Desmoid tumor overview: Difference between revisions

Jump to navigation Jump to search
 
(46 intermediate revisions by 3 users not shown)
Line 1: Line 1:
{{Desmoid tumor}}
{{Desmoid tumor}}
__NOTOC__
__NOTOC__
{{CMG}} {{AE}}{{Faizan}}
 
{{CMG}} {{AE}}{{S.M.}}
==Overview==
==Overview==
'''Aggressive fibromatosis''' is a rare condition marked by the presence of '''desmoid tumors'''.  Desmoid tumors are tumors that arise from cells called fibroblasts. Fibroblasts are found throughout our body and their main function is to provide structural support and protection to the vital organs such as lung, liver, blood vessels, heart, kidneys, skin, intestines etc. and they also play a critical role in wound healing. When fibroblast cells undergo mutations they can become cancerous and become desmoid tumors (also known as "aggressive fibromatosis"). Desmoid tumors can arise in virtually any part of the body. These tumors often occur in women in their 30's, but can occur in anyone at any age. Desmoid tumors can be slow growing or extremely aggressive. These are slow-growing musculoaponeurotic tumors without any [[metastasis|metastatic]] potential. However, aggressive fibromatosis is locally aggressive. When they are aggressive they can cause life threatening problems or even death when they compress vital organs such as intestines, kidney, lungs, blood vessels, nerves etc. Most cases are sporadic, but some are associated with [[familial adenomatous polyposis]] (FAP). Approximately 10% of individuals with [[Gardner's syndrome]], a type of FAP with extracolonic features, have desmoid tumors.<ref name="pmid18237870">{{cite journal |author=Nieuwenhuis MH, De Vos Tot Nederveen Cappel W, Botma A |title=Desmoid tumors in a Dutch cohort of patients with familial adenomatous polyposis |journal=Clin. Gastroenterol. Hepatol. |volume=6 |issue=2 |pages=215–9 |date=February 2008 |pmid=18237870 |doi=10.1016/j.cgh.2007.11.011 |url=http://linkinghub.elsevier.com/retrieve/pii/S1542-3565(07)01107-X|display-authors=etal}}</ref>
[[Desmoid tumor|Desmoid tumors]] are the [[benign]] [[tumors]] that arise from monoclonal [[proliferation]] of well-differentiated [[fibroblasts]] (which are found throughout the [[body]]). Main function of [[fibroblasts]] is in [[wound healing]] and to provide structural support and protection to the vital [[organs]] such as [[lung]], [[liver]], [[blood vessels]], [[heart]], [[kidneys]], [[skin]], [[intestines]]. Depending upon the underlying [[etiology]], [[Desmoid tumor|desmoid tumors]] can be classified as [[abdominal]], intra-abdominal, extra-abdominal, multiple [[familial]], associated with [[Gardner's syndrome|Gardner syndrome]] and associated with [[Turcot syndrome]]. [[Desmoid tumor|Desmoids]] can arise in virtually any part of the [[body]]. [[Desmoid tumor|Desmoids]] appear as well-differentiated, firm overgrowths of [[fibrous tissue]] with marked cellularity and aggressive local [[Infiltration (medical)|infiltration]]. [[Histologically]], [[desmoid tumor]]<nowiki/>s consist of linearly arranged elongated [[fibroblasts]] and [[myofibroblasts]] surrounded and separated from each other by [[collagen]]. Most common frequent causes of [[desmoid tumor]]<nowiki/>s at molecular level include [[mutations]] in the [[Β-catenin|β-catenin gene]], CTNNB1, or the [[Adenomatous polyposis coli|adenomatous polyposis coli gene]], [[APC]], all involved in [[Wnt signaling pathway|Wnt]]/[[beta-catenin]] [[signaling pathway]]. [[Pediatric]] [[Desmoid tumor|desmoid tumors]] have [[AKT1 gene|AKT1 E17K]], [[BRAF (gene)|BRAF V600E]] and [[TP53|TP53 R273H]] [[mutations]] also in addition to CTNNB1 [[mutations]]. [[Desmoid tumor|Desmoid tumors]] account for approximately 0.03 percent of all [[neoplasm]] and less than 3% of all the [[soft tissue]] [[tumors]].They are more common in women (of fertile age) than [[men]], and mostly occur in [[age]] of 30's to 40's. These [[tumors]] can be slow growing or extremely aggressive, musculoaponeurotic [[tumors]] without any [[metastasis|metastatic]] potential. When they are aggressive they can cause life threatening problems or even death due to compression of vital [[organs]] such as the [[intestines]], [[kidneys]], [[lungs]], [[blood vessels]], and [[nerves]]. Common [[risk factors]] for [[Desmoid tumor|desmoid tumors]] include personal or [[family history]] of [[FAP]], [[Gardner's syndrome|Gardner syndrome]], [[Turcot syndrome]], [[female]] gender, [[pregnancy]], [[estrogen]] [[therapy]], history of [[Antecedent (logic)|antecedent]] surgical or accidental [[trauma]] or [[irradiation]] at the [[tumor]] site, history of [[breast cancer]] and [[androgens]].
 
[[Desmoid tumor|Desmoids]] may be diagnosed on an imaging test done for another reason in [[asymptomatic]] [[patients]]. In [[symptomatic]] [[patients]], it can present as a painless or [[painful]] [[mass]]/[[lump]], [[insomnia]], difficulty [[moving]], [[Nausea and vomiting|nausea, vomiting]], [[anxiety]] depending upon size and location of [[tumor]]. [[Gold standard (test)|Gold standard]] for [[diagnosis]] is [[histological]] [[examination]] of a [[biopsy]] specimen followed by [[immunohistochemistry]] for [[nuclear]] [[beta-catenin]]. Various [[imaging studies]] like [[CT]], [[Magnetic resonance imaging|MRI]], [[ultrasonography]], [[color]] [[Doppler ultrasound|doppler]], plain [[Radiography|radiograph]] and [[angiography]] may aid in further [[diagnosis]] and deciding treatment strategy especially for highly recurrent [[tumors]]. Wait and watch [[therapy]] is applied for treatment of [[asymptomatic]] [[patients]]. For [[symptomatic]] [[patients]] various [[therapeutic]] options are available such as [[surgery]], [[radiation therapy]], [[tumor]] ablation and [[Medical therapy template|medical therapy]] with [[chemotherapeutic agents]], anti-hormonal agents, [[Non-steroidal anti-inflammatory drug|NSAIDs]] and [[tyrosine kinase inhibitors]].
 
==Historical Perspective==
==Historical Perspective==
Muller first coined the term desmoid in 1858 to describe [[tumors]] with [[tendon]]-like [[Consistency (statistics)|consistency]]. It origniates from a Greek word "desmos" meaning band or [[tendon]]-like. Gradner first described the [[development]] of [[Desmoid tumor|desmoid tumors]] in [[FAP]] [[patients]] in 1951.
==Classification==
==Classification==
Desmoid tumor may be classified according to etiology into 5 subtypes.<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>
Depending upon the underlying [[etiology]], [[Desmoid tumor|desmoid tumors]] can be classified as [[abdominal]], intra-abdominal, extra-abdominal, multiple [[familial]], associated with [[Gardner's syndrome|Gardner syndrome]] and associated with [[Turcot syndrome]].
==Pathophysiology==
==Pathophysiology==
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.<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>
[[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]] 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.


==Causes==
==Causes==
There are no established direct causes for desmoid tumor.
The exact [[etiology]] of [[Desmoid tumor|desmoid tumors]] is unknown. However, [[Wnt signaling pathway|Wnt]]/[[beta-catenin]] [[signaling pathway]], [[APC gene|APC]] [[mutations]], CTNNB1 [[Beta-catenin|(beta-catenin) gene]] [[mutations]], sporadic [[tumors]] and [[trisomy 8]] and [[trisomy]] 20 seem to play a role in [[development]] of sporadic [[Desmoid tumor|desmoids]] in adults. [[Familial]] [[Desmoid tumor|desmoids]] in [[FAP]] [[patients]] are associated with [[germline]] [[APC]] [[mutations]]. [[Pediatric]] [[Desmoid tumor|desmoids]] have [[AKT1 gene|AKT1 E17K]], [[BRAF (gene)|BRAF V600E]] and [[TP53|TP53 R273H]] [[mutations]] in addition to CTNNB1 [[mutations]].


==Differentiating Desmoid tumor from other Diseases==
==Differentiating Desmoid tumor from other Diseases==
Desmoid tumor must be differentiated from acute hematoma, [[lymphoma]], and [[fibrosarcoma]].<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>
Extra-[[abdominal]] [[desmoid tumor]] must be differentiated from [[fibrosarcoma]], low-grade fibromyxoid [[sarcoma]] and Gardner [[fibroma]]. Intra-[[abdominal]] [[desmoid tumor]] must be differentiated from [[gastrointestinal stromal tumor|gastrointestinal stromal tumor (GIST)]], [[benign]] [[Fibrous tumor of the pleura|fibrous tumor]]/[[Solitary fibrous tumor of the pleura|solitary fibrous tumor]] (SFT), [[inflammatory]] myofibroblastic [[tumor]] (IMT), sclerosing mesenteritis and [[retroperitoneal fibrosis]]. Furthermore, generally all [[Desmoid tumor|desmoid tumors]] must be differentiated from acute [[hematoma]], [[lymphoma]], [[rhabdomyosarcoma]], [[liposarcoma]], [[leiomyosarcoma]], [[neurofibroma]], [[nodular fasciitis]], [[Hypertrophic scars|hypertrophic scars,]][[keloids]] and [[primitive neuroectodermal tumor]].


==Epidemiology and Demographics==
==Epidemiology and Demographics==
Desmoid tumor occurs in less than 0.03% of all tumors. The incidence of desmoid tumor is approximately 30 per 100,000 individuals worldwide. Females are more commonly affected with desmoid tumor than males. Desmoid tumor commonly affects individuals between 20 to 40 years of age.<ref name=aaa>Desmoid tumor. Dr Tim Luijkx and Radswiki et al.Radiopaedia 2015.http://radiopaedia.org/articles/desmoid-tumour. Accessed on January 21, 2016</ref><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>
[[Desmoid tumor]] accounts for 0.03% of all [[tumors]] and less than 3% of all the [[soft tissue]] [[tumors]]. It affects 1 to 2 per 500,000 people worldwide. [[Incidence]] of [[desmoid tumor]] is approximately two to four per million [[population]] per year in general [[population]]. [[Familial]] [[Desmoid tumor|desmoids]] are present in 10% to 25% of [[FAP]] [[patients]]. Gender ratio is 2:1 for females to males and commonly affects individuals between 20 to 60 years of [[age]].


==Risk Factors==
==Risk Factors==
Risk factors for desmoid disease amongst FAP patients include female sex, a 3' [[Adenomatous polyposis coli|APC mutation]], a positive family history and a history of previous abdominal surgery.<ref name="pmid20528895">{{cite journal |author=Sinha A, Clark SK|title=Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis |journal=Colorectal Dis. |pages=no |year=2010|pmid=20528895 |doi=10.1111/j.1463-1318.2010.02345.x |url= |volume=13 |issue=11}}</ref>
Common [[risk factors]] for the [[development]] of [[desmoid tumor]] include personal or [[family history]] of [[Familial adenomatous polyposis|familial adenomatous polyposis (FAP)]], [[Gardner's syndrome|Gardner syndrome]], [[Turcot syndrome]], specific location of [[APC]] [[Adenomatous polyposis coli|(adenomatous polyposis coli) gene]] [[mutation]] i.e. 3' of [[codon]] 1444, [[family history]] of [[desmoid tumor]], [[estrogen]] [[therapy]], [[oral contraceptive pills]], [[pregnancy]], history of antecedent surgical or accidental [[trauma]] or repeated [[irradiation]] at the [[tumor]] site, [[female]] gender and [[androgens]].
==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
If left untreated, desmoid tumor produces few symptoms early in the course. Common complications of desmoid tumor include progression to agressive fibromatosis, involvement of intra abdominal viscera and metastasis. The prognosis varies with the associated disease of desmoid tumor. Desmoid tumor associated with FAP has the most unfavorable prognosis.
[[Desmoid tumor|Desmoids]] can develop virtually at any site of [[body]] causing wide range of [[clinical]] [[symptoms]] depending on size and [[tumor]] location or they can cause no [[symptoms]] at all. They may be accidentally picked up on a [[scan]] or a routine [[physical examination]] done for other [[medical]] reasons. They might grow aggressively or slowly or remian stable, hence, exhibiting wide range of behaviors in different individuals. Common [[complications]] of [[desmoid tumor]] include progression to agressive [[fibromatosis]], involvement of intra-abdominal [[viscera]] that may lead to [[rupture]] of [[intestines]], compression of the [[kidneys]] or [[ureters]], [[rectal bleeding]], compression of critical [[blood vessels]] such as the mesenteric [[vessels]] and the [[Vena cavae|vena cava]], [[amputation]] and loss of significant portions of [[foregut]] [[Surgery|post-surgery]]. Five-year progression-free [[survival rate]] is 50% in [[patients]] with a primary or recurrent [[Desmoid tumor|desmoid]] who are not treated initially with [[surgery]], [[Radiotherapy|radiotherapy (RT)]], or [[systemic therapy]]. Massive and [[inoperable]] [[Desmoid tumor|desmoids]] have become an important cause of [[Morbidity & Mortality|morbidity and mortality]] in [[FAP]] [[patients]] [[Colectomy|post-colectomy]]. [[Desmoid tumor]] associated with [[FAP]] has the least favorable [[prognosis]] due to high recurrence rate. Whereas, non-[[FAP]]-associated intra-abdominal [[fibromatosis]] has a low recurrence rate after [[surgical resection]].
 
==Diagnostic study of choice==
Definitive [[diagnosis]] of a [[desmoid tumor]] can only be established by [[Histological|histological examination]] of a [[Biopsy|biopsy specimen]]. [[Electron microscopy]] can be done which shows [[spindle cells]] of [[Desmoid tumor|desmoids]] appearing as [[myofibroblasts]].


==History and Symptoms==
==History and Symptoms==
Depending on size, location and spread of [[tumor]], [[patients]] may remain [[asymptomatic]] for long time period or may show [[symptoms]] like painless/[[painful]] [[lump]] appearning as a [[swelling]] in affected [[area]], [[Nausea and vomiting|nausea, vomiting]], [[anxiety]], loss of [[sleep]], [[pain]] or soreness caused by compressed [[nerves]] or [[muscles]], limping and decreased [[Movement disorder|movement]] or [[range of motion]] or other difficulty using the [[legs]], [[feet]], arms or [[hands]] or other affected part of the [[Human body|body]]. Intra-abdominal [[Desmoid tumor|desmoids]] can present with [[abdominal pain]], [[abdominal mass]], [[constipation]] due to [[intestinal obstruction]], [[bowel ischemia]], functional deterioration in an ileoanal [[anastomosis]] (especially in post-[[colectomy]] [[FAP]] [[patient]]), [[bloating]], [[rupture]] of [[intestine]], compression of the [[kidneys]] or [[ureters]], [[rectal bleeding]], and compression of critical [[blood vessels]] such as the mesenteric [[vessels]] and the [[vena cava]].
==Physical Examination==
==Physical Examination==
==Laboratory Findings==
Common [[physical examination]] findings of [[desmoid tumor]] include [[lump]] or [[swelling]] in the affected [[area]], [[abdominal tenderness]], [[pallor]], and elevated [[temperature]].
==CT==
==MRI==
==Other Imaging Findings==
==Other Diagnostic Studies==
 


==Laboratory findings==
[[Immunohistochemical staining]] of [[spindle cells]] of [[Desmoid tumor|desmoid tumors]] are positive for nuclear [[beta-catenin]], [[vimentin]], alpha [[smooth muscle]] [[actin]], [[muscle]] [[Actin filament|actin]] and negative for [[desmin]], cytokeratins, and [[S-100]]. [[Antibodies]] like [[smooth muscle]] [[actin]], [[desmin]] and KIT may be helpful in distinguishing [[Desmoid tumor|desmoid tumors]] from other [[tumors]]. In addition, [[APC]] [[Germline mutation|germline mutations]] may be performed in [[patients]] with sporadic [[Desmoid tumor|desmoid tumors]] with no [[clinical]] or famililal [[signs]] of [[FAP]] but having a [[family history]] of [[colorectal carcinoma]] in at least one [[Family|family member]].


==CT==
[[CT scan]] can be done in order to define the relationship of [[desmoid tumor]] to adjacent structures, assess resectibility and find out the need for treatment. On [[Computed tomography|CT scan]], [[desmoid tumor]] is characterized by a [[Homogeneous|homogeneously]] or focally hyperattenuating well circumscribed [[mass]] which may demonstrate enhancement following administration of [[intravenous]] contrast.


==MRI==
[[Magnetic resonance imaging|MRI]] is preferred over [[Computed tomography|CT]], especially for [[Trunk|truncal]] and extremity [[Desmoid tumor|desmoid tumors]]. On [[MRI]], [[desmoid tumor]] has variable characteristics depending on their cellularity and [[fibrous]] content with loss of signal following [[fat]] [[saturation]]. They appear isointense/hypointense on [[T1]] and hyperintense on T2.


==Other Imaging Findings==
Other [[imaging studies]] for the [[diagnosis]] of [[desmoid tumor]] include [[ultrasonography]], which demonstrates [[tumor]] size and location. On [[ultrasonography]], [[Desmoid tumor|desmoid tumors]] appear as well-defined [[lesions]] with variable [[echogenicity]], and ill defined/irregular borders. On [[Doppler ultrasound|color Doppler,]] [[Desmoid tumor|desmoids]] appear like [[muscles]], may be lobulated and may show [[vascularity]]. [[Radiograph|Plain radiographs]] and [[angiography]] may be of [[diagnostic]] help in some cases.


==Medical Therapy==
Wait and watch [[Strategy (NLP)|strategy]] is applied to [[Desmoid tumor|desmoid tumors]] which are [[asymptomatic]], unresectable, non-life threatening, not causing any significant [[impairment]], and resectable [[tumors]] with increased [[morbidity]] associated with [[surgery]].Different [[drugs]] including [[chemotherapeutic agents]], [[Non-steroidal anti-inflammatory drug|NSAIDs]], anti-hormonal agents and [[tyrosine kinase inhibitors]] can be used to shrink or [[Stabilizer (chemistry)|stabilize]] the [[tumor]] size and to improve the [[symptoms]]. [[Radiation therapy]] and [[tumor]] [[ablation]] with [[heat]], [[cold]], [[microwave]] and/or high-frequency [[Ultrasound|ultrasound waves]] can also be of [[therapeutic]] use as required.


==Surgery==
The goals of [[surgery]] include [[tumor]] removal and functional restoration at the [[tumor]] site. [[Standard]] surgical goal is [[wide local excision]] with a grossly negative [[microscopic]] margin followed by reconstruction of [[defect]] with [[skin graft]], rotational [[muscle]] flap or free [[muscle]] flap. [[Abdominal wall]] [[resection]] may be required to close the [[defect]] and minimize the risk of [[hernias]]. Incomplete [[tumor]] removal or involved [[excision]] margins may lead to local recurrence in 25% to 40% of [[patients]]. Hence, because of high recurrence risk post-[[surgery]], [[imaging]] of the [[tumor]] site with [[ultrasound]] or [[MRI scans]] may be recommended to closely monitor [[Patient|patient’s]] [[health]] on follow up visits after [[surgery]].


==Future or investigational therapies==
[[Angiogenesis inhibitor|Angiogenesis inhibitors]] and different [[chemotherapy agents]] are under [[Investigational new drug|investigation]] nowadays which might prove fruitful for treatment of [[Desmoid tumor|desmoid tumors]] in future. Furthermore, [[Mutation|mutational]] [[analysis]] for [[Beta-catenin|beta-catenin gene]] may soon be used to predict the recurrence risk and to aid in designing the individual therapies.


==Reference==
==Reference==
Line 45: Line 65:
{{WikiDoc Sources}}
{{WikiDoc Sources}}
[[Category:Disease]]
[[Category:Disease]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]

Latest revision as of 12:12, 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]

Overview

Desmoid tumors are the benign tumors that arise from monoclonal proliferation of well-differentiated fibroblasts (which are found throughout the body). Main function of fibroblasts is in wound healing and to provide structural support and protection to the vital organs such as lung, liver, blood vessels, heart, kidneys, skin, intestines. Depending upon the underlying etiology, desmoid tumors can be classified as abdominal, intra-abdominal, extra-abdominal, multiple familial, associated with Gardner syndrome and associated with Turcot syndrome. Desmoids can arise in virtually any part of the body. Desmoids appear as well-differentiated, firm overgrowths of fibrous tissue with marked cellularity and aggressive local infiltration. Histologically, desmoid tumors consist of linearly arranged elongated fibroblasts and myofibroblasts surrounded and separated from each other by collagen. Most common frequent causes of desmoid tumors at molecular level include mutations in the β-catenin gene, CTNNB1, or the adenomatous polyposis coli gene, APC, all involved in Wnt/beta-catenin signaling pathway. Pediatric desmoid tumors have AKT1 E17K, BRAF V600E and TP53 R273H mutations also in addition to CTNNB1 mutations. Desmoid tumors account for approximately 0.03 percent of all neoplasm and less than 3% of all the soft tissue tumors.They are more common in women (of fertile age) than men, and mostly occur in age of 30's to 40's. These tumors can be slow growing or extremely aggressive, musculoaponeurotic tumors without any metastatic potential. When they are aggressive they can cause life threatening problems or even death due to compression of vital organs such as the intestines, kidneys, lungs, blood vessels, and nerves. Common risk factors for desmoid tumors include personal or family history of FAP, Gardner syndrome, Turcot syndrome, female gender, pregnancy, estrogen therapy, history of antecedent surgical or accidental trauma or irradiation at the tumor site, history of breast cancer and androgens.

Desmoids may be diagnosed on an imaging test done for another reason in asymptomatic patients. In symptomatic patients, it can present as a painless or painful mass/lump, insomnia, difficulty moving, nausea, vomiting, anxiety depending upon size and location of tumor. Gold standard for diagnosis is histological examination of a biopsy specimen followed by immunohistochemistry for nuclear beta-catenin. Various imaging studies like CT, MRI, ultrasonography, color doppler, plain radiograph and angiography may aid in further diagnosis and deciding treatment strategy especially for highly recurrent tumors. Wait and watch therapy is applied for treatment of asymptomatic patients. For symptomatic patients various therapeutic options are available such as surgery, radiation therapy, tumor ablation and medical therapy with chemotherapeutic agents, anti-hormonal agents, NSAIDs and tyrosine kinase inhibitors.

Historical Perspective

Muller first coined the term desmoid in 1858 to describe tumors with tendon-like consistency. It origniates from a Greek word "desmos" meaning band or tendon-like. Gradner first described the development of desmoid tumors in FAP patients in 1951.

Classification

Depending upon the underlying etiology, desmoid tumors can be classified as abdominal, intra-abdominal, extra-abdominal, multiple familial, associated with Gardner syndrome and associated with Turcot syndrome.

Pathophysiology

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. 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-catenin signaling 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 tissue with 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.

Causes

The exact etiology of desmoid tumors is unknown. However, Wnt/beta-catenin signaling pathway, APC mutations, CTNNB1 (beta-catenin) gene mutations, sporadic tumors and trisomy 8 and trisomy 20 seem to play a role in development of sporadic desmoids in adults. Familial desmoids in FAP patients are associated with germline APC mutations. Pediatric desmoids have AKT1 E17K, BRAF V600E and TP53 R273H mutations in addition to CTNNB1 mutations.

Differentiating Desmoid tumor from other Diseases

Extra-abdominal desmoid tumor must be differentiated from fibrosarcoma, low-grade fibromyxoid sarcoma and Gardner fibroma. Intra-abdominal desmoid tumor must be differentiated from gastrointestinal stromal tumor (GIST), benign fibrous tumor/solitary fibrous tumor (SFT), inflammatory myofibroblastic tumor (IMT), sclerosing mesenteritis and retroperitoneal fibrosis. Furthermore, generally all desmoid tumors must be differentiated from acute hematoma, lymphoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, neurofibroma, nodular fasciitis, hypertrophic scars,keloids and primitive neuroectodermal tumor.

Epidemiology and Demographics

Desmoid tumor accounts for 0.03% of all tumors and less than 3% of all the soft tissue tumors. It affects 1 to 2 per 500,000 people worldwide. Incidence of desmoid tumor is approximately two to four per million population per year in general population. Familial desmoids are present in 10% to 25% of FAP patients. Gender ratio is 2:1 for females to males and commonly affects individuals between 20 to 60 years of age.

Risk Factors

Common risk factors for the development of desmoid tumor include personal or family history of familial adenomatous polyposis (FAP), Gardner syndrome, Turcot syndrome, specific location of APC (adenomatous polyposis coli) gene mutation i.e. 3' of codon 1444, family history of desmoid tumor, estrogen therapy, oral contraceptive pills, pregnancy, history of antecedent surgical or accidental trauma or repeated irradiation at the tumor site, female gender and androgens.

Natural History, Complications and Prognosis

Desmoids can develop virtually at any site of body causing wide range of clinical symptoms depending on size and tumor location or they can cause no symptoms at all. They may be accidentally picked up on a scan or a routine physical examination done for other medical reasons. They might grow aggressively or slowly or remian stable, hence, exhibiting wide range of behaviors in different individuals. Common complications of desmoid tumor include progression to agressive fibromatosis, involvement of intra-abdominal viscera that may lead to rupture of intestines, compression of the kidneys or ureters, rectal bleeding, compression of critical blood vessels such as the mesenteric vessels and the vena cava, amputation and loss of significant portions of foregut post-surgery. Five-year progression-free survival rate is 50% in patients with a primary or recurrent desmoid who are not treated initially with surgery, radiotherapy (RT), or systemic therapy. Massive and inoperable desmoids have become an important cause of morbidity and mortality in FAP patients post-colectomy. Desmoid tumor associated with FAP has the least favorable prognosis due to high recurrence rate. Whereas, non-FAP-associated intra-abdominal fibromatosis has a low recurrence rate after surgical resection.

Diagnostic study of choice

Definitive diagnosis of a desmoid tumor can only be established by histological examination of a biopsy specimen. Electron microscopy can be done which shows spindle cells of desmoids appearing as myofibroblasts.

History and Symptoms

Depending on size, location and spread of tumor, patients may remain asymptomatic for long time period or may show symptoms like painless/painful lump appearning as a swelling in affected area, nausea, vomiting, anxiety, loss of sleep, pain or soreness caused by compressed nerves or muscles, limping and decreased movement or range of motion or other difficulty using the legs, feet, arms or hands or other affected part of the body. Intra-abdominal desmoids can present with abdominal pain, abdominal mass, constipation due to intestinal obstruction, bowel ischemia, functional deterioration in an ileoanal anastomosis (especially in post-colectomy FAP patient), bloating, rupture of intestine, compression of the kidneys or ureters, rectal bleeding, and compression of critical blood vessels such as the mesenteric vessels and the vena cava.

Physical Examination

Common physical examination findings of desmoid tumor include lump or swelling in the affected area, abdominal tenderness, pallor, and elevated temperature.

Laboratory findings

Immunohistochemical staining of spindle cells of desmoid tumors are positive for nuclear beta-catenin, vimentin, alpha smooth muscle actin, muscle actin and negative for desmin, cytokeratins, and S-100. Antibodies like smooth muscle actin, desmin and KIT may be helpful in distinguishing desmoid tumors from other tumors. In addition, APC germline mutations may be performed in patients with sporadic desmoid tumors with no clinical or famililal signs of FAP but having a family history of colorectal carcinoma in at least one family member.

CT

CT scan can be done in order to define the relationship of desmoid tumor to adjacent structures, assess resectibility and find out the need for treatment. On CT scan, desmoid tumor is characterized by a homogeneously or focally hyperattenuating well circumscribed mass which may demonstrate enhancement following administration of intravenous contrast.

MRI

MRI is preferred over CT, especially for truncal and extremity desmoid tumors. On MRI, desmoid tumor has variable characteristics depending on their cellularity and fibrous content with loss of signal following fat saturation. They appear isointense/hypointense on T1 and hyperintense on T2.

Other Imaging Findings

Other imaging studies for the diagnosis of desmoid tumor include ultrasonography, which demonstrates tumor size and location. On ultrasonography, desmoid tumors appear as well-defined lesions with variable echogenicity, and ill defined/irregular borders. On color Doppler, desmoids appear like muscles, may be lobulated and may show vascularity. Plain radiographs and angiography may be of diagnostic help in some cases.

Medical Therapy

Wait and watch strategy is applied to desmoid tumors which are asymptomatic, unresectable, non-life threatening, not causing any significant impairment, and resectable tumors with increased morbidity associated with surgery.Different drugs including chemotherapeutic agents, NSAIDs, anti-hormonal agents and tyrosine kinase inhibitors can be used to shrink or stabilize the tumor size and to improve the symptoms. Radiation therapy and tumor ablation with heat, cold, microwave and/or high-frequency ultrasound waves can also be of therapeutic use as required.

Surgery

The goals of surgery include tumor removal and functional restoration at the tumor site. Standard surgical goal is wide local excision with a grossly negative microscopic margin followed by reconstruction of defect with skin graft, rotational muscle flap or free muscle flap. Abdominal wall resection may be required to close the defect and minimize the risk of hernias. Incomplete tumor removal or involved excision margins may lead to local recurrence in 25% to 40% of patients. Hence, because of high recurrence risk post-surgery, imaging of the tumor site with ultrasound or MRI scans may be recommended to closely monitor patient’s health on follow up visits after surgery.

Future or investigational therapies

Angiogenesis inhibitors and different chemotherapy agents are under investigation nowadays which might prove fruitful for treatment of desmoid tumors in future. Furthermore, mutational analysis for beta-catenin gene may soon be used to predict the recurrence risk and to aid in designing the individual therapies.

Reference

Template:WikiDoc Sources