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Giant cell tumor

Tumor biology and incidence

  • Generally benign, locally aggressive lesions that can cause significant bony destruction
  • Accounts for approximately 15% of all symptomatic benign bone tumors
  • Rarely metastasize (< 5%)
  • Mesenchymal origin

Age

  • Generally occurs in patients with closed physes; less than 5% occur in patients with open growth plates
    • Most common in patients between ages 20 and 40; 80% of cases occur in patients over age 20
    • Extremely rare in patients younger than age 13 
    • Only 10% of cases occur in patients over age 65

Gender

M:F = 2:3

Presentation

  • Pain at involved site
  • Localized swelling and tenderness on palpation
  • Pathologic fracture
  • Back pain and occasionally neurologic compromise in spinal lesions

Physical findings

  • Pain, swelling, and decreased range of motion in area of lesion
  • Intra-articular pathologic fracture in about 10-20% of patients

Plain films

  • Lesions appear mostly lytic, lucent and eccentrically located within epiphysis
  • Lesions often efface subchondral bone
  • Lesions often characterized by extensive local destruction, cortical breakthrough and expansion into adjacent soft tissue
  • When located near epiphysis, lesions can penetrate through articular surfaces into adjacent joint
  • Mineralization of primary giant cell tumors rare, although recurrence or soft tissue lesions commonly demonstrates peripheral calcification
Site
  • Most commonly found in distal femur and proximal tibia (50% of lesions)
  • Also found in distal radius, proximal humerus, vertebrae, and sacrum
  • 75% found in epiphysis/metaphysis of long bones.
  • Eccentrically located in long bones
  • Centrally located in thin, tubular bones (hands, feet, fibula, ulna)
Size

Usually involves at least one half the diameter of the bone

Tumor effect on bone
  • Large lytic focus, typically with geographic margin
  • May extend into metaphysis or diaphysis of long bone
  • Often extends to involve subchondral bone
Bone response to tumor
  • Expansile, well marginated lesion
  • Margins of tumor typically nonsclerotic, although sclerotic peripheral margination may be seen
  • Erosion through cortex into soft tissues often outlined by thin rim of periosteal new bone (neo-corticalization)
Matrix

None present

Cortex
  • Lesion often expansile and thins cortices
  • Cortical breakthrough may be present
Soft tissue mass
  • May be present -- 20% of lesions invade cortex and break through to yield limited soft tissue mass
  • Soft tissue mass formed by giant cell tumor always results from cortical erosion
    • Osteosarcoma, Ewing sarcoma: Tumor may spread into soft tissues through Haversian canals in cortex
    • Produces pattern of soft tissue mass overlying intact cortex; pattern not seen in giant cell tumor
Radiographic Classification by Campanacci

Stage I (10% of lesions)

  • Early lesions
  • Involved bone maintains normal contour
  • Lesion is radiolucent, enlarging with sharply defined margination

Stage II (active lesion, 60% of lesions)

  • Lesion causes cortical erosion, deformity and expansion of bone
  • Limited endosteal response

Stage III (aggressive lesion, 30% of lesions)

  • Destructive lesion
  • Poorly outlined
  • Extends into subchondral bone or soft tissue
  • Cortical breakthrough and soft tissue mass may be present
  • Pathologic fracture may be present

Bone scan

  • Usually not required, although should be done as part of work up if lesion simulates primary malignant tumor of bone
  • Depending on aggressiveness of lesion, bone scan can be cold, suggesting a mostly lytic tumor

CT scan

  • Useful to determine exactly where intact bone remains prior to planning biopsy and definitive surgical approach
    • Surgical approach should be planned through region of weakened bone to maintain as much intact cortical bone as possible for reconstruction

MRI

  • May show fluid-fluid levels if aneurysmal bone cyst co-exists with giant cell tumor
  • May be more difficult to visualize residual cortical bone on MRI than on CT.
  • Helpful in defining the extent of soft tissue extension in Stage III lesions
  • Useful in cases where plain x-rays/CT scan do not adequately define the local extent of tumor
  • Intralesional hemosiderin deposition (focal regions of low T1 and T2-weighted signal) reported to be helpful differential feature typical for giant cell tumors

Differential diagnosis

If epiphyses closed

  • Aneurysmal bone cyst
  • Brown tumor of hyperparathyroidism
    • Lesions look very much alike histologically; measure serum calcium in all cases of giant cell tumor
  • Chondroblastoma
  • Osteoblastoma
  • Osteosarcoma
  • Fibrosarcoma of bone

If epiphysis open

  • Osteoblastoma
  • Aneurysmal bone cyst
  • Giant cell tumor rare in children

Pathology

  • Gross: Dark brown, hemorrhagic tissue
  • Microscopic: Sheets of multinucleated giant cells intermixed with oval mononuclear stromal cells
  • Stromal cells can have a variable appearance and may become spindled, but there is no atypia; giant cells less frequent in these areas
  • Mitoses may be frequent but have no clinical significance
  • Small amounts of bone or osteoid may be evident

Diagnosis and treatment

  • Depends on the site.
  • May consider bones as expendable or nonexpendable

Expendable bones (fibula, rib)

  • Resect lesion using wide en bloc excision to reduce risk of recurrence
  • May be wise to excise distal radius en bloc if cortex is extensively eroded with soft tissue mass

Nonexpendable bones

  • Perform intralesional curettage through large cortical window with extensive burring back to normal bone
  • Adjuvant treatment of the bony bed with phenol or liquid nitrogen may lower the recurrence risk
  • Fill defect with bone graft and/or methacrylate cement
  • Consider internal fixation with extensive lesion
  • If patient has spinal lesions with neurologic deficit, perform decompression of dura by whatever means necessary
  • Consider radiation after partial removal of axial lesions (spine, sacrum)
    • Possible risk of sarcomatous transformation after radiation; however, data regarding risk of radiation-associated malignant change are controversial

Complications

  • Pathologic fracture, either before or after surgery
  • 10-25% recurrence after intra-lesional treatment
    • Recurrence probably depends on the completeness of tumor removal: Recent reports suggest risk of recurrence may be decreased by use of adjuvant therapy (phenol, liquid nitrogen) and bone cement (methacrylate)
    • Use of liquid nitrogen may be associated with a risk of injury to soft tissues and nerves, as well as risk of later fracture
  • Less than 5% of patients with benign giant cell tumor develop metastases, usually to lungs
  • Rare malignant transformation of benign lesion may be observed with or without use of adjuvant radiotherapy

Recommended reading

Local Recurrence of Giant Cell Tumor of Bone After Intralesional Treatment with and without Adjuvant Therapy. Knochentumoren,A. 2008. J Bone Joint Surg Am. 2008; 90:1060-7Musculoskeletal Tumors OKU: AAOS. Giant Cell Tumor of Bone. James O. Johnston, MD.  2002 pp 113-118

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