Fibrosarcoma

Tumor biology and incidence

• Rare malignant spindle-cell neoplasm of mesenchymal origin
  • Accounts for fewer than 5% of bone sarcomas and 10% of all musculoskeletal sarcomas
• Demonstrates fibroblastic differentiation and produces a collagen-rich fibrous tissue matrix
• Spindle cells and matrix characteristically arranged as intersecting fascicles that form herringbone pattern
• Differentiated from osteosarcoma by absence of osteoid production
• Lacks the degree of pleomorphism and the bizarre cell typical of malignant fibrous histiocytoma of bone
• At least 50% of tumors arise from metaphysis of distal femur or proximal tibia
• Rarely, arises from surface of a bone; referred to as periosteal fibrosarcoma
• May arise from underlying bone condition
  • Secondary to irradiation, Paget's disease, fibrous dysplasia, giant cell tumor, bone infarct, or chronic osteomyelitis
• Multicentric lesions involving multiple bones rarely present at time of diagnosis

Age

• Typically, patients older than age 50 years; however, wide range of ages has been observed, from children to older patients
• Infantile form of fibrosarcoma exists (children <10yrs); has excellent prognosis when treated with adjuvant/neoadjuvant chemo and resection

Gender

M:F = 1:1

Presentation

• Pain, localized tenderness and swelling
• Restricted motion in the adjacent joint
• Pathologic fracture (18% on initial presentation)

Plain films

• Lesion usually purely lytic, permeative, or has a moth-eaten appearance
• Arises eccentrically from metaphysis of bone extending into diaphysis
• Cortical destruction and soft tissue extension usually evident

Site

• Distal femur, proximal tibia, and pelvis
• Few cases reported in humerus, scapula, hand, foot, radius, ribs, and spin
• Location in bone: medullary versus periosteal, 2:1

Size

• Variable
• Usually larger than 5 cm

Tumor effect on bone

• Lytic
• Periosteal reaction, Codman's triangle, and hair-on-end patterns usually not present
• No ossification or mineralization

Bone response to tumor

• Permeative margin frequently observed
• Sclerosis absent or scant

Matrix

• Often totally radiolucent; no calcium or bone production
• Dystrophic calcification may be seen
• Background calcification/ossification of pre-existing lesion that has undergone sarcomatous degeneration may be present (such as bone infarct, Paget's disease)

Cortex

• Cortical thinning and destruction
• Periosteal reaction may be present; variable and generally less prominent than in osteosarcoma

Soft tissue mass

• Commonly present
• Can breach cortex and extend extraosseously into adjacent soft tissue
• May also be seen as an isolated soft tissue lesion in the thigh or posterior knee arising deep to muscular fascia

Bone scan and chest CT

• Nonspecific, but helpful in showing the extent of the lesion or the presence of additional sites of involvement
• Necessary for systemic staging
• Chest CT appropriate to rule out pulmonary metastases.

CT scan

• Characterize extent of bony involvement, bone destruction, or bone reaction
• Density of fibrosarcomas similar to that of surrounding normal muscle

MRI

Helps to define intraosseous spread and soft tissue extension or involvement of adjacent neurovascular structures

Differential diagnosis

• Multiple myloma
• Solitary metastasis
• Malignant fibrous histiocytoma
• Chondrosarcoma (dedifferentiated)
• Ewing sarcoma (if less than 25 years old)
• Giant cell tumor

Pathology

• Gross: Tan to grayish white with rubbery consistency
• Larger tumors may have myxoid, hemmorhagic, or necrotic foci
• Microscopic: Varies with the level of differentiation
  • Well-differentiated, low-grade tumor
    • Homogeneous spindle-shaped fibroblasts with ovoid nuclei
    • Little pleomorphism
    • Infrequent mitoses
    • Prominent  herringbone pattern of fascicles of cells
  • Poorly differentiated, high-grade tumor
    • Pleomorphic cells
    • Abundant mitoses
    • Hyperchromic nuclei
    • Higher propensity for metastasizing early

• Cellularity of tumor generally in inverse proportion to collagen production
• IHC: Positive for vimentin, very weakly positive for smooth muscle actin
• No definite etiology of fibrosarcoma known; genetic mutations likely play a role
• Patients with multiple neurofibromas may have a 10% lifetime risk of developing fibrosarcoma

Diagnosis and treatment

• Biopsy, in consultation with a musculoskeletal surgical oncologist
• Tumor grade guides treatment regimen
  • Grade I tumor
    • Surgery, in many cases limb-sparing surgery (wide excision with reconstruction)
    • Survival rate: 80% at 10 years
  • Grade II tumor
    • Surgery plus adjuvant chemotherapy, although no definitive recommendations exist regarding chemotherapy for these intermediate-grade tumors
  • Grade III tumor
    • Induction chemotherapy, limb-sparing surgical resection, and postoperative chemotherapy. 
    • Overall 5-year survival rate ranges from 35% to 70%, depending on the study
• Radiation usually administered only as a palliative measure for unresectable tumors or as a postoperative measure if margins were close or microscopically positive
• Aggressive thoracotomy has been advocated for resection of pulmonary metastases (similar to treatment for osteosarcoma lung metastases)

Prognosis/outcome

• Young age is favorable prognostic factor
  • According to Papagelopoulos et al, 5-year disease-free survival rate is 40% for patients 40 years or younger; only 12% for patients older than 40 years
• Fibrosarcomas of bone carry worse prognosis than those of soft tissue
• 15% local recurrence rate for surgically treated patients according to recent studies 
  • Univariate analysis of surgically treated patients: Age, location, grade, stage, surgical margins, and type of surgical procedure significantly affect disease-free survival and overall survival
• Prognosis  most closely correlated with the grade of the tumor and presence of metastases at time of diagnosis
  • Patients with low-grade tumor have better survival rate than patients with a high-grade tumor
  • Overall survival rates at 5 years range from 28% to 34% for high-grade tumors and 50%-83% for low-grade tumors

Recommended reading

Papagelopoulos et al.  Primary Fibrosarcoma of Bone: Outcome after Primary Surgical Treatment.  CORR 2000 Apr;(373):88-103.

Wittig J. and Villalobos C.  Other Skeletal Sarcomas OKU 2 Musculoskeletal Tumors Ch19 pg 198-200.

Papagelopoulos et al.  Clinicopathologic Features, Diagnosis, and Treatment of Fibrosarcoma of Bone.  Am J Orthop 2002;31:253-257.