Desmoid tumor pathophysiology: Difference between revisions

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{{CMG}} {{AE}}{{S.M.}}{{Faizan}}
{{CMG}} {{AE}}{{S.M.}}{{Faizan}}
==Overview==
==Overview==
[[Desmoid tumor|Desmoid tumors]] are [[benign tumors]] arising 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.
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==
*[[Desmoid tumor|Desmoid tumors]] have following characteristics:
*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>
**Arise from monoclonal [[proliferation]] of well-differentiated [[fibroblasts]]<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>
**Arise from monoclonal [[proliferation]] of well-differentiated [[fibroblasts]]
**Can grow almost anywhere in [[Human body|body]]
**Can grow almost anywhere in [[Human body|body]]
**Appear as well-differentiated, firm overgrowths of [[fibrous tissue]]
**Appear as well-differentiated, firm overgrowths of [[fibrous tissue]]
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*'''APC mutations'''
*'''APC mutations'''
**[[Function (biology)|Function]] of normal [[APC (protein)|APC protein]] is to prevent the accumulation of [[beta-catenin]] by mediating its [[phosphorylation]] and resultant [[degradation]]
**[[Function (biology)|Function]] of normal [[APC (protein)|APC protein]] is to prevent the accumulation of [[beta-catenin]] by mediating its [[phosphorylation]] and resultant [[degradation]]
**[[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>
**[[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]]
**[[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
**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
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*[[Gardner syndrome]]
*[[Gardner syndrome]]
*[[Familial adenomatous polyposis]]
*[[Familial adenomatous polyposis]]
**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)]]
**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==
*[[Desmoid tumor|Desmoid tumors]] look like [[dense]] [[scar tissue]]
*[[Desmoid tumor|Desmoid tumors]] look like [[dense]] [[scar tissue]].
*Adhere tenaciously to surrounding structures and [[organs]] just like a [[scar tissue]] hence, difficult to remove
*Adhere tenaciously to surrounding structures and [[organs]] just like a [[scar tissue]] hence, difficult to remove.
*[[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>
*[[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>
**[[Connective tissue]]
**[[Connective tissue]]
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**[[Aponeuroses]]
**[[Aponeuroses]]
*[[Abdominal wall]] [[Desmoid tumor|desmoid tumors]] arise from:
*[[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)
:*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]]
:*[[External oblique muscle]] and the [[Transversalis fascia|transversalis muscle or fascia]]
:*Mostly measure 5 cm by 15 cm in [[diameter]]
:*Mostly measure 5 cm by 15 cm in [[diameter]]
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*[[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 tumor|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]] and [[myofibroblasts]]
*Elongated [[fibroblasts]] and [[myofibroblasts]]
*[[Myofibroblasts]] are characterized by elongated, tapered [[cytoplasm]]; elongated, [[vesicular]], typical-appearing [[nuclei]]; and multiple small [[nucleoli]]  
*[[Myofibroblasts]] are characterized by elongated, tapered [[cytoplasm]]; elongated, [[vesicular]], typical-appearing [[nuclei]]; and multiple small [[nucleoli]]  
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{| class="wikitable"
{| class="wikitable"
|+Stages of evolution of desmoid tumors
|+Stages of evolution of desmoid tumors
!Stage
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Stage
!Histological features
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Histological features
|-
|-
|'''First stage'''
| style="background:#DCDCDC;" align="center" + |'''First stage'''
|
|
* More cellular [[lesions]]
* More cellular [[lesions]]
* Fewer [[Area|areas]] of hyalinized [[collagen]]
* Fewer [[Area|areas]] of hyalinized [[collagen]]
|-
|-
|'''Second stage'''
| style="background:#DCDCDC;" align="center" + |'''Second stage'''
|
|
* Increased amount of [[collagen]] [[Deposition (physics)|deposition]] in [[central]] and peripheral [[tumor]] [[Area|areas]]
* Increased amount of [[collagen]] [[Deposition (physics)|deposition]] in [[central]] and peripheral [[tumor]] [[Area|areas]]
|-
|-
|'''Third stage'''
| style="background:#DCDCDC;" align="center" + |'''Third stage'''
|
|
* Increased [[fibrous]] composition
* Increased [[fibrous]] composition
* Decreased cellularity  
* Decreased cellularity  
* Decreased [[water]] content
* 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]]]
|
[[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]]]
|
[[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]]]
|}
|}



Latest revision as of 14:35, 16 May 2019

Desmoid tumor Microchapters

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Pathophysiology

Causes

Differentiating Desmoid tumor from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

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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

Reference

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