title: Pancreatic B-cell proliferation in persistent hyperinsulinemic hypoglycemia of infancy: an immunohistochemical study of 18 cases.
abstract: 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.
authors.affiliation: Department of Pathology, University Hospital St. Luc, Louvain Medical School, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Sempoux
authors.forename: Y
authors.initials: Y
authors.lastname: Guiot
authors.forename: D
authors.initials: D
authors.lastname: Dubois
authors.forename: M C
authors.initials: MC
authors.lastname: Nollevaux
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: C
authors.initials: C
authors.lastname: Nihoul-Fekete
authors.forename: J
authors.initials: J
authors.lastname: Rahier
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D002455:Cell Division / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007003:Hypoglycemia / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D007150:Immunohistochemistry; D007223:Infant; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D010180:Pancreatectomy / Q000379:methods; D013577:Syndrome
chemical_list: D007328:Insulin; D019394:Ki-67 Antigen