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Black swans - neuroendocrine tumors of rare locations

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Abstract

Neuroendocrine neoplasms (NEN) are rare and heterogeneous. Therefore, they often remain unrecognized for many years, causing significant disease burden. We here report on four unusual NEN presentations including a metastatic NEN of the kidney, hypoglycemia caused by an insulin-like growth factor-2-oma (previously called non-islet-cell tumor hypoglycemia), multifocal pheochromocytoma in von Hippel Lindau syndrome, and ileal NEN metastatic to the heart. One could say that each one of these tumors were “black swans” and learning about them will increase further awareness of the spectrum of NEN.

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References

  1. Klöppel G, Dege K, Remmele W, Kapran Y, Tuzlali S, Modlin IM. Siegfried Oberndorfer: a tribute to his work and life between Munich, Kiel, Geneva, and Istanbul. Virchows Arch. 2007;451(Suppl 1):S3–7.

    Article  Google Scholar 

  2. Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3(10):1335–42.

    Article  Google Scholar 

  3. WHO Classification of Tumours of Endocrine Organs. 4th Edition. Vol.10. Editors: Lloyd RV, Osamura RY, Kloppel G, Rosai J. ISBN 978-92-832-4493-6. WHO Blue Book Series 2017.

  4. Fasshauer M, Lincke T, Witzigmann H, Kluge R, Tannapfel A, Moche M, et al. Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery. BMC Cancer. 2006;6:108.

    Article  Google Scholar 

  5. Müssig K, Petersenn S, Wehrmann M, Horger M, Vierling P, Häring HU, et al. Somatostatin receptor expression in a parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour causing severe hypercalcaemia. Eur J Gastroenterol Hepatol. 2007;19(8):719–23.

    Article  Google Scholar 

  6. Fottner C, Ferrata M, Weber MM. Hormone secreting gastro-entero-pancreatic neuroendocrine neoplasias (GEP-NEN): when to consider, how to diagnose? Rev Endocr Metab Disord. 2017;18(4):393–410.

    Article  CAS  Google Scholar 

  7. Koch CA, Brouwers FM, Rosenblatt K, Burman KD, Davis MM, Vortmeyer AO, et al. Adrenal ganglioneuroma in a patient presenting with severe hypertension and diarrhea. Endocr Relat Cancer. 2003;10(1):99–107.

    Article  CAS  Google Scholar 

  8. Salgado LR, Fragoso MC, Knoepfelmacher M, Machado MC, Domenice S, Pereira MA, et al. Ectopic ACTH syndrome: our experience with 25 cases. Eur J Endocrinol. 2006;155(5):725–33.

    Article  CAS  Google Scholar 

  9. Korytnaya E, Liu J, Camelo-Piragua S, Sullivan S, Auchus RJ, Barkan A. Ectopic prolactin secretion from a perivascular epithelioid cell tumor (PEComa). J Clin Endocrinol Metab. 2014;99(11):3960–4.

    Article  CAS  Google Scholar 

  10. Koch CA, Azumi N, Furlong MA, Jha RC, Kehoe TE, Trowbridge CH, et al. Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. J Clin Endocrinol Metab. 1999;84(11):4209–13.

    Article  CAS  Google Scholar 

  11. Miehle K, Tannapfel A, Lamesch P, Borte G, Schenker E, Kluge R, et al. Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production upon second recurrence. J Clin Endocrinol Metab. 2004;89(8):3731–6.

    Article  CAS  Google Scholar 

  12. Langton K, Gruber M, Masjkur J, Steenblock C, Peitzsch M, Meinel J, et al. Hypertensive crisis in pregnancy due to a metamorphosing pheochromocytoma with postdelivery Cushing's syndrome. Gynecol Endocrinol. 2018;34(1):20–4.

    Article  Google Scholar 

  13. Maton PN, Gardner JD, Jensen RT. Cushing's syndrome in patients with the Zollinger-Ellison syndrome. N Engl J Med. 1986;315(1):1–5.

    Article  CAS  Google Scholar 

  14. Oki K, Yamane K, Oda Y, Kamei N, Watanabe H, Tominaga A, et al. Combined acromegaly and subclinical Cushing disease related to high-molecular-weight adrenocorticotropic hormone. J Neurosurg. 2009;110(2):369–73.

    Article  CAS  Google Scholar 

  15. Melcescu E, Gannon AW, Parent AD, Fratkin JF, Nicholas WC, Galhom A, et al. Silent or subclinical Corticotroph pituitary macroadenoma transforming into Cushing disease: 11-year follow-up. Neurosurgery. 2013;72(1):E144–6.

    Article  Google Scholar 

  16. Melcescu E, Hogan RB 2nd, Brown K, Boyd SA, Abell TL, Koch CA. The various faces of autoimmune endocrinopathies: non-tumoral hypergastrinemia in a patient with lymphocytic colitis and chronic autoimmune gastritis. Exp Mol Pathol. 2012;93(3):434–40.

    Article  CAS  Google Scholar 

  17. Grozinsky-Glasberg S, Alexandraki KI, Angelousi A, Chatzellis E, Sougioultzis S, Kaltsas G. Gastric Carcinoids. Endocrinol Metab Clin N Am. 2018;47(3):645–60.

    Article  Google Scholar 

  18. East HE, Subauste JS, Gandhi A, Koch CA. About secondary causes of diabetes mellitus. J Miss State Med Assoc. 2012;53(11):380–3.

    PubMed  Google Scholar 

  19. Vinik A, Perry RR, Casellini C, Hughes MS, Feliberti E. Pathophysiology and Treatment of Pancreatic Neuroendocrine Tumors (PNETs): New Developments. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. 2018 Jun 12. https://www.ncbi.nlm.nih.gov/books/NBK279074/

  20. Vinik A, Hughes MS, Feliberti E, Perry RR, Casellini C, Sinesi M, Vingan H, Johnson L. Carcinoid Tumors. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. 2018 Feb 5. https://www.ncbi.nlm.nih.gov/books/NBK279162/

  21. Petersenn S, Koch CA. Neuroendocrine neoplasms - still a challenge despite major advances in clinical care with the development of specialized guidelines. Rev Endocr Metab Disord. 2017;18(4):373–8.

    Article  Google Scholar 

  22. Phillips J, East HE, French SE, Melcescu E, Hamilton RD, Nicholas WC, et al. What causes a prolactinoma to be aggressive or to become a pituitary carcinoma? Hormones. 2012;11(4):477–82.

    Article  Google Scholar 

  23. Deutschbein T, Fassnacht M, Weismann D, Reincke M, Mann K, Petersenn S. Treatment of malignant phaeochromocytoma with a combination of cyclophosphamide, vincristine and dacarbazine: own experience and overview of the contemporary literature. Clin Endocrinol (Oxf). 2015;82(1):84–90.

    Article  CAS  Google Scholar 

  24. Poeppel TD, Binse I, Petersenn S, Lahner H, Schott M, Antoch G, et al. Differential uptake of (68)Ga-DOTATOC and (68)Ga-DOTATATE in PET/CT of gastroenteropancreatic neuroendocrine tumors. Recent Results Cancer Res. 2013;194:353–71.

    Article  CAS  Google Scholar 

  25. Anlauf M, Schlenger R, Perren A, Bauersfeld J, Koch CA, Dralle H, et al. Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. Am J Surg Pathol. 2006;30(5):560–74.

    Article  Google Scholar 

  26. Anlauf M, Bauersfeld J, Raffel A, Koch CA, Henopp T, Alkatout I, et al. Insulinomatosis: a multicentric insulinoma disease that frequently causes early recurrent hyperinsulinemic hypoglycemia. Am J Surg Pathol. 2009;33(3):339–46.

    Article  Google Scholar 

  27. Huang SC, Koch CA, Vortmeyer AO, Pack SD, Lichtenauer UD, Mannan P, et al. Duplication of the mutant RET allele in trisomy 10 or loss of the wild-type allele in multiple endocrine neoplasia type 2-associated pheochromocytomas. Cancer Res. 2000;60(22):6223–6.

    CAS  PubMed  Google Scholar 

  28. Gläsker S, Neumann HPH, Koch CA, Vortmeyer A. Von Hippel-Lindau Disease. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth: MDText.com, Inc.; 2000-. 2018 Sep 12. https://www.ncbi.nlm.nih.gov/pubmed/25905347.

  29. Pieterman CRC, de Laat JM, Twisk JWR, van Leeuwaarde RS, de Herder WW, Dreijerink KMA, et al. Van der Horst-Schrivers ANA, Drent ML, Bisschop PH, Havekes B, Borel Rinkes IHM, Vriens MR, Valk GD. Long-term natural course of small nonfunctional pancreatic neuroendocrine tumors in MEN1-results from the Dutch MEN1 study group. J Clin Endocrinol Metab. 2017;102(10):3795–805.

    Article  Google Scholar 

  30. Tulipano G, Schulz S. Novel insights in somatostatin receptor physiology. Eur J Endocrinol. 2007;156(Suppl 1):S3–11.

    Article  CAS  Google Scholar 

  31. Angelousi A, Kaltsas G, Koumarianou A, Weickert MO, Grossman A. Chemotherapy in NETs: when and how. Rev Endocr Metab Disord. 2017;18(4):485–97.

    Article  Google Scholar 

  32. Pavel M, Valle JW, Eriksson B, Rinke A, Caplin M, Chen J, et al. ENETS consensus guidelines for the standards of Care in Neuroendocrine Neoplasms: systemic therapy - biotherapy and novel targeted agents. Neuroendocrinology. 2017;105(3):266–80.

    Article  CAS  Google Scholar 

  33. Woltering EA, Mamikunian PM, Zietz S, Krutzik SR, Go VL, Vinik AI, et al. Effect of octreotide LAR dose and weight on octreotide blood levels in patients with neuroendocrine tumors. Pancreas. 2005;31(4):392–400.

    Article  CAS  Google Scholar 

  34. Romero FR, Rais-Bahrami S, Permpongkosol S, Fine SW, Kohanim S, Jarrett TW. Primary carcinoid tumors of the kidney. J Urol. 2006;176(6 Pt 1):2359–66.

    Article  Google Scholar 

  35. Shimbori M, Osaka K, Kawahara T, Kasahara R, Kawabata S, Makiyama K, et al. Large cell neuroendocrine carcinoma of the kidney with cardiac metastasis: a case report. J Med Case Rep. 2017;11(1):297.

    Article  Google Scholar 

  36. Gauthé M, Lièvre A, Alberini JL. Primary neuroendocrine tumor in a horseshoe kidney with positive 111In-Pentetreotide somatostatin receptor scintigraphy and negative 18F-DOPA PET/CT. Clin Nucl Med. 2015;40(11):e516–7.

    Article  Google Scholar 

  37. Maletzki P, Diener PA, Bjasch D, Schmid HP, Gramann T. Primary neuroendocrine tumor of the kidney. A rarity. Urologe A. 2015;54(6):844–8.

    Article  CAS  Google Scholar 

  38. Mardi K, Negi L, Srivastava S. Well differentiated neuroendocrine tumor of the kidney: report of a rare case with review of literature. Indian J Pathol Microbiol. 2017;60(1):105–7.

    PubMed  Google Scholar 

  39. Moch H. Neuroendocrine tumors of the kidneys. Pathologe. 2015;36(3):278–82.

    Article  CAS  Google Scholar 

  40. Gu X, Cheng M, Herrera GA. Kidney carcinoid tumor: histological, immunohistochemical and ultrastructural features. Ultrastruct Pathol. 2018;42(1):18–22.

    Article  Google Scholar 

  41. Claessens T, Weppler SA, van Geel M, Creytens D, Vreeburg M, Wouters B, et al. Neuroendocrine carcinoma in a patient with Birt-Hogg-Dubé syndrome. Nat Rev Urol. 2010;7(10):583–7.

    Article  Google Scholar 

  42. Dynkevich Y, Rother KI, Whitford I, Qureshi S, Galiveeti S, Szulc AL, et al. Tumors, IGF-2, and hypoglycemia: insights from the clinic, the laboratory, and the historical archive. Endocr Rev. 2013;34(6):798–826.

    Article  CAS  Google Scholar 

  43. Murakami K, Nakamura Y, Felizola SJ, Morimoto R, Satoh F, Takanami K, et al. Pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome. Mol Cell Endocrinol. 2016;436:268–73.

    Article  CAS  Google Scholar 

  44. Yabuki H, Sakurada A, Niikawa H, Notsuda H, Endo C, Matsuda Y, et al. Serum β-hCG as an Indicator of recurrence after the complete resection of a malignant solitary fibrous tumor of the pleura. Ann Thorac Surg. 2016;102(6):e551–3.

    Article  Google Scholar 

  45. Osinga TE, van den Eijnden MH, Kema IP, Kerstens MN, Dullaart RP, de Jong WH, et al. Van der Horst-Schrivers AN. Unilateral and bilateral adrenalectomy for pheochromocytoma requires adjustment of urinary and plasma metanephrine reference ranges. J Clin Endocrinol Metab. 2013;98(3):1076–83.

    Article  CAS  Google Scholar 

  46. Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915–42.

    Article  CAS  Google Scholar 

  47. Majumdar S, Friedrich CA, Koch CA, Megason GC, Fratkin JD, Moll GW. Compound heterozygous mutation with a novel splice donor region DNA sequence variant in the succinate dehydrogenase subunit B gene in malignant paraganglioma. Pediatr Blood Cancer. 2010;54(3):473–5.

    Article  Google Scholar 

  48. O'Shea T, Druce M. When should genetic testing be performed in patients with neuroendocrine tumours? Rev Endocr Metab Disord. 2017;18(4):499–515.

    Article  CAS  Google Scholar 

  49. Koch CA, Chrousos GP. Overview of Endocrine Hypertension. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; .2000–.2016 Oct 26. https://www.ncbi.nlm.nih.gov/pubmed/25905214

  50. Hannah-Shmouni F, Melcescu E, Koch CA. Testing for Endocrine Hypertension In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; .2000–.2016 Dec 30.

  51. Hannah-Shmouni F, Stratakis CA, Koch CA. Flushing in (neuro)endocrinology. Rev Endocr Metab Disord. 2016;17(3):373–80.

    Article  CAS  Google Scholar 

  52. Singer J, Werner F, Koch CA, Bartels M, Aigner T, Lincke T, et al. Ectopic Cushing's syndrome caused by a well differentiated ACTH-secreting neuroendocrine carcinoma of the ileum. Exp Clin Endocrinol Diabetes. 2010;118(8):524–9.

    Article  CAS  Google Scholar 

  53. Castillo JG, Naib T, Zacks JS, Adams DH. Echocardiography in functional midgut neuroendocrine tumors: when and how often. Rev Endocr Metab Disord. 2017;18(4):411–21.

    Article  CAS  Google Scholar 

  54. Jann H, Wertenbruch T, Pape U, Ozcelik C, Denecke T, Mehl S, et al. A matter of the heart: myocardial metastases in neuroendocrine tumors. Horm Metab Res. 2010;42(13):967–76.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Medicover GmbH, Berlin / Hannover, Germany

    Christian A. Koch

  2. Carl von Ossietzky University of Oldenburg, Oldenburg, Germany

    Christian A. Koch

  3. Technical University of Dresden, Dresden, Germany

    Christian A. Koch

  4. University of Louisville, Louisville, KY, USA

    Christian A. Koch

  5. ENDOC Center for Endocrine Tumors, Hamburg, Germany

    S. Petersenn

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  1. Christian A. Koch
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Correspondence to Christian A. Koch.

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Conflict of interest

Prof. Koch declares no direct conflict with this article. He has served on the Advisory Board of Novartis on the topic acromegaly and has participated in educational conferences on the topics neuroendocrine tumors and acromegaly sponsored by Novartis and Ipsen. Prof. Petersenn declares no direct conflict with this article. He has served on the Advisory Board of Ipsen on the topics of acromegaly and NEN.

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Patients provided informed consent for publication.

Additional information

Some of the material has been presented in poster form at international meetings, for instance:

Koch CA, Paschke R, Witzigmann H, Petersenn S, Josten C, Kluge R, Bigler S, Tannapfel A. Long-term survival of a patient with a malignant neuroendocrine tumor of the kidney. Poster P3-797, Endocrine Society, Toronto, Canada, June 2007

Vijayakumar V, Koch CA. Update on the role of nuclear medicine in the diagnosis and therapy of patients with pheochromocytoma. The 41st Annual Scientific Meeting ANZ SNM, Darwin, Australia, July 17/18, Poster P-80, published in Internal Medicine Journal, July 2011, Vol.41 (Suppl 3):43

Case 2 has been presented in figure illustration format in reference 42.

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Koch, C.A., Petersenn, S. Black swans - neuroendocrine tumors of rare locations. Rev Endocr Metab Disord 19, 111–121 (2018). https://doi.org/10.1007/s11154-018-9473-0

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