Development of human intrahepatic peribiliary glands. Histological, keratin immunohistochemical, and mucus histochemical analyses.

BACKGROUND

Intrahepatic peribiliary glands are important components of the intrahepatic biliary tree. Although the development of extrahepatic and intrahepatic bile ducts has been studied extensively, that of intrahepatic peribiliary glands is still unclear.

EXPERIMENTAL DESIGN

The development of human intrahepatic peribiliary glands was examined using histology, keratin immunohistochemistry, and mucus histochemistry.

RESULTS

At 7 weeks gestation, the ductal plate was present in the periportal immature hepatocytes around the portal veins at the hepatic hilum. At 10 weeks gestation, biliary cells began to bud from the ductal plate into the mesenchyme and formed double-layered cords and tubules. The double-layered cords had transformed completely into tubules by 30 weeks gestation. The tubules then gradually increased in number and aggregated to form immature peribiliary glands at approximately 40 weeks gestation. After birth, the acini of the immature peribiliary glands continued to increase in number and reached an adult state by approximately 15 years. Cytokeratin immunohistochemistry revealed that the ductal plate, precursor cords and tubules in the mesenchyme, and developing and developed peribiliary glands were positive for monoclonal anticytokeratin antibodies CAM5.2, AE1, KL1, and the polyclonal anticytokeratin antibody. Mucus acini containing neutral mucin, sialomucin, and sulfomucin were absent in fetal and neonatal peribiliary glands, appeared at 3 months after birth, and increased gradually after that time. In some cases, ectopic exocrine pancreatic tissue differentiated from the peribiliary glands. This was first observed 3 months after birth and persisted to adult life.

CONCLUSIONS

These data indicate that 1) intrahepatic peribiliary glands arise from the periportal immature hepatocytes at the hepatic hilum, 2) the cytokeratin profile does not change during development of peribiliary glands, and 3) differentiation of peribiliary glands into mucus acini and ectopic exocrine pancreatic tissue occurs 3 months after birth.