Introduction
Gross appearance of a giant cell tumor in the distal radius. The tumor has a predominance of foam cells, which cause the bright-yellow color.
CT scan of the abdomen shows an expanding mass that arose from one of the left ribs. The histologic findings indicated that the mass was a giant cell tumor.
Background
Giant cell tumor of the bone is a relatively uncommon tumor that is characterized by the presence of multinucleated giant cells. This type of tumor is usually regarded as benign. In most patients, giant cell tumors have an indolent course, but they can recur locally in as many as 50% of cases. Metastasis to the lungs may occur.
Cooper first reported giant cell tumors in the 18th century; in 1940, Jaffe and Lichtenstein defined giant cell tumor more strictly to distinguish it from other tumors. Giant cell tumors usually occur de novo but may also occur as a rare complication of Paget disease of the bone.
Related eMedicine topics:
Giant Cell Tumor (Orthopedic Surgery)
Paget Sarcoma
Benign Skull Tumors
Skull Base Tumors
Bone Metastases
Frequency
International
Giant cell tumor of the bone accounts for 4-5% of primary bone tumors and 18.2% of benign bone tumors. The incidence is increased in patients with Paget disease of the bone, in which giant cell tumor is a rare neoplastic complication. Giant cell tumor is a rare complication compared with Paget sarcoma,1 which has an incidence of sarcomatous change of <5%.
Mortality/Morbidity
- Giant cell tumors are commonly benign.
- The tumors are malignant in 5-10% of patients.
- Malignant giant cell tumors of bone usually result from secondary malignant transformation after radiation treatment.
Race
- All races are affected.
- A higher incidence is noted in people of Chinese descent, in whom the incidence is approximately 20% among those with primary bone tumors (which is 4-5% in other groups).
Sex
A slight female predominance is noted; approximately 50-57% of cases involve female patients.
Age
Typically, giant cell tumors occur in skeletally mature patients aged 20-40 years. The incidence peaks in those aged 20-30 years.
- Giant cell tumors are much less common in children; the rate is 5.7% in skeletally immature patients.
- Vertebral tumors tend to occur in younger patients; 29% of these tumors occur in patients younger than 20 years.
- Multicentric giant cell tumors also occur in a younger group, with a peak incidence in patients aged 10-20 years. Multicentric tumors are found in fewer than 1% of patients.
Presentation
Natural history and presentation
Most giant cell tumors (60%) occur in the long bones, and almost all are located at the articular end of the bone (see Image below and Image 5 in Multimedia). Metaphyseal involvement may occur in skeletally immature patients. Common sites include the proximal tibia, distal femur, distal radius, and proximal humerus, although giant cell tumors have also been reported to occur in the pubic bone, calcaneus, and feet.
Anteroposterior radiograph of the right shoulder shows a pathologic fracture through a giant cell tumor in the proximal humerus. The tumor involves both the epiphysis and the metaphysis.
Giant cell tumors may also occur in the vertebrae (see Image below and Image 6 in Multimedia). Giant cell tumors are 3-4 times as common in the sacrum as they are in the rest of the spine. Sacral tumors may be so extensive that they involve the entire sacrum. Rarely, the tumor may extend across the sacroiliac joint to involve the adjacent ilium or may extend across the L5-S1 disk to involve the posterior elements of the L5 vertebra.
Lateral radiograph of the L3 vertebra shows a giant cell tumor as a lytic lesion in the vertebral body, with expansion of the bone and internal septa.
The location of giant cell tumors within the spine can vary, and the most commonly involved areas are the vertebral body and the vertebral arch. Rarely, giant cell tumors develop in the ribs (see Image below and Image 7 in Multimedia).
CT scan of the abdomen shows an expanding mass that arose from one of the left ribs. The histologic findings indicated that the mass was a giant cell tumor.
Giant cell tumors typically occur in adults aged 20-40 years. Patients often complain of pain and swelling at the affected site. Pathologic fracture is present in 10% of patients (see Image below and Image 8 in Multimedia).
Anteroposterior radiograph of the knee shows a pathologic fracture through a giant cell tumor in the distal femur. The tumor extends to the subarticular surface of the femur.
Vertebral giant cell tumors may extend into the spinal canal and compress the spinal cord, resulting in neurologic symptoms. Giant cell tumors are rarely multicentric (see Image below and Image 9 in Multimedia). This condition should be considered when patients present with giant cell tumors in the hands, because the incidence of tumors in the small bones of the hand and sacrum is increased.2,3,4
Anteroposterior radiograph of the pelvis shows multicentric giant cell tumors. Giant cell tumors are demonstrated in the left ilium and in the greater trochanter of the left femur.
Giant cell tumor of the bone has a distinctive microscopic appearance, and its diagnosis is usually not difficult, despite the fact that the gross appearance of a giant cell tumor is less characteristic. The tumor is usually seen as a soft, brown mass; areas of hemorrhage, which appear dark red, and areas of collagen, which appear gray, may be observed.
On cut sections, necrosis and blood-filled spaces are commonly seen. Intact resected specimens of giant cell tumor are rare because most patients are treated by curettage. Grossly, the curettage material is soft, friable, and dark brown. Although called giant cell tumor, the basic proliferating cell is the background mononuclear stromal cell,5 in which the characteristic osteoclastlike giant cells are uniformly distributed (see Image below and Image 1 in Multimedia). The origin of these mononuclear cells is not fully known, but they are believed to be derived from primitive mesenchymal stem cells or cells of a histiocytic macrophage origin.
Typical histologic appearance of giant cell tumor of the bone. Note the uniform distribution of osteoclastlike giant cells in a background of mononuclear cells (stained with hematoxylin and eosin, original magnification X80).
Osteoclastlike giant cells have an identical nuclear morphology, presumably formed by the fusion of mononuclear stromal cells. Mononuclear cells commonly have a round or ovoid nucleus, but occasionally they can be spindle shaped. They possess a variable amount of eosinophilic cytoplasm. No intercellular matrix is produced by the mononuclear cells or the multinucleated giant cells. Mitotic activity is highly variable and of no prognostic significance. Similarly, the grade of a giant cell tumor of the bone has no prognostic significance.
Although a typical giant cell tumor of the bone is easy to diagnose, a few histologic variants are commonly seen. Small foci of aneurysmal bone cysts are common in giant cell tumor (see Image below and Image 2 in Multimedia).
Foci of aneurysmal bone cyst areas are common in giant cell tumors (stained with hematoxylin and eosin, original magnification X80).
In rare circumstances, these foci may dominate the histologic features; therefore, thorough sampling for an underlying giant cell tumor is indicated. Occasionally, a giant cell tumor is composed predominantly of spindle cells and foam cells to the extent that no discernible osteoclastlike giant cells are found. Such tumors can be easily mistaken for benign fibrous histiocytoma or xanthoma (see Image below and Image 3 in Multimedia). Again, if the clinical and radiologic impressions suggest a giant cell tumor, thorough tissue sampling of areas in which giant cell tumors typically occur is warranted; usually, a minute residual focus of giant cell tumor is found.
Gross appearance of a giant cell tumor in the distal radius. The tumor has a predominance of foam cells, which cause the bright-yellow color.
Although giant cell tumor forms no intercellular matrix, foci of reactive bone formation can be seen, especially in tumors complicated by fracture. Areas of infarct are not uncommon in giant cell tumors. Intravascular tumor emboli may be found in the periphery of some giant cell tumors, but this finding does not appear to be correlated with its metastatic potential. Occasionally, an otherwise typical giant cell tumor of the bone can metastasize, usually to the lungs (see Image below and Image 4 in Multimedia). Surprisingly, metastatic giant cell tumor does not have an ominous prognosis; patients can expect long-term survival after the metastases are surgically excised.
Giant cell tumor metastasis to the lung (stained with hematoxylin and eosin, original magnification X20).
Note that multinucleated osteoclastlike giant cells are not pathognomonic of giant cell tumor of bone. Osteoclastlike giant cells can be found in a wide variety of normal, reactive, benign, and malignant neoplastic conditions. Brown tumor in hyperparathyroid bone disease is an important nonneoplastic mimic of giant cell tumors. Hyperparathyroid bone disease is a generalized metabolic disease with increased serum calcium levels, whereas giant cell tumor is a localized disease; while the 2 can be histologically identical, they have different clinical presentations and radiologic appearances.
Giant cell reparative granuloma is a benign reparative lesion that affects the small bones of the hands and feet. It is histologically similar to giant cell tumors of bone. Other primary bone tumors that contain osteoclastlike giant cells include chondroblastoma, chondromyxoid fibroma, and giant cell osteosarcoma.
Preferred Examination
The radiographic appearance of giant cell tumors is often characteristic.
Magnetic resonance imaging (MRI) is sensitive for the detection of soft-tissue changes, intra-articular extension, and marrow changes. MRI is the best method for assessing subchondral breakthrough and extension of tumor into an adjacent joint. Its diagnostic accuracy is high, especially when MRIs are interpreted in conjunction with plain radiographs.
Computed tomography (CT) scans and bone scans are usually less useful than other examinations.
Limitations of Techniques
On radiographs, typical giant cell tumors are usually easily distinguished from other bone tumors. Giant cell tumors are lytic, subarticular, and eccentric, and they are often lacking a sclerotic rim; however, unusual variants may make the radiographic diagnosis difficult.
The disadvantages of MRI are its relatively high cost and limited availability. In addition, some patients experience claustrophobia during the examination and may require sedation. MRI is also contraindicated in patients with cardiac pacemakers, orbital foreign bodies, and noncompatible aneurysmal clips.
Differential Diagnoses
Aneurysmal Bone Cyst
Chondroblastoma
Hyperparathyroidism, Primary
Other Problems to Be Considered
Telangiectatic or fibrogenic variants of osteosarcoma
Malignant fibrous histiocytoma (bone)
Metastasis
Plasmacytoma
More on Giant Cell Tumor |
 Overview: Giant Cell Tumor |
| Imaging: Giant Cell Tumor |
| Multimedia: Giant Cell Tumor |
| References |
| Further Reading |
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References
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Further Reading
Related eMedicine topics:
Giant Cell Tumor (Orthopedic Surgery)
Paget Sarcoma
Benign Skull Tumors
Skull Base Tumors
Bone Metastases
Keywords
giant cell tumor, osteoclastoma, multinucleated giant cells, Paget disease, aneurysmal bone cysts, osteoclastlike giant cells
