Skip to main content
SpringerLink
Log in

The Diagnosis of Neuroendocrine Neoplasms

  • Chapter
  • First Online:
The Spectrum of Neuroendocrine Neoplasia

Abstract

The diagnosis of neuroendocrine tumors is based on the recognition of signs and symptoms of the structural and functional effects of these tumors. The structural impact depends on the location of the tumor; in some, such as the pituitary, the structural impact can be significant because of mass effects in a small enclosed and critical area, whereas in others, such as distal pancreas or retroperitoneal sites like adrenal, tumors can grow to be very large without major mass effects. The functional aspects of these tumors involve biochemical confirmation that can be very complex. In this chapter, the various hormone excess syndromes are discussed, along with the specific structural considerations at the common sites of neuroendocrine tumors. The wide array of clinical manifestations of neuroendocrine tumors emphasizes the importance of careful clinical history, sophisticated biochemical investigations, and thoughtful consideration of the potential for germline predisposition syndromes that are common in these disorders.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Christakis I, Qiu W, Silva Figueroa AM, et al. Clinical features, treatments, and outcomes of patients with thymic carcinoids and multiple endocrine neoplasia type 1 syndrome at MD Anderson Cancer Center. Horm Cancer. 2016;7(4):279–87. https://doi.org/10.1007/s12672-016-0269-y.

    Article  CAS  PubMed  Google Scholar 

  2. Lowney JK, Frisella MM, Lairmore TC, et al. Pancreatic islet cell tumor metastasis in multiple endocrine neoplasia type 1: correlation with primary tumor size. Surgery. 1998;124(6):1043–9. https://doi.org/10.1067/msy.1998.92561.

    Article  CAS  PubMed  Google Scholar 

  3. Larouche V, Akirov A, Thain E, Kim RH, Ezzat S. Co-occurrence of breast cancer and neuroendocrine tumours: new genetic insights beyond multiple endocrine neoplasia syndromes. Endocrinol Diabetes Metab. 2019;2(4):1–8. https://doi.org/10.1002/edm2.92.

    Article  Google Scholar 

  4. Scarpa A, Chang D, Grimmond S, et al. Co-occurrence of breast cancer and neuroendocrine tumours: new genetic insights beyond Multiple Endocrine Neoplasia syndromes. Nature. 2017;543:65–71.

    Article  CAS  PubMed  Google Scholar 

  5. Ro C, Chai W, Yu VE, Yu R. Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment. Chin J Cancer. 2013;32(6):312–24. https://doi.org/10.5732/cjc.012.10295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Laskaratos FM, Rombouts K, Caplin M, Toumpanakis C, Thirlwell C, Mandair D. Neuroendocrine tumors and fibrosis: an unsolved mystery? Cancer. 2017;123(24):4770–90. https://doi.org/10.1002/cncr.31079.

    Article  PubMed  Google Scholar 

  7. Shah MH, Goldner WS, Halfdanarson TR, et al. Neuroendocrine and adrenal tumors, version 2.2018 featured updates to the NCCN guidelines. JNCCN J Natl Compr Canc Netw. 2018;16(6):693–702. https://doi.org/10.6004/jnccn.2018.0056.

    Article  CAS  PubMed  Google Scholar 

  8. Falconi M, Eriksson B, Kaltsas G, et al. ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology. 2016;103(2):153–71. https://doi.org/10.1159/000443171.Consensus.

    Article  CAS  PubMed  Google Scholar 

  9. Rubin de Celis Ferrari AC, Glasberg J, Riechelmann RP. Carcinoid syndrome: update on the pathophysiology and treatment. Clinics. 2018;73:1–9. https://doi.org/10.6061/clinics/2018/e490s.

    Article  Google Scholar 

  10. Melmed S, Koenig R, Al E. Williams textbook of endocrinology. Elsevier, Philadelphia. 13th ed. 2015.

    Google Scholar 

  11. Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Current status of gastrointestinal carcinoids. Gastroenterology. 2005;128(6):1717–51. https://doi.org/10.1053/j.gastro.2005.03.038.

    Article  PubMed  Google Scholar 

  12. Placzkowski KA, Vella A, Thompson GB, et al. Secular trends in the presentation and management of functioning insulinoma at the mayo clinic, 1987-2007. J Clin Endocrinol Metab. 2009;94(4):1069–73. https://doi.org/10.1210/jc.2008-2031.

    Article  CAS  PubMed  Google Scholar 

  13. Service FJ, Dale AJ, Elveback LRJN. Insulinoma: clinical and diagnostic features of 60 consecutive cases. Mayo Clin Proc. 1976;51(7):417.

    PubMed  Google Scholar 

  14. F.J. Service. Hypoglycemic disorders. N Engl J Med. 1995;332(17). https://doi.org/10.1177/1461444810365020.

  15. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2009. https://doi.org/10.1210/jc.2008-1410.

  16. Roy PK, Venzon DJ, Shojamanesh H, et al. Zollinger-Ellison syndrome: clinical presentation in 261 patients. Medicine (Baltimore). 2000. https://doi.org/10.1097/00005792-200011000-00004.

  17. Wermers RA, Fatourechi V, Wynne AG, Kvols LK, Lloyd RV. The glucagonoma syndrome: clinical and pathologic features in 21 patients. Medicine (Baltimore). 1996. https://doi.org/10.1097/00005792-199603000-00002.

  18. Lévy-Bohbot N, Merle C, Goudet P, et al. Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol. 2004. https://doi.org/10.1016/S0399-8320(04)95184-6.

  19. Schwartz TW. Pancreatic-polypeptide (PP) and endocrine tumours of the pancreas. Scand J Gastroenterol. 1979;53:93–100.

    CAS  Google Scholar 

  20. Vinik A, Feliberti E, Perry RR, Al E. Pancreatic polypeptide. Endotext [Internet] South Dartmouth.

    Google Scholar 

  21. Soga J, Yakuwa Y. Somatostatinoma/inhibitory syndrome: a statistical evaluation of 173 reported cases as compared to other pancreatic endocrinomas. J Exp Clin Cancer Res. 1999;18(1):13–22.

    CAS  PubMed  Google Scholar 

  22. Ligiero Braga T, Santos-Oliveira R. PPoma review: epidemiology, aetiopathogenesis, prognosis and treatment. Diseases. 2018;6(1):8. https://doi.org/10.3390/diseases6010008.

    Article  CAS  PubMed Central  Google Scholar 

  23. Akirov A, Larouche V, Alshehri S, Asa SL, Ezzat S. Treatment options for pancreatic neuroendocrine tumors. Cancers (Basel). 2019;11(6). https://doi.org/10.3390/cancers11060828.

  24. Lenders J, Eishenhofer G, Mannelli M, Al E. Phaeochromocytoma. Lancet. 2005;366:665–75. https://doi.org/10.1016/S0300-595X(85)80070-0.

    Article  PubMed  Google Scholar 

  25. Berends AMA, Buitenwerf E, de Krijger RR, et al. Incidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: a nationwide study and systematic review. Eur J Intern Med. 2018;51(November 2017):68–73. https://doi.org/10.1016/j.ejim.2018.01.015.

    Article  PubMed  Google Scholar 

  26. Ranaweera M. Bladder paraganglioma: a report of case series and critical review of current literature. World J Clin Cases. 2014;2(10):591. https://doi.org/10.12998/wjcc.v2.i10.591.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Foo SH, Chan SP, Ananda V, Al E. Dopamine-secreting phaeochromocytomas and paragangliomas: clinical features and management. Singapore Med J. 2010;51(5):e89.

    CAS  PubMed  Google Scholar 

  28. Yi JW, Oh EM, Lee KE, et al. An exclusively dopamine secreting paraganglioma in the retroperitoneum: a first clinical case in Korea. J Korean Surg Soc. 2012;82(6):389–93. https://doi.org/10.4174/jkss.2012.82.6.389.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Neumann HPH, Young WF, Eng C. Pheochromocytoma and paraganglioma. N Engl J Med. 2019;381(6):552–65. https://doi.org/10.1056/NEJMra1806651.

    Article  CAS  PubMed  Google Scholar 

  30. Asa S, Ezzat S, Mete O. The diagnosis and clinical significance of Paragangliomas in unusual locations. J Clin Med. 2018;7(9):280. https://doi.org/10.3390/jcm7090280.

    Article  CAS  PubMed Central  Google Scholar 

  31. Canu L, Van Hemert JAW, Kerstens MN, et al. CT characteristics of pheochromocytoma: relevance for the evaluation of adrenal incidentaloma. J Clin Endocrinol Metab. 2018;104(2):312–8. https://doi.org/10.1210/jc.2018-01532.

    Article  Google Scholar 

  32. Fernandez A, Karavitaki N, Wass JAH. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol. 2010;72(3):377–82. https://doi.org/10.1111/j.1365-2265.2009.03667.x.

    Article  Google Scholar 

  33. Lüdecke DK, Buchfelder M, Fahlbusch R, Quabbe HJ, Petersenn S, Saeger W. Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol. 2007;156(2):203–16. https://doi.org/10.1530/eje.1.02326.

    Article  CAS  PubMed  Google Scholar 

  34. Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(4):894–904. https://doi.org/10.1210/jc.2010-1048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Grubb MR, Chakeres D, Malarkey WB. Patients with primary hypothyroidism presenting as prolactinomas. Am J Med. 1987;83(4):765–9. https://doi.org/10.1016/0002-9343(87)90911-9.

    Article  CAS  PubMed  Google Scholar 

  36. Molitch ME. Drugs and prolactin. Pituitary. 2008;11(2):209–18. https://doi.org/10.1007/s11102-008-0106-6.

    Article  CAS  PubMed  Google Scholar 

  37. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273–88. https://doi.org/10.1210/jc.2010-1692.

    Article  CAS  PubMed  Google Scholar 

  38. Olsen LJS, Irizarry LR, Chao ST, et al. Radiotherapy for prolactin-secreting pituitary tumors. Pituitary. 2012;15(2):135–45. https://doi.org/10.1007/s11102-011-0348-6.

    Article  Google Scholar 

  39. St-Jean E, Blain FCR. High prolactin levels may be missed by immunoradiometric assay in patients with macroprolactinomas. Clin Endocrinol. 1996;44(3):305.

    Article  CAS  Google Scholar 

  40. Nieman LK, Biller BMK, Findling JW, et al. The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008;93(5):1526–40. https://doi.org/10.1210/jc.2008-0125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Feelders RA, Newell-price J, Pivonello R, Nieman LK, Hofland LJ, Lacroix A. Advances in the medical treatment of Cushing’s syndrome. Lancet Diabetes Endocrinol. 2018;8587(2). https://doi.org/10.1016/S2213-8587(18)30155-4.

  42. Liddle GW. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 1960;20(12). https://doi.org/10.1097/01.ten.0000188392.60458.56.

  43. Zhou C, Jiao Y, Wang R, Ren SG, Wawrowsky K, Melmed S. STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion. J Clin Invest. 2015;125(4):1692–702. https://doi.org/10.1172/JCI78173.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Katznelson L, Laws ER, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933–51. https://doi.org/10.1210/jc.2014-2700.

    Article  CAS  PubMed  Google Scholar 

  45. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004;25(1):102–52. https://doi.org/10.1210/er.2002-0022.

    Article  CAS  PubMed  Google Scholar 

  46. Giustina A, Chanson P, Kleinberg D, et al. Expert consensus document: a consensus on the medical treatment of acromegaly. Nat Rev Endocrinol. 2014;10(4):243–8. https://doi.org/10.1038/nrendo.2014.21.

    Article  CAS  PubMed  Google Scholar 

  47. Bilezikian JP, Cusano NE, Khan AA, Liu JM, Marcocci C, Bandeira F. Primary hyperparathyroidism. Nat Rev Dis Primers. 2016;2:1–16. https://doi.org/10.1038/nrdp.2016.33.

    Article  Google Scholar 

  48. Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016;151(10):959–68. https://doi.org/10.1001/jamasurg.2016.2310.

    Article  PubMed  Google Scholar 

  49. Marcocci C, Cetani F, Rubin MR, Silverberg SJ, Pinchera A, Bilezikian JP. Parathyroid carcinoma. J Bone Miner Res. 2008;23(12):1869–80. https://doi.org/10.1359/jbmr.081018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Akirov A, Asa SL, Larouche V, et al. The clinicopathological spectrum of parathyroid carcinoma. Front Endocrinol (Lausanne). 2019;10(October):1–10. https://doi.org/10.3389/fendo.2019.00731.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Endocrine Oncology Site Group, Princess Margaret Cancer Centre, Toronto, ON, Canada

    Jessica Chbat, Lama Amer, Amit Akirov & Shereen Ezzat

Authors
  1. Jessica Chbat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lama Amer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amit Akirov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shereen Ezzat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shereen Ezzat .

Editor information

Editors and Affiliations

  1. University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA

    Sylvia L. Asa

  2. Institute of Pathology, University Hospital of Lausanne, Lausanne, Vaud, Switzerland

    Stefano La Rosa

  3. Department of Pathology, University Health Network, Toronto, ON, Canada

    Ozgur Mete

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chbat, J., Amer, L., Akirov, A., Ezzat, S. (2021). The Diagnosis of Neuroendocrine Neoplasms. In: Asa, S.L., La Rosa, S., Mete, O. (eds) The Spectrum of Neuroendocrine Neoplasia. Springer, Cham. https://doi.org/10.1007/978-3-030-54391-4_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-54391-4_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-54390-7

  • Online ISBN: 978-3-030-54391-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation