Desmoid Tumors: A Comprehensive Review

Abstract

Desmoid tumors (DT) are rare, locally aggressive, fibroblastic soft-tissue tumors that are characterized by infiltrative growth and can affect organs and adjacent structures, resulting in substantial clinical burden impacting patients’ health-related quality of life. Searches of PubMed, Embase, Cochrane, and key conferences were conducted in November 2021 and updated periodically through March 2023 to identify articles describing the burden of DT. Of 651 publications identified, 96 relevant ones were retained. Diagnosis of DT is challenging because of its morphologic heterogeneity and variable clinical presentation. Patients visit multiple healthcare providers, often facing delays in correct diagnosis. The low incidence of DT (estimated 3–5 cases per million person-years) limits disease awareness. Patients with DT experience a high symptom burden: up to 63% of patients experience chronic pain, which leads to sleep disturbance (73% of cases), irritability (46% of cases), and anxiety/depression (15% of cases). Frequently mentioned symptoms are pain, limited function and mobility, fatigue, muscle weakness, and swelling around the tumor. Overall, quality of life in patients with DT is lower than in healthy controls. There is no treatment approved by the US Food and Drug Administration for DT; however, treatment guidelines reference available options, such as active surveillance, surgery, systemic therapy, and locoregional therapy. Choice of active treatment may depend on tumor location, symptoms, and risk of morbidity. The substantial burden of illness of DT is related to difficulties in timely and accurate diagnosis, high symptom burden (pain and functional limitations), and decreased quality of life. There is a high unmet need for treatments that specifically target DT and improve quality of life. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02592-0.

Diagnosis and Management of Desmoid Fibromatosis of the Breast

“…While controversy exists regarding precise mechanisms, it is likely that the Wnt/beta-catenin/adenomatous polyposis coli (APC) pathway is the driver of mutations leading to desmoid fibromatosis. Two known mutations, CTNNB1 and APC, have been posited to lead to beta-catenin accumulation [ 3 ]. A strong association exists between the development of desmoid tumors and germline mutations of the APC gene in patients with FAP.…”

“…In general, the incidence is approximately 1,000 times higher in patients known to have germline mutation of APC gene leading to FAP [ 1 ]. A second pathway implicated in the development of desmoid tumors is the Notch pathway, which is activated in response to dysregulation of the Wnt pathway [ 3 ].…”

“…While it may be possible that patients may receive appropriate management regardless of the diagnosis, this has a particular impact on patient counseling and expectations for recurrence post-operatively. Misdiagnosis is a significant concern with regards to desmoid tumor in general, due to the rarity of these tumors and similarities in pathological features with other tumors derived from myofibroblasts [ 3 ].…”

“…Other groups have trialed combinations including cyclophosphamide/doxorubicin, mitomycin/doxorubicin/cisplatin, and ifosfamide/etoposide, with moderate success [ 65 ]. While these successes point to a role for systemic therapy, these treatments are typically reserved for patients with rapidly progressing, symptomatic tumors [ 3 ].…”

“…The differential diagnosis for this tumor is broad and includes multiple benign and malignant lesions. Patients diagnosed with desmoid tumors may experience significant symptoms including chronic pain, edema, and limited functionality [ 3 ]. Our interest in desmoid tumor of the breast was sparked by an unusual presentation of a large breast mass in a 16-year-old patient with familial adenomatous polyposis (FAP) syndrome.…”