[[Carcinoid Syndrome|Carcinoid syndrome]] (CS) is a [[paraneoplastic Syndromes|paraneoplastic syndrome]] caused by the [[Secretions|secretion]] of [[serotonin]] [[5-hydroxytryptamine|(5-hydroxytrptamine]]) but can be caused by the [[secretion]] of [[histamine|histamine,]] [[kallikrein]], [[prostaglandins]], and [[tachykinins.]].[[Carcinoid Syndrome|Carcinoid syndrome]] is most commonly caused by [[neuroendocrine]] [[tumors]] of [[midgut]]. In patients with carcinoid syndrome, 70% of [[tryptophan]] is converted into [[serotonin]] which leads to secondary deficiency of [[niacin]]. [[Serotonin]] is metabolized into 5-hydroxy indoleacetic acid (5-HIAA) by [[aldehyde dehydrogenase]], which is [[eliminated]] into the [[urine]]. Deficiency of [[niacin]] results in [[Pellagra]] which manifests as [[dermatitis]], [[dementia]], and [[diarrhea]]. [[Carcinoid]] [[tumors]] arising in the [[bronchi]] reach the [[systemic]] [[circulation]] before passing through the [[liver]] and may be associated with [[bronchoconstriction]] and manifestations of [[carcinoid]] [[syndrome]] without [[liver]] [[Metastases|metastases.]] [[Bronchospasm]] leading to [[wheezing]] is caused by release of [[histamine]]. [[5-HT2B receptor|5-HT2B]] is the [[receptor]] of [[serotonin]] in the [[cardiovascular]] [[system]] that may be involved in [[fibrogenesis]]. [[Fibrosis]] leads to [[Tricuspid]] and [[Pulmonic Regurgitation|pulmonic]] [[regurgitation]], [[pulmonary stenosis]] and [[Cardiac arrythmia|cardiac arrhythmias]][[arrhythmias|.]] [[Serotonin]] and [[TGF-beta]] are secreted by [[Neuroendocrine tumor|neuroendocrine tumors]] and appear to play a central role in the development of [[mesenteric]] [[fibrosis]]. [[Carcinoid]] [[tumors]] are normally found throughout the [[gastrointestinal]] [[tract]] from [[mouth]] to [[anus]], with the highest concentration of [[cells]] in the [[appendix]] and [[small intestine]]. [[Lung]] is the second most common site for [[Neuroendocrine tumour|neuroendocrine tumours]] . In the [[gastric]] or [[intestinal]] [[wall]], [[Carcinoid|carcinoids]] may occur as firm [[white]], yellow, or gray [[nodules]] and may be [[intramural]] [[masses]] or may protrude into the lumen as [[polypoid]] [[nodules]]. Neuroendocrine tumors arise from [[enterochromaffin]] [[cells]]. The name "enterochromaffin" refers to the ability to stain the cell with [[potassium]] [[chromate]] (chromaffin), a feature of [[cells]] that contain [[serotonin]].
[[Carcinoid Syndrome|Carcinoid syndrome]] (CS) is a [[paraneoplastic Syndromes|paraneoplastic syndrome]] caused by the [[Secretions|secretion]] of [[serotonin]] [[5-hydroxytryptamine|(5-hydroxytrptamine]]) but can be caused by the [[secretion]] of [[histamine|histamine,]] [[kallikrein]], [[prostaglandins]], and tachykinins..[[Carcinoid Syndrome|Carcinoid syndrome]] is most commonly caused by [[neuroendocrine]] [[tumors]] of [[midgut]]. In patients with carcinoid syndrome, 70% of [[tryptophan]] is converted into [[serotonin]] which leads to secondary deficiency of [[niacin]]. [[Serotonin]] is metabolized into 5-hydroxy indoleacetic acid (5-HIAA) by [[aldehyde dehydrogenase]], which is [[eliminated]] into the [[urine]]. Deficiency of [[niacin]] results in [[Pellagra]] which manifests as [[dermatitis]], [[dementia]], and [[diarrhea]]. [[Carcinoid]] [[tumors]] arising in the [[bronchi]] reach the [[systemic]] [[circulation]] before passing through the [[liver]] and may be associated with [[bronchoconstriction]] and manifestations of [[carcinoid]] [[syndrome]] without [[liver]] [[Metastases|metastases.]] [[Bronchospasm]] leading to [[wheezing]] is caused by release of [[histamine]]. [[5-HT2B receptor|5-HT2B]] is the [[receptor]] of [[serotonin]] in the [[cardiovascular]] [[system]] that may be involved in [[fibrogenesis]]. [[Fibrosis]] leads to [[Tricuspid]] and [[Pulmonic Regurgitation|pulmonic]] [[regurgitation]], [[pulmonary stenosis]] and [[Cardiac arrythmia|cardiac arrhythmias]][[arrhythmias|.]] [[Serotonin]] and [[TGF-beta]] are secreted by [[Neuroendocrine tumor|neuroendocrine tumors]] and appear to play a central role in the development of [[mesenteric]] [[fibrosis]]. [[Carcinoid]] [[tumors]] are normally found throughout the [[gastrointestinal]] [[tract]] from [[mouth]] to [[anus]], with the highest concentration of [[cells]] in the [[appendix]] and [[small intestine]]. [[Lung]] is the second most common site for [[Neuroendocrine tumour|neuroendocrine tumours]] . In the [[gastric]] or [[intestinal]] [[wall]], [[Carcinoid|carcinoids]] may occur as firm [[white]], yellow, or gray [[nodules]] and may be intramural [[masses]] or may protrude into the lumen as [[polypoid]] [[nodules]]. Neuroendocrine tumors arise from [[enterochromaffin]] [[cells]]. The name "[[Enterochromaffin cell|enterochromaffin]]" refers to the ability to stain the cell with [[potassium]] [[chromate]] (chromaffin), a feature of [[cells]] that contain [[serotonin]].
=Pathophysiology=
=Pathophysiology=
* [[Carcinoid Syndrome|Carcinoid syndrome]] (CS) is a [[Paraneoplastic Syndromes|paraneoplastic syndrome]] associated with the [[Secretions|secretion]] of several hormones.<ref name="pmid30133565">{{cite journal |vauthors=Rubin de Celis Ferrari AC, Glasberg J, Riechelmann RP |title=Carcinoid syndrome: update on the pathophysiology and treatment |journal=Clinics (Sao Paulo) |volume=73 |issue=suppl 1 |pages=e490s |date=August 2018 |pmid=30133565 |pmc=6096975 |doi=10.6061/clinics/2018/e490s |url=}}</ref>
* [[Carcinoid Syndrome|Carcinoid syndrome]] (CS) is a [[Paraneoplastic Syndromes|paraneoplastic syndrome]] associated with the [[Secretions|secretion]] of several [[hormones]].<ref name="pmid30133565">{{cite journal |vauthors=Rubin de Celis Ferrari AC, Glasberg J, Riechelmann RP |title=Carcinoid syndrome: update on the pathophysiology and treatment |journal=Clinics (Sao Paulo) |volume=73 |issue=suppl 1 |pages=e490s |date=August 2018 |pmid=30133565 |pmc=6096975 |doi=10.6061/clinics/2018/e490s |url=}}</ref>
* The primary marker is [[serotonin]] ([[5-hydroxytryptamine|5-hydroxytrptamine]]) but the syndrome can be caused by the [[secretion]] of [[histamine|histamine,]] [[kallikrein]], [[prostaglandins]], and [[tachykinins.]]
* The primary marker is [[serotonin]] ([[5-hydroxytryptamine|5-hydroxytrptamine]]) but the syndrome can be caused by the [[secretion]] of [[histamine|histamine,]] [[kallikrein]], [[prostaglandins]], and tachykinins.
*[[Carcinoid Syndrome|Carcinoid syndrome]] is most commonly caused by [[neuroendocrine]] [[tumors]] of the [[midgut]].
*[[Carcinoid Syndrome|Carcinoid syndrome]] is most commonly caused by [[neuroendocrine]] [[tumors]] of the [[midgut]].
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#Extensive [[bone]] [[metastases]]
#Extensive [[bone]] [[metastases]]
*Only 1% of dietary [[tryptophan]] is converted into [[serotonin]]. However, in a patient with [[neuroendocrine tumors]], up to 70% of [[tryptophan]] is converted into [[serotonin]].
*Only 1% of dietary [[tryptophan]] is converted into [[serotonin]]. However, in a patient with [[neuroendocrine tumors]], up to 70% of [[tryptophan]] is converted into [[serotonin]].
*[[Serotonin]] undergoes oxidative reaction and leads to the formation of [[5-hydroxy indoleacetic acid (5-HIAA]]) by [[aldehyde dehydrogenase]], which is [[eliminated]] into the [[urine]].
*[[Serotonin]] undergoes [[oxidative]] reaction and leads to the formation of 5-hydroxy indoleacetic acid (5-HIAA) by [[aldehyde dehydrogenase]], which is eliminated into the [[urine]].
*[[Serotonin]] causes increased [[motility]] and [[secretions]] of the GIT resulting in [[diarrhea]].
*[[Serotonin]] causes increased [[motility]] and [[secretions]] of the [[GIT]] resulting in [[diarrhea]].
*As most of the body's [[tryptophan]] is diverted to [[serotonin]] formation pathway by [[neuroendocrine]] [[tumors]], [[tryptophan]] (which is needed for niacin synthesis) becomes deficient.
*As most of the body's [[tryptophan]] is diverted to [[serotonin]] formation pathway by [[neuroendocrine]] [[tumors]], [[tryptophan]] (which is needed for [[niacin]] synthesis) becomes deficient.
*Deficiency of [[niacin]] results in [[Pellagra]] which manifests as [[dermatitis]], [[dementia]], and [[diarrhea]].
*Deficiency of [[niacin]] results in [[Pellagra]] which manifests as [[dermatitis]], [[dementia]], and [[diarrhea]].
*[[Prostaglandins]] also mediate increased [[intestinal]] [[motility]] and [[fluid]] [[secretion]] in [[gastrointestinal]] [[tract]] causing [[diarrhea]].
*[[Prostaglandins]] also mediate increased [[intestinal]] [[motility]] and [[fluid]] [[secretion]] in [[gastrointestinal]] [[tract]] causing [[diarrhea]].
*Skin [[flushing]] results from the [[secretion]] of [[kallikrein]], the [[enzyme]] that [[catalyzes]] the conversion of [[kininogen]] to [[lysyl]]-[[bradykinin]].
*Skin [[flushing]] results from the [[secretion]] of [[kallikrein]], the [[enzyme]] that [[catalyzes]] the conversion of [[kininogen]] to [[lysyl]]-[[bradykinin]].
*[[Lysyl]]-[[bradykinin]] is further converted to [[bradykinin]], a strong [[vasodilators|vasodilator.]]
*Lysyl-[[bradykinin]] is further converted to [[bradykinin]], a strong [[vasodilators|vasodilator.]]
*Large amounts of [[serotonin]] produces [[pellagra]]-like features including [[diarrhea]].
*Large amounts of [[serotonin]] produces [[pellagra]]-like features including [[diarrhea]].
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===[[Carcinoid]] [[Heart]] [[Disease]]===
===[[Carcinoid]] [[Heart]] [[Disease]]===
*[[5-HT2B]] is the [[receptor]] of [[serotonin]] in the [[cardiovascular]] [[system]] that may be involved in [[fibrogenesis]].<ref name="pmid25871411">{{cite journal |vauthors=Grozinsky-Glasberg S, Grossman AB, Gross DJ |title=Carcinoid Heart Disease: From Pathophysiology to Treatment--'Something in the Way It Moves' |journal=Neuroendocrinology |volume=101 |issue=4 |pages=263–73 |date=2015 |pmid=25871411 |doi=10.1159/000381930 |url=}}</ref>
*5-HT2B is the [[receptor]] of [[serotonin]] in the [[cardiovascular]] [[system]] that may be involved in [[fibrogenesis]].<ref name="pmid25871411">{{cite journal |vauthors=Grozinsky-Glasberg S, Grossman AB, Gross DJ |title=Carcinoid Heart Disease: From Pathophysiology to Treatment--'Something in the Way It Moves' |journal=Neuroendocrinology |volume=101 |issue=4 |pages=263–73 |date=2015 |pmid=25871411 |doi=10.1159/000381930 |url=}}</ref>
*Activation of the [[5-HT2B]] [[receptor]] triggers distinct [[intracellular]] [[signaling]] [[pathways]], which in turn may result in a stronger [[inflammatory]] response and release of [[cytokines]] including [[TNF-alpha]], activation of the MAPK [[signaling]] [[pathway]] and hyperexpression of [[TGF-beta]] leading to to [[cardiac]] [[fibrosis]].<ref name="pmid8621713">{{cite journal |vauthors=Launay JM, Birraux G, Bondoux D, Callebert J, Choi DS, Loric S, Maroteaux L |title=Ras involvement in signal transduction by the serotonin 5-HT2B receptor |journal=J. Biol. Chem. |volume=271 |issue=6 |pages=3141–7 |date=February 1996 |pmid=8621713 |doi= |url=}}</ref><ref name="pmid19023134">{{cite journal |vauthors=Jaffré F, Bonnin P, Callebert J, Debbabi H, Setola V, Doly S, Monassier L, Mettauer B, Blaxall BC, Launay JM, Maroteaux L |title=Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy |journal=Circ. Res. |volume=104 |issue=1 |pages=113–23 |date=January 2009 |pmid=19023134 |doi=10.1161/CIRCRESAHA.108.180976 |url=}}</ref><ref name="pmid12466135">{{cite journal |vauthors=Xu J, Jian B, Chu R, Lu Z, Li Q, Dunlop J, Rosenzweig-Lipson S, McGonigle P, Levy RJ, Liang B |title=Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells |journal=Am. J. Pathol. |volume=161 |issue=6 |pages=2209–18 |date=December 2002 |pmid=12466135 |doi=10.1016/S0002-9440(10)64497-5 |url=}}</ref>
*Activation of the 5-HT2B [[receptor]] triggers distinct [[intracellular]] [[signaling]] [[pathways]], which in turn may result in a stronger [[inflammatory]] response and release of [[cytokines]] including [[TNF-alpha]], activation of the MAPK signaling [[pathway]] and hyperexpression of [[TGF-beta]] leading to to [[cardiac]] [[fibrosis]].<ref name="pmid8621713">{{cite journal |vauthors=Launay JM, Birraux G, Bondoux D, Callebert J, Choi DS, Loric S, Maroteaux L |title=Ras involvement in signal transduction by the serotonin 5-HT2B receptor |journal=J. Biol. Chem. |volume=271 |issue=6 |pages=3141–7 |date=February 1996 |pmid=8621713 |doi= |url=}}</ref><ref name="pmid19023134">{{cite journal |vauthors=Jaffré F, Bonnin P, Callebert J, Debbabi H, Setola V, Doly S, Monassier L, Mettauer B, Blaxall BC, Launay JM, Maroteaux L |title=Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy |journal=Circ. Res. |volume=104 |issue=1 |pages=113–23 |date=January 2009 |pmid=19023134 |doi=10.1161/CIRCRESAHA.108.180976 |url=}}</ref><ref name="pmid12466135">{{cite journal |vauthors=Xu J, Jian B, Chu R, Lu Z, Li Q, Dunlop J, Rosenzweig-Lipson S, McGonigle P, Levy RJ, Liang B |title=Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells |journal=Am. J. Pathol. |volume=161 |issue=6 |pages=2209–18 |date=December 2002 |pmid=12466135 |doi=10.1016/S0002-9440(10)64497-5 |url=}}</ref>
*[[Fibrosis]] leads to [[thickening]] of [[mural]] and [[valvular]] [[endothelial]] surfaces of [[right]]-sided [[cardiac]] structures.<ref>Carcinoid cardiac lesions. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia. http://radiopaedia.org/articles/carcinoid-cardiac-lesions</ref><ref name="pmid26971851">{{cite journal |vauthors=Luis SA, Pellikka PA |title=Carcinoid heart disease: Diagnosis and management |journal=Best Pract. Res. Clin. Endocrinol. Metab. |volume=30 |issue=1 |pages=149–58 |date=January 2016 |pmid=26971851 |doi=10.1016/j.beem.2015.09.005 |url=}}</ref>
*[[Fibrosis]] leads to thickening of mural and [[valvular]] [[endothelial]] surfaces of [[right]]-sided [[cardiac]] structures.<ref>Carcinoid cardiac lesions. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia. http://radiopaedia.org/articles/carcinoid-cardiac-lesions</ref><ref name="pmid26971851">{{cite journal |vauthors=Luis SA, Pellikka PA |title=Carcinoid heart disease: Diagnosis and management |journal=Best Pract. Res. Clin. Endocrinol. Metab. |volume=30 |issue=1 |pages=149–58 |date=January 2016 |pmid=26971851 |doi=10.1016/j.beem.2015.09.005 |url=}}</ref>
* [[Fibrosis]] leads to
* [[Fibrosis]] leads to
#[[Tricuspid]] and [[pulmonic]] [[regurgitation]].
#[[Tricuspid]] and pulmonic [[regurgitation]].
#[[Pulmonary stenosis|Pulmonary stenosis.]]
#[[Pulmonary stenosis|Pulmonary stenosis.]]
#[[Cardiac arrythmia|Cardiac arhythmias]].
#[[Cardiac arrythmia|Cardiac arhythmias]].
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* [[Vascular]] [[ischemia]] can lead to [[bowel]] [[congestion]] and result in decreased [[Absorption (digestive)|absorption]] of [[nutrients]] and can also cause [[ascites]] and more severe cases of [[mesenteric]] [[ischemia.]]<ref name="pmid7839976">{{cite journal |vauthors=Pantongrag-Brown L, Buetow PC, Carr NJ, Lichtenstein JE, Buck JL |title=Calcification and fibrosis in mesenteric carcinoid tumor: CT findings and pathologic correlation |journal=AJR Am J Roentgenol |volume=164 |issue=2 |pages=387–91 |date=February 1995 |pmid=7839976 |doi=10.2214/ajr.164.2.7839976 |url=}}</ref><ref name="pmid27861745">{{cite journal |vauthors=Daskalakis K, Karakatsanis A, Stålberg P, Norlén O, Hellman P |title=Clinical signs of fibrosis in small intestinal neuroendocrine tumours |journal=Br J Surg |volume=104 |issue=1 |pages=69–75 |date=January 2017 |pmid=27861745 |doi=10.1002/bjs.10333 |url=}}</ref>
* [[Vascular]] [[ischemia]] can lead to [[bowel]] [[congestion]] and result in decreased [[Absorption (digestive)|absorption]] of [[nutrients]] and can also cause [[ascites]] and more severe cases of [[mesenteric]] [[ischemia.]]<ref name="pmid7839976">{{cite journal |vauthors=Pantongrag-Brown L, Buetow PC, Carr NJ, Lichtenstein JE, Buck JL |title=Calcification and fibrosis in mesenteric carcinoid tumor: CT findings and pathologic correlation |journal=AJR Am J Roentgenol |volume=164 |issue=2 |pages=387–91 |date=February 1995 |pmid=7839976 |doi=10.2214/ajr.164.2.7839976 |url=}}</ref><ref name="pmid27861745">{{cite journal |vauthors=Daskalakis K, Karakatsanis A, Stålberg P, Norlén O, Hellman P |title=Clinical signs of fibrosis in small intestinal neuroendocrine tumours |journal=Br J Surg |volume=104 |issue=1 |pages=69–75 |date=January 2017 |pmid=27861745 |doi=10.1002/bjs.10333 |url=}}</ref>
==Genetics==
==Genetics==
*Gastrointestinal carcinoids occur in association with [[inherited syndromes]], such as [[multiple endocrine neoplasia type 1]] and [[neurofibromatosis type 1]].<ref name="aaa">General Information About Gastrointestinal (GI) Carcinoid Tumors.<nowiki><ref name="pmid2886072"></nowiki>{{cite journal |vauthors=Duh QY, Hybarger CP, Geist R, Gamsu G, Goodman PC, Gooding GA, Clark OH |title=Carcinoids associated with multiple endocrine neoplasia syndromes |journal=Am. J. Surg. |volume=154 |issue=1 |pages=142–8 |date=July 1987 |pmid=2886072 |doi= |url=}}</ref>
*Gastrointestinal carcinoids occur in association with inherited syndromes, such as [[multiple endocrine neoplasia type 1]] and [[neurofibromatosis type 1]].<ref name="aaa">General Information About Gastrointestinal (GI) Carcinoid Tumors.<nowiki><ref name="pmid2886072"></nowiki>{{cite journal |vauthors=Duh QY, Hybarger CP, Geist R, Gamsu G, Goodman PC, Gooding GA, Clark OH |title=Carcinoids associated with multiple endocrine neoplasia syndromes |journal=Am. J. Surg. |volume=154 |issue=1 |pages=142–8 |date=July 1987 |pmid=2886072 |doi= |url=}}</ref>
*[[Multiple endocrine neoplasia type 1]] is caused by alterations of the [[MEN1]] [[gene]] located at [[chromosomal]] region [[11q13]].
*[[Multiple endocrine neoplasia type 1]] is caused by alterations of the [[MEN1]] [[gene]] located at [[chromosomal]] region 11q13.
*Most [[Carcinoid|carcinoids]] associated with [[multiple endocrine neoplasia type 1]] appear to be of [[foregut]] origin.
*Most [[Carcinoid|carcinoids]] associated with [[multiple endocrine neoplasia type 1]] appear to be of [[foregut]] origin.
*[[Neurofibromatosis type 1]] is an [[autosomal dominant]] [[genetic]] [[disorder]] caused by alteration of the ''[[NF1]]'' [[gene]] at [[chromosome]] [[17q11]].
*[[Neurofibromatosis type 1]] is an [[autosomal dominant]] [[genetic]] [[disorder]] caused by alteration of the ''[[NF1]]'' [[gene]] at [[chromosome]] 17q11.
*[[Carcinoid|Carcinoids]] in patients with [[neurofibromatosis type 1]] appear to arise primarily in the [[periampullary]] region.<ref name="pmid10873367">{{cite journal |vauthors=Karatzas G, Kouraklis G, Karayiannakis A, Patapis P, Givalos N, Kaperonis E |title=Ampullary carcinoid and jejunal stromal tumour associated with von Recklinghausen's disease presenting as gastrointestinal bleeding and jaundice |journal=Eur J Surg Oncol |volume=26 |issue=4 |pages=428–9 |date=June 2000 |pmid=10873367 |doi=10.1053/ejso.1999.0911 |url=}}</ref>
*[[Carcinoid|Carcinoids]] in patients with [[neurofibromatosis type 1]] appear to arise primarily in the periampullary region.<ref name="pmid10873367">{{cite journal |vauthors=Karatzas G, Kouraklis G, Karayiannakis A, Patapis P, Givalos N, Kaperonis E |title=Ampullary carcinoid and jejunal stromal tumour associated with von Recklinghausen's disease presenting as gastrointestinal bleeding and jaundice |journal=Eur J Surg Oncol |volume=26 |issue=4 |pages=428–9 |date=June 2000 |pmid=10873367 |doi=10.1053/ejso.1999.0911 |url=}}</ref>
* A [[hereditary]] form of [[small intestinal]] [[carcinoid]] [[Tumour|tumour has]] been found which is caused by [[Mutations|mutation]] in the IPMK [[gene]] leads to higher risk of developing [[carcinoid]] [[tumors]] in the [[Small intestinal|small intestine]].<ref name="pmid25865046">{{cite journal |vauthors=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, Schäffer AA, Hughes MS, Bailey-Wilson JE, Wank SA |title=A Hereditary Form of Small Intestinal Carcinoid Associated With a Germline Mutation in Inositol Polyphosphate Multikinase |journal=Gastroenterology |volume=149 |issue=1 |pages=67–78 |date=July 2015 |pmid=25865046 |pmc=4858647 |doi=10.1053/j.gastro.2015.04.008 |url=}}</ref>
* A [[hereditary]] form of [[small intestinal]] [[carcinoid]] [[Tumour|tumour has]] been found which is caused by [[Mutations|mutation]] in the IPMK [[gene]] leads to higher risk of developing [[carcinoid]] [[tumors]] in the [[Small intestinal|small intestine]].<ref name="pmid25865046">{{cite journal |vauthors=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, Schäffer AA, Hughes MS, Bailey-Wilson JE, Wank SA |title=A Hereditary Form of Small Intestinal Carcinoid Associated With a Germline Mutation in Inositol Polyphosphate Multikinase |journal=Gastroenterology |volume=149 |issue=1 |pages=67–78 |date=July 2015 |pmid=25865046 |pmc=4858647 |doi=10.1053/j.gastro.2015.04.008 |url=}}</ref>
*The most frequently reported [[mutated]] [[gene]] in [[gastrointestinal]] carcinoids is [[β-catenin|''β-catenin'']] (CTNNB1).<ref name="pmid11559529">{{cite journal |vauthors=Fujimori M, Ikeda S, Shimizu Y, Okajima M, Asahara T |title=Accumulation of beta-catenin protein and mutations in exon 3 of beta-catenin gene in gastrointestinal carcinoid tumor |journal=Cancer Res. |volume=61 |issue=18 |pages=6656–9 |date=September 2001 |pmid=11559529 |doi= |url=}}</ref>
*The most frequently reported [[mutated]] [[gene]] in [[gastrointestinal]] carcinoids is [[β-catenin|''β-catenin'']] (CTNNB1).<ref name="pmid11559529">{{cite journal |vauthors=Fujimori M, Ikeda S, Shimizu Y, Okajima M, Asahara T |title=Accumulation of beta-catenin protein and mutations in exon 3 of beta-catenin gene in gastrointestinal carcinoid tumor |journal=Cancer Res. |volume=61 |issue=18 |pages=6656–9 |date=September 2001 |pmid=11559529 |doi= |url=}}</ref>
==Embryology==
==Embryology==
*[[Carcinoid tumors]] originate from [[neuroendocrine cells]] ([[enterochromaffin]] or [[amine]] precursor uptake and [[decarboxylase]] [[APUD cell|[APUD]]<nowiki>] </nowiki>[[cells]]) which are derived from [[neural crest cells]] [[embrologically]].
*[[Carcinoid tumors]] originate from [[neuroendocrine cells]] ([[enterochromaffin]] or [[amine]] precursor uptake and [[decarboxylase]] [[APUD cell|[APUD]]<nowiki>] </nowiki>[[cells]]) which are derived from [[neural crest cells]] embrologically.
*[[Gastrointestinal|Gastrointestina]]<nowiki/>l [[Carcinoid tumors|carcinoids]] derive from [[cells]] that migrate from the [[Neural crest cell|neural crest]] to the [[foregut]], [[midgut]] and [[hindgut]].<ref name="pmid17114072">{{cite journal| author=Reznek RH| title=CT/MRI of neuroendocrine tumours. | journal=Cancer Imaging | year= 2006 | volume= 6 | issue= | pages= S163-77 | pmid=17114072 | doi=10.1102/1470-7330.2006.9037 | pmc=PMC1805060 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17114072 }} </ref>
*[[Gastrointestinal|Gastrointestina]]<nowiki/>l [[Carcinoid tumors|carcinoids]] derive from [[cells]] that migrate from the [[Neural crest cell|neural crest]] to the [[foregut]], [[midgut]] and [[hindgut]].<ref name="pmid17114072">{{cite journal| author=Reznek RH| title=CT/MRI of neuroendocrine tumours. | journal=Cancer Imaging | year= 2006 | volume= 6 | issue= | pages= S163-77 | pmid=17114072 | doi=10.1102/1470-7330.2006.9037 | pmc=PMC1805060 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17114072 }} </ref>
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==Gross Pathology==
==Gross Pathology==
===Gastrointestinal Carcinoid===
===Gastrointestinal Carcinoid===
In the [[gastric]] or [[intestinal]] wall, [[Carcinoid tumors|carcinoids tumors]] may occur as firm white, yellow, or gray nodules and may be [[intramural masses]] or may protrude into the [[lumen]] as polypoid [[nodules]]. The overlying [[gastric]] or [[intestinal mucosa]] may be intact or have focal [[ulceration]].
In the [[gastric]] or [[intestinal]] wall, [[Carcinoid tumors|carcinoids tumors]] may occur as firm white, yellow, or gray nodules and may be intramural masses or may protrude into the [[lumen]] as polypoid [[nodules]]. The overlying [[gastric]] or [[intestinal mucosa]] may be intact or have focal [[ulceration]].
*Well-differentiated [[neuroendocrine tumors]] of the [[tubular]] [[gastrointestinal tract]] are often [[Circumscribed|well-circumscribed]] round lesions in the [[Submucosal|submucosa]] or extending to the [[Muscular|muscular layer]].
*Well-differentiated [[neuroendocrine tumors]] of the [[tubular]] [[gastrointestinal tract]] are often well-circumscribed round lesions in the [[Submucosal|submucosa]] or extending to the [[Muscular|muscular layer]].
*The cut surface appears red to tan, reflecting the abundant [[microvasculature]], or sometimes yellow because of high [[lipid]] content.
*The cut surface appears red to tan, reflecting the abundant [[microvasculature]], or sometimes yellow because of high [[lipid]] content.
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*Lung is the second most common site for [[neuroendocrine tumor]].
*Lung is the second most common site for [[neuroendocrine tumor]].
*[[Lung]] [[Neuroendocrine tumor|neuroendocrine tumors]] are classified on the basis of [[Histology|histology:]]<ref name="pmid20664470">{{cite journal |vauthors=Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S |title=The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems |journal=Pancreas |volume=39 |issue=6 |pages=707–12 |date=August 2010 |pmid=20664470 |doi=10.1097/MPA.0b013e3181ec124e |url=}}</ref><ref name="pmid17400673">{{cite journal |vauthors=Aubry MC, Thomas CF, Jett JR, Swensen SJ, Myers JL |title=Significance of multiple carcinoid tumors and tumorlets in surgical lung specimens: analysis of 28 patients |journal=Chest |volume=131 |issue=6 |pages=1635–43 |date=June 2007 |pmid=17400673 |doi=10.1378/chest.06-2788 |url=}}</ref>
*[[Lung]] [[Neuroendocrine tumor|neuroendocrine tumors]] are classified on the basis of [[Histology|histology:]]<ref name="pmid20664470">{{cite journal |vauthors=Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S |title=The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems |journal=Pancreas |volume=39 |issue=6 |pages=707–12 |date=August 2010 |pmid=20664470 |doi=10.1097/MPA.0b013e3181ec124e |url=}}</ref><ref name="pmid17400673">{{cite journal |vauthors=Aubry MC, Thomas CF, Jett JR, Swensen SJ, Myers JL |title=Significance of multiple carcinoid tumors and tumorlets in surgical lung specimens: analysis of 28 patients |journal=Chest |volume=131 |issue=6 |pages=1635–43 |date=June 2007 |pmid=17400673 |doi=10.1378/chest.06-2788 |url=}}</ref>
#Typical [[neuroendocrine tumor]] :well-differentiated, low-grade, slowly growing [[neoplasms]] that seldom [[metastasize]] to [[extrathoracic]] structures and localized.
#Typical [[neuroendocrine tumor]] :well-differentiated, low-grade, slowly growing [[neoplasms]] that seldom [[metastasize]] to extrathoracic structures and localized.
#Poorly [[differentiated]] and high-grade [[Neuroendocrine tumor|neuroendocrine carcinomas]], as typified by [[small cell lung cancer]] and [[large cell carcinomas]] which behaves [[aggressively]], with rapid [[tumor]] growth and early distant [[dissemination]].
#Poorly [[differentiated]] and high-grade [[Neuroendocrine tumor|neuroendocrine carcinomas]], as typified by [[small cell lung cancer]] and large cell carcinomas which behaves aggressively, with rapid [[tumor]] growth and early distant [[dissemination]].
#Atypical [[neuroendocrine tumor]], which are of intermediate grade and differentiation, is intermediate between typical [[neuroendocrine tumor]] and [[small cell lung cancer]].
#Atypical [[neuroendocrine tumor]], which are of intermediate grade and differentiation, is intermediate between typical [[neuroendocrine tumor]] and [[small cell lung cancer]].
Carcinoid syndrome is encountered uncommonly and most often with tumors of large size (>5 cm).
Left upper lobe": A lung lobe 185x110x55mm with bronchovascular remnants up to 25mm. Arising in the hilum and involving the bronchus is a rubbery tan-pink tumor 21x20x19mm. The tumor is 6mm from the bronchovascular margins and 3mm from the hilar margin. 26mm from the tumor and 1mm from the pleura there is a firm white nodule 6mm. Peripheral to the tumor is an area where the lung shows dilated bronchi up to 12mm in diameter which lie 2mm from the pleura.Source: Radiopedia
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↑Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S (August 2010). "The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems". Pancreas. 39 (6): 707–12. doi:10.1097/MPA.0b013e3181ec124e. PMID20664470.
↑Aubry MC, Thomas CF, Jett JR, Swensen SJ, Myers JL (June 2007). "Significance of multiple carcinoid tumors and tumorlets in surgical lung specimens: analysis of 28 patients". Chest. 131 (6): 1635–43. doi:10.1378/chest.06-2788. PMID17400673.
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