Are You Confident of the Diagnosis?
What you should be alert for in the history
There are no salient clinical features specific for fibrosarcoma. Most patients lack constitutional symptoms; however, those with larger tumors or those with metastatic disease may have weight loss. The pediatric variant, infantile fibrosarcoma, also presents as a painless mass of variable dimensions. Some masses are present at birth, whereas most become evident during the first year of life.
Characteristic findings on physical examination
Patients will usually present with a painless mass. It may affect all aspects of the body, but has a predilection for the deep soft tissues of the lower extremities, followed by the upper extremities and trunk. Adult fibrosarcoma usually presents as a slow-growing mass, and may be present for a few weeks to years (Figure 1).
Unlike the adult form, infantile fibrosarcoma presents as a rapidly growing painless mass.
Expected results of diagnostic studies
Patients who present with soft tissue masses warrant the following diagnostic measures:
Physical exam: Evaluate the size, consistency, location, and mobility of the mass. Note its proximity to important neurovascular structures.
Imaging: Computed tomography (CT) scan of the chest to evaluate for metastatic lesions. Magnetic resonance imaging (MRI) with contrast of the primary site.
Biopsy: Histologic analysis is important to confirm the diagnosis and grade of the lesion.
Determine the stage (evidence of metastases), which will help dictate treatment modalities to be employed.
Pathologic evaluation will reveal: Spindle-shaped cells with indistinct borders, organized in a parallel (herringbone) fashion, and cells separated by collagen fibers.
The differential diagnosis should include fibromatosis, synovial sarcoma, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor.
Fibromatosis (desmoid tumor)
Usually differentiated histologically
Contains more collagen and is less cellullar
Fascicular growth pattern not present, as it is in fibrosarcoma
The easiest method of differentiation is identification of t(x;18) via fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR).
Undifferentiated pleomorphic sarcoma
Typically arise in adults in the seventh decade
Histologically, cells exhibit a storiform to disorganized growth pattern with giant cells
Siderophages and xanthoma cells are also common
Malignant peripheral nerve sheath tumor (MPNST)
Histologically, lacks the long sweeping fascicles characteristic of fibrosarcoma, and cells will exhibit nerve sheath differentiation
S-100 protein, while not specific for MPNST, supports its diagnosis
Who is at Risk for Developing this Disease?
In adults, fibrosarcoma accounts for approximately 1%-3% of all soft tissue sarcomas. While once very prevalent, with an incidence of 65% in 1936, the incidence of fibrosarcoma has declined significantly. This can be attributed to a change in categorization by pathologists, enhanced histologic criteria, improved staining techniques, cytogenetics, and molecular genetics.
Fibrosarcoma usually affects middle-aged and older adults, specifically those aged 30-55 years of age. There is a slight male predominance. The current 5-year survival rate of 36% has been shown to negatively correlate with increasing tumor grade and inadequate surgical margins. The rate of local recurrence is increased in patients with inadequate surgical margins. The rate of metastasis is increased with increased grade and stage, however it is not associated with surgical margins. Sites of metastasis include the lung, followed by the skeleton.
Soft tissue sarcoma is rare in children, accounting for less than 1% of all childhood cancers and 10% of all childhood soft tissue sarcomas. It is usually diagnosed in the first year of life. Some are present at birth, but most become evident during the first year of life. There is a slight male predominance.
Infantile fibrosarcoma is characterized by t(12;15)(p13;q25) translocation and the fusion of ETV6 gene with neurotrophin-3 receptor (NTRK3). Infantile fibrosarcoma demonstrates a gain of chromosomes 8,11,17, and 20. The infantile form has a better prognosis than the adult form, with survival rates of 89%-100%. Incidence of metastases is less than 10% in children younger than 5 years of age, and increases to greater than 50% when the patient presents beyond 10 years of age.
In general, there are no patient populations specifically at risk for development of fibrosarcoma. Genetic factors may predispose to the development of sarcoma, e.g. Li-Fraumeni syndrome.
What is the Cause of the Disease?
The etiology of fibrosarcoma, like most soft tissue sarcomas, is unknown. Most arise sporadically.
In the adult form, there has been an association with trauma, chronic draining sinuses (i.e. draining osteomyelitis), areas where prosthetic vascular grafts have been placed, and in the vicinity of knee arthroplasty. The fibrous intra/intermuscular structures, fascia, tendons, and aponeurosis usually serve as the origin of fibrosarcoma. It may affect all aspects of the body but has a predilection for the deep soft tissues of the lower extremities, followed by the upper extremities and trunk.
Systemic Implications and Complications
There are no systemic disorders that are currently associated with the diagnosis of fibrosarcoma.
The preferred treatment method is wide surgical resection, to obtain negative margins. Wide surgical resection is associated with improved survival and decreased rate of local recurrence. In the event that negative margins are not obtained, radiation therapy may be considered.
Chemotherapy is usually reserved for patients with metastatic disease. There is a suggested role of pre-operative chemotherapy in infants, specifically with vincristine, actinomycin-D, and cyclophosphamide at 3-month intervals, especially in cases where amputation is required.
It has been suggested that the rate of local recurrence and overall survival may be improved with a multimodal approach that includes preoperative chemotherapy and radiation therapy, followed by local control and postoperative adjuvant chemotherapy or surgery and post-operative radiation.
Optimal Therapeutic Approach for this Disease
Preoperative radiation, followed by wide resection, or wide resection followed by radiation, is the standard of care. Preoperative radiation offers a smaller area of radiation field (only the tumor region is radiated), but an increased risk of postoperative wound complications. Postoperative radiation offers fewer wound complications, but an increased area of radiation field (the entire surgical bed is radiated).
Radiation can increase the risk of radiation-induced sarcoma in the surgical bed of survivors greater than 3 years out from treatment. Radiation near joints can increase the risk of postradiation fibrosis joint contracture.
Chemotherapy can be offered to treat the primary tumor, in conjunction with radiation, depending on grade (high), or size (>8cm) of tumor, and depending on individual institutional protocol. Chemotherapy may be considered if limb salvage (especially upper extremity) is in jeopardy, or in difficult-to-resect locations (pelvis, axial skeleton). Chemotherapy options may be limited because of patient’s comorbidities (e.g. advanced age, cardiac/lung disease), precluding the use of more effective/toxic chemotherapeutic agents.
There is an increased risk of second primary cancers in long-term survivors of sarcoma.
Amputation of the involved extremity can be a primary treatment option in the following situations: extensive disease precluding limb salvage, prior unplanned surgical resection precluding limb salvage, and disease encasing the neurovascular bundle. Amputation offers better local disease control than limb salvage, but no difference in patient survival, and may preclude the use of chemotherapy/radiation in nonmetastatic, negative pathology margin cases.
After appropriate treatment, patients should be managed in accordance to the most recent National Comprehensive Cancer Network guidelines (NCCN). Surveillance is based on staging at the time of diagnosis. According to 2007 NCCN guidelines, after primary therapy, patients with stage I-III should be evaluated every 3-6 months, for 2 years, with a history and physical exam, chest imaging, and periodic imaging of the extremity affected. After 2 years, patients should be followed yearly with the same clinical evaluation.
Unusual Clinical Scenarios to Consider in Patient Management
Fibrosarcomas have been reported to arise adjacent to metal joint prostheses or other metal implants; however, the incidence of fibrosarcomas in these patients is no higher than that in the non-metal joint prosthesis population. This may be because a tumor was missed at initial presentation or may arise in an occult chronically infected case; fibrosarcomas arising within infection sinus tracts have been reported.
There have also been case reports of Paget’s disease of bone with malignant degeneration to sarcoma in 0.9%-2% of cases, with osteosarcoma accounting for 50% of cases, but fibrosarcoma was also reported.
Radiation (as mentioned in Optimal Therapeutic Approach above), can predispose to sarcomatous degeneration of the treated field; incidence increases with dose received.
What is the Evidence?
Weiss, SW, Goldblum, JR. “Enzinger and Weiss's soft tissue tumors”. 2008. pp. 257-370. (A comprehensive review of fibrous tumors of childhood, and fibrosarcoma specifically. The focus is on pathologic diagnosis and presentation, with brief discussions on management.)
Wong, SL. “Diagnosis and management of desmoid tumors and fibrosarcoma”. J Surg Oncol. vol. 97. 2008. pp. 554-8. (A review of fibrous tumors. A thorough presentation of epidemiology, pathology, genetics, clinical features, and treatment of desmoid tumors and fibrosarcoma.)
Damron, TA. “Orthopaedic surgery essentials: oncology and basic science”. 2008. pp. 294-300. (This is a concise presentation of the various soft tissue sarcomas. It describes appropriate workup and treatment of soft tissue sarcoma. The authors also present the pathogenesis, epidemiology, and diagnosis of the various types of soft tissue sarcomas.)
Scott, SM, Reiman, HM, Pritchard, DJ, Ilstrup, DM. “Soft tissue fibrosarcoma”. Cancer. vol. 64. 1989. pp. 925-31. (This is a retrospective review, from a single institution, of soft tissue sarcomas consistent with fibrosarcoma. The review documents the clinical presentation and outcome after treatment, with particular attention to grade, stage, and surgical treatment.)
2007. (Provides guidelines regarding treatment and surveillance of patients with soft tissue sarcoma.)
Kurkchubasche, AG, Halvorson, ER, Forman, EN, Terek, RM, Ferguson, WS. “The role of preoperative chemotherapy in the treatment of infantile fibrosarcoma”. J Pediatr Surg. vol. 35. 2000. pp. 880-3. (This is a case series of two patients, treated with preoperative chemotherapy in an attempt to avoid an amputation that would have been warranted. The patients were treated with a vincristine, actinomycin-D and cyclophosphamide regimen, given at 3-month intervals over a 9-month period of time.)
Morris, JM, Lucas, DB. “Fibrosarcoma within a sinus tract of chronic draining osteomyelitis”. J Bone Joint Surg [Am]. vol. 46. 1964. pp. 853-7. (Case report and review of the literature.)
Fechner, RE, Mills, SE. ” Tumors of the bones and joints; Fascicle 8, Third Series”. 1992. pp. 17-23. (This is a concise summary of tumors of bones and joints, benign and malignant, detailing the tumor definition, general and clinical features, sites, radiographic appearance, gross and microscopic findings, and treatment and prognosis, based on case series at the AFIP, as well as other institutions. The chapter “Sarcomas Arising in Benign Neoplasms or Non-Neoplastic Conditions” outlines unusual scenarios of sarcomas arising in benign conditions.)
Mankin, HJ, Hornicek, FJ. “Paget's sarcoma: a historical and outcome review”. Clin Orthop Related Research. vol. 438. 2005. pp. 97-102. (The most comprehensive review of sarcomas arising in Paget's disease.)
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