Development of intrahepatic bile ducts in humans. Possible role of laminin

Laminin, a major extracellular matrix-attachment glycoprotein, may play an important role in the differentiation and migration of epithelial cells during normal development. Therefore, the morphogenesis of bile ducts in human liver of fetuses at sequential gestational ages, neonates, children, and adults was examined by single and double immunohistochemical staining for laminin and for cytokeratins. The latter served as a marker for developing and mature bile duct epithelial cells. A close association was observed between laminin deposition and the differentiating ductal plate cells at the epithelial-mesenchymal interface of portal tracts and during the subsequent migration of ductular structures into the center of portal tracts. Simultaneously, laminin disappeared from the margins of portal tracts, but scattered ductal plate-like structures with laminin remained demonstrable in neonates, children, and even adults. These observations were substantiated by semiquantitative evaluation of laminin at the periphery of portal tracts. Thus, clear evidence is provided that laminin accompanies bile duct epithelial cells during all successive stages of differentiation and migration during the development of the human hepatobiliary system. The persisting ductal plate cells may represent a common stem cell for proliferation of bile ductules and hepatocytes.     

Immunohistochemical distinction of human carcinomas by cytokeratin typing with monoclonal antibodies.

Carcinomas of different origin have been tested in immunofluorescence microscopy with the monoclonal murine antibodies CK1-CK4, which recognize a single cytokeratin polypeptide (human cytokeratin No. 18) present in simple but not in stratified squamous epithelia, and with the monoclonal antibody KG8.13 and guinea pig kerA antibodies, both of which recognize a variety of cytokeratins common to almost all epithelial cell types. Tumors derived from simple epithelia, including adenocarcinomas and some other tumors such as ductal breast carcinomas, were strongly stained by all three antibodies. So was a transitional carcinoma of the bladder. In contrast, basal cell epithelioma, cloacogenic carcinoma, and squamous cell carcinoma of skin, tongue, and esophagus appeared negative with CK1-CK4 but positive with the other two antibodies. Other squamous cell carcinomas derived from epiglottis and cervix uteri showed a mixture of positive and negative cells when tested with CK1-CK4, although all tumor cells were positive when tested with KG8.13 and with kerA. Thus, use of an appropriate collection of cytokeratin antibodies with different specificities not only allows tumors of epithelial origin to be distinguished from other tumor types but, in addition, allows a further subdivision of carcinomas in relation to their histologic origin.     

Hypoplasia of the intrahepatic bile ducts. A clinicopathologic study

Paucity of intrahepatic bile ducts is considered part of the differential diagnosis of cholestatic syndromes in infancy. The purpose of this work is to inform the experience at the Hospital Infantil de Mexico Federico Gómez in the last few years on this entity. We reviewed the clinical charts as well as the biopsies of 31 patients with paucity of intrahepatic bile ducts. We find a slight male preponderance; the vast majority of patients were under three months of age. Cholestasis was the most frequent finding with significant clinicopathologic correlation. The remaining findings were similar to those previously reported, except for a peculiar distortion of the hepatic architecture which may be secondary to the hypoplastic development of the biliary tree. Finally, it is possible that the failure to thrive observed in this patient may commence in utero.     

Immunohistochemical study of nasopharyngeal carcinoma using monoclonal keratin antibodies

Nasopharyngeal carcinoma (NPC) provides a unique opportunity to evaluate distinctive epidemiologic features and a possible etiologic relationship with Epstein-Barr virus (EBV) in human malignancy. The lack of a uniformly accepted pathologic classification for NPC has limited the application of this data, although the World Health Organization (WHO) developed a classification that may solve this problem. Monoclonal keratin antibodies were used for staining of NPC for evaluation of its assistance in diagnosis and classification. In the present immunohistochemical study, monoclonal keratin antibodies, designated AE1, AE2, and AE3, and a polyclonal keratin antibody (RAK) were used for study of the presence of keratin in 121 cases of NPC obtained from China and the United States. AE1 monoclonal antibody, which recognizes keratin protein classes 56.5K, 50K, and 40K, was shown to be the most sensitive and specific for NPC tumor cells among the keratin antibodies studied. In addition, some different keratin expression patterns could be identified between different kinds of epithelium and different tumor groups, with possible relevance to the histogenesis of the histologic subtypes of NPC.     

Development of intrahepatic bile ducts in rat foetal liver explants in vitro.

The origin of intrahepatic bile ducts was investigated in organ cultures of 13, 16 and 19-day foetal rat livers embedded for up to 10 days in a semi-solid agar gel on a filter-raft assembly. Following 10 days in culture, 13-day foetal explants consisted of liver cell trabeculae lined by endothelial cells. Although maturation of the liver cells and bile canaliculi was observed, duct development was found in less than 10% of the explants. Supplementation of the media with putative inducers of bile duct development or culture of explants adjacent to other tissues did not induce regular duct development. By contrast, explants from the porta hepatis of 19-day foetuses cultured for 4 days, but not 10 days, regularly contained duct-like structures. The formation of the few ducts in cultures of 13-day foetal liver explants indicates that these cells can arise by transformation of hepatoblasts but that specific inducers of development are required for predictable and continuous differentiation of biliary epithelial cells.     

Topometry of normal intrahepatic bile ducts

Summary This paper focusses on pratical problems which may also prove to be of theoretical importance, by presenting a method of establishing an exact topometry of the intrahepatic bile ducts. Measurements were made on corrosive casts of the intrahepatic bile ducts from 13 human livers. On the basis of the topometric results presented it is possible to construct an adequate model by means of plastic tubes and to use it for the study of bile flow.

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Topométrie des conduits biliaires intra-hépatiques normaux

Résumé Ce travail, centré sur des problèmes pratiques qui peuvent aussi se révéler être d'une certaine importance théorique, présente une méthode destinée à la réalisation d'une topométrie exacte des conduits biliaires intra-hépatiques. Les mesures ont été réalisées sur des moules des conduits biliaires intrahépatiques de 13 foies humains après corrosion. Sur la base des résultats topométriques présentés ici, il est possible de construire, avec des tubes en plastique, un modèle adapté et de l'utiliser pour l'étude du flux biliaire.

     

Morphological examination of intrahepatic bile ducts in hepatolithiasis

Summary Numerous glandular elements are characteristically found within and around the intrahepatic bile duct walls in hepatolithiasis. These glandular elements were studied by reconstruction of serial sections and mucus histochemistry. The glands were of two types: glands within the thickened ductal wall (intramural) and those outside the wall (extramural). The former were mucous glands arranged in tubular pattern and the latter seromucous glands arranged in tubuloalveolar pattern. Mucous acini of both glands were rich in neutral, carboxylated and sulfated mucus glycoproteins. Serial section observations showed that the intramural glands communicated with bile duct lumina directly, and the extramural glands with ductal lumina via their own conduits. The intramural glands were usually continuous with the epithelia lining bile ducts, suggesting that they were derived from an invagination and subsequently proliferating epithelium lining bile ducts. The extramural glands may have arisen from a proliferation of the pre-existing peribiliary glands. Hypersecreted mucus from the intramural and extramural glands might be causally related to the development and growth of calculi in the intrahepatic biliary tree.     

Abnormalities of intrahepatic bile ducts in extrahepatic biliary atresia

The infantile cholangiopathies are a group of conditions associated with neonatal jaundice, which include extrahepatic biliary atresia, paucity of intra-hepatic bile ducts and disorders associated with persistence of fetal biliary structures, the so-called ductal plate malformations. Although previously regarded as distinct entities, it has recently been suggested that they may represent parts of a disease spectrum in which the principal process is one of bile duct destruction, the morphological manifestations in individual cases being influenced by the stage of intra-uterine development at which such injury occurs and by the site within the biliary system at which there is maximum damage. To further examine this concept, we have studied liver biopsy specimens from 37 neonates with extrahepatic biliary atresia, with particular reference to abnormalities of the intrahepatic bile ducts. Paucity of intrahepatic ducts, defined as a bile duct: portal tract ratio of less than 0.9, was identified in six cases (16.2%). In eight cases (21.6%) we found concentric tubular ductal structures similar to those observed in ductal plate malformations. In one case, both abnormalities could be demonstrated. Our findings support the concept that there is overlap between the various types of infantile cholangiopathy.     

New monoclonal antibodies reacting with bile ducts: further insights into the pathogenesis of bile ductular proliferation in biliary diseases.

We have produced a range of monoclonal antibodies which stain human intrahepatic bile ducts of different sizes. Amongst 26 monoclonal antibodies produced, five clones reacted specifically with bile ducts of different sizes, of which three have been maintained in culture and their viability following freezing and thawing confirmed. Staining patterns varied between normal adult liver tissue, normal fetal liver tissue and a variety of hepatobiliary diseases. The antibodies provide further evidence of the immunological heterogeneity of the human intrahepatic biliary tree and support the hypothesis that proliferating bile ductules are derived from periseptal hepatocytes. The preparation of the antibodies, their staining reactions in normal adult, normal fetal and a variety of liver diseases are described.     

Morphogenesis of intrahepatic bile ducts of the human fetus

Summary The development of the intrahepatic bile ducts of the human fetus was investigated by light and electron microscopy. Bile canaliculi with microvilli and junctional complexes are already found in the embryo of 7 mm. Some of them are of the intracellular type. At six to seven weeks, large bile canaliculi bounded by four to seven liver cells appear. Subsequently, bile canaliculi are formed predominantly between three to four adjoining liver cells and this arrangement persists throughout later fetal life.The early intrahepatic bile ducts develop around the portal vein as epithelial cell plates derived from the hepatic duct and the branches sprout from the epithelial cell plates in several different places. The epithelial cell plates are separated from each other by primitive connective tissue and they change into a complex network of bile ducts. Formation of the intrahepatic bile ducts is completed by three months.Biliary duct cells at the end of the developing bile ducts are thought to transform into liver cells. Therefore, at the ducts of Hering various transitional cells appear between biliary duct cells and liver cells.The fine structure of the developing liver cells and biliaryduct cells is also described.     

Congenital dilatation of the intrahepatic bile ducts with cholangiocarcinoma

Intrahepatic cholangiocarcinomas were found at necropsy in two previously reported cases of congenital dilatation of the intrahepatic bile ducts. The nature of the developmental abnormality is discussed and compared with other forms of biliary dilatation. Slow-flowing bile for many years probably leads to cholangiocarcinoma.     

Nonsyndromatic paucity of intrahepatic bile ducts in congenital syphilis. A case report

The first case of nonsyndromatic paucity of the intrahepatic bile ducts is reported in congenital syphilis. The patient, a 2-week-old female, was born at the 31st week of gestation, weighing 1,910 g. She had a high titer of IgM antibody to Treponema pallidum and sera from both parents also showed a positive reaction in the hemagglutination test for Treponema pallidum. The patient had hepatosplenomegaly and increasing jaundice, and died of respiratory failure on the 70th hospital day. Autopsy examination revealed paucity of the intrahepatic bile ducts, prominent giant cell transformation of hepatocytes, cholestasis and extramedullary hematopoiesis of the liver. The ratio of the number of intrahepatic bile ducts to that of the portal tracts was approximately 0.2:1. There was marked proliferation of atypical bile ductules at the margin of the portal tracts. The exact relation of this paucity to Treponema pallidum remains unknown.