Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The ultrastructure of focal islet cell adenomatosis in the newborn with hypoglycemia and hyperinsulinism

Contribution to the classification of neonatal insulinomas


In a newborn severe persistent hypoglycemia due to an insulin-producing tumorous proliferation of pancreatic islet cells (insulinoma) was observed. The insulinoma showed the histologic pattern of focal adenomatosis of islet cells. According to the present literature the focal proliferation of islet cell complexes seems to be a frequent and particular feature of insulinomas in the newborn. Differential islet cell staining identified 80%–90% of the proliferated islet cells as B cells. 10%–20% of the cells were found to be A or D cells. Ultrastructurally the majority of the proliferated islet cells were well differentiated B cells. The remaining cells represented either A or D cells or a fourth islet cell type with small spheric granules. Electronmicroscopic evidence of transitions between differentiated islet cells, particularly B cells, and the fourth islet cell type suggests that the fourth islet cell type might represent a precursor cell within the APUD-cell system.


Bei einem Neugeborenen wurde eine schwere persistierende Hypoglykämie als Folge einer Insulin-produzierenden tumorösen Proliferation des Inselzellsystems (Insulinom) beobachtet. Das Insulinom zeigte das histologische Bild einer fokalen Adenomatose der Inselzellen. Nach der vorliegenden Literatur scheint die fokale Proliferation von Inselzellkomplexen ein häufiges und besonderes histologisches Merkmal des neonatalen Insulinoms darzustellen. 80%–90% der proliferierenden Inselzellen konnten mit Hilfe differenzierender Inselzellfärbungen als B-Zellen identifiziert werden, 10%–20% als A- oder D-Zellen. Bei der elektronenmikroskopischen Untersuchung konnte die Mehrzahl der proliferierten Inselzellen als gut differenzierte B-Zellen klassifiziert werden. Die übrigen Zellen repräsentierten entweder A- oder D-Zellen oder einen vierten Inselzelltyp mit kleinen sphärischen Granula. Elektronenmikroskopische Hinweise für Übergangsformen zwischen differenzierten Inselzellen, besonders B-Zellen, und dem vierten Inselzelltyp lassen vermuten, daß der vierte Inselzelltyp eine Vorläuferzelle innerhalb des APUD-Zellsystems darstellt.

This is a preview of subscription content, log in to check access.


  1. Arnold, R., Fuchs, K., Siewert, R., Peiper, H.-J., Creutzfeldt, W.: Zur Morphologie, Klinik, Diagnostik und Therapie des Zollinger-Ellison-Syndroms. Dtsch. med. Wschr. 99, 607–616 (1974)

  2. Aronsen, K. F., Boquist, L., Falkmer, S., Hägerstrand, I., Steiner, H., Studnitz, W.: Carcinoid syndrome and hyperinsulinism. Acta path. microbiol. scand., Sect. A 78, 265–276 (1970)

  3. Assche, F. A. van, Gepts, W.: The cytological composition of the foetal endocrine pancreas in normal and pathological conditions. Diabetologia 7, 434–444 (1971)

  4. Baerentsen, H.: Neonatal hypoglycaemia due to an islet-cell adenoma. Acta paediat. (Uppsala) 62, 207–210 (1973)

  5. Björkman, N., Hellerström, C., Hellman, B., Peterson, B.: The cell types in the endocrine pancreas of the human fetus. Z. Zellforsch. 72, 425–445 (1966)

  6. Broder, L. E., Carter, S. K.: Pancreatic islet cell carcinoma. Ann. intern. Med. 79, 101–107 (1973)

  7. Brown, R. E., Young, R. B.: A possible role for the exocrine pancreas in the pathogenesis of neonatal leucine-sensitivity. Amer. J. dig. Dis. 15, 65–72 (1970)

  8. Buist, N. R. M., Campbell, J. R., Castro, A., Brant, B.: Congenital islet-cell adenoma causing hypoglycemia in a newborn. Pediatrics 47, 605–609 (1971)

  9. Creutzfeldt, W., Arnold, R., Creutzfeldt, C., Deuticke, U., Frerichs, H., Track, N. S.: Biochemical and morphological investigations of 30 human insulinomas. Correlation between the tumour content of insulin and proinsulin-like components and the histological and ultrastructural appearance. Diabetologia 9, 217–231 (1973)

  10. Crigler, J. F.: Massachusetts General Hospital case records. New Engl. J. Med. 266, 1269 (1962)

  11. Deconinck, J. F., Assche, F. A. van, Potvliege, P. R., Gepts, W.: The ultrastructure of the human pancratic islets. II. The islets of neonates. Diabetologia 8, 326–333 (1972)

  12. Deconinck, J. F., Potvliege, P. R., Gepts, W.: The ultrastructure of the human pancreatic islets. I. The islets of adults. Diabetologia 7, 266–282 (1971)

  13. Fonkalsrud, E. W., Trout, H. H., Lippe, B., LaFranchi, S., Dakake, C.: Idiopathic hypoglycemia in infancy. Arch. Surg. 108, 801–804 (1974)

  14. Francois, R., Pradon, M., Sherrer, M., Ugliengo, A. R.: Hypoglycaemia due to pancreatic islet cell adenoma. J. Pediat. 60, 721–729 (1962)

  15. Frantz, V. K.: Atlas of tumor pathology. Tumors of the pancreas, p. 106–109. Washington: Armed Forces Institute of Pathology 1959

  16. Garces, L. Y., Drash, A., Kenny, F. M.: Islet cell tumor in the neonate. Pediatrics 41, 789–796 (1968)

  17. Grant, D. B., Barbor, P. R. H.: Islet-cell tumour causing hypoglycaemia in a newborn infant. Arch. Dis. Childh. 45, 434–436 (1970)

  18. Greider, M. H., Bencosme, S. A., Lechago, J.: The human pancreatic islet cells and their tumors. I. The normal pancreatic islet. Lab. Invest. 22, 344–354 (1970)

  19. Greider, M. H., Rosai, J., McGuigan, J. E.: The human pancreatic islet cells and their tumors. II. Ulcerogenic and diarrheogenic tumors. Cancer (Philad.) 33, 1423–1443 (1974)

  20. Hedinger, C.: Origin and morphology of islet cell tumors with single or multiple hormone production. In: Diabetes. Proceedings of the VIII. Congress of the International Diabetes Federation, Brussels, 1973. Excerpta med. Congr. Series No 312, 292–303 (1974)

  21. Heitz, P., Steiner, H., Halter, F., Egli, F., Kapp, J. P.: Multihormonal, amyloid producing tumour of the islets of Langerhans in a twelve year old boy. Clinical, morphological and biochemical data and review of the literature. Virchows Arch. Abt. A 353, 312–324 (1971)

  22. Klöppel, G., Altenähr, E., Reichel, W., Willig, R., Freytag, G.: Morphometric and ultrastructural studies in an infant with leucine-sensitive hypoglycemia, hyperinsulinism and islet hyperplasia. Diabetologia 10, 245–252 (1974)

  23. Misugi, K., Misugi, N., Sotos, J., Smith, B.: The pancreatic islet of infants with severe hypoglycemia. Arch. Path. 89, 208–220 (1970)

  24. Mitschke, H.: Immunhistologische, cytochemische und elektronenoptische Untersuchungen beim Zollinger-EIlison-Syndrom. Virchows Arch. Abt. A 361, 335–348 (1973)

  25. Munger, B. L.: The biology of secretory tumors of the pancreatic islets. In: Handbook of physiology, vol. 1, sect. 7, D. F. Steiner and N. Freinkel, eds., p. 305–314. Washington, D.C.: American Physiology Society 1972

  26. Pearse, A. G. E.: The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series, and the embryologic, physiologic and pathologic implications of the concept. J. Histochem. Cytochem. 17, 303–313 (1969)

  27. Pearse, A. G. E., Polak, J. M., Heath, C. M.: Development, differentiation and derivation of the endocrine polypetide cells of the mouse pancreas. Diabetologia 9, 120–129 (1973)

  28. Perheentupa, J., Louhimo, I., Taskinen, M.: Congenital insulinoma. J. pediat. Surg. 2, 75–79 (1967)

  29. Potet, F., Martin, E., Thiery, J. P., Bader, J. P., Bonfils, S., Lambling, A.: Etude histologique et cytologique du pancréas endocrine tumoral et non tumoral dans le syndrome de Zollinger-Ellison. Rev. int. Hépat. 16, 737–761 (1966)

  30. Robinson, M. J., Clarke, A. M., Gold, H., Connely, J. F.: Islet cell adenoma in the newborn: report of two patients. Pediatrics 47, 232–236 (1971)

  31. Salinas, E. D., Mangurten, H. H., Roberts, S. S., Simon, W. H., Cornblath, M.: Functioning islet cell adenoma in the newborn. Pediatrics 41, 646–653 (1964)

  32. Schwartz, J. F., Zwiren, G. T.: Islet cell adenomatosis. J. Pediat. 79, 232–238 (1971)

  33. Sherman, H.: Islet-cell tumor in a newborn infant. Amer. J. Dis. Child. 74, 58–79 (1947)

  34. Shibasaki, S., Ito, T.: Electron microscopic study on the human pancreatic islets. Arch. histol. jap. 31, 119–154 (1969)

  35. Sholten, H. G., van der Vegt, J. H.: Functionerend eilandceladenoom van het pancreas bij een pasgeborene. Maandschr. Kindergeneeesk. 28, 140 (1960)

  36. Todd, R. M., Rickham, P. P., Coulter, J. B. S.: Islet cell tumour in the newborn. Helv. paediat. Acta 27, 131–141 (1972)

  37. Vasallo, G., Solcia, E., Bussolati, G., Polak, J. M., Pearse, A. G. E.: Non-G cell gastrin-producing tumours of the pancreas. Virchows Arch. Abt. B 11, 66–79 (1972)

  38. Wermer, P.: Endocrine adenomatosis and peptic ulcer in a large kindred. Amer. J. Med. 35, 205–212 (1963)

  39. Yakovac, W. C., Baker, L., Hummler, K.: Beta cell nesidioblastosis in idiopathic hypoglycemia of infancy. J. Pediat. 79, 226–231 (1971)

Download references

Author information

Additional information

Supported by Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 34, Endocrinology, Hamburg.

The authors are grateful to Prof. Dr. med. J. Kühnau, Department of Internal Medicine, University of Hamburg, Germany, for radioimmunological determination of serum insulin levels. Sincere thanks are also due to Mrs. Katrin Baack and Miss Claudia Drescher for skilful technical assistance.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Klöppel, G., Altenähr, E. & Menke, B. The ultrastructure of focal islet cell adenomatosis in the newborn with hypoglycemia and hyperinsulinism. Virchows Arch. A Path. Anat. and Histol. 366, 223–236 (1975).

Download citation


  • Hypoglycemia
  • Islet Cell
  • Pancreatic Islet
  • Insulinoma
  • Cell Complex