Scirrhous hepatocellular carcinoma (SHCC) is a rare variation of HCC, for which characteristics of tumor cells and the fibrotic stroma have not been clarified in detail. The present study was therefore carried out to elucidate cytological features of tumor and stromal cells and components of the stromal extracellular matrix in 15 SHCC patients undergoing hepatectomy without preoperative transarterial embolization. Diagnosis was on the basis of a scirrhous histological pattern exceeding 50% of the tumor area. Expression of cytoplasmic and extracellular matrix proteins was compared among SHCC, HCC and intrahepatic cholangiocarcinoma (ICC) cases with immunohistochemical staining. The lesions could be histologically divided into radiating and sinusoidal types. Common stromal components of SHCC and ICC were collagen types I and III. There was no expression of laminin-5 in the stroma of SHCC, but it was present in almost all ICC cases. Tenascin-C expression was significantly lower in the SHCC cases and its distribution differed between SHCC and ICC. Matrix metalloproteinase-7 (MMP-7) expression was significantly higher in SHCC compared with HCC. Almost all stromal cells were alpha-smooth muscle actin-positive both in SHCC and ICC, whereas glial fibrillary acid protein (GFAP)-positive stromal cells were significantly more increased in ICC than in SHCC. SHCC clearly differed from HCC with respect to collagen types I, III and MMP-7 expression, and from ICC with regard to stromal components including laminin-5, tenascin-C and GFAP(+) stromal cells.

These results suggest that fasudil has beneficial effects on retinal vascular complications associated with chronic hypertension.

We report a case of congenital telangiectatic focal nodular hyperplasia, a rare variant form of the disease. The patient was a 2-month-old boy whose parents noticed abdominal distention about 2 weeks after birth, and ultrasonogram revealed a large mass in the liver. He underwent right lobectomy, and gross findings showed an ill-defined mass without any central scar. Histologic findings demonstrated proliferating hepatocytes without atypia arranged in cords of 1- or 2-cell thickness with marked sinusoidal dilatation and extramedullary hematopoiesis. In addition, a significantly increased Ki-67 labeling index in the tumor compared with non-tumor liver cells, and cytogenetic analysis of 23 G-banded metaphase preparations revealed 3 abnormal karyotypes, suggesting hyperplastic or neoplastic features. To the best of our knowledge, the present case is only the third documented case of congenital telangiectatic focal nodular hyperplasia.

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Mild periodic acid-Schiff (mPAS) staining can discriminate non-Oacetylated (mPAS-positive) from O-acetylated (mPAS-negative) epithelial sialoglycoproteins in human colonic mucosa, allowing the three haplotypes expressed from a single polymorphic autosomal gene (oat) to be distinguished. In heterozygotes, we previously demonstrated wholly mPAS-positive (stem cell mutated ) crypts and clusters of two or more mPAS-positive crypts to be significantly increased with duration of ulcerative colitis. To establish whether such an increase in the number of mutated crypts with age also occurs in normal individuals or in cases with diverticulosis, the O-acetylation phenotype in the non-cancerous colonic mucosa of 47 sporadic colorectal cancer patients who were heterozygotes for oat was tested with mild-PAS staining. PAS-positive crypts were assessed histologically in relation to age and compared between the left (sigmoid colon and rectum) and right (cecum and ascending colon) sides of the colorectum. I t is widely accepted that the likelihood of developing sporadic colorectal carcinoma increases with age.(1-3) Colorectal tumorigenesis is a multistage process, (4) with increased colonic mucosal cell proliferation believed to be important for initiation and subsequent growth, (5,6) acting together with the cumulative effects of protracted exposure to cancer-causing agents. Recently, it was demonstrated that mPAS staining can discriminate non-O-acetylated (mPAS-positive) from O-acetylated (mPASnegative) epithelial sialoglycoproteins. . In fact, the frequency distribution of these three phenotypes in different racial groups, including Japanese and British people, is consistent with that predicted by the Hardy-Weinberg law. (8) This suggests that they result from expression of a single polymorphic autosomal gene (oat) encoding the O-acetyl transferase active in generating colonic sialomucins. Further, the three phenotypes are similar to those seen in C57BL/6 J × SWR F1 mice, where the Dlb-1 gene determines another intestinal mucus glycoprotein phenotype that can be visualized by virtue of Dolichos biflorus agglutinin binding. (9) In this mouse model, discordant crypts are produced in heterozygotes by mutation. The altered crypts seen in humans using the mPAS technique are also similar in morphology to carcinogen-induced crypts with changes in glucose-6-phosphate dehydrogenase expression in the mouse colon, indicating a role for somatic mutations. (10) It is conceivable that somatic mutations of the high acetylator allele in colonic crypt stem cells in heterozygous subjects followed by crypt colonization by mutant progeny leads to conversion of the crypt phenotype from mPAS negative to mPAS positive. In fact, radiotherapy of heterozygotes induces a considerable increase in the mPAS-positive crypt frequency, which subsequently remains significantly elevated for 2-34 years, indicating that crypts with a mutant phenotype are stable. (11,12) Recently, we demonstrated that the number of wholly mPASpositive (stem cell mutated) crypts a...