Practice Essentials
Desmoid tumors are cytologically bland fibrous neoplasms originating from the musculoaponeurotic structures throughout the body. The term desmoid, coined by Muller in 1838, is derived from the Greek word desmos, which means tendonlike.
Desmoid tumors often appear as infiltrative, usually well-differentiated, firm overgrowths of fibrous tissue, and they are locally aggressive. The synonym aggressive fibromatosis describes the marked cellularity and aggressive local behavior. This course and the tendency for recurrence make the treatment of these relatively rare fibrous tumors challenging. [1]
Signs and symptoms
Also see Physical Examination.
Although desmoid tumors can arise in any skeletal muscle, they most commonly develop in the anterior abdominal wall and shoulder girdle.
Retroperitoneal neoplasms are more common in familial polyposis coli and Gardner syndrome after abdominal surgery than in other conditions. [2]
Clusters of cases in families without evidence of any associated syndromes have also been reported. [3]
A history of trauma (often surgical) to the site of the desmoid tumor is elicited in 1 in 4 cases. [4] . Implant-associated breast desmoid tumors may occur. [5]
Diagnostics
See Workup for a full discussion.
Immunostaining with vimentin, alpha smooth muscle actin, muscle actin, and desmin are helpful in distinguishing the tumors in the differential diagnosis of desmoid tumors.
Management
See Treatment for a full discussion.
Primary surgery with negative surgical margins is the most successful primary treatment modality for desmoid tumors. Positive margins after surgery reflect a high risk for recurrence. [6] Surgery plus the administration of nonsteroidal anti-inflammatory medication, hormonal therapy, and cytotoxic chemotherapy is sometimes used, the latter being the most effective pharmacological approach. [7] Since desmoid tumors do not metastasize, many approaches are nonoperative in nature. [8] Since desmoid tumors may stabilize and regress, active observation is an option.
Pathophysiology
Although desmoid tumors most commonly arise from the rectus abdominis muscle in postpartum women and in scars due to abdominal surgery, they may arise in any skeletal muscle. Desmoid tumors tend to infiltrate adjacent muscle bundles, frequently entrapping them and causing their degeneration. [9] They may be derived from mesenchymal stem cells. [10] Although fixation to musculoaponeurotic structures is apparent, the overlying skin is normal. The myofibroblast is the cell considered to be responsible for the development of desmoid tumors (see Procedures).
Gardner syndrome or familial adenomatous polyposis (FAP) is characterized by colorectal adenomatous polyps and soft and hard tissue neoplasms. The former may number in the hundreds to thousands. Gardner syndrome was regarded as a separate disease until the identification of the APC (adenomatous polyposis coli) gene, at which point mutations in the APC gene were recognized as the underlying cause of both Gardner syndrome and FAP. Some authors regard Gardner syndrome as a subset of FAP, and some have even suggested that the term Gardner syndrome be replaced by FAP. Additionally, evidence also exists for a genetic predisposition to desmoid tumors in FAP, independent of the APC mutation.
Desmoid tumors occur at a rate of 10-15% in patients with FAP, an autosomal inherited disease caused by germline mutations in the APC gene. Sporadic forms have no hereditary background. [11] Desmoid tumors show biallelic APC mutation, with one change usually occurring distal to the second beta-catenin binding/degradation repeat of the gene (3' to codon 1399). [12, 13] The relationship between extracolonic manifestations and the site of the APC mutation suggests a specific role of the APC protein in different tissues. However, unknown genetic factors independent of APC may be important in the susceptibility to desmoid tumors in patients with FAP.
In desmoid tumors, one of the two mutations usually occurs distal to the second beta-catenin binding/degradation repeat of the gene (3' to codon 1399). Catenin and catenin-binding genes have been found to be associated with neoplastic processes in a number of ways. Independent predictors of increased desmoid risk in one study were said to be (1) germline mutation distal to codon 1399, (2) any family history of gastrointestinal disease, and (3) a strong family history of desmoid tumors. Most sporadic desmoid tumors are linked with β-catenin gene mutations. [14]
The relationship between certain extracolonic manifestations and sites of the APC mutation suggests specific roles of the APC protein in different tissues. These different roles may correspond to specific sites of missense mutations in the APC gene. For example, dental manifestations of Gardner syndrome have been suggested to be associated with mutations at or near codon 1556. However, the influence of unknown genetic factors independent of APC in susceptibility to desmoid tumors in FAP needs to be explored.
FAP results from a germline mutation in the APC gene. Desmoid tumors are associated with a biallelic APC mutation in the affected tissue. This usually results from a spontaneous somatic mutation in the unaffected APC gene of a single cell in a patient with the FAP syndrome. This process is an example of the Knudsen "two hit" hypothesis, in which a tumor suppressor gene, such as APC, must be biallelically mutated in order for a specific type of tumor to occur.
In genetically normal individuals, with normal germline genes, this necessitates a rare combination of events, such that at least 2 somatic mutations must occur in both alleles of a single tumor suppressor gene, in this case the APC gene. In FAP syndrome patients, one APC germline gene is already mutated in every cell in the body (barring a rare reverse somatic mutation in some cells), and, therefore, only one new somatic mutation is required in the opposite APC gene for the tumor to develop.
FAP may be associated with mutations in the APC gene, but mutations in several other genes, particularly mismatch DNA repair genes, which are primarily responsible for ensuring integrity of polymerases responsible for DNA replication, may also result in familial colonic polyposis. These patients with familial colonic polyposis typically do not show other manifestations of Gardner syndrome. Conversely, extracolonic manifestations characteristic of Gardner syndrome may occur independent of intestinal polyps or a mutation in the APC gene. Nuclear localization of β-catenin may be evident in pediatric desmoids regardless of mutation status, with most showing somatic mutations in CTNNB1. [15] However, many harbor germline mutations in APC. CTNNB1 mutations are common in sporadic desmoid tumors. [16] CTNNB1 mutations and APC mutations are mutually exclusive in this entity; accordingly, the presence of a somatic CTNNB1 mutation facilitates exclusion of a syndromic disorder. [17]
Etiology
The cause of desmoid tumors is uncertain and may be related to trauma or hormonal factors, or they may have a genetic association.
The familial polyposis gene on chromosome 5 has been extensively studied. [13, 18]
An endocrine etiology is suggested. Desmoid tumors most commonly appear in young women during or after pregnancy. The tumors regress during menopause [19] and after tamoxifen treatment. [20] Desmoid tumors may regress after exposure to oral contraceptives. [21]
The proliferative response of fibroblasts to estrogen has been established. [22]
Epidemiology
Frequency
Overall, desmoid tumors are reported to account for 0.03% of all neoplasms. [23] When present in patients with familial polyposis of the colon, the prevalence of desmoid tumors is as high as 13%. [24]
Sex
Desmoid tumors most commonly occur in women after childbirth. Desmoid tumors are twice as common in females than in males; however, 60 patients were described, [25] and the female-to-male ratio was 1.2:1. In children, the sex incidence is equal.
Age
Although desmoid tumors are more common in persons aged 10-40 years than in others, they do occur in young children and older adults. Sixty patients were described by Lee et al in 2006, with an average age at diagnosis of 41.3 years. [25]
Prognosis
Despite their benign histologic appearance and negligible metastatic potential, the tendency of desmoid tumors to cause local infiltration is significant in terms of (1) deformity, morbidity, and mortality resulting from pressure effects and (2) potential obstruction of vital structures and organs.
Local desmoid tumor recurrence rates are reported to be as high as 70%. A positive surgical margin is a significant risk factor for recurrence. [26, 27] The prognostic value of miRNA expression profiling has been suggested as a way to delineate surgical candidates from those who might be monitored without treatment. [28]
Intra-abdominal desmoid tumors may kill patients with familial adenomatous polyposis. [29] Five-year survival rates of such patients with stage I, II, III, and IV intra-abdominal desmoid tumors were found to be 95%, 100%, 89%, and 76%, respectively. The 5-year survival rate of stage IV patients with severe pain/narcotic dependency, tumor size larger than 10 cm, and need for total parenteral nutrition was only 53%.
A study of 179 patients with primary, sporadic desmoid tumors who had complete surgical resection found that those with the S45F mutation had a greater tendency for local recurrence than those without it. [30]
-
Bland fibrocytic cells of a desmoid tumor growing in a haphazard-to-storiform manner and producing collagen (hematoxylin-eosin, original magnification X100).
-
Desmoid tumor spindle cells invading skeletal muscle (hematoxylin-eosin, original magnification X100).
-
Dermoid tumor spindle cells surrounding and destroying skeletal muscle cells (hematoxylin-eosin, original magnification X100)
