What is desmoid fibromatosis and is it malignant?

What is Desmoid Fibromatosis and Is It Malignant?

Desmoid fibromatosis is NOT malignant—it is a rare, locally aggressive soft tissue tumor that cannot metastasize, making it biologically benign despite its aggressive local behavior. 1

Definition and Classification

Desmoid fibromatosis (DF), also called desmoid tumor or aggressive fibromatosis, is defined by the World Health Organization as a "clonal fibroblastic proliferation that arises in the deep soft tissues and is characterized by infiltrative growth and a tendency toward local recurrence but an inability to metastasize." 1 This critical distinction—the inability to spread to distant sites—is what separates it from true malignancies, even though it behaves aggressively at the local level. 1, 2

The WHO classifies DF as an "intermediate, locally aggressive" tumor rather than a malignant neoplasm. 3 It is classified under ICD code D48.1, which designates neoplasms of uncertain behavior. 1

Key Epidemiologic Features

• DF is a rare entity with an incidence of 5-6 cases per 1 million population per year (some sources report 2-4 per million). 1, 3
• Peak age of occurrence is 30-40 years, though it can occur between ages 15-60. 1, 3
• It is more prevalent in females. 3
• Approximately 5-10% of cases arise in the context of familial adenomatous polyposis (FAP), while the majority are sporadic. 1

Clinical Behavior: Why It's Not Truly Malignant

The defining characteristic that makes DF non-malignant is its complete inability to metastasize—it will never spread to distant organs or lymph nodes. 1, 2 However, this does not mean it is harmless:

• DF demonstrates infiltrative growth with tentacle-like extensions into surrounding tissues, making complete surgical removal challenging. 1
• It has a high propensity for local recurrence after surgical resection, with recurrence rates around 30-33%. 4, 5
• In rare instances, DF can be fatal secondary to invasion into critical structures such as the airway or major blood vessels, particularly in head and neck locations. 5
• Despite its aggressive local behavior, more than half of cases may spontaneously stop growing or even shrink without treatment. 2

Molecular Characteristics

• Approximately 85-90% of DF harbor mutations in the β-catenin gene (CTNNB1), leading to nuclear accumulation of β-catenin protein. 1
• The most common mutations are T41A and S45F, accounting for roughly 50% of cases. 1
• β-catenin mutations and APC mutations are mutually exclusive—if β-catenin is wild-type, suspect FAP and perform colonoscopy. 1
• Activating mutations in CTNNB1 are confined to DF in the differential diagnostic setting, making molecular testing valuable for diagnostically ambiguous cases. 1

Common Pitfalls to Avoid

• Do not confuse DF with malignant sarcoma: Despite its aggressive local behavior and the fact that it was historically managed like sarcomas with radical resection, DF cannot metastasize and should not be treated as aggressively as true malignancies. 2
• Misdiagnosis rates are high: Reference centers report misdiagnosis rates of 30-40% during initial work-up, so confirmation by an expert soft tissue pathologist is mandatory. 1
• Do not perform excisional biopsy initially: Core needle biopsy (14G or 16G) is sufficient and preferred for diagnosis. 1
• Recognize that aggressive surgery may not be necessary: Given the high recurrence rates and potential for spontaneous regression, a conservative "wait-and-see" approach is now often preferred over mutilating surgery. 2, 5