Desmoid tumor pathophysiology

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Desmoid tumor Microchapters

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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

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Other Diagnostic Studies

Treatment

Medical Therapy

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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 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.
  7. ↑ Barker N (2008). "The canonical Wnt/beta-catenin signalling pathway". Methods Mol Biol. 468: 5–15. doi:10.1007/978-1-59745-249-6_1. PMID 19099242.
  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.
  10. ↑ Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P; et al. (1999). "Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor)". Oncogene. 18 (47): 6615–20. doi:10.1038/sj.onc.1203041. PMID 10597266.
  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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