Structural and developmental abnormalities of the exocrine pancreas in cystic fibrosis.

Normal infants from 32 to 54 weeks post-conceptional age show a clear pathway of development in the exocrine pancreas, involving differentiation of acinar tissue, reflected by increased acinar to connective tissue volumes. In contrast, an abnormal pattern of development has been found in cystic fibrosis. Early signs of a deficiency in exocrine tissue at 32-38 weeks post-conceptional age suggest that there is a lack of normal maturation of pancreatic exocrine tissue that occurs in utero, with a degenerative process supervening after birth. The volumes of the acinar and duct lumen is markedly increased, up to 10 fold normal volume in cystic fibrosis subjects. However, the lumenal changes are not a function of age. Accumulation of secretory material in the duct is a characteristic feature in cystic fibrosis and may cause dilation of the duct and acinar lumen and degradation of acini. Alternatively, the greater volume and lack of direct relationship to exocrine acinar volume may reflect a persistence of the fetal pattern of pancreatic development in cystic fibrosis. The diagnosis of cystic fibrosis within the first few months of life is difficult when based on conventional or subjective histologic criteria. By quantitative microscopy of the pancreas, an objective approach is available that clearly distinguishes cystic fibrosis from control subjects. In this retrospective survey, 93% of cystic fibrosis infants were discriminated from normals; only 2 of 30 cases (70%) were not clearly differentiated from controls. As a genetic disorder, the manifestation of cystic fibrosis would be expected to result in pancreatic dysfunction in utero. Other predisposing factors, however, may be involved in the pancreatic lesions such as obstruction of the pancreatic duct, failure in the synthesis or secretion of pancreatic enzymes or abnormal mucus production in the intestine. Further ultrastructural and functional investigations will be important to understand the underlying defect in cystic fibrosis.