Desmoid tumors: clinical features and treatment options for advanced disease

Abstract

Desmoid tumors describe a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Although histologically benign, desmoids are locally invasive and associated with a high local recurrence rate, but lack metastatic potential. On the molecular level, desmoids are characterized by mutations in the β-catenin gene, CTNNB1, or the adenomatous polyposis coli gene, APC. Proof of a CTNNB1 mutation may be useful when the pathological differential diagnosis is difficult and location might be predictive for disease recurrence. Many issues regarding the optimal treatment of patients with desmoids remain controversial; however, surgery is the therapeutic mainstay, except if mutilating and associated with considerable function loss. Postoperative radiotherapy reduces the local recurrence rate, in cases of involved surgical margins. Because of the heterogeneity of the biological behavior of desmoids, including long periods of stable disease or even spontaneous regression, treatment needs to be individualized to optimize local tumor control and preserve patients' quality of life. Therefore, the application of a multidisciplinary assessment with multimodality treatment forms the basis of care for these patients. Watchful waiting may be the most appropriate management in selected asymptomatic patients. Patients with desmoids located at the mesentery or in the head and neck region could present with life-threatening complications and often need more aggressive treatment. This review describes treatment options and management strategies for patients with desmoid tumors with a focus on advanced disease.

Figure 1.

Typical localizations of desmoid tumors and treatment solutions. (A) Pregnancy-associated desmoid of the rectus abdominis muscle (38-year-old female, treated with resection, no evidence of disease 4 years later). (B) Recurrent, symptomatic desmoid of the head and neck area extending to the upper thoracic wall and brachial plexus (28-year-old male, treated with transcervical resection and adjuvant radiation therapy, free from recurrence at 34 months). (C) Desmoid of the lower pelvis, preventing vaginal delivery (34-year-old pregnant female, treated with imatinib, stable disease since March 2008). (D) Multiply recurrent desmoid reaching from the thigh to the popliteal fossa in a patient suffering from Recklinghausen's disease (37-year-old male, treated by isolated limb perfusion with rhTNF-α and melphalan, stable disease since August 2006).

Figure 2.

Case of a 66-year-old patient with a desmoid tumor of the right musculus deltoideus diagnosed in April 2009 (A); staging in October 2009 demonstrated a spontaneous tumor remission (B). The diagnosis was confirmed by β-catenin mutation analysis with a characteristic S45P mutation in exon 3 of the CTNNB1 gene.

Figure 3.

(A) Classic fibroblastic, spindle cell morphology of a desmoid tumor (hematoxylin and eosin, x200); (B) desmoid tumor with the characteristic expression of β-catenin (endothelial cells as negative control, x200).

Figure 4.

Case of a 19-year-old male with a desmoid of the thoracic/abdominal wall, diagnosed in 2007, treated preoperatively with imatinib 800 mg daily. FDG-PET showed a decrease of the average standardized uptake value (SUV) from 3.3 and of the SUV_max from 5.5 (A) to 1.7 and 3.1 (B), respectively. Corresponding conventional magnetic resonance imaging documented stable disease.

Figure 5.

Possible treatment algorithm for desmoid tumors. Adapted from Lev et al. [25] and Lazar et al. [57], University of Texas MD Anderson Cancer Center.