Desmoid tumor pathophysiology: Difference between revisions

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{{CMG}} {{AE}}{{S.M.}}{{Faizan}}
==Overview==
==Overview==
Desmoid tumor may occur as part of [[Gardner syndrome]]. A minority of desmoid tumors are associated with [[Turcot syndrome]], [[Familial adenomatous polyposis]], and estrogen therapy.
Desmoid tumors arises from [[monoclonal]] [[proliferation]] of well-differentiated [[fibroblasts]]. They appear as firm overgrowths of [[fibrous tissue]] with marked cellularity and aggressive local [[Infiltration (medical)|infiltration]]. The exact [[etiology]] remains uncertain, however, they are seem to be associated with antecedent surgical or accidental [[trauma]] at the [[tumor]] site and various [[mutations]] at the [[molecular]] level including [[beta-catenin]] [[gene]], CTNNB1 or [[APC (gene)|APC gene]] involved in [[Wnt signaling pathway|Wnt]]/[[beta-catenin]][[signaling pathway]]. [[Pediatric]] [[Desmoid tumor|desmoids]] have [[AKT1 gene|AKT1 E17K]], [[BRAF (gene)|BRAF V600E]] and [[TP53|TP53 R273H]] [[mutations]] in addition to CTNNB1 [[mutation]]. [[Immunohistochemistry]] shows an elevated [[Beta-catenin|beta-catenin protein]] level in all [[tumors]], regardless of the mutational status. Associated conditions include [[Turcot syndrome]], [[Gardner syndrome]], [[Familial adenomatous polyposis]] and [[estrogen]] [[therapy]]. [[Desmoid tumor|Desmoid tumors]] arise from [[connective tissue]], [[fasciae]] and [[aponeuroses]] and appear as dense [[scar tissue]]<nowiki/>with most common sites of [[abdominal]] involvement being [[abdominal wall]], root of the [[mesentery]] and [[retroperitoneum]]. [[Histologically]], [[Desmoid tumor|desmoid tumors]] consist of linearly arranged elongated [[fibroblasts]] and [[Myofibroblasts|myofibroblas]] surrounded and separated from each other by [[collagen]]. These [[tumors]] show a tendency to evolve over time.
 
 


==Pathophysiology==
==Pathophysiology==
*Their exact aetiology remains uncertain, although they are frequently associated with previous trauma or surgical incision. On the molecular level, desmoids are characterised by mutations in the [[β-catenin gene]], CTNNB1, or the adenomatous polyposis coli gene, APC.<ref name="radio"> Desmoid tumor. Dr Tim Luijkx and Radswiki et al. Radiopedia 2015 http://radiopaedia.org/articles/aggressive-fibromatosis. Accessed on January 20, 2015</ref>
*It is understood that desmoid toomurs is the result of:<ref name="pmid21225148">{{cite journal| author=Leal RF, Silva PV, Ayrizono Mde L, Fagundes JJ, Amstalden EM, Coy CS| title=Desmoid tumor in patients with familial adenomatous polyposis. | journal=Arq Gastroenterol | year= 2010 | volume= 47 | issue= 4 | pages= 373-8 | pmid=21225148 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21225148  }} </ref>
*The exact etiology of desmoid tumors is unknown. However, the following etiologies seem to play a role in development of desmoid tumors:<ref name="pmid11048801">{{cite journal| author=De Wever I, Dal Cin P, Fletcher CD, Mandahl N, Mertens F, Mitelman F et al.| title=Cytogenetic, clinical, and morphologic correlations in 78 cases of fibromatosis: a report from the CHAMP Study Group. CHromosomes And Morphology. | journal=Mod Pathol | year= 2000 | volume= 13 | issue= 10 | pages= 1080-5 | pmid=11048801 | doi=10.1038/modpathol.3880200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11048801  }} </ref><ref name="pmid10732754">{{cite journal| author=Middleton SB, Frayling IM, Phillips RK| title=Desmoids in familial adenomatous polyposis are monoclonal proliferations. | journal=Br J Cancer | year= 2000 | volume= 82 | issue= 4 | pages= 827-32 | pmid=10732754 | doi=10.1054/bjoc.1999.1007 | pmc=2374411 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10732754  }} </ref><ref name="pmid9736021">{{cite journal| author=Li C, Bapat B, Alman BA| title=Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor). | journal=Am J Pathol | year= 1998 | volume= 153 | issue= 3 | pages= 709-14 | pmid=9736021 | doi= | pmc=1853030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9736021  }} </ref><ref name="pmid21859899">{{cite journal| author=Escobar C, Munker R, Thomas JO, Li BD, Burton GV| title=Update on desmoid tumors. | journal=Ann Oncol | year= 2012 | volume= 23 | issue= 3 | pages= 562-9 | pmid=21859899 | doi=10.1093/annonc/mdr386 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21859899  }} </ref><ref name="pmid9744495">{{cite journal| author=Giarola M, Wells D, Mondini P, Pilotti S, Sala P, Azzarelli A et al.| title=Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumours. | journal=Br J Cancer | year= 1998 | volume= 78 | issue= 5 | pages= 582-7 | pmid=9744495 | doi= | pmc=2063069 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744495  }} </ref>
**Arise from monoclonal [[proliferation]] of well-differentiated [[fibroblasts]]
**Can grow almost anywhere in [[Human body|body]]
**Appear as well-differentiated, firm overgrowths of [[fibrous tissue]]
**Marked cellularity
**[[Benign tumors]]
**Aggressive [[local]] [[Infiltration (medical)|infiltration]]
**[[Superficial]] [[Desmoid tumor|desmoids]] are less aggressive than the deep [[Desmoid tumor|desmoids]] ([[abdominal]], extra [[abdominal]], [[mesenteric]])
**High [[local]] [[Recurrence plot|recurrence]] rate (25% to 85%)
**Don't [[metastasize]]
**Typically affects easily movable [[elastic]] [[tissues]]
*Their exact [[etiology]] remains uncertain, although they are frequently associated with previous [[trauma]] or surgical [[incision]]. On the [[molecular]] level, [[Desmoid tumor|desmoids]] are characterised by [[mutations]] in the [[Beta catenin|β-catenin gene]], CTNNB1, or the [[Adenomatous polyposis coli|adenomatous polyposis coli gene, APC]].<ref name="radio">Desmoid tumor. Dr Tim Luijkx and Radswiki et al. Radiopedia 2015 http://radiopaedia.org/articles/aggressive-fibromatosis. Accessed on January 20, 2015</ref><ref name="pmid11048801">{{cite journal| author=De Wever I, Dal Cin P, Fletcher CD, Mandahl N, Mertens F, Mitelman F et al.| title=Cytogenetic, clinical, and morphologic correlations in 78 cases of fibromatosis: a report from the CHAMP Study Group. CHromosomes And Morphology. | journal=Mod Pathol | year= 2000 | volume= 13 | issue= 10 | pages= 1080-5 | pmid=11048801 | doi=10.1038/modpathol.3880200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11048801  }} </ref><ref name="pmid10732754">{{cite journal| author=Middleton SB, Frayling IM, Phillips RK| title=Desmoids in familial adenomatous polyposis are monoclonal proliferations. | journal=Br J Cancer | year= 2000 | volume= 82 | issue= 4 | pages= 827-32 | pmid=10732754 | doi=10.1054/bjoc.1999.1007 | pmc=2374411 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10732754  }} </ref><ref name="pmid9736021">{{cite journal| author=Li C, Bapat B, Alman BA| title=Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor). | journal=Am J Pathol | year= 1998 | volume= 153 | issue= 3 | pages= 709-14 | pmid=9736021 | doi= | pmc=1853030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9736021  }} </ref><ref name="pmid21859899">{{cite journal| author=Escobar C, Munker R, Thomas JO, Li BD, Burton GV| title=Update on desmoid tumors. | journal=Ann Oncol | year= 2012 | volume= 23 | issue= 3 | pages= 562-9 | pmid=21859899 | doi=10.1093/annonc/mdr386 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21859899  }} </ref><ref name="pmid9744495">{{cite journal| author=Giarola M, Wells D, Mondini P, Pilotti S, Sala P, Azzarelli A et al.| title=Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumours. | journal=Br J Cancer | year= 1998 | volume= 78 | issue= 5 | pages= 582-7 | pmid=9744495 | doi= | pmc=2063069 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744495  }} </ref>


==Genetics==
==Genetics==
*The key factor in [[pathogenesis]] of [[Desmoid tumor|desmoids]] at [[genetic]] level is [[beta-catenin]] [[Stabilization (medicine)|stabilization]] implicated by [[mutations]] in two [[Mediator|mediators]] of [[Wnt signaling pathway|Wnt]]-[[APC]]-[[beta-catenin]] [[Signaling pathway|pathway]].<ref name="pmid10597266">{{cite journal| author=Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P et al.| title=Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor). | journal=Oncogene | year= 1999 | volume= 18 | issue= 47 | pages= 6615-20 | pmid=10597266 | doi=10.1038/sj.onc.1203041 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10597266  }} </ref> 
===Normal function of CTNNB1 and APC genes===
*CTNNB1 [[gene]] provides instructions for making a [[protein]] called [[beta-catenin]] which is involved in [[cell]]-[[signaling pathway]]
*[[Beta-catenin]] interacts with other [[proteins]] to control the [[Activity (chemistry)|activity]] ([[expression]]) of particular [[genes]], which helps promote [[Cell (biology)|cell]] [[proliferation]] and [[differentiation]]
*[[Protein]] produced by [[APC|APC gene]] helps to regulate [[cellular]] [[beta-catenin]] levels
*When [[beta-catenin]] is no longer needed, [[glycogen]] [[synthase]] [[kinase]] 3beta (GSK3beta) binds to the [[APC (protein)|APC protein]]
*[[Phosphorylation]] of GSK3beta (bound to [[APC]]) leads to [[beta-catenin]] binding to this [[APC]] site
*[[Kinase]] [[Activity (chemistry)|activity]] of [[APC]] [[Complex (chemistry)|complex]] leads to [[phosphorylation]] of [[beta-catenin]] at its [[serine]] and [[threonine]] sites encoded in [[exon]] 3
*This leads to [[ubiquitin]]-mediated [[protein]] [[degradation]] of [[beta-catenin]] in [[proteasome]]
===Mutations in adults===
===Mutations in adults===
*'''Wnt/beta-catenin signaling pathway'''
*'''Wnt/beta-catenin signaling pathway'''
**Mutations in APC gene/Beta-catenin gene (CTNNB1) lead to dysregulation of beta-catenin levels in cell leading to its accumulation in nucleus which is association with transcription activation of CYCD1 and MYC genes. This leads to promotion of proliferation and enhanced survival associated with development of desmoid tumor.<ref name="pmid19099242">{{cite journal| author=Barker N| title=The canonical Wnt/beta-catenin signalling pathway. | journal=Methods Mol Biol | year= 2008 | volume= 468 | issue= | pages= 5-15 | pmid=19099242 | doi=10.1007/978-1-59745-249-6_1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19099242 }} </ref><ref name="pmid19436199">{{cite journal| author=Lazar AJ, Hajibashi S, Lev D| title=Desmoid tumor: from surgical extirpation to molecular dissection. | journal=Curr Opin Oncol | year= 2009 | volume= 21 | issue= 4 | pages= 352-9 | pmid=19436199 | doi=10.1097/CCO.0b013e32832c9502 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19436199  }} </ref><ref name="pmid25838078">{{cite journal| author=Aitken SJ, Presneau N, Kalimuthu S, Dileo P, Berisha F, Tirabosco R et al.| title=Next-generation sequencing is highly sensitive for the detection of beta-catenin mutations in desmoid-type fibromatoses. | journal=Virchows Arch | year= 2015 | volume= 467 | issue= 2 | pages= 203-10 | pmid=25838078 | doi=10.1007/s00428-015-1765-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25838078  }} </ref><ref name="pmid10597266">{{cite journal| author=Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P et al.| title=Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor). | journal=Oncogene | year= 1999 | volume= 18 | issue= 47 | pages= 6615-20 | pmid=10597266 | doi=10.1038/sj.onc.1203041 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10597266 }} </ref><ref name="pmid16505440">{{cite journal| author=Heinrich MC, McArthur GA, Demetri GD, Joensuu H, Bono P, Herrmann R et al.| title=Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor). | journal=J Clin Oncol | year= 2006 | volume= 24 | issue= 7 | pages= 1195-203 | pmid=16505440 | doi=10.1200/JCO.2005.04.0717 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16505440  }} </ref><ref name="pmid11983872">{{cite journal| author=Cheon SS, Cheah AY, Turley S, Nadesan P, Poon R, Clevers H et al.| title=beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. | journal=Proc Natl Acad Sci U S A | year= 2002 | volume= 99 | issue= 10 | pages= 6973-8 | pmid=11983872 | doi=10.1073/pnas.102657399 | pmc=124513 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11983872  }} </ref><ref name="pmid11823972">{{cite journal| author=Abraham SC, Reynolds C, Lee JH, Montgomery EA, Baisden BL, Krasinskas AM et al.| title=Fibromatosis of the breast and mutations involving the APC/beta-catenin pathway. | journal=Hum Pathol | year= 2002 | volume= 33 | issue= 1 | pages= 39-46 | pmid=11823972 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11823972  }} </ref><ref name="pmid17785554">{{cite journal| author=Signoroni S, Frattini M, Negri T, Pastore E, Tamborini E, Casieri P et al.| title=Cyclooxygenase-2 and platelet-derived growth factor receptors as potential targets in treating aggressive fibromatosis. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 17 | pages= 5034-40 | pmid=17785554 | doi=10.1158/1078-0432.CCR-07-0336 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17785554  }} </ref><ref name="pmid15654359">{{cite journal| author=Cheon S, Poon R, Yu C, Khoury M, Shenker R, Fish J et al.| title=Prolonged beta-catenin stabilization and tcf-dependent transcriptional activation in hyperplastic cutaneous wounds. | journal=Lab Invest | year= 2005 | volume= 85 | issue= 3 | pages= 416-25 | pmid=15654359 | doi=10.1038/labinvest.3700237 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15654359  }} </ref><ref name="pmid10570430">{{cite journal| author=Merchant NB, Lewis JJ, Woodruff JM, Leung DH, Brennan MF| title=Extremity and trunk desmoid tumors: a multifactorial analysis of outcome. | journal=Cancer | year= 1999 | volume= 86 | issue= 10 | pages= 2045-52 | pmid=10570430 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10570430  }} </ref><ref name="pmid26998061">{{cite journal| author=Kim HS, Kim J, Nam KH, Kim WH| title=Clinical significance of midkine expression in sporadic desmoid tumors. | journal=Oncol Lett | year= 2016 | volume= 11 | issue= 3 | pages= 1677-1684 | pmid=26998061 | doi=10.3892/ol.2016.4129 | pmc=4774436 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26998061  }} </ref><ref name="pmid17952864">{{cite journal| author=Kotiligam D, Lazar AJ, Pollock RE, Lev D| title=Desmoid tumor: a disease opportune for molecular insights. | journal=Histol Histopathol | year= 2008 | volume= 23 | issue= 1 | pages= 117-26 | pmid=17952864 | doi=10.14670/HH-23.117 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17952864 }} </ref><ref name="pmid26171757">{{cite journal| author=Crago AM, Chmielecki J, Rosenberg M, O'Connor R, Byrne C, Wilder FG et al.| title=Near universal detection of alterations in CTNNB1 and Wnt pathway regulators in desmoid-type fibromatosis by whole-exome sequencing and genomic analysis. | journal=Genes Chromosomes Cancer | year= 2015 | volume= 54 | issue= 10 | pages= 606-15 | pmid=26171757 | doi=10.1002/gcc.22272 | pmc=4548882 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26171757 }} </ref>
**[[Mutation|Mutational]] [[analysis]] shows that [[Wnt signaling pathway|Wnts]] play an important role in controlling diverse [[developmental]] [[Process (anatomy)|processes]] such as [[Pattern|patterning]] of the [[Human body|body]] axis, [[central nervous system]] and [[limbs]], and the regulation of [[Inductive effect|inductive]] events during [[organogenesis]].<ref name="pmid11029008">{{cite journal| author=Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC| title=An LDL-receptor-related protein mediates Wnt signalling in mice. | journal=Nature | year= 2000 | volume= 407 | issue= 6803 | pages= 535-8 | pmid=11029008 | doi=10.1038/35035124 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11029008 }} </ref>
**Sporadic [[tumors]] occur due to [[Somatic mutation|somatic mutations]] in [[Beta-catenin]]/[[APC]] [[Coding region|coding]] [[genes]]
**[[Activating group|Activating]] [[mutations]] in [[APC|APC gene]]/[[Beta-catenin]] [[gene]] (CTNNB1) lead to dysregulation of [[beta-catenin]] (a [[cytosolic]] and [[nuclear protein]] which acts as a [[cellular adhesion molecule]]) levels in [[cell]] leading to its accumulation in [[nucleus]] which is associated with [[transcription]] [[Activation energy|activation]] of CYCD1 and MYC [[genes]].<ref name="pmid10597266">{{cite journal| author=Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P et al.| title=Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor). | journal=Oncogene | year= 1999 | volume= 18 | issue= 47 | pages= 6615-20 | pmid=10597266 | doi=10.1038/sj.onc.1203041 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10597266  }} </ref><ref name="pmid11983872">{{cite journal| author=Cheon SS, Cheah AY, Turley S, Nadesan P, Poon R, Clevers H et al.| title=beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. | journal=Proc Natl Acad Sci U S A | year= 2002 | volume= 99 | issue= 10 | pages= 6973-8 | pmid=11983872 | doi=10.1073/pnas.102657399 | pmc=124513 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11983872  }} </ref>
**This leads to promotion of [[proliferation]] and enhanced [[Survival function|survival]] associated with [[development]] of [[desmoid tumor]].<ref name="pmid19099242">{{cite journal| author=Barker N| title=The canonical Wnt/beta-catenin signalling pathway. | journal=Methods Mol Biol | year= 2008 | volume= 468 | issue| pages= 5-15 | pmid=19099242 | doi=10.1007/978-1-59745-249-6_1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19099242  }} </ref><ref name="pmid19436199">{{cite journal| author=Lazar AJ, Hajibashi S, Lev D| title=Desmoid tumor: from surgical extirpation to molecular dissection. | journal=Curr Opin Oncol | year= 2009 | volume= 21 | issue= 4 | pages= 352-9 | pmid=19436199 | doi=10.1097/CCO.0b013e32832c9502 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19436199  }} </ref><ref name="pmid25838078">{{cite journal| author=Aitken SJ, Presneau N, Kalimuthu S, Dileo P, Berisha F, Tirabosco R et al.| title=Next-generation sequencing is highly sensitive for the detection of beta-catenin mutations in desmoid-type fibromatoses. | journal=Virchows Arch | year= 2015 | volume= 467 | issue= 2 | pages= 203-10 | pmid=25838078 | doi=10.1007/s00428-015-1765-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25838078  }} </ref><ref name="pmid10597266">{{cite journal| author=Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P et al.| title=Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor). | journal=Oncogene | year= 1999 | volume= 18 | issue= 47 | pages= 6615-20 | pmid=10597266 | doi=10.1038/sj.onc.1203041 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10597266  }} </ref><ref name="pmid16505440">{{cite journal| author=Heinrich MC, McArthur GA, Demetri GD, Joensuu H, Bono P, Herrmann R et al.| title=Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor). | journal=J Clin Oncol | year= 2006 | volume= 24 | issue= 7 | pages= 1195-203 | pmid=16505440 | doi=10.1200/JCO.2005.04.0717 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16505440  }} </ref><ref name="pmid11983872">{{cite journal| author=Cheon SS, Cheah AY, Turley S, Nadesan P, Poon R, Clevers H et al.| title=beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. | journal=Proc Natl Acad Sci U S A | year= 2002 | volume= 99 | issue= 10 | pages= 6973-8 | pmid=11983872 | doi=10.1073/pnas.102657399 | pmc=124513 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11983872  }} </ref><ref name="pmid11823972">{{cite journal| author=Abraham SC, Reynolds C, Lee JH, Montgomery EA, Baisden BL, Krasinskas AM et al.| title=Fibromatosis of the breast and mutations involving the APC/beta-catenin pathway. | journal=Hum Pathol | year= 2002 | volume= 33 | issue= 1 | pages= 39-46 | pmid=11823972 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11823972  }} </ref><ref name="pmid17785554">{{cite journal| author=Signoroni S, Frattini M, Negri T, Pastore E, Tamborini E, Casieri P et al.| title=Cyclooxygenase-2 and platelet-derived growth factor receptors as potential targets in treating aggressive fibromatosis. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 17 | pages= 5034-40 | pmid=17785554 | doi=10.1158/1078-0432.CCR-07-0336 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17785554 }} </ref><ref name="pmid15654359">{{cite journal| author=Cheon S, Poon R, Yu C, Khoury M, Shenker R, Fish J et al.| title=Prolonged beta-catenin stabilization and tcf-dependent transcriptional activation in hyperplastic cutaneous wounds. | journal=Lab Invest | year= 2005 | volume= 85 | issue= 3 | pages= 416-25 | pmid=15654359 | doi=10.1038/labinvest.3700237 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15654359 }} </ref><ref name="pmid10570430">{{cite journal| author=Merchant NB, Lewis JJ, Woodruff JM, Leung DH, Brennan MF| title=Extremity and trunk desmoid tumors: a multifactorial analysis of outcome. | journal=Cancer | year= 1999 | volume= 86 | issue= 10 | pages= 2045-52 | pmid=10570430 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10570430  }} </ref><ref name="pmid26998061">{{cite journal| author=Kim HS, Kim J, Nam KH, Kim WH| title=Clinical significance of midkine expression in sporadic desmoid tumors. | journal=Oncol Lett | year= 2016 | volume= 11 | issue= 3 | pages= 1677-1684 | pmid=26998061 | doi=10.3892/ol.2016.4129 | pmc=4774436 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26998061  }} </ref><ref name="pmid17952864">{{cite journal| author=Kotiligam D, Lazar AJ, Pollock RE, Lev D| title=Desmoid tumor: a disease opportune for molecular insights. | journal=Histol Histopathol | year= 2008 | volume= 23 | issue= 1 | pages= 117-26 | pmid=17952864 | doi=10.14670/HH-23.117 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17952864  }} </ref><ref name="pmid26171757">{{cite journal| author=Crago AM, Chmielecki J, Rosenberg M, O'Connor R, Byrne C, Wilder FG et al.| title=Near universal detection of alterations in CTNNB1 and Wnt pathway regulators in desmoid-type fibromatosis by whole-exome sequencing and genomic analysis. | journal=Genes Chromosomes Cancer | year= 2015 | volume= 54 | issue= 10 | pages= 606-15 | pmid=26171757 | doi=10.1002/gcc.22272 | pmc=4548882 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26171757  }} </ref>
**Following is a [[Summary statistics|summary]] of all the events that occur at [[molecular]] level secondary to [[Activating group|activating]] [[mutations]] in [[APC gene]]/[[Beta-catenin|Beta-catenin gene]] (CTNNB1)/[[Wnt signaling pathway]], eventually leading to [[development]] of [[desmoid tumor]].
{{Family tree/start}}
{{Family tree/start}}
{{Family tree | | | | A01 | | | |A01= External ligand binds }}
{{Family tree | | | | A01 | | | |A01= Binding of an activating external/Wnt ligand to a receptor complex (a member of a seven-transmembrane-domain receptor of the frizzled family) and a LRP5/6 co-receptor(LDL-receptor-related protein family)<ref name="pmid8717036">{{cite journal| author=Bhanot P, Brink M, Samos CH, Hsieh JC, Wang Y, Macke JP et al.| title=A new member of the frizzled family from Drosophila functions as a Wingless receptor. | journal=Nature | year= 1996 | volume= 382 | issue= 6588 | pages= 225-30 | pmid=8717036 | doi=10.1038/382225a0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8717036  }} </ref><ref name="pmid11029008">{{cite journal| author=Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC| title=An LDL-receptor-related protein mediates Wnt signalling in mice. | journal=Nature | year= 2000 | volume= 407 | issue= 6803 | pages= 535-8 | pmid=11029008 | doi=10.1038/35035124 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11029008  }} </ref> }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | B01 | | | |B01= Wnt pathway activation}}
{{Family tree | | | | B01 | | | |B01= Canonical [[Wnt (Wingless) signaling pathway]] activation}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | C01 | | | |C01= Inhibition of kinase activity of APC complex (which tightly binds and regulates Beta-catenin levels by its phosphorylation in proteasome leading to its destruction) }}
{{Family tree | | | | C01 | | | |C01= [[Inhibition]] of [[kinase]] [[activity]] of [[APC]] complex (which tightly binds and [[regulates]] [[Beta-catenin]] levels by its [[phosphorylation]] in [[proteasome]] at [[serine]] and [[threonine]] sites encoded in [[exon]] 3, leading to [[ubiquitin]]-mediated [[protein]] [[degradation]]) }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | D01 | | | |D01= Elevated Beta-catenin levels in cell (due to non-phosphorylation) }}
{{Family tree | | | | D01 | | | |D01= Elevated [[Beta-catenin]] levels in [[cytoplasm]] (due to non-[[phosphorylation]]) }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | E01 | | | |E01= Beta-catenin translocates to nucleus}}
{{Family tree | | | | E01 | | | |E01= [[Beta-catenin]] [[translocates]] to [[nucleus]]}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | F01 | | | |F01= B-catenin acts with other proteins to activate transcription of genes such as CYCD1 and MYC}}
{{Family tree | | | | F01 | | | |F01= [[B-catenin]] together with TCF/LEF [[transcription factors]], acts to [[activate]] [[transcription]] of [[genes]] such as [[CYCD1]] and [[MYC]]}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | G01 | | | |G01= Promotion of proliferation and enhanced survival}}
{{Family tree | | | | G01 | | | |G01= [[Promotion]] of [[proliferation]] and enhanced [[survival]]}}
{{Family tree/end}}
{{Family tree/end}}


*APC mutations<ref name="pmid9736021">{{cite journal| author=Li C, Bapat B, Alman BA| title=Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor). | journal=Am J Pathol | year= 1998 | volume= 153 | issue= 3 | pages= 709-14 | pmid=9736021 | doi= | pmc=1853030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9736021 }} </ref><ref name="pmid11241320">{{cite journal| author=Bertario L, Russo A, Sala P, Eboli M, Giarola M, D'amico F et al.| title=Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis. | journal=Int J Cancer | year= 2001 | volume= 95 | issue= 2 | pages= 102-7 | pmid=11241320 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11241320 }} </ref><ref name="pmid23334997">{{cite journal| author=Schiessling S, Kihm M, Ganschow P, Kadmon G, Büchler MW, Kadmon M| title=Desmoid tumour biology in patients with familial adenomatous polyposis coli. | journal=Br J Surg | year= 2013 | volume= 100 | issue= 5 | pages= 694-703 | pmid=23334997 | doi=10.1002/bjs.9053 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23334997 }} </ref><ref name="pmid17064931">{{cite journal| author=Nieuwenhuis MH, Vasen HF| title=Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. | journal=Crit Rev Oncol Hematol | year= 2007 | volume= 61 | issue= 2 | pages= 153-61 | pmid=17064931 | doi=10.1016/j.critrevonc.2006.07.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17064931 }} </ref><ref name="pmid20528895">{{cite journal| author=Sinha A, Tekkis PP, Gibbons DC, Phillips RK, Clark SK| title=Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis. | journal=Colorectal Dis | year= 2011 | volume= 13 | issue= 11 | pages= 1222-9 | pmid=20528895 | doi=10.1111/j.1463-1318.2010.02345.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20528895 }} </ref><ref name="pmid7795585">{{cite journal| author=Caspari R, Olschwang S, Friedl W, Mandl M, Boisson C, Böker T et al.| title=Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. | journal=Hum Mol Genet | year= 1995 | volume= 4 | issue= 3 | pages= 337-40 | pmid=7795585 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7795585 }} </ref><ref name="pmid12721244">{{cite journal| author=Bertario L, Russo A, Sala P, Varesco L, Giarola M, Mondini P et al.| title=Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis. | journal=J Clin Oncol | year= 2003 | volume= 21 | issue= 9 | pages= 1698-707 | pmid=12721244 | doi=10.1200/JCO.2003.09.118 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12721244 }} </ref><ref name="pmid11247896">{{cite journal| author=Friedl W, Caspari R, Sengteller M, Uhlhaas S, Lamberti C, Jungck M et al.| title=Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. | journal=Gut | year= 2001 | volume= 48 | issue= 4 | pages= 515-21 | pmid=11247896 | doi= | pmc=1728231 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11247896 }} </ref><ref name="pmid9950360">{{cite journal| author=Wallis YL, Morton DG, McKeown CM, Macdonald F| title=Molecular analysis of the APC gene in 205 families: extended genotype-phenotype correlations in FAP and evidence for the role of APC amino acid changes in colorectal cancer predisposition. | journal=J Med Genet | year= 1999 | volume= 36 | issue= 1 | pages= 14-20 | pmid=9950360 | doi= | pmc=1762945 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9950360 }} </ref><ref name="pmid25751801">{{cite journal| author=Church J, Xhaja X, LaGuardia L, O'Malley M, Burke C, Kalady M| title=Desmoids and genotype in familial adenomatous polyposis. | journal=Dis Colon Rectum | year= 2015 | volume= 58 | issue= 4 | pages= 444-8 | pmid=25751801 | doi=10.1097/DCR.0000000000000316 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25751801 }} </ref><ref name="pmid9744495">{{cite journal| author=Giarola M, Wells D, Mondini P, Pilotti S, Sala P, Azzarelli A et al.| title=Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumours. | journal=Br J Cancer | year= 1998 | volume= 78 | issue= 5 | pages= 582-7 | pmid=9744495 | doi= | pmc=2063069 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744495 }} </ref><ref name="pmid10077730">{{cite journal| author=Halling KC, Lazzaro CR, Honchel R, Bufill JA, Powell SM, Arndt CA et al.| title=Hereditary desmoid disease in a family with a germline Alu I repeat mutation of the APC gene. | journal=Hum Hered | year= 1999 | volume= 49 | issue= 2 | pages= 97-102 | pmid=10077730 | doi=10.1159/000022852 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10077730 }} </ref>
*'''APC mutations'''
*Mutations in CTNNB1 (Beta-catenin gene) (64%) (sporadic desmoids) <ref name="pmid19436199">{{cite journal| author=Lazar AJ, Hajibashi S, Lev D| title=Desmoid tumor: from surgical extirpation to molecular dissection. | journal=Curr Opin Oncol | year= 2009 | volume= 21 | issue= 4 | pages= 352-9 | pmid=19436199 | doi=10.1097/CCO.0b013e32832c9502 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19436199 }} </ref><ref name="pmid18832571">{{cite journal| author=Lazar AJ, Tuvin D, Hajibashi S, Habeeb S, Bolshakov S, Mayordomo-Aranda E et al.| title=Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. | journal=Am J Pathol | year= 2008 | volume= 173 | issue= 5 | pages= 1518-27 | pmid=18832571 | doi=10.2353/ajpath.2008.080475 | pmc=2570141 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18832571 }} </ref><ref name="pmid23960186">{{cite journal| author=Mullen JT, DeLaney TF, Rosenberg AE, Le L, Iafrate AJ, Kobayashi W et al.| title=β-Catenin mutation status and outcomes in sporadic desmoid tumors. | journal=Oncologist | year= 2013 | volume= 18 | issue= 9 | pages= 1043-9 | pmid=23960186 | doi=10.1634/theoncologist.2012-0449 | pmc=3780636 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23960186 }} </ref>
**[[Function (biology)|Function]] of normal [[APC (protein)|APC protein]] is to prevent the accumulation of [[beta-catenin]] by mediating its [[phosphorylation]] and resultant [[degradation]]
*Sporadic tumors and trisomy 8 and 20<ref name="pmid7889507">{{cite journal| author=Fletcher JA, Naeem R, Xiao S, Corson JM| title=Chromosome aberrations in desmoid tumors. Trisomy 8 may be a predictor of recurrence. | journal=Cancer Genet Cytogenet | year= 1995 | volume= 79 | issue= 2 | pages= 139-43 | pmid=7889507 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7889507  }} </ref><ref name="pmid9363449">{{cite journal| author=Kouho H, Aoki T, Hisaoka M, Hashimoto H| title=Clinicopathological and interphase cytogenetic analysis of desmoid tumours. | journal=Histopathology | year= 1997 | volume= 31 | issue= 4 | pages= 336-41 | pmid=9363449 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9363449  }} </ref><ref name="pmid10079250">{{cite journal| author=Bridge JA, Swarts SJ, Buresh C, Nelson M, Degenhardt JM, Spanier S et al.| title=Trisomies 8 and 20 characterize a subgroup of benign fibrous lesions arising in both soft tissue and bone. | journal=Am J Pathol | year= 1999 | volume= 154 | issue= 3 | pages= 729-33 | pmid=10079250 | doi=10.1016/S0002-9440(10)65319-9 | pmc=1866419 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10079250  }} </ref><ref name="pmid8976373">{{cite journal| author=Qi H, Dal Cin P, Hernández JM, Garcia JL, Sciot R, Fletcher C et al.| title=Trisomies 8 and 20 in desmoid tumors. | journal=Cancer Genet Cytogenet | year= 1996 | volume= 92 | issue= 2 | pages= 147-9 | pmid=8976373 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8976373  }} </ref><ref name="pmid7591262">{{cite journal| author=Mertens F, Willén H, Rydholm A, Brosjö O, Carlén B, Mitelman F et al.| title=Trisomy 20 is a primary chromosome aberration in desmoid tumors. | journal=Int J Cancer | year= 1995 | volume= 63 | issue= 4 | pages= 527-9 | pmid=7591262 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7591262  }} </ref>
**[[Familial]] cases of [[Desmoid tumor|desmoid]] (aka [[hereditary]] [[Desmoid tumor|desmoid disease]]) are associated with [[Germline mutation|germline mutations]] in the [[APC (gene)|''APC'' gene.]]<ref name="pmid9250146">{{cite journal| author=Alman BA, Li C, Pajerski ME, Diaz-Cano S, Wolfe HJ| title=Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). | journal=Am J Pathol | year= 1997 | volume= 151 | issue= 2 | pages= 329-34 | pmid=9250146 | doi= | pmc=1857985 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9250146 }} </ref>
**[[APC gene]] [[mutation]] on [[chromosome]] 5q is responsible for [[FAP]]
**Generally, [[Desmoid tumor|desmoid tumors]] occur more frequently when [[mutations]] are in the 3' end of the [[APC gene]], specifically between [[codons]] 1445 and 1580
**More than 300 [[mutations]] have been described leading to frame shifts or [[premature]] stop codons, resulting in a [[premature]] truncated [[APC gene]] product which causes loss of the [[beta-catenin]] regulatory domain<ref name="pmid9736021">{{cite journal| author=Li C, Bapat B, Alman BA| title=Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor). | journal=Am J Pathol | year= 1998 | volume= 153 | issue= 3 | pages= 709-14 | pmid=9736021 | doi= | pmc=1853030 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9736021 }} </ref><ref name="pmid11241320">{{cite journal| author=Bertario L, Russo A, Sala P, Eboli M, Giarola M, D'amico F et al.| title=Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis. | journal=Int J Cancer | year= 2001 | volume= 95 | issue= 2 | pages= 102-7 | pmid=11241320 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11241320 }} </ref><ref name="pmid23334997">{{cite journal| author=Schiessling S, Kihm M, Ganschow P, Kadmon G, Büchler MW, Kadmon M| title=Desmoid tumour biology in patients with familial adenomatous polyposis coli. | journal=Br J Surg | year= 2013 | volume= 100 | issue= 5 | pages= 694-703 | pmid=23334997 | doi=10.1002/bjs.9053 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23334997 }} </ref><ref name="pmid17064931">{{cite journal| author=Nieuwenhuis MH, Vasen HF| title=Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. | journal=Crit Rev Oncol Hematol | year= 2007 | volume= 61 | issue= 2 | pages= 153-61 | pmid=17064931 | doi=10.1016/j.critrevonc.2006.07.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17064931 }} </ref><ref name="pmid20528895">{{cite journal| author=Sinha A, Tekkis PP, Gibbons DC, Phillips RK, Clark SK| title=Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis. | journal=Colorectal Dis | year= 2011 | volume= 13 | issue= 11 | pages= 1222-9 | pmid=20528895 | doi=10.1111/j.1463-1318.2010.02345.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20528895 }} </ref><ref name="pmid7795585">{{cite journal| author=Caspari R, Olschwang S, Friedl W, Mandl M, Boisson C, Böker T et al.| title=Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. | journal=Hum Mol Genet | year= 1995 | volume= 4 | issue= 3 | pages= 337-40 | pmid=7795585 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7795585 }} </ref><ref name="pmid12721244">{{cite journal| author=Bertario L, Russo A, Sala P, Varesco L, Giarola M, Mondini P et al.| title=Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis. | journal=J Clin Oncol | year= 2003 | volume= 21 | issue= 9 | pages= 1698-707 | pmid=12721244 | doi=10.1200/JCO.2003.09.118 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12721244 }} </ref><ref name="pmid11247896">{{cite journal| author=Friedl W, Caspari R, Sengteller M, Uhlhaas S, Lamberti C, Jungck M et al.| title=Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. | journal=Gut | year= 2001 | volume= 48 | issue= 4 | pages= 515-21 | pmid=11247896 | doi= | pmc=1728231 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11247896 }} </ref><ref name="pmid9950360">{{cite journal| author=Wallis YL, Morton DG, McKeown CM, Macdonald F| title=Molecular analysis of the APC gene in 205 families: extended genotype-phenotype correlations in FAP and evidence for the role of APC amino acid changes in colorectal cancer predisposition. | journal=J Med Genet | year= 1999 | volume= 36 | issue= 1 | pages= 14-20 | pmid=9950360 | doi= | pmc=1762945 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9950360 }} </ref><ref name="pmid25751801">{{cite journal| author=Church J, Xhaja X, LaGuardia L, O'Malley M, Burke C, Kalady M| title=Desmoids and genotype in familial adenomatous polyposis. | journal=Dis Colon Rectum | year= 2015 | volume= 58 | issue= 4 | pages= 444-8 | pmid=25751801 | doi=10.1097/DCR.0000000000000316 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25751801 }} </ref><ref name="pmid9744495">{{cite journal| author=Giarola M, Wells D, Mondini P, Pilotti S, Sala P, Azzarelli A et al.| title=Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumours. | journal=Br J Cancer | year= 1998 | volume= 78 | issue= 5 | pages= 582-7 | pmid=9744495 | doi= | pmc=2063069 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744495 }} </ref><ref name="pmid10077730">{{cite journal| author=Halling KC, Lazzaro CR, Honchel R, Bufill JA, Powell SM, Arndt CA et al.| title=Hereditary desmoid disease in a family with a germline Alu I repeat mutation of the APC gene. | journal=Hum Hered | year= 1999 | volume= 49 | issue= 2 | pages= 97-102 | pmid=10077730 | doi=10.1159/000022852 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10077730 }} </ref>
**This leads to accumulation of [[beta catenin]] which binds to, and activate the [[transcription factor]] tcf-4
**[[Sex hormones]] seem to play a role in [[Activation energy|activation]] of these [[mutations]] and [[Signaling pathway|signaling pathways]] leading to [[Desmoid tumor|desmoids]]<ref name="pmid21468052">{{cite journal| author=Hong H, Nadesan P, Poon R, Alman BA| title=Testosterone regulates cell proliferation in aggressive fibromatosis (desmoid tumour). | journal=Br J Cancer | year= 2011 | volume= 104 | issue= 9 | pages= 1452-8 | pmid=21468052 | doi=10.1038/bjc.2011.107 | pmc=3101926 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21468052 }} </ref>
*'''Mutations in CTNNB1''' '''(Beta-catenin gene) (85%)'''<ref name="pmid19436199">{{cite journal| author=Lazar AJ, Hajibashi S, Lev D| title=Desmoid tumor: from surgical extirpation to molecular dissection. | journal=Curr Opin Oncol | year= 2009 | volume= 21 | issue= 4 | pages= 352-9 | pmid=19436199 | doi=10.1097/CCO.0b013e32832c9502 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19436199 }} </ref><ref name="pmid18832571">{{cite journal| author=Lazar AJ, Tuvin D, Hajibashi S, Habeeb S, Bolshakov S, Mayordomo-Aranda E et al.| title=Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. | journal=Am J Pathol | year= 2008 | volume= 173 | issue= 5 | pages= 1518-27 | pmid=18832571 | doi=10.2353/ajpath.2008.080475 | pmc=2570141 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18832571  }} </ref><ref name="pmid23960186">{{cite journal| author=Mullen JT, DeLaney TF, Rosenberg AE, Le L, Iafrate AJ, Kobayashi W et al.| title=β-Catenin mutation status and outcomes in sporadic desmoid tumors. | journal=Oncologist | year= 2013 | volume= 18 | issue= 9 | pages= 1043-9 | pmid=23960186 | doi=10.1634/theoncologist.2012-0449 | pmc=3780636 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23960186  }} </ref>
**Associated with sporadic [[Desmoid tumor|desmoids]]
**Following are the three particular sites for CTNNB1 [[mutations]]:<ref name="pmid18832571">{{cite journal| author=Lazar AJ, Tuvin D, Hajibashi S, Habeeb S, Bolshakov S, Mayordomo-Aranda E et al.| title=Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. | journal=Am J Pathol | year= 2008 | volume= 173 | issue= 5 | pages= 1518-27 | pmid=18832571 | doi=10.2353/ajpath.2008.080475 | pmc=2570141 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18832571  }} </ref><ref name="pmid23960186">{{cite journal| author=Mullen JT, DeLaney TF, Rosenberg AE, Le L, Iafrate AJ, Kobayashi W et al.| title=β-Catenin mutation status and outcomes in sporadic desmoid tumors. | journal=Oncologist | year= 2013 | volume= 18 | issue= 9 | pages= 1043-9 | pmid=23960186 | doi=10.1634/theoncologist.2012-0449 | pmc=3780636 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23960186  }} </ref>
***T41A (59%)
***S45F (33%)(associated with a higher [[Recurrence plot|recurrence]] rate after [[surgical resection]] of a primary [[desmoid tumor]])
***S45P (8%)
*Other '''sporadic tumors'''
**[[Benign]] [[fibrous]] [[bone]] [[lesions]] arising in both [[soft tissue]] and [[bone tumors]] such as:
***[[Dupuytrens contracture|Dupuytren's contracture]]
***Plantar fibrosis
***[[Peyronie's disease]]
***[[Carpal tunnel syndrome]]
***Infantile [[fibrosarcoma]]
***[[Fibrous dysplasia]]
*'''[[Trisomy 8]]''' (frequent finding in [[hematologic]] [[malignancies]])
*'''[[Trisomy]]''' '''20'''<ref name="pmid7889507">{{cite journal| author=Fletcher JA, Naeem R, Xiao S, Corson JM| title=Chromosome aberrations in desmoid tumors. Trisomy 8 may be a predictor of recurrence. | journal=Cancer Genet Cytogenet | year= 1995 | volume= 79 | issue= 2 | pages= 139-43 | pmid=7889507 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7889507  }} </ref><ref name="pmid9363449">{{cite journal| author=Kouho H, Aoki T, Hisaoka M, Hashimoto H| title=Clinicopathological and interphase cytogenetic analysis of desmoid tumours. | journal=Histopathology | year= 1997 | volume= 31 | issue= 4 | pages= 336-41 | pmid=9363449 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9363449  }} </ref><ref name="pmid10079250">{{cite journal| author=Bridge JA, Swarts SJ, Buresh C, Nelson M, Degenhardt JM, Spanier S et al.| title=Trisomies 8 and 20 characterize a subgroup of benign fibrous lesions arising in both soft tissue and bone. | journal=Am J Pathol | year= 1999 | volume= 154 | issue= 3 | pages= 729-33 | pmid=10079250 | doi=10.1016/S0002-9440(10)65319-9 | pmc=1866419 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10079250  }} </ref><ref name="pmid8976373">{{cite journal| author=Qi H, Dal Cin P, Hernández JM, Garcia JL, Sciot R, Fletcher C et al.| title=Trisomies 8 and 20 in desmoid tumors. | journal=Cancer Genet Cytogenet | year= 1996 | volume= 92 | issue= 2 | pages= 147-9 | pmid=8976373 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8976373  }} </ref><ref name="pmid7591262">{{cite journal| author=Mertens F, Willén H, Rydholm A, Brosjö O, Carlén B, Mitelman F et al.| title=Trisomy 20 is a primary chromosome aberration in desmoid tumors. | journal=Int J Cancer | year= 1995 | volume= 63 | issue= 4 | pages= 527-9 | pmid=7591262 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7591262  }} </ref>


===Additional mutations in pediatric desmoids===
===Additional mutations in pediatric desmoids===
*In addition to CTNNB1 mutations, following mutations contribute to pediatric desmoids:<ref name="pmid27062580">{{cite journal| author=Meazza C, Belfiore A, Busico A, Settanni G, Paielli N, Cesana L et al.| title=AKT1 and BRAF mutations in pediatric aggressive fibromatosis. | journal=Cancer Med | year= 2016 | volume= 5 | issue= 6 | pages= 1204-13 | pmid=27062580 | doi=10.1002/cam4.669 | pmc=4924379 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27062580  }} </ref>
*In addition to CTNNB1 [[mutations]], following [[mutations]] contribute to [[pediatric]] [[Desmoid tumor|desmoids]]:<ref name="pmid27062580">{{cite journal| author=Meazza C, Belfiore A, Busico A, Settanni G, Paielli N, Cesana L et al.| title=AKT1 and BRAF mutations in pediatric aggressive fibromatosis. | journal=Cancer Med | year= 2016 | volume= 5 | issue= 6 | pages= 1204-13 | pmid=27062580 | doi=10.1002/cam4.669 | pmc=4924379 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27062580  }} </ref>
**AKT1 E17K mutation (31%)
**[[AKT1 gene|AKT1 E17K]] [[mutation]] (31%)
**BRAF V600E mutation (19%)
**[[BRAF (gene)|BRAF V600E]] [[mutation]] (19%)
**TP53 R273H mutation (9%)
**[[TP53|TP53 R273H]] [[mutation]] (9%)
 


===Immunohistochemistry===
*[[Immunohistochemistry]] shows an elevated [[beta-catenin]] [[protein]] level in all [[tumors]], regardless of the [[Mutation|mutational]] status


===Associated Diseases===
===Associated Diseases===
*Some cases have been associated with estrogen therapy
*Some cases have been associated with [[estrogen]] [[therapy]]
*[[Turcot syndrome]]
*[[Turcot syndrome]]
*[[Gardner syndrome]]
*[[Gardner syndrome]]
*[[Familial adenomatous polyposis]]
*[[Familial adenomatous polyposis]]
**In the case of mesenteric desmoid they are seen either sporadically or in association with familial polyposis coli syndrome(FAP)
**In the case of mesenteric [[Desmoid tumor|desmoid]] they are seen either sporadically or in association with [[Familial adenomatous polyposis|familial polyposis coli syndrome (FAP)]]


==Gross Pathology==
==Gross Pathology==
*Abdominal wall desmoid tumors arise from:
*[[Desmoid tumor|Desmoid tumors]] look like [[dense]] [[scar tissue]].
:*Musculoaponeurotic structures of the abdominal wall (especially the rectus and internal oblique muscles and their fascial coverings)
*Adhere tenaciously to surrounding structures and [[organs]] just like a [[scar tissue]] hence, difficult to remove.
:*External oblique muscle and the transversalis muscle or fascia
*[[Desmoid tumor|Desmoid tumors]] arise from:<ref name="pmid26181076">{{cite journal| author=Tanaka K, Toiyama Y, Okugawa Y, Hiro J, Kawamoto A, Inoue Y et al.| title=Cytoreductive strategy for multiple intra-abdominal and abdominal wall desmoid tumors in familial adenomatous polyposis: report of three cases. | journal=Clin J Gastroenterol | year= 2012 | volume= 5 | issue= 5 | pages= 361-6 | pmid=26181076 | doi=10.1007/s12328-012-0330-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26181076  }} </ref><ref name="pmid16739877">{{cite journal| author=Ferenc T, Sygut J, Kopczyński J, Mayer M, Latos-Bieleńska A, Dziki A et al.| title=Aggressive fibromatosis (desmoid tumors): definition, occurrence, pathology, diagnostic problems, clinical behavior, genetic background. | journal=Pol J Pathol | year= 2006 | volume= 57 | issue= 1 | pages= 5-15 | pmid=16739877 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16739877  }} </ref>
*These masses have a firm, gritty texture. On the cut surface, they are glistening white and coarsely trabeculated, resembling scar tissue
**[[Connective tissue]]
**[[Fasciae]]
**[[Aponeuroses]]
*[[Abdominal wall]] [[Desmoid tumor|desmoid tumors]] arise from:
:*Musculoaponeurotic structures of the [[abdominal wall]] (especially the [[Rectus abdominis|rectus]] and [[Internal oblique muscle|internal oblique muscles]] and their [[Fascial compartment|fascial]] coverings).
:*[[External oblique muscle]] and the [[Transversalis fascia|transversalis muscle or fascia]]
:*Mostly measure 5 cm by 15 cm in [[diameter]]
:*Firm and gritty texture
:*Appears as glistening white and coarsely trabeculated, resembling [[scar tissue]] on cut surface
:*No distinct [[capsule]]
:*Ill defined margins
:*Well circumscribed on [[imaging]]
===Location===
===Location===
Frequent locations in the abdomen are:
Frequent locations in the [[abdomen]] are:
*Abdominal wall
*[[Abdominal wall]]
*Root of the [[mesentery]]
*[[Root]] of the [[mesentery]]
*[[Retroperitoneum]]
*[[Retroperitoneum]]
{|
|
[[File:Chest wall desmoid.png|thumb|250px|none|Patient presenting a large desmoid tumor on the posterior thoracic wall.[https://openi.nlm.nih.gov/detailedresult?img=PMC3093803_cln-66-04-705-g001&query=desmoid&it=xg&req=4&npos=80 Source: Abrao FC. et al, Thoracic Surgery Department, Instituto do Corao InCor, Hospital das Clnicas da Faculdade de Medicina da Universidade de Sã Paulo HCFMUSP, Sã Paulo, Brazil.]]]
|
[[File:Preg abd desmoid.png|thumb|250px|none| Rapid progression of a pregnancy-associated intra-abdominal desmoid tumor in the post-partum period: A case report. (A) Intra-operative view of intra-abdominal desmoid tumor with adherent portion of small bowel. (B) Desmoid tumor after surgical resection.[https://openi.nlm.nih.gov/detailedresult?img=PMC5094289_gr2&query=desmoid%20tumor&it=xg&req=4&npos=11 Source: Hanna D. et al, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, United States]]]
|
[[File:Breast desmoid.png|thumb|250px|none|Breast Desmoid Tumor after Ductal Carcinoma Treatment: Salvaging a DIEP Flap Reconstruction. Chest wall defect after desmoid tumor resection (A) and resected desmoid tumor (B). [https://openi.nlm.nih.gov/detailedresult?img=PMC5142502_gox-4-e1142-g001&query=desmoid%20tumor&it=xg&req=4&npos=15 Source: Zavlin D. et al, *Institute for Reconstructive Surgery, Houston Methodist Hospital, Weill Cornell Medicine, Houston, Tex.; and †College of Medicine, Texas A&M University College of Medicine, Houston, Tex.]]]
|
[[File:Extraabdomianl desmoid gross.png|thumb|250px|none|Extra-Abdominal Fibromatosis (Desmoid Tumor): A Rare Tumor of the Lower Extremity Arising from the Popliteal Fossa. Gross cross-sectional view of pathologyic resected specimen. The gross lesion is poorly circumscribed and usually measures between 5 and 15 cm. On cut section, it is hard and tan-white. The lesion is poorly circumscribed and is centered in skeletal muscle and the adjacent fascia. There often are infiltration and obliteration of adjacent structures. [https://openi.nlm.nih.gov/detailedresult?img=PMC3420745_CRIM.VASMED2011-184906.002&query=&req=4 Source: Ali Kaygain M. et al, Department of Cardiovascular Surgery, Erzurum Regional Training and Research Hospital, 25020 Erzurum, Turkey]]]
|}


==Microscopic Pathology==
==Microscopic Pathology==
Histologically, desmoid tumors consist of:<ref name="EconomouPitta2011">{{cite journal|last1=Economou|first1=Athanasios|last2=Pitta|first2=Xanthi|last3=Andreadis|first3=Efstathios|last4=Papapavlou|first4=Leonidas|last5=Chrissidis|first5=Thomas|title=Desmoid tumor of the abdominal wall: a case report|journal=Journal of Medical Case Reports|volume=5|issue=1|year=2011|pages=326|issn=1752-1947|doi=10.1186/1752-1947-5-326}}</ref>
On [[microscopic]] [[Histopathology|histopathological]] analysis, the characteristic findings of desmoid tumors inclde:<ref name="EconomouPitta2011">{{cite journal|last1=Economou|first1=Athanasios|last2=Pitta|first2=Xanthi|last3=Andreadis|first3=Efstathios|last4=Papapavlou|first4=Leonidas|last5=Chrissidis|first5=Thomas|title=Desmoid tumor of the abdominal wall: a case report|journal=Journal of Medical Case Reports|volume=5|issue=1|year=2011|pages=326|issn=1752-1947|doi=10.1186/1752-1947-5-326}}</ref>
*Elongated fibroblasts.
*Elongated [[fibroblasts]] and [[myofibroblasts]]
*Myofibroblasts characterized by elongated, tapered cytoplasm; elongated, vesicular, typical-appearing nuclei; and multiple small nucleoli. The cells are linearly arranged and are surrounded and separated from each other by collagen.
*[[Myofibroblasts]] are characterized by elongated, tapered [[cytoplasm]]; elongated, [[vesicular]], typical-appearing [[nuclei]]; and multiple small [[nucleoli]]
*These tumors show a tendency to evolve over time.
*[[Cell (biology)|Cells]] are linearly arranged
*Vandevenne et al described three stages of evolution of desmoid tumors:
*[[Cells (biology)|Cells]] are surrounded and separated from each other by [[collagen]]
:*In the first stage, lesions are more cellular and have fewer areas of hyalinized collagen.
*These [[tumors]] show a tendency to [[evolve]] over time
:*In the second stage, there is an increasing amount of collagen deposition in the central and peripheral areas of the tumor.  
===Stages of evolution of desmoid tumors===
:*In the third stage, there is an increase in the fibrous composition with a decrease in cellularity and water content.
'''Vandevenne et al''' described three stages of [[Evolve|evolution]] of [[Desmoid tumor|desmoid tumors]] as follows:
:*
{| class="wikitable"
|+Stages of evolution of desmoid tumors
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Stage
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Histological features
|-
| style="background:#DCDCDC;" align="center" + |'''First stage'''
|
* More cellular [[lesions]]
* Fewer [[Area|areas]] of hyalinized [[collagen]]
|-
| style="background:#DCDCDC;" align="center" + |'''Second stage'''
|
* Increased amount of [[collagen]] [[Deposition (physics)|deposition]] in [[central]] and peripheral [[tumor]] [[Area|areas]]
|-
| style="background:#DCDCDC;" align="center" + |'''Third stage'''
|
* Increased [[fibrous]] composition
* Decreased cellularity
* Decreased [[water]] content
|}
 
{|
|
[[File:Desmoid histology.png|thumb|250px|none|Histological features of desmoid tumors in the proximal part of the left thigh of a 29-year-old woman (arrows) (a–d). (a) Desmoid tumors invaded into the skeletal striated muscle aggressively. Degeneration of skeletal muscle cells could be seen (HE × 100). (b) Budding-like protrusion of the lesions invading into the muscles could be seen on the juncture of tumors and muscles (HE × 40). (c) Isolated small lesions in muscles were found away from the main part of the tumor (HE × 40). (d) Microscopically, desmoid tumors were poorly circumscribed on tumor-ligament boundary (HE × 40).[https://openi.nlm.nih.gov/detailedresult?img=PMC4329213_12957_2015_450_Fig2_HTML&query=desmoid%20tumor&it=xg&req=4&npos=9 Source: Wang YF. et al, Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044 P.R. China]]]
|
[[File:Desmoid histo.png|thumb|250px|none|Histological features of postoperative recurrent desmoid tumors in the right forearm of a 15-year-old man (arrows) (a–d). (a) Lesions with adipose tissue involvement (HE × 40). (b) Desmoid tumors around vessels could not invade into the vessel wall to form tumor thrombus (HE × 40). (c) Desmoid tumors invaded into the connective tissue and perineurium around nerve tissue (HE × 40). (d) Desmoid tumors with bone involvement penetrated into the periosteum and cortical bone and invaded into the bone marrow cavity along the bone trabecula (HE × 40).[https://openi.nlm.nih.gov/detailedresult?img=PMC4329213_12957_2015_450_Fig3_HTML&query=desmoid%20tumor&it=xg&req=4&npos=6 Source: Wang YF. et al, Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044 P.R. China]]]
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[[File:Desmoid immuno.jpg|thumb|250px|none|Immunological features of desmoid tumors in the middle section of the left thigh of a 35-year-old woman with femur involvement (a–d). (a) β-catenin staining of desmoid tumors (EnVision × 200). (b) Vimentin staining of desmoid tumors (EnVision × 200). (c) Desmin staining of desmoid tumors (EnVision × 200). (d) Ki-67 staining of desmoid tumors (EnVision × 200).[https://openi.nlm.nih.gov/detailedresult?img=PMC4329213_12957_2015_450_Fig4_HTML&query=desmoid%20tumor&it=xg&req=4&npos=7 Source: Wang YF. et al, Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044 P.R. China]]]
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[[File:Extraabdomianl desmoid histo.png|thumb|250px|none|Extra-Abdominal Fibromatosis (Desmoid Tumor): A Rare Tumor of the Lower Extremity Arising from the Popliteal Fossa. Desmoid fibromatosis showing fascicular arrangement of bland fibroblasts, which are interrupted by thin-walled, compressed vascular channels resulting in an appearance akin to a hypocellular scar. Note entrapped muscle fibers. No mitotic activity or nuclear pleomorphism is present (H&E, original magnification, 40x). [https://openi.nlm.nih.gov/detailedresult?img=PMC3420745_CRIM.VASMED2011-184906.003&query=&req=4 Source: Ali Kaygain M. et al, Department of Cardiovascular Surgery, Erzurum Regional Training and Research Hospital, 25020 Erzurum, Turkey]]]
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==Reference==
==Reference==

Latest revision as of 14:35, 16 May 2019

Desmoid tumor Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Desmoid tumor from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

CT

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]Faizan Sheraz, M.D. [3]

Overview

Desmoid tumors arises from monoclonal proliferation of well-differentiated fibroblasts. They appear as firm overgrowths of fibrous tissue with marked cellularity and aggressive local infiltration. The exact etiology remains uncertain, however, they are seem to be associated with antecedent surgical or accidental trauma at the tumor site and various mutations at the molecular level including beta-catenin gene, CTNNB1 or APC gene involved in Wnt/beta-cateninsignaling pathway. Pediatric desmoids have AKT1 E17K, BRAF V600E and TP53 R273H mutations in addition to CTNNB1 mutation. Immunohistochemistry shows an elevated beta-catenin protein level in all tumors, regardless of the mutational status. Associated conditions include Turcot syndrome, Gardner syndrome, Familial adenomatous polyposis and estrogen therapy. Desmoid tumors arise from connective tissue, fasciae and aponeuroses and appear as dense scar tissuewith most common sites of abdominal involvement being abdominal wall, root of the mesentery and retroperitoneum. Histologically, desmoid tumors consist of linearly arranged elongated fibroblasts and myofibroblas surrounded and separated from each other by collagen. These tumors show a tendency to evolve over time.


Pathophysiology

Genetics

Normal function of CTNNB1 and APC genes

Mutations in adults

 
 
 
Binding of an activating external/Wnt ligand to a receptor complex (a member of a seven-transmembrane-domain receptor of the frizzled family) and a LRP5/6 co-receptor(LDL-receptor-related protein family)[22][9]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Canonical Wnt (Wingless) signaling pathway activation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inhibition of kinase activity of APC complex (which tightly binds and regulates Beta-catenin levels by its phosphorylation in proteasome at serine and threonine sites encoded in exon 3, leading to ubiquitin-mediated protein degradation)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Elevated Beta-catenin levels in cytoplasm (due to non-phosphorylation)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Beta-catenin translocates to nucleus
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
B-catenin together with TCF/LEF transcription factors, acts to activate transcription of genes such as CYCD1 and MYC
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Promotion of proliferation and enhanced survival
 
 
 

Additional mutations in pediatric desmoids

Immunohistochemistry

Associated Diseases

Gross Pathology

Location

Frequent locations in the abdomen are:

Patient presenting a large desmoid tumor on the posterior thoracic wall.Source: Abrao FC. et al, Thoracic Surgery Department, Instituto do Corao InCor, Hospital das Clnicas da Faculdade de Medicina da Universidade de Sã Paulo HCFMUSP, Sã Paulo, Brazil.
Rapid progression of a pregnancy-associated intra-abdominal desmoid tumor in the post-partum period: A case report. (A) Intra-operative view of intra-abdominal desmoid tumor with adherent portion of small bowel. (B) Desmoid tumor after surgical resection.Source: Hanna D. et al, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, United States
Breast Desmoid Tumor after Ductal Carcinoma Treatment: Salvaging a DIEP Flap Reconstruction. Chest wall defect after desmoid tumor resection (A) and resected desmoid tumor (B). Source: Zavlin D. et al, *Institute for Reconstructive Surgery, Houston Methodist Hospital, Weill Cornell Medicine, Houston, Tex.; and †College of Medicine, Texas A&M University College of Medicine, Houston, Tex.
Extra-Abdominal Fibromatosis (Desmoid Tumor): A Rare Tumor of the Lower Extremity Arising from the Popliteal Fossa. Gross cross-sectional view of pathologyic resected specimen. The gross lesion is poorly circumscribed and usually measures between 5 and 15 cm. On cut section, it is hard and tan-white. The lesion is poorly circumscribed and is centered in skeletal muscle and the adjacent fascia. There often are infiltration and obliteration of adjacent structures. Source: Ali Kaygain M. et al, Department of Cardiovascular Surgery, Erzurum Regional Training and Research Hospital, 25020 Erzurum, Turkey

Microscopic Pathology

On microscopic histopathological analysis, the characteristic findings of desmoid tumors inclde:[45]

Stages of evolution of desmoid tumors

Vandevenne et al described three stages of evolution of desmoid tumors as follows:

Stages of evolution of desmoid tumors
Stage Histological features
First stage
Second stage
Third stage
  • Increased fibrous composition
  • Decreased cellularity
  • Decreased water content
Histological features of desmoid tumors in the proximal part of the left thigh of a 29-year-old woman (arrows) (a–d). (a) Desmoid tumors invaded into the skeletal striated muscle aggressively. Degeneration of skeletal muscle cells could be seen (HE × 100). (b) Budding-like protrusion of the lesions invading into the muscles could be seen on the juncture of tumors and muscles (HE × 40). (c) Isolated small lesions in muscles were found away from the main part of the tumor (HE × 40). (d) Microscopically, desmoid tumors were poorly circumscribed on tumor-ligament boundary (HE × 40).Source: Wang YF. et al, Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044 P.R. China
Histological features of postoperative recurrent desmoid tumors in the right forearm of a 15-year-old man (arrows) (a–d). (a) Lesions with adipose tissue involvement (HE × 40). (b) Desmoid tumors around vessels could not invade into the vessel wall to form tumor thrombus (HE × 40). (c) Desmoid tumors invaded into the connective tissue and perineurium around nerve tissue (HE × 40). (d) Desmoid tumors with bone involvement penetrated into the periosteum and cortical bone and invaded into the bone marrow cavity along the bone trabecula (HE × 40).Source: Wang YF. et al, Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044 P.R. China
Immunological features of desmoid tumors in the middle section of the left thigh of a 35-year-old woman with femur involvement (a–d). (a) β-catenin staining of desmoid tumors (EnVision × 200). (b) Vimentin staining of desmoid tumors (EnVision × 200). (c) Desmin staining of desmoid tumors (EnVision × 200). (d) Ki-67 staining of desmoid tumors (EnVision × 200).Source: Wang YF. et al, Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044 P.R. China
Extra-Abdominal Fibromatosis (Desmoid Tumor): A Rare Tumor of the Lower Extremity Arising from the Popliteal Fossa. Desmoid fibromatosis showing fascicular arrangement of bland fibroblasts, which are interrupted by thin-walled, compressed vascular channels resulting in an appearance akin to a hypocellular scar. Note entrapped muscle fibers. No mitotic activity or nuclear pleomorphism is present (H&E, original magnification, 40x). Source: Ali Kaygain M. et al, Department of Cardiovascular Surgery, Erzurum Regional Training and Research Hospital, 25020 Erzurum, Turkey

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