Metaplasia Of Gallbladder Research Articles

An Immunohistochemical Profile of the So-called Bile Duct Adenoma

The so-called bile duct adenoma and peribiliary glands are characterized by the expression of two foregut antigens (designated D10 and 1F6) and secretion of acid mucin. On account of this similarity in phenotype and their frequent close association with a large caliber bile duct, it was earlier suggested that bile duct adenoma represent a peribiliary gland hamartoma. Here, we compare the expression of 13 tissue antigens in bile duct adenomas, other benign bile duct lesions, and various foregut-derived tissues, to further investigate the bile duct adenoma phenotype and pathogenesis. Antibodies to 4 intestinal mucins, 3 cytokeratins, and CDX2, were not informative. Five foregut antigens (D10, 1F6, MUC6, MUC5AC, and TFF2) and secretion of acid mucin were of use in distinguishing bile duct adenoma from other hepatic lesions. 1F6 and MUC6 were normally present in bile ductules and canals of Hering, whereas the epithelium lining the larger bile ducts stained focally for D10, MUC5AC, MUC6, or TFF2 in, respectively, 21%, 36%, 43%, and 100% of the livers examined. Thirty-six bile duct adenomas examined were distinguished by expression of MUC6 (94% of bile duct adenoma), MUC5AC (90%), TFF2 (80%), D10 (67%), and 1F6 (61%), and varying degrees of acid mucin secretion (100%). Of 30 bile duct adenoma tested for all 5 antigens, 40% expressed all 5, 27% expressed 4, 17% expressed 3, 13% expressed 2, and 1 expressed only MUC6. Peribiliary glands invariably expressed D10, 1F6, MUC6, and TFF2, and showed acid mucin secretion, with MUC5AC present in the inflamed peribiliary glands of 3/4 livers with recurrent pyogenic cholangitis, but none of the glands of the other 23 normal or diseased livers tested. The acini of pyloric gland metaplasia in gallbladder and terminal ileum also stained for D10, 1F6, MUC6, and TFF2, with MUC5AC focally present in the gastric foveolar metaplasia overlying the pyloric gland metaplasia but not in the metaplastic glands. MUC6 was expressed in 92% of ductular reactions, 1F6 in 42%, and D10 in 25%. Focal expression of MUC6, or TFF2 was observed in 1 or 2 examples of 14 von Meyenburg complexes and 6 polycystic livers, with staining for acid mucin generally obvious only in the glycocalyx of the epithelium of these two types of lesions. The distinguishing feature of so-called bile duct adenoma is their display of the same phenotype as pyloric gland metaplasia. It is concluded that they develop as a localized biliary healing response equivalent to the function of a peribiliary gland or pyloric gland metaplasia in the foregut.

Intestinal metaplasia in gallbladder correlates with high amylase levels in bile in patients with a morphologically normal pancreaticobiliary duct

We reported previously that intestinal metaplasia in the gallbladder is strongly associated with expression of caudal-related homeobox transcription factor Cdx2. It has been documented that occult pancreatobiliary reflux, even in the absence of pancreaticobiliary maljunction, is associated with elevated risk of biliary malignancy. We ascertained the correlation between intestinal metaplasia in the gallbladder and occult pancreatobiliary reflux. In 196 patients with a normal pancreaticobiliary ductal arrangement who had undergone laparoscopic cholecystectomy, we performed intraoperative cholangiography and measured amylase levels in bile sampled from the gallbladder. The cutoff value for high cystic amylase was defined as a biliary amylase level higher than the normal upper limit of serum amylase (215 IU/L). We also retrospectively reviewed the cholecystectomized tissue specimens to investigate the presence of intestinal metaplasia and expression of Cdx2. Then, we explored the relationship between intestinal metaplasia in the gallbladder and occult choledocho-pancreatic reflux. Intestinal metaplasia was found in 16.8% (33/196) of the gallbladders. The prevalence of choledocho-pancreatic reflux revealed by intraoperative cholangiography was not significantly different between cases with intestinal metaplasia (5/33, 15.2%) and those without (25/163, 15.3%; P = .81). However, in cases with intestinal metaplasia, the rate of high cystic amylase (13/33, 39.4%) was significantly higher compared with cases without intestinal metaplasia (26/163, 16.0%, P = .005). In conclusion, intestinal metaplasia in the gallbladder is significantly correlated with high amylase levels in bile in patients with a morphologically normal pancreaticobiliary ductal arrangement.

Helicobacter pylori in areas of gastric metaplasia in the gallbladder and isolation of H. pylori DNA from gallstones

To assess if the areas of gastric metaplasia in the gallbladder are colonised by Helicobacter pylori and to conduct a molecular study of gallstones for presence of H. pylori DNA. Sections from 111 gallbladders with evidence of gastric metaplasia on H&E and Alcian blue-periodic acid-Schiff (pH 2.5) stain were stained with Loeffler's methylene blue and Warthin Starry stain for demonstration of H. pylori. Presence of H. pylori was confirmed by immunohistochemistry. Formalin fixed mucosal tissues and gallstones from 11 cases showing heavy colonisation were subjected to molecular analysis. Helicobacter pylori was present in 50 of 111 (45%) sections with gastric metaplasia. Areas adjacent to gastric metaplasia in gallbladder showed acute inflammation (6%) and lymphoid follicle formation in 58% of cases with H. pylori that were significantly higher than those seen in sections without H. pylori. In molecular study, 8 of 11 gallstones showed 16S rDNA. Amplification of material from one stone showed positivity for atpA, efp, mutY, ppa, trpC, UreI and vacA genes. Phylogenetic affiliation study of the isolates indicated that H. pylori sequence from the gallstones clustered with Indian strains of H. pylori. No considerable difference was observed in phylogenetic affiliations of eight stones studied. H. pylori colonises areas of gastric metaplasia in gallbladder producing histological changes similar to those seen in gastric mucosa. Isolation of H. pylori DNA from gallstones further support its presence in the gallbladder.

Inappropriate mucin production in gall bladder metaplasia and neoplasia–an immunohistological study

This study demonstrates the presence of three antigens in glandular metaplasia occurring in patients with cholecystitis and cholelithiasis: specifically carcinoembryonic antigen (CEA), large intestinal mucin antigen (LIMA) and small intestinal mucin antigen (SIMA). These antigens could not be detected in normal gall bladder mucosa or in squamous metaplasia of the gall bladder. The occurrence of the three intestine-associated antigens in three carcinomas was irregular. In one mucinous carcinoma, only SIMA could be demonstrated. In one adenocarcinoma, SIMA was present in small areas of mucinous change, whilst CEA was present in the non-mucinous malignant tissue. In a mixed mucinous and non-mucinous adenocarcinoma with widespread dissemination, the three antigens were present both in the primary tumour and the metastases. These observations suggest that all forms of glandular metaplasia of the gall bladder are intestinal in nature and at least a proportion of gall bladder carcinomas are of an intestinal type. Finally they provide further immunological evidence that glandular metaplasia of the gall bladder should be considered a pre-malignant condition.

‘Haematoxylin and eosin’ with a difference (but OH, what a difference!)

Supplementing the standard H & E section with alcian blue gives valuable additional information in many cases. It may show that a particular carcinoma metastasis is mucin-producing; draw attention to mucinous degeneration of vessels, tumours and other tissues, or to some forms of amyloid; identify mast cells in skin and other sections; pinpoint cartilage cells in osteoid or tumours; reveal intestinal metaplasia in gall bladder or gastric mucosa; and many hundreds of other applications. The difficulty in practice is that the resultant section may not look sufficiently like the ordinary routine H & E to be acceptable for everyday use. Careful planning of, and the order in which, the various solutions are used, together with a technique that favours progressive staining rather than differentiation to obtain good contrast, has enabled this difficulty to be overcome. The resultant method may be used as an automated procedure on a staining machine; or for individual sections stained by hand. The final result looks just like an H & E section, except that mucopolysaccharides stain a clear blue, that is optically quite distinct from the grey-blue to grey-black of nuclei and other haematoxyphil material. Omission of the first stage results in a classical H & E-type section, with good differentiation of eosinophil from neutrophil polymorphs, muscle from collagen and so on. Reversing the order of Alcian Blue and Haematoxylin (HABET) results in stronger alcian blue staining of sulphomucins. This variant identifies the histiocytes in Whipple's disease, and distinguishes differences in intensity of staining between the mucus of small and large intestine—but connective tissue sulphomucin is so prominent that it may conceal important detail in some sections, and is likely to present an unfamiliar appearance to the pathologist whose previous experience has been limited to H & E. The ABHET method (Alcian Blue, ferric alum, Haematoxylin, and Erythrosin with Tungstophosphoric acid) is recommended as <i>the</i> routine stain for all biopsy and post-mortem material, rather than as a special stain for occasional use. Substitution of eosin Y for erthrosin may be preferred as this gives a more transparent section with less dominant reds.