Characterization of hyperplastic foci observed in surgical specimens of hepatocellular carcinoma

By reviewing previous surgical specimens of hepatocellular carcinoma, 17 cases with hyperplastic foci (HPF) characterized by discernible increase in nuclear densities, could be histologically selected. Nuclear densities of HPF and control hepatic parenchyma were assessed quantitatively by counting the nuclear number of hepatic cells, and proliferating cell nuclear antigen labeling index was measured. HPF occurred multifocally, confined within a lobular unit, smoothly merging into surrounding hepatic parenchyma. Nuclear densities of HPF were 1.71 times greater than those of control hepatic parenchyma. The hepatocytes of HPF also showed significantly higher proliferative activities than those of control parenchyma. In addition, noticeable structural distortions, such as focal trabecular thickening or microacinar formation of hepatocytes, were sometimes observed in HPF. However, these HPF seemed to be distinguished from minute de novo hepatocellular carcinoma (HCC) or intrahepatic HCC metastasis, because of paucity of distinctive atypical changes, and intimate correlation with neighboring hepatocytes. Several adjacent HPF were aggregated to form a much larger unit of a hyperplastic area with loss of fibrous septa of liver cirrhosis. It was suggested that grossly detectable large regenerative nodules are produced via fusion of several adjacent HPF.     

Comparative study of fibrous dysplasia and osteofibrous dysplasia: histopathological, immunohistochemical, argyrophilic nucleolar organizer region and DNA ploidy analysis

Fibrous dysplasia and osteofibrous dysplasia are both benign fibro-osseous lesions of the bone. We retrospectively studied the clinicopathological findings in 90 cases of fibrous dysplasia and 17 cases of osteofibrous dysplasia. In these cases, the expression of proliferating cell nuclear antigen (PCNA) and the presence of argyrophilic nucleolar organizer regions (AgNOR), as well as DNA ploidy, were examined. The bones affected by fibrous dysplasia were the maxilla, femur and frontal bone. Osteofibrous dysplasia occurred exclusively in the tibia or fibula. The average age of patients with fibrous dysplasia (24.0 years) was higher than that of patients with osteofibrous dysplasia (12.9 years). Fibrous dysplasias were divided into four major histological subtypes: Pagetoid, Chinese alphabet, small bone and parallel bone. Bone lining cells, which are known as resting osteoblasts, were seen in some cases of fibrous dysplasia. Cartilage differentiation was not seen in osteofibrous dysplasia. PCNA expression was strongly positive in the nuclei of osteoblasts around the bone trabeculae in osteofibrous dysplasia, but negative in the nuclei of bone lining cells around the bone trabeculae in fibrous dysplasia. The number of AgNOR in osteofibrous dysplasia was slightly higher than that in fibrous dysplasia. Both fibrous dysplasia and osteofibrous dysplasia were diploid. These features suggest that fibrous dysplasia can be differentiated from osteofibrous dysplasia by anatomical site, patient age, histological appearance, cartilage differentiation and PCNA positivity. DNA content by image cytometry is not a useful tool for differentiating these two diseases.     

Argyrophilic nucleolar organizer regions in colorectal malignancy: application of typing by their density

Colorectal neoplasms obtained at colonoscopy were examined by argyrophilic nucleolar organizer region (AgNOR) staining to evaluate the usefulness of AgNOR as a discriminant for malignancy. AgNOR dots were divided into two kinds: 'structures' (larger and less-densely stained) corresponding to the nucleolus, and 'units' (smaller and densely stained) presumed to be true AgNOR within the structure. The number of structures per nucleus did not differ between the adenoma and carcinoma groups, whereas the number of units per nucleus showed a significant difference. However there were several cases showing an overlap between the adenoma and carcinoma groups, leading to a difficulty in deciding whether any given case was benign or malignant. Three types of AgNOR patterns were categorized based on the ratio of units to structure. Type I was defined as the unit being indistinguishable from the structure, Type II as each structure having one to five units, and Type III as at least one structure having six or more units, irrespective of total number of units per nucleus. The colorectal lesions in which more than half of the neoplastic cells showed Type III coincided well with carcinomas histologically diagnosed, with the exception of adenomas with severe atypia. Labeling index of proliferating cell nuclear antigen (PCNA LI) differed between the adenoma and carcinoma groups with a considerable extent of overlap, and correlated to some extent with the AgNOR values. These results showed that the AgNOR staining was useful for determining malignancy and its usefulness appeared superior to PCNA LI.     

Histological and immunohistological findings in biliary intraepithelial neoplasia arising from a background of chronic biliary disease compared with liver cirrhosis of non-biliary aetiology

Aishima S, Iguchi T, Fujita N, Taketomi A, Maehara Y, Tsuneyoshi M & Oda Y (2011) Histopathology 59 , 867–875 Histological and immunohistological findings in biliary intraepithelial neoplasia arising from a background of chronic biliary disease compared with liver cirrhosis of non‐biliary aetiology Aims: Hitherto, biliary intraepithelial neoplasia (BilIN) has been described in chronic biliary disease but rarely in non‐biliary liver cirrhosis (LC). Intraepithelial neoplasia of the pancreas shows alterations in the expression of cell cycle and mucin core proteins. The aim of this study was to evaluate BilIN and reactive biliary lesions in biliary disease and non‐biliary LC. Methods and results: BilIN was found in 51% (33 of 65) of liver tissue cases of biliary disease, and in 11% (34 of 310) of the LC group. Immunohistologically, MUC5AC, an ‘early phase’ protein, and Ki67, reflecting ‘late phase’ expression, were identified with increasing degrees of dysplasia in both groups, but that expression was significantly higher in the biliary disease group. ‘Early phase’ cell cycle proteins, p16 (decrease) and p21 (increase) altered in both biliary and LC groups with increasing degrees of dysplasia. Conclusions: We found BilIN in the large bile ducts of hepatitis B virus‐ and hepatitis C virus‐related LC as well as in cases related to a biliary aetiology. The LC group was significantly less likely to show changes in the expression of MUC5AC and proliferative activity than the biliary group. Alterations in p16 and p21 reflected increasing degrees of dysplasia in both groups.