Enhanced Islet Cell Nucleomegaly Defines Diffuse Congenital Hyperinsulinism in Infancy but Not Other Forms of the Disease

Bing Han; Melanie Newbould; Gauri Batra; Edmund Cheesman; Ross Craigie; Zainaba Mohamed; Lindsey Rigby; Raja Padidela; Mars Skae; Aleksandr Mironov; Tobias Starborg; Karl Kadler; Karen Cosgrove; Indraneel Banerjee; Mark Dunne

doi:10.1093/ajcp/aqw075

Enhanced Islet Cell Nucleomegaly Defines Diffuse Congenital Hyperinsulinism in Infancy but Not Other Forms of the Disease

Bing Han, Melanie Newbould, Gauri Batra, Edmund Cheesman, Ross Craigie, Zainaba Mohamed, Lindsey Rigby, Raja Padidela, Mars Skae, Aleksandr Mironov, Tobias Starborg, Karl Kadler, Karen Cosgrove, Indraneel Banerjee, Mark Dunne

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVES: 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.

Original language	English
Pages (from-to)	757-68
Number of pages	12
Journal	American journal of clinical pathology
Volume	145
Issue number	6
Early online date	22 Jun 2016
DOIs	https://doi.org/10.1093/ajcp/aqw075
Publication status	Published - Jun 2016

Keywords

Cell Nucleus/pathology
Child, Preschool
Congenital Hyperinsulinism/pathology
Female
Humans
Infant
Infant, Newborn
Islets of Langerhans/pathology
Male
Microscopy, Electron

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Han, B., Newbould, M., Batra, G., Cheesman, E., Craigie, R., Mohamed, Z., Rigby, L., Padidela, R., Skae, M., Mironov, A., Starborg, T., Kadler, K., Cosgrove, K., Banerjee, I., & Dunne, M. (2016). Enhanced Islet Cell Nucleomegaly Defines Diffuse Congenital Hyperinsulinism in Infancy but Not Other Forms of the Disease. American journal of clinical pathology, 145(6), 757-68. https://doi.org/10.1093/ajcp/aqw075

@article{f29976a803544563a783acb91cdf64d9,

title = "Enhanced Islet Cell Nucleomegaly Defines Diffuse Congenital Hyperinsulinism in Infancy but Not Other Forms of the Disease",

abstract = "OBJECTIVES: 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.",

keywords = "Cell Nucleus/pathology, Child, Preschool, Congenital Hyperinsulinism/pathology, Female, Humans, Infant, Infant, Newborn, Islets of Langerhans/pathology, Male, Microscopy, Electron",

author = "Bing Han and Melanie Newbould and Gauri Batra and Edmund Cheesman and Ross Craigie and Zainaba Mohamed and Lindsey Rigby and Raja Padidela and Mars Skae and Aleksandr Mironov and Tobias Starborg and Karl Kadler and Karen Cosgrove and Indraneel Banerjee and Mark Dunne",

note = "{\textcopyright} American Society for Clinical Pathology, 2016.",

year = "2016",

month = jun,

doi = "10.1093/ajcp/aqw075",

language = "English",

volume = "145",

pages = "757--68",

journal = "American journal of clinical pathology",

issn = "0002-9173",

publisher = "Oxford University Press",

number = "6",

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Han, B, Newbould, M, Batra, G, Cheesman, E, Craigie, R, Mohamed, Z, Rigby, L, Padidela, R, Skae, M, Mironov, A, Starborg, T, Kadler, K , Cosgrove, K, Banerjee, I & Dunne, M 2016, 'Enhanced Islet Cell Nucleomegaly Defines Diffuse Congenital Hyperinsulinism in Infancy but Not Other Forms of the Disease', American journal of clinical pathology, vol. 145, no. 6, pp. 757-68. https://doi.org/10.1093/ajcp/aqw075

TY - JOUR

T1 - Enhanced Islet Cell Nucleomegaly Defines Diffuse Congenital Hyperinsulinism in Infancy but Not Other Forms of the Disease

AU - Han, Bing

AU - Newbould, Melanie

AU - Batra, Gauri

AU - Cheesman, Edmund

AU - Craigie, Ross

AU - Mohamed, Zainaba

AU - Rigby, Lindsey

AU - Padidela, Raja

AU - Skae, Mars

AU - Mironov, Aleksandr

AU - Starborg, Tobias

AU - Kadler, Karl

AU - Cosgrove, Karen

AU - Banerjee, Indraneel

AU - Dunne, Mark

N1 - © American Society for Clinical Pathology, 2016.

PY - 2016/6

Y1 - 2016/6

N2 - OBJECTIVES: 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.

AB - OBJECTIVES: 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.

KW - Cell Nucleus/pathology

KW - Child, Preschool

KW - Congenital Hyperinsulinism/pathology

KW - Female

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Islets of Langerhans/pathology

KW - Male

KW - Microscopy, Electron

U2 - 10.1093/ajcp/aqw075

DO - 10.1093/ajcp/aqw075

M3 - Article

C2 - 27334808

SN - 0002-9173

VL - 145

SP - 757

EP - 768

JO - American journal of clinical pathology

JF - American journal of clinical pathology

IS - 6

ER -

Enhanced Islet Cell Nucleomegaly Defines Diffuse Congenital Hyperinsulinism in Infancy but Not Other Forms of the Disease

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