.46 and 79.9+/-9.70; P=0.000). Among TCCs of the same tumor stage, the histologic grade affected the PCNA index. However, TCCs of the same histologic grade revealed similar PCNA indices regardless of tumor stage. These results indicate that the PCNA index is an objective and reliable prognostic factor in TCCs, which is superior to the conventional histologic grade.

Hepatic veno-occlusive disease (VOD) is a rare disease due to occlusion of the terminal hepatic venules and/or sublobular veins, which is a result of endothelial damage from pyrrolizidine alkaloids in herbal teas, irradiation of the liver, or chemotherapy particularly in association with bone marrow transplantation. We recently experienced three cases of VOD developed after radiation therapy. Two cases occurred in hepatocellular carcinoma patients of a 37-year-old man with B viral chronic hepatitis and a 22-year-old man with B viral cirrhosis and the other in a 64-year-old patient with esophageal squamous cell carcinoma. For the treatment of hepatocellular carcinoma, chemoembolization with lipiodol and adriamycin, and external irradiation on the liver mass were done. The total radiation dose was 5400 cGy and 3000 cGy in each case. Five months and 3 months after irradiation, respectively, the resected liver masses showed extensive necrosis due to pre-operative treatment. To treat esophageal carcinoma, pre-operative concurrent chemotherapy of 5-FU and radiation of 4500 cGY were done. One month after irradiation, the radical esophgectomy and wedge biopsy of the liver were done. The liver of all 3 cases showed a dark red appearance with severe congestion in contrast to the pale brown normal liver, which was not included in the radiation field. On micoscopic examination, the terminal hepatic venules and sublobular veins showed subintimal edema, fibrin deposition, and partial or total luminal occlusion by loose fibrous tissue. The centrizonal sinusoids were markedly dilatated and congested with atrophy of hepatocytes.
Adult ; Atrophy ; Teas, Herbal ; Biopsy ; Bone Marrow Transplantation ; Carcinoma, Hepatocellular ; Carcinoma, Squamous Cell ; Doxorubicin ; Drug Therapy ; Edema ; Estrogens, Conjugated (USP) ; Ethiodized Oil ; Fibrin ; Fibrosis ; Fluorouracil ; Hepatic Veno-Occlusive Disease* ; Hepatitis, Chronic ; Hepatocytes ; Humans ; Liver ; Middle Aged ; Necrosis ; Phenobarbital ; Pyrrolizidine Alkaloids ; Rare Diseases ; Veins ; Venules ; Young Adult

p21 is a universal inhibitor of cyclin-dependent kinase (cdk) and of cell-cycle progression. p21 expression is variable according to the type of tissue and the pathologic condition. To study the role of p21 in the multistep hepatocarcinogenesis, the expression of p21, p53 and Ki-67 was investigated in 53 cases of inactive liver cirrhosis, 4 cases of low grade dysplastic nodules, 3 cases of high grade dysplastic nodules, 7 cases of early hepatocellular carcinomas (HCCs), 27 cases of small HCCs (< or =3 cm), and 52 cases of advanced HCCs (>3 cm). p21 expression was not detected in liver cirrhosis, low grade dysplastic nodules, high grade dysplastic nodules and early HCCs which were mitotically inactive. p21 expression was significantly increased in small HCCs and advanced HCCs which were mitotically active. p21 expression was significantly correlated with Ki-67 labelling indices. p53 protein was not expressed in liver cirrhosis, dysplastic nodules, and early HCCs. The expression of p53 protein was, however, significantly increased in small and advanced HCCs. The p21 expression was not correlated with p53 expression. Therefore, p21 is suggested to play a role in the mitotically active small and advanced HCCs, but not in the mitotically inactive lesion of dysplastic nodules and early HCC in multistep hepatocarcinogenesis. These findings suggest that homeostatic mechanism of growth control is not totally destroyed in HCC.
Carcinoma, Hepatocellular ; Cell Proliferation* ; Humans* ; Liver Cirrhosis ; Phosphotransferases

This report presents a case of an atypical nodule arising in a hepatocellular adenoma(HCA) in a non-cirrhotic liver of a 42-year-old man. The patient had been relatively healthy until he developed right upper abdominal pain. Abdominal sonography and computerized tomogram revealed a 7.5x7cm sized mass in the right inferior segment of liver. The mass revealed the histologic features of HCA. At near center of the HCA, was found a I cm sized discrete nodule, a nodule within a nodule. The nodule revealed higher cellularity than the HCA and was composed of monotonous hepatocytes with an increased nuclear-cytoplasmic ratio, resembling atypical adenomatous hyperplasia. Interestingly, the atypical nodule showed a focal pseudoacinar arrangement of tumor cells. The histologic features of the atypical nodule arising in HCA may the morphological sequence of transformation from HCA to hepatocellular carcinoma
Carcinoma, Hepatocellular