Abstract
Carcinoid tumours arise in cells of the diffuse neuroendocrine system and can develop in a number of anatomical sites including the lungs and the gastrointestinal tract. There has been a move away from the use of the term carcinoid tumour to the more appropriate use of neuroendocrine tumour (NET) to highlight the potential for invasion and metastasis associated with some NETs. Although most cases are sporadic, 15–20 % of cases are related to a hereditary syndrome, the most common of these being multiple endocrine neoplasia 1 (MEN1) . Other hereditary syndromes include the following: von Hippel–Lindau (VHL) , neurofibromatosis 1 and tuberous sclerosis complex (TSC) , which are all associated with a germline mutation of the associated tumour suppressor gene and an autosomal dominant inheritance pattern. Familial small intestinal NET (SI NET) is a recently described condition which is also inherited in an autosomal dominant manner. There appears to be more than one causative gene; thus far, only the IPMK gene has been identified as a causative germline mutation. This was identified by carrying out whole-exome sequencing of germline and tumour DNA in a family with multiple members diagnosed with SI NET. Identification of NET predisposition genes in other families via these methods will allow the development of dedicated NET gene panels which can be used to screen NET patients and at-risk relatives for hereditary mutations. Close surveillance of at-risk individuals is important to detect NETs early when curative surgery can be offered and the morbidity and mortality of metastatic NETs can be avoided.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Agarwal SK, Mateo CM, Marx SJ (2009) Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states. J Clin Endocrinol Metab 94:1826–1834
Bergsland EK (2013) The evolving landscape of neuroendocrine tumors. Semin Oncol 40:4–22
Blansfield JA, Choyke L, Morita SY, Choyke PL, Pingpank JF, Alexander HR, Seidel G, Shutack Y, Yuldasheva N, Eugeni M, Bartlett DL, Glenn GM, Middelton L, Linehan WM, Libutti SK (2007) Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs). Surgery 142:814–818; discussion 818 e1–e2
Chetty R (2008) Requiem for the term ‘carcinoid tumour’ in the gastrointestinal tract? Can J Gastroenterol 22:357–358
Chou A, Toon C, Pickett J, Gill AJ (2013) von Hippel-Lindau syndrome. Front Horm Res 41:30–49
Cnossen MH, van der Est MN, Breuning MH, van Asperen CJ, Breslau-Siderius EJ, van der Ploeg AT, De Goede-Bolder A, van den Ouweland AM, Halley DJ, Niermeijer MF (1997) Deletions spanning the neurofibromatosis type 1 gene: implications for genotype-phenotype correlations in neurofibromatosis type 1? Hum Mutat 9:458–464
Cunningham JL, Diaz de Stahl T, Sjoblom T, Westin G, Dumanski JP, Janson ET (2011) Common pathogenetic mechanism involving human chromosome 18 in familial and sporadic ileal carcinoid tumors. Genes Chromosomes Cancer 50:82–94
Dworakowska D, Grossman AB (2009) Are neuroendocrine tumours a feature of tuberous sclerosis? A systematic review. Endocr Relat Cancer 16:45–58
Elston MS, McDonald KL, Clifton-Bligh RJ, Robinson BG (2009) Familial pituitary tumor syndromes. Nat Rev Endocrinol 5:453–461
Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, Upadhyaya M, Towers R, Gleeson M, Steiger C, Kirby A (2007) Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet 44:81–88
Garcia-Carbonero R, Capdevila J, Crespo-Herrero G, Diaz-Perez JA, Martinez Del Prado MP, Alonso Orduna V, Sevilla-Garcia I, Villabona-Artero C, Beguiristain-Gomez A, Llanos-Munoz M, Marazuela M, Alvarez-Escola C, Castellano D, Vilar E, Jimenez-Fonseca P, Teule A, Sastre-Valera J, Benavent-Vinuelas M, Monleon A, Salazar R (2010). Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). Ann Oncol 21:1794–1803
Goudet P, Murat A, Binquet C, Cardot-Bauters C, Costa A, Ruszniewski P, Niccoli P, Menegaux F, Chabrier G, Borson-Chazot F, Tabarin A, Bouchard P, Delemer B, Beckers A, Bonithon-Kopp C (2010) Risk factors and causes of death in MEN1 disease. A GTE (Groupe d’Etude des Tumeurs Endocrines) cohort study among 758 patients. World J Surg 34:249–255
Hauso O, Gustafsson BI, Kidd M, Waldum HL, Drozdov I, Chan AK, Modlin IM (2008) Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer 113:2655–2664
Hirbe AC, Gutmann DH (2014) Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 13:834–843
Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S (2010) The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 39:707–712
Krueger DA, Northrup H, International Tuberous Sclerosis Complex Consensus Group (2013) Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 49:255–265
Kunz PL (2015) Carcinoid and neuroendocrine tumors: building on success. J Clin Oncol 33:1855–1863
Larson AM, Hedgire SS, Deshpande V, Stemmer-Rachamimov AO, Harisinghani MG, Ferrone CR, Shah U, Thiele EA (2012) Pancreatic neuroendocrine tumors in patients with tuberous sclerosis complex. Clin Genet 82:558–563
Lemos MC, Thakker RV (2008) Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat 29:22–32
Lin AL, Gutmann DH (2013) Advances in the treatment of neurofibromatosis-associated tumours. Nat Rev Clin Oncol 10:616–624
Maher ER, Neumann HP, Richard S (2011) von Hippel-Lindau disease: a clinical and scientific review. Eur J Hum Genet 19:617–623
Marcos HB, Libutti SK, Alexander HR, Lubensky IA, Bartlett DL, Walther MM, Linehan WM, Glenn GM, Choyke PL (2002) Neuroendocrine tumors of the pancreas in von Hippel-Lindau disease: spectrum of appearances at CT and MR imaging with histopathologic comparison. Radiology 225:751–758
Marini F, Giusti F, Brandi ML (2015) Genetic test in multiple endocrine neoplasia type 1 syndrome: an evolving story. World J Exp Med 5:124–129
Modlin IM, Shapiro MD, Kidd M (2004) Siegfried oberndorfer: origins and perspectives of carcinoid tumors. Hum Pathol 35:1440–1451
Molatore S, Marinoni I, Lee M, Pulz E, Ambrosio MR, Degli Uberti EC, Zatelli MC, Pellegata NS (2010) A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization. Hum Mutat 31:E1825–E1835
Nikou GC, Angelopoulos TP (2012) Current concepts on gastric carcinoid tumors. Gastroenterol Res Pract 2012:287825
Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group (2013) Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 49:243–254
Oberg K, Hellman P, Ferolla P, Papotti M, Group EGW (2012) Neuroendocrine bronchial and thymic tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii120–vii123
Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, Fend F, Graw J, Atkinson MJ (2006) Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci USA 103:15558–15563
Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Horsch D, Hammel P, Wiedenmann B, van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P (2011) Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364:501–513
Sei Y, Zhao X, Forbes J, Szymczak S, Li Q, Trivedi A, Voellinger M, Joy G, Feng J, Whatley M, Jones MS, Harper UL, Marx SJ, Venkatesan AM, Chandrasekharappa SC, Raffeld M, Quezado MM, Louie A, Chen CC, Lim RM, Agarwala R, Schaffer AA, Hughes MS, Bailey-Wilson JE, Wank SA (2015) A hereditary form of small intestinal carcinoid associated with a germline mutation in inositol polyphosphate multikinase. Gastroenterology 149:67–78
Strosberg J (2012) Neuroendocrine tumours of the small intestine. Best Pract Res Clin Gastroenterol 26:755–773
Taal BG, Visser O (2004) Epidemiology of neuroendocrine tumours. Neuroendocrinology 80(Suppl 1):3–7
Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML, Endocrine S (2012) Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 97:2990–3011
Thomas-Marques L, Murat A, Delemer B, Penfornis A, Cardot-Bauters C, Baudin E, Niccoli-Sire P, Levoir D, Choplin Hdu B, Chabre O, Jovenin N, Cadiot G, Groupe des Tumeurs E (2006) Prospective endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. Am J Gastroenterol 101:266–273
Toledo SP, Lourenço DM Jr, Toledo RA (2013) A differential diagnosis of inherited endocrine tumors and their tumor counterparts. Clinics 68(7):1039–1056
Triponez F, Dosseh D, Goudet P, Cougard P, Bauters C, Murat A, Cadiot G, Niccoli-Sire P, Chayvialle JA, Calender A, Proye CA (2006a) Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg 243:265–272
Triponez F, Goudet P, Dosseh D, Cougard P, Bauters C, Murat A, Cadiot G, Niccoli-Sire P, Calender A, Proye CA, French Endocrine Tumor Study G (2006b) Is surgery beneficial for MEN1 patients with small (< or =2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg 30:654–662; discussion 663–664
Ullmann U, Unuane D, Velkeniers B, Lissens W, Wuyts W, Bonduelle M (2013) A new double substitution mutation in the MEN1 gene: a limited penetrance and a specific phenotype. Eur J Hum Genet 21:695–697
Woodward ER, Maher ER (2006) Von Hippel-Lindau disease and endocrine tumour susceptibility. Endocr Relat Cancer 13:415–425
Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB (2008) One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26:3063–3072
Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Oberg K, RAD001 in advanced neuroendocrine tumors TTSG (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364:514–523
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Benafif, S., Eeles, R. (2016). Diagnosis and Management of Hereditary Carcinoids. In: Pichert, G., Jacobs, C. (eds) Rare Hereditary Cancers. Recent Results in Cancer Research, vol 205. Springer, Cham. https://doi.org/10.1007/978-3-319-29998-3_9
Download citation
DOI: https://doi.org/10.1007/978-3-319-29998-3_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-29996-9
Online ISBN: 978-3-319-29998-3
eBook Packages: MedicineMedicine (R0)