Ten cases of intrahepatic cholangiocarcinoma showing a highly differentiated adenocarcinoma mimicking ductal plate malformation (DPM) are reported. The patients included 7 males and 3 females with an average age of 69.5 years. Six cases were associated with chronic liver disease and the remaining 4 cases showed mild fatty change in the parenchyma and/or minimal to mild portal inflammation. Grossly, the tumor was a single nodule 1.5 to 6.6 cm in diameter, and was whitish and solid without a fibrous capsule. Microscopically, the tumor was composed of many vague, small nodular carcinomatous areas with desmoplastic reactions, and neoplastic glands had an irregularly dilated lumen lined with a single layer of cuboidal or low columnar carcinoma cells and irregular protrusions and bulges, resembling DPM. At its border, the carcinoma seemed to replace the non-neoplastic hepatic lobules or regenerative nodules. The central parts of the tumor were variably hypocellular and fibrotic. Although these carcinomas were negative for mucin and HepParI, they were frequently positive for CK19, epithelial cell adhesion molecule, and epithelial membrane antigen. Neural cell adhesion molecule was also expressed variably. The Ki-67 labeling index was <10% and p53 was scarcely expressed. In conclusion, a new subtype of intrahepatic cholangiocarcinoma with predominant DPM pattern was identified.

Our results suggest that vasculo-Behçet disease should be classified as a neutrophilic vasculitis targeting the vasa vasorum. Aneurysm formation may be related to degeneration of arterial wall caused by inflammation of the vasa vasorum.

We report a case of extramammary Paget's disease with underlying adenocarcinoma simulating breast carcinoma of the vulva. An 82-year-old woman was found to have a 5 x 3-cm bulky tumor located in the left labium major, infiltrating to the clitoris, left labium minor, and left lateral tissue of the vulva. Small biopsy of the vulva showed intraepidermal proliferation of Paget cells. The patient underwent wide local excision of the vulvar tumor and dissection of left inguinal lymph nodes. Histopathological examination of the resected specimens revealed that Paget cells were distributed singly or tended to form small nests in the epidermis, and that association of these cells with the underlying carcinoma invading to the subcutis could be seen. The underlying carcinoma was composed of squamoid solid nests with central necrotic debris, mimicking 'comedocarcinoma' of the breast. In other areas, the tumor cells were present in tubular formations and solid cords reminiscent of invasive ductal carcinoma of the breast. Immunohistochemically, the Paget cells and the underlying carcinoma cells were positive for carcinoembryonic antigen, epithelial membrane antigen, estrogen receptors, and glandular keratins except for CK 20. We speculate that our case is vulvar Paget's disease presenting as a manifestation of underlying breast carcinoma of the vulva, which might have arisen from either the ectopic breast tissue or anogenital mammary-like glands.

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are mucin-producing neoplasms of the main and/or branch pancreatic ducts. To assess differences between various IPMN subtypes, immunohistochemical markers of gastric surface mucous cells (MUC5AC), gastric gland mucous cells (MUC6 and GlcNAcα1→4Galβ→R), gastric pyloric and duodenal epithelial cells (PDX1), intestinal cells (MUC2 and CDX2), small intestinal cells (CPS1) and large intestinal cells (SATB2) were evaluated in 33 surgically treated IPMNs. MUC2 expression classified IPMNs into gastric (n=17), intestinal (n=8) and mixed gastric and intestinal type (collision=7, composite=1). No differences in age or sex were observed among these types. MUC5AC and PDX1 were expressed in all IPMNs. MUC6 expression was higher in gastric and mixed types than in intestinal type. GlcNAcα1→4Galβ→R was detected in gastric and mixed type, but not in intestinal type. MUC2 and CDX2 expression were higher in intestinal type than gastric and mixed type. CPS1 expression was higher in intestinal type than gastric type. SATB2 was not observed in any IPMNs. Frequent abrupt transition between the two IPMN types in mixed-type IPMNs was observed. Gastric pyloric and small intestinal differentiation are characteristic of gastric and intestinal type IPMN, respectively, and these two IPMN types may have distinct pathogenesis.

Although oxygen is essential for promoting energy metabolism and for enhancing cell proliferation, early mouse embryos are very sensitive to high oxygen concentration. Because the tissue-specificity and sequential changes of the expression of antioxidative enzymes in rodent embryos have not been investigated systematically, we examined the ontogenesis of thioredoxin (TRX) and glutaredoxin (GRX) in mouse embryos and fetuses by using immunohistochemical methods. These compounds were found to be localized in most tissues examined, with some tissue specificity and temporal sequence. In many tissues, both TRX and GRX began to be expressed at embryonic day 11 (E11) or E13 and appeared to increase later in development, but the heart and great vessels of E8.5 embryos were already positive for their immunoreactivity. The stage at which the antioxidative enzymes begin to be expressed seems to coincide with the stage at which rodent embryos acquire the capacity of aerobic energy metabolism. Although TRX and GRX were co-localized in many tissues and showed similar sequential changes of expression, their expression patterns were different in the fetal cartilage, suggesting that they may play different roles in endochondral ossification. Their immunoreactivity was not homogeneous in the liver and the epithelium of uriniferous tubules, probably because their expression is associated with the proliferating and metabolic activities of the cell, as suggested by previous investigators. These results suggest that TRX and GRX play some tissue-specific roles in mammalian morphogenesis as well as general roles as antioxidant enzymes.