Desmoid tumors are fibroproliferative disorders arising within musculoaponeurotic tissue, observed in nearly every part of the body. Numerous sites in the trunk and extremities have been identified, and two forms of the disease are distinguished; an extra-abdominal and an intra-abdominal form. Generally, desmoids usually occur in three locations; the extremities (commonly around the limb girdles or the proximal extremities); the abdominal wall (commonly found in women, especially during and after pregnancy); and the bowel wall and mesentery (often associated with Gardner syndrome) 515.

In approximately 10% of the cases, multicentric disease has been reported 1617. Multicentricity is defined as the presence of disease in more than one location at the time of diagnosis. Multicentric lesions tend to be in the same limb or anatomic region, and it is possible that many cases of distant or local recurrence of primary lesions within the same region represent multicentric disease that were not clinically apparent at the initial diagnosis 416171819.

The clinical behaviour and natural history of desmoid tumours remain unpredictable. They are usually slow-growing, locally aggressive and invasive to surrounding tissues. Although both spontaneous regression and disappearance have been reported, as has spontaneous regression after biopsy 252021, most lesions will progress refractory to multiple surgical procedures and adjuvant therapy. They often recur after surgery, particularly after marginal or intralesional excision. Distant haematogenous or lymph nodes metastases have not been observed, and multicentric disease and recurrence or reactivation at sites other than the primary location have been reported 1617. Extra-abdominal head and neck lesions are more aggressive than extra-abdominal desmoids arising elsewhere and are capable of massive destruction of adjacent bone and erosion of the base of the scull, and occasionally encroach on the trachea, some times with fatal outcome. 219222324. Loss of function may be observed with extra-abdominal tumours involving the extremities, as result of wide resection, local recurrence, and radiation therapy 25.

Although computed tomography shows the extent of the tumour and its relationship to the neurovascular structures (Figure 1), magnetic resonance imaging (MRI) is the modality of choice for the diagnosis and the evaluation of the tumours' extent and the progression of the disease after treatment (Fig 2). MRI features vary. Heterogeneous changes are common, depending on the distribution of collagen and the cellularity of the lesions 2526. The lesions may be hypo- or hyper-intense relative to surrounding muscle or adipose tissue (Fig 2B,C), on both T1- and T2-weighted sequences, with both sharply and poorly defined margins 2627.

MRI with gadolinium injection may also be helpful in differentiating tumour progression from post-surgical fibrosis 26. Multicentric and recurrent lesions tend to occur within the same limb or anatomic region, which outlines the role of scanning the entire extremity once the diagnosis is made 17.

On gross examination, the tumours are always confined to the musculature and the overlying aponeurosis or fascia (Figure 3). Their size varies from 5 to 20 cm. The tumours are firm, cut with a gritty sensation, and on cross section reveal a glistening white, coarsely trabeculated surface resembling scar tissue 24.

Microscopically, desmoid tumours are poorly circumscribed, infiltrating the surrounding tissue. The proliferation consists of elongated, slender, spindle-shaped cells of uniform appearance. The tumour cells are surrounded and separated from one another by abundant collagen, with little to no cell-to-cell contact (Figure 4A,B). The cells lack atypia, but cellularity may vary within the same lesion. Nuclei are small, pale-staining, and sharply defined. One to three small nucleoli are usual 2428.

Ultrastructurally, desmoid tumours consist of a uniform population of elongated fibroblast-like cells, often terminating in long, slender processes 2429. Most nuclei are rounded or oval, but some cells show prominent nuclear indentations or clefts. There is a prominent rough endoplasmic reticulum, partly dilated, containing granular or fibrillary material within the dilated spaces. The cytoplasm has a small number of mitochondria, a prominent Golgi apparatus, free ribosomes, and occasional pinocytotic vesicles and microtubules. Some cells contain intracytoplasmic bundles of actin-type microfilaments, and incomplete or clumped basal lamina along the cell borders, all features characteristic of myofibroblasts. The stroma contains considerable amounts of collagen and ground substance 2429.

Differential diagnosis includes fibrosarcoma, reactive fibroblastic proliferations, desmoplastic fibroma, myxoma, and nodular fasciitis 2430.

Desmoids most closely resemble fibrosarcomas. An inadequate biopsy specimen may lead to misdiagnosis, as some examples of fibrosarcomas have areas indistinguishable from desmoid tumours and vice versa 24. Desmoids may also be difficult to be distinguished from reactive fibroblastic proliferations following injuries such as trauma, minor muscle tears, or intramuscular injections. Cytologically, these reactive proliferations are composed of cells indistinguishable from those found in desmoid tumours, and the low-magnification appearance is more useful for differential diagnosis of these two entities. Desmoplastic fibroma of bone may also be indistinguishable from desmoid tumours, especially when presents as a soft tissue mass after breaking through the thinned or expanded cortex of the involved bone. Confusion with myxoma or nodular fasciitis is possible, particularly if only a small amount of tissue or FNA is available for examination 24.

Fibrosarcomatous transformation of desmoid tumours is rare, and it may be erroneously suggested by occasional foci of increased cellularity and by exceptionally well-differentiated fibromatosis-like areas in some fibrosarcomas 24.

Current management of desmoid tumours involves a multidisciplinary approach. Radiation therapy or brachytherapy have been used in the adjuvant setting. Antiestrogens, goserelin, progesterone, non-steroidal anti-inflammatory drugs (NSAIDs), interferon (IFN-alpha), cytotoxic chemotherapeutic agents, and radiation therapy have all been employed in the management of desmoids 12453132333435363738394041.

External-beam radiation therapy has been shown to improve local control of desmoid tumours, both in the adjuvant and primary settings 5621464748. It has been used as adjuvant mainly in adults for the treatment of unresectable or inaccessible disease, for gross residual tumour with positive or equivocal surgical margins, and to avoid mutilating surgery 6192122424647485051. Radiation doses of 50 to 60 Gy are currently suggested as curative 2562242444647. Lower doses are associated with higher rates of tumour progression and local recurrence. Higher doses have resulted in complications, including fibrosis, oedema, skin ulceration, neurological deficits including paresthesias and paresis, pathologic fractures, cellulitis, and secondary malignant transformation, which may also lead to a second stage amputation 424748495253.

When used as adjuvant, irradiation is reported to achieve disease control in 77 to 90% of patients 6124254. In cases of positive surgical margins, adjuvant radiation therapy is recommended when the potential morbidity of a second operation is high 5612424445505455. Intralesional excision in addition to radiotherapy is ineffective, with high local recurrence rates and life threatening complications for the patient. Under these circumstances doses above 50 Gy are recommended 212.

In children, desmoid tumours are highly aggressive, and data are not in favour of the use of irradiation because of the previously mentioned complications and the risks of contractures development and growth disturbance 1819405253. Most children are treated with radiation therapy using guidelines outlined for adults. External beam radiation therapy in children should be performed as a last resort, in patients reaching skeletal maturity, in cases with potential mortality or significant morbidity, and in tumours showing active growth adjacent to vital structures or progressive disease after multiple attempts at control with surgery and chemotherapy. Otherwise, when safe surgical margins can be achieved, no additional therapy is recommended, despite a risk of recurrence ranging from 5% to 50% 412181954.

The role of radiation therapy is discussed above. Because of its low toxicity endocrine therapy is frequently the first line of treatment for recurrent desmoid tumours, which are not candidates for surgical or radiation approaches. The use of hormonal therapy for the treatment of these tumours is based on the association of oestrogen levels with the growth of desmoid tumours, and on estrogen receptor expression in desmoids 5657. A higher incidence of these tumours, especially in the abdominal wall, is reported during or soon after pregnancy, or during treatment with oral contraceptives 375859. There have also been reports of spontaneous regression of desmoids after menopause and oophorectomy 445. Endocrine treatment with agents such as tamoxifene have resulted in response rates of up to 50% in older series 38. Other hormonal agents employed in the treatment of desmoids include medroxyprogesterone acetate, megace, toremifen, and gonadotropin releasing hormone analog goserelin in tamoxifen failures

Non-steroid anti-inflammatory drugs such as indomethacin or sulindac as single agents or in combination with antioestrogens 6061 have also been used in the treatment of desmoid tumours, with variable response rates being reported mostly based on small series and case reports 537.

Use of IFN-alpha in desmoids has also been reported in inoperable cases 62, and in combination with tretinoin in order to delay of local recurrence. Without clear evidence for long term benefits however, IFN-alpha therapy because of its relative lack of toxicity, it might be appropriate to consider in cases where mutilating surgery or more toxic medical treatment would be the other treatment alternative 132343545636465.

Although neither haematogenous nor lymphatic metastases have been observed, most lesions will progress refractory to treatment. Spontaneous regression and disappearance, regression after biopsy, multicentric disease, and recurrence or reactivation at sites other than the primary location have all been reported 252021. Mortality is rare in extra-abdominal desmoid tumours, but has been reported in head and neck lesions. Loss of function is often observed with involvement of the extremities 192223.

Overall local recurrence rates range from 19% to 75% 4182122244251. Most recurrences are usually observed within 3 years, and nearly all by 6 years 218. Age may affect recurrence rates, and although unclear, local recurrence may be more likely in younger patients with extra-abdominal lesions 24. The region of involvement also affects local recurrence, which is reported higher in extra-abdominal lesions of the foot and calf. Extremity tumours, because of their locally aggressive behaviour have the higher propensity for local recurrent growth 5. Local recurrence rates for intra-abdominal tumours are higher than those reported for extra-abdominal tumours, ranging from 57% to 86% after complete resection, with a higher complications rate and even death 515.