Fibrosarcoma of Bone

DEFINITION AND PATHOGENESIS

• Primary fibrosarcoma: a fibroblastic malignancy producing variable amounts of collagen
• Central: arising from within the intramedullary canal
• Peripheral: arising from periosteal tissues
• Secondary fibrosarcoma: arises from a pre-existing lesion (with generally a poorer prognosis)
  • Post XRT
  • Ameloblastic fibroma
  • GCT
  • Fibrous dysplasia
  • Paget's disease
  • Dedifferentiated lwo-grade chondrosarcoma
  • Bone infarct
  • Chronic osteomyelitis
• Multicentric fibrosarcoma: rule out spindle cell melanoma or carcinoma metastases
• Congenital fibrosarcoma: extremely rare

IMPORTANCE

• Early dx and differentiation from benign lesions may be important for an otherwise dismal prognosis
• <5% of primary malignancies of bone

CLINICAL FEATURES

• Can present at any age but most likely in the fourth decade of life usually in the lower extremities with the femur and tibia being the most common sites
• Unusual sites reported:
  • Distal phalanx of a toe in a 12-yr old
• Can be primary or develop secondary to FD, GCT, XRT, Paget's, bone infarcts, and chronic osteomyelitis
• Often have a long duration of symptoms prior to their diagnosis
• Better prognosis if dxd prior to 10 years of age

RADIOLOGIC FEATURES

• Osteolytic with "motheaten" premeative appearance
• No sclerosis with cortical destruction
• Sequestrum may be seen

GROSS PATHOLOGY

• White and firm with marked collagen production
• Higher grade lesions permeate through cortical bone and are softer and fleshy

HISTOLOGIC/MOLECULAR FEATURES

• Spindled fibroblasts with nuclear pleomorphism
• Not as much collagen present with 'herring bone' pattern
• Frequent mitoses; sparse giant cells present
• No osteoid or cartilage production
• Immunohistochemistry
  • 12/17 + for PDGFRA and/or PDGFRB
    • (Recurrent coamplification of KIT, PDGFRA, and KDR)
• Molecular
  • Losses were most commonly detected at 6q, 8p, 9p, 10, 13q, and 20p
    • CDKN2A|CDKN2A was homozygously deleted in 7/11 patients\ homozygously deleted in 7/11 pts
  • Gains were seen at 1q, 4q, 5p, 8q, 12p, 15q, 16q, 17q, 20q, 22q (most frequent), and Xp
    • PDGF-B gene at 22q12.3-q13.1
      • 40% with presence of PDGF-B proteins
    • IGF1R at 15q26.3
    • CHD1L at 1q21.1
  • Ring chromosome
    • Reported on chromosome 6

DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS

• NOF
• Fibrous dysplasia
• GCT
• Fibromatosis (desmoid tumor)
• Osteosarcoma
• MFH
• Mesenchymal chondrosarcoma
• Metastasis, esp. melanoma and carcinoma

DISEASE COURSE AND TREATMENT

• Tx remains wide excision; chemotx not proven but treat as osteosarcoma
• Dismal results overall with 1/3 survival rate at 10 years for high grade lesions
• Prognosis most dependant upon histologic grade
• 5YS overall reported 28-34% in high grade tumors; 50-83% in low grade tumors
• Secondary fibrosarcomas carry a more ominous prognosis (10% 10 year survival)
• Congenital fibrosarcoma has a more favorable prognosis (directly related to age of dx) and may be amenable to intralesional excision + adjuvant (? neoadjuvant better) chemotx (controversial) without recurrence
  • <10 yrs old at dx, metastatic rate @ 5 yrs = 5%
  • < 5 yrs old at dx, metastatic rate @ 5 yrs = 7.3%
• LR in 43%

SPECIAL CONSIDERATION

• MULTIPLE DIFFUSE FIBROSARCOMA OF BONE
  
  

  • Rarely reported presenting with multiple osteolytic lesions
  • ? ESR reported (rule out myeloma)

• MYOFIBROSARCOMA OF BONE
  
  

  • Lytic destructive lesions, ± soft tissue extension, distal femur and pelvis reported; age 60-71
  • Cellular fascicular/storiform and hypocellular fibrous areas
  • Immunohistochemistry
    • + vimentin
    • + muscle actin (HHF35)
    • + ?-smooth muscle actin
    • +calponin and desmin
    • high molecular weight caldesmon
  • Wide resection required; distant metastases reported

• SECONDARY FIBROSARCOMA OF BONE

  • • Has been reported arising from a non-ossifying fibroma of bone with development of metastatic disease
      • Initial response to a single agent ifosfamide
      • Intra-abdominal metastasis associated with extrapancreatic tumor hypoglycemia

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