title: Enhanced Islet Cell Nucleomegaly Defines Diffuse Congenital Hyperinsulinism in Infancy but Not Other Forms of the Disease.
abstract: OBJECTIVE
  To quantify islet cell nucleomegaly in controls and tissues obtained from patients with congenital hyperinsulinism in infancy (CHI) and to examine the association of nucleomegaly with proliferation.
  
  
  METHODS
  High-content analysis of histologic sections and serial block-face scanning electron microscopy were used to quantify nucleomegaly.
  
  
  RESULTS
  Enlarged islet cell nuclear areas were 4.3-fold larger than unaffected nuclei, and the mean nuclear volume increased to approximately threefold. Nucleomegaly was a normal feature of pediatric islets and detected in the normal regions of the pancreas from patients with focal CHI. The incidence of nucleomegaly was highest in diffuse CHI (CHI-D), with more than 45% of islets containing two or more affected cells. While in CHI-D nucleomegaly was negatively correlated with cell proliferation, in all other cases, there was a positive correlation.
  
  
  CONCLUSIONS
  Increased incidence of nucleomegaly is pathognomonic for CHI-D, but these cells are nonproliferative, suggesting a novel role in the pathobiology of this condition.
authors.affiliation: From the Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Paediatric Histopathology.
authors.forename: Melanie
authors.initials: M
authors.lastname: Newbould
authors.affiliation: Paediatric Histopathology.
authors.forename: Gauri
authors.initials: G
authors.lastname: Batra
authors.affiliation: Paediatric Histopathology.
authors.forename: Edmund
authors.initials: E
authors.lastname: Cheesman
authors.affiliation: Paediatric Surgery.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Craigie
authors.affiliation: From the Faculty of Life Sciences, University of Manchester, Manchester, UK Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, UK.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Mohamed
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, UK.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Rigby
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, UK.
authors.forename: Raja
authors.initials: R
authors.lastname: Padidela
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, UK.
authors.forename: Mars
authors.initials: M
authors.lastname: Skae
authors.affiliation: From the Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Mironov
authors.affiliation: From the Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Tobias
authors.initials: T
authors.lastname: Starborg
authors.affiliation: From the Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Karl E
authors.initials: KE
authors.lastname: Kadler
authors.affiliation: From the Faculty of Life Sciences, University of Manchester, Manchester, UK karen.e.cosgrove@manchester.ac.uk mark.j.dunne@manchester.ac.uk.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Cosgrove
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester, UK.
authors.forename: Indraneel
authors.initials: I
authors.lastname: Banerjee
authors.affiliation: From the Faculty of Life Sciences, University of Manchester, Manchester, UK karen.e.cosgrove@manchester.ac.uk mark.j.dunne@manchester.ac.uk.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dunne
mesh_terms: D002467:Cell Nucleus / Q000473:pathology* / Q000648:ultrastructure; D002675:Child, Preschool; D044903:Congenital Hyperinsulinism / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron
keywords: Congenital hyperinsulinism; Hyperplasia; Hypoglycemia; Insulin; Islet; Nucleomegaly; Pancreas; Serial block-face scanning electron microscopy; β cell