Neuroendocrine Tumors of the Lung

  • Dan GranbergEmail author


Neuroendocrine lung tumors are divided into typical carcinoids, atypical carcinoids, large-cell neuroendocrine carcinomas (LCNEC), and small-cell lung carcinomas (SCLC), depending on the appearance in light microscopy. Typical and atypical carcinoids are slow-growing tumors, yet with malignant potential, while LCNEC and SCLC are highly malignant tumors with early development of metastases. Respiratory symptoms, such as cough, hemoptysis, and recurrent pneumonias, are common on presentation in patients with carcinoids, but many of these cases are asymptomatic and detected on routine chest X-ray or CT scan. Patients with LCNEC and SCLC may present with respiratory or general symptoms, including weight loss. Ectopic hormone production leading to endocrine symptoms, such as Cushing’s syndrome, is uncommon in carcinoid patients but more common in SCLC. Diagnosis is made by chest X-ray, CT scan, positron emission tomography (PET), biopsy for histopathology, and, in patients with endocrine symptoms, hormone measurements. The main treatment of patients with carcinoids is surgery, leading to cure in most cases. Metastatic disease can be treated with chemotherapy, peptide receptor radionuclide therapy (PRRT), newer targeted therapies such as everolimus, or biotherapy including somatostatin analogues. Patients with LCNEC are treated with surgery (if possible) and platinum + etoposide. First-line therapy for patients with SCLC is platinum-based chemotherapy, in patients with limited disease combined with thoracic radiotherapy. Prophylactic cranial irradiation is added in responding cases. The prognosis for patients with typical carcinoids is excellent; the vast majority are cured by surgery. Atypical carcinoids are more malignant, with higher risk for distant metastases. Patients with LCNEC and SCLC have a poor prognosis, with short expected survival.


Positron Emission Tomography Neuroendocrine Tumor Peptide Receptor Radionuclide Therapy Carcinoid Syndrome Prophylactic Cranial Irradiation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Arrigoni MG, Woolner LB, Bernatz PE (1972) Atypical carcinoid tumors of the lung. J Thorac Cardiovasc Surg 64:413–421PubMedGoogle Scholar
  2. 2.
    Capella C, Heitz PU, Höfler H et al (1994) Revised classification of neuroendocrine tumors of the lung, pancreas and gut. Digestion 55(Suppl 3):11–23PubMedGoogle Scholar
  3. 3.
    Paladugu RR, Benfield JR, Pak HY et al (1985) Bronchopulmonary kulchitzky cell carcinomas. Cancer 55:1303–1311PubMedGoogle Scholar
  4. 4.
    Travis WD, Linnoila RI, Tsokos MG et al (1991) Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 15:529–553PubMedGoogle Scholar
  5. 5.
    Warren WH, Gould VE, Faber LP et al (1985) Neuroendocrine neoplasms of the bronchopulmonary tract. A classification of the spectrum of carcinoid to small cell carcinoma and intervening variants. J Thorac Cardiovasc Surg 89:819–825PubMedGoogle Scholar
  6. 6.
    Travis WD, Colby TV, Corrin B et al (1999) World Health Organization. Histological typing of lung and pleural tumours, 3rd edn. Springer, BerlinGoogle Scholar
  7. 7.
    Travis WD, Rush W, Flieder DB et al (1998) Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 22:934–944PubMedGoogle Scholar
  8. 8.
    Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC (eds) (2004) Pathology & genetics. Tumours of the lung, pleura, thymus and heart, World Health Organization classification of tumours. IARC Press, LyonGoogle Scholar
  9. 9.
    Rindi G, Klersy C, Inzani F et al (2014) Grading the neuroendocrine tumors of the lung: an evidence-based proposal. Endocr Relat Cancer 21:1–16PubMedGoogle Scholar
  10. 10.
    Gorshtein A, Gross DJ, Barak D et al (2012) Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and the associated lung neuroendocrine tumors: clinical experience with a rare entity. Cancer 118:612–619PubMedGoogle Scholar
  11. 11.
    Nassar AA, Jaroszewski DE, Helmers RA et al (2011) Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a systematic overview. Am J Respir Crit Care Med 184:8–16PubMedGoogle Scholar
  12. 12.
    Modlin IM, Lye KD, Kidd M (2003) A 5-decade analysis of 13,715 carcinoid tumors. Cancer 97:934–959PubMedGoogle Scholar
  13. 13.
    Warren WH, Memoli VA, Gould VE (1984) Immunohistochemical and ultrastructural analysis of bronchopulmonary neuroendocrine neoplasms. I. Carcinoids. Ultrastruct Pathol 6:15–27PubMedGoogle Scholar
  14. 14.
    McCaughan BC, Martini N, Bains MS (1985) Bronchial carcinoids—review of 124 cases. J Thorac Cardiovasc Surg 89:8–17PubMedGoogle Scholar
  15. 15.
    Barbareschi M, Frigo B, Mosca L et al (1990) Bronchial carcinoids with S-100 positive sustentacular cells. A comparative study with gastrointestinal carcinoids, pheochromocytomas and paragangliomas. Pathol Res Pract 186:212–222PubMedGoogle Scholar
  16. 16.
    El-Salhy M, Lundqvist M, Wilander E (1986) Bronchial carcinoids and pheochromocytomas—a comparative study with special emphasis on S-100 protein, serotonin and neuron-specific enolase (NSE) immunoreactivity. Acta Path Microbiol Immunol Scand A 94:229–235Google Scholar
  17. 17.
    Granberg D, Wilander E, Öberg K, Skogseid B (1999) Decreased survival in patients with CD44-negative typical bronchial carcinoid tumors. Int J Cancer (Pred Oncol) 84:484–488Google Scholar
  18. 18.
    Barbareschi M, Girlando S, Mauri FA et al (1992) Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms. J Pathol 166:343–350PubMedGoogle Scholar
  19. 19.
    Gouyer V, Gazzeri S, Bolon I et al (1998) Mechanism of retinoblastoma gene inactivation in the spectrum of neuroendocrine lung tumors. Am J Respir Cell Mol Biol 18:188–196PubMedGoogle Scholar
  20. 20.
    Coppola D, Clarke M, Landreneau R et al (1996) Bcl-2, p53, CD44, and CD44v6 isoform expression in neuroendocrine tumors of the lung. Mod Pathol 9:484–490PubMedGoogle Scholar
  21. 21.
    Lohmann D, Pütz B, Reich U et al (1993) Mutational spectrum of the p53 gene in human small-cell lung cancer and relationship to clinicopathological data. Am J Pathol 142:907–915PubMedPubMedCentralGoogle Scholar
  22. 22.
    Cai Y-C, Banner B, Glickman J, Odze RD (2001) Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors. Hum Pathol 32:1087–1093PubMedGoogle Scholar
  23. 23.
    Du EZ, Goldstraw P, Zacharias J et al (2004) TTF-1 expression is specific for lung primary in typical and atypical carcinoids: TTF-1-positive carcinoids are predominantly in peripheral location. Hum Pathol 35:825–831PubMedGoogle Scholar
  24. 24.
    Walch AK, Zitzelsberger HF, Aubele MM et al (1998) Typical and atypical carcinoid tumors of the lung Are characterized by 11q deletions as detected by comparative genomic hybridization. Am J Pathol 153:1089–1098PubMedPubMedCentralGoogle Scholar
  25. 25.
    Debelenko LV, Brambilla E, Agarwal SK et al (1997) Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung. Hum Mol Genet 6:2285–2290PubMedGoogle Scholar
  26. 26.
    El-Naggar AK, Ballance W, Abdul Karim FW et al (1991) Typical and atypical bronchopulmonary carcinoids—a clinicopathologic and flow cytometric study. Am J Clin Pathol 95:828–834PubMedGoogle Scholar
  27. 27.
    Jones DJ, Hasleton PS, Moore N (1988) DNA ploidy in bronchopulmonary carcinoid tumours. Thorax 43:195–199PubMedPubMedCentralGoogle Scholar
  28. 28.
    Thunnissen FBJM, van Eijk J, Baak JPA et al (1988) Bronchopulmonary carcinoids and regional lymph node metastases—a quantitative pathologic investigation. Am J Pathol 132:119–122PubMedPubMedCentralGoogle Scholar
  29. 29.
    Bertelsen S, Aasted A, Lund C et al (1985) Bronchial carcinoid tumors—a clinicopathologic study of 82 cases. Scand J Thorac Cardiovasc Surg 19:105–111PubMedGoogle Scholar
  30. 30.
    Harpole DH Jr, Feldman JM, Buchanan S et al (1992) Bronchial carcinoid tumors: a retrospective analysis of 126 patients. Ann Thorac Surg 54:50–55PubMedGoogle Scholar
  31. 31.
    Mårtensson H, Böttcher G, Hambraeus G et al (1987) Bronchial carcinoids: an analysis of 91 cases. World J Surg 11:356–364PubMedGoogle Scholar
  32. 32.
    Davila DG, Dunn WF, Tazelaar HD, Pairolero PC (1993) Bronchial carcinoid tumors. Mayo Clin Proc 68:795–803PubMedGoogle Scholar
  33. 33.
    Dusmet ME, McKneally MF (1996) Pulmonary and thymic carcinoid tumors. World J Surg 20:189–195PubMedGoogle Scholar
  34. 34.
    Ricci C, Patrassi N, Massa R et al (1973) Carcinoid syndrome in bronchial adenoma. Am J Surg 126:671–677PubMedGoogle Scholar
  35. 35.
    Ezzat S, Asa SL, Stefaneanu L et al (1994) Somatotroph hyperplasia without pituitary adenoma associated with a long standing growth hormone-releasing hormone-producing bronchial carcinoid. Endokrina Tumörer MEN 1 78:555–560Google Scholar
  36. 36.
    Huber RM, Schopohl J, Losa M et al (1991) Growth-hormone releasing hormone in a bronchial carcinoid. Cancer 67:2538–2542PubMedGoogle Scholar
  37. 37.
    Colby TV (1994) Carcinoid and other neuroendocrine tumors. In: Tumors of the lower respiratory tract. Armed Forces Institute of Pathology, Bethesda, pp 287–317Google Scholar
  38. 38.
    Okike N, Bernatz PE, Woolner LB (1976) Carcinoid tumors of the lung. Ann Thorac Surg 22:270–277PubMedGoogle Scholar
  39. 39.
    Granberg D, Sundin A, Janson ET et al (2003) Octreoscan in patients with bronchial carcinoid tumours. Clin Endocrinol 59:793–799Google Scholar
  40. 40.
    Vaidya B, Richardson D, Hilton CJ, Kendall-Taylor P (1997) Adrenocorticotropin-secreting carcinoid tumour identified and treated 12 years after presentation with Cushing’s syndrome. Postgrad Med J 73:737–739PubMedPubMedCentralGoogle Scholar
  41. 41.
    Örlefors H, Sundin A, Garske U et al (2005) Whole-body 11C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors – comparison with somatostatin receptor scintigraphy and computed tomography. J Clin Endocrinol Metab 90:3392–3400PubMedGoogle Scholar
  42. 42.
    Chong S, Lee KS, Kim BT et al (2007) Integrated PET/CT of pulmonary neuroendocrine tumors: diagnostic and prognostic implications. AJR Am J Roentgenol 188:1223–1231PubMedGoogle Scholar
  43. 43.
    Erasmus JJ, McAdams HP, Patz EF Jr et al (1998) Evaluation of primary pulmonary carcinoid tumors using FDG PET. AJR Am J Roentgenol 170:1369–1373PubMedGoogle Scholar
  44. 44.
    Daniels CE, Lowe VJ, Aubry MC et al (2007) The utility of fluorodeoxyglucose positron emission tomography in the evaluation of carcinoid tumors presenting as pulmonary nodules. Chest 131:255–260PubMedGoogle Scholar
  45. 45.
    Hurt R, Bates M (1984) Carcinoid tumours of the bronchus: a 33 year experience. Thorax 39:617–623PubMedPubMedCentralGoogle Scholar
  46. 46.
    Aslan DL, Gulbahce HE, Pambuccian SE et al (2005) Ki-67 immunoreactivity in the differential diagnosis of pulmonary neuroendocrine neoplasms in specimens with extensive crush artifact. Am J Clin Pathol 123:874–878PubMedGoogle Scholar
  47. 47.
    Pelosi G, Rodriguez J, Viale G, Rosai J (2005) Typical and atypical pulmonary carcinoid tumor overdiagnosed as small-cell carcinoma on biopsy specimens: a major pitfall in the management of lung cancer patients. Am J Surg Pathol 29:179–187PubMedGoogle Scholar
  48. 48.
    Brokx HA, Risse EK, Paul MA et al (2007) Initial bronchoscopic treatment for patients with intraluminal bronchial carcinoids. J Thorac Cardiovasc Surg 133:973–978PubMedGoogle Scholar
  49. 49.
    Neyman K, Sundset A, Naalsund A et al (2012) Endoscopic treatment of bronchial carcinoids in comparison to surgical resection: a retrospective study. J Bronchology Interv Pulmonol 19:29–34PubMedGoogle Scholar
  50. 50.
    van Essen M, Krenning EP, Bakker WH et al (2007) Peptide receptor radionuclide therapy with (177)Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin. Eur J Nucl Med Mol Imaging 34:1219–1227PubMedGoogle Scholar
  51. 51.
    Imhof A, Brunner P, Marincek N et al (2011) Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 29:2416–2423PubMedGoogle Scholar
  52. 52.
    De Dosso S, Bajetta E, Procopio G et al (2007) Pulmonary carcinoid tumours: indolent but not benign. Oncology 73:162–168PubMedGoogle Scholar
  53. 53.
    Granberg D, Eriksson B, Wilander E et al (2001) Experience in treatment of metastatic pulmonary carcinoid tumors. Ann Oncol 12:1383–1391PubMedGoogle Scholar
  54. 54.
    Turner NC, Strauss SJ, Sarker D et al (2010) Chemotherapy with 5-fluorouracil, cisplatin and streptozocin for neuroendocrine tumours. Br J Cancer 102:1106–1112PubMedPubMedCentralGoogle Scholar
  55. 55.
    Wirth LJ, Carter MR, Jänne PA, Johnson BE (2004) Outcome of patients with pulmonary carcinoid tumors receiving chemotherapy or chemoradiotherapy. Lung Cancer 44:213–220PubMedGoogle Scholar
  56. 56.
    Chong CR, Wirth LJ, Nishino M et al (2014) Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors. Lung Cancer 86:241–246PubMedPubMedCentralGoogle Scholar
  57. 57.
    Crona J, Fanola I, Lindholm DP et al (2013) Effect of temozolomide in patients with metastatic bronchial carcinoids. Neuroendocrinology 98:151–155PubMedGoogle Scholar
  58. 58.
    Ekeblad S, Sundin A, Tiensuu Janson E et al (2007) Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res 13:2986–2991PubMedGoogle Scholar
  59. 59.
    Fazio N, Granberg D, Grossman A et al (2013) Everolimus plus octreotide LAR in patients with advanced lung neuroendocrine tumors: analysis of the phase III, randomized, placebo-controlled RADIANT-2 study. Chest 143:955–962Google Scholar
  60. 60.
    Granberg D, Wilander E, Öberg K (2006) Expression of tyrosine kinase receptors in lung carcinoids. Tumour Biol 27:153–157PubMedGoogle Scholar
  61. 61.
    Chughtai TS, Morin JE, Sheiner NM et al (1997) Bronchial carcinoid—twenty years’ experience defines a selective surgical approach. Surgery 122:801–808PubMedGoogle Scholar
  62. 62.
    Soga J, Yakuwa Y (1999) Bronchopulmonary carcinoids: an analysis of 1,875 reported cases with special reference to a comparison between typical carcinoids and atypical varieties. Ann Thorac Cardiovasc Surg 5:211–219PubMedGoogle Scholar
  63. 63.
    Thomas CF Jr, Tazelaar HD, Jett JR (2001) Typical and atypical pulmonary carcinoids : outcome in patients presenting with regional lymph node involvement. Chest 119:1143–1150PubMedGoogle Scholar
  64. 64.
    Granberg D, Wilander E, Öberg K, Skogseid B (2000) Prognostic markers in patients with typical bronchial carcinoid tumors. Endokrina Tumörer MEN 1 85:3425–3430Google Scholar
  65. 65.
    Beasley MB, Thunnissen FBJM, Brambilla E et al (2000) Pulmonary atypical carcinoid: predictors of survival in 106 cases. Hum Pathol 31:1255–1265PubMedGoogle Scholar
  66. 66.
    Dresler CM, Ritter JH, Patterson GA et al (1997) Clinical-pathologic analysis of 40 patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg 63:180–185PubMedGoogle Scholar
  67. 67.
    Jiang S-X, Kameya T, Shoji M et al (1998) Large cell neuroendocrine carcinoma of the lung: a histologic and immunohistochemical study of 22 cases. Am J Surg Pathol 22:526–537PubMedGoogle Scholar
  68. 68.
    Brambilla E, Negoescu A, Gazzeri S et al (1996) Apoptosis-related factors p53, Bcl2, and Bax in neuroendocrine lung tumors. Am J Pathol 149:1941–1952PubMedPubMedCentralGoogle Scholar
  69. 69.
    Yamazaki S, Sekine I, Matsuno Y et al (2005) Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy. Lung Cancer 49:217–223PubMedGoogle Scholar
  70. 70.
    Tokito T, Kenmotsu H, Watanabe R et al (2014) Comparison of chemotherapeutic efficacy between LCNEC diagnosed using large specimens and possible LCNEC diagnosed using small biopsy specimens. Int J Clin Oncol 19:63–67PubMedGoogle Scholar
  71. 71.
    Sun JM, Ahn MJ, Ahn JS et al (2012) Chemotherapy for pulmonary large cell neuroendocrine carcinoma: similar to that for small cell lung cancer or non-small cell lung cancer? Lung Cancer 77:365–370PubMedGoogle Scholar
  72. 72.
    Shimada Y, Niho S, Ishii G et al (2012) Clinical features of unresectable high-grade lung neuroendocrine carcinoma diagnosed using biopsy specimens. Lung Cancer 75:368–373PubMedGoogle Scholar
  73. 73.
    Igawa S, Watanabe R, Ito I et al (2010) Comparison of chemotherapy for unresectable pulmonary high-grade non-small cell neuroendocrine carcinoma and small-cell lung cancer. Lung Cancer 68:438–445PubMedGoogle Scholar
  74. 74.
    Yoshida H, Sekine I, Tsuta K et al (2011) Amrubicin monotherapy for patients with previously treated advanced large-cell neuroendocrine carcinoma of the lung. Jpn J Clin Oncol 41:897–901PubMedGoogle Scholar
  75. 75.
    De Pas TM, Giovannini M, Manzotti M et al (2011) Large-cell neuroendocrine carcinoma of the lung harboring EGFR mutation and responding to gefitinib. J Clin Oncol Off J Am Soc Clin Oncol 29:e819–e822Google Scholar
  76. 76.
    Kozuki T, Fujimoto N, Ueoka H et al (2005) Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma. J Cancer Res Clin Oncol 131:147–151PubMedGoogle Scholar
  77. 77.
    Filosso PL, Ruffini E, Oliaro A et al (2005) Large-cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighteen cases and the efficacy of adjuvant treatment with octreotide. J Thorac Cardiovasc Surg 129:819–824PubMedGoogle Scholar
  78. 78.
    Iyoda A, Travis WD, Sarkaria IS et al (2011) Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma. Exp Ther Med 2:1041–1045PubMedPubMedCentralGoogle Scholar
  79. 79.
    Asamura H, Kameya T, Matsuno Y et al (2006) Neuroendocrine neoplasms of the lung: a prognostic spectrum. PDF-artiklar Somatuline 24:70–76Google Scholar
  80. 80.
    Battafarano RJ, Fernandez FG, Ritter J et al (2005) Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung cancer. J Thorac Cardiovasc Surg 130:166–172PubMedGoogle Scholar
  81. 81.
    Iyoda A, Hiroshima K, Toyozaki T et al (2001) Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology. Cancer 91:1992–2000PubMedGoogle Scholar
  82. 82.
    Paci M, Cavazza A, Annessi V et al (2004) Large cell neuroendocrine carcinoma of the lung: a 10-year clinicopathologic retrospective study. Ann Thorac Surg 77:1163–1167PubMedGoogle Scholar
  83. 83.
    Rossi G, Cavazza A, Marchioni A et al (2005) Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung. J Clin Oncol 23:8774–8785PubMedGoogle Scholar
  84. 84.
    Skuladottir H, Hirsch FR, Hansen HH, Olsen JH (2002) Pulmonary neuroendocrine tumors: incidence and prognosis of histological subtypes. A population-based study in Denmark. Lung Cancer 37:127–135PubMedGoogle Scholar
  85. 85.
    Veronesi G, Morandi U, Alloisio M et al (2006) Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases. Lung Cancer 53:111–115PubMedGoogle Scholar
  86. 86.
    Iyoda A, Hiroshima K, Moriya Y et al (2006) Prognostic impact of large cell neuroendocrine histology in patients with pathologic stage Ia pulmonary non-small cell carcinoma. J Thorac Cardiovasc Surg 132:312–315PubMedGoogle Scholar
  87. 87.
    Takei H, Asamura H, Maeshima A et al (2002) Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg 124:285–292PubMedGoogle Scholar
  88. 88.
    Cook RM, Miller YE, Bunn PA Jr (1993) Small cell lung cancer: etiology, biology, clinical features, staging, and treatment. Curr Probl Cancer 17:69–141PubMedGoogle Scholar
  89. 89.
    Curran WJ Jr (2001) Combined-modality therapy for limited-stage small cell lung cancer. Semin Oncol 28:14–22PubMedGoogle Scholar
  90. 90.
    Komaki R, Byhardt RW, Anderson T et al (1985) What is the lowest effective biologic dose for prophylactic cranial irradiation? Am J Clin Oncol 8:523–527PubMedGoogle Scholar
  91. 91.
    Samson DJ, Seidenfeld J, Simon GR et al (2007) Evidence for management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 132:314S–323SPubMedGoogle Scholar
  92. 92.
    Folpe AL, Gown AM, Lamps LW et al (1999) Thyroid transcription factor-1: immunohistochemical evaluation in pulmonary neuroendocrine tumors. Mod Pathol 12:5–8PubMedGoogle Scholar
  93. 93.
    Kaufmann O, Dietel M (2000) Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites. Histopathology 36:415–420PubMedGoogle Scholar
  94. 94.
    Cuttitta F, Carney DN, Mulshine J et al (1985) Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 316:823–826PubMedGoogle Scholar
  95. 95.
    Ben-Ezra JM, Kornstein MJ, Grimes MM, Krystal G (1994) Small cell carcinomas of the lung express the Bcl-2 protein. Am J Pathol 145:1036–1040PubMedPubMedCentralGoogle Scholar
  96. 96.
    Jiang S-X, Kameya T, Sato Y et al (1996) Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation. Am J Pathol 148:837–846PubMedPubMedCentralGoogle Scholar
  97. 97.
    Cagle PT, el-Naggar AK, Xu H-J et al (1997) Differential retinoblastoma protein expression in neuroendocrine tumors of the lung. Potential diagnostic implications. Am J Pathol 150:393–400PubMedPubMedCentralGoogle Scholar
  98. 98.
    Vuitch F, Sekido Y, Fong K et al (1997) Neuroendocrine tumors of the lung. Pathology and molecular biology. Chest Surg Clin N Am 7:21–47PubMedGoogle Scholar
  99. 99.
    Balsara BR, Testa JR (2002) Chromosomal imbalances in human lung cancer. Oncogene 21:6877–6883PubMedGoogle Scholar
  100. 100.
    Onuki N, Wistuba II, Travis WD et al (1999) Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer 85:600–607PubMedGoogle Scholar
  101. 101.
    Johnson BE, Russell E, Simmons AM et al (1996) MYC family DNA amplification in 126 tumor cell lines from patients with small cell lung cancer. J Cell Biochem Suppl 24:210–217PubMedGoogle Scholar
  102. 102.
    Shivapurkar N, Toyooka S, Eby MT et al (2002) Differential inactivation of caspase-8 in lung cancers. Cancer Biol Ther 1:65–69PubMedGoogle Scholar
  103. 103.
    Petersen I, Hidalgo A, Petersen S et al (2000) Chromosomal imbalances in brain metastases of solid tumors. Brain Pathol 10:395–401PubMedGoogle Scholar
  104. 104.
    Planchard D, Le Pechoux C (2011) Small cell lung cancer: new clinical recommendations and current status of biomarker assessment. Eur J Cancer 47(Suppl 3):S272–S5283PubMedGoogle Scholar
  105. 105.
    van Meerbeeck JP, Fennell DA, De Ruysscher DK (2011) Small-cell lung cancer. Lancet 378:1741–1755PubMedGoogle Scholar
  106. 106.
    Detterbeck FC, Boffa DJ, Tanoue LT (2009) The new lung cancer staging system. Chest 136:260–271PubMedGoogle Scholar
  107. 107.
    Mirsadraee S, Oswal D, Alizadeh Y et al (2012) The 7th lung cancer TNM classification and staging system: review of the changes and implications. World J Radiol 4:128–134PubMedPubMedCentralGoogle Scholar
  108. 108.
    Micke P, Faldum A, Metz T et al (2002) Staging small cell lung cancer: veterans administration lung study group versus international association for the study of lung cancer–what limits limited disease? Lung Cancer 37:271–276PubMedGoogle Scholar
  109. 109.
    O’Byrne KJ, Ennis JT, Freyne PJ et al (1994) Scintigraphic imaging of small-cell lung cancer with [111In]pentetreotide, a radiolabelled somatostatin analogue. Br J Cancer 69:762–766PubMedPubMedCentralGoogle Scholar
  110. 110.
    Reisinger I, Bohuslavitzki KH, Brenner W et al (1998) Somatostatin receptor scintigraphy in small-cell lung cancer: results of a multicenter study. J Nucl Med 39:224–227PubMedGoogle Scholar
  111. 111.
    Valkema R, Steens J, Cleton F, Pauwels E (1996) The diagnostic utility of somatostatin receptor scintigraphy in oncology. J Cancer Res Clin Oncol 122:513–532PubMedGoogle Scholar
  112. 112.
    Byers LA, Rudin CM (2015) Small cell lung cancer: where do we go from here? Cancer 121: 664–672Google Scholar
  113. 113.
    Simon GR, Turrisi A, American College of Chest Physicians (2007) Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 132:324S–339SPubMedGoogle Scholar
  114. 114.
    Foster NR, Mandrekar SJ, Schild SE et al (2009) Prognostic factors differ by tumor stage for small cell lung cancer: a pooled analysis of North Central Cancer Treatment Group trials. Cancer 115:2721–2731PubMedPubMedCentralGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Medical SciencesUppsala University, Division of Endocrine Oncology, University HospitalUppsalaSweden

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