What is a desmoid tumor

A desmoid tumor also called desmoid fibromatosis or aggressive fibromatosis, is an abnormal growth that arises from connective tissue, which is the tissue that provides strength and flexibility to structures such as bones, ligaments, muscles, lung, liver, blood vessels, heart, kidneys, skin, intestines, etc. Desmoid tumors are fibrous, much like scar tissue. A desmoid tumor is a benign locally invasive soft tissue tumor. Desmoid tumors are generally not considered cancerous (non-malignant) because they do not spread to other parts of the body (metastasize); however, they can aggressively invade the surrounding tissue and can be very difficult to remove surgically with a high recurrence rate, even after apparently complete removal.

The clinical course of desmoid tumor (desmoid fibromatosis) varies widely; in some instances, the lesions remain stable for long periods with no intervention, while in others desmoid tumors grow rapidly ¹.

One very interesting aspect of desmoid tumors is that on some occasions they can shrink or become quiescent (deep sleep) without any therapy. Other desmoid tumors may be stable or grow very slowly over a period of months and years. A small subset of desmoid tumors may be aggressive and grow rapidly. In conclusion, these tumors exhibit a wide range of behaviors and therefore their management is very different.

Desmoid tumors are rare, accounting for < 3% of soft tissue tumors. Desmoid tumors annual incidence is estimated to range between 1/250,000-1/500,000 people worldwide. In the United States, 900 to 1,500 new cases are diagnosed per year. Sporadic desmoid tumors are more common than those associated with familial adenomatous polyposis (FAP). Desmoid tumors predominantly affect women than in men (2:1) and can occur between the ages of 15-60 years, but frequently during early adolescence and with a peak age of about 30-40 years. There is no significant racial or ethnic distribution.

Typically, a single desmoid tumor develops, although some people have multiple desmoid tumor. The tumors can occur anywhere in the body. Desmoid tumors that form in the abdominal wall from muscle fascia or the abdominal/chest wall are called abdominal desmoid tumors; those that arise from the tissue that connects the abdominal organs in the mesentery or retroperitoneum are called intra-abdominal desmoid tumors; and tumors found in other regions of the body are called extra-abdominal desmoid tumors. Extra-abdominal tumors occur most often in the shoulders, upper arms, and upper legs.

The most common symptom of desmoid tumors is pain. Usually, desmoid tumors are firm and smooth palpable masses upon discovery. Depending on the size and location of the tumor, symptoms may include pain, fever, and functional impairment or loss of function of the organ involved, which are often caused by growth of the tumor into surrounding tissue. Desmoid tumors may appear after surgical resections, typically after Caesarian section. Intra-abdominal desmoid tumors are often observed in patients with an association of familial adenomatous polyposis (FAP) or Gardner syndrome. Intra-abdominal desmoid tumors can block the bowel, causing constipation. Extra-abdominal desmoid tumors can restrict the movement of affected joints and cause limping or difficulty moving the arms or legs.

Most (~85 percent) desmoid tumors are sporadic and are not inherited. Sporadic tumors result from gene mutations that occur during a person’s lifetime, called somatic mutations. A somatic mutation in one copy of the gene is sufficient to cause the disorder. Somatic mutations in either the CTNNB1 or the APC gene can cause sporadic desmoid tumors.

Familial desmoid tumor cases (about 5-10 %) are associated with an inherited form of colon cancer called familial adenomatous polyposis (FAP). An inherited mutation in one copy of the APC gene causes familial adenomatous polyposis (FAP) and predisposes affected individuals to develop desmoid tumors. The desmoid tumors occur when a somatic mutation occurs in the second copy of the APC gene. Patients with mutations in the APC gene are predisposed to forming hundreds of polyps in the intestines and go on to develop colon cancers. Patients with familial adenomatous polyposis (FAP) are often recommended to undergo surgical removal of their intestines. These patients are at a very high risk of developing intra-abdominal desmoid tumors which can arise deep in the abdomen or in the abdominal wall in addition to abnormal growths (called polyps) and cancerous tumors in the colon. In older scientific literature, the combination of FAP and desmoid tumors is termed Gardner’s Syndrome or the condition is sometimes called hereditary desmoid disease.

In some rare cases, desmoid tumors can occur in women who are pregnant. This happens during pregnancy or after a surgical delivery. Many believe that this is caused by a combination of elevated hormones and surgery, however, there is no strong scientific evidence to support this claim. The relationship between pregnancy and desmoid tumors is very rare and consists of mostly anecdotes in the scientific literature.

Other names for desmoid tumor

• aggressive fibromatosis
• deep fibromatosis
• desmoid fibromatosis
• familial infiltrative fibromatosis
• hereditary desmoid disease
• musculoaponeurotic fibromatosis

Figure 1. Abdominal desmoid tumor

Figure 2. Intra-abdominal desmoid

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Desmoid tumor survival rate

Local recurrence occurs in around 70 percent of cases. Prognosis depends on the type of tumor. Life expectancy is normal for abdominal and extra-abdominal tumors. However, it is lower in cases of intra-abdominal desmoid tumors due to complications such as intestinal obstruction, hydronephrosis or sepsis. Repeated surgical resections are associated with a greater risk of morbidity.

Desmoid tumor life expectancy

Desmoid tumors were treated surgically in 495 patients (between July 1, 1982, and November 1, 2011 with a median follow-up 60 months) at the Memorial Sloan Kettering Cancer Center. Of 439 patients undergoing complete gross resection, 100 (23%) had recurrence. Of 439 patients undergoing complete gross resection, 100 had recurrence. Among these, 92 (92%) had their recurrence within 5 years. Five-year local recurrence–free survival was 69% (Figure 3) ².

Size of the patient’s primary desmoid tumor was associated with outcome. Desmoid tumors over 10 cm in largest diameter were associated with 5-year local recurrence–free survival rates of 57% compared to 72% for tumors ≤5 cm and 74% for tumors >5 cm and ≤10 cm (Figure 3B). There was a striking association between site and local recurrence–free survival. Intra-abdominal, chest wall, and extremity tumors had relatively poor outcomes (5-year local recurrence–free survival 76%, 72%, and 60% respectively). Desmoid tumors in the neck, which were considered collectively with extremity lesions in the main analyses, behaved nearly identically to extremity tumors (5-year local recurrence–free survival 43% for neck versus 47% for lower extremity). Abdominal wall tumors had the best outcome (5-year local recurrence–free survival 90% [Figure 3C] vs. 34% in patients ≤25 y.o. with large, extremity tumors [n=11]). Only 8 of 79 patients with abdominal wall tumors had recurrence. All were 40 or younger, and 3 of the 8 had tumors over 10 cm. Only one abdominal wall desmoid tumor that recurred, a rectus sheath lesion, was <5 cm.

A multivariate analysis demonstrated that age, tumor size, and tumor site are independent predictors of recurrence. Margin status (R1 vs. R0) was not associated with altered outcome in the cohort as a whole or in subgroups defined by age or tumor site. However, among patients with small desmoid tumors (<5 cm), R0 resection was associated with longer local recurrence–free survival compared to R1 resection (76 vs. 60%). Margin was not associated with recurrence in larger lesions.

• For access to the Local Recurrence-Free Survival After Surgery tool based on data from patients treated at Memorial Sloan Kettering Cancer Center please go here: The Memorial Sloan Kettering Cancer Centerat https://www.mskcc.org/nomograms/sarcoma/desmoid

Figure 3. Desmoid tumor life expectancy – Recurrence-free survival in 439 patients undergoing complete gross resection of a desmoid tumor stratified by (A) patient age, (B) tumor size, and (C) tumor location.

[Source ²]

Adjuvant radiation therapy

The role of radiation therapy in desmoid tumors has been debated. In the same study as above ², there was no improvement in outcomes in patients who had received radiation therapy during the course of their treatment (5-year local recurrence–free survival 68% vs 72% without radiation; Figure 4A). Additionally, adjuvant radiation therapy was not significantly associated with improved local recurrence–free survival in any subset of tumors (stratified by size, site, and patient age at diagnosis) except extremity tumors. Adjuvant radiation was most commonly used for extremity tumors (in 23% of these patients), and radiation for extremity tumors was associated with a 15% absolute reduction in local recurrence; local recurrence–free survival among patients with extremity tumors was 71% with radiation vs. 56% without.

Figure 4. Desmoid tumor life expectancy in patients receiving adjuvant radiation

Note: (A) Recurrence-free survival in patients receiving adjuvant radiation versus those not treated with radiation. (B) Recurrence-free survival in patients treated before 1997, when 30% of patients received adjuvant radiation, versus during 1997 and later, when only 7% of patients received adjuvant radiation.

[Source ²]

Desmoid tumor causes

Desmoid tumors result from the proliferation of well-differentiated myofibroblasts or fibroblasts. The exact cause is still unknown, but they seem to have a multi-factorial origin with hormonal and genetic factors being involved. Somatic mutations in the CTNNB1 gene (3q21) encoding beta-catenin have been found in about 85 percent of sporadic desmoid tumors. In cases with familial adenomatous polyposis (FAP) as well as 10 to 15 percent of sporadic desmoid tumors, the tumors have been associated with mutations in the tumor suppressor gene APC (5q21-q22) encoding the adenomatous polyposis coli protein.

Mutations in the CTNNB1 gene or the APC gene cause desmoid tumors. Both genes are involved in an important cell signaling pathway that controls the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation).

The CTNNB1 gene provides instructions for making a protein called beta-catenin. As part of the cell-signaling pathway, beta-catenin interacts with other proteins to control the activity (expression) of particular genes, which helps promote cell proliferation and differentiation. CTNNB1 gene mutations lead to an abnormally stable beta-catenin protein that is not broken down when it is no longer needed. The protein accumulates in cells, where it continues to function in an uncontrolled way.

The protein produced from the APC gene helps regulate levels of beta-catenin in the cell. When beta-catenin is no longer needed, the APC protein attaches (binds) to it, which signals for it to be broken down. Mutations in the APC gene that cause desmoid tumors lead to a short APC protein that is unable to interact with beta-catenin. As a result, beta-catenin is not broken down and, instead, accumulates in cells. Excess beta-catenin, whether caused by CTNNB1 or APC gene mutations, promotes uncontrolled growth and division of cells, allowing the formation of desmoid tumors.

Desmoid tumor symptoms

Desmoid tumors can develop at virtually any site in the body. Desmoid tumors can have a wide range of clinical symptoms or no symptoms at all. Many desmoid tumors are accidentally picked up on a scan or a routine physical exam done for other medical reasons. Many people have no symptoms at the time of diagnosis or even after many years. Some people feel a range of symptoms that range from slight to severe pain, decrease in their movement or range of motion, swelling of the area affected by the desmoid tumor, loss of sleep, anxiety and many other symptoms.

Desmoids deep inside the abdomen or pelvis can also be entirely without symptoms or they can cause bloating, severe pain, rupture of intestines, compression of the kidneys or ureters or rectal bleeding. They can compress critical blood vessels such as the mesenteric vessels and the vena cava. It is important to know that the desmoid tumors that present superficially on the abdominal wall behave much differently than the ones that are deep inside the abdomen or pelvis.

Desmoid tumor diagnosis

Initial diagnosis is based on imaging techniques (computed tomography [CT scan] and magnetic resonance imaging [MRI scan]) revealing the presence of an infiltrative growing mass. Diagnosis is confirmed by tumor biopsy showing abundant collagen surrounding elongated spindle-shaped cells containing small and regular nuclei and pale cytoplasm. Immunohistological examination shows expression of muscle cell markers (e.g. actin, desmin, vimentine) and absence of CD34. Moreover, diagnosis can be confirmed by screening for mutations of CTNNB1.

In rare circumstance, a biopsy may not be safe or feasible. When a biopsy is recommended, there are a variety of options which include: a core needle biopsy which takes a small piece, usually 1 mm wide by 10 mm long; and, surgical biopsies which may take a portion of the tumor (“incisional biopsy”) or may remove the entire visible tumor (“excisional biopsy”). While an excisional biopsy may remove all visible tumor, when pursuing this option it is necessary to discuss with your surgeon the possibility of leaving some tumor behind – either gross or microscopic – and most importantly, what are the short-term and long-term side effects of the excisional biopsy. The pathologist takes very fine sections of the biopsy material and examines them under the microscope looking for special features that define desmoid tumors.

Desmoid tumor treatment

Watchful waiting

Desmoid tumors display a wide range of behaviors and often unpredictable clinical course. This can range from shrinking spontaneously without any intervention, to remaining stable or growing rapidly. In some circumstances especially when patients are asymptomatic, it is reasonable to just watch the tumor carefully with images and/or physical examination. How often you need scans and/or physical exams during a “wait and watch” period will vary for each situation and your treating physician will discuss this with you.

Surgery

Complete surgical resection remains the therapeutic mainstay of desmoid tumors. However, it can be difficult during surgery to determine the outer extent of the tumor. This is because desmoid tumors are not well encapsulated and they often intertwine with other tissues. Historically, most people with desmoid tumors underwent some form of surgery. Over the last few decades, it is increasingly being recognized that these tumors have a high risk of returning even with surgery. While statistics may vary, about 25 to 40 percent of patients who undergo surgery can have a local recurrence (return at or near the original site). The goal of surgery is to remove the entire tumor and minimize the risk of recurrence. Scientific research has shown that some types of desmoid have much higher risk of recurrence after surgery than others. This can be calculated using an online calculator (MSKCC nomogram here: https://www.mskcc.org/nomograms/sarcoma/desmoid). All nomograms are estimations and not always accurate. When making a decision to undergo surgery, you have to have an open conversation with your surgeon about the risk of recurrence, time to recurrence and the short-term and long-term side-effects of the surgery. Increasingly, surgery is falling out of favor for desmoid tumors given their high risk of recurrence and other side effects. In some circumstances, surgery may be the best option and can result in great outcomes including a cure. In conclusion, the decision to undergo surgery is a complex one and should be weighted carefully. As desmoid tumors often recur, a surveillance strategy every 3-6 months is essential.

Desmoid tumors frequently invade a limb’s vital nerves and blood vessels. Because of this, full removal of the tumor may impair function in the surrounding area. Limited surgery, combined with additional treatments, such as radiation or chemotherapy, may be successful in these cases.

For unresectable desmoid tumors or those not amenable to surgical resection with R0 (microscopic tumor clearance) intent or accompanied by an unacceptable function loss, non-surgical treatments comprise radiotherapy, anti-estrogen therapy, non-steroidal anti-inflammatory agents, chemotherapy (e.g. methotrexate, vinblastine/vinorelbine, pegylated liposomal doxorubicin) and/or tyrosine kinase inhibitors (e.g. imatinib, sorafenib).

Hormone therapy

Desmoid tumors are known to have estrogen receptors. This means that their growth may be stimulated by the hormone estrogen. Drugs that block the hormonal stimulation of the tumor are sometimes effective at controlling the tumor growth.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Medications such as ibuprofen and naproxen, as well as a special kind of NSAID called a COX-II inhibitor, can be effective in treating desmoid tumors.

Radiation Therapy

Radiation therapy may be an effective option for a few patients in special circumstances. The dose and duration of radiation is highly variable and your radiation oncologist will discuss that with you. Both the short-term and long-term side effects from radiation should be carefully considered. In general, many sarcoma experts do NOT recommend radiation out of the concern for developing a new (aggressive) cancer due to the radiation. In conclusion, the decision to undergo radiation is a complex one and needs to be discussed carefully.

Chemotherapy

Low doses of chemotherapy drugs are effective in management of desmoid tumors. Long-term use of these drugs is difficult, however, due to their cumulative effects in the body.

Thermal ablation

Thermal ablation does not use radiation but rather heat or cold to kill the desmoid tumor. This is an emerging technique where needles are inserted into the tumor and thermal waves are used to heat or freeze the tumor. High-frequency ultrasound is another technique which uses ultrasound waves to destroy the tumor. These techniques are only suitable for certain types of desmoid tumors. Overall, this is a relatively new technique and the experience to date is limited to a few centers, and the long-term results are not yet known. In conclusion, the decision to undergo ablation (hot, cold or ultrasound) is a very technical and complex one and needs to be discussed carefully with the interventional radiologist. Only a few highly specialized centers have expertise in treating desmoid tumors using these techniques.

Medical Therapy

There is no single accepted medical treatment for desmoid tumors. Based on your medical health and nature of your desmoid tumor, your medical oncologist will discuss with you the best options for you. Numerous reports of individual cases show shrinkage or stabilization of tumor size or at least improvement in symptoms after a very wide variety of treatments. Chemotherapy is a chemical drug that is usually injected in the veins. A few chemotherapies that are commonly used include: doxorubicin, Doxil (liposomal doxorubicin), dacarbazine, methotrexate, vinorelbine and vinblastine. These are toxic chemotherapies that can have a wide range of short and long term side effects. There have also been anecdotal reports of using sulindac (non-steroidal anti-inflammatory) or anti-hormonal agents such as tamoxifen, however the true efficacy of these drugs has not been fully investigated in clinical trials. A new class of agents called tyrosine kinase inhibitors (e.g. sorafenib) has shown benefit in desmoid tumors by shrinking the tumors or slowing down the growth. These are pills taken by mouth at home.

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2. Crago AM, Denton B, Salas S, et al. A prognostic nomogram for prediction of recurrence in desmoid fibromatosis. Annals of surgery. 2013;258(2):347-353. doi:10.1097/SLA.0b013e31828c8a30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096320/[↩][↩][↩][↩]