Abstract
Pulmonary carcinoid tumors are neuroendocrine malignant tumors that make up 1% to 2% of all lung tumors. According to histopathologic criteria, carcinoids can be divided into typical (TC) and atypical (AC) carcinoids. Carcinoids can be placed in a spectrum of neuroendocrine tumors, ranging from low-grade malignant TC to intermediate AC to high-grade large-cell neuroendocrine carcinoma and small-cell lung carcinoma. Familial pulmonary carcinoids are rare. The most common symptoms are hemoptysis, cough, recurrent pulmonary infection, fever, chest discomfort and chest pain, unilateral wheezing, and shortness of breath. Paraneoplastic syndromes are rare and include carcinoid syndrome, Cushing’s syndrome, and ectopic growth hormone–releasing hormone secretion. The diagnosis is usually established by flexible bronchoscopy and biopsy, although occasionally this can result in severe hemorrhage. Immunoscintigraphy by somatostatin analogs can also be useful in diagnosis. The treatment of choice is surgical resection, and prognosis is relatively good in TC, although it is worse in AC. The role of radiotherapy and chemotherapy as part of multimodality treatment or palliation is still debated.
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REFERENCES
Lubarch O. Ueber den primären Krebs des Ileum, nebst Bemerkungen über das gleichzeitige Vorkommen von Krebs und Tuberkolose. Virchows Arch 1888; 111:280–317.
Fröhlich F. Die “Helle Zelle” der Bronchialschleimhaut und ihre Beziehungen zum Problem der Chemoreceptoren. Frankfurter Z Pathol 1949; 60:517.
Travis WD, Rush W, Flieder DB, et al. Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 1998; 22:934–44.
Arrigoni MG, Woolner LB, Bernatz PE. Atypical carcinoid tumors of the lung. J Thorac Cardiovasc Surg 1972; 64:413–21.
Travis WD, Colby TV, Corrin B. Histological Typing of Lung and Pleural Tumours. 3rd ed. Berlin: Springer, 1999.
Quaedvlieg PFHJ, Visser O, Lamers CBHW, Janssen-Heijen MLG, Taal BG. Epidemiology and survival in patients with carcinoid disease in the Netherlands. An epidemiological study with 2391 patients. Ann Oncol 2001; 12:1295–300.
Skuladottir H, Hirsch FR, Hansen HH, Olsen JH. Pulmonary neuroendocrine tumors: incidence and prognosis of histological subtypes. A population-based study in Denmark. Lung Cancer 2002; 37:127–35.
Filosso PL, Rena O, Donati G, et al. Bronchial carcinoid tumors: surgical management and long-term outcome. J Thorac Cardiovasc Surg 2002; 123:303–9.
El Jamal M, Nicholson AG, Goldstraw P. The feasibility of conservative resection for carcinoid tumors: is pneumonectomy ever necessary for uncomplicated cases? Eur J Cardiothorac Surg 2000; 18:301–6.
Onuki N, Wistuba II, Travis WD, et al. Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer 1999; 85:600–7.
Beasley MB, Thunnissen FBJM, Brambilla E, et al. Pulmonary atypical carcinoid: predictors of survival in 106 cases. Hum Pathol 2000; 31:1255–65.
Erasmus JJ, McAdams HP, Patz EF Jr, Coleman RE, Ahuja V, Goodman PC. Evaluation of primary pulmonary carcinoid tumors using FDG PET. AJR Am J Roentgenol 1998; 170:1369–73.
Kayser K, Kayser C, Rahn W, Bovin NV, Gabius H-J. Carcinoid tumors of the lung: immuno- and ligandohistochemistry, analysis of integrated optical density, syntactic structure analysis, clinical data, and prognosis of patients treated surgically. J Surg Oncol 1996; 63:99–106.
Harpole DH Jr, Feldman JM, Buchanan S, Young WG, Wolfe WG. Bronchial carcinoid tumors: a retrospective analysis of 126 patients. Ann Thorac Surg 1992; 54:50–5.
Vadasz P, Palffy G, Egervary M, Schaff Z. Diagnosis and treatment of bronchial carcinoid tumors: clinical and pathological review of 120 operated patients. Eur J Cardiothorac Surg 1993; 7:8–11.
Martini N, Zaman MB, Bains MS, et al. Treatment and prognosis in bronchial carcinoid involving regional lymph nodes. J Thorac Cardiovasc Surg 1994; 107:1–7.
Sen F, Borczuk AC. Combined carcinoid tumor of the lung: a combination of carcinoid and adenocarcinoma. Lung Cancer 1998; 2:53–8.
Ullmann R, Schwendel A, Klemen H, Wolf G, Petersen I, Popper HH. Unbalanced chromosomal aberrations in neuroendocrine lung tumors as detected by comparative genomic hybridization. Hum Pathol 1998; 29:1145–9.
Przygodzki RM, Finkelstein SD, Langer JC, et al. Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors: correlation with histological subtype and clinical outcome. Am J Pathol 1996; 148:1531–41.
Brambilla E, Negoescu A, Gazzeri S, et al. Apoptosis-related factors p53, Bcl2, and Bax in neuroendocrine lung tumors. Am J Pathol 1996; 149:1941–52.
Gouyer V, Gazzeri S, Bolon I, Drevet C, Brambilla C, Brambilla E. Mechanism of retinoblastoma gene inactivation in the spectrum of neuroendocrine lung tumors. Am J Respir Cell Mol Biol 1998; 18:188–96.
Gouyer V, Gazzeri S, Brambilla E, et al. Loss of heterozygosity at the RB locus correlates with loss of RB protein in primary malignant neuro-endocrine lung carcinomas. Int J Cancer 1994; 58:18–24.
Gugger M, Burckhardt E, Kappeler A, Hirsiger H, Laissue JA, Mazzucchelli L. Quantitative expression of structural genomic alterations in the spectrum of neuroendocrine lung carcinomas. J Pathol 2002; 196:408–15.
Ullmann R, Petzmann S, Klemen H, Fraire AE, Hasleton P, Popper HH. The position of pulmonary carcinoids within the spectrum of neuroendocrine tumors of the lung and other tissues. Genes Chromosomes Cancer 2002; 34:78–85.
Rusch VW, Klimstra DS, Venkatraman ES. Molecular markers help characterize neuroendocrine lung tumors. Ann Thorac Surg 1996; 62:798–809.
Walch AK, Zitzelsberger HF, Aubele MM, et al. Typical and atypical carcinoid tumors of the lung are characterized by 11q deletions as detected by comparative genomic hybridization. Am J Pathol 1998; 153:1089–98.
Debelenko LV, Brambila E, Agarwal SK, et al. Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung. Hum Mol Genet 1997; 6:2285–90.
Debelenko LV, Swalwell JI, Kelley MJ, et al. MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma. Genes Chromosomes Cancer 2000; 28:58–65.
Oliveira AM, Tazelaar HD, Wentzlaff KA, et al. Familial pulmonary carcinoid tumors. Cancer 2001; 91:2104–9.
Cooper WA, Thourani VH, Gal AA, Lee RB, Mansour KA, Miller JI. The surgical spectrum of pulmonary neuroendocrine neoplasms. Chest 2001; 119:114–8.
McCaughan BC, Martini N, Bains MS. Bronchial carcinoids. Review of 124 cases. J Thorac Cardiovasc Surg 1985; 89:8–17.
Fink G, Krelbaum T, Yellin A, et al. Pulmonary carcinoid: presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature. Chest 2001; 119:1647–51.
Thomas CF, Tazelaar HD, Jett JR. Typical and atypical pulmonary carcinoids. Outcome in patients presenting with regional lymph node involvement. Chest 2001; 119:1143–50.
Takada T, Takami H. Solitary splenic metastasis of a carcinoid tumor of the lung eight years postoperatively. J Surg Oncol 1998; 67:47–8.
Nakamura Y, Shimokawa S, Ishibe R, Ikee T, Taire A. Pulmonary carcinoid found in a patient who presented with initial symptoms of brain metastasis: report of a case. Surg Today 2001; 31:510–2.
Schreurs AJM, Westermann CJJ, Van den Bosch JMM, Vanderschueren RGJ, Brutel de la Rivière A, Knaepen PJ. A twenty-five year follow-up of ninety-three resected typical carcinoid tumors of the lung. J Thorac Cardiovasc Surg 1992; 104:1470–5.
Godshall D. The carcinoid syndrome: an unusual cause of valvular heart disease. J Emerg Med 2001; 21:21–5.
Karmy-Jones R, Vallières E. Carcinoid crisis after biopsy of a bronchial carcinoid. Ann Thorac Surg 1993; 56:1403–5.
Mehta AC, Rafanan AL, Bulkley R, Walsh M, DeBoer GE. Coronary spasm and cardiac arrest from carcinoid crisis during laser bronchoscopy. Chest 1999; 115:598–600.
Thorson Å, Biörck G, Björkman G, Waldenström J. Malignant carcinoid of the small intestine with metastases to the liver, valvular disease of the right side of the heart (pulmonary stenosis and tricuspidal regurgitation without septal defects), peripheral vasomotor symptoms, bronchoconstriction, and an unusual type of cyanosis: a clinical and pathological syndrome. Am Heart J 1954; 47:795–817.
Connolly HM, Schaff HV, Mullany CJ, Rubin J, Abed MD, Pelikka PA. Surgical management of left-sided carcinoid heart disease. Circulation 2001; 104:136–40.
Aniszewski JP, Young WF Jr, Thompson GB, Grant CS, Van Heerden JA. Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. World J Surg 2001; 25:934–40.
Melmed S, Ziel FH, Braunstein GD, Downs T, Frohman LA. Medical management of acromegaly due to ectopic production of growth hormone-releasing hormone by a carcinoid tumor. J Clin Endocrinol Metab 1988; 67:395–9.
Kristofferson A, Olsson T, Bjornebrink J, Hagg E. Diagnosis of ectopic ACTH production from a bronchial carcinoid by imaging with octreotide scintigraphy. Eur J Surg 1996; 162:515–8.
Kwekkeboom DJ, Krenning EP, Bakker WH, Oei HY, Kooij PPM, Lamberts SWJ. Somatostatin analogue scintigraphy in carcinoid tumors. Eur J Nucl Med 1993; 20:283–92.
Musi M, Carbone RG, Bertocchi C, et al. Bronchial carcinoid tumors: a study on clinicopathological features and role of octreotide scintigraphy. Lung Cancer 1998; 22:97–102.
Taal BG, Hoefnagel CA, Valdes Olmos RA, Boot H, Beijnen JH. Palliative effect of metaiodobenzylguanidine in metastatic carcinoid tumors. J Clin Oncol 1996; 14:1829–38.
Marom EM, Sarvis S, Herndon JE II, Patz EF Jr. T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET. Radiology 2002; 223:453–9.
Dusmet ME, McKneally MF. Pulmonary and thymic carcinoid tumors. World J Surg 1996; 20:189–95.
Carretta A, Ceresoli GL, Arrigoni G, et al. Diagnostic and therapeutic management of neuroendocrine lung tumors: a clinical study of 44 cases. Lung Cancer 2000; 29:217–25.
Marty-Ané CH, Costes V, Pujol JL, Alauzen M, Baldet P, Mary H. Carcinoid tumors of the lung: do atypical features require aggressive management? Ann Thorac Surg 1995; 59:78–83.
Sutedja G, Golding RP, Postmus PE. High resolution computed tomography in patients referred for intraluminal bronchoscopic therapy with curative intent. Eur Respir J 1996; 9:1020–3.
Codrington H, Sutedja T, Golding R, van Mourik J, Risse E, Postmus PE. Unusual pulmonary lesions: case 2. Endobronchial carcinoid of the lung. J Clin Oncol 2002; 20:2747–8.
Kurimoto N, Murayama M, Yoshioka S, Nishisaka T, Inai K, Dohi K. Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion. Chest 1999; 115:1500–6.
Van Boxem TJ, Golding RP, Venmans BJ, Postmus PE, Sutedja TG. High-resolution CT in patients with intraluminal typical bronchial carcinoid tumors treated with bronchoscopic therapy. Chest 2000; 117:125–8.
Sutedja TG, Schreurs AJ, Vanderschueren RG, Kwa B, vd Werf TS, Postmus PE. Bronchoscopic therapy in patients with intraluminal typical bronchial carcinoid. Chest 1995; 107:556–8.
Mills SE, Cooper PH, Walker AN, Kron IL. Atypical carcinoid tumor of the lung. A clinicopathologic study of 17 cases. Am J Surg Pathol 1982; 6:643–54.
Grote TH, Macon WR, Davis B, Greco AF, Johnson DH. Atypical carcinoid of the lung. A distinct clinicopathologic entity. Chest 1988; 93:370–5.
Moertel CG, Kvols LK, O’Connell MJ, Rubin J. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer 1991; 68:227–32.
Granberg D, Eriksson B, Wilander E, et al. Experience in treatment of metastatic pulmonary carcinoid tumors. Ann Oncol 2001; 12:1383–91.
Öberg K. Chemotherapy and biotherapy in the treatment of neuroendocrine tumours. Ann Oncol 2001; 12:S111–4.
Nobels FR, Kwekkeboom DJ, Coopmans W, et al. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. J Clin Endocrinol Metab 1997; 82:2622–8.
Hofland LJ, Lamberts SWJ. Somatostatin receptor subtype expression in human tumors. Ann Oncol 2001; 12:S31–6.
Torre M, Barberis M, Barbieri B, Bonacina E, Belloni P. Typical and atypical bronchial carcinoids. Respir Med 1989; 83:305–8.
Rea F, Binda R, Spreafico G, et al. Bronchial carcinoids: a review of 60 patients. Ann Thorac Surg 1989; 47:412–4.
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Hage, R., de la Rivière, A.B., Seldenrijk, C.A. et al. Update in Pulmonary Carcinoid Tumors: A Review Article. Ann Surg Oncol 10, 697–704 (2003). https://doi.org/10.1245/ASO.2003.09.019
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DOI: https://doi.org/10.1245/ASO.2003.09.019