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