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Last updated:
11/29/2023
Years published: 2008, 2012, 2015, 2018, 2019, 2023
NORD gratefully acknowledges Valerie Grignol, MD, Associate Professor of Surgery, The Ohio State University-The James Cancer Hospital, and the Desmoid Tumor Research Foundation, for assistance in the preparation of this report.
Summary
Desmoid tumor commonly develops in the fibrous (connective) tissues of the body that connect, support and surround other body parts and organs. Desmoid tumors grow from a fibroblast cell known as myofibroblast, which make up connective tissue and are also important for wound healing. They can develop anywhere in the body. Superficial desmoids tend to be less aggressive than deep desmoids (abdominal, extra abdominal, mesenteric). Desmoid tumors look like dense scar tissue. They adhere to surrounding structures and organs and are often difficult to remove. Surgery has been the traditional therapy for desmoid tumors but up to 20-30% will recur after surgery.
Introduction
Desmoid tumor is called aggressive fibromatosis as it has similarities with a malignant (cancerous) tumor called fibrosarcoma. Desmoid tumors do not spread (metastasize) to other parts of the body.
While each child or adult may experience symptoms differently, the following are the most common symptoms of desmoid tumors. The symptoms vary greatly depending on size and location:
• A painless swelling or lump
• Pain or soreness caused by compressed nerves or muscles
• Pain and obstruction of the bowels
• Limping or other difficulty using the legs, feet, arms or hands or other affected part of the body
The cause of the desmoid tumor is not known. Desmoid tumors may occur sporadically or may be part of a disease called familial adenomatous polyposis (FAP).
FAP is a familial cancer predisposition syndrome. People affected with FAP often develop intra-abdominal desmoid tumors as well as abnormal growths called polyps and cancerous tumors in the part of the intestine called the colon. Desmoid tumors that are not part of an inherited condition are described as sporadic. Reports in the medical literature state that 3.5-32% of people with FAP develop desmoid tumors sometime in their life. These desmoid tumors are the result of changes (pathogenic variants or mutations) in the adenomatous polyposis coli (APC) gene.
However, in most people, the desmoid tumor occurs sporadically, which means that it is not caused by a predisposing genetic disease. Variants in the CTNNB1 gene or the APC gene may cause sporadic desmoid tumors. APC gene variants cause desmoid tumors associated with FAP, as well as 10% to 15% of sporadic desmoid tumors. Variants in the CTNNB1 gene have been seen in up to 85% of sporadic desmoid tumors. Both genes, APC and CTNNB1, are involved in an important cell signaling pathway that controls the cell growth and cell division as well as the process by which cells mature to carry out specific functions (differentiation).
People who develop sporadic desmoid tumors do not have the other health problems seen in people with FAP who have variants in the APC gene.
Other factors that may increase the risk of developing desmoid tumor are irritation or repeated trauma to a certain area of the body (including surgical trauma) and the female hormone called estrogen.
Inheritance
Most desmoid tumors are sporadic and are not inherited. Sporadic tumors result from genetic mutations that occur during a person’s lifetime, called somatic mutations. Somatic mutations in the CTNNB1 or APC gene can cause sporadic desmoid tumors. These mutations are not inherited.
FAP is inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of a mutated gene is necessary to cause the disease. The mutated gene can be inherited from either parent or can be the result of a changed gene in the affected individual. The risk of passing the mutated gene from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
Desmoid tumors constitute 0.03% of all tumors. The estimated incidence in the general population is 2-4 per million people per year. Desmoid tumors are observed to be more common in persons aged 10-40 years but can occur in other age groups. Desmoid tumors can commonly occur in women after childbirth. The female: male gender ratio is 2:1. In children, the incidence is the same in males and females.
The conclusive diagnosis of desmoid tumor requires a biopsy. Microscopic examination of the biopsy tissue confirms the diagnosis. On microscopic examination, the spindle cells of desmoid tumors appear to be myofibroblasts and are thought to be an abnormal proliferation of myofibroblasts, which normally gradually disappear during the later stages of wound healing. Additionally, immunohistochemical stains can establish the nuclear accumulation of beta-catenin, a protein that is caused by the genetic mutations usually found in desmoid tumors. Nuclear reactivity shows relatively high specificity, detected in up to 90% of desmoids, regardless of site. Finally, antibodies are often examined in desmoid tumors, including smooth muscle actin, desmin and KIT, to aid in distinguishing them from other tumors.
Treatment
Depending on the extent of the tumor growth and the overall condition of the patient, the following treatment options are utilized. Over the past several years first-line treatment has transitioned from surgery to a period of watchful waiting as initial therapy.
Watchful waiting is a manner of treating the tumor with close surveillance utilizing imaging and exams. Desmoid tumors do not metastasize and have been shown to spontaneously regress in up to 20% of patients. Treatment with surgery, chemotherapy and/or radiation can cause significant illness and even death, so patients with asymptomatic or minimally symptomatic disease that has stable appearance on screening modalities are treated with watchful waiting.
For those with significant symptoms or concern that growth would lead to impact on nearby structures, treatment with surgery and medical therapies is the next step in treatment. Surgery alone is often the only treatment needed. However, the recurrence rate of desmoid tumor is often as high as 30% and more than one surgery may be needed. The tumor tends to become more aggressive when it recurs after resection.
Sorafenib is an oral chemotherapy known as a molecular-targeted therapy. In a clinical trial 33% of patients had shrinkage of their tumor with sorafenib and up to 70% of tumors did not grow. This led to sorafenib being a first line treatment for many, particularly patients for whom surgery is not an option.
Pazopanib is another multi-kinase inhibitor that has shown similar results. Intravenous chemotherapy including anthracylcline agents (i.e., doxorubicin), methotrexate/vinblasticne are another class of medications used to treat tumors when they are not surgically removable due to size or location. These have more toxicities than the targeted therapies and are often a second choice.
Anti-inflammatory drugs may make the tumor slowly shrink. Non-steroidal anti-inflammatory drugs (NSAIDs) alone and in conjunction with other therapies mentioned here have been used to treat desmoid tumors. Some hormones seem to increase the growth of desmoid tumors, so anti-hormonal medications such as anti-estrogens and prostaglandin inhibitors have also been used. Since the advent of targeted therapies with better response rates the use of NSAIDS and hormone therapy is limited.
High-energy rays (radiation) from a specialized machine can be used to damage or kill cancer cells and shrink tumors. For desmoids it is used as treatment for recurrent disease that doesn’t respond to other treatments or as primary therapy to avoid surgical or medical therapy toxicities.
After surgery, MRI is used to monitor recurrence in the arms and legs. CAT scans are used to monitor intra-abdominal and chest desmoids.
In 2023, nirogacestat (Ogsiveo) was approved by the U.S. Food and Drug Administration (FDA) to treat adult patients with progressing desmoid tumors who require systemic treatment.
Newer substances that target specific receptors or pathways in desmoid tumors to prevent the growth of tumors are being studied.
Researchers are also testing several chemotherapy drugs, or combination of drugs, that could prove to be most effective in treating desmoid tumors to avoid radical surgery.
Mutations in the gene for beta-catenin have been found to commonly occur in desmoid tumors. Mutation analysis may soon be used to predict the risk of recurrence and to aid in the design of individual therapies.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Litchman, C, ed. Desmoid Tumors. 1st ed. New York, NY: Springer Publishing; 2012:221.
James WD, Berger TG, ElstonDMeds. Andrews’ Diseases of The Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: W.B. Saunders Company; 2011:959.
Thoene JG, Coker NP, eds. Physician’s Guide to Rare Diseases. Montvale, NJ: Dowden Publishing Company Inc.; 1995:70-71.
JOURNAL ARTICLES
Desmoid Tumor Working Group. The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients. Eur J Cancer. 2020 Mar; 127:96-107. doi: 10.1016/j.ejca.2019.11.013. Epub 2020 Jan 28. PMID: 32004793.
Gounder MM, Mahoney MR, Van Tine BA, Ravi V, Attia S, Deshpande HA, Gupta AA, Milhem MM, Conry RM, Movva S, Pishvaian MJ, Riedel RF, Sabagh T, Tap WD, Horvat N, Basch E, Schwartz LH, Maki RG, Agaram NP, Lefkowitz RA, Mazaheri Y, Yamashita R, Wright JJ, Dueck AC, Schwartz GK. Sorafenib for advanced and refractory desmoid tumors. N Engl J Med. 2018 Dec 20;379(25):2417-2428. doi: 10.1056/NEJMoa1805052. PMID: 30575484; PMCID: PMC6447029.
Lev D, Kotilingam D, Wei C, Ballo MT, Zagars GK, Pisters PW, Lazar AA, Patel SR, Benjamin RS, Pollock RE. Optimizing treatment of desmoid tumors. J ClinOnc. 2007;25:1785-1791.
Shi B, Zhu Y, Xu Z, et al. Aggressive fibromatosis in the urological system.Report of two adult patients and review of the literature.Urol Int. 2007;78(1):93-6.
Schwartz RA, Trovato MJ, Lambert PC. The desmoid tumor — a locally aggressive neoplasm.Cesko-SlovenskaDermatologie. 2007;82:34-8.
Neri HA, Villagra EJ, Alvarez AC, et al. Ethmoidal desmoid tumor in a pediatric patient.Otolaryngol Head Neck Surg. 2007;136(1):137-8.
Bhama PK, Chugh R, Baker LH, Doherty GM. Gardner’s syndrome in a 40-year-old woman: successful treatment of locally aggressive desmoid tumors with cytotoxic chemotherapy. World J SurgOncol. 2006;4:96.
Lee JC, Thomas JM, Phillips S, et al. Aggressive fibromatosis: MRI features with pathologic correlation. AJR Am J Roentgenol. 2006;186(1):247-54.
Rajesh A, Sandrasegaran K. Mesenteric desmoid mimicking recurrent testicular cancer. Abdom Imaging. 2005;30(6):777-9.
Mendenhall WM, Zlotecki RA, Morris CG, et al. Aggressive fibromatosis.Am J ClinOncol. 2005;28(2):211-5.
Moon JI, Selvaggi G, Nishida S, et al. Intestinal transplantation for the treatment of neoplastic disease.J SurgOncol. 2005;92(4):284-91.
Erguvan-Dogan B, Dempsey PJ, Ayyar G, Gilcrease MZ.Primary desmoid tumor (extra-abdominal fibromatosis) of the breast. AJR Am J Roentgenol. 2005;185(2):488-9.
Thuret R, Renaudin K, Leclere J, et al. Uncommon malignancies: case 3. Paratesticular desmoplastic small round-cell tumor.J ClinOncol. 2005; 23(25):6253-5.
Brueckl WM, Ballhausen WG, Förtsch T, et al. Genetic testing for germline mutations of the APC gene in patients with apparentlysporadicdesmoid tumors but a family history of colorectal carcinoma. Dis Colon Rectum. 2005;48(6):1275-81.
Buitendijk S, van de Ven CP, Dumans TG, et al. Pediatric aggressive fibromatosis: a retrospective analysis of 13 patients and review of literature. Cancer. 2005;104(5):1090-9.
Sturt NJ, Gallagher MC, Bassett P, et al. Evidence for genetic predisposition to desmoidtumours in familial adenomatous polyposis independent of the germline APC mutation. Gut. 2004; 53(12):1832-6.
Lindor NM, Dozois R, Nelson H, Wolff B, King J, Boardman L, Wilson M, Greene MH, Karnes W, Mesa R, Welch T, Edmonson J, Limburg P. Desmoid tumors in familial adenomatous polyposis: a pilot project evaluating efficacy of treatment with pirfenidone. Am J Gastroenterol. 2003; 98(8):1868-74
Dormans JP, Spiegel D, Meyer J, et al. Fibromatoses in childhood: the desmoid/fibromatosis complex. Med PediatrOncol. 2001;37(2):126-31.
Abdelkader M, Riad M, Williams A. Aggressive fibromatosis of the head and neck (desmoidtumours). J Laryngol Otol. 2001;115(10):772-6.
Rai AT, Nguyen TP, Hogg JP, Gabriele FJ.Aggressive fibromatosis of the neck in a patient with Gardner’s syndrome.Neuroradiology. 2001; 43(8):650-2.
Shields CJ, Winter DC, Kirwan WO, Redmond HP. Desmoidtumours.Eur J SurgOncol. 2001; 27(8):701-6.
INTERNET
Schwartz RA, Trovato MJ, Lambert PC. Desmoid Tumor. Medscape. Updated: Mar 23, 2021. https://emedicine.medscape.com/article/1060887-overview Accessed March 15, 2023.
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