- Author: Cameron K Tebbi, MD; Chief Editor: Max J Coppes, MD, PhD, MBA more...
Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells in the gut wall, but they can be seen in other organs, including the lungs, mediastinum, thymus, liver, pancreas, bronchus, ovaries, prostate, and kidneys (see the image below). Carcinoid tumors have high potential for metastasis.
Signs and symptoms
Signs and symptoms of carcinoid tumors vary greatly and depend on the tumor location and size as well as on the presence of metastases. Findings range from no tumor-related symptoms (most carcinoid tumors) to full symptoms of carcinoid syndrome (primarily in adults). Due to their vague and intermittent symptoms, diagnosis of carcinoid tumors may be delayed, especially in children, in whom the tumor is rare and the diagnosis is unexpected.
Signs and symptoms may include the following:
Periodic abdominal pain: Most common presentation for a small intestinal carcinoid; often associated with malignant carcinoid syndrome
Cutaneous flushing: Early and frequent (94%) symptom; typically affects head and neck; often associated with an unpleasant warm feeling, itching, palpitation, upper-body erythema and edema, salivation, diaphoresis, lacrimation, and diarrhea
Diarrhea and malabsorption (84%): Watery, frothy, or bulky stools, or steatorrhea; may or may not be associated with abdominal pain, flushing, and cramps
Cardiac manifestations (60%): Valvular heart lesions, fibrosis of the endocardium; may lead to heart failure
Wheezing or asthmalike syndrome (25%): Due to bronchial constriction; some tremors are relatively indolent and result in chronic symptoms such as cough and dyspnea 
Carcinoid tumors generally are classified based on the location in the primitive gut that gives rise to the tumor, as follows:
Foregut carcinoid tumors: Divided into sporadic primary tumors (lung, bronchus, stomach, proximal duodenum, pancreas) and tumors secondary to achlorhydria
Midgut carcinoid tumors: Derived from the second portion of the duodenum, the jejunum, the ileum, and the right colon
Hindgut carcinoid tumors: Includes the transverse colon, descending colon, and rectum
See Clinical Presentation for more detail.
The etiology of carcinoid tumors is not known, but genetic abnormalities are suspected. Reported chromosomal abnormalities include changes in chromosomes, such as loss of heterogeneity, and numerical imbalances. The diagnosis is sometimes made because of unrelated findings, such as anemia, endocrine disease, or autoimmune disease.
Laboratory diagnosis of carcinoid tumors depends on the identification of the characteristic biomarkers of the disease. Measurement of biogenic amine levels (eg, serotonin, 5-hydroxyindoleacetic acid [5-HIAA], catecholamines, histamine) and its metabolites in the platelets, plasma, and urine of patients can be helpful in making the diagnosis.
Depending on the location of the tumor and metastasis, a combination of the following imaging modalities may be used to evaluate suspected carcinoid tumors:
Upper and lower GI radiography with oral contrast agents
Computed tomography scanning
Magnetic resonance imaging
Positron emission tomography scanning
Scintigraphy with metaiodobenzylguanidine (MIBG) and octreotide [8, 9]
Radionuclide imaging with somatostatin analogs attached to the radioactive tracer
Technetium-99m bone scanning
Endoscopic procedures, such as the following, may be used for biopsy and diagnosis:
See Workup for more detail.
If feasible, the treatment of choice for carcinoid tumors is surgical excision. The surgical technique may vary according to the type or location of the tumor. When total resection is not possible, debulking may provide symptomatic relief. In selected cases, cryotherapy can be effective.
If metastasis of carcinoid tumor has occurred and in cases where surgical excision is not suitable, consider treatment with currently recommended chemotherapeutic agents, individually or in combination, such as the following:
Somatostatin analogs with a radioactive load
See Treatment for more detail.
Origin and general involvement and presentation
Carcinoid tumors are derived from primitive stem cells in the gut wall but can be seen in other organs, including the lungs, mediastinum, thymus, liver, pancreas, bronchus, ovaries, prostate, and kidneys. In children, most tumors occur in the appendix and are benign and asymptomatic.
Most carcinoid tumors are slow growing and indolent without symptoms. Nevertheless, aggressive and metastatic disease (eg, to the brain) does occur. Even tumors in the appendix can metastasize.[10, 11] Depending on the size and location, carcinoid tumors can cause various symptoms, including carcinoid syndrome. Carcinoid tumors of the ileum and jejunum, especially those larger than 1 cm, are most prone to produce this syndrome, at least in adults.
Carcinoid tumors generally are classified based on the location in the primitive gut (ie, foregut, midgut, hindgut) that gives rise to the tumor.
Foregut carcinoid tumors are divided into sporadic primary tumors and tumors secondary to achlorhydria. The term sporadic primary foregut tumor encompasses carcinoids of the lung, bronchus, stomach, proximal duodenum, and pancreas.
Midgut tumors are derived from the second portion of the duodenum, the jejunum, the ileum, and the right colon. The image below shows the distribution of carcinoid tumors.
These account for 60-80% of all carcinoid tumors (especially those of the appendix and distal ileum) in adults and are also seen in children. Appendicular carcinoid tumors are most common.[13, 14] In children, more than 70% of these tumors occur at the tip of the appendix and are often an incidental finding in appendectomy specimens. In one study, carcinoid tumors were found in 0.169% of 4747 appendectomies. Bulky tumors are relatively rare and require somewhat extensive cecectomy or, when tumor infiltration is beyond the cecum, ileocecal resection.[16, 17, 14]
Hindgut carcinoid tumors include those of the transverse colon, descending colon, and rectum.
Carcinoid tumors can also arise from the Meckel diverticulum, cystic duplications, and the mesentery. Each of these entities has distinctive clinical, histochemical, and secretory features. For example, foregut carcinoids are argentaffin negative and have low serotonin content but secrete 5-hydroxytryptophan (5-HTP), histamine, and several polypeptide hormones. These tumors can metastasize to bone and may be associated with atypical carcinoid syndrome, acromegaly, Cushing disease, other endocrine disorders, telangiectasia, or hypertrophy of the skin in the face and upper neck.
Midgut carcinoids are argentaffin positive and can produce high levels of serotonin 5-hydroxytryptamine (5-HT), kinins, prostaglandins, substance P (SP), and other vasoactive peptides. These tumors have a rare potential to produce corticotropic hormone (previously adrenocorticotropic hormone [ACTH]). Bone metastasis is uncommon.
Hindgut carcinoids are argentaffin negative and rarely secrete 5-HT, 5-HTP, or any other vasoactive peptides. Therefore, they do not produce related symptomatology. Bone metastases are not uncommon in these tumors.
Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells, which can give rise to multiple cell lineages. In the intestinal tract, these tumors develop deep in the mucosa, growing slowly and extending into the underlying submucosa and mucosal surface. This results in the formation of small firm nodules, which bulge into the intestinal lumen. These tumors have a yellow, tan, or gray-brown appearance that can be observed through the intact mucosa. The yellow color is a result of cholesterol and lipid accumulation within the tumor. Tumors can have a polypoid appearance and occasionally become ulcerated. With expansion and infiltration through the submucosa into the muscularis propria and serosa, carcinoid tumors can involve the mesentery. Metastases to the mesenteric lymph node and liver, ovaries, peritoneum, and spleen can occur.
Upon histologic examination, carcinoid tumors have 5 distinctive patterns: (1) solid, nodular, and insular cords; (2) trabecular or ribbons with anastomosing features; (3) tubules and glands or rosettelike patterns; (4) poorly differentiated or atypical patterns; and (5) mixed patterns. A combination of these patterns is often observed. Tubules can contain mucinous secretions, and individual tumor cells can contain mucin-positive material, which includes the various acidic and neutral intestinal mucin. Tumors rarely have eosinophilic stroma. Capillaries are often prominent. Cells are uniformly round or polygonal with a central nucleus and punctate chromatin as well as small nucleoli and infrequent mitosis. The cytoplasm can be slightly acidophilic, basophilic, or amphophilic. Eosinophilic granules may be present. Immunohistochemically, these tumors have a strong positive reaction to keratin and neuroendocrine markers. These include chromogranin and synaptophysin.
In midgut carcinoids, cells are arranged in closely packed, round, regular, monomorphous masses. In the appendix, carcinoids appear as discrete yellow nodules in the lumen. Lesions associated with diffuse wall thickening are relatively uncommon. Carcinoid tumors commonly affect the tip of the appendix. Most carcinoid tumors invade the wall of the appendix, and lymphatic involvement is nearly universal. About 75% of patients have evidence of peritoneal involvement. However, only a few patients have regional or distant dissemination. The size of the tumor can be correlated with outcome of the disease; tumors smaller than 1.5 cm in diameter (after formalin fixation) rarely result in distant metastases or recurrences.
Carcinoid tumors can be associated with concentric and elastic vascular sclerosis that results in obliteration of vascular lumina and ischemia. A common finding is elastosis and fibrosis that surround nests of the tumor cells and that result in matting of the involved tissues and lymph nodes. Fibroblastic proliferation may result from the stimulation of fibroblast cells by growth factor. This stimulation may be a result of a local release of tumor growth factor (TGF)-beta, beta–fibroblast growth factor (beta-FGF), and platelet-derived growth factor.
Other products of carcinoid tumors include the following:
Atrial natriuretic polypeptide
Fibroblast growth factor
Gastrin-releasing peptide (bombesin)
5-Hydroxyindoleacetic acid (5-HIAA)
Platelet-dermal growth factor
Somatostatin (ie, SRIF)
Substance P (SP)
Transforming growth factor-beta
Vasoactive intestinal polypeptide (VIP)
Classic carcinoid tumor cells are argentaffinic and argyrophilic. At present, immunostain and hormonal markers are used for diagnosis. Carcinoid tumors of mediastinum can be misclassified as thymoma.
Carcinoids may have somatostatin receptors. Five identified somatostatin receptors are members of the G-protein receptor family. Five distinct genes on chromosomes 11, 14, 16, 17, and 20 encode somatostatin receptors. Somatostatin receptors are used to advantage for diagnosing and treating this disease.
Carcinoid tumors have high potential for metastasis. These cells produce a significant amount of beta-catenin, which enables the tumor cell adhesion, thus promoting metastasis. Induction of Raf1 results in decreased adhesion of carcinoid cells and may be important in the metastatic process.
Carcinoids are the most common neuroendocrine tumors, with an estimated 1.5 clinical cases per 100,000 population. The incidence in autopsy cases is higher than this at 650 cases per 100,000 population. Evidence in adults suggests that overall incidence of carcinoid tumors has been steadily increasing. The exact incidence in children is not known. Most tumors occur in adults and are rare in children.
In 1980-1989, the overall age-standardized incidence rate for male and female populations in England were estimated to be 0.71 (0.68-0.75 and 0.87 (0.83-0.91), respectively. In Scotland, the respective rates were 1.17 (0.91-1.44) per 100,000 population and 1.36 (1.09-1.63) per 100,000 population.
Broaddus RR, Herzog CE, Hicks MJ. Neuroendocrine tumors (carcinoid and neuroendocrine carcinoma) presenting at extra-appendiceal sites in childhood and adolescence. Arch Pathol Lab Med. 2003 Sep. 127(9):1200-3. [Medline].
Moraes TJ, Langer JC, Forte V, et al. Pediatric pulmonary carcinoid: a case report and review of the literature. Pediatr Pulmonol. 2003 Apr. 35(4):318-22. [Medline].
Soga J, Yakuwa Y, Osaka M. Evaluation of 342 cases of mediastinal/thymic carcinoids collected from literature: a comparative study between typical carcinoids and atypical varieties. Ann Thorac Cardiovasc Surg. 1999 Oct. 5(5):285-92. [Medline].
Piura B, Dgani R, Zalel Y, et al. Malignant germ cell tumors of the ovary: a study of 20 cases. J Surg Oncol. 1995 Jul. 59(3):155-61. [Medline].
Murali R, Kneale K, Lalak N, Delprado W. Carcinoid tumors of the urinary tract and prostate. Arch Pathol Lab Med. 2006 Nov. 130(11):1693-706. [Medline].
Romero FR, Rais-Bahrami S, Permpongkosol S, Fine SW, Kohanim S, Jarrett TW. Primary carcinoid tumors of the kidney. J Urol. 2006 Dec. 176(6 Pt 1):2359-66. [Medline].
Uskul BT, Turker H, Dincer IS, Melikoglu A, Tasolar O, Tahaoglu C. A primary tracheal carcinoid tumor masquerading as chronic obstructive pulmonary disease. South Med J. 2008 May. 101(5):546-9. [Medline].
Monsieurs MA, Thierens HM, Vral A, et al. Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours. Nucl Med Commun. 2001 Apr. 22(4):367-74. [Medline].
Shi W, Johnston CF, Buchanan KD, et al. Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging. QJM. 1998 Apr. 91(4):295-301. [Medline].
Hlatky R, Suki D, Sawaya R. Carcinoid metastasis to the brain. Cancer. 2004 Dec 1. 101(11):2605-13. [Medline].
Volpe A, Willert J, Ihnken K, et al. Metastatic appendiceal carcinoid tumor in a child. Med Pediatr Oncol. 2000 Mar. 34(3):218-20. [Medline].
Schmittenbecher PP. Carcinoid tumours of the appendix in children--epidemiology, clinical aspects and procedures. Eur J Pediatr Surg. 2001 Dec. 11(6):428. [Medline].
Bethel CA, Bhattacharyya N, Hutchinson C, et al. Alimentary tract malignancies in children. J Pediatr Surg. 1997 Jul. 32(7):1004-8; discussion 1008-9. [Medline].
Pelizzo G, La Riccia A, Bouvier R, et al. Carcinoid tumors of the appendix in children. Pediatr Surg Int. 2001 Jul. 17(5-6):399-402. [Medline].
Doede T, Foss HD, Waldschmidt J. Carcinoid tumors of the appendix in children--epidemiology, clinical aspects and procedure. Eur J Pediatr Surg. 2000 Dec. 10(6):372-7. [Medline].
Soreide JA, van Heerden JA, Thompson GB, et al. Gastrointestinal carcinoid tumors: long-term prognosis for surgically treated patients. World J Surg. 2000 Nov. 24(11):1431-6. [Medline].
D'Aleo C, Lazzareschi I, Ruggiero A, Riccardi R. Carcinoid tumors of the appendix in children: two case reports and review of the literature. Pediatr Hematol Oncol. 2001 Jul-Aug. 18(5):347-51. [Medline].
Greenblatt DY, Kunnimalaiyaan M, Chen H. Raf-1 activation in gastrointestinal carcinoid cells decreases tumor cell adhesion. Am J Surg. 2007 Mar. 193(3):331-5; discussion 335. [Medline].
Robertson RG, Geiger WJ, Davis NB. Carcinoid tumors. Am Fam Physician. 2006 Aug 1. 74(3):429-34. [Medline].
Newton JN, Swerdlow AJ, dos Santos Silva IM, et al. The epidemiology of carcinoid tumours in England and Scotland. Br J Cancer. 1994 Nov. 70(5):939-42. [Medline].
Lal DR, Clark I, Shalkow J, et al. Primary epithelial lung malignancies in the pediatric population. Pediatr Blood Cancer. 2005 Oct 15. 45(5):683-6. [Medline].
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 Jun. 119(6):1647-51. [Medline].
Fauroux B, Aynie V, Larroquet M, et al. Carcinoid and mucoepidermoid bronchial tumours in children. Eur J Pediatr. 2005 Dec. 164(12):748-52. [Medline].
Wang WP, Guo C, Berney DM, et al. Primary carcinoid tumors of the testis: a clinicopathologic study of 29 cases. Am J Surg Pathol. 2010 Apr. 34(4):519-24. [Medline].
Atoui R, Almarzooqi S, Saleh W, Marcovitz S, Mulder D. Bronchopulmonary carcinoid tumor associated with Cushing syndrome. Ann Thorac Surg. 2008 Nov. 86(5):1688-90. [Medline].
Capovilla M, Kambouchner M, Bernier M, Soulier A, Tissier F, Saintigny P. Late cerebellar relapse of a juvenile bronchial carcinoid. Clin Lung Cancer. 2007 Mar. 8(5):339-41. [Medline].
Igaz P. MEN1 clinical background. Adv Exp Med Biol. 2009. 668:1-15. [Medline].
Lin ZM, Chang YL, Lee CY, Wang CP, Hsiao TY. Simultaneous typical carcinoid tumour of larynx and occult papillary thyroid carcinoma. J Laryngol Otol. 2008 Jan. 122(1):93-6. [Medline].
Aubry MC, Thomas CF Jr, Jett JR, Swensen SJ, Myers JL. Significance of multiple carcinoid tumors and tumorlets in surgical lung specimens: analysis of 28 patients. Chest. 2007 Jun. 131(6):1635-43. [Medline].
Petrou A, Papalambros A, Papaconstantinou I, et al. Gastric carcinoid tumor in association with hepatocellular carcinoma: a case report. South Med J. 2008 Nov. 101(11):1170-2. [Medline].
[Guideline] Dreijerink KM, Roijers JF, van der Luijt RB, et al. [Multiple endocrine neoplasia type 1: recent developments and guidelines for DNA diagnosis and periodic clinical monitoring]. Ned Tijdschr Geneeskd. 2000 Dec 16. 144(51):2445-9. [Medline].
Yazawa K, Kuroda T, Watanabe H, et al. Multiple carcinoids of the duodenum accompanied by type I familial multiple endocrine neoplasia. Surg Today. 1998. 28(6):636-9. [Medline].
Hemminki K, Li X. Familial carcinoid tumors and subsequent cancers: a nation-wide epidemiologic study from Sweden. Int J Cancer. 2001 Nov 1. 94(3):444-8. [Medline].
Vageli D, Danill Z, Dahabreh J. Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung carcinoid tumors: a novel approach using real-time PCR with melting curve analysis in histopathologic material. Oncol Rep. 2006. 15:557-64.
D'Adda T, Pizzi S, Azzoni C. Different patterns of 11q allelic losses in digestive endocrine tumors. Hum Pathol. 2002. 33:322-9.
Pizzi S, D'Adda T, Azzoni c. Malignancy-associated allelic losses on the X-chromosome in foregut but not in midgut endocrine tumours. J Pathol. 2002. 196:401-7.
Pizzi S, D'Adda T, Azzoni C, et al. Malignancy-associated allelic losses on the X-chromosome in foregut but not in midgut endocrine tumours. J Pathol. 2002 Apr. 196(4):401-7. [Medline].
Jakobovitz O, Nass D, DeMarco L. Carcinoid tumors frequently display genetic abnormalities involving chromosome 11. J Clin Endocrinol Metab. 1996. 81:3164-7.
Jakobovitz O, Nass D, DeMarco L, et al. Carcinoid tumors frequently display genetic abnormalities involving chromosome 11. J Clin Endocrinol Metab. 1996 Sep. 81(9):3164-7. [Medline].
Yamaguchi M, Hirose K, Hirai N. HER2 expression in gastrointestinal carcinoid tumors: high in intestinal but not in gastric tumors. Surg Today. 2007. 37(3):270-1. [Medline].
Fujiki K, Duerr EM, Kikuchi H, et al. Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology. 2008 Sep. 135(3):907-16, 916.e1-2. [Medline].
Moertel CG. Karnofsky memorial lecture. An odyssey in the land of small tumors. J Clin Oncol. 1987 Oct. 5(10):1502-22. [Medline].
Moertel CG. Treatment of the carcinoid tumor and the malignant carcinoid syndrome. J Clin Oncol. 1983 Nov. 1(11):727-40. [Medline].
Moertel CG, Weiland LH, Nagorney DM, Dockerty MB. Carcinoid tumor of the appendix: treatment and prognosis. N Engl J Med. 1987 Dec 31. 317(27):1699-701. [Medline].
Delcore R, Friesen SR. Gastrointestinal neuroendocrine tumors. J Am Coll Surg. 1994 Feb. 178(2):187-211. [Medline].
Mani S, Modlin IM, Ballantyne G, et al. Carcinoids of the rectum. J Am Coll Surg. 1994 Aug. 179(2):231-48. [Medline].
Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999 Mar 18. 340(11):858-68. [Medline].
Carling RS, Degg TJ, Allen KR, et al. Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease. Ann Clin Biochem. 2002 Nov. 39(Pt 6):577-82. [Medline].
Saqi A, Alexis D, Remotti F, Bhagat G. Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids. Am J Clin Pathol. 2005 Mar. 123(3):394-404. [Medline].
Pattenden HA, Leung M, Beddow E, Dusmet M, Nicholson AG, Shackcloth M, et al. Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. Thorax. 2015 Apr. 70 (4):379-81. [Medline].
Boggs W. PET-CT of Little Use in Mediastinal Lymph Node Staging of Pulmonary Carcinoid Tumors. Reuters Health Information. Available at http://www.medscape.com/viewarticle/831316. September 09, 2014; Accessed: June 16, 2015.
Kaltsas G, Korbonits M, Heintz E, et al. Comparison of somatostatin analog and meta-iodobenzylguanidine radionuclides in the diagnosis and localization of advanced neuroendocrine tumors. J Clin Endocrinol Metab. 2001 Feb. 86(2):895-902. [Medline].
Dubois S, Morel O, Rodien P, et al. A Pulmonary adrenocorticotropin-secreting carcinoid tumor localized by 6-Fluoro-[18F]L-dihydroxyphenylalanine positron emission/computed tomography imaging in a patient with Cushing's syndrome. J Clin Endocrinol Metab. 2007 Dec. 92(12):4512-3. [Medline].
Bloomston M, Al-Saif O, Klemanski D, et al. Hepatic artery chemoembolization in 122 patients with metastatic carcinoid tumor: lessons learned. J Gastrointest Surg. 2007 Mar. 11(3):264-71. [Medline].
Lefebvre S, De Paepe L, Abs R, et al. Subcutaneous octreotide treatment of a growth hormone-releasing hormone-secreting bronchial carcinoid: superiority of continuous versus intermittent administration to control hormonal secretion. Eur J Endocrinol. 1995 Sep. 133(3):320-4. [Medline].
Rubin J, Ajani J, Schirmer W, et al. Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol. 1999 Feb. 17(2):600-6. [Medline].
Corleto VD, Angeletti S, Schillaci O, et al. Long-term octreotide treatment of metastatic carcinoid tumor. Ann Oncol. 2000 Apr. 11(4):491-3. [Medline].
Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011 Dec 10. 378(9808):2005-12. [Medline].
Alvarez MC, Macias AA, Saurez MG, Fernandez ML, Lage DA. Bronchial carcinoid tumor treated with interferon and a new vaccine against NeuGcGM3 antigen expressed in malignant carcinoid cells. Cancer Biol Ther. 2007 Jun. 6(6):853-5. [Medline].
Kwaan MR, Goldberg JE, Bleday R. Rectal carcinoid tumors: review of results after endoscopic and surgical therapy. Arch Surg. 2008 May. 143(5):471-5. [Medline].
Givi B, Pommier SJ, Thompson AK, Diggs BS, Pommier RF. Operative resection of primary carcinoid neoplasms in patients with liver metastases yields significantly better survival. Surgery. 2006 Dec. 140(6):891-7; discussion 897-8. [Medline].
Bertoletti L, Elleuch R, Kaczmarek D, Jean-Francois R, Vergnon JM. Bronchoscopic cryotherapy treatment of isolated endoluminal typical carcinoid tumor. Chest. 2006 Nov. 130(5):1405-11. [Medline].
Fornaro R, Frascio M, Sticchi C, et al. Appendectomy or right hemicolectomy in the treatment of appendiceal carcinoid tumors?. Tumori. 2007 Nov-Dec. 93(6):587-90. [Medline].
Bamboat ZM, Berger DL. Is right hemicolectomy for 2.0-cm appendiceal carcinoids justified?. Arch Surg. 2006 Apr. 141(4):349-52; discussion 352. [Medline].
Spunt SL, Pratt CB, Rao BN, et al. Childhood carcinoid tumors: the St Jude Children's Research Hospital experience. J Pediatr Surg. 2000 Sep. 35(9):1282-6. [Medline].
Landry CS, Woodall C, Scoggins CR, McMasters KM, Martin RC 2nd. Analysis of 900 appendiceal carcinoid tumors for a proposed predictive staging system. Arch Surg. 2008 Jul. 143(7):664-70; discussion 670. [Medline].
Turner GB, Johnston BT, McCance DR, McGinty A, Watson RG, Patterson CC, et al. Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours. Gut. 2006 Nov. 55(11):1586-91. [Medline].
Anderson JR, Wilson BG. Carcinoid tumours of the appendix. Br J Surg. 1985 Jul. 72(7):545-6. [Medline].
Andersson A, Bergdahl L. Carcinoid tumors of the appendix in children. A report of 25 cases. Acta Chir Scand. 1977. 143(3):173-5. [Medline].
Arnold R, Frank M, Kajdan U. Management of gastroenteropancreatic endocrine tumors: the place of somatostatin analogues. Digestion. 1994. 55 Suppl 3:107-13. [Medline].
Carrasco CH, Charnsangavej C, Ajani J, et al. The carcinoid syndrome: palliation by hepatic artery embolization. AJR Am J Roentgenol. 1986 Jul. 147(1):149-54. [Medline].
Carretta A, Chiesa G, Magnani P, et al. Imaging of bronchial carcinoid tumors associated to Cushing syndrome with 111In-Octreoscan scintigraphy and immunoscintigraphy with anti-chromogranin monoclonal antibodies. Report of two cases. J Cardiovasc Surg (Torino). 1997 Apr. 38(2):191-4. [Medline].
Chaudhry A, Funa K, Oberg K. Expression of growth factor peptides and their receptors in neuroendocrine tumors of the digestive system. Acta Oncol. 1993. 32(2):107-14. [Medline].
Chejfec G, Capella C, Solcia E, et al. Amphicrine cells, dysplasias, and neoplasias. Cancer. 1985 Dec 1. 56(11):2683-90. [Medline].
Chow CW, Sane S, Campbell PE, Carter RF. Malignant carcinoid tumors in children. Cancer. 1982 Feb 15. 49(4):802-11. [Medline].
Cohen T, Gluzman-Poltorak Z, Brodzky A, et al. Neuroendocrine cells along the digestive tract express neuropilin-2. Biochem Biophys Res Commun. 2001 Jun 8. 284(2):395-403. [Medline].
Corpron CA, Black CT, Herzog CE, et al. A half century of experience with carcinoid tumors in children. Am J Surg. 1995 Dec. 170(6):606-8. [Medline].
Craig SR, Hamzah M, Walker WS. Video-assisted thoracoscopic pneumonectomy for bronchial carcinoid tumor in a 14-year-old girl. J Pediatr Surg. 1996 Dec. 31(12):1724-6. [Medline].
de Jong M, Bakker WH, Krenning EP, et al. Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy. Eur J Nucl Med. 1997 Apr. 24(4):368-71. [Medline].
Diaco DS, Hajarizadeh H, Mueller CR, et al. Treatment of metastatic carcinoid tumors using multimodality therapy of octreotide acetate, intra-arterial chemotherapy, and hepatic arterial chemoembolization. Am J Surg. 1995 May. 169(5):523-8. [Medline].
Feldman JM. Carcinoid tumors and syndrome. Semin Oncol. 1987 Sep. 14(3):237-46. [Medline].
Fine RL, Gulati A, Tsushima D, et al. New, rationally-based chemotherapy combination appears highly effective in patients with treatment-resistant neuroendocrine tumors. Presented at: 2014 Symposium Highlights Treatment Advances for Multiple GI Cancers [press release]; January 14, 2014; Alexandria, Va. Available at http://www.asco.org/press-center/2014-symposium-highlights-treatment-advances-multiple-gi-cancers. Accessed: January 17, 2014.
Fine RL, Gulati A, Tsushima D, et al. Prospective phase II study of capecitabine and temozolomide (CAPTEM) for progressive, moderately, and well-differentiated metastatic neuroendocrine tumors. Clin Oncol 2014:32 (suppl 3); abstr 179. Available at http://abstracts.asco.org/143/AbstView_143_122616.htm.
Gartner LA, Voorhess ML. Adrenocorticotropic hormone--producing thymic carcinoid in a teenager. Cancer. 1993 Jan 1. 71(1):106-11. [Medline].
Hajarizadeh H, Ivancev K, Mueller CR, et al. Effective palliative treatment of metastatic carcinoid tumors with intra-arterial chemotherapy/chemoembolization combined with octreotide acetate. Am J Surg. 1992 May. 163(5):479-83. [Medline].
Han HS, Kim HS, Woo DK, et al. Loss of heterozygosity in gastric neuroendocrine tumor. Anticancer Res. 2000 Sep-Oct. 20(5A):2849-54. [Medline].
Hause DW, Harvey JC. Endobronchial carcinoid and mucoepidermoid carcinoma in children. J Surg Oncol. 1991 Apr. 46(4):270-2. [Medline].
Hulka GF, Rothschild MA, Warner BW, Bove KE. Carcinoid tumor of the trachea in a pediatric patient. Otolaryngol Head Neck Surg. 1996 Jun. 114(6):822-5. [Medline].
Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK. Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health. J Clin Endocrinol Metab. 2005 Aug. 90(8):4955-62. [Medline].
Johnson LA, Lavin P, Moertel CG, et al. Carcinoids: the association of histologic growth pattern and survival. Cancer. 1983 Mar 1. 51(5):882-9. [Medline].
Kamiyoshihara M, Hirai T, Kawashima O, et al. Low-grade malignant tumors of the lung: is lymph node dissection necessary?. Oncol Rep. 1998 Jul-Aug. 5(4):841-3. [Medline].
Kema IP, Willemse PH, De Vries EG. Carcinoid tumors. N Engl J Med. 1999 Aug 5. 341(6):453-4; discussion 454-5. [Medline].
Kerr DJ, Ledermann JA, McArdle CS, et al. Phase I clinical and pharmacokinetic study of leucovorin and infusional hepatic arterial fluorouracil. J Clin Oncol. 1995 Dec. 13(12):2968-72. [Medline].
King MD, Young DG, Hann IM, Patrick WJ. Carcinoid syndrome: an unusual cause of diarrhoea. Arch Dis Child. 1985 Mar. 60(3):269-71. [Medline].
Krishnamurthy SC, Dutta V, Pai SA, et al. Primary carcinoid tumor of the liver: report of four resected cases including one with gastrin production. J Surg Oncol. 1996 Jul. 62(3):218-21. [Medline].
Kytola S, Hoog A, Nord B, et al. Comparative genomic hybridization identifies loss of 18q22-qter as an early and specific event in tumorigenesis of midgut carcinoids. Am J Pathol. 2001 May. 158(5):1803-8. [Medline]. [Full Text].
La Ferla G, Baxter RA, Tavadia HB, Harper DR. Multiple colonic carcinoid tumours in a child. Br J Surg. 1984 Nov. 71(11):843. [Medline].
Leake J, Levitt G, Ramani P. Primary carcinoid of the testis in a 10-year-old boy. Histopathology. 1991 Oct. 19(4):373-5. [Medline].
Lee GH, Dietrich RB, Pais MJ, Wang NS. Pediatric case of the day. Neuroendocrine carcinoma (atypical carcinoid/Kulchitzky-cell carcinoma II). Radiographics. 1994 Jan. 14(1):188-91. [Medline].
Lin KL, Chen CY, Hsu HH, et al. Ectopic ACTH syndrome due to thymic carcinoid tumor in a girl. J Pediatr Endocrinol Metab. 1999 Jul-Aug. 12(4):573-8. [Medline].
Loftus JP, van Heerden JA. Surgical management of gastrointestinal carcinoid tumors. Adv Surg. 1995. 28:317-36. [Medline].
Loh KC, Yap WM, Chia FK. Ectopic Cushing's syndrome in a young female with atypical [corrected] bronchial carcinoid tumour. Singapore Med J. 1997 Jan. 38(1):29-31. [Medline].
McDougall JC, Gorenstein A, Unni K, O'Connell EJ. Carcinoid and mucoepidermoid carcinoma of bronchus in children. Ann Otol Rhinol Laryngol. 1980 Sep-Oct. 89(5 Pt 1):425-7. [Medline].
Moertel CG, Dockerty MB, Judd ES. Carcinoid tumors of the vermiform appendix. Cancer. 1968 Feb. 21(2):270-8. [Medline].
Mulcahy N. Unprecedented responses seen in neuroendocrine tumors. Medscape Medical News. January 15, 2014. Available at http://www.medscape.com/viewarticle/819220. Accessed: January 17, 2014.
Oliveira AM, Tazelaar HD, Wentzlaff KA, et al. Familial pulmonary carcinoid tumors. Cancer. 2001 Jun 1. 91(11):2104-9. [Medline].
Parkes SE, Muir KR, al Sheyyab M, et al. Carcinoid tumours of the appendix in children 1957-1986: incidence, treatment and outcome. Br J Surg. 1993 Apr. 80(4):502-4. [Medline].
Petzmann S, Ullmann R, Klemen H, et al. Loss of heterozygosity on chromosome arm 11q in lung carcinoids. Hum Pathol. 2001 Mar. 32(3):333-8. [Medline].
Roberts WC, Sjoerdsma A. The cardiac disease associated with the carcinoid syndrome (carcinoid heart disease). Am J Med. 1964 Jan. 36:5-34. [Medline].
Rutledge RH, Alexander JW. Primary appendiceal malignancies: rare but important. Surgery. 1992 Mar. 111(3):244-50. [Medline].
Ryden SE, Drake RM, Franciosi RA. Carcinoid tumors of the appendix in children. Cancer. 1975 Oct. 36(4):1538-42. [Medline].
Sabback MS, O'Brien PH. Clinical study of 81 gastrointestinal carcinoid tumors. South Med J. 1979 Apr. 72(4):386-90. [Medline].
Scully RE, Mark EJ, McNeely WF. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 9-1997. A 39-year-old woman with pernicious anemia and a gastric mass. N Engl J Med. 1997 Mar 20. 336(12):861-7. [Medline].
Slodkowska J, Sikora J, Androsiuk W, et al. Lung carcinoids. Tumor angiogenesis in relation to clinicopathologic characteristics. Anal Quant Cytol Histol. 1999 Jun. 21(3):267-72. [Medline].
Soga J, Tazawa K. Pathologic analysis of carcinoids. Histologic reevaluation of 62 cases. Cancer. 1971 Oct. 28(4):990-8. [Medline].
Soreide O, Berstad T, Bakka A, et al. Surgical treatment as a principle in patients with advanced abdominal carcinoid tumors. Surgery. 1992 Jan. 111(1):48-54. [Medline].
Teh BT, Hayward NK, Walters MK, et al. Genetic studies of thymic carcinoids in multiple endocrine neoplasia type 1. J Med Genet. 1994 Mar. 31(3):261-2. [Medline].
Wada K, Asoh T, Imamura T, et al. Rectal carcinoid tumor associated with the Peutz-Jeghers syndrome. J Gastroenterol. 1998 Oct. 33(5):743-6. [Medline].
Weissberg D. Video-assisted thoracoscopic pneumonectomy for bronchial carcinoid tumor in a 14-year-old girl. J Pediatr Surg. 1997 Jul. 32(7):1135. [Medline].
Whelan T, Gatfield CT, Robertson S, et al. Primary carcinoid of the prostate in conjunction with multiple endocrine neoplasia IIb in a child. J Urol. 1995 Mar. 153(3 Pt 2):1080-2. [Medline].
Wilkin JK. Flushing reactions: consequences and mechanisms. Ann Intern Med. 1981 Oct. 95(4):468-76. [Medline].
Williams ED, Sandler M. The classification of carcinoid tum ours. Lancet. 1963 Feb 2. 1:238-9. [Medline].
Wong VG, Melmon KL. Ophthalmic manifestations of the carcinoid flush. N Engl J Med. 1967 Aug 24. 277(8):406-9. [Medline].
Young RH, Kozakewich HP, Scully RE. Metastatic ovarian tumors in children: a report of 14 cases and review of the literature. Int J Gynecol Pathol. 1993 Jan. 12(1):8-19. [Medline].