Advertisement

World Journal of Surgery

, Volume 42, Issue 1, pp 143–152 | Cite as

Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study

  • P. Lecomte
  • C. Binquet
  • M. Le Bras
  • A. Tabarin
  • C. Cardot-Bauters
  • F. Borson-Chazot
  • C. Lombard-Bohas
  • E. Baudin
  • B. Delemer
  • M. Klein
  • B. Vergès
  • T. Aparicio
  • E. Cosson
  • A. Beckers
  • Ph. Caron
  • O. Chabre
  • Ph. Chanson
  • H. Du Boullay
  • I. Guilhem
  • P. Niccoli
  • V. Rohmer
  • J. Guigay
  • C. Vulpoi
  • J. Y. Scoazec
  • P. Goudet
Original Scientific Report

Abstract

Objective

To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death.

Summary background data

br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis.

Methods

The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5–59.6] years by the Groupe d’étude des Tumeurs Endocrines was analyzed using time-to-event techniques.

Results

br-NETs were found in 51 patients (4.8%, [95% CI 3.6–6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28–66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02–5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10−4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths.

Conclusions

Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

Notes

Acknowledgements

The authors thank Annie Costa and Sandrine Daniel for the data management and Philip Bastable for checking the English.

Compliance with ethical standards

Conflict of interest

The authors have nothing to disclose.

References

  1. 1.
    Wermer P (1968) Duality of pancreatogenous peptic ulcer. N Engl J Med 278:397–398PubMedGoogle Scholar
  2. 2.
    Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang Z, Lubensky IA, Liotta LA, Crabtree JS, Wang Y, Roe BA, Weisemann J, Boguski MS, Agarwal SK, Kester MB, Kim YS, Heppner C, Dong Q, Spiegel AM, Burns AL, Marx SJ (1997) Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 18(276):404–407CrossRefGoogle Scholar
  3. 3.
    Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671CrossRefPubMedGoogle Scholar
  4. 4.
    Kouvaraki MA, Lee JE, Shapiro SE, Gagel RF, Sherman SI, Sellin RV et al (2002) Genotype-phenotype analysis in multiple endocrine neoplasia type 1. Arch Surg 137:641–647CrossRefPubMedGoogle Scholar
  5. 5.
    Sachithanandan N, Harle RA, Burgess JR (2005) Bronchopulmonary carcinoid in multiple endocrine neoplasia type 1. Cancer 103:509–515CrossRefPubMedGoogle Scholar
  6. 6.
    De Laat JM, Pieterman CR, van den Broek MF, Twisk JW, Hermus AR, Dekkers OM et al (2014) Natural Course and survival of neuroendocrine tumors of thymus and lung in MEN1 patients. J Clin Endocrinol Metab 99:3325–3333CrossRefPubMedGoogle Scholar
  7. 7.
    Goudet P, Bonithon-Kopp C, Murat A, Ruszniewski P, Niccoli P, Ménégaux F, Chabrier G, Borson-Chazot F, Tabarin A, Bouchard P, Cadiot G, Beckers A, Guilhem I, Chabre O, Caron P, Du Boullay H, Verges B, Cardot-Bauters C (2011) Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d’étude des Tumeurs Endocrines. Eur J Endocrinol 165:97–105CrossRefPubMedGoogle Scholar
  8. 8.
    Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR et al (2012) Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 97(9):2990–3011CrossRefPubMedGoogle Scholar
  9. 9.
    Thakker RV (2010) Multiple endocrine neoplasia type 1 (MEN1). In: De Groot L, Jameson JL (eds) Endocrinology, 6th edn. Elsevier, Philadelphia, pp 2719–2741Google Scholar
  10. 10.
    Singh Ospina N, Thompson GB, Nichols FC 3rd, Cassivi SD, Young WF Jr (2015) Thymic and bronchial carcinoid tumors in multiple endocrine neoplasia type 1: the mayo clinic experience from 1977 to 2013. Horm Cancer. 6(5–6):247–253CrossRefPubMedGoogle Scholar
  11. 11.
    Bartsch DK, Albers MB, Lopez CL, Apitzsch JC, Walthers EM, Fink L, Fendrich V, Slater EP, Waldmann J, Anlauf M (2016) Bronchopulmonary neuroendocrine neoplasms and their precursor lesions in multiple endocrine neoplasia type 1. Neuroendocrinology. 103(3–4):240–247.CrossRefPubMedGoogle Scholar
  12. 12.
    Goudet P, Murat A, Binquet C, Cardot-Bauters C, Costa A, Ruszniewski P et al (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. doi: 10.1007/s00268-009-0290-1 CrossRefPubMedGoogle Scholar
  13. 13.
    Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (eds) (2001) World Health Organization classification of tumours. Pathology & genetics of tumours of the lung, pleura, thymus and heart. IARC Press, LyonGoogle Scholar
  14. 14.
    Travis W, Brambilla E, Burke AP, Marx A, Nicholson AG (eds) (2014) WHO classification of tumours of the lung, pleura, thymus and heart, 4th edn. IARC Press, LyonGoogle Scholar
  15. 15.
    Steuer CE, Behera M, Kim S, Chen Z, Saba NF, Pillai RN, Owonikoko TK, Khuri FR, Ramalingam SS (2015) Atypical carcinoid tumor of the lung: a surveillance, epidemiology, and end results database analysis. J Thorac Oncol 10:479–485CrossRefPubMedGoogle Scholar
  16. 16.
    Fink G, Krelbaum T, Yellin A, Bendayan D, Saute M, Glazer M et al (2001) Pulmonary carcinoid: presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature. Chest 119:1647–1651CrossRefPubMedGoogle Scholar
  17. 17.
    Thevenon J, Bourredjem A, Faivre L, Cardot-Bauters C, Calender A, Murat A et al (2013) Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d’etude des Tumeurs Endocrines (GTE) cohort study. Hum Mol Genet 22:1940–1948CrossRefPubMedGoogle Scholar
  18. 18.
    Farid NR, Buehler S, Russell NA, Maroun FB, Allerdice P, Smyth HS (1980) Prolactinomas in familial multiple endocrine neoplasia syndrome type I. Relationship to HLA and carcinoid tumors. Am J Med 69(6):874–880CrossRefPubMedGoogle Scholar
  19. 19.
    Debelenko LV, Brambilla E, Agarwal SK, Swalwell JI, Kester MB, Lubensky IA, Zhuang Z, Guru SC, Manickam P, Olufemi SE, Chandrasekharappa SC, Crabtree JS, Kim YS, Heppner C, Burns AL, Spiegel AM, Marx SJ, Liotta LA, Collins FS, Travis WD, Emmert-Buck MR (1997) Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung. Hum Mol Genet 6(13):2285–2290CrossRefPubMedGoogle Scholar
  20. 20.
    Hao W, Skarulis MC, Simonds WF, Weinstein LS, Agarwal SK, Mateo C, James-Newton L, Hobbs GR, Gibril F, Jensen RT, Marx SJ (2004) Multiple endocrine neoplasia type 1 variant with frequent prolactinoma and rare gastrinoma. J Clin Endocrinol Metab 89(8):3776–3784CrossRefPubMedGoogle Scholar
  21. 21.
    den Bakker MA, Willemsen S, Grünberg K, Noorduijn LA, van Oosterhout MF, van Suylen RJ, Timens W, Vrugt B, Wiersma-van Tilburg A, Thunnissen FB (2010) Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability. Histopathology 56:356–363CrossRefGoogle Scholar
  22. 22.
    Volante M, Righi L, Berruti A, Rindi G, Papotti M (2011) The pathological diagnosis of neuroendocrine tumors: common questions and tentative answers. Virchows Arch 458:393–402CrossRefPubMedGoogle Scholar
  23. 23.
    Swarts DR, van Suylen RJ, den Bakker MA, van Oosterhout MF, Thunnissen FB, Volante M, Dingemans AM, Scheltinga MR, Bootsma GP, Pouwels HM, van den Borne BE, Ramaekers FC, Speel EJ (2014) Interobserver variability for the WHO classification of pulmonary carcinoids. Am J Surg Pathol 38:1429–1436CrossRefPubMedGoogle Scholar
  24. 24.
    Rindi G, Klersy C, Inzani F, Fellegara G, Ampollini L, Ardizzoni A, Campanini N, Carbognani P, De Pas TM, Galetta D, Granone PL, Righi L, Rusca M, Spaggiari L, Tiseo M, Viale G, Volante M, Papotti M, Pelosi G (2013) Grading the neuroendocrine tumors of the lung: an evidence-based proposal. Endocr Relat Cancer 21:1–16CrossRefPubMedGoogle Scholar
  25. 25.
    Yeh YC, Chou TY (2014) Pulmonary neuroendocrine tumors: study of 90 cases focusing on clinicopathological characteristics, immunophenotype, preoperative biopsy, and frozen section diagnoses. J Surg Oncol 109:280–286CrossRefPubMedGoogle Scholar
  26. 26.
    Ferolla P, Faggiano A, Avenia N, Milone F, Masone S, Giampaglia F, Puma F, Daddi G, Angeletti G, Lombardi G, Santeusanio F, Colao A (2007) Epidemiology of non-gastroenteropancreatic (neuro)endocrine tumours. Clin Endocrinol (Oxf) 66:1–6Google Scholar
  27. 27.
    Onuki N, Wistuba II, Travis WD, Virmani AK, Yashima K, Brambilla E, Hasleton P, Gazdar AF (1999) Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer 85:600–607CrossRefPubMedGoogle Scholar
  28. 28.
    Debelenko LV, Swalwell JI, Kelley MJ, Brambilla E, Manickam P, Baibakov G, Agarwal SK, Spiegel AM, Marx SJ, Chandrasekharappa SC, Collins FS, Travis WD, Emmert-Buck MR (2000) MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma. Genes Chromosomes Cancer 28:58–65CrossRefPubMedGoogle Scholar
  29. 29.
    Hörsch D, Schmid KW, Anlauf M, Darwiche K, Denecke T, Baum RP, Spitzweg C, Grohé C, Presselt N, Stremmel C, Heigener DF, Serke M, Kegel T, Pavel M, Waller CF, Deppermann KM, Arnold R, Huber RM, Weber MM, Hoffmann H (2014) Neuroendocrine tumors of the bronchopulmonary system (typical and atypical carcinoid tumors): current strategies in diagnosis and treatment. Conclusions of an expert meeting February 2011 in Weimar, Germany. Oncol Res Treat 37(5):266–276CrossRefPubMedGoogle Scholar
  30. 30.
    Journy N, Ancelet S, Rehel JC, Mezzarobba M, Aubert B, Laurier D, Bernier MO (2014) Predicted cancer risks induced by computed tomography examinations during childhood, by a quantitative risk assessment approach. Radiat Environ Biophys 53:39–54CrossRefPubMedGoogle Scholar
  31. 31.
    Pearce MS, Salotti JA, Little MP, McHugh K, Lee C, Kim KP, Howe NL, Ronckers CM, Rajaraman P, Craft AW, Parker L, Berrington de González A (2012) Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 380:499–505CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2017

Authors and Affiliations

  • P. Lecomte
    • 1
  • C. Binquet
    • 2
    • 3
    • 4
  • M. Le Bras
    • 5
  • A. Tabarin
    • 6
  • C. Cardot-Bauters
    • 7
  • F. Borson-Chazot
    • 8
    • 9
  • C. Lombard-Bohas
    • 10
  • E. Baudin
    • 11
  • B. Delemer
    • 12
  • M. Klein
    • 13
  • B. Vergès
    • 14
  • T. Aparicio
    • 15
  • E. Cosson
    • 16
  • A. Beckers
    • 17
  • Ph. Caron
    • 18
  • O. Chabre
    • 19
  • Ph. Chanson
    • 20
  • H. Du Boullay
    • 21
  • I. Guilhem
    • 22
  • P. Niccoli
    • 23
  • V. Rohmer
    • 24
  • J. Guigay
    • 25
  • C. Vulpoi
    • 26
  • J. Y. Scoazec
    • 27
  • P. Goudet
    • 28
  1. 1.Service d’Endocrinologie, Nutrition, Diabétologie ENDCentre Hospitalier Regional Universitaire de ToursToursFrance
  2. 2.CIC, module épidémiologie clinique/essais cliniquesCentre Hospitalier Universitaire de DijonDijonFrance
  3. 3.INSERM U866Universite de BourgogneDijonFrance
  4. 4.UMR866, équipe EPICADUniversité de Bourgogne-Franche ComtéDijonFrance
  5. 5.Clinique d’EndocrinologieCentre Hospitalier Universitaire de NantesNantesFrance
  6. 6.Service d’Endocrinologie, Hôpital de Haut LévêqueCentre Hospitalier Universitaire de BordeauxBordeauxFrance
  7. 7.Service de Médecine Interne et EndocrinologieCentre Hospitalier Régional et Universitaire de LilleLilleFrance
  8. 8.Groupement Hospitalier Est, Fédération d’EndocrinologieCentre Hospitalier Universitaire de LyonLyonFrance
  9. 9.Fédération Hospitalo Universitaire d’EndocrinologieUniversité Lyon 1LyonFrance
  10. 10.Service d’Oncologie MédicaleHôpital Edouard HerriotLyonFrance
  11. 11.Département de Médecine Nucléaire et d’Oncologie EndocrinienneGustave RoussyVillejuifFrance
  12. 12.Département d’EndocrinologieCentre Hospitalier Universitaire de ReimsReimsFrance
  13. 13.Service d’EndocrinologieCentre Hospitalier Universitaire de NancyVandœuvre-lès-NancyFrance
  14. 14.Service d’EndocrinologieCentre Hospitalier Universitaire de DijonDijonFrance
  15. 15.Service de Gastro-Entérologie et Cancérologie DigestiveHopital AvicenneBobignyFrance
  16. 16.Polyclinique d’Endocrinologie, Diabétologie, Métabolisme et NutritionHopital Jean VerdierBondyFrance
  17. 17.Service d’EndocrinologieCentre hospitalier universitaire de LiegeLiègeBelgium
  18. 18.Service d’Endocrinologie et Maladies MétaboliquesCentre Hospitalier Universitaire de ToulouseToulouseFrance
  19. 19.Service d’EndocrinologieCentre Hospitalier Universitaire de GrenobleGrenobleFrance
  20. 20.Service d’Endocrinologie et des maladies de la reproductionCentre Hospitalier Universitaire du Kremlin-BicêtreLe Kremlin-BicêtreFrance
  21. 21.Service d’EndocrinologieCentre Hospitalier Metropole SavoieChambéryFrance
  22. 22.Service d’Endocrinologie, Diabétologie, NutritionCentre Hospitalier Universitaire de RennesRennesFrance
  23. 23.Département d’Oncologie MédicaleInstitut Paoli-CalmettesMarseilleFrance
  24. 24.Département d’EndocrinolgieCentre Hospitalier Universitaire d’AngersAngersFrance
  25. 25.Center anti Cancer A. Lacassagne of NiceNiceFrance
  26. 26.Service d’EndocrinologieUniversité de Médecine et Pharmacie “Grigore T.Popa”IaşiRomania
  27. 27.Service de Pathologie Morphologique et MoléculaireGustave RoussyVillejuifFrance
  28. 28.Service de Chirurgie Digestive, Cancérologique et EndocrinienneCentre Hospitalier Universitaire de DijonDijonFrance

Personalised recommendations