Argentaffin cells, intestinal metaplasia and antral metaplasia in carcinoma of the gall bladder

The occurrence of argentaffin cells, intestinal metaplasia, and antral metaplasia has been studied in 20 gall bladders with carcinomas, in a papilloma, and in 20 specimens of cholelithiasis. Argentaffin cells were present in six carcinomas, but in only one specimen were they present in large numbers. Only one adenocarcinoma contained occasional argyrophil cells and no argentaffin or argyrophil cells were seen in the papilloma. Five of the 20 specimens of cholelithiasis contained occasional argentaffin cells. Intestinal and antral metaplasia were found in four carcinomas, in the papilloma, and in seven of the 20 specimens of cholelithiasis. It is suggested that metaplastic changes may play a role in the pathogenesis of carcinoma of the gall bladder.     

Expression of MUC1 and MUC2 mucin core proteins and their messenger RNA in gall bladder carcinoma: an immunohistochemical and in situ hybridization study

Expression of mucin core protein MUC1 and MUC2 was examined at the protein and mRNA level in 55 cases of carcinoma and 20 of dysplasia, and in 15 non-dysplastic epithelia of the gall bladder. In non-dysplastic epithelium, MUC1 protein was not expressed, while in dysplasia, MUC1 was focally expressed in ten cases, particularly in those associated with carcinoma. In carcinoma, MUC1 was expressed heterogeneously, and the frequency and extent of MUC1 expression increased with histological dedifferentiation. MUC1 was found on the apical cell surface and also in the cytoplasm in well- and moderately-differentiated carcinoma, and on the cell border in poorly-differentiated cases. In infiltrative regions, MUC1 expression was more predominant and MUC1 frequently leaked outside the foci of carcinoma. By contrast, MUC2 was focally expressed in non-dysplastic as well as in dysplastic epithelia and more frequently in well-differentiated adenocarcinoma. MUC2-positive cells resembled goblet cells, whether in non-dysplastic epithelium, dysplasia or carcinoma. Cell proliferative activity was higher in MUC1-positive than in MUC1-negative carcinoma cells. Distributions of MUC1 and MUC2 mRNA signals and of MUC1 and MUC2 proteins were similar in carcinoma and dysplasia. These results suggest that MUC1 expression by gall bladder carcinoma may reflect histological dedifferentiation, increased proliferative activity, and invasiveness, while MUC2 expression is related to lower proliferative activity and reflects some differentiation towards goblet cells; and that MUC1 expression in gall bladder dysplasia reflects malignant transformation. Copyright © 1999 John Wiley & Sons, Ltd.     

A study of vesical adenocarcinoma, intestinal metaplasia and related lesions using mucin histochemistry

Biopsy and autopsy material from the urinary bladder was studied using PAS and PAS-D techniques to identify glycogen and neutral mucins, the alcian blue/high iron diamine method to distinguish sialo- and sulphamucins and the PB/KOH/PAS technique to localize O-acylated sialomucins. All of 10 examples of normal urothelium and both of two cases of transitional carcinoma in situ contained glycogen, but no mucin. Other lesions displayed one of two patterns of mucin production: the extracellular mucin seen focally in 17 cases of cystitis cystica consisted of sialo- and/or neutral mucins only, a pattern also displayed by mucins produced in 10 of 13 examples of transitional cell carcinomas and by three of nine tumours purely or in part adenocarcinomas. The intracellular mucins expressed in five of the 17 cases of cystitis glandularis and in all of eight cases of frank intestinal metaplasia with goblet cells displayed a colonic phenotype, with production of O-acylated sialomucins. A similar profile was expressed by six adenocarcinomas and this included tumours likely to be of vesical and also of urachal origin. It is concluded that identification of O-acylated mucins cannot distinguish between primary bladder tumours and metastases from a colonic primary, or between carcinomas of vesical and urachal origin.     

Hepatobiliary cystadenocarcinoma with cystadenoma elements of the gall bladder in an old man

Hepatobiliary cystadenoma and cystadenocarcinoma of the gall bladder have rarely been reported. An 88-year-old Japanese man was admitted to our clinic because of hypochondralgia and jaundice. Imaging techniques revealed hemobilia and a multilocular cystic tumor in the fundus of the gall bladder, and cholecystectomy was performed. Grossly, the tumor (3.5 x 3 x 3 cm) was multicystic, containing seromucous fluid. The tumor was located in the fibromuscular layer and subserosa of the gall bladder fundus, and protruded into the serosal surface, not into gall bladder lumen. The mucosa appeared free of tumor involvement, and no gall stones were recognized. Microscopically, the tumor was located in the fibromuscular layer, subserosa and tiny focus of the mucosal surface. The tumor consisted of mucin-rich benign columnar cells, dysplastic mucous cells, malignant papillotubular cells and invasive carcinoma cells. Malignant and atypical tumor cells were located in the center of the tumor and in the tiny area of the mucosal surface, while benign tumor cells were located in the peripheral portions of the tumor and in the serosal side. Neither ovarian stroma-like mesenchymal stroma nor an oncocytic change in tumor cells was recognized. Non-tumorous gall bladder showed chronic cholecystitis. Immunohistochemically, benign and carcinoma cells were positive for cytokeratins, epithelial membrane antigen, CA19-9, MUC1, MUC5AC and MUC6, and carcinoma cells were also positive for carcinoembryonic antigen and p53 protein. The present case indicates that hepatobiliary cystadenocarcinoma without mesenchymal stroma may occur in the gall bladder of old men, and suggests that hepatobiliary cystadenoma without mesenchymal stroma may transform into hepatobiliary cystadenocarcinoma in the gall bladder.     

Mucin histochemistry and lectin binding sites in intestinal metaplasia of the urinary bladder

We report a case of intestinal metaplasia of the bladder urothelium associated with dysplastic foci and a transitional cell carcinoma. A mixture of sialomucins, O -acetylated sialomucins and sulphomucins was found in the goblet cells. Neuraminidase resistant binding of the lectin peanut agglutinin was demonstrated in the brush border of columnar cells in intestinal metaplasia and diffusely in columnar cells in dysplastic foci. The histochemical findings are compared with those described in normal, dysplastic and neoplastic colonic mucosa.     

Morphological changes in human gall bladder carcinoma cell line-NOZ due to epirubicin and doxorubicin

Epirubicin is widely used in various cancer therapies because its side effects and less than those of doxorubicin. We compared the direct effects of doxorubicin and epirubicin to cellsin vitro. In this study, we used the human gall bladder carcinoma cell line-NOZ. We evaluated the cytocidal effects using a DNA fluorimetric assay with fluorochrome Hoechst 33342. The addition of epirubicin in a culture medium showed stronger cytocidal effects than the addition of doxorubicin. Morphologically, after treatments with the two drugs, cells were enlarged, large vacuoles appeared in the cytoplasm, and concentrated microvillus-like structures due to doxorubicin were observed by transmission electron microscopy. This study was presented at the 25th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Matsumoto, September 28–30, 1993.     

Ultrastructural changes in the mucosa of the gall bladder during temporary experimental ischemia

Temporary ischemia of the gall bladder was produced in rabbits by application of a silk ligature to the cystic artery. Histological examination revealed vascular disturbances, consisting of hyperemia, stasis of blood, and focal hemorrhages. Electron-microscopic investigation showed an increase in the number of dark epithelial cells, widening of the intercellular space, and loosening of the structure of the basement membrane with the formation of defects in it and invagination of epithelial cells into the submucosa. The most marked changes were found after occlusion of the cystic artery for 30 min on three occasions. The severity of the destructive changes depend not so much on the duration of ischemia as on the number of occlusions.Department of Pathological Anatomy, Stomatological Faculty, Medical Stomatological Institute, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR, A. I. Strukov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 4, pp. 489–492, April, 1976.     

Mechanism of the inhibitory action of oxytocin on transport of isotonic fluid through the gall bladder epithelium

The effect of oxytocin on the intensity of absorption of Ringer's solution by the epithelium of the isolated frog gall bladder and on the total Mg-, Na-, K-ATPase activity in its cells was studied. In doses of 0.5–20 m.u/ml, added on the side of the serosal surface of the organ, oxytocin reduced the intensity of isotonic fluid transport and the Na, K-ATPase activity of the epithelial cells of the gall bladder; Mg-ATPase activity was unchanged under these conditions. With an increase in the oxytocin concentration the values of the parameters studied fell exponentially. It is concluded that inhibition of the transport function of the gall bladder epithelium by oxytocin is connected with its inhibitory action on the Na, K-ATPase of the epithelial cells.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Gorev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 11, pp. 10–12, November, 1974.     

The L1 antigen and squamous metaplasia in the bladder

The L1 antigen was investigated as a marker of squamous differentiation in urothelium using a monoclonal antibody Mac387, and the results were compared with the expression of high molecular weight cytokeratins. L1 antigen was consistently demonstrated in all instances of partial and complete squamous metaplasia and in squamous carcinomas. In contrast, pure transitional cell carcinomas (except one with minor focal staining), adenocarcinomas and normal and hyperplastic urothelium did not label. In a few squamous carcinomas in situ, the pattern of labelling obtained with Mac387 was different from that seen in invasive squamous carcinomas and metaplasias. Compared with high molecular weight cytokeratins, the expression of L1 was more intense in areas of squamous differentiation. L1 expression, as identified by antibody Mac387, may therefore serve as a useful marker of squamous differentiation in urothelial lesions.     

Molecular evidence for progression of nephrogenic metaplasia of the urinary bladder to clear cell adenocarcinoma

Nephrogenic metaplasia or nephrogenic adenoma of the urinary tract may present a diagnostic challenge in surgical pathology practice. Previous case reports suggest the possibility of nephrogenic metaplasia progressing to clear cell adenocarcinoma, but a malignant potential of nephrogenic metaplasia is generally not acknowledged. A case of a 70-year-old female patient with multiple recurrences of nephrogenic metaplasia of the urinary bladder and subsequent development of clear cell adenocarcinoma is described. Immunohistochemical studies help to differentiate the 2 entities. Results of molecular studies, particularly comparative genomic hybridization analysis, suggest clonal evolution of nephrogenic metaplasia to clear cell adenocarcinoma in this case.     

Defective development of the gall bladder and cystic duct in Lgr4‐ hypomorphic mice

Leucine‐rich repeat (LRR) ‐containing G protein coupled receptor (LGR) family members are characterized by the presence of a seven‐transmembrane domain and LRR motifs. We describe a new function for Lgr4 in the development of the gall bladder and cystic duct and in the epithelium–mesenchyme interaction. Lgr4 expression was observed in the gall bladder epithelium when the gall bladder primordium elongated ventrally. Although Lgr4 hypomorphic mutant (Lgr4^Gt/Gt) embryos developed a normal gall bladder bud at embryonic day (E) 10.25, no further elongation was observed at later stages. At E12.5, the mesenchyme surrounding the gall bladder had completely disappeared in Lgr4^Gt/Gt embryos, while the gall bladder remained unelongated. Neighboring tissues such as liver and pancreas were unaffected, as revealed by expression of marker genes. This is the first report of a mutant mouse that lacks a gall bladder and cystic duct without affecting the other tissues that derive from the same hepatic diverticulum. Developmental Dynamics 238:993–1000, 2009. © 2009 Wiley‐Liss, Inc.     

肝炎和肝硬化患者胆囊B超改变的观察与分析

目的研究肝炎肝硬化患者胆囊彩色B超声像图变化，并探讨其临床意义。方法采用彩色超声诊断仪对139例肝炎和肝硬化患者及65例非肝炎体检者进行胆囊超声检查。结果慢性肝炎、重型肝炎、肝硬化患者组与非肝炎对照组彩色B超胆囊异常率比较均差异非常显著（P〈0．01）。慢性肝炎与重型肝炎、肝硬化组之间胆囊异常率也存在明显的差异（P〈0．05）。结论慢性肝病患者胆囊异常并不是胆囊本身炎症所致，胆囊声像图的改变对判断肝脏实质性病变的严重程度及指导临床治疗有一定的作用。     

Adenomatous hyperplasia of the rete testis in the undescended testis.

Multiple foci of micronodular or tubulopapillary structures were noted in the rete testis of 13 cases of undescended testes. These structures were lined by low columnar to cuboidal epithelium, showed back-to-back crowding, and were supported by a thin lamina propria. These changes, referred to as adenomatous hyperplasia of the rete testis, appear to be a frequent finding in the undescended testis. An age-matched control group did not show any of these features.     

Gastric-type mucin and TFF-peptide expression in Barrett's oesophagus is disturbed during increased expression of MUC2

AIMS: Barrett's oesophagus constitutes metaplastic epithelium, often diagnosed by mucin histochemistry. We determined the mucins and trefoil factor family (TFF)-peptides that were expressed in Barrett's oesophagus, in order to study changes in protein expression in early stages of Barrett's oesophagus development. METHODS AND RESULTS: Biopsy specimens of 71 Barrett's oesophagus patients were collected, and sections were stained for secretory mucins by histochemistry. Immunohistochemistry was performed for secretory mucins (MUC2, MUC5AC, MUC5B, MUC6), TFFs (TFF1, TFF2, TFF3), and proliferation (Ki67). Protein expression in the tissue was measured semiquantitatively. MUC5AC and TFF1 showed high levels and strong colocalization in the surface epithelium, whereas MUC6, MUC5B and TFF3 were found in the deeper glandular structures. TFF2 was found in both surface and glandular epithelium. The co-ordinate expression patterns of these six markers were similar to gastric antrum epithelium. MUC2 expression was ubiquitously associated with goblet cells within intestinal metaplasia, occurring in 68% of patients, and was correlated with increasing proliferation in the epithelium. CONCLUSIONS: Virtually all cells in Barrett's oesophagus epithelium displayed a secretory phenotype, demonstrating a co-ordinate gastric-type MUC and TFF expression. When MUC2 expression was more pronounced, the expression patterns of the other MUCs and the TFFs were increasingly disturbed. MUC2 expression may constitute a marker for early change in the phenotype of Barrett's oesophagus as a precancerous lesion.     

Tubal metaplasia: A cytologic study with comparison to other neoplastic and non-neoplastic conditions of the endocervix

Tubal metaplasia of the endocervix (TME), a condition that may be con/used morphologically with glandular neoplasia, is frequently found in cone or hysterectomy specimens. To determine the frequency of detecting TME in cytologic smears, we retrospectively reviewed 28 Papanicolaou (Pap) smears from 22 women (mean age 39.1 yr; range 25-60 yr) with histologically proven TME. Our criteria for TME were the presence of two cell types in addition to endocervical secretory cells, i.e., peg cells (cells with dark and granular cytoplasm and elongate nuclei) and ciliated cells. All women had cervical cytology specimens obtained with an endocervical brush shortly before the procedures in which TME was diagnosed, and five also had at least one post-procedure smear. Of 20 smears with an adequate, non-neoplastic endocervical component, TME was found in 2 (10%). In these two, TME cells constituted 10% and < 5% of all the glandular cells, respectively, and the percentage of ciliated cells in the TME was approximately 25% and 75%. In conclusion, TME was noted infrequently (10%) on the cervical cytosmears of women with histologically-proven TME. This result corresponds to the histologic finding that TME typically involves the upper endocervix and glandular epithelium, with only 13% of the women having TME on the surface of the lower endocervix. Atypical glandular cells on cervical cytology are a problem for clinicians and pathologists alike. The differential diagnosis of such atypia, including TME, cells of the lower uterine segment, squamous intraepithelial lesion in glands and glandular neoplasia, is discussed.