Eight patients with ulcerative colitis complicated by carcinoma were investigated histopathologically on their resected colorectal specimens. Four patients carried multiple tumors, another four patients a solitary tumor. The age at the onset of the colitis in patients with multiple carcinoma was younger in average (27 years old) than that in the patients with a solitary carcinoma (45 years old). Duration of the disease before surgery exceeded 10 years in six of the eight patients. A total of eight tumors of 10 mm or more in dimension were found in four multiple cases, six of them being located in the rectum. These tumors presented peculiar macroscopic features, such as villous, putty-like, nodular, or flat, and were advanced histopathologically, well or moderately differentiated adenocarcinomas in most cases. Six of the eight accompanied areas of epithelial dysplasia adjacent to the carcinoma, the border between carcinoma and dysplasia being vague in three of the six. All multiple cases showed active changes of ulcerative colitis or chronic inflammatory processes such as thickening of the muscularis mucosa, submucosal fibrosis and Paneth cell metaplasia in the crypts. Furthermore, all multiple cases had minute adenocarcinomas, less than 10 mm in diameter, the tumor being restricted to the mucosa or to the mucosa and submucosa. Four of the nine minute carcinomas coexisted with epithelial dysplasia, suggesting that carcinoma developed from dysplasia. On the contrary, the remaining carcinomas carried no dysplasic area with a possibility that carcinoma developed also from nondysplastic atrophic mucosa. Three of the four solitary tumors were conventional adenocarcinomas associated with chronic inflammatory or dysplastic change in the bowel. The specific stainings by lectins and high-iron-diamine (HID) gave no appreciable help in diagnosing the epithelial dysplasia because of unsettled staining results. A large number of argyrophil cells were present in dysplastic epithelia, although the number of such cells was small in carcinomas.
The authors present two cases of anomalous pancreaticobiliary duct union that occurred in a mother and her daughter; the former was associated with gallbladder adenocarcinoma, and the latter, gallbladder adenoma with high grade dysplasia. This disorder has been considered a developmental anomaly, although the true etiology has not been known. This is the first report of familial occurrence of this anomaly, and it may point to the presence of a genetic factor in its development. Another implication is the presence of histological features which suggest the possible sequence of anomalous pancreaticobiliary duct union to intestinal metaplasia to adenoma or dysplasia to cancer of the gallbladder.
Background Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiveness in Asian patients with MS and NMO. Methods/Principal Findings Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD), six with MS, and 20 with other neurological diseases (OND). Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) and chronic inactive (n=23). Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090). Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296). Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients. Conclusions These findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.
