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ARCHIVES OF DISEASE IN CHILDHOOD

What's in a word? Nesidioblastosis is a word shrouded in confusion because it has been used to mean different things at different times. Coined by Laidlaw in 1938 to describe a diffuse ductoendocrine proliferation ofB cells in the pancreas of a patient with a B cell tumour,' the word remained a histopathological curiosity until the development of radioimmunoassays in the 1960s led to the recognition of neonatal hyperinsulinaemic hypoglycaemia as an entity. The association of a characteristic clinical picture with hyperinsulinaemic hypoglycaemia focused attention in fatal cases on the pancreas. Nesidioblastosis rapidly acquired a clinical connotation2 and for a time the word enjoyed vogue as a clinical diagnosis. Subsequent experience has shown that the clinical presentation of neonatal hyperinsulinaemic hypoglycaemia is its most consistent feature and that both the biochemical findings and especially the histopathology are diverse. This led some authors to use clumsier labels such as 'persistent neonatal hyperinsulinaemic hypoglycaemia (PNHH)' and 'persistent hyperinsulinaemia hypoglycaemia of infancy (PHHI)' to describe the disease, while others now use the term nesidioblastosis either for the clinical condition or to describe a histopathological entity. Hence the confusion. In this review I shall argue that the clinical condition referred to above does not have a single aetiology but arises from convergence of a variety of molecular pathologies. Likewise, the histopathological features we call nesidioblastosis have a spectrum of causes and are no more than a common pancreatic response to precocious growth or regeneration that may occur in human pathology or animal experimentation. In order to unravel nesidioblastosis I have to use the word loosely as a portmanteau term in an account of clinical disease, chemical pathology, histopathology, and their molecular and genetic antecedents.