Pancreatic B-cell proliferation in persistent hyperinsulinemic hypoglycemia of infancy: an immunohistochemical study of 18 cases

Mod Pathol. 1998 May;11(5):444-9.


Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characterized by severe hypoglycemia related to inappropriate insulin secretion. Morphologically, a tumoral and a nontumoral form are recognized. The tumoral form can be subdivided into adenomatous hyperplasia (in infants) and adenoma (in children). On the other hand, nesidioblastosis, considered until recently as a persistent B-cell replication, has repeatedly been proposed as the condition responsible for the nontumoral form of PHHI. We studied the proliferation rate of B cells in 18 patients affected by PHHI (7 nontumoral and 11 tumoral cases, including 4 adenomas and 7 adenomatous hyperplasias) and in 18 age-matched controls, using a double immunohistochemical technique detecting Ki-67, a nuclear endogenous antigen only present during cell proliferation, and insulin as pancreatic B-cell markers. Our results clearly show that "nesidioblastosis" is not related to an abnormal B-cell proliferation, because the B-cell labeling index (LI), reported as the mean plus or minus the standard error of the mean, is not statistically different between nontumoral PHHI (29.4 +/- 7.4) and age-matched controls (19.6 +/- 5.3). Furthermore, the Ki-67 positivity was not more prominent in small clusters of B cells in nesidioblastosis than in large islets. In tumoral PHHI, the LI was significantly higher in cases of focal adenomatous hyperplasia (77.6 +/- 10.9) than in either age-matched controls (19.9 +/- 6.9; P < .005) or in adenomas (27.9 +/- 13.7; P < .025); the values of this last group did not differ from those of age-matched controls (18.5 +/- 8.5). These data definitely demonstrate that nesidioblastosis does not correspond to an abnormal B-cell proliferation and that the focal forms of PHHI must be subclassified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / metabolism
  • Adenoma / pathology
  • Adolescent
  • Cell Division / physiology
  • Child
  • Child, Preschool
  • Humans
  • Hyperinsulinism / metabolism
  • Hyperinsulinism / pathology*
  • Hyperinsulinism / surgery
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Hypoglycemia / metabolism
  • Hypoglycemia / pathology*
  • Hypoglycemia / surgery
  • Immunohistochemistry
  • Infant
  • Insulin / metabolism
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology*
  • Ki-67 Antigen / metabolism
  • Pancreatectomy / methods
  • Syndrome


  • Insulin
  • Ki-67 Antigen