PANCREATIC B-CELL PROLIFERATION IN PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA OF INFANCY - AN IMMUNOHISTOCHEMICAL STUDY OF 18 CASES

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characte rized by severe hypoglycemia related to inappropriate insulin secretio n. Morphologically, a tumoral and a nontumoral form are recognized. Th e tumoral form can be subdivided into adenomatous hyperplasia tin infa nts) and adenoma tin children). On the other hand, nesidioblastosis, c onsidered until recently as a persistent B-cell replication, has repea tedly been proposed as the condition responsible for the nontumoral fo rm of PHHI. We studied the proliferation rate of B cells in 18 patient s affected by PHHI (7 nontumoral and 11 tumoral cases, including 4 ade nomas and 7 adenomatous hyperplasias) and in 18 age-matched controls, using a double immunohistochemical technique detecting Ki-67, a nuclea r endogenous antigen only present during cell proliferation, and insul in as pancreatic B-cell markers, Our results clearly show that ''nesid ioblastosis'' is not related to an abnormal B-cell proliferation, beca use the B-cell labeling index (LI), reported as the mean plus or minus the standard error of the mean, is not statistically different betwee n 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 tumor al 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 valu es of this last group did not differ from those of age-matched control s (18.5 +/- 8.5). These data definitely demonstrate that nesidioblasto sis does not correspond to an abnormal B-cell proliferation and that t he focal forms of PHHI must be subclassified.