Desmoid tumors are mesenchymal neoplasms which are considered locally invasive but non-metastasizing. They are also known as aggressive fibromatosis. Even though they do not metastasize, they are locally invasive and have a high rate of local resection even after complete resection. Management of Desmoid tumors requires a difficult decision for the patient, physician, and surgeon due to the extent of surgical resection needed, high local recurrence risk, and long natural history.
Most desmoid tumors occur sporadically, and 85% have a mutation in CTNNB1 encoding beta-catenin pathway. The three distinct mutations identified are 41A, 45F, and 45. Mutation 45F is associated with a high risk of recurrence. The 5-year recurrence-free survival was 23% for 45F, 57% for 41A, and 68% for no mutation. Desmoid tumor is seen at increased frequency in familial adenomatous polyposis (FAP), mostly abdominal FAP caused by a mutation in APC gene. Desmoids arising in FAP have a prediction for the prior surgical site, and previous surgery is a risk factor. In patients who are treated with prophylactic colectomy, desmoid is the more important cause of morbidity and mortality than colon cancer. The desmoid tumor occurs with increased frequency in the female during or after pregnancy, and anecdotal evidence suggests abdominal wall trauma and high estrogen states are the possible reason. Pregnancy-associated desmoids have overall better outcomes.
These tumors are rare and account for less than 3% of all soft tissue sarcomas. The prevalence rises to as high as 13% in patients with familial adenomatosis of the colon. Women are more affected than men, especially after childbirth. In persons at risk, the desmoid tumor can arise after elective abdominal surgical procedures. No significant racial, ethnic, or geographical predilection has been linked to the desmoid tumor. It is more common in the 15 to 50 age group, but it can occur at any age group.
The exact molecular pathogenesis of desmoid tumor is not entirely understood. Evidence suggests that components of the WNT pathway, namely APC and beta-catenin, are involved in pathogenesis. While in FAP, APC inactivation leads to beta-catenin accumulation; in sporadic, desmoids arise from a mutation in the gene for beta-catenin, CTNNB1.
The characteristic feature of the desmoid tumor is small bundles of spindle cells in an abundant, fibrous stroma. These spindles are composed of proliferating monoclonal fibroblasts. The cellularity is low, and cells lack nuclear and cytoplasmic features of malignancy. Regarding immunohistochemistry, the spindle cells stain for vimentin, smooth muscle actin, and nuclear beta-catenin and are negative for desmin, cytokeratin’s, and S-100. Immunoreactivity to nuclear beta-catenin supports the diagnosis of a desmoid tumor. Next-generation sequencing can be very sensitive for the detection of CTNNB1 mutations in desmoid-type fibromatoses.
Most desmoids present as slow-growing, deep-seated, painless, or minimally painful masses. Common sites of the presentation include the abdominal wall, intraabdominal and trunk, or extremity; but it can occur anywhere. FAP patients with a predilection for intraabdominal desmoids predominate. A multifocal presentation is rare. Breast desmoid can be associated with surgery or implants. One in four cases has a history of trauma or surgery at the site of desmoid.
Imaging studies like CT scan and MRI can be done during diagnosis and follow up. Imaging can determine the extent of the tumor, which organs are infiltrated, and a surgical resection plan. MRI seems to be more useful than CT scan in helping to establish the extent of tumor and relationship to nearby organs. On T1-weighted images, desmoids are hypo- or isointense to muscle, while on T2-weighted images they are hyperintense. With gadolinium contrast, desmoid tumor shows moderate enhancement with hypo-intense bands because of collagen bundles.
The treatment of desmoid can be divided broadly into asymptomatic resectable, symptomatic resectable, unresectable, and recurrent desmoids.
Asymptomatic Resectable: Retrospective evidence suggests that observation in the form of “wait and watch” approach may be a valid option for asymptomatic, small desmoids located in the region when growth would not lead to functional limitation or change the outcome of surgery. If the tumor progress, definitive therapy in the form of surgery or radiation therapy (RT) can be done.
Symptomatic Resectable: The main modality of treatment for symptomatic resectable desmoid is surgery. The risk of recurrence depends on following factors: (1) size, (2) location of the mass, (3) the age of the patient, and (4) margin status. Extra-abdominal tumors have a higher rate of recurrence than abdominal tumors. A controversy remains regarding the positive resection margins and risk of recurrence. Based on recent evidence, if physical therapy is followed carefully, there is no difference in outcomes between R0 and R1 resection. So, if achieving R0 resection would lead to excessive morbidity, then R1 resection is acceptable. One meta-analysis concluded that adjuvant radiotherapy appears to reduce the risk of recurrence after incomplete surgical resection, particularly in patients with recurrent tumors. Therefore, postoperative RT can be considered in high-risk patients.
Unresectable Desmoid: The options for unresectable tumor include systemic therapy, radiotherapy, and observation. Radical resection such as amputation should be avoided at all costs but is a reasonable option for the unresectable lesion. Response to RT is slow, and the continued response was seen even after 3 years. In a multicenter, phase 2 study at a median follow up of 4.8 years, the local control rate was 81.5%.
Systemic Therapy: Systemic therapy such as the use of nonsteroidal anti-inflammatory drugs like sulindac; celecoxib, hormonal agents like tamoxifen; biologics like l=interferomn; tyrosine kinase inhibitors like imatinib or sorafenib; and chemotherapy like liposomal doxorubicin, vinblastine, and methotrexate have shown promising results. In a phase 2 study for unresectable desmoid tumors, imatinib led to a one-year PFS of 66%. Long-term follow-up suggested that 2-year PFS and OS were 55% and 95% respectively. One study showed a good disease response rate with a combination of sulindac and tamoxifen, especially in FAP-associated desmoid. Doxorubicin-based chemotherapy has proven to be well tolerated and useful in advanced desmoid tumors.
Desmoids may occasionally be encountered by the nurse practitioner, primary care provider or the internist. Because the diagnosis and treatment is complex, it is important to consult with an oncologist, pathologist, and a radiologist. The treatment of desmoid can be divided broadly into asymptomatic resectable, symptomatic resectable, unresectable, and recurrent desmoids. These lesions do not normally respond well to chemotherapy and radiation and surgery is the only treatment. However, recurrences are common. The prognosis for most patients is guarded. (Level V)
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