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Classic and recent special stains used in differential diagnosis of endocrine tumors

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Abstract

During the twentieth century, stains for endocrine cells and tumors were developed from empiric cytologic procedures aimed at modern cytochemical methods. Before the 1970s, endocrine stains were mainly based on silver reaction, although other reactions were also proposed; however, the chemical basis of most of these reactions is still unclear. The development of fluorescence procedures for detecting biogenic amines at the cellular level provided information about endocrine cell function of normal cells and related tumors. However, the application of immunocytochemical reactions brought greater and more definitive insights. Several immunocytochemical markers are now available. Some are specific for a definite cell type, while others detect endocrine differentiation in general. Some of these “pan-endocrine” markers are highly specific, and others are highly sensitive but less specific. They all play a definite role in diagnostic pathology. The use of molecular procedures to detect specific mRNA or genetic mutations of diagnostic interest in endocrine pathology should complement immunophenotyping, especially in some problematic fields, such as that of “poorly differentiated” tumors.

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References

  1. Ciaccio C. Sur une nouvelle espece cellulaire dans les glandes de Lieberkünn. CR Soc Biol 60:76, 77, 1906.

    Google Scholar 

  2. Oberdorfer S. Karzinoide tumoren des dunndarms. Frankf Z Pathol 1:426–432, 1907.

    Google Scholar 

  3. Bodian D. A new method for staining nerve fibres and nerve endings in mounted paraffin section. Anat Rec 656:89–97, 1936.

    Article  Google Scholar 

  4. Sevier AC, Munger BL. Technical note: a silver method for paraffin section of neural tissue. J Neuropathol Exp Neurol 24:130–135, 1965.

    PubMed  CAS  Google Scholar 

  5. Masson P. Le glande endocrine de l’intestin chez l’homme. CR Acad Sci 158:52–61, 1914.

    Google Scholar 

  6. Vialli M, Erspamer V. Contributo alla conoscenza istochimica delle cellule enterocromaffini. Arch It Anat Embriol 37:411–436, 1936.

    Google Scholar 

  7. Feyrter F. Über diffuse endokrine epitheliale organe. Leipzig, Germany: Johann Ambrosius Barth, 1938.

    Google Scholar 

  8. Hellerstrom C, Hellman B. Some aspects of silver impregnations of the islets of Langerhans in the rat. Acta Endocrinol 35:518–532, 1960.

    Google Scholar 

  9. Nouet JC, Olivier L, Racadot J. Coloration par l’hematoxyline au plomb de Mac Conaill de certaines cellules n’appartenant pas au système nerveux. CR Soc Biol 163:2018–2020, 1969.

    Google Scholar 

  10. Treblay G, Pearse AGE. histochemistry of oxidative enzyme system in the human thyroid, with special reference to Askanazy cells. J Pathol Bacteriol 80:353–358, 1960.

    Article  Google Scholar 

  11. Welsch U, Pearse AGE. Electron cytochemistry of BuChE and AChE in thyroid and parathyroid C-cells under normal and experimental conditions. Histochemie 17:1–10, 1969.

    Article  PubMed  CAS  Google Scholar 

  12. Pearse AGE. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implication of the concept. J Histochem Cytochem 17:303–313, 1969.

    PubMed  CAS  Google Scholar 

  13. Manocchio I. Metachromatische Färbung der A-zellen in Pancreasinseln von Canis Familiaris. Zentbl Allg Path Anat 101:1–4, 1960.

    CAS  Google Scholar 

  14. Grimelius L. A silver nitrate stain for a2 cells in human pancreatic islets. Acta Soc Med Upsa 73:243–270, 1968.

    CAS  Google Scholar 

  15. Rindi G, Buffa R, Sessa F, Tortora O, Solcia E. Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Histochemistry 85:19–28, 1986.

    Article  PubMed  CAS  Google Scholar 

  16. Ersparmer V, Asero B. Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5-hydroxytryptamine. Nature 169:800, 801, 1952.

    Article  Google Scholar 

  17. Hillarp N-Ä, Hökfelt B. Histochemical demonstration of noradrenaline and adrenaline in the adrenal medulla. J Histochem Cytochem 3:1–5, 1955.

    PubMed  CAS  Google Scholar 

  18. Eränkö O. Distribution of fluorescing islets, adrenaline and noradrenaline in the adrenal medulla of the hamster. Acta Endocrinol 18:174–179, 1955.

    PubMed  Google Scholar 

  19. Falck B, Hillarp NA. A note on the chromaffin reaction. J Histochem Cytochem 7:149, 1959.

    PubMed  CAS  Google Scholar 

  20. Falk B, Hellman B. A fluorescent reaction for monoamines in the insulin producing cells of the guinea pig. Acta Endocrinol 45:133–138, 1964.

    Google Scholar 

  21. Ritzén M, Hammartström L, Ullberg S. Autoradiographic distribution of 5-hydroxytryptamine and 5-hydroxytryptophan in the mouse. Biochem Pharmacol 14:313–321, 1965.

    Article  PubMed  Google Scholar 

  22. Larson B, Owman C, Sundler F. Monoaminergic mechanisms in parafollicular cells of the mouse thyroid gland. Endocrinology 78:109–114, 1966.

    Google Scholar 

  23. Pearse AGE. Common cytochemical properties of cells producing polypeptide hormones, with particular reference to calcitonin and the thyroid C cells. Vet Rec 79:547–590, 1966.

    Google Scholar 

  24. Capella C, Heitz PHU, Hoefler H, Solcia E, Kloppel G. Revised classification of neuroendocrine tumors of the lung, pancreas and gut. Digestion 55 (Suppl. 3):11–23, 1994.

    PubMed  Google Scholar 

  25. Stefaneanu L, Kovacs K, Sasano H. Molecular and cellular endocrine pathology. London: Arnold, 2000.

    Google Scholar 

  26. Majo G, Ferrer I, Marsal J, Blasi J, Aguad F. Immunocytochemical analysis of the synaptic proteins SNAP-25 and Rab 3A in human pituitary adenomas: overexpression of SNAP-25 in the mammosomatotroph lineages. J Pathol 183:440–446, 1997.

    Article  PubMed  CAS  Google Scholar 

  27. Smith TW, Nikulasson S, De Girolami U, De Gennaro LJ. Immunohistochemistry of synaptophysin in human nervous system and neuroendocrine tumors: applications in diagnostic neuro-oncology. Clin Neuropathol 12:335–342, 1993.

    PubMed  CAS  Google Scholar 

  28. Wiedenmann B, Franke WW, Kuhn C, Moll R, Gould VE. Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci USA 83:3500–3504, 1986.

    Article  PubMed  CAS  Google Scholar 

  29. Lloyd RV, Mervak T, Schmidt K, Warner TFCS, Wilson BS. Immunohistochemical detection of chromogranin and neurone specific enolase in pancreatic endocrine neoplasms. Am J Surg Pathol 8:607–614, 1984.

    Article  PubMed  CAS  Google Scholar 

  30. Weiler R, Fischer-Colbrie R, Schmid KW, Feichtinger H, Bussolati G, Grimelius L, Krischk Kerl H, O’Connor D, Winkler H. Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors. Am J Surg Pathol 12:877–884, 1988.

    Article  PubMed  CAS  Google Scholar 

  31. Balaton AJ, Galet BA. Detection of chromogranin A mRNA in small cell lung carcinoma using a new, highly sensitive in situ hybridisation method with a non radioisotope oligonucleotide probe. Cancer 83:1469, 1470, 1998.

    Article  PubMed  CAS  Google Scholar 

  32. Lantuejoul S, Moro D, Michaelides RJAM, Brambilla C, Brambilla E. Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors. Am J Surg Pathol 22:1267–1276, 1998.

    Article  PubMed  CAS  Google Scholar 

  33. Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J. PGP9.5—new marker for vertebrate neurons and neuroendocrine cells. Brain Res 278:224–228, 1983.

    Article  PubMed  CAS  Google Scholar 

  34. Bussolati G, Papotti M, Sapino A. Binding of antibodies against human prealbumin to intestinal and bronchial carcinoids and to pancreatic endocrine tumours. Virchows Arch B Cell Pathol Incl Mol Pathol 45:15–22, 1984.

    Article  PubMed  CAS  Google Scholar 

  35. Jacobsson B, Carlstrom A, Collins VP, Grimelius L. Transthyretin in endocrine pancreatic tumors. Am J Pathol 134:465–471, 1989.

    PubMed  CAS  Google Scholar 

  36. Gultekin SH, Rosai J, Demopoulos A, Graus YF, Posner JB, Dalmau J, Rosenblum MK. Hu immunolabeling as a marker of neural and neuroendocrine differentiation in normal and neoplastic human tissues: assessment using a recombinant anti-Hu Fab fragment. Int J Surg Pathol 8:109–117, 2000.

    CAS  PubMed  Google Scholar 

  37. Viberti L, Bongiovanni M, Croce S, Gugliotta P, Bussolati G. 34βE12 cytokeratin immunodetection in the differential diagnosis of small cell tumors in lung biopsy specimens. Int J Surg Pathol 2000 8:317–322, 2000.

    Google Scholar 

  38. Papotti M, Sapino A, Righi L, Chiappone S, Bussolati G. 34βE12 Cytokeratin immunodetection in the differential diagnosis of neuroendocrine carcinoma of the breast. Appl Immunohistochem Mol Morphol 9:229–233, 2001.

    Article  PubMed  CAS  Google Scholar 

  39. Lamberts SWJ, Hofland LJ, Koetsveld PM, Reubi JC, Bruining HA, Bakker WH, Krenning EP. Parallel in vivo and in vitro detection of functional somatostatin receptors in human endocrine pancreatic tumors: consequences with regard to diagnosis, localisation and therapy. J Clin Endocrinol Metab 71:566–574, 1990.

    Article  PubMed  CAS  Google Scholar 

  40. Reubi JC, Schaer JC, Waser B, Mengod G. Expression and localisation of somatostatin receptors SSTR1, SSTR2, SSTR3 messenger RNA in primary human tumors using in situ hybridisation. Cancer Res 54:3455–3459, 1994.

    PubMed  CAS  Google Scholar 

  41. Reubi JC, Kappeler A, Waser B, Laissue J, Hipkin RW, Schonbrunn A. Immunohistochemical localisation of somatostatin receptor sst2A in human tumors. Am J Pathol 153:233–245, 1998.

    PubMed  CAS  Google Scholar 

  42. Papotti M, Croce S, Macrì L, Funaro A, Pecchioni C, Schindler M, Bussolati G. Correlative immunohistochemical and reserve transcriptase polymerase chain reaction analysis of somatostatin receptor type 2 in neuroendocrine tumors of the lung. Diagn Mol Pathol 9:47–57, 2000.

    Article  PubMed  CAS  Google Scholar 

  43. Pagani A, Papotti M, Höfler H, Weiler R, Winkler H, Bussolati G. Chromogranin A and B gene expression in carcinomas of the breast. Am J Pathol 136:319–327, 1990.

    PubMed  CAS  Google Scholar 

  44. Pagani A, Cerrato M, Bussolati G. Nonspecific in situ hybridization reaction in neuroendocrine cells and tumors of the gastrointestinal tract using oligonucleotide probes. Diagn Mol Pathol 2:125–130, 1993.

    PubMed  CAS  Google Scholar 

  45. Pagani A, Forni M, Tonini GP, Papotti M, Bussolati G. Expression of members of the chromogranin family in primary neuroblastomas. Diagn Mol Pathol 1:16–24, 1992.

    PubMed  CAS  Google Scholar 

  46. Pagani A, Papotti M, Abbona GC, Bussolati G. Chromogranin gene expression in colorectal adenocarcinomas. Mod Pathol 8:626–632, 1995.

    PubMed  CAS  Google Scholar 

  47. Komminoth P, Long AA. In-situ polymerase chain reaction: an overview of methods, application and limitation of a new molecular technique. Virchows Archiv B Cell Pathol 64:67–73, 1993.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Sciences and Oncology, University of Turin, Via Santena 7, I-10126, Torino, Italy

    Gianni Bussolati MD, FRCPATH, Marco Volante MD & Mauro Papotti MD

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  1. Gianni Bussolati MD, FRCPATH
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  2. Marco Volante MD
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  3. Mauro Papotti MD
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Correspondence to Gianni Bussolati MD, FRCPATH.

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Bussolati, G., Volante, M. & Papotti, M. Classic and recent special stains used in differential diagnosis of endocrine tumors. Endocr Pathol 12, 379–387 (2001). https://doi.org/10.1385/EP:12:4:379

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