Nesidiodysplasia and nesidioblastosis of infancy: ultrastructural and immunohistochemical analysis of islet cell alterations with and without associated hyperinsulinaemic hypoglycaemia.

The pancreata of hyperinsulinaemic, hypoglycaemic infants, having the anatomic anomalies characterised as "nesidioblastosis', were compared with age matched control infants by light microscopy, and electron microscopy. While the hyperinsulinaemic infants showed an apparent increase in total endocrine volume compared with control infants, the light microscopic alterations of topographic maldistribution of endocrine cells, irregularly defined islets and intermingling of endocrine with exocrine elements were common to both hypoglycaemic and control groups. In at least one control case, the total endocrine cell volume was comparable to that seen in hypoglycaemic infants and was not associated with endocrine dysfunction. The ratios of insulin: somatostatin: glucagon cells in hypoglycaemic infants were similar to those of control infants. The results of both immunohistochemistry and electron microscopy gave strong indications of endocrine cells containing more than one immunoreactive peptide and heterogenous granule populations respectively. Ultrastructurally, "composite' cells with features of both exocrine and endocrine differentiation were found with some frequency in two hypoglycaemic infants. These findings are discussed in the light of current notions of gastroentero-pancreatic endocrine system development. We conclude that "nesidioblastosis' as currently defined is not the anatomic substratum of infantile hyperinsulaemic hypoglycaemia. We propose the term "nesidiodysplasia' to encompass the apparently increased and possibly maldistributed and/or malregulated endocrine cells associated with the clinical manifestations of hyperinsulinaemia. The precise relationship between the presumed anatomic abnormalities and abnormal insulin secretion remains to be clarified by further investigations.