Desmoid-type fibromatosis: What works best?

Abstract

Desmoid-type fibromatosis (DF) is a rare monoclonal proliferative disease of fibroblastic origin. It accounts for 0.03% of all malignancies and 3% of all soft tissue sarcomas [1]. It usually occurs sporadically but it can also be associated to Gardner’s syndrome. DF is considered a benign disease, since it does not have the capacity to metastasise. Nevertheless, it may harbour some features distinctive of malignant behaviour that may be the cause of its local aggressive course. Cytogenetic studies revealed that chromosome abnormalities are present in some cases, including trisomy 8, trisomy 20 or absence of 5q [1]. The locoregional course, especially when the disease is located at critical sites, may seldom lead to death. DF occurs more frequently in patients affected by Gardner’s syndrome than in the general population: in these patients the germline mutation of the adenomatous polyposis coli (APC) gene predisposes to develop hundreds of colonic polyps and several other neoplastic diseases. The APC protein regulates the level of b-catenin in the cell; b-catenin is a mediator in the Wingless/Wnt signalling pathway related to cell proliferation and is also involved in cell adhesion. The majority of APC mutations result in a truncated protein that lacks normal regulatory function resulting in b-catenin accumulation that mimics activation of Wnt signalling [1]. Familial adenomatous polyposis (FAP) patients are characterised by germline inactivating mutations of the APC gene whereas patients with sporadic DF usually harbour somatic b-catenin activating mutations. Some authors demonstrated an overexpression of COX-2 in DF. This over-expression was hypothesised to conduct the inhibition of apoptosis, and stimulation of angiogenesis and cell proliferation mediated by platelet-derived growth factor (PDGF) [1]. The role of trauma and surgery in the development of DF is not completely understood. Some authors presented a correlation beetween abdominal surgery and the development of desmoid tumors in the vicinity of surgical scars. There is a higher incidence of DF in females but the role of oestrogen receptors is not yet well established. Some authors showed that 17bE2 induced both cell proliferation and matrix synthesis by desmoid cells in primary culture, while tamoxifen counteracted 17bE2 effects in these cells [1]. The main pathologic characteristic of this tumour is the growth pattern: infiltration of deep tissues along muscle planes is the main cause of the frequent recurrences. Surgery with wide microscopic resection margins has been the treatment mainstay so far, especially if function and cosmesis can be preserved. Local failure rates have been reported to be as high as 25–60% at 5 years. Interestingly, many authors have claimed that the outcome of primary disease is quite unpredictable and not influenced by surgical margins [2–4]. The explanation provided has been that DFs are made by different diseases. There seems to be a subset with an aggressive behaviour and a worse local outcome. This subset maybe constituted by tumours characterised by a different molecular profile, even if with an undistinguishable morphology [5]. This hypothesis has recently been supported by the finding that a particular beta-catenin gene mutation subtype could correlate with the outcome. The results of this study, though needing to be prospectively validated, look very attractive. This issue, along with the natural history of the disease, the lack of metastatic potential, and the possible implication of inflammatory agents in further tumour re-growth, have all become arguments in favour of a less aggressive primary approach. Pursuing wide margin resection in primary surgery should always be weighted with function preservation and cosmesis. At recurrence, repeated surgical excisions are usually not the first choice, and again, preservations of function and cosmesis are always to be carefully taken into account. Some authors advanced the hypothesis that a group of patients could be managed with a front-line non aggressive approach [6]. The wait and see policy or medical therapy could select patients who will most benefit from a surgical approach. As a matter of fact,