Pathomorphology of the atypical form of congenital hyperinsulinism on the example of three clinical cases

Abstract

Background . Congenital hyperinsulinism (CH) is characterized by persistent hypoglycemia, leading to irreversible damage to the cerebral cortex. The atypical form of CH (ACH) remains practically unexplored. Objective . Description of histological and immunohistochemical features of the pancreas in ACH. Design and methods . Material for research — fragments of the resected pancreas of 3 children with ACH aged 3, 6 and 7 months. Control group — pancreas of 9 children who died from heart malformations. Pancreatic tissue was stained with hematoxylin and eosin, an immunohistochemical reaction was performed with antibodies to chromogranin A, somatostatin, and transcription factors (TF) NeuroD1, Nkx2.2, and Isl1. Results . In all patients, numerous hyperplastic islets of Langerhans were observed, which in places merged with each other. In two patients, the lesion was limited to the pancreas area, and in one it covered the entire gland. All patients showed a sharp increase (p < 0.01) in the expression of NeuroD1 both in the exocrine and endocrine parts of the pancreas in the affected area: in 79.0 ± 23.4 % of endocrinocytes and in 88.0 ± 8.2 % of exocrinocytes (in the control 10.5 ± 7.9 % and 4.0 ± 4.9 % respectively). The expression of chromogranin A and TF Isl1 and Nkx2.2 increased statistically significantly (p < 0.01) only in affected endocrinocytes (chromogranin A — 62.3 ± 15.4 % of endocrinocytes, Isl1 — 82.0 ± 4.6 %, Nkx2.2 — 81.3 ± 4.6 %; in the control — 39.4 ± 7.9 %, 30.2 ± 16.2 % and 26.4 ± 11.9 % respectively). In 2 patients, there was a tendency to an increase in the number of somatostatin + endocrinocytes. Conclusion . ACH is morphologically very heterogeneous. Like other forms of CH, ACH was characterized by a statistically significant increase in the expression of chromogranin A and TF NeuroD1, Nkx2.2, Isl1, while the expression of somatostatin in general remained unchanged.