Giant Cell Tumor Imaging

Updated: Oct 01, 2020
  • Author: Wilfred C G Peh, MD, MHSc, MBBS, FRCP(Glasg), FRCP(Edin), FRCR; Chief Editor: Felix S Chew, MD, MBA, MEd  more...
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Practice Essentials

Giant cell tumor (GCT) of 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. GCTs typically occur in adults aged 20-40 years. In most patients, giant cell tumors have an indolent course, but they can recur locally in as many as 50% of cases. Giant cell tumors usually occur de novo but may also occur as a rare complication of Paget disease of bone. [1, 2]  About 1-6% of benign tumors metastasize, most often to the  lung. Although benign metastases are usually indolent, they can compromise pulmonary function and occasionally result in death. [3, 4] Reported risk factors for lung metastasis are local recurrence, high Campanacci grading, and curettage and local irradiation of the primary lesion. [3, 5, 6, 7, 8, 9]  

GCTs constitute 5% of all primary bone tumors, and spinal GCTs (SGCTs) account for 2-15% of all GCTs. GCT is characterized genetically by highly recurrent somatic mutations at the G34 position of the H3F3A gene, encoding the histone variant H3.3, in stromal cells. When GCT complicates Paget disease of bone (GCT/PDB), it shows a more malignant phenotype, with 5-year survival being less than 50%. GCT/PDB is caused by a germline mutation in the ZNF687 gene. [7, 8]  

Radiography and MRI are the imaging modalities of choice for diagnosis. [6] The radiographic appearance of giant cell tumors is often characteristic. 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 degree of confidence is high for radiography in the appendicular skeleton. In the spine, the degree of diagnostic confidence is not high, as giant cell tumors usually cannot be differentiated from other types of tumors. Tumors in the sacrum are recognizable, and these may be diagnosed on the basis of their appearance and location.

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. [10]  The diagnostic accuracy of MRI is high, especially when MRIs are interpreted in conjunction with plain radiographs. [11, 12, 13, 14, 15, 16]  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.

CT scans and bone scans are usually less useful than other examinations. CT does not usually add much diagnostic information to the radiographic results. CT scans are more useful in complex-shaped bones, such as the vertebrae or pelvic bones, because the details of the lesion may not be depicted well on radiographs. Uptake in giant cell tumors is usually diffuse in all phases. The degree of uptake is not correlated with the grade of the tumor or the malignancy. Bone scanning is not usually required in the evaluation of a giant cell tumor, except for the rare case in which multicentric giant cell tumors are suspected. [14, 17] ​Giant cell tumors cannot be confidently differentiated from other tumors and diseases by using bone scans alone. [18]

(Radiologic features of giant cell tumors are demonstrated in the images below.)

Lateral radiograph of the L3 vertebra shows a gian 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.
CT scan of the abdomen shows an expanding mass tha 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.

Most giant cell tumors occur in the long bones (see the images below), and almost all are located at the articular end of the bone. 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 shows a septate lytic l Anteroposterior radiograph shows a septate lytic lesion in the subarticular location of the proximal femur. After curettage of the giant cell tumor, infection developed, and the insertion of antibiotic beads was required.
Anteroposterior radiograph of the left wrist shows Anteroposterior radiograph of the left wrist shows an expanded lytic lesion in the subarticular position of the distal ulna, which is typical for a giant cell tumor.

Giant cell tumors may also occur in the vertebrae (as seen in the image below). 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.

CT scan of the L3 vertebra shows a giant cell tumo CT scan of the L3 vertebra shows a giant cell tumor causing the vertebral body to expand and extending into the spinal canal.

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, as the CT scan below demonstrates.

CT scan of the abdomen shows an expanding mass tha 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.

Patients often complain of pain and swelling at the affected site. Pathologic fracture (seen in the images below) is present in 10% of patients.

Anteroposterior radiograph of the right shoulder s 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.
Anteroposterior radiograph of the knee shows a pat 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 (multicentric tumors are shown in the images below). 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. [19, 20, 21, 11, 12, 22]

Anteroposterior radiograph of the pelvis shows mul 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.

Campanacci and Enneking classification systems

The Campanacci grading system for GCTs is based on the radiographic appearance of the tumors, as follows [6, 23]

  • A grade 1 lesion (latent) has a well-defined margin and an intact cortex.
  • A grade 2 lesion (active) has a relatively well-defined margin but no radiopaque rim, and the cortex is thinned and moderately expanded.
  • A grade 3 lesion (aggressive) has indistinct borders and cortical destruction.

The Enneking clinicoradiologic classification consists of 4 stages, as follows [6] :

  • Stage 1 (latent):  confined totally by bone, asymptomatic, inactive on bone scan, histologically benign lesion.
  • Stage 2 (active): expanded cortex with no breakthrough, symptomatic (often with a pathologic fracture), active on bone scan, histologically benign lesion.
  • Stage 3 (aggressive): rapidly growing mass, cortical perforation with soft-tissue mass, may metastasize, symptomatic, extensive activity on bone scan, histologically benign.
  • Stage IV (malignant): sarcomatous lesion contiguous with a benign GCT.

 

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Radiography

The most important radiographic findings of giant cell tumor are the location of the tumor, its lytic nature, and the lack of a host response. Typically, giant cell tumors are expansile, osteolytic, radiolucent lesions without sclerotic margins and usually without a periosteal reaction. Septa, found in the image below, may be seen in the lesion in 33-57% of patients; these represent nonuniform growth of the tumor rather than true septa. The tumors are typically in the range of 5-7 cm in diameter when they are discovered. [13]

Anteroposterior radiograph shows a septate lytic l Anteroposterior radiograph shows a septate lytic lesion in the subarticular location of the proximal femur. After curettage of the giant cell tumor, infection developed, and the insertion of antibiotic beads was required.

Most giant cell tumors occur in the long bones; approximately 50% are located in the bones around the knee. Location is important in the diagnosis of giant cell tumor. Most tumors are eccentric and are seen in a subarticular location (see the first 2 images below); however, the tumor originates in the metaphysis, and the common epiphyseal involvement is the result of the patient's skeletal maturity (see the third image below).

Anteroposterior radiograph of the knee shows a pat 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.
Anteroposterior radiograph of the left wrist shows Anteroposterior radiograph of the left wrist shows an expanded lytic lesion in the subarticular position of the distal ulna, which is typical for a giant cell tumor.
Anteroposterior radiograph of the right shoulder s 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.

Early lesions may lie solely in the metaphysis. A narrow zone of transition with a lack of sclerosis at its margins is a distinctive finding and strongly suggestive of the diagnosis. When sclerosis of the tumor margins is present, it is seldom complete. Periosteal reactions are not usually seen; the lack of a host-reactive response is typical of giant cell tumors.

Giant cell tumors in the spine (seen below) are uncommon and account for only 5% of giant cell tumors. The sacrum is the most common location. Patients with these tumors tend to be slightly younger than those with tumors in the appendicular skeleton. The location in the vertebrae can vary, but the tumor most commonly involves the vertebral body. On radiographs, the tumors may be seen in areas of destruction of the vertebral body with invasion of the posterior elements. The tumor can cause vertebral collapse and spinal cord compression, especially when it involves the posterior elements.

Lateral radiograph of the L3 vertebra shows a gian 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.

Degree of confidence

The degree of confidence is high for radiography in the appendicular skeleton. In the spine, the degree of diagnostic confidence is not high, as giant cell tumors usually cannot be differentiated from other types of tumors. Tumors in the sacrum are recognizable, and these may be diagnosed on the basis of their appearance and location.

Unusual forms of certain tumors may mimic giant cell tumors, as follows:

  • Telangiectatic or fibrogenic variants of osteosarcoma may not produce visible ossifications or calcifications. These variants may be eccentric and may extend to the subarticular surface, mimicking a giant cell tumor. Malignant fibrous histiocytomas occur in a similar age group and can also mimic a giant cell tumor.
  • Brown tumors of hyperparathyroidism are well known in the differential diagnosis of giant cell tumors. [17]
  • Chondroblastomas may be mistaken for giant cell tumors because of their subarticular location; however, careful review of the radiographs usually reveals that the epicenter lies in the epiphysis rather than in the metaphysis. The presence of chondroid calcifications further supports the diagnosis of chondroblastoma.
  • Aneurysmal bone cysts may be only slightly expansile in the early stages, and they can extend to the subarticular cortex, mimicking a giant cell tumor. These cysts usually occur in younger patients. Approximately 29% of aneurysmal bone cysts are reported to be associated with some other solid bone lesion, 39% of which are giant cell tumors.
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Computed Tomography

CT findings are similar to radiographic findings for giant cell tumor of bone. Marginal sclerosis, cortical destruction, and soft-tissue masses are seen more clearly on CT scans than on radiographs, and fluid-fluid levels are occasionally seen but are not specific. [24]  The degree of confidence is high when CT is used in conjunction with radiography, but CT does not usually add much diagnostic information to the radiographic results. CT scans are more useful in complex-shaped bones, such as the vertebrae or pelvic bones, because the details of the lesion may not be depicted well on radiographs. CT is also useful in surgical planning.

(CT scan characteristics of giant cell tumors are demonstrated in the images below.)

CT scan of the abdomen shows an expanding mass tha 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.
Coronal CT scan of a giant cell tumor of the dista Coronal CT scan of a giant cell tumor of the distal ulna. The radiographic findings showed an expanded subarticular lesion.
Coronal CT scan of the skull shows a giant cell tu Coronal CT scan of the skull shows a giant cell tumor arising from the temporal bone. The large extraosseous component that extends into the middle cranial fossa is well visualized on images obtained by using a soft-tissue window.
CT scan of the L3 vertebra shows a giant cell tumo CT scan of the L3 vertebra shows a giant cell tumor causing the vertebral body to expand and extending into the spinal canal.
Axial CT scan of the skull base shows a giant cell Axial CT scan of the skull base shows a giant cell tumor arising from the left temporal bone.
CT scan shows the full extent of a giant cell tumo CT scan shows the full extent of a giant cell tumor in the left ilium. Septa are seen in the lesion.

 

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Magnetic Resonance Imaging

On T1-weighted images, giant cell tumors may show heterogeneous or homogeneous signal intensity characteristics. The signal intensity is usually low or intermediate, but areas of high signal intensity, caused by recent hemorrhage, may be noted.

On T2-weighted images, heterogeneous low-to-intermediate signal intensity is seen in solid areas of the tumor (see the image below). Areas of low signal intensity may be exaggerated on T2-weighted, spin-echo images, and these may be even more exaggerated on gradient-echo weighted images because of the presence of hemosiderin. Hemosiderin is detected in more than 63% of giant cell tumors, and its presence is probably the result of extravasated red blood cells coupled with the phagocytic function of the tumor cells. [25]

T2-weighted coronal MRIs of the wrist show a giant T2-weighted coronal MRIs of the wrist show a giant cell tumor located in a subarticular position in the distal radius. The lesion is heterogeneous and hyperintense.

Cystic areas are common and are seen as areas of high signal intensity on T2-weighted images. Fluid-fluid levels may be seen, as in the image below. Peritumoral edema is uncommon in the absence of a fracture. The tumor is usually heterogeneously enhancing with the intravenous administration of contrast material.

T2-weighted axial MRI of the knee shows multiple f T2-weighted axial MRI of the knee shows multiple fluid-fluid levels in a giant cell tumor of the distal femur.

Degree of confidence

The degree of confidence is high for MRI in imaging the appendicular skeleton. This modality is sensitive in detecting soft-tissue changes, intra-articular extension, and marrow changes. MRI is the best method for assessing subchondral breakthrough and the extension of tumor into an adjacent joint. Its diagnostic accuracy is high, especially when MRIs are interpreted in conjunction with plain radiographs.

In the spine, tumors such as osteoblastomas and aneurysmal bone cysts, as well as metastases, may be found in the same location as giant cell tumors, and they may have overlapping MRI characteristics.

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Angiography

Angiography is not usually required in the evaluation of a giant cell tumor. Neovascularity is demonstrated in 80% of giant cell tumors, along with an intense, inhomogeneous capillary blush. Unfortunately, overlap in the angiographic features of malignant bone tumors, benign tumors, and nonneoplastic lesions precludes the use of angiography in making the differential diagnosis. Although angiography can be used to assess the intraosseous and extraosseous extent of a tumor, which is useful in planning surgery, MRI has largely replaced it in surgical planning.

Preembolization angiogram of the right lower limb Preembolization angiogram of the right lower limb (left) shows a hypervascular giant cell tumor located at the lateral aspect of the distal femur. After embolization of the feeder artery to the tumor, the image (right) shows markedly reduced tumor vascularity.

 

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