Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Combined hepatocellular-cholangiocarcinoma (CHC) forms a small but significant proportion of primary liver carcinomas. However, its diagnostic features are not well established, and this has possibly contributed to the variability in its reported clinical outcome in the literature. Many such tumors with features intermediate between hepatocellular carcinoma and cholangiocarcinoma (CC) may have been considered CC in the past based on positivity for "biliary differentiation" cytokeratins and the lack of availability of highly sensitive and specific hepatocellular markers. The utility of in situ hybridization for albumin mRNA, a recently available sensitive and specific hepatocellular marker, has not been reported in CHC. We investigated 27 CHCs with regard to their histomorphologic spectrum and association of these morphologies with immunohistochemical staining for different cytokeratins (CK7, CK19, and CK20; AE1; Cam 5.2), epithelial membrane antigen, polyclonal carcinoembryonic antigen and alpha-fetoprotein, and in situ hybridization for albumin mRNA. All 27 tumors contained areas morphologically intermediate between hepatocellular carcinoma and CC (transitional-type tumors), and in each case such areas formed at least 25% of the tumor. Nine (33%) tumors showed areas with "antler-like" morphology, a feature not previously described in CHC. Twenty-two of 23 tumors (96%) showed positive signals on in situ hybridization for albumin mRNA. Positivity for both hepatocellular (albumin mRNA) and biliary (keratin immunohistochemical profile) markers confirmed the light microscopic impression of biphenotypic differentiation in these tumors. Immunohistochemical positivity for all cytokeratins (except CK7) and epithelial membrane antigen, as well as the expression of albumin mRNA by in situ hybridization, did not show significant differences between hepatocellular carcinoma and CC-like areas. Based on the cytokeratin profile and results on polyclonal carcinoembryonic antigen/alpha-fetoprotein alone, many such tumors would be classified as CC. However, the positivity for albumin mRNA by in situ hybridization proves that such an interpretation would not have been accurate. Clinically, CHCs showed many differences from pure hepatocellular carcinoma, including the absence of cirrhosis (0 of 27), rarity of serum hepatitis B or C marker positivity (4 of 27), and normal to only mildly elevated serum alpha-fetoprotein levels (median 187 ng/mL). The tumor followed an aggressive clinical course, with overall 3-and 5-year survival rates of 30% and 18%, and in the resected cases of 38% and 24%, respectively.
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PMID:Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study. 1217 85

Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer, featuring both hepatocellular and biliary epithelial differentiations. An intrahepatic tumor may be considered as a metastatic lesion. It has been suggested in the literature that the likelihood of metastasis in the cirrhotic liver is lower than that in the non-cirrhotic liver. A rare case of combined hepatocellular-cholangiocarcinoma and second primary colon adenocarcinoma in a 67-year-old male patient with liver cirrhosis is presented. Histologically, the intrahepatic mass was composed of a spindle cell sarcomatous component; a hepatocellular carcinoma component; and a cholangiocarcinoma component. There were focal transitional regions among the different components. Immunohistochemically, the cholangiocarcinoma component of the intrahepatic mass showed positive reactions for CK-7 but negative reactions for CK-20. The adenocarcinoma of the colon showed positive reactions for CK-20 but negative reactions for CK-7.
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PMID:[A case of combined hepatocellular-cholangiocarcinoma with sarcomatous transformation and second primary colon cancer]. 1521 48

We experienced a resected case of a small hepatocellular carcinoma, which required differential diagnosis from intrahepatic cholangiocellular carcinoma. The patient was a 76-year-old man. While his course had been being observed because of hepatitis C antibody-positive liver cirrhosis, ultrasonographic examination of the abdomen revealed dilation of biliary branches in the anterior segment of the liver and a hyperechoic mass 10 mm in diameter at the origin of the branch. A dynamic computed tomography scan showed a high-density tumor in the early phase. After embolization of the right branch of the portal vein, resection of the right lobe of the liver and the extrahepatic bile duct was performed. A resected specimen showed a white-colored mass 8 mm in diameter at the origin of the anterior segmental biliary branch. In the pathological findings, the diagnosis was a poorly differentiated hepatocellular carcinoma with strong nuclear atypia; the tumor filled the bile duct, forming a trabecular structure. The immunohistological stains of the tumor were positive for cytokeratin (CK) 8, CK18, and HepParl and negative for alpha-fetoprotein, carcinoembryonic antigen, CA19-9, CK7, CK19, and CK20. There was atypia in the biliary lining epithelium adjacent to the tumor, and the hepatocellular carcinoma may have developed from the biliary epithelium.
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PMID:A resected case of a small hepatocellular carcinoma developing within the bile duct. 1523 93

Liver cirrhosis is reportedly one of the conditions preceding peripheral-type intrahepatic cholangiocarcinoma but not hilar/perihilar cholangiocarcinoma. Herein, we report a case of perihilar cholangiocarcinoma arising in a hepatitis C virus-related cirrhotic liver. The patient was a 69-year-old man. He was diagnosed with hepatitis C virus-related chronic hepatitis at the age of 56 years, and 9 years later, multiple hepatocellular carcinomas were detected by imaging modalities. Despite treatments, including chemotherapy, he died of hepatic failure at the age of 69 years. At autopsy, in addition to multiple nodules of hepatocellular carcinoma, we found a white mucinous and fibrous tumor spreading from the hepatic hilum to the periphery along the left lateral segmental bile ducts in the advanced cirrhotic liver. This tumor was histologically a cholangiocarcinoma that involved mainly the peribiliary glands and showed variable cystic dilation, suggesting that it might have been derived from these peribiliary glands. Immunohistochemically, the cholangiocarcinoma cells were positive for cytokeratin 7 and mucin core protein 1, and negative for cytokeratin 20 and mucin core protein 2. Hilar/perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis has rarely been reported. This case warrants further studies to clarify the possible involvement of hepatitis C virus in tumorigenesis of hilar/perihilar cholangiocarcinoma.
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PMID:Perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis with hepatocellular carcinoma. 1770 Nov 35

Reported herein is an unusual case of intrahepatic cholangiocarcinoma with lymphoepithelioma-like appearance in a 64-year-old man who was found to have an intrahepatic mass without cirrhosis. The tumor had two distinct histological patterns with dense lymphoplasmacytic infiltrate. The first was similar to nasopharyngeal undifferentiated carcinoma; the second pattern was a well-differentiated adenocarcinoma. Transition between the two components was observed in the same duct. Immunohistochemistry indicated that the tumor was immunoreactive with AE1/AE3 and cytokeratin (CK) 7, but negative for CEA and CK20. Stromal inflammatory infiltrate primarily consisted of plasma cells and lymphocytes. Immunohistochemical examination and in situ hybridization for EBV showed no integration of the virus in the tumor cells. Intrahepatic lymphoepithelioma-like carcinoma is rare, and most are associated with EBV. Only three cases were not associated with EBV. The authors would like to add one more example of the tumors not associated with EBV.
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PMID:Lymphoepithelioma-like cholangiocarcinoma not associated with EBV. 1806 45

Keratins 18 and 19 (K18/K19) are epithelial-specific intermediate filament proteins. Apoptosis induces caspase cleavage at the highly conserved K18 or K19 Asp237, which in K18 is preceded by cleavage at Asp396. We characterized the keratin N-terminal fragments that are generated upon caspase digestion of K18/K19 at Asp237 in order to study keratin dynamics during apoptosis. This was carried out by generating and characterizing antibodies selective to K18/K19 Asp237. K18 or K19 peptides that expose Asp237 in 234VEVD were used for rabbit immunization. The generated antibodies recognized cleaved but not intact K18/K19, exclusively, as determined by blotting or immunofluorescence staining of apoptotic human HT29 cells or livers isolated from Fas-Ab-injected mice. Antibodies to K18/K19 Asp237 recognized the common VEVD-motif as determined by immunoblotting of cells transfected with K18, K19 or K20. The K18/K19 VEVD-directed antibodies demonstrated sequential Asp396 then Asp237 K18 cleavage during apoptosis. Specific-keratin selectivity of the anti-Asp237 antibodies was confirmed by their inability to recognize K14 after UV-induced apoptosis in transfected cells. The Asp237-containing apoptotic keratin fragments are secreted into the medium of cultured HT29 cells and are stable up to 96 h after inducing apoptosis. Furthermore, the generated antibodies recognize keratin apoptotic fragments in sera of mice undergoing hepatocyte apoptosis and sera of patients with cirrhosis, and also recognize apoptotic cells in various epithelial human tumours. Therefore, the N-terminal caspase-generated K18 fragment is stable in tissues and biological fluids. The Asp237-directed antibodies provide a powerful tool to study apoptosis in human and mouse tissues, cells and serum, using a broad range of detection modalities.
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PMID:Monitoring of epithelial cell caspase activation via detection of durable keratin fragment formation. 1839 69

Fibrolamellar carcinoma is a rare malignant primary liver neoplasm with characteristic histological features that typically arises in young patients without viral hepatitis or cirrhosis. Previous studies on this entity have been limited by small numbers of patients. In contrast to classical hepatocellular carcinoma, individual cases of fibrolamellar carcinoma have been reported to express cytokeratin 7. In addition, ultrastructural and serological studies have suggested that fibrolamellar carcinoma may show neuroendocrine differentiation. The cellular differentiation of fibrolamellar carcinoma has not been studied and little is reported about its immunohistochemical profile. We studied 26 cases of fibrolamellar carcinoma and 62 cases of classical hepatocellular carcinoma by immunohistochemistry for HepPar1, glypican-3, pCEA, CD10, alpha-fetoprotein, cytokeratin 20, neuroendocrine markers, and surrogate markers for biliary differentiation (cytokeratin 7, cytokeratin 19, epithelial membrane antigen, EpCAM, mCEA, B72.3, and CA19.9). In situ hybridization for albumin mRNA was also performed. Tumor cells of fibrolamellar carcinoma and hepatocellular carcinoma showed positive signals for albumin mRNA by in situ hybridization in all cases. Both tumor types stained uniformly positively with HepPar1 and most showed a canalicular staining pattern for pCEA, confirming their hepatocellular differentiation. In addition, 39% of hepatocellular carcinoma cases and 59% of fibrolamellar carcinoma cases were positive for glypican-3. All 22 fibrolamellar carcinoma cases tested showed positive staining for cytokeratin 7 and epithelial membrane antigen, whereas less than one-third of hepatocellular carcinoma cases were positive for these markers (P<0.0001). Further, 36% of fibrolamellar carcinoma cases showed staining for B72.3, cytokeratin 19, EpCAM, or mCEA. Minimal evidence of neuroendocrine differentiation in either tumor was found with any of the usual immunohistochemical markers used for this purpose. Therefore, cytokeratin 7 and epithelial membrane antigen may be useful to differentiate between fibrolamellar carcinoma and hepatocellular carcinoma. On the basis of immunohistochemistry, fibrolamellar carcinoma seems to show both hepatocellular and bile duct differentiation.
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PMID:Fibrolamellar carcinoma of the liver exhibits immunohistochemical evidence of both hepatocyte and bile duct differentiation. 2049 35

We report two patients with unique biliary tumors histologically similar to pancreatic intraductal tubulopapillary neoplasm (ITPN). One patient underwent right hepatectomy for a partly cystic mass in the hepatic hilum. The other patient had liver transplantation for cryptogenic cirrhosis and multiple hilar cysts detected in the explanted liver, some obliterated by papillary nodules. Histologically both tumors consisted of intracystic non-invasive and well differentiated adenocarcinoma with a papillary and tubular architecture. Associated cysts were peribiliary cysts partly lined by carcinoma cells that were continuous with the intracystic papillotubular masses. Both tumors shared the same immunophenotype: K7(+)/K20(-)/MUC1(+)/MUC2(-)/MUC5AC(-)/MUC6(+). Genetic analysis of KRAS and BRAF revealed wild type genotypes. These pathological and genetic features are similar to those of pancreatic ITPNs. This report suggested that ITPNs may rarely develop in the bile duct seemingly in association with peribiliary cysts.
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PMID:Intraductal tubulopapillary neoplasm of the bile duct: potential origin from peribiliary cysts. 2181 59

The differential diagnosis between hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and metastatic colorectal adenocarcinoma (MCA) may be difficult when only based on morphology. For this purpose immunohistochemical analyses are often required, utilizing antibodies directed against CK8-18, Hep-Par1, glypican 3, CK7, CK19, CK20. Here we report a case of a 65-year-old man who presented with a clinical picture of decompensated cirrhosis. Ultrasonography revealed two nodular areas in the right liver lobe. Liver needle biopsy revealed micro-macronodular cirrhosis associated with HCC with trabecular and pseudoglandular patterns. Immunohistochemically, tumour cells were diffusely positive for CK8-18 and also diffusely immunostained by glypican 3 and Hep-Par1. Interestingly, a diffuse and strong staining for CK20 was detected in the vast majority of tumor cells, particularly in the areas showing a pseudo-glandular pattern. No immunostaining for CK7 and CK19 was found in the tumor cells. The tumor behaved aggressively, with a rapid diffusion to the whole liver. The patient died from the disease few months after presentation. These findings underline that the interpretation of the expression of CK20 alone in the differential diagnosis among HCC, CC and MCA should be done with caution because a diffuse immunoreactivity for CK20 alone may not rule out the diagnosis of HCC.
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PMID:Cytokeratin 20-positive hepatocellular carcinoma. 2207 64

The clear cell variant of hepatocellular carcinoma is a rare entity, occurring at a frequency of less than 10% of hepatocellular carcinoma, with a female prevalence and usually associated with hepatitis C and cirrhosis. We reported a case of primary clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without history of hepatitis. Our examination included gross pathology, histopathology, immunohistochemistry, special stains, and electron microscopy evaluation. The tumor was composed of sheets of medium-to-large cells with foamy and reticulated cytoplasm and small-to-medium sized nuclei with variably prominent nucleoli. Oil red O stain showed abundant intracellular lipid. Periodic Acid-Schiff stain confirmed the presence of abundant glycogen deposition. Immunohistochemically the tumor cells were positive for Hep Par1, negative for epithelial membrane antigen, steroidogenic factor-1, HMB45, melan A, CK7 and CK20. Electron microscopy study was performed, which was first done in a clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without elevation of liver function tests. Ultrastructural evaluation of the clear cells showed scarce cellular organelles, cytoplasmic lipid vacuoles and swollen mitochondria.
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PMID:A case of primary clear cell hepatocellular carcinoma in a non-cirrhotic liver: an immunohistochemical and ultrastructural study. 2282 86


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