Histochemistry of glandular metaplasia at the trigone of the urinary bladder in cows.

The epithelium at the trigone of the urinary bladder showed intestinal metaplasia of a colonic type in three Holstein-Friesian cows affected with chronic polypoid cystitis. Except for Ricinus communis (RCA-I), almost all goblet cells in the whole crypt were positive to periodic acid-Schiff (PAS), alcian blue (AB) pH 2.5, AB pH 1.0, periodate borohydride-potassium hydroxide-PAS (PB-KOH-PAS), Ulex europaeus (UEA-I), Triticum vulgare (WGA) and Arachis hypogaea (PNA) after neuraminidase digestion. This result indicated that most goblet cells contained acidic and neutral glycoconjugates as O-acetylated sialomucin, L-fucose, N-acetyl-glucosamine, neuraminic acid residues and sialic acid-galactose dimers and were devoid of beta-D-galactose. The goblet cells at the surface in the upper half of the crypt contained both sulpho- and sialo-mucins with N-acetyl-galactosamine residues by AB (pH 2.5)-PAS, high iron diamine (HID)-AB (pH 2.5), Dolichos biflorus (DBA) and Glycine maximus (SBA) reactions. On the other hand, the lower goblet cells were found to contain predominantly sulphated mucins with D-mannose and D-glucose residues by AB-PAS, HID-AB and Concanavalia ensiformis (Con A) reactivities. This suggested that mucin secreted from these cells was similar to that secreted from the goblet cells of the large intestine in cattle.     

Intestinal metaplasia in glandular and cystic formations and human urothelial adenocarcinoma]

Thirteen cases of inflammatory changes in the urothelium with formation of glandular and cystous structures, 3 cases of glandular metaplasia in transitional cell carcinoma and 8 adenocarcinomas were examined. In inflammation, initial glandular and cystic structures have signs of somehow incompleted metaplasia of the intestinal type. In advanced glandular structures metaplasia is completed and urothelium acquires similarity in the structure and properties of the produced mucus with the large intestine epithelium (numerous goblet, cylindrical limbic and non-differentiated cells, prevalence of argentaffinic cells over argirophilic, lack of Panet cells, secretion of sulfomucines). In loci of glandular metaplasia of transitional cell carcinoma there are also signs of somehow incompleted intestinal differentiation. Most typical variants of urothelial adenocarcinoma are quite similar to glandular carcinoma by the structure and properties of the produced mucus.     

Squamous and glandular lesions of the urinary bladder

A wide range of squamous and glandular lesions can arise within the urinary bladder. Familiarity with benign entities is important as florid examples can mimic a neoplastic process while certain histologically bland lesions have a potential malignant association.When dealing with overtly malignant lesions, careful morphologic assessment and clinicopathologic correlation are essential. This paper provides a broad overview of the spectrum of squamous and glandular lesions encountered in the bladder with an emphasis on important morphologic features, relevant clinical implications and common differential diagnoses in routine diagnostic practice.     

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.     

O-acetylated sialic acid variants in intestinal glandular metaplasia of the urinary tract

Two cases of chronic cystitis, two of chronic ureteritis, one of chronic pyelitis and two transitional cell carcinomas of the urinary tract showed glandular metaplasia or focal mucin production. Positive staining for O-acetylated sialic acid variants (sites 7 and 8) detected by the PB-KOH-PAS method was found in the two cases of cystitis, in one of chronic ureteritis and in one of chronic pyelitis. Positive staining was observed only in areas showing an intestinal type of metaplasia and in which goblet cells and argyrophil cells were also identified. These findings taken together with earlier studies on ovarian cystadenomas lead the authors to believe that O-acetylated variants are markers of an intestinal type of epithelium. Evaluation of O-acetylated sialomucins may be useful in further studies on the histogenesis of primary adenocarcinomas of the bladder.     

Immunohistochemical demonstration of human chorionic gonadotropin in tumors of the urinary bladder

All transitional cell carcinomas of the bladder diagnosed in male patients within a five year period were studied for human chorionic gonadotropin (hCG) production. Biotin-avidin immunoperoxidase analysis for hCG was performed on all paraffin blocks containing carcinoma-in-situ, grade I, grade II, and grade III transitional cell carcinoma. Of a total of 29 patients, one case of carcinoma-in-situ (1/5), and five cases of grade III transitional cell carcinoma (5/15) were found to have hCG-positive tumor cells. The findings indicate that transitional cell carcinoma should be added to the list of malignant tumors capable of producing hCG.     

Hepatoid adenocarcinoma of the urinary bladder

A new case of hepatoid adenocarcinoma was diagnosed in fragments obtained at transurethral resection (TUR) from a 71-year-old man who had complained of haematuria. The tumour was composed of trabeculae and small solid nests of polygonal atypical cells simulating hepatocarcinoma, together with glandular areas of an otherwise typical adenocarcinoma. Immunohistochemistry showed cytoplasmic reactivity to AFP, AAT, albumin and CAM 5.2. Membrane reactivity was seen in EMA immunostaining, and there was also positivity to polyclonal CEA following a canalicular pattern. Immunoperoxidase studies of hepatocyte growth factor (HGF) and its receptor, c-met, were positive. Their expression may be related to the aggressive behaviour of this tumour.     

Hepatoid adenocarcinoma of the urinary bladder

Hepatoid adenocarcinoma is rare in the urinary bladder with only three well-illustrated previously reported cases. Pathological diagnosis is based on a combination of histological features resembling hepatocellular carcinoma and the positive immunostaining for alpha-fetoprotein. We present the clinicopathological features of four additional cases. The patients were males 66, 85, 61 and 68 years old. Hematuria was the initial symptom in all four patients. Two cases were treated by cystoprostatectomy and the remaining two by transurethral resection of the bladder. On histology, the cases showed a mixture of cells growing in a solid fashion and sheets or anastomosing trabeculae of hepatoid cells merging focally with a secondary glandular pattern of adenocarcinoma. Intracytoplasmic hyaline globules in all and bile production in three of the cases also supported the impression of hepatocytic differentiation. Immunoreactivity for alpha-fetoprotein, low molecular weight cytokeratin, alpha-1-antitrypsin, albumin, epithelial membrane antigen and a striking canalicular pattern when stained against polyclonal carcinoembryonic antigen (CEA), all indicate hepatocellular differentiation. The hepatic nature of the cells was further assessed by detecting the recently incorporated marker hepatocyte paraffin 1, by means of immunohistochemistry and albumin gene mRNA non-isotopic in situ hybridization, both of which had positive signals in all four cases. Three patients died 12, 14 and 19 months after diagnosis. The fourth patient was alive with disease at 26 months of follow-up. In conclusion, hepatoid adenocarcinoma seems to be an aggressive malignant neoplasm that is rare in the bladder whose correct diagnosis may need appropriate immunohistochemical and in situ hybridization means in addition to a complete patient clinical and pathological evaluation. The exact histogenesis and classification of these tumors remains to be established.     

Intestinal metaplasia of mucosal epithelium of the urinary bladder

4 cases of urinary bladder intestinal metaplasia are reported. One adenoma and one adenocarcinoma of intestinal type were discovered. Immunohistochemically, expression of meconial intestinal antigen beta 1 MA in the cytoplasm and on the apical surface of goblet-like cells was observed.     

Malignant glandular lesions and glandular differentiation in invasive/noninvasive urothelial carcinoma of the urinary bladder

Although the lumen of the urinary bladder is covered with only urothelial epithelium, malign glandular lesions (eg, nonurachal adenocarcinoma) and benign lesions (eg, cystitis cystica and cystitis glandularis) can also rarely occur in this site due to its characteristic embryologic development. Glandular differentiation is uncommon in urothelial carcinomas and is even less common in noninvasive urothelial cancers. In addition, in situ urothelial carcinomas are more likely to progress in the presence of glandular differentiation toward high-grade urothelial carcinomas and/or aggressive urothelial carcinomas. Pure nonurachal adenocarcinomas and mixed carcinomas (urothelial carcinoma and adenocarcinoma) are very rare, and their pathogenesis is not clear. Most of the nonurachal adenocarcinomas are thought to arise on the grounds of cystitis glandularus with intestinal metaplasia. Here, I present 2 cases with noninvasive urothelial carcinoma with substantial glandular differentiation showing progression to signet ring cell carcinoma and invasive urothelial carcinoma, one case with mixed carcinoma (urothelial carcinoma and adenocarcinoma) and another case with pure adenocarcinoma developing from cystitis glandularis with intestinal metaplasia, and discuss malign glandular lesions in the bladder and invasive/noninvasive urothelial carcinomas with glandular differentiation.     

Primary adenocarcinomas of the human urinary bladder: Histochemical,immunological and ultrastructural studies

Summary Neoplastic and non-neoplastic tissue specimens from ten patients with primary adenocarcinoma of the urinary bladder were examined. Most of these tumors were associated with either foci of transitional cell carcinoma and/or with glandular metaplasia of the bladder epithelium. The mucin produced by the neoplastic cells was PAS, alcian blue, mucicarmine, PB/KOH/PAS, and RPB/KOH/PAS-positive. ABH isoantigens of these tumors were not always deleted. Ultrastructurally, the neoplastic cells resembled goblet cells. Their plasma membrane had numerous microvilli with prominent glycocalyx. Proliferation and attenuation of tight junctions were noted. The gap junctions were few and small. Two types of desmosomes were found. The ultrastructural features of the neoplastic cells were attributed in part to the malignant transformation and in part to the direction of their differentiation. We have not observed any distinctive morphologic, histochemical, immunologic or ultrastructural features that might be diagnostic for these adenocarcinomas.This study was supported by the Institute of International Education, New York; the Charlton Fund, Tufts University School of Medicine; and Grants#CA-15776 and CA 23776 from the National Cancer Institute     

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 nonmucinous 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.     

Deglycosylation of neutral and acidic human colonic mucin

Human colonic mucin has been isolated from normal colonic mucosa by a phenol-water extraction procedure and purified by Sepharose 2B column chromatography. The mucin was further purified by cesium bromide density gradient centrifugation. Sodium dodecyl sulfate-polyacrylamide gel (5%) electrophoresis of this material showed high-molecular-weight mucin component(s) at the top of the gel. Chemical analyses of this preparation indicated a typical mucin profile of amino acids and carbohydrates. Ion-exchange chromatography resulted in the separation of two major fractions, one being more acidic than the other. Chemical deglycosylation of the purified preparation at 20°C for 3 1/2 showed loss of sialic acid, fucose, galactose, andN-acetylglucosamine, whereas traces ofN-acetylgalactosamine were still detected. High-pressure liquid chromatography of the deglycosylated material resulted in the purification of a major peptide, P₁; with high levels of threonine, serine, and proline, resembling, in most respects, the profile of native mucin. The molecular weight of the peptide was determined to be approximately 97 kDa and serine was the single NH₂ terminus.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or Department of Defense.A part of this study was presented to the 17th Annual Meeting of the Society for Complex Carbohydrates, San Antonio, Texas, November 3–5, 1988 (Glycoconjugate Journal 5:313, (1988)).     

膀胱良性腺样病变的病理学诊断

膀胱可发生各种腺性和假腺样病变,这些病变可从完全良性到生物学行为呈侵袭性的原发或继发恶性肿瘤.膀胱良性腺性病变如囊性膀胱炎和腺性膀胱炎在小的活检标本中可误诊为恶性病变.同样,苗勒起源的异位组织偶可见于膀胱,这些病变应与膀胱真性腺样肿瘤区分开来,否则会引起不适当的治疗.本文就发生于膀胱的各种腺性和腺样病变进行介绍,重点是这些腺样病变的鉴别诊断和临床意义.     

Widespread mucous metaplasia of the urinary bladder with nephrogenic adenoma

We describe widespread metaplastic changes observed in nonexstrophic urinary bladder mucosa in a 32-year-old man. Extensive areas of the luminal surface were covered by two types of metaplastic epithelium. One type was bilayered while the other was single layered with columnar cells of varying electron density as well as mucus-secreting cells. An area of adenomatoid metaplasia was also observed.     

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.