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Clinical and morphological differential diagnosis of congenital hyperinsulinism before the stage of immunohistochemical study of paraffin-embedded specimens of pancreas in children

https://doi.org/10.24884/1607-4181-2020-27-3-41-49

Abstract

Introduction.Differential diagnosis of various forms of congenital hyperinsulinism (CH) is required at the stage of urgent histological examination, but the difference between the exo- and endocrine parts of the pancreas in frozen sections is visualized very poorly.

The objective was to search for differential diagnostic criteria of focal and diffuse forms of CH, suitable for urgent histological examination.

Methods and materials. Pancreatic surgery material from 25 children with CH, of which 15 cases of focal form (FCH) and 10 cases of diffuse (DСH), and autopsy material from 10 children without CH (K). Frozen and paraffin sections stained with hematoxylin-eosin and histochemical stains were made from the tissue of the pancreas. The number of endocrinocytes with large nuclei was estimated in 10 fields of view for each case.

Results. The average proportion of endocrinocytes with large nuclei was significantly (p <0.01) higher compared to the control both with FCH (in the affected area) and DCH (FCH – (1.82±0.50) %, DCH – (4.68±1.66) %, K – (0.34±0.21) %). We found a tendency to detect a higher absolute number of cells with large nuclei in DCH ((4.95±1.24) DCH and (3.71±1.56) FCH). Staining with azure-eosin, picro Mallory and the PAS reaction gave unstable result, and staining with toluidine blue and May-Grunwald did not allow differentiating exo- and endocrine parts of the pancreas.

Conclusion. An increase in the size of the endocrinocyte nuclei was the unsuitable criterion for the differential diagnosis of CH forms, and histochemical stains did not give a stable qualitative result. For urgent biopsy examination, new immunohistochemical methods are needed.

About the Authors

A. A. Perminova
Almazov National Medical Research Centre
Russian Federation

Perminova Anastasiia A., Pathologist, 1st year Postgraduate Student

2, Akkuratova str., Saint Petersburg, 197341

 


Competing Interests:

Authors declare no conflict of interest.

The authors confirm that they respect the rights of the people participated in the study, including obtaining informed consent when it is necessary, and the rules of treatment of animals when they are used in the study. Author Guidelines contains the detailed information. The study was approved by the Ethics Committee of Almazov National Medical Research Centre. Protocol № 10-19 of 14.10.19.



L. B. Mitrofanova
Almazov National Medical Research Centre
Russian Federation

Mitrofanova Lubov B., Dr. of Sci. (Med.), Professor of the Department of Pathology of the Institute of Medical Education, Chief Research Fellow of the Scientific Research Laboratory of Pathomorphology

Saint Petersburg


Competing Interests:

Authors declare no conflict of interest.

The authors confirm that they respect the rights of the people participated in the study, including obtaining informed consent when it is necessary, and the rules of treatment of animals when they are used in the study. Author Guidelines contains the detailed information. The study was approved by the Ethics Committee of Almazov National Medical Research Centre. Protocol № 10-19 of 14.10.19.



A. A. Sukhotskaya
Almazov National Medical Research Centre
Russian Federation

Sukhotskaya Anna A., Cand. of Sci. (Med.), Associate Professor, Head of the Department of Pediatric Surgery for Congenital Pathology

Saint Petersburg


Competing Interests:

Authors declare no conflict of interest.

The authors confirm that they respect the rights of the people participated in the study, including obtaining informed consent when it is necessary, and the rules of treatment of animals when they are used in the study. Author Guidelines contains the detailed information. The study was approved by the Ethics Committee of Almazov National Medical Research Centre. Protocol № 10-19 of 14.10.19.



V. G. Bairov
Almazov National Medical Research Centre
Russian Federation

Bairov Vladimir G., Dr. of Sci. (Med.), Professor, Chief Research Fellow of the Scientific Research Laboratory of Surgery for Congenital and Genetic Pathology, Institute of Perinatology and Pediatrics, Professor of the Department of Surgical Diseases of the Institute of Medical Education

Saint Petersburg


Competing Interests:

Authors declare no conflict of interest.

The authors confirm that they respect the rights of the people participated in the study, including obtaining informed consent when it is necessary, and the rules of treatment of animals when they are used in the study. Author Guidelines contains the detailed information. The study was approved by the Ethics Committee of Almazov National Medical Research Centre. Protocol № 10-19 of 14.10.19.



References

1. Menni F., de Lonlay P., Sevin C. et al. Neurologic outcomes of 90 neonates and infants with persistent hyperinsulinemic hypoglycemia // Pediatrics. – 2001. – Vol. 107. – P. 476–479. Doi: 10.1542/peds.107.3.476.

2. Lord K., De León D. D. Hyperinsulinism in the Neonate // Clinics in Perinatology. – 2018. – Vol. 45, № 1. – Р. 61–74. Doi: 10.1016/j.clp.2017.10.007.

3. Stanley C. A. Advances in diagnosis and treatment of hyperinsulinism in infants and children // J. Clin. Endocrinol. Metab. – 2002. – Vol. 87. – P. 4857–4859. Doi: 10.1210/jc.2002-021403.

4. Otonkoski T., Ammala C., Huopio H. et al. A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland // Diabetes. – 1999. – Vol. 48, № 2. – Р. 408–415. Doi: 10.2337/diabetes.48.2.408.

5. Mathew P. M., Young J. M., Abu-Osba Y. K. et al. Persistent neonatal hyperinsulinism // Clinical Pediatrics (Phila). – 1988. – Vol. 27, № 3. – P. 148–151. Doi: 10.1177/000992288802700307.

6. Galcheva S., Demirbilek H., Al-Khawaga S. et al. The genetic and molecular mechanisms of congenital hyperinsulinism // Front. Endocrinol. – 2019. – Vol. 10. – P. 111. Doi: 10.3389/fendo.2019.00111.

7. Sempoux Ch., Guiot Y., Jaubert F. et al. Focal and diffuse forms of congenital hyperinsulinism: the keys for differential diagnosis // Endocrine Pathology. – 2004. – Vol. 15, № 3. – Р. 241–246. Doi: 10.1385/ep:15:3:241.

8. Han B., Mohamed Z., Estebanez M. S. et al. Atypical forms of congenital hyperinsulinism in infancy are associated with mosaic patterns of immature islet cells // J. Clin. Endocrinol. Metab. – 2017. – Vol. 102, № 9. – Р. 3261–3267. Doi: 10.1210/jc.2017-00158.

9. Houghton J., Banerjee I., Shaikh G. et al. Unravelling the genetic causes of mosaic islet morphology in congenital hyperinsulinism // J. Pathol. Clin. Res. – 2020. – Vol. 6, № 1. – Р. 12–16. Doi: 10.1002/cjp2.144.

10. Lord K., Dzata E., Snider K. E. et al. Clinical presentation and management of children with diffuse and focal hyperinsulinism: a review of 223 cases // J. Clin. Endocrinol. Metab. – 2013. – Vol. 98, № 11. – Р. E1786–1789. Doi: 10.1210/jc.2013-2094.

11. Ni J., Ge J., Zhang M. et al. Genotype and phenotype analysis of a cohort of patients with congenital hyperinsulinism based on DOPA-PET CT scanning // European Journal of Pediatrics. – 2019. – Vol. 178. – P. 1161–1169. Doi: 10.1007/s00431-019-03408-6.

12. Han B., Newbould M., Batra G. et al. Enhanced islet cell nucleomegaly defines diffuse congenital hyperinsulinism in infancy but not other forms of the disease // Am. J. Clin. Pathol. – 2016. – Vol. 145. – P. 757–768. Doi: 10.1093/ajcp/aqw075.

13. Usta A., Usta C. S., Yildiz A. et al. Frequency of fetal macrosomia and the associated risk factors in pregnancies without gestational diabetes mellitus // Pan. Afr. Med. J. – 2017. – Vol. 26. – P. 62. Doi: 10.11604/pamj.2017.26.62.11440.

14. Júnior A. E., Peixoto A. B., Zamarian A. C. et al. Macrosomia // Best Pract. Res. Clin. Obstet. Gynaecol. – 2017. – Vol. 38. – P. 83–96. Doi: 10.1016/j.bpobgyn.2016.08.003.

15. Ping F., Wang Z., Xiao X. Clinical and enzymatic phenotypes in congenital hyperinsulinemic hypoglycemia due to glucokinase-activating mutations: a report of two cases and a brief overview of the literature // J. Diabetes Investig. – 2019. – Vol. 10, № 6. – Р. 1454–1462. Doi: 10.1111/jdi.13072.

16. Rosenfeld E., Ganguly A., De Leon D. D. Congenital hyperinsulinism disorders: genetic and clinical characteristics // Am. J. Med. Genet. C Semin. Med. Genet. – 2019. – Vol. 181, № 4. – Р. 682–692. Doi: 10.1002/ajmg.c.31737.

17. Christiansen C. D., Petersen H., Nielsen A. L. et al. 18F-DO-PA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation // Eur. J. Nucl. Med. Mol. Imaging. – 2018. – Vol. 45, № 2. – Р. 250– 261. Doi: 10.1007/s00259-017-3867-1.

18. Lord K., Radcliffe J., Gallagher P. R. et al. High risk of diabetes and neurobehavioral deficits in individuals with surgically treated hyperinsulinism // J. Clin. Endocrinol. Metab. – 2015. – Vol. 100, № 11. – Р. 4133–4139. Doi: 10.1210/jc.2015-2539.

19. Bensley R. R. Studies on the pancreas of the Guinea pig // Am. J. Anat. – 1911. – Vol. 12, № 3. – Р. 308–311.

20. Bowie D. J. Cytological studies of the islets of Langerhans in a teleost, Neomaenis griseus // Anat. Rec. – 1924. – Vol. 29, № 1. – Р. 57–73.

21. Lillie R. D. Histopathologic technic and practical histochemistry. Moscow, MIR, 1969:274–279. (In Russ.).


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For citations:


Perminova A.A., Mitrofanova L.B., Sukhotskaya A.A., Bairov V.G. Clinical and morphological differential diagnosis of congenital hyperinsulinism before the stage of immunohistochemical study of paraffin-embedded specimens of pancreas in children. The Scientific Notes of the Pavlov University. 2020;27(3):41-49. (In Russ.) https://doi.org/10.24884/1607-4181-2020-27-3-41-49

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