Desmoid-type fibromatosis of the lower extremity: A unique case of complete lesion resolution following core needle biopsy

We present a case of a 50-year-old female with a left thigh vastus medialis intramuscular mass which underwent imaging work-up and subsequent core needle ultrasound-guided biopsy showing results of desmoid-type fibromatosis. Following biopsy, the tumor showed prompt, complete regression with complete MRI resolution 2 months following biopsy. The patient showed no evidence of disease recurrence out to one year on MRI surveillance. To our knowledge there have been no reported cases of DF spontaneous regression 2 months following a core needle biopsy. Understanding the variable behavior of desmoid-type fibromatosis can assist the radiologist in guiding management of these lesions with the goal of optimizing clinical outcomes and preventing unnecessary aggressive treatments for stable or regressing disease.

Desmoid-type fibromatosis (DF) are locally aggressive neoplasms, with a need for effective systemic treatment in case of progression, in order to avoid the short- and long-term complications of local treatments. We retrospectively analyzed the outcomes of adult patients with DF treated with oral vinorelbine (90 mg once weekly) at Gustave Roussy Cancer Institute. Only patients with documented progressive disease (PD) according to RECIST v1.1 over 3 months (±2 weeks) before treatment initiation were included. From 2009 to 2019, of 438 patients with DF, 90 were eligible for this analysis. Vinorelbine was given alone in 56 patients (62%), or concomitantly with endocrine therapy in 34, for a median duration of 6.7 months. A partial response was observed in 29%, and stable disease in another 57%. With a median follow-up of 52.4 months, the median time to treatment failure (TTF) was not reached. Progression-free rates at 6 and 12 months were 88.7% and 77.5%, respectively. Concomitant endocrine therapy was associated with longer TTF in women (HR: 2.16, 95%CI: 1.06-4.37, p = 0.03). Among 64 patients with documented CTNNB1 mutational status, p.S45F or p.S45P mutations were associated with longer TTF compared to p.T41A or wild type tumors (HR : 2.78, 95%CI: 1.23-6.27, p = 0.04). Toxicity profile was favorable, without grade 3-4 toxicity but one grade 3 neutropenia. Oral vinorelbine is an effective, affordable and well tolerated regimen in patients with advanced, progressive DF. Prolonged activity was observed in patients with tumors harboring CTNNB1 p.S45F or p.S45P mutations.

Low-dose methotrexate (MTX) plus vinblastine (VBL) chemotherapy is an effective treatment for desmoid-type fibromatosis (DF). However, previous reports have described a weekly regimen, with no reports available on a biweekly one. The aim of this study was to determine the clinical outcomes of a biweekly regimen in a cohort prospectively treated in our single institution. Since 2010, we have prospectively treated refractory DF patients with biweekly MTX (30mg/m2) + VBL (6mg/m2). Efficacy, progression-free survival (PFS), and correlating factors were analyzed. Adverse events were recorded. In total, 38 patients received low-dose MTX + VBL therapy, and its efficacy was assessed in 37 of them. Nineteen (51%) patients showed partial response (PR). Clinical benefit rate was 95%. PFS at 5 years was 80.8 %. Only 3 adverse events of Grade 3/4 were observed. Tumor regrowth after MTX + VBL discontinuation was observed in 5 (20%) of 25 cases. Biweekly administration of MTX + VBL chemotherapy was well tolerated compared with weekly administration, and its efficacy was anticipated in DF patents, although the time needed to achieve a response may be relatively long. The treatment interval should be determined taking into account both the condition of the tumor and the patient’s preference.

A 6-year-old female patient came with a rapidly growing non-painful mass of 6 months duration, involving lower jaw region on the left side. Examination revealed a significantly large and firm non-mobile mass involving the left mandibular and submandibular region, with limited mouth opening. The lesion appeared on imaging as an expansile heterogeneous mass, with evidence of destructive bony changes involving the mandible. Incisional biopsy initially performed followed by surgical excision with segmental resection of the mandible. Without adjuvant therapy, no recurrence observed during >2 years follow up period, and bone grafting subsequently performed. Head and neck pediatric fibromatosis is a rare and aggressive tumor, and its management often constitutes a major challenge to the clinicians. Surgical excision with preservation of cosmetic and functional demands and long-term follow up often result in good outcomes, and adjuvant therapy usually reserved for recurrence or gross residual lesions.

Desmoid fibromatosis (DF) is a rare, locally aggressive, nonmetastasizing fibroblastic/myofibroblastic tumor with a tendency to recur and an unpredictable clinical course. A “wait-and-see” policy is the new standard of care. DF are characterized by activating alterations of the wnt/Beta-catenin pathway: CTNNB1 or adenomatous polyposis coli gene (APC) mutations (these mutations being mutually exclusive). Desmoid-type fibromatosis of the breast (DFB) is rare with an incidence of 0.2% of breast tumors. The diagnosis of DFB is difficult, as it must be distinguished from metaplastic carcinoma and other spindle cell lesions. Sequencing of 128 DFB identified a lower rate of CTNNB1 mutations using Sanger (65.6%) or Sanger+next-generation sequencing (77.7%) and a higher rate of APC mutations (11.8%) than in all-site DF. By excluding patients with familial adenomatous polyposis (n=2), the rate of APC mutations in DFB was high (10.7%). The distribution of CTNNB1 mutations in DFB was different from all-site DF, with a higher rate of T41A (68.9%), a lower rate of S45F (5.7%), and a similar rate of S45T (12.6%). By combining the 2 molecular techniques in a 2-step manner (Sanger, then next-generation sequencing), we increased the detection rate of CTNNB1 mutations and lowered the rate of wild-type tumors from 34.4% to 9.8%, therefore improving the diagnosis of DFB. The identification of the exon 3 CTNNB1 mutation in breast spindle cell lesions is a highly specific tool for the diagnosis of DFB, in addition to extensive immunohistochemical analysis. Our study also underlines the importance of APC in DFB tumorigenesis. These findings have significant implications for patient care and management.

The mainstay of the treatment for desmoid-type fibromatoses has been shifting from surgery to drug treatment, making accurate prediction of the efficacy of drug treatment of extreme importance. On the other hand, desmoid-type fibromatoses arise everywhere in the body. The purpose of this systematic review was to address the clinical question of whether tumour location has an impact on the efficacy of drug treatment. A literature search from January 1990 to August 2017 was conducted. Four reviewers independently assessed and screened the literature for eligibility and determined the final articles. In total, 128 articles were extracted. After the screenings, 5 were chosen for the final evaluation. The drugs used in these articles were one each of toremifene, sorafenib, and methotrexate and vinblastine and of meloxicam. There were no randomized controlled trials, and two prospective and three retrospective case series were included. Therapeutic effects were observed slightly more markedly in extremity using meloxicam or methotrexate and vinblastine. In contrast, the efficacy of toremifene was slightly higher in non-extremity. However, the evidence level of all of the reports was judged to be low. Considering the low evidence level, we concluded that the site-specific therapeutic effects of drugs could not be confirmed in desmoid-type fibromatoses.