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

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.

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

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

Forty-nine lobectomized hepatocellular carcinomas(HCC) were classified according to the gross anatomical features. Because the presence of cirrhosis in the remaining liver has a good clinico-pathological implication, cases of HCC were divided into non-cirrhotic(non-LC) and cirrhotic(LC) groups. In both groups, the tumors themselves belonged to either expanding, focal spreading, spreading or mixed type. Another special type, which has been called a "diffuse type" is added in the LC group with the name of "cirrhotomimetic type" Among 49 cases, 21 belonged to the non-LC group and 28 to the LC group. Most common was expanding type(20 cases, 40.8%), which was followed by spreading(32.7%), focal spreading(16.3%), mixed(6.1%) and cirrhotomimetic(4.1%) types. Expanding type of the LC group was the single most common type(13 cases, 26.5%). The accordance rate of gross typing was 0.94. Tumor masses of the LC group showed a greater tendency of having a fibrous capsule(60.7%) and a lobulated cut surface(82.1%), in contrast to those of the non-LC group (28.6% and 42.9% respectively). The patient's age and the HBsAg seropositivity were not different between the groups and between the types. Increased serum level of AFP was particularly frequent in the spreading type(81.3%) of both groups and in the cirrhotomimetic type(100%).
Carcinoma, Hepatocellular

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

Kupffer cells are tissue macrophages (histiocytes) fixed in hepatie sinusoids. Since malignant hepatocytes are the only tumor parencymal cells of the hepatocellular carcinoma, theoretically there are no Kupffer cells within the hepatocellular carcinoma. To clarify whether it is true or not, 12 cases of hepatocellular carcinoma of the trabecular type with some extents of the non-neoplastic surrounding liver were subjected to immunoperoxidase staining for lysozyme and S-100 protein and the results are as follows. 1) Kupffer cells were stained positively by the immunoperoxidase staining for lysozyme but not for S-100 protein, indicating that they are monocyte derived macrophages. 2) Kupffer cells were also present within the hepatocellular carcinoma, but were 2-7 times fewer within the hepatocellular carcinoma than in the non-neoplastic areas (p<0.05). 3) The non-neoplastic hepatic tissue of patients with serum HBsAg shows a tendency to have more kupffer cells than those without HBsAg.
Carcinoma, Hepatocellular