Fibrosarcoma 

Updated: May 12, 2020
Author: Ian D Dickey, MD, FRCSC, LMCC; Chief Editor: Omohodion (Odion) Binitie, MD 

Overview

Background

Fibrosarcoma is a tumor of mesenchymal cell origin that can occur as a soft-tissue mass or as a primary or secondary bone tumor. In the past, fibrosarcoma was diagnosed much more frequently than it is now; in current practice, it can be more reliably distinguished histologically from similar lesions, such as desmoid tumors, undifferentiated pleomorphic sarcoma, malignant fibrous histiocytoma,[1] malignant schwannoma, and high-grade osteosarcoma.

As with all soft-tissue and bone sarcomas, the mainstay of treatment for fibrosarcoma has been complete excision with an adequate margin; this procedure became prevalent following the publication and wide acceptance of Enneking's surgical principles of musculoskeletal oncology, in the early 1980s. This surgery normally consists of resecting a cuff of normal tissue along with the tumor.

The long-term survival and ultimate functional outcome of fibrosarcoma treatment depend on many interrelated factors.[2, 3] Among these are the size and location of the tumor, its histologic grade, and the presence of metastatic disease (eg, pulmonary metastases). These factors are taken into account with careful evaluation (staging) of the tumor and determine the success of treatment in obtaining good local control and preventing subsequent disease spread.

Continued advances in the molecular biology of sarcomas may further elucidate the very distinct clinical behavior of the various types of fibrosarcoma and ultimately provide better solutions to their respective treatment.

Pathophysiology

Fibrosarcoma is a tumor of mesenchymal cell origin that is composed of malignant fibroblasts in a collagen background. There are two main types: primary and secondary. Primary fibrosarcoma is a fibroblastic malignancy that produces variable amounts of collagen. Fibrosarcoma of bone may be either central (arising within the medullary canal) or peripheral (arising from the periosteum). Secondary fibrosarcoma of bone arises from a preexisting lesion or after radiotherapy to an area of bone or soft tissue. This is a more aggressive tumor and has a poorer prognosis.

Several inherited syndromes are associated with sarcomas. For example, patients with multiple neurofibromas may have a 10% lifetime risk of developing a neurosarcoma or a fibrosarcoma.

The occurrence of fibrosarcoma in conjunction with metallic implants used for fracture fixation or joint reconstruction has been reported, albeit very rarely.[4] The cause of this transformation is unknown.

Fibrosarcoma has also been noted to arise from preexisting lesions, such as bone infarcts and lesions associated with fibrous dysplasia, chronic osteomyelitis, and Paget disease,[5] as well as in previously irradiated areas of bone. This form of fibrosarcoma is very aggressive and is associated with a much poorer outcome than is the primary fibrosarcoma of bone.

Etiology

No definite cause of fibrosarcoma is known, though genetic mutations may play a role.[6] Current research indicates that many sarcomas are associated with such mutations. The more common genetic defects include allele loss, point mutations, and chromosome translocations.

Epidemiology

Fibrosarcoma represents only about 10% of musculoskeletal sarcomas and fewer than 5% of all primary tumors of bone. It can be diagnosed in patients of any age, but it is diagnosed more commonly in patients in the fourth decade of life. It is usually located in the lower extremities, especially the femur and tibia.

Fibrosarcoma of the soft tissues usually affects a wider age spectrum of patients than fibrosarcoma of the bone does, with an age range of 35-55 years. It often arises in the soft tissues of the thigh and the posterior knee. It is generally a large, painless mass deep to fascia and has an ill-defined margin.

An infantile form (in children < 10 years) of fibrosarcoma exists. Unlike fibrosarcoma in adults, it has an excellent prognosis—even in the face of metastatic disease at presentation—when treated with a combination of neoadjuvant and adjuvant chemotherapy and resection.[7, 8, 9, 10]

Fibrosarcoma of bone occurs slightly more commonly in men than in women. No known racial predilection exists.

Prognosis

If all grades are included, primary fibrosarcoma of the bone has a worse prognosis than osteosarcoma, with a 5-year survival rate of 65%. In high-grade primary fibrosarcoma, the 10-year survival rate is less than 30%. Secondary fibrosarcoma is associated with a very poor outcome, the survival rate at 10 years being less than 10%.

For congenital fibrosarcoma of bone in children, the prognosis (which is related to age and to time to diagnosis) is much better, with the disease having long-term survival rates of higher than 50%.

Soft-tissue fibrosarcoma is associated with a 40-60% survival rate at 5 years. The infantile form has an even better 5-year survival rate, in excess of 80%.

Russell et al reported on four patients with infantile fibrosarcoma treated with chemotherapy and surgical resection, all of whom had excellent functional outcome.[7]  The patient with fibrosarcoma of the neck displayed rapid tumor shrinkage. Two of the lower-extremity tumors had only modest changes in dimensions, but on resection, the tumor bed contained fibrous tissue with exaggerated small caliber vessels. In the fourth case, metastatic lesions developed in the central nervous system, orbits, lungs, and kidney after complete removal of the primary tumor.

 

Presentation

History and Physical Examination

Sarcomas involving bone often present with pain and swelling after a long duration of symptoms. They may even grow large enough to threaten the structural integrity of the bone and cause pathologic fracture as the initial presentation.

Generally, lesions that involve more than 50% of the bone cortex, that are larger than 2 cm, or that involve the medial calcar of the femur are associated with the greatest risk of fracture. A prior history of bone infarct, irradiation, or other such risk factors should alert the physician to the possibility of a secondary fibrosarcoma.

Soft-tissue sarcomas most often present as painless masses. The time to presentation, however, is often shorter than with lesions involving bone. Because these lesions frequently arise deep to the muscular fascia, they may become extremely large tumors before being diagnosed.

Most lesions occur around the knee, in the proximal femur and hip region, or in the proximal arm. Findings are nonspecific and can range from a fixed, firm mass to a localized area of tenderness. Neurologic or vascular changes are late findings and indicate extensive disease involvement.

 

DDx

Diagnostic Considerations

Differential diagnoses include the following:

 

Workup

Imaging Studies

Plain radiography

Plain radiographs of the involved anatomic region are needed to evaluate for primary or secondary involvement of bone. (See the image below.) Typically, an osteolytic area of destruction with a permeative or moth-eaten appearance is present. Little periosteal reaction or reactive sclerosis is depicted.

Although fibrosarcoma of bone can arise anywhere, Although fibrosarcoma of bone can arise anywhere, it is found most commonly about the knee and femur. The radiograph here shows a typical appearance of a lesion in bone.

For bony lesions, plain radiographs often greatly assist in diagnosis and the determination of location, size, and local extent of involvement. For soft-tissue masses, size often can be estimated, any bone involvement can be seen, and intralesional content (matrix) can sometimes be determined.

Computed tomography

For sarcomas arising in bone, computed tomography (CT) is used to delineate bone involvement, bone destruction, or bone reaction. The density of fibrosarcomas is similar to that of surrounding normal muscle. Signs of fracture or impending fracture may be seen, and the tumor can be more accurately localized. CT of the chest may be appropriate. CT is highly sensitive for metastatic disease.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) may be the best modality overall for examining soft-tissue masses and for detecting the intraosseous and extraosseous extent of many bony sarcomas.[11] It is useful in providing information about the local extent, lesion size, and involvement of the neurovascular structures. Fibrosarcoma of bone typically has extraosseous extension.

Canale et al performed a retrospective review of MRI features in six cases of infantile fibrosarcoma (patient age range, 0-6 months).[8] A well-circumscribed single mass was the most common finding (five patients), and all the tumors were on limbs. The initial tumor signal was isointense to muscle on T1-weighted images and hyperintense on T2-weighted images, with all tumors being well circumscribed and half of them containing internal fibrous septa.

In three patients, the internal signal was homogeneous; in the other three, it was heterogeneous.[8] An intense enhancement was seen in the three contrast-enhanced images that were available: heterogeneous in two and homogeneous in one. There was osseous erosion observed in the patient with distant metastasis. The tumors in all cases disappeared with chemotherapy and limited surgery.[8]

Bone scanning

Bone scanning with technetium-99m is a very useful adjunct in the evaluation of tumor stage.

It aids in the detection of bone metastatic or polyostotic disease. For fibrosarcoma, bone scanning has largely been supplanted by MRI. The main limitation of bone scanning is that it often is nonspecific.

Other modalities

Some authors have suggested the use of gallium and ultrasound scans for diagnosis. At present, the value of these tests for staging of sarcomas remains limited.

Biopsy

Ultimately, the diagnosis of fibrosarcoma is made with tissue obtained from a biopsy. Biopsy should be thought of as the first step toward treatment, rather than the last step in diagnosis. Biopsy should always follow a full radiographic workup.

Biopsy is best performed by the treating surgeon because that physician will be responsible for any final tumor resection and reconstruction. In addition, it is best performed at a center where a team approach is used in treating these rare tumors. At such centers, groups of oncologists, pathologists, radiologists, and surgeons, all with a specific interest in these problems, often are present. This broad pool of experience contributes greatly to the interpretation of tests and to the ultimate treatment outcome.

Any biopsy performed must include an adequate volume of tissue. In centers with expert interpretation, core needle biopsy (CNB) may be acceptable.

The biopsy must be performed in a way that avoids compromising any planned surgical excision or reconstruction. It must not contaminate significant neurovascular structures.

Histologic Findings

Fibrosarcomas are tumors of malignant fibroblasts and collagen. They vary in histologic grade.

Well-differentiated forms have multiple plump fibroblasts with deeply staining nuclei in a rich collagen background. Intermediate-grade tumors have the typical herringbone pattern, showing the diagnostic parallel sheets of cells arranged in intertwining whorls (see the image below). A slight degree of cellular pleomorphism exists.

Most pathologists describe the histologic picture Most pathologists describe the histologic picture of fibrosarcoma as a herringbone pattern. It is an interlacing pattern of sheets of spindle-shaped fibroblasts in a collagen background. This pattern is very distinctive and usually confirms the diagnosis of fibrosarcoma.

High-grade lesions are very cellular, with marked cellular atypia and mitotic activity. The matrix is sparse. No malignant osteoid formation should be present. Higher grades are extremely anaplastic and pleomorphic, with bizarre nuclei that bring to mind the histologic features of malignant fibrous histiocytoma. In fact, some pathologists believe that the division between malignant fibrous histiocytoma, high-grade osteosarcoma, and fibrosarcoma may be artificial.

Wojcik et al assessed clinicopathologic and immunohistochemical features of primary sclerosing epithelioid fibrosarcoma (SEF) in eight patients (median age, 52 years; range, 25-73 years).[12] Tumors mostly involved long bones of the extremities, were predominantly lytic, and were poorly marginated. Histologically, six tumors had pure SEF morphology; two had hybrid SEF/low-grade fibromyxoid sarcoma morphology; one showed focal dystrophic mineralization (limited to areas of necrosis); and none showed the lacelike mineralization pattern typical of osteosarcoma.

The majority of the tumors (6/8) strongly expressed MUC4.[12] All but one patient tested negative for SATB2; in that case, variable weak to moderate staining occurred in approximately 50% of nuclei. The authors concluded that the combination of morphology, MUC4 expression, and the absence of SATB2 expression was highly useful in helping to establish the correct diagnosis.

Staging

Several staging systems are used for tumors of the musculoskeletal system. The two most common systems are that of the Musculoskeletal Tumor Society and that of the American Joint Committee on Cancer. Both systems include histologic grade, tumor site, and presence or absence of metastasis. Other factors that may be important in staging are the size and depth of the tumor.

 

Treatment

Approach Considerations

To obtain local control, surgical resection with a cuff of normal tissue (wide margins) and reconstruction of the subsequent defect are necessary.

Surgical treatment (including biopsy) of fibrosarcoma should not proceed unless complete patient care is available. Complete care includes biopsy and interpretation of biopsy findings, access to oncologists and radiation oncologists, and definitive resection.

Fibrosarcomas should be removed by trained orthopedic oncologists who can provide a state-of-the-art treatment program; this would involve a team of well-trained specialists with advanced experience in treating these tumors.

Medical Therapy

Adjunctive therapy, such as radiation treatment and chemotherapy, can improve local control and may make the appearance of clinically evident metastatic disease less likely. The use of chemotherapy is controversial, but chemotherapy is generally used in bone lesions. Radiation therapy is employed in conjunction with surgery for soft-tissue fibrosarcomas, with or without chemotherapy.

Surgical Therapy

In general terms, treatment of fibrosarcoma involves a combination of adequate local tumor control and avoidance or treatment of distant disease. Many factors are involved and contribute to the ultimate prognosis. To obtain local control, surgical resection with a cuff of normal tissue (wide margins) and reconstruction of the subsequent defect are necessary.

Infantile fibrosarcoma

Sulkowski et al conducted a retrospective, nonrandomized study aimed at defining the extent of surgical resection needed in the treatment of infantile fibrosarcoma (IFS), as well as the role of chemotherapy in management.[13] The study cohort consisted of 224 patients aged 0-2 years. Of the 64 patients (28.6%) with positive margins, 36 (56.3%) had microscopic disease, and 12 (18.8%) had macroscopic disease; margin status was unknown for 16 (25%). None of the patients had metastases. In all, 171 (76.4%) were treated with surgical resection.

The disease-free survival rate was 90.6%.[13] No significant survival difference was noted with regard to margin status, nodal involvement, tumor size, or treatment modality. The use of multimodal therapy (surgery in conjunction with chemotherapy) increased over time. A small increase in survival was associated with negative margins and multimodal therapy, but neither result was statistically significant. The authors suggested that future studies investigating tumor biology and chemosensitivity may determine optimal management of IFS.

The European Paediatric Soft Tissue Sarcoma Study Group evaluated a conservative therapeutic strategy in 50 infants (median age, 1.4 months) with localized IFS.[14] Initial surgery was suggested only if it could be done without mutilation. No further therapy was administered to those with initial complete (group I/R0; n = 11) or microscopic incomplete (group II/R1; n = 8) resection; vincristine-actinomycin (VA) chemotherapy was administered to those with initial inoperable tumors (group III/R2; n = 31), with delayed conservative surgery planned after tumor reduction.

After delivery of VA chemotherapy to 25 children with group III/R2 and one with group II/R1 disease, there was a 68% rate of response to VA; only three children required mutilating surgery.[14] The 3-year event-free survival was 84% and the overall survival 94.0% at a median follow-up of 4.7 years (range, 1.9-9.0 years). Alkylating or anthracycline based chemotherapy was avoided in 71.0% of patients needing chemotherapy.

Complications

Local recurrence may occur in up to 60% of cases and is the reason that postoperative radiation, preoperative radiation, or both are often recommended. Local recurrence is reduced to about 25% when postoperative irradiation is used.

Long-Term Monitoring

With fibrosarcoma, as with all sarcomas of the musculoskeletal system, successful treatment must be accompanied by an organized plan for clinical follow-up. This often involves a schedule of repeat examinations and diagnostic studies. Patients often are monitored for a minimum of 5 years. At preset intervals, the patient is reexamined, and plain radiographs of the involved site are obtained. Repeat staging studies of the local area and of the chest also are performed.

 

Questions & Answers