Desmoid tumor pathophysiology: Difference between revisions

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==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>
*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>
*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>
 
==Genetics===
===Mutations in adults===
*Wnt/beta-catenin signaling pathway<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>
*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>
*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>
*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>
===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>
**AKT1 E17K mutation (31%)
**BRAF V600E mutation (19%)
**TP53 R273H mutation (9%)
 
 


===Associated Diseases===
===Associated Diseases===

Revision as of 21:04, 27 February 2019

Desmoid tumor Microchapters

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Differentiating Desmoid tumor from other Diseases

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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 tumor may occur as part of Gardner syndrome. A minority of desmoid tumors are associated with Turcot syndrome, Familial adenomatous polyposis, and estrogen therapy.

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.[1]
  • The exact etiology of desmoid tumors is unknown. However, the following etiologies seem to play a role in development of desmoid tumors:[2][3][4][5][6]

Genetics=

Mutations in adults

Additional mutations in pediatric desmoids

  • In addition to CTNNB1 mutations, following mutations contribute to pediatric desmoids:[37]
    • AKT1 E17K mutation (31%)
    • BRAF V600E mutation (19%)
    • TP53 R273H mutation (9%)


Associated Diseases

Gross Pathology

  • Abdominal wall desmoid tumors arise from:
  • Musculoaponeurotic structures of the abdominal wall (especially the rectus and internal oblique muscles and their fascial coverings)
  • External oblique muscle and the transversalis muscle or fascia
  • These masses have a firm, gritty texture. On the cut surface, they are glistening white and coarsely trabeculated, resembling scar tissue

Location

Frequent locations in the abdomen are:

Microscopic Pathology

Histologically, desmoid tumors consist of:[38]

  • Elongated fibroblasts.
  • 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.
  • These tumors show a tendency to evolve over time.
  • Vandevenne et al described three stages of evolution of desmoid tumors:
  • In the first stage, lesions are more cellular and have fewer areas of hyalinized collagen.
  • In the second stage, there is an increasing amount of collagen deposition in the central and peripheral areas of the tumor.
  • In the third stage, there is an increase in the fibrous composition with a decrease in cellularity and water content.

Reference

  1. ↑ Desmoid tumor. Dr Tim Luijkx and Radswiki et al. Radiopedia 2015 http://radiopaedia.org/articles/aggressive-fibromatosis. Accessed on January 20, 2015
  2. ↑ De Wever I, Dal Cin P, Fletcher CD, Mandahl N, Mertens F, Mitelman F; et al. (2000). "Cytogenetic, clinical, and morphologic correlations in 78 cases of fibromatosis: a report from the CHAMP Study Group. CHromosomes And Morphology". Mod Pathol. 13 (10): 1080–5. doi:10.1038/modpathol.3880200. PMID 11048801.
  3. ↑ Middleton SB, Frayling IM, Phillips RK (2000). "Desmoids in familial adenomatous polyposis are monoclonal proliferations". Br J Cancer. 82 (4): 827–32. doi:10.1054/bjoc.1999.1007. PMC 2374411. PMID 10732754.
  4. ↑ 4.0 4.1 Li C, Bapat B, Alman BA (1998). "Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor)". Am J Pathol. 153 (3): 709–14. PMC 1853030. PMID 9736021.
  5. ↑ Escobar C, Munker R, Thomas JO, Li BD, Burton GV (2012). "Update on desmoid tumors". Ann Oncol. 23 (3): 562–9. doi:10.1093/annonc/mdr386. PMID 21859899.
  6. ↑ 6.0 6.1 Giarola M, Wells D, Mondini P, Pilotti S, Sala P, Azzarelli A; et al. (1998). "Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumours". Br J Cancer. 78 (5): 582–7. PMC 2063069. PMID 9744495.
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  8. ↑ 8.0 8.1 Lazar AJ, Hajibashi S, Lev D (2009). "Desmoid tumor: from surgical extirpation to molecular dissection". Curr Opin Oncol. 21 (4): 352–9. doi:10.1097/CCO.0b013e32832c9502. PMID 19436199.
  9. ↑ Aitken SJ, Presneau N, Kalimuthu S, Dileo P, Berisha F, Tirabosco R; et al. (2015). "Next-generation sequencing is highly sensitive for the detection of beta-catenin mutations in desmoid-type fibromatoses". Virchows Arch. 467 (2): 203–10. doi:10.1007/s00428-015-1765-0. PMID 25838078.
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  11. ↑ Heinrich MC, McArthur GA, Demetri GD, Joensuu H, Bono P, Herrmann R; et al. (2006). "Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor)". J Clin Oncol. 24 (7): 1195–203. doi:10.1200/JCO.2005.04.0717. PMID 16505440.
  12. ↑ Cheon SS, Cheah AY, Turley S, Nadesan P, Poon R, Clevers H; et al. (2002). "beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds". Proc Natl Acad Sci U S A. 99 (10): 6973–8. doi:10.1073/pnas.102657399. PMC 124513. PMID 11983872.
  13. ↑ Abraham SC, Reynolds C, Lee JH, Montgomery EA, Baisden BL, Krasinskas AM; et al. (2002). "Fibromatosis of the breast and mutations involving the APC/beta-catenin pathway". Hum Pathol. 33 (1): 39–46. PMID 11823972.
  14. ↑ Signoroni S, Frattini M, Negri T, Pastore E, Tamborini E, Casieri P; et al. (2007). "Cyclooxygenase-2 and platelet-derived growth factor receptors as potential targets in treating aggressive fibromatosis". Clin Cancer Res. 13 (17): 5034–40. doi:10.1158/1078-0432.CCR-07-0336. PMID 17785554.
  15. ↑ Cheon S, Poon R, Yu C, Khoury M, Shenker R, Fish J; et al. (2005). "Prolonged beta-catenin stabilization and tcf-dependent transcriptional activation in hyperplastic cutaneous wounds". Lab Invest. 85 (3): 416–25. doi:10.1038/labinvest.3700237. PMID 15654359.
  16. ↑ Merchant NB, Lewis JJ, Woodruff JM, Leung DH, Brennan MF (1999). "Extremity and trunk desmoid tumors: a multifactorial analysis of outcome". Cancer. 86 (10): 2045–52. PMID 10570430.
  17. ↑ Kim HS, Kim J, Nam KH, Kim WH (2016). "Clinical significance of midkine expression in sporadic desmoid tumors". Oncol Lett. 11 (3): 1677–1684. doi:10.3892/ol.2016.4129. PMC 4774436. PMID 26998061.
  18. ↑ Kotiligam D, Lazar AJ, Pollock RE, Lev D (2008). "Desmoid tumor: a disease opportune for molecular insights". Histol Histopathol. 23 (1): 117–26. doi:10.14670/HH-23.117. PMID 17952864.
  19. ↑ Crago AM, Chmielecki J, Rosenberg M, O'Connor R, Byrne C, Wilder FG; et al. (2015). "Near universal detection of alterations in CTNNB1 and Wnt pathway regulators in desmoid-type fibromatosis by whole-exome sequencing and genomic analysis". Genes Chromosomes Cancer. 54 (10): 606–15. doi:10.1002/gcc.22272. PMC 4548882. PMID 26171757.
  20. ↑ Bertario L, Russo A, Sala P, Eboli M, Giarola M, D'amico F; et al. (2001). "Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis". Int J Cancer. 95 (2): 102–7. PMID 11241320.
  21. ↑ Schiessling S, Kihm M, Ganschow P, Kadmon G, Büchler MW, Kadmon M (2013). "Desmoid tumour biology in patients with familial adenomatous polyposis coli". Br J Surg. 100 (5): 694–703. doi:10.1002/bjs.9053. PMID 23334997.
  22. ↑ Nieuwenhuis MH, Vasen HF (2007). "Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature". Crit Rev Oncol Hematol. 61 (2): 153–61. doi:10.1016/j.critrevonc.2006.07.004. PMID 17064931.
  23. ↑ Sinha A, Tekkis PP, Gibbons DC, Phillips RK, Clark SK (2011). "Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis". Colorectal Dis. 13 (11): 1222–9. doi:10.1111/j.1463-1318.2010.02345.x. PMID 20528895.
  24. ↑ Caspari R, Olschwang S, Friedl W, Mandl M, Boisson C, Böker T; et al. (1995). "Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444". Hum Mol Genet. 4 (3): 337–40. PMID 7795585.
  25. ↑ Bertario L, Russo A, Sala P, Varesco L, Giarola M, Mondini P; et al. (2003). "Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis". J Clin Oncol. 21 (9): 1698–707. doi:10.1200/JCO.2003.09.118. PMID 12721244.
  26. ↑ Friedl W, Caspari R, Sengteller M, Uhlhaas S, Lamberti C, Jungck M; et al. (2001). "Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families". Gut. 48 (4): 515–21. PMC 1728231. PMID 11247896.
  27. ↑ Wallis YL, Morton DG, McKeown CM, Macdonald F (1999). "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". J Med Genet. 36 (1): 14–20. PMC 1762945. PMID 9950360.
  28. ↑ Church J, Xhaja X, LaGuardia L, O'Malley M, Burke C, Kalady M (2015). "Desmoids and genotype in familial adenomatous polyposis". Dis Colon Rectum. 58 (4): 444–8. doi:10.1097/DCR.0000000000000316. PMID 25751801.
  29. ↑ Halling KC, Lazzaro CR, Honchel R, Bufill JA, Powell SM, Arndt CA; et al. (1999). "Hereditary desmoid disease in a family with a germline Alu I repeat mutation of the APC gene". Hum Hered. 49 (2): 97–102. doi:10.1159/000022852. PMID 10077730.
  30. ↑ Lazar AJ, Tuvin D, Hajibashi S, Habeeb S, Bolshakov S, Mayordomo-Aranda E; et al. (2008). "Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors". Am J Pathol. 173 (5): 1518–27. doi:10.2353/ajpath.2008.080475. PMC 2570141. PMID 18832571.
  31. ↑ Mullen JT, DeLaney TF, Rosenberg AE, Le L, Iafrate AJ, Kobayashi W; et al. (2013). "β-Catenin mutation status and outcomes in sporadic desmoid tumors". Oncologist. 18 (9): 1043–9. doi:10.1634/theoncologist.2012-0449. PMC 3780636. PMID 23960186.
  32. ↑ Fletcher JA, Naeem R, Xiao S, Corson JM (1995). "Chromosome aberrations in desmoid tumors. Trisomy 8 may be a predictor of recurrence". Cancer Genet Cytogenet. 79 (2): 139–43. PMID 7889507.
  33. ↑ Kouho H, Aoki T, Hisaoka M, Hashimoto H (1997). "Clinicopathological and interphase cytogenetic analysis of desmoid tumours". Histopathology. 31 (4): 336–41. PMID 9363449.
  34. ↑ Bridge JA, Swarts SJ, Buresh C, Nelson M, Degenhardt JM, Spanier S; et al. (1999). "Trisomies 8 and 20 characterize a subgroup of benign fibrous lesions arising in both soft tissue and bone". Am J Pathol. 154 (3): 729–33. doi:10.1016/S0002-9440(10)65319-9. PMC 1866419. PMID 10079250.
  35. ↑ Qi H, Dal Cin P, Hernández JM, Garcia JL, Sciot R, Fletcher C; et al. (1996). "Trisomies 8 and 20 in desmoid tumors". Cancer Genet Cytogenet. 92 (2): 147–9. PMID 8976373.
  36. ↑ Mertens F, Willén H, Rydholm A, Brosjö O, Carlén B, Mitelman F; et al. (1995). "Trisomy 20 is a primary chromosome aberration in desmoid tumors". Int J Cancer. 63 (4): 527–9. PMID 7591262.
  37. ↑ Meazza C, Belfiore A, Busico A, Settanni G, Paielli N, Cesana L; et al. (2016). "AKT1 and BRAF mutations in pediatric aggressive fibromatosis". Cancer Med. 5 (6): 1204–13. doi:10.1002/cam4.669. PMC 4924379. PMID 27062580.
  38. ↑ Economou, Athanasios; Pitta, Xanthi; Andreadis, Efstathios; Papapavlou, Leonidas; Chrissidis, Thomas (2011). "Desmoid tumor of the abdominal wall: a case report". Journal of Medical Case Reports. 5 (1): 326. doi:10.1186/1752-1947-5-326. ISSN 1752-1947.

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