Version July 2025
INTRODUCTION —
Desmoid tumors are locally aggressive tumors with no known potential for metastasis or dedifferentiation. These tumors are also referred to as aggressive fibromatosis or deep musculoaponeurotic fibromatosis and were previously called fibrosarcoma grade I of the desmoid type. The term "desmoid" originates from the Greek word "desmos," meaning band or tendon-like, and was first applied in the 1800s to describe tumors with a tendon-like consistency.
Although they lack the capacity to establish metastases, tumor-related destruction of vital structures and/or organs can be fatal, particularly when these tumors arise in patients with familial adenomatous polyposis (FAP; Gardner syndrome).
This topic review will discuss the epidemiology, risk factors, molecular pathogenesis, clinical presentation, and diagnosis of desmoid tumors. Treatment of desmoids is discussed elsewhere. (See "Desmoid tumors: Treatment".)
EPIDEMIOLOGY AND RISK FACTORS
Sporadic tumors — Desmoid tumors are rare and most arise sporadically. They account for approximately 0.03 percent of all neoplasms and fewer than 3 percent of all soft tissue tumors. The estimated incidence in the general population is two to four per million people per year [1].
Most patients diagnosed with a desmoid tumor are between the ages of 15 and 60. They are slightly more common in females than in males [2]. There is no significant racial or ethnic predilection.
Familial adenomatous polyposis and Gardner syndrome — In patients with familial adenomatous polyposis (FAP) desmoid tumors occur in 10 to 20 percent of patients [3-11]. FAP-associated desmoids represent between 5 and 15 percent of all desmoids [12-14]. FAP is caused by mutations in the APC (adenomatous polyposis coli) gene, located on chromosome 5q21-q22. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis", section on 'Genetics' and 'Screening for FAP in selected patients' below.)
Most desmoids that occur in the setting of FAP are intra-abdominal or located in the abdominal wall (image 1) [11]. The term Gardner syndrome is used to describe patients with FAP who develop extraintestinal manifestations such as desmoids. In some individuals desmoids may be the only manifestation of an APC mutation [15,16].
Pregnancy — Desmoid tumors have been associated with high estrogen states like those seen during pregnancy. However, the data linking high estrogen levels and desmoid tumors is largely based on anecdotal and retrospective reports [17]. The classic presentation during pregnancy is an abdominal mass that is separate from the uterus [18]. Trauma related to the pregnancy (including a scar from a prior Cesarean section [19]) and exposure to elevated hormone levels may both be contributory. (See "Desmoid tumors: Treatment", section on 'Considerations with pregnancy'.)
Antecedent trauma — Desmoid tumors have been associated with episodes of antecedent trauma. Up to 30 percent of patients with desmoid tumors have a history that involves antecedent trauma [20,21], particularly, as noted above, surgical intervention in patients with FAP. A similar relationship has been observed in some sporadically occurring desmoid tumors. In one series, an antecedent history of trauma at the tumor site was elicited in 28 percent of 32 primary desmoid tumors [22].
The association between antecedent trauma and the development of desmoids is particularly compelling in view of emerging data implicating a molecular connection between wound healing processes and fibroproliferative disorders of mesenchymal tissue. (See 'Etiology and molecular pathogenesis' below.)
ETIOLOGY AND MOLECULAR PATHOGENESIS —
The molecular events that lead to desmoid tumor formation are incompletely understood. Emerging evidence implicates dysregulated wound healing, clonal chromosomal changes, and involvement of the Wnt/beta-catenin pathway in many cases [23,24]. Since the natural history of desmoids is highly variable, an understanding of molecular pathogenesis would be useful from a therapeutic standpoint and is a subject of active investigation.
Certain mutations are more commonly associated with certain clinical presentations. For instance, desmoids in familial adenomatous polyposis (FAP) arise from APC inactivation and subsequent accumulation of beta-catenin in cells [25]. Sporadic desmoids typically arise from mutations in the gene for beta-catenin, CTNNB1 [26,27]. However, trisomies in chromosomes 8 and 20 have also been reported in sporadic desmoids. Pediatric desmoids can also have mutations in CTNNB1, but have also been associated with mutations in AKT1, BRAF, and TP53 [28].
Wnt/beta-catenin pathway — The Wnt/beta-catenin signaling pathway is thought to play a key role in the molecular pathogenesis of desmoid tumors, both those associated with FAP and sporadic tumors. The basic features of the Wnt signaling pathway are depicted in the figure (figure 1).
Beta-catenin plays an active role in transcription within mesenchymal cells [29]. The APC complex tightly regulates levels of beta-catenin in the cell by phosphorylation, which results in destruction of beta-catenin in the proteasome. Activation of the Wnt pathway initiated by binding of an external ligand causes inhibition of the kinase activity of the APC complex resulting in greater levels of beta-catenin in the cell. This non-phosphorylated beta-catenin translocates to the nucleus where it acts with other proteins to activate the transcription of genes such as CYCD1 and MYC, thereby promoting proliferation and enhanced survival [30]. Mutations in either the APC gene or the beta-catenin gene (CTNNB1) can result in dysregulation of the levels of beta-catenin in the cell that leads to its accumulation in the nucleus. Whole exome sequencing and genomic analysis identify alterations in CTNNB1 and Wnt pathway regulators in nearly all patient samples [31].
Data supports involvement in the Wnt signaling pathway in desmoid tumor formation. Mutations involving the Wnt signaling pathway are associated with the majority of sporadic desmoids [32-36]. In addition, beta-catenin protein levels and T-cell factor (Tcf) transcriptional activity are elevated in fibroblasts during the proliferative phase of wound healing, which is a known risk factor for the development of desmoids [34,37,38].
Activation of Wnt signaling through constitutively active beta-catenin has been shown to increase expression of midkine (also known as neurite growth-promoting factor 2 [NEGF2], a protein encoded by the MDK gene), which may have a role in pathogenesis in desmoid tumors. Midkine expression correlates with the recurrence of desmoids [39,40], but this awaits further confirmation. It is hoped that the elucidation of the central role of beta-catenin in the pathogenesis of desmoid tumors will lead to future therapeutic advances targeting this molecule [41].
●Adenomatous polyposis coli (APC) mutations – A normal APC protein prevents the accumulation of beta-catenin, a cytosolic and nuclear protein, by mediating its phosphorylation and resultant degradation. The majority of germline as well as sporadic mutations in the APC gene lead to premature truncation of the APC protein and loss of the beta-catenin regulatory domain. This allows beta-catenin to accumulate, bind to, and activate the transcription factor Tcf-4 [25]. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis", section on 'Genetics'.)
In general, desmoid tumors occur more frequently when mutations are in the 3' end of the APC gene, specifically between codons 1445 and 1580 [9,42-49]. For example, in one series of 36 patients from 20 families with FAP and mutations in codons 1445 to 1578, all developed desmoid tumors with the exception of three prepubertal children [45]. In another study of 953 FAP patients from 187 families, mutations between codons 1310 and 2011 were associated with a sixfold risk of desmoid tumors relative to the low-risk reference region (159 to 495) [46]. Similarly, another study of 269 patients found that desmoid tumors were present in 61 percent of patients with mutations between codons 1445 and 1580 compared with 18 percent of patients with mutations at sites 3' to that region [47].
Although desmoids can occur with mutations in any APC gene location, mutations of the APC gene on chromosome 5q are responsible for FAP [26,43,50]. More than 300 mutations have been described, most of which lead to frame shifts or premature stop codons, resulting in a truncated APC gene product.
●Mutations in the beta-catenin gene – Mutations in CTNNB1 have been found in sporadic desmoid tumors with variable prevalence (39 to 87 percent); however, other studies place the prevalence estimate at around 85 percent [30]. CTNNB1 gene mutations are therefore the most common route of Wnt pathway activation in desmoids. Phosphorylation of beta-catenin is mediated by a portion of the protein encoded by exon 3 of CTNNB1 gene. Three specific mutations are encountered in desmoid tumors: T41A, S45F, and S45P. At least some data suggest that S45F mutations are associated with a higher rate of recurrence after resection of a primary desmoid tumor [51], although other data do not support a statistically significant difference in recurrence risk according to either CTNNB1 mutation status or the specific CTNNB1 mutation [52].
Trisomy 8 and 20 — Other genetic aberrations have been described in sporadic desmoids. As an example, nonrandom clonal chromosomal changes, particularly trisomy 8 and/or 20, occur in one-third or more of sporadic desmoid tumors [53-57]. Similar nonrandom genetic aberrations have been found in benign fibrous bone lesions (such as fibrous dysplasia), suggesting a similar pathogenesis [55]. Although the clinical relevance of these genetic abnormalities is unclear, their presence has been associated with a higher risk of local recurrence in some reports [53,54].
Mutations in AKT1, BRAF, and TP53 — While adult desmoid tumors are exclusively driven by Wnt/beta-catenin activation [58], pediatric desmoids can harbor additional mutations, suggesting a more complex molecular pathogenesis in this population. In addition to CTNNB1 mutations (64 percent), alterations were identified in AKT1 E17K (31 percent), BRAF V600E (19 percent), and TP53 R273H (9 percent) in a 28-patient study of pediatric desmoids [28]. These mutations can be present in pediatric desmoids that are CTNNB1 wild-type (36 percent) or in combination with CTNNB1 mutations (64 percent).
CLINICAL FEATURES
Clinical findings are as follows:
●General findings – Most desmoid tumors present as a deeply seated painless or minimally painful mass with a history of slow growth. Desmoid tumors can develop at virtually any body site, but three main anatomic sites are described: trunk/extremity, abdominal wall, and intra-abdominal (bowel and mesentery). Desmoid tumors may be multifocal at one site (typically the extremity [59]), but they rarely occur at different regions in the same patient.
Symptoms, if any, depend on the location of the tumor. Intra-abdominal desmoids can present with nausea, early satiety [60], intestinal obstruction, bowel ischemia, or functional deterioration in an ileoanal anastomosis (typically in a patient who has undergone colectomy for familial adenomatous polyposis [FAP]) [61-63]. Desmoids that develop on the trunk/extremity may present as a slow-growing, often painless, mass.
●Differences in presentation of FAP versus non-FAP-associated desmoid – FAP-associated tumors are typically located in the abdomen or abdominal wall. Non-FAP desmoids more commonly occur in the shoulder girdle, hip-buttock region, and the extremities, where the location is usually deep in the muscles or along fascial planes [20].
●Breast desmoids – Desmoid tumors are an unusual cause of a breast mass, and they may be mistaken for a primary or recurrent breast cancer. Many patients have a history of breast cancer or breast surgery. In a series of 32 patients with a breast desmoid, eight (25 percent) had a previous history of breast cancer, and 14 (44 percent) had prior breast surgery [64]. The spectrum of molecular abnormalities seen in breast desmoids is similar to that described for desmoid tumors of the abdomen, trunk, and extremities [35].
EVALUATION
Radiographic findings — We prefer magnetic resonance imaging (MRI) imaging, especially for truncal and extremity masses suspected to be desmoid tumors. However, computed tomography (CT) is also an acceptable alternative (image 1). There are no radiographic characteristics that can reliably distinguish desmoids from malignant soft tissue tumors. (See "Clinical presentation, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Imaging of the primary tumor'.)
MRI characteristics of desmoid tumors are variable and relate to their cellularity and fibrous content. Desmoids may be hypointense or isointense to muscle on T1-weighted images; they are predominantly hyperintense on T2-weighted images, but hypointense bands may be seen that represent dense collections of collagen bundles [65]. T2 hyperintensity may diminish over time as tumor cellularity decreases and collagen deposition increases [66]. With the administration of gadolinium, desmoids typically show moderate to marked enhancement, and the hypointense bands may become more apparent because collagen bundles are not enhanced by contrast material [67].
For suspected breast desmoids MRI is also the preferred test. In a series of 32 patients with a breast desmoid presenting as a palpable mass, the desmoid was seen on MRI in all eight patients who had the test versus mammography, which only detected the tumor in 6 out of 16 patients [64].
Ultrasound may sometimes be helpful in determining the extent of desmoids involving the chest or abdominal wall [68,69]. Desmoids frequently appear as oval, well or poorly defined solid soft tissue masses with variable echogenicity, and no central necrosis or calcifications. However, there are no pathognomonic sonographic features.
Laboratory findings — There are no laboratory studies or tumor markers that are specific to desmoids.
DIAGNOSIS —
Desmoid tumors should be suspected with slow-growing, usually painless masses. The diagnosis of a desmoid tumor can only be established, however, by histologic examination of a biopsy specimen. In the hands of an experienced pathologist, a core needle biopsy is usually sufficient for diagnosis. However, if there is discordance between radiologic appearances and core needle biopsy findings, then resection would be reasonable. In general, incisional biopsies should be discouraged.
Histologically, desmoids are characterized by a monoclonal [70] fibroblastic proliferation appearing as small bundles of spindle cells in an abundant fibrous stroma. The fibroblasts have a propensity to concentrate at the periphery of the lesion, and the cellularity is low. The infiltrative connective tissue process may resemble that of a low-grade fibrosarcoma, but the cells lack nuclear and cytoplasmic features of malignancy. There are usually few mitotic figures and necrosis is absent. Histologically, sporadic and familial adenomatous polyposis (FAP)-associated desmoids are indistinguishable.
Next-generation sequencing is reported to be highly sensitive for the detection of CTNNB1 mutations in desmoid-type fibromatoses [31], and can be obtained from a core needle biopsy specimen. Even in true CTNNB1 wild-type tumors (by next-generation sequencing), genomic alterations that result in Wnt activation (such as chromosome 6 loss/BMI1 mutation) may be present [58] and can aid molecular evaluation of these tumors.
Immunohistochemistry may aid the histologic diagnosis. The spindle cells usually stain for vimentin and smooth muscle actin and nuclear beta-catenin but are generally negative for desmin, cytokeratins, and S-100. (See 'Wnt/beta-catenin pathway' above.)
Nuclear beta-catenin immunoreactivity supports the diagnosis of a desmoid tumor; positive staining was identified in 80 and 67 percent of sporadic and FAP-associated desmoids in one large series [71]. However, it is not definitive because other entities (superficial fibromatoses, low-grade myofibroblastic sarcomas, solitary fibrous tumors) also stain for nuclear beta-catenin [71]. Furthermore, beta-catenin negativity does not preclude the diagnosis of fibromatosis.
FURTHER EVALUATION
Screening for FAP in selected patients — Given the association of desmoids and familial adenomatous polyposis (FAP), it is important to obtain an accurate family history, particularly of colon cancer, after a diagnosis of a desmoid tumor. The approach to patients with a known family history of FAP is discussed elsewhere. (See "Familial adenomatous polyposis: Screening and management of patients and families".)
For others, we restrict screening for FAP to an "enriched population" of individuals with desmoid tumors who have a higher likelihood of having FAP. Our practice is to discuss colonoscopy and germline genetic testing with patients with desmoid tumors who have at least two of the following risk factors (listed below, with incidence of FAP in parentheses) [72]:
●Age <40 years (11 percent)
●Intra-abdominal or retroperitoneal tumors (5.4 percent)
●Multifocal disease (29 percent)
●Family history of colorectal cancer (8 percent)
However, practice is variable. Some centers recommend screening for FAP (colonoscopy, genetic screening) in patients with intra-abdominal or truncal desmoid tumors [14]. However, the chance of discovering FAP in patients who develop a desmoid without a prior history of FAP is relatively low (4 to 5 percent in two separate series [14,72]), and in our view, this does not justify screening for FAP in all individuals with an intra-abdominal or truncal desmoid tumor.
No staging studies needed — There is no need to obtain staging radiographic studies of any other site because desmoids lack the propensity for regional or distant spread.
There is no commonly used or agreed upon staging system for desmoids. The eighth edition of the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system for soft tissue sarcomas specifically excludes desmoids. (See "Clinical presentation, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Staging'.)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Soft tissue sarcoma".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Soft tissue sarcoma (The Basics)" and "Patient education: Familial adenomatous polyposis (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Natural history – Desmoid tumors (also called aggressive fibromatosis) are benign, slowly-growing fibroblastic neoplasms with no metastatic potential but a propensity for local recurrence, even after complete surgical resection. The natural history of desmoid tumors is prolonged, variable, and unpredictable. Despite being histologically benign, they are locally infiltrative and, uncommonly, can cause death through destruction of adjacent vital structures and organs. (See 'Introduction' above.)
●Risk factors – Risk factors for desmoid tumors include the following:
•Familial adenomatous polyposis – The risk of desmoids is increased in patients with familial adenomatous polyposis (FAP). Desmoid tumors occur in 10 to 20 percent of patients who have FAP. (See "Familial adenomatous polyposis: Screening and management of patients and families".)
•Desmoid tumors and pregnancy – Desmoid tumors have been associated with high estrogen states like those seen during pregnancy. However, the data linking high estrogen levels and desmoid tumors is largely based on anecdotal and retrospective reports. (See 'Pregnancy' above.)
•Antecedent trauma – Up to 30 percent of patients with desmoid tumors have a history that involves antecedent trauma.
●Etiology and molecular pathogenesis – The molecular events that lead to desmoid tumor formation are incompletely understood. Emerging evidence implicates dysregulated wound healing, clonal chromosomal changes, and involvement of the Wnt/beta-catenin pathway in many cases. (See 'Etiology and molecular pathogenesis' above.)
●Clinical features – Most desmoid tumors present as a deeply seated painless or minimally painful mass with a history of slow growth. Desmoid tumors can develop at virtually any body site, but three main anatomic sites are described: trunk/extremity, abdominal wall, and intra-abdominal (bowel and mesentery). FAP-associated desmoids typically occur in the abdominal wall or intra-abdominally. (See 'Clinical features' above.)
●Radiographic findings – We prefer MRI imaging to evaluate suspected desmoid tumors, especially for truncal and extremity masses. However, CT is also an acceptable alternative. (See 'Radiographic findings' above.)
●Diagnosis – The diagnosis of a desmoid tumor can only be established by histologic examination of a biopsy specimen. In the hands of experienced pathologists, tissue from a core biopsy is typically sufficient to make the diagnosis. (See 'Diagnosis' above.)
●Screening selected patients for FAP – We offer colonoscopy and germline genetic testing for FAP to patients with desmoid tumors who have two or more of the following risk factors for FAP:
•Age <40
•Intra-abdominal or retroperitoneal tumors
•Multifocal disease
•Family history of colorectal cancer (see 'Screening for FAP in selected patients' above)
●Staging – There is no commonly used or agreed upon staging system for desmoids. (See 'No staging studies needed' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Thomas F DeLaney, MD, who contributed to an earlier version of this topic review.
