bromochloroacetic-acid and Adenoma--Bile-Duct

Topics: Adenoma, Bile Duct; Antibodies, Monoclonal; Bile Duct Neoplasms; Hamartoma; Humans; Keratins; Liver; Terminology as Topic

Published surveys of feline neoplasia have not specifically included biliary cystadenoma, and there is only one case report in the literature. This report is a compilation of 13 feline cases and provides a description of clinical, pathologic, immunohistochemical, and ultrastructural aspects of biliary cystadenoma as well as a discussion of comparative pathology of biliary cystadenoma in human beings and speculative histogenesis.

Topics: Adenoma, Bile Duct; Animals; Bile Duct Neoplasms; Cat Diseases; Cats; Cystadenoma; Female; Immunohistochemistry; Keratins; Liver; Male; Microscopy, Electron

Hepatocellular carcinoma (HCC) is a well-known complication of genetic hemochromatosis (GH). However, the frequency of primary liver carcinoma (PLC) with biliary differentiation, such as cholangiocarcinoma (CC) and combined hepatocholangiocarcinoma (CHCC), in GH remains unclear We analyzed the histologic type of 20 PLCs occurring in the background of GH; all patients were homozygotic for the C282Y mutation. Ten were depleted of iron by successive phlebotomies, while the remaining 10 were untreated. Histologically, 13 cases were classified as HCC, 3 as CC, and 4 as CHCC. Immunohistochemical detection of Hep Par 1, cytokeratin 19 (CK19), and MUC1 supported this classification; PLC with biliary differentiation was immunoreactive for MUC1 in 86% (6/7) of cases and for CK19 in 100% (7/7) of cases. The nontumoral liver exhibited no cirrhosis or extensive fibrosis in 6 cases. Von Meyenburg complexes were present in 11 cases and intraparenchymal bile duct adenomas in 3. These data suggest that PLCs in patients with GH present a wide histologic spectrum, with tumors showing frequent biliary differentiation; may arise on a nonfibrotic or a cirrhotic liver; and often are associated with Von Meyenburg complexes and to a lesser extent with bile duct adenomas.

Topics: Adenoma, Bile Duct; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Hemochromatosis; Homozygote; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Middle Aged; Mucin-1; Mutation

Distinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangiocarcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72(B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18(71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4(83%) and mCEA(71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC. AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas.

Topics: Adenocarcinoma; Adenoma, Bile Duct; alpha-Fetoproteins; Antibodies, Monoclonal; Antigens, Differentiation, Myelomonocytic; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Membrane Glycoproteins; Mucin-1; Retrospective Studies

Although there have been a few reports dealing with the sarcomatous changes of intrahepatic cholangiocarcinoma, its clinicopathologic features as well as immunohistochemical nature remain obscure.. Among 155 cases of intrahepatic cholangiocarcinoma, 7 cases of sarcomatous cholangiocarcinoma were chosen. Immunohistochemical studies using the avidin-biotin-peroxidase complex method were performed on these cases.. The tumor showed both mucin-producing adenocarcinoma areas and sarcomatous areas, the latter being predominant in three cases and focal in the other four. All the sarcomatous areas consisted of atypical spindle cells arranged in sheets or bundles. Pleomorphic giant cells were observed in some sarcomatous components in five cases. Immunohistochemical staining for keratin and epithelial membrane antigen revealed apparent positivity in the sarcomatous components of five cases. The patients with these tumors showed aggressive intrahepatic spreading and widespread metastasis of the sarcomatous cells, and demonstrated poorer prognosis than those with ordinary cholangiocarcinoma, with one exception, a patient who remained disease-free for 3 years after surgery.. These findings favor the possible epithelial origin of sarcomatous cells. Radical operation would be necessary for patients with this special type of cholangiocarcinoma.

Topics: Adenocarcinoma, Mucinous; Adenoma, Bile Duct; Adult; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Sarcoma

Human liver parenchymal cells have a very simple cytokeratin composition and express only one cytokeratin pair: cytokeratin 8 (a type II cytokeratin, molecular weight 52 kD) and cytokeratin 18 (a type I cytokeratin, molecular weight 45 kD). Intrahepatic bile duct cells contain in addition to cytokeratins 8 and 18 also cytokeratins 7 (a type II cytokeratin, molecular weight 54 kD) and cytokeratin 19 (a type I cytokeratin, molecular weight 40 kD). The paper deals with the cytokeratin expression in various types of benign and malignant primary liver tumors as assessed by immunohistochemical methods or by the use of gel electrophoresis and immunoblotting of cytoskeletal extracts.

Topics: Adenoma, Bile Duct; Biomarkers; Carcinoma, Hepatocellular; Histocytochemistry; Humans; Hyperplasia; Keratins; Liver Diseases; Liver Neoplasms

Hepatocytes and bile duct epithelium express several types of cytokeratins, the characteristic intermediate-filament proteins of epithelial cells. The cytokeratin antigen expression was studied in normal and diseased livers, intrahepatic cholangiocarcinomas, and hepatocellular carcinomas by immunohistochemical methods using a panel of polyclonal and monoclonal antibodies to cytokeratins. Ten percent formaldehyde solution-fixed, paraffin-embedded sections obtained from ten patients without liver disease, 18 patients without liver disease, 18 patients with different stages of primary biliary cirrhosis, 14 patients with alcoholic hepatitis, ten patients with fatty liver hepatitis secondary to diabetes mellitus or morbid obesity, five patients with hepatocellular carcinomas, and five patients with cholangiocarcinomas were examined. The results suggested that hepatocytes and bile duct epithelium retain their distinct cytokeratin profiles in liver disease, including malignant transformation. Therefore, demonstration of cytokeratins in the liver is useful in establishing the cellular origin of neoplasms and understanding the pathogenesis of liver diseases.

Topics: Adenoma, Bile Duct; Carcinoma, Hepatocellular; Fatty Liver; Hepatitis; Humans; Keratins; Liver; Liver Cirrhosis, Biliary; Liver Diseases; Liver Neoplasms; Reference Values; Tissue Distribution

The case of a 61-year-old woman with a surgically resected solitary cholangiocarcinoma of the liver is reported, where many discrete multiple bile duct hamartoma (MBDH) were also seen. The latter is a congenital lesion of the liver that potentially may be confused with widespread metastatic disease. The relationship between cholangiocarcinoma and MBDH was studied histologically by the use of an immunoperoxidase technique for cytokeratin. MBDH was strongly positive for cytokeratin, while the neoplasm showed this to a lesser extent, but a clear continuity between the MBDH epithelial cells and those of the neoplasm was demonstrated by the use of this technic. The potential use for the various cytokeratins in the differentiation of primary from secondary liver tumors, is discussed. This differentiation is a significant problem to the pathologist. Although cholangiocarcinoma may, on occasion, be associated with various congenital lesions of the bile ducts, the association with MBDH is extremely rare, this being only the third reported case.

Topics: Adenoma, Bile Duct; Bile Duct Neoplasms; Bile Ducts; Bile Ducts, Intrahepatic; Carcinoembryonic Antigen; Female; Hamartoma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasms, Multiple Primary

A series of 10 cases of biliary obstruction due to primary cholangiocarcinoma has been studied with histological and immunocytochemical means. The total duration of cholestasis (as manifested by jaundice) was between 2 and 11 weeks with variable period of preoperative drainage. Liver biopsy specimens taken during surgery for cholangiocarcinoma were investigated for the presence of ductular proliferation and the development of fibrosis, as demonstrated by Sirius Red F3BA collagen staining. The differentiation of epithelial components was evaluated by AEC-immunostaining with chain-specific monoclonal antibodies specifically directed against human keratins type 7, 18 and 19. Keratin 7, normally occurring only in the ductular system, was expressed in hepatocytes at the periphery of the hepatic lobule (zone I) following about 4 weeks' cholestasis, when an increase of ductular profiles in the enlarged portal areas had become manifest. Such keratin 7 positive cells, however, still retained all morphological aspects of hepatocytes. Keratin 19, normally also restricted to the ductular system in liver, is not expressed by zone I hepatocytes even after longer duration (up to 11 weeks) of cholestasis. It is concluded that the increase in ductular profiles during the first week is mainly due do proliferation of pre-existing ductules, while ductular metaplasia occurs in more chronic cholestasis. Development of fibrosis, not always strictly paralleling the multiplication of ductular profiles in sections through a portal tract, represents an early change, and is clearly apparent after 2 weeks of obstruction.

Topics: Acute Disease; Adenoma, Bile Duct; Aged; Antibodies, Monoclonal; Azo Compounds; Bile Duct Neoplasms; Cholestasis, Extrahepatic; Collagen; Coloring Agents; Female; Hepatic Duct, Common; Humans; Immunohistochemistry; Keratins; Liver; Male; Middle Aged

A polyclonal anti-cytokeratin antibody has been used to examine the expression of this intermediate filament both during normal development in the rat and in a variety of pathological states in the rat and mouse. Bile duct proliferation induced by the administration of alpha-naphthylisothiocyanate (ANIT) as well as the oval cell proliferation induced by 3'-methyl-4-dimethylaminoazobenzene (3-MeDAB) have been used to examine the expression of the rodent cytokeratins in the proliferating cells regarded as being of bile duct origin. Examples of cholangiofibrosis and cholangiocarcinomas were also examined for evidence of cytokeratin expression using this antibody, as well as proliferations of a morphological intermediate type between epithelial and mesenchymal. In all cases we have been able to demonstrate continuity of phenotypic expression of the cytokeratins recognized by this antibody in cells which are recognized as bile duct in origin, even where their morphological appearance does not resemble an epithelial cell type. Because this antibody can be used on formalin-fixed, paraffin-processed tissues, after trypsin treatment, it is proposed that it can be used routinely in the toxicological evaluation (even retrospectively) of bile duct related proliferations and tumours.

Topics: 1-Naphthylisothiocyanate; Adenoma, Bile Duct; Animals; Bile Duct Diseases; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Immunoenzyme Techniques; Keratins; Liver; Male; Methyldimethylaminoazobenzene; Rats; Rats, Inbred Strains

Using 109 hepatocellular carcinomas (HCG), 34 cholangiocellular carcinomas (CCC), 4 mixed hepatocellular-cholangiocellular carcinomas (MHC) and 24 metastatic adenocarcinomas in the liver (MA), an immunohistochemical study on primary carcinoma of the liver was performed by means of the ABC method for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), tissue polypeptide antigen (TPA) and keratin. The material consisted of surgical specimens of Kosin Medical College including 50 HCC, 17 CCC and 1 MHC, surgical specimens of 20 HCC from the University of Occupational and Environmental Health, Japan (UOEH) and autopsied specimens from UOEH that included 39 HCC, 17 CCC, 3 MHC and 24 MA. All the specimens were fixed with 10-15% formalin and embedded in paraplast manually at Kosin Medical College and by utilizing an automatic embedding machine with a decompressing procedure at UOEH. The antigenicity of TPA and keratin was preserved better in the specimens of Kosin Medical College than in those from UOEH. It is therefore assumed that manually embedded specimens are superior to specimens embedded by using an embedding machine with regard to the preservation of some antigenicities. The immunoreactivity of the 4 antigens in CCC cells was significantly higher than that in HCC cells, and the intracellular localization of antigens generally showed several characteristics in HCC and CCC. However, as the same localization of antigens is also seen in both HCC cells and CCC cells, it is considered that the immunohistochemical examination using plural antibodies is not always useful for a differential diagnosis between HCC and CCC, which is difficult in conventional sections. That TPA in HCC may be an oncodevelopmental antigen is suggested by the facts that the higher the grade of HCC, the higher the immunoreactivity of HCC cells, that hepatocytes with possible higher activity sometimes showed a positive reaction in the present study and that TPA is expressed in fetal hepatocytes in a fetus up to 20 weeks in the literature.

Topics: Adenoma, Bile Duct; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Peptides; Tissue Polypeptide Antigen

A total of 32 hepatocellular carcinomas (HCC), 10 cholangiocarcinomas (CC), one combined HCC-CC, and 10 adenocarcinomas metastatic to the liver were studied immunohistochemically using AE1 and Cam 5.2, monoclonal antikeratin antibodies with different specificities. AE1 recognizes keratins with molecular weights of 56.5, 50/50', 48, and 40 kd (keratin nos. 10, 14, 15, 16, and 19, according to Moll's catalog), and labels many epithelia, including bile duct epithelium, but not hepatocytes. Both biliary epithelium and hepatocytes are stained by Cam 5.2, which reacts with keratins of molecular weights 50, 43, and 39 kd (corresponding to keratin nos. 8, 18, and 19). Tissues were formalin fixed, paraffin embedded, and a three-stage immunoperoxidase technique was employed. Of 32 pure HCCs, 29 were unreactive with AE1 yet were positive with Cam 5.2. The intensity and extent of immunostaining with Cam 5.2 did not correlate with tumor grade. In contrast to the HCCs, all 10 CCs and the 10 hepatic metastases were strongly positive with both AE1 and Cam 5.2. The combined HCC-CC was also labeled by both antibodies. We conclude that most HCCs express an immunohistochemical keratin profile identical to that of nonneoplastic hepatocytes, which differs from the keratin patterns of bile ducts, CCs, and metastatic adenocarcinomas from a variety of primary sites. These differences in immunoreactivity with antikeratin antibodies may prove useful in diagnostic surgical pathology.

Topics: Adenoma, Bile Duct; Bile Duct Neoplasms; Carcinoma, Hepatocellular; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Neoplasm Staging

An adult case of combined hepatocellular-cholangiocarcinoma with variable sarcomatous changes is presented. Histologically, the tumor was composed of hepatocellular carcinoma, cholangiocarcinoma, and sarcomatous portions, including spindle-shaped, pleomorphic, and osteoplastic varieties. There was a transitional cell form between the carcinoma and sarcomatous cells. These tumor elements showed both independent and concurrent metastases. Immunohistochemical examination for keratin revealed positive staining in the tumor cells except for osteoplastic immature cells, whereas vimentin had positive results only in some sarcomatous cells. On the basis of these findings, the possibility of sarcomatous transformation of combined hepatocellular-cholangiocarcinoma was discussed.

Topics: Adenoma, Bile Duct; Aged; Carcinoma, Hepatocellular; Gastric Mucosa; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Lymph Nodes; Male; Neoplasm Metastasis; Sarcoma; Vimentin

An antiserum to carcinoembryonic antigen (CEA) and a monoclonal antibody to cytokeratin 19 (CK 19) were studied for their suitability as diagnostic reagents for the differential diagnosis of primary and secondary malignant epithelial tumours of the liver, on paraffin sections. With the antiserum to CEA, positive bile canalicular structures were found in 60 per cent of the hepatocellular carcinomas. All the cholangiocarcinomas and 66.6 per cent of the metastatic carcinomas were positive for CEA, without displaying a canalicular staining pattern. All the hepatocellular carcinomas were negative for CK 19. All the cholangiocellular carcinomas and the metastatic carcinomas were positive for CK 19. This staining profile may prove helpful in difficult diagnostic cases.

Topics: Adenocarcinoma; Adenoma, Bile Duct; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Keratins; Liver Neoplasms

A combined hepatocellular-cholangiocarcinoma (CHC) of transitional subtype and the surrounding cirrhotic liver tissue were investigated immunocytochemically by monoclonal antibodies specific for each of the keratin polypeptides 7, 8, 18 and 19. Different keratin subsets were found in different parts of the tumour. The hepatocellular component reveals keratins 8 and 18, with the bordering cells of trabecular formations additionally expressing keratins 7 and 19. The same keratins i.e. 7, 8, 18, 19 were found in normal bile duct epithelium as well as in cholangiocarcinomatous and transitional areas of hepatocellular and cholangiocellular differentiation. Normal hepatocytes express only keratin 8 and 18. In cirrhotic liver some modified hepatocytes additionally express keratin 7. When ductal transformation is observed in the marginal parts of portal tracts and fibrous septa the keratin polypeptide pattern mimics that of bile duct epithelium. The cholangiocellular metaplasia of hepatocytes observed here correlates well with findings in hepato-organogenesis and hepatocarcinogenesis and suggests that the transitional subtype of combined hepatocellular-cholangiocarcinoma is a variant of hepatocellular carcinoma.

Topics: Adenoma, Bile Duct; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratins; Liver; Liver Cirrhosis; Liver Neoplasms

Five monoclonal antibodies recognizing different keratin polypeptides in immunoblotting or different epithelial cell types in complex tissues were studied for their suitability as reagents for the differential diagnosis of primary and secondary malignant epithelial liver tumors. The broad specificity keratin antibodies lu-5 and KL-1 stained all epithelial liver neoplasms. In contrast the antibodies CK-7 (Ker-7-specific), CK-2 (Ker-18-specific) and KA-4 (Ker-19-specific in liver) allow these neoplasms to be divided into three groups: Hepatocellular carcinomas were CK-2-positive and CK-7-negative. Cholangiocellular carcinomas, liver metastases of extrahepatic bile duct carcinomas, liver metastases of a ductal carcinoma of breast, and a follicular thyroid carcinoma were stained positively by CK-2, CK-7, and KA-4. In 1 of 6 hepatocellular carcinomas neoplastic hepatocytes were focally labeled by KA-4. In a focal nodular hyperplasia of the liver modified hepatocytes were decorated not only by CK-2 but also by CK-7 and KA-4. Liver metastases of colorectal adenocarcinomas and of a carcinoid tumor were stained positively by CK-2 and KA-4 but not by CK-7.

Topics: Adenoma, Bile Duct; Antibodies, Monoclonal; Antibody Specificity; Bile Ducts; Carcinoma, Hepatocellular; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms

Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. In a review of 24 cases of this tumor, three histologic types were encountered. Four cases were Type I or "collision tumors," apparently a coincidental occurrence of both hepatocellular carcinoma and cholangiocarcinoma in the same patient. Twelve cases were Type II or "transitional tumors," in which there were areas of intermediate differentiation and an identifiable transition between hepatocellular carcinoma and cholangiocarcinoma. Eight cases were Type III or "fibrolamellar tumors" which resembled the fibrolamellar variant of hepatocellular carcinoma but which also contained mucin-producing pseudoglands. Type III tumors differ from other combined tumors, occurring at a younger age, in the absence of cirrhosis, and having a slightly longer survival. Immunohistochemical (immunoperoxidase) staining for intracellular antigens showed that alpha-fetoprotein is a fairly specific, although insensitive, marker of hepatocellular differentiation in primary liver cancers, being present in 50% of typical hepatocellular carcinomas and in hepatocellular areas in 29% of combined tumors, but in no cholangiocarcinomas or cholangiocellular areas of combined tumors. Keratin is a good marker of biliary epithelial differentiation, being found in 90% of cholangiocarcinomas and in 52% of combined hepatocellular cholangiocarcinomas, but in no hepatocellular carcinomas. Alpha-1-antitrypsin, fibrinogen, IgG, and carcinoembryonic antigen may be found in both hepatocellular carcinoma, cholangiocarcinoma, and in combined tumors; these antigens are therefore of limited use in differential diagnosis.

Topics: Adenoma, Bile Duct; Adolescent; Adult; Aged; alpha-Fetoproteins; Carcinoma, Hepatocellular; Female; Fibrinogen; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis

Antibodies against constitutive proteins of different types of intermediate-sized filaments were used in immunofluorescence microscopy on frozen sections of normal rat liver and various rat liver tumors induced by treatment with nitrosamines. Antibodies to tonofilament prekeratin stained bile duct epithelia and hepatocytes of normal liver and hepatocellular carcinoma cells and ductal cells of cholangiofibromas. These cells were not significantly stained by antibodies to vimentin. By contrast, antibodies to vimentin stained mesenchymal cells of normal liver and cells of early and advanced angiosarcomas and of undifferentiated spindle cell sarcoma. These mesenchymal tumor cells were not stained with antibodies to prekeratin. The presence of intermediate-sized filaments in these tumors, often in large whorl-like aggregates, was also demonstrated by electron microscopy. The results show that immunofluorescence microscopy with antibodies to cytoskeletal proteins is a powerful tool for the classification and differential diagnosis of mesenchymal and epithelial liver tumors. We propose that staining with antibodies to proteins of different types of intermediate filaments can be used to improve the identification of tumors of other organs, including metastases, as well as non-neoplastic proliferative lesions.

Topics: Adenoma, Bile Duct; Animals; Cytoskeleton; Hemangiosarcoma; Keratins; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Muscle Proteins; Rats; Sarcoma; Vimentin