Epidemiology (incidence rates) of
Desmoid Tumors 
Desmoid tumors are uncommon. The estimated incidence in the general population is 2-4 per million people per year. In the United States, this would represent approximately 900 new tumors annually. The numbers are likely to be far greater because of the lack of recognition of the type of tumor by pathologists and the various terminologies used to describe it . Because of inconsistent and inaccurate reporting procedures, accurate statistics about the number of desmoid tumor cases have not been kept.
Individuals between the ages of 15 and 60 are most often affected. Desmoids are rare in the young and in the elderly. They are slightly more common in women than in men, and there is no significant racial or ethnic distribution.
Desmoid tumors may occur sporadically, or in association with familial adenomatous polyposis (FAP) (a genetic abnormality). The combination of familial polyposis and desmoid tumors, along with other non-intestinal manifestations, has been referred to as Gardner’s syndrome. The term Gardner’s syndrome is not used as frequently as in the past, because it is now recognized that patients with familial polyposis with or without desmoid tumors may have the same genetic abnormality – thus, there is not a separate “syndrome” just for people with polyposis and desmoids.
Etiology (causes) of Desmoid Tumors
The cause of most desmoid tumors is unknown. The linkage between desmoid tumors and familial polyposis has given us some major clues about the genetic basis of at least some desmoids. The estimated risk of developing a desmoid tumor in patients with FAP is between 4 and 20 percent. Familial polyposis is caused by a mutation in the APC gene. People with this mutated gene develop intestinal polyps that frequently turn into cancers, as well as desmoid tumors and other non-intestinal manifestations. Different mutations in the APC gene have been discovered. Some mutations seem to be less severe, with fewer intestinal polyps, while others are associated with thousands of polyps at a very young age as well as desmoid tumors and other manifestations.
The desmoid tumors that do occur in patients with polyposis frequently develop in areas of previous surgical procedures, such as in the abdomen after partial or complete removal of the large intestine. Surgical trauma is also a possible factor in abdominal wall desmoids, which tend to occur in women during or following pregnancy, often in the scar of a ceasarian section incision. Trauma related to pregnancy and surgery and exposure to elevated hormone levels may both be contributory.
Clinical Presentation
Desmoid tumors usually manifest themselves as a painless or slightly painful mass (lump). Desmoid tumors can develop virtually at any body site. Superficial desmoids tend to be less aggressive than deep desmoids (abdominal, extra-abdominal, mesenteric). Desmoids inside the abdomen can cause gastrointestinal symptoms: change in bowel habits, pain, or rectal bleeding. They can invade the large mesenteric vessels and the vena cava. Desmoid tumors may have multiple sites of origin on an extremity, but they rarely occur at different regions in the same patient (although this can happen in patients with FAP).
Diagnosis
A biopsy specimen is necessary to diagnose a desmoid tumor. Ultrasound is often the first method of examination of a soft tissue tumor. If the mass is solid, a CT and/or MRI scan is used to determine whether it adheres to nearby structures and whether it can be safely removed. A variety of options are available for biopsying a suspected desmoid: a core needle biopsy takes a small piece, usually 1 mm wide by 10 mm long; surgical biopsies may take a portion of the tumor (“incisional biopsy”) or may remove all the visible tumor (“excisional biopsy”). While an excisional biopsy may remove all visible tumor, it rarely completely removes all microscopic traces of the tumor – usually leaving a positive margin, that is, tumor at the edge of the biopsy site.
Behavior of Desmoid Tumors
Although they do not metastasize, desmoid tumors are locally aggressive, infiltrating and sometimes causing destruction of adjacent vital structures and organs. The disease process may be devastating and occasionally fatal. Fortunately, the growth rate is typically (but not always) slow, and there may be periods of stability and temporary regression. Desmoid tumors may be influenced by external factors, particularly hormones (whether from pregnancy, from contraceptive or hormone replacement pills).
Treatment
Treatment of desmoid tumors is indicated when they cause symptoms, when there is risk to adjacent structures, or when they create cosmetic concerns . Under some circumstances, it is appropriate to monitor a desmoid tumor without any treatment.
Surgery
Desmoid tumors are surgically removed when feasible . The goal is to attempt to obtain tumor-free margins while preserving function and cosmesis. Surgery may be difficult and even impossible for desmoids within the abdomen. Medical therapy (see below) may be considered as an initial alternative, particularly for tumors that involve the intestines, blood vessels, nerves, or organs.
Desmoid tumors can have a high rate of recurrence with surgery alone. While statistics vary, as many as 25 to 40 percent of patients who undergo surgery can have a local recurrence, that is, return of the desmoid at or near the original site. However, when they recur, treatment with radiation and/or repeat surgery may be successful.
Radiation Therapy
Radiation therapy (RT) is an effective option for many patients who cannot have surgery, or as an adjunct to surgery or chemotherapy. The duration of radiation treatment typically is 6 to 8 weeks. Radiographic evidence of tumor shrinkage may take months to years to become apparent. RT is often not considered an option in intraabdominal tumors because of the size of the area needed to be irradiated and the risk of radiation damage to vital structures.
Medical Therapy
There is no single accepted medical treatment for desmoid tumors. 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. Patients with desmoid tumors have been treated with non-steroidal anti-inflammatory drugs (NSAIDs), the class of drugs including aspirin, Advil and other compounds. The most widely used NSAID for treatment of desmoid tumors is Clinoril, also known as sulindac. (Most approved drugs have a brand name, which is capitalized, and a generic name, which is not. In this case, sulindac is generic while Clinoril is the brand name.) Clinoril was initially shown to decrease the polyps associated with familial polyposis, and during treatment of some patient’s polyps their desmoid tumors were found to shrink as well. More recently, COX-2 inhibitors have been used for polyposis patients, and for desmoid tumors as well. It was hoped that the COX-2 inhibitors would have fewer side effects than other NSAIDs, including sulindac . However, concerns about increased clotting and even increased risk of heart attacks led to the withdrawal of some COX-2 inhibitors and more restricted use of others. Celebrex, or celecoxib, is still available and has been used for many patients with desmoids, with or without polyposis. In most but not all cases, NSAIDs are combined with an anti-estrogen (see below).
Clear evidence suggests the hormonal dependency of some desmoid tumors. Hormonal agents such as tamoxifen (brand name Nolvadex), toremifene, raloxifene and progesterones have all been used, often in combination with NSAIDs. Of these, tamoxifen has been used most widely. Most physicians prescribe tamoxifen at standard doses, similar to those used for breast cancer, but some have recommended much higher doses. There is no firm evidence to suggest that higher doses of tamoxifen are better than lower doses. Treatment with hormones and NSAIDs, both alone and in combination, result in detectable improvement in pain and other symptoms in about half of patients, but lead to major shrinkage in only a small minority of patients and complete disappearance of the tumor in very few cases.
Chemotherapy
Chemotherapy may be effective in patients with unresectable tumors, and is often used if tumors do not respond to tamoxifen and/or sulindac. Low doses of the chemotherapeutic agents methotrexate and vinblastine produce impressive responses, particularly in children. The combination of methotrexate and vinorelbine may produce a similar benefit with less nerve damage. Liposomal doxorubicin (brand name Doxil) may also be useful. Low-dose chemotherapy is often given for a year, then stopped to observe whether long-term improvement will occur.
More aggressive, high-dose chemotherapy treatments seem to be more active and more toxic, and are usually given for a shorter duration – often about six months. Most physicians reserve high-dose chemotherapy for patients unresponsive to other therapies or with very rapidly growing or very symptomatic tumors. The most commonly used drug is doxorubicin (brand name Adriamycin), often combined with dacarbazine (also known as DTIC). Other chemotherapy combinations have been used, with no consensus as yet as to which is best.
New Drugs
Desmoid tumors sometimes respond to the tyrosine kinase inhibitor imatinib, brand name Gleevec, an effect that is presumably due to expression of one of Gleevec’s molecular targets, PDGF receptor, on desmoid tumors. Antifibrotic agents seem to represent a rational choice for therapy. Experience with one such agent, pirfenidone, is promising but still very limited.
Intralesional Therapy
Another new area of treatment is with intralesional therapy, where something is introduced or applied directly to the inside of the desmoid tumor. Intralesional injections of irritating solutions, such as acetic acid, has led to tumor shrinkage in some cases. Radiofrequency ablation is a technique where needles are inserted into tumors and radiofrequency waves conducted through the needles lead to intense heating of the tumor. This has also led to some desmoid tumor shrinkage, but the experience to date is limited to a few centers and the long-term results are not yet known.
Follow Up
Frequency of follow-up CT or MRI scans must be determined on a case-by-case basis based on the location and extent of the tumor. Other types of imaging studies (x-rays, bone scans, PET scans, etc.) are rarely if ever indicated in patients with desmoid tumors that have been completely removed.
*Please note that this summary is intended solely to provide general information for your reference only. This is a very generic document and individual cases will vary considerably. This information is not intended as medical advice for any individual problem, or as a diagnosis, treatment plan, or recommendation for a particular course of action, and should not be used as a substitute for professional medical advice and services. Please do not delay in obtaining professional medical advice regarding your individual circumstances.
Sam Agresta, MD, Fellow in Medical Oncology
Audrey Walker, RN, Sarcoma Program
Vernon K. Sondak, MD
H. Lee Moffitt Cancer Center and Research Institute,
Tampa, Florida
