Christina Gutowski, MD MPH

Fibromatosisis a generic term for multiple conditions that involve the development of abenign, locally-aggressive fibroblastic tumor in an inter - or intramuscular location. On the plantar surface of the foot, this condition is known as Ledderhose disease, on the penis, Peyronie's disease, and on the palm, Dupuytren's contracture.

Theterm “desmoid tumor” is used when fibromatosis develops in soft tissuelocations other than those listed above. When a tumor with similar histologydevelops in bone, it is called a desmoplastic fibroma. Desmoplastic fibromas arebenign but locally aggressive lesions.

Desmoidtumors are characterized by abundant collagen and fibroblastic cells that infiltrate the surrounding muscle. They are benign with no malignant transformation potential (unless radiated), however they can grow rapidly and invade surrounding structures. Due to the infiltrative growth pattern, complete “margin-negative” surgical excision can be difficult to achieve and isassociated with a high local recurrence rate. Surgical procedures can be technically challenging and extremely morbid. For this reason, multiple medical treatment shave been developed.

Epidemiology

Desmoidtumors develop at a rate of 3-4 cases per million people per year, and are typically diagnosed in a dolescents and young adults. These lesions are rarely seen inpatients over the age of 35.

Approximately 1,000 new cases are diagnosed per year in the United States. These lesions are more frequently seen in females (3:1) and can develop as a solitary desmoid, or as acollection of multiple lesions with in the same extremity.

Clinical Features

Desmoidtumors develop with in the superficial or deep muscles, often associated with fascia. Their most common locations are the shoulder, torso, and thigh. The high collagen component and intimate interdigitation with surrounding muscles cause desmoid tumors to feel immobile and “hard as a rock” on physical exam. Desmoidtumors can be locally painful, and compression of nearby neurovascular structures can cause neuropathic pain or swelling distal to the tumor itself.

Desmoidtumors tend to grow for a period of time and follow an unpredictable naturalhistory, a small portion will spontaneously resolve without treatment, some willexpand to a point and stop growing, and some will continue to grow unlesstreated.

Radiologic Features

Desmoids are soft tissue tumors without calcifications, therefore radiographs play a minimal role in diagnosis. Occasionally, the tumorwill cause pressure erosion on a neighboring bone, which will be the only radiographic abnormality detectable on an x-ray.

CT scans are not good at delineating these tumors but may illustrate a soft tissue mass that is slightly denser than the surrounding muscle, due to the high amount of collagen with in the tumor.

MRI is the most diagnostically useful imaging study for desmoid fibromatosis. On T1 imaging, the tumor is primarily isointense to muscle, consistent with most soft tissue tumors, it may also demonstrate thickbands of lower signal, representing the prominent collagenization. This highcollagen content also explains a heterogeneous, and relatively low, signalintensity is seen on fluid-sensitive sequences such as fat-saturated T2, orSTIR. This is a key imaging characteristic that helps to recognize a desmoidtumor from other soft tissue masses.

Another differentiating quality of desmoids is the irregular, infiltrative, non-geographic border between the tumor and surrounding muscle on MRI. Desmoid tumors exhibit an infiltrative growth pattern, unlike most soft tissue tumors, indicated by the infiltrative margin at the tumor-muscle interface (Figure 1 and Figure 2). On post-contrast images, desmoids display an unpredictable and heterogeneous enhancement pattern.

Figure 1: T1 axial image of the right humerus, demonstrating hypo-intense soft tissue mass growing with in the posterior compartment of the arm, with dark areas representing collagenization

Figure 2: STIR axial image of the distal femur, demonstrating heterogeneously hyper - and hypointense desmoid in posterior compartment of thigh

When the process of fibromatosis involves bone as well, the condition is known as a desmoplastic fibroma [see below]. These lesions arewell-characterized on radiographs, which reveal trabeculated, expansile, andradiolucent bone lesions often with lobulated margins. These aggressive bonetumors may erode through the cortex and have an associated soft tissue mass.

Figure 3: Lateral x-ray of the femur, demonstrating desmoplastic fibroma with osteolysisand cortical thinning

Pathology

Grossly, desmoid tumors are poorly-circumscribed, infiltrative masses that vary from pink to gray-white in color, and from firmto rock-hard in consistency. There is no capsule or pseudocapsule at the periphery. They are relatively hypovascular and often appear to be a mass offibrous scar tissue (Figure 4).

Figure 4: Gross pathology, desmoid tumor

Histologically, bundles of uniform, elongatedspindle cells weave amongst abundant collagen. The spindle cells show no atypiaor pleiomorphism on a higher power. At the margin with neighboring muscle, the tumorcells can be seen invading the muscle fibers (Figure 5). These tumors stain positively for estrogen receptor beta and nuclear beta-catenin.

Figure 5: H& E stain, desmoid tumor. Sweepingelongated fibroblast-like spindle cells among collagenous (pink) matrix

Recent genetic analysis of desmoplastic fibromas has demonstrated that although its infiltrative pattern of growth resembles that of desmoids histologically, they lack the mutation in exon 3 of CTNNB1 thatencoded for B-catenin as seen in desmoid tumors. As such, it is best to consider desmoplastic fibromas not merely as osseous counter parts to desmoidtumors but as genetically distinct entities of their own.

Fibromatosis has been associated with Familial Adenomatous Polyposis (also known as Gardnersyndrome) is due to a common underlying gene mutation that drives both disorders, namely, that of the B-catenin gene.

Desmoids have estrogen receptors (and thus hormonal treatments can be used, as noted below).

Differential Diagnosis

Desmoid tumors tend to be harder than other soft tissue lesions when palpated on physical exam, but this finding is not sufficient lyreliable for diagnosis.

As noted, desmoid tumors have two characteristic MRI findings that will aid in their diagnosis, relative hypointensity onfluid-sensitive imaging and an infiltrative growth pattern. None the less, the sefeatures are neither pathognomonic nor always demonstrated. Therefore, the diagnosis of a desmoid cannot be definitively established on imaging, andbiopsy is necessary for complete diagnosis.

The differential diagnosis for desmoid fibromatosis in most locations includes most benign and malignant soft tissue tumors.

Desmoplastic fibromas like wise cannot be definitively diagnosed with imaging studies, as many bone tumors can cause lucency with cortical destruction. Here, the differential diagnosis includes fibrous dysplasia, simple bone cyst, aneurysmal bone cyst, non-ossifyingfibroma, eosinophilic granuloma, neoplasms containing dystrophic calcifications (e.g., synovialsarcoma and liposarcoma) and chondromyxoid fibroma.

Disease Course: Treatment and Prognosis

Treatment strategies for desmoid fibromatosis include surgery, chemotherapy, hormonal therapy, and radiation therapy, either individually or in combination.

Local recurrence is reported to be approximately 40% when positive-margin excision is performed. Wide-margin resections often involve large amounts of muscle being resected, with subsequent dysfunction and disfigurement. Even extensive resection does not always prevent local recurrence, given the tumor’s infiltrative growth pattern.

Historically, high-dose radiation was combined with surgery to reduce the local recurrence rate. In recent years, radiation has been avoided, due to its propensity to cause malignant transformation. As aresult, several relatively effective medical treatment options have replaced surgical resection as the first-line treatment for desmoid fibromatosis.

Medical management exists on a spectrum of off setting effectiveness and morbidity. The easiest and least morbid treatment option is non-steroidalanti-inflammatory drugs such as sulindac, or more recently, meloxicam. The sedrugs induce partial responses and often control symptoms enough to satisfy topatients.

Other medical strategies include low-dosechemotherapy with methotrexate and either vinblastine or vinorelbine. Low-dosechemotherapy has been reported to provide reliable symptom relief, at leastpartial response (if not complete regression) in over half of patients, and 70% relapse-free interval with a median of 10 years. Importantly, this low-dosechemotherapy regimen was not associated with significant adverse side effects,as other combinations involving doxorubicin tend to have.

Hormonal therapies such as tamoxifen can be tried,either as a frontline treatment or after other approaches have failed. Whilehead-to-head data is limited, Tamoxifen has not shown the efficacy that the methotrexate-vinblastine/vinorelbine combination has. Newer systemic agents have also been shown to be effective against desmoid tumors, inducing tumorstability, partial response, or regression in most cases. Due to desmoid’ sexpression of PDGF receptors, treatment with the tyrosine kinase in hibitorimatinib mesylate has been shown to induce at least partial response and improve quality of life. The multitargeted oral tyrosine kinase inhibitor sorafenib hasmore recently been shown to result in tumor shrinkage and symptom relief to a greater degree than imatinib.

Things That Tend to Come up on Examinations

1. Rock-hard to palpation on physical exam
2. Imaging characteristics: infiltrative margin, hypointensity onT1 and T2
3. Surgical resection is no longer the standard of care due to infiltrative growth pattern leading to morbid wide resections and high localrecurrence rate, first line treatment is medical management
4. No malignant transformation unless radiated.
5. Staining pattern: estrogen receptor-beta, beta-catenin
6. Associated with familial adenomatous polyposis