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Histopathology of congenital hyperinsulinism: retrospective study with genotype correlations. Pediatr Dev Pathol 2003 Jul-Aug;6(4):322-33

Date

12/25/2003

Pubmed ID

14692646

DOI

10.1007/s10024-002-0026-9

Scopus ID

2-s2.0-0141650394   59 Citations

Abstract

The majority of the most severe cases of congenital hyperinsulinism (HI) are caused by defects in the beta-cell adenosine triphosphate (ATP)-sensitive potassium channel and usually require pancreatectomy to control blood sugar levels. In contrast to the recent advances in understanding the pathophysiology and genetic bases of HI, the histologic classification of this condition remains controversial. A recent proposal to classify the HI pancreata into diffuse and focal forms has drawn much interest because of its relative simplicity and its good correlation with the genetic abnormalities. We undertook a retrospective study to determine whether this classification scheme could be applied to 38 pancreata resected for HI at our institution. We also obtained leukocyte genomic DNA from 29 cases and screened the exons of ABCC8 and KCNJ11 genes for the presence of mutations. Nineteen cases (50.0%) were histologically classified as diffuse HI and 14 cases (36.8%) were categorized as focal form. The mutational analysis revealed that 14 of the 16 diffuse cases analyzed had either homozygous or compound heterozygous mutations of ABCC8 or KCNJ11 and 7 of 10 focal cases had only the paternally inherited mutations, consistent with the previous observations. Two patients (5.3%) had normal pancreatic histology but had persistent hypoglycemia postoperatively, leaving the possibility of residual focal lesion. Three of 38 cases (7.9%) did not fit well into either diffuse or focal category. Two cases differed from the described pattern for the diffuse form in that the nuclear enlargement was confined to a single area of the pancreas. The other case had a focal lesion but beta-cell nuclear enlargement was present in nonadjacent areas. Mutations for typical diffuse or focal HI were not identified in two of these three equivocal cases. We conclude from this study that nearly 90% of HI cases can be classified into either a diffuse or a focal form. However, a small percentage of cases represented a diagnostic challenge.

Author List

Suchi M, MacMullen C, Thornton PS, Ganguly A, Stanley CA, Ruchelli ED

Author

Mariko Suchi MD, PhD Associate Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

ATP-Binding Cassette Transporters
Blood Glucose
Case-Control Studies
Genotype
Heterozygote
Homozygote
Humans
Hyperinsulinism
Infant
Infant, Newborn
Mutation
Pancreas
Point Mutation
Potassium Channels
Potassium Channels, Inwardly Rectifying
Receptors, Drug
Retrospective Studies
Sulfonylurea Receptors
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a