Focal and diffuse forms of congenital hyperinsulinism: the keys for differential diagnosis

Congenital hyperinsulinism is clinically characterized by an inappropriate insulin secretion resulting in recurrent severe hypoglycemia. Nesidioblastosis, the proliferation of islets cells budding off from pancreatic ducts, has been considered for years as the histological lesion responsible for the syndrome. In our morphological studies, we demonstrated that nesidioblastosis is not specific for the disease, which is actually not a single entity. Indeed, we recognized the existence of two different forms--a diffuse form and a focal form--and demonstrated that they can be differentiated on the basis of morphological criteria, even on frozen sections during surgery. This histological distinction directs the therapeutic approach because the patients suffering from the focal form of the syndrome can be completely cured by a very limited pancreatectomy. Molecular findings confirmed the reliability of this histological distinction, showing a specific genetic background for each form.