Desmoid tumor

A desmoid tumor is an abnormal growth that arises from connective tissue, which is the tissue that provides strength and flexibility to structures such as bones, ligaments, and muscles. Typically, a single tumor develops, although some people have multiple tumors. The tumors can occur anywhere in the body. Tumors that form in the abdominal wall are called abdominal desmoid tumors; those that arise from the tissue that connects the abdominal organs 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.

Desmoid tumors are fibrous, much like scar tissue. They are generally not considered cancerous (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. These tumors often recur, even after apparently complete removal.

The most common symptom of desmoid tumors is pain. Other signs and symptoms, which are often caused by growth of the tumor into surrounding tissue, vary based on the size and location of the tumor. 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.

Desmoid tumors occur frequently in people with an inherited form of colon cancer called familial adenomatous polyposis (FAP). These individuals typically develop intra-abdominal desmoid tumors in addition to abnormal growths (called polyps) and cancerous tumors in the colon. Desmoid tumors that are not part of an inherited condition are described as sporadic.

Desmoid tumors are rare, affecting an estimated 1 to 2 per 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.

Mutations in the CTNNB1 gene or the APC gene cause desmoid tumors. CTNNB1 gene mutations account for around 85 percent of sporadic desmoid tumors. APC gene mutations cause desmoid tumors associated with familial adenomatous polyposis as well as 10 to 15 percent of sporadic 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.

Genetic Testing Information

• Genetic Testing Registry: Desmoid disease, hereditary

Genetic and Rare Diseases Information Center

• Desmoid tumor

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• DESMOID DISEASE, HEREDITARY; DESMD

Scientific Articles on PubMed

• PubMed

• Alman BA, Li C, Pajerski ME, Diaz-Cano S, Wolfe HJ. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). Am J Pathol. 1997 Aug;151(2):329-34. Citation on PubMed or Free article on PubMed Central
• Escobar C, Munker R, Thomas JO, Li BD, Burton GV. Update on desmoid tumors. Ann Oncol. 2012 Mar;23(3):562-569. doi: 10.1093/annonc/mdr386. Epub 2011 Aug 22. Citation on PubMed
• Huss S, Nehles J, Binot E, Wardelmann E, Mittler J, Kleine MA, Kunstlinger H, Hartmann W, Hohenberger P, Merkelbach-Bruse S, Buettner R, Schildhaus HU. beta-catenin (CTNNB1) mutations and clinicopathological features of mesenteric desmoid-type fibromatosis. Histopathology. 2013 Jan;62(2):294-304. doi: 10.1111/j.1365-2559.2012.04355.x. Epub 2012 Sep 28. Citation on PubMed
• Kotiligam D, Lazar AJ, Pollock RE, Lev D. Desmoid tumor: a disease opportune for molecular insights. Histol Histopathol. 2008 Jan;23(1):117-26. doi: 10.14670/HH-23.117. Citation on PubMed
• Lips DJ, Barker N, Clevers H, Hennipman A. The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol. 2009 Jan;35(1):3-10. doi: 10.1016/j.ejso.2008.07.003. Epub 2008 Aug 21. Citation on PubMed
• Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P, Van Cutsem E, Bapat B, van Roy F, Cassiman JJ, Alman BA. Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor). Oncogene. 1999 Nov 11;18(47):6615-20. doi: 10.1038/sj.onc.1203041. Citation on PubMed