Architecture of human pancreas: implications for early changes in pancreatic disease

An increased proportion of ductulelike structures, sometimes dilated, occurs in association with pancreatic adenocarcinoma, chronic pancreatitis, cystic fibrosis, and pancreatic ectasia associated with conditions such as uremia. This frequently is interpreted as ductular proliferation, implying origin in ductal elements. Recent animal studies have provided an altered view of pancreatic architecture that is consistent with acinar dedifferentiation leading to the ductulelike structures, or tubular complexes. The architecture of pancreas from organ donors was studied by light and scanning electron microscopy and by wax reconstruction of serial sections. It is concluded that the zymogen granule-containing cells of normal human exocrine pancreas are arranged as branching tubules that vary in diameter and curve acutely. The tubules frequently end blindly to form acinar structures; less frequently they anastomose. This arrangement is consistent with the interpretation that tubular complexes associated with pancreatic disease result from dedifferentiative changes in acinar cells. Tubular complexes may reflect a defect or defects common to pancreatic disease rather than ductular proliferation specific to each one.