Giant cell tumor (GCT) of bone is typically a benign neoplasm occurring primarily in long bones of skeletally mature individuals.
It is characterized by richly vascularized tissue,
containing proliferating mononuclear stromal cells and multinucleated giant cells uniformly distributed.
It was first described by Sir Astley Cooper in 1818 [1] and has previously been referred by numerous terms,
namely osteoclastoma due to the similar appearance of multinucleated giant cells and osteoclasts.
Despite the benign histological appearance,
some GCT may be locally aggressive and recur after surgical excision.
Epidemiology and clinical characteristics
GCT is the sixth most common primary osseous neoplasm,
accounting for 5% of all primary bone tumors and approximately 20% of benign skeletal tumors.
[2,3]
It shows a slight female preponderance,
with 80% of GCT occurring in patients between 20 and 50 years of age,
with peak prevalence in the third decade of life.
It is rare in patients above 50 years of age (13%) and extremely rare below 14 years of age (3%).
[2,3]
Most GCT are located in long bones (75%–90%),
being the knee the most common specific location (50%–65%) and the distal femur the single most common site (23%–30%).
Other preferred sites include the proximal tibia (20%–25%),
distal radius (10%–12%),
sacrum (4%-9%) and proximal humerus (4%–8%).
When GCT occurs in the sacrum it usually displays an eccentric position relative to midline (which is a helpful finding in differentiating GCT in this location from chordoma).
Less frequent sites of involvement include the proximal femur (4%),
ilium (3%),
vertebral bodies (3%– 6%),
distal tibia (2%–5%),
proximal fibula (3%– 4%),
hand and wrist (1%–5%) and foot (1–2%).
GTC may also occur in sesamoid bones and in apophyses,
the latter being epiphyseal equivalents.
[1,2]
GCT are typically located in the meta-epiphyseal region,
often extending to the articular subchondral bone or even abutting the cartilage.
These lesions are thought to arise in the metaphysis and extend into the epiphyseal region after physeal closure.
As such,
in the rare instances when GCT occurs in skeletally immature patients,
it will be centered in the metaphysis.
Multifocal GCT are rare (less than 1% of cases) and most commonly arise in patients with Paget disease.
[1,4] In cases of patients with multifocal lesions or GCT-like lesions with unusual clinicoradiographic features,
one should consider brown tumor of hyperparathyroidism,
which is also rich in giant cells.
When in doubt,
patients should be tested for serum calcium,
phosphorus,
and parathyroid hormone levels.
About 5-10% of GCT are said to be malignant.
The term malignant GCT is used to describe tumors capable of malignant behavior and of producing distant metastasis to the lung.
This entity comprises benign metastasizing GCT,
malignant transformation of a former benign GCT (including primary malignant transformation from spontaneous tumor dedifferentiation and secondary malignant transformation following radiation therapy,
repeated curettage or resection),
and osteoclastic (giant-cell) sarcoma.
Benign metastasizing GCT,
reported in 1–6% of cases,
is thought to arise from hematogenous seeding of the tumor to the lungs (usually after treatment),
with implants demonstrating histologically benign appearance identical to that of the primary tumor.
Both malignant transformation of GCT and osteoclastic (giant-cell) sarcoma consist of sarcomatous growth,
the former occurring at the site of a previously documented GCT,
and the latter arising de novo in a patient with no history of GCT or in association with severe polyostotic Paget disease.
[1,2,5]
Patients with GCT commonly experience pain (usually reduced by rest),
local swelling and limited range of motion.
Acute onset of pain is usually related to pathologic fracture,
which may be the presenting symptom in 10-12% of patients.
[1,4]
Diagnosis and staging
Though radiographic findings usually suggest the diagnosis,
there is considerable overlap in imaging features of benign and malignant GCT,
as well as with other entities that may mimic this tumor.
As such,
accurate diagnosis of GCT demands not only careful clinicoradiographic correlation,
but also histological confirmation with core-needle or open biopsy.
Histologic diagnosis of GCT requires numerous multinucleated giant cells,
uniformly dispersed among a large population of mononuclear cells.
Other characteristic features include a highly vascular stroma,
containing numerous thin-walled capillaries,
often with small areas of hemorrhage.
Blood-filled cavities may also be seen amongst solid GCT areas,
denoting the presence of secondary aneurysmal bone cyst (ABC).
For precise assessment of tumor extension,
a full staging strategy should also be conducted.
This strategy could include:
- Computed tomography (CT) and/or magnetic resonance (MR) for local staging
- Total body bone scan to rule out additional asymptomatic bone lesions
- Chest radiograph/chest CT to exclude lung involvement