(Radiographics. 2001;21:1283-1309.)
© RSNA, 2001
Imaging of Giant Cell Tumor and Giant Cell Reparative Granuloma of Bone: Radiologic-Pathologic Correlation1
Mark D. Murphey, MD,
George C. Nomikos, MD,
Donald J. Flemming, CDR, USN, MC,
Francis H. Gannon, MD,
H. Thomas Temple, MD and
Mark J. Kransdorf, MD
1 From the Departments of Radiologic Pathology (M.D.M., G.C.N.) and Orthopedic Pathology (F.H.G.), Armed Forces Institute of Pathology, 6825 16th St NW, Bldg 54, Rm M-133A, Washington, DC 20306; the Departments of Radiology and Nuclear Medicine, Uniformed Services University of Health Sciences, Bethesda, Md (M.D.M., D.J.F.); the Department of Radiology, National Naval Medical Center, Bethesda, Md (D.J.F.); the Department of Orthopedic Surgery, University of Miami School of Medicine, Miami, Fla (H.T.T.); the Department of Radiology, University of Maryland School of Medicine, Baltimore, Md (M.D.M.); and the Department of Radiology, Mayo Clinic, Jacksonville, Fla (M.J.K.). Received April 9, 2001; revision requested April 17 and received May 17; accepted May 18. Address correspondence to M.D.M. (e-mail: murphey@afip.osd.mil).
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Abstract
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The radiologic features of giant cell tumor (GCT) and giant cell reparative granuloma (GCRG) of bone often strongly suggest the diagnosis and reflect their pathologic appearance. At radiography, GCT often demonstrates a metaepiphyseal location with extension to subchondral bone. GCRG has a similar appearance but most commonly affects the mandible, maxilla, hands, or feet. Computed tomography and magnetic resonance (MR) imaging are helpful in staging lesions, particularly in delineating soft-tissue extension. Cystic (secondary aneurysmal bone cyst) components are reported in 14% of GCTs. However, biopsy must be directed at the solid regions, which harbor diagnostic tissue. These solid components demonstrate low to intermediate signal intensity at T2-weighted MR imaging, a feature that can be helpful in diagnosis. Multiple GCTs, although rare, do occur and may be associated with Paget disease. Malignant GCT accounts for 5%–10% of all GCTs and is usually secondary to previous irradiation of benign GCT. Treatment of GCT usually consists of surgical resection. Recurrence is seen in 2%–25% of cases, and imaging is vital for early detection. Recognition of the spectrum of radiologic appearances of GCT and GCRG is important in allowing prospective diagnosis, guiding therapy, and facilitating early detection of recurrence.
Index Terms: Bone neoplasms, 20.274, 20.3182, 30.3182, 40.3182 • Bone neoplasms, diagnosis, 40.11, 40.1211, 40.1214, 40.1216 • Giant cell tumor, 20.3182, 30.3182, 40.3182 • Granuloma, giant-cell reparative, 20.274
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LEARNING OBJECTIVES FOR TEST 6
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After reading this article and taking the test, the reader will be able to:
- Describe the spectrum of radiologic findings in GCT and GCRG of bone.
- Explain the pathologic basis for the radiologic features of GCT and GCRG of bone.
- Determine the presence of and diseases associated with multiple GCT and the significance of the diagnosis of malignant GCT.
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Introduction
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Giant cell tumor (GCT) of bone was first described by Sir Astley Cooper in 1818 (1). Historically, the lesion has been referred to by numerous terms, including myeloid sarcoma, tumor of myeloplaxus, osteoblastoclastoma, and osteoclastoma (2–5).
GCT is a relatively common skeletal tumor, accounting for 4%–9.5% of all primary osseous neoplasms and 18%–23% of benign bone neoplasms (6–11). Radiography often strongly suggests the diagnosis and reveals an eccentric, lytic lesion centered in the metaepiphysis and extending to subchondral bone with expansile remodeling but lacking internal mineralization. Additional imaging modalities including bone scintigraphy, computed tomography (CT), and magnetic resonance (MR) imaging are frequently used to evaluate these lesions for staging purposes and especially to evaluate lesions in unusual locations.
GCT is typically benign and solitary. However, multiple lesions have been described (although they are rarely associated with Paget disease), and 5%–10% of lesions may be malignant (6–11). Giant cell reparative granuloma (GCRG) is a related lesion that most frequently affects the mandible, maxilla, hands, or feet. This lesion represents a reactive process rather than a true neoplasm. The radiographic features of GCRG are similar to those of GCT, although extension to subchondral bone in lesions of the appendicular skeleton is uncommon. In this article, we discuss and illustrate the imaging appearances of GCT and GCRG of bone with emphasis on the pathologic causes of these features. We also discuss treatment, recurrence, and prognosis in these disease entities.
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Giant Cell Tumor
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Pathologic Features
At histologic analysis, GCTs contain a prominent and diffuse osteoclastic giant cell component and have been referred to in the past as osteoclastomas. However, although the mere presence of giant cells may suggest the diagnosis, this finding is by no means specific, and numerous lesions may demonstrate a similar histologic appearance (12,13). Diagnosis requires careful clinical and radiologic correlation and histologic evaluation of the mononuclear component to exclude other entities (Fig 1). A true GCT of bone should contain a large number of giant cells in a diffuse distribution in a background of mononuclear cells. These mononuclear cells are predominantly round, oval, or polygonal and may resemble normal histiocytes. Moreover, fusion of these cells may result in giant cell formation (Fig 1). The nuclei of the stromal cells are indistinguishable from those of the multinucleated giant cells, a feature that can be helpful in distinguishing GCT from other lesions in the pathologic differential diagnosis. Mitotic figures in the mononuclear cells may be abundant, particularly in women with increased endogenous or exogenous hormone levels owing to pregnancy or use of oral contraceptives (10).
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Figure 1a. Typical pathologic appearance of a GCT. (a) Photograph of a coronally sectioned whole mounted specimen (hematoxylin-eosin [H-E] stain) shows a GCT replacing the marrow of the distal radius (*) and extending to subchondral bone (large arrowheads). The lesion has a narrow zone of transition between the tumor margin and normal trabecular bone (small arrowheads). (b) High-power photomicrograph (original magnification, x250; H-E stain) shows both multinucleated giant cells (arrows) and intervening mononuclear cells.
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Figure 1b. Typical pathologic appearance of a GCT. (a) Photograph of a coronally sectioned whole mounted specimen (hematoxylin-eosin [H-E] stain) shows a GCT replacing the marrow of the distal radius (*) and extending to subchondral bone (large arrowheads). The lesion has a narrow zone of transition between the tumor margin and normal trabecular bone (small arrowheads). (b) High-power photomicrograph (original magnification, x250; H-E stain) shows both multinucleated giant cells (arrows) and intervening mononuclear cells.
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The stroma of most GCTs is vascular and contains numerous thin-walled capillaries, often with small areas of hemorrhage (14). These lesions may be associated with secondary aneurysmal bone cyst (ABC) formation but also contain solid areas with the typical histologic appearance of GCT (6–11). The identification of these solid areas of GCT allows differentiation from primary ABC, which contains only hemorrhagic cystic regions. The pathologic differential diagnosis of GCT is extensive, including (but not limited to) GCRG, brown tumor of hyperparathyroidism, osteoblastoma, chondroblastoma, ABC, nonossifying fibroma, foreign body reaction, and osteosarcoma with abundant giant cells. These lesions can be difficult to distinguish from one another, particularly at fine-needle aspiration or with frozen section specimens, emphasizing the need for careful and thorough clinical, pathologic, and radiologic correlation (6–15). This is particularly true of brown tumor of hyperparathyroidism, which can be indistinguishable from GCT at pathologic analysis. Laboratory analysis (calcium, phosphate, and parathormone levels) should be performed to exclude this possibility in all cases.
At gross pathologic examination, GCTs are relatively large lesions eccentrically located in metaepiphyseal bone and extending to the articular surface (Fig 1). Cortical bone is usually expanded, and, although a periosteal rim is typically maintained, soft-tissue extension is not uncommon. The GCT tissue is often soft, friable, and fleshy, with a variable appearance including areas of fibrosis (white), hemorrhage (red to brown depending on chronicity), and xanthomatous regions (yellow).
Clinical Characteristics
As mentioned earlier, GCT is a relatively common skeletal tumor. Although GCT affects all races, there is an unusually high prevalence in China and southern India (state of Andhra Pradesh) (16–18). Unlike the majority of osseous neoplasms, benign GCT affects women more commonly than men in most series, with ratios ranging from 1.1:1 to 1.5:1 (6,8,11,19–21). Lesions in younger patients and those involving the spine demonstrate an even higher female predilection (2.3–2.5:1 ratio) (22,23). In contrast, malignant GCT occurs more frequently in men (3:1 ratio) (9–11). The vast majority of GCTs affect skeletally mature patients, with approximately 80% occurring in patients between 20 and 50 years of age (6–11,24). The peak prevalence is in the third decade of life. A diagnosis of GCT in patients under 14 years old (ie, skeletally immature patients) should be viewed with caution and skepticism because only 1%–3% of GCTs are reported in patients in this age range (6–11,25). On the other hand, 9%–13% of affected patients are over 50 years of age (9–19). Clinical symptoms are nonspecific and include (in order of decreasing frequency) pain, local swelling, and limited range of motion of the adjacent joint. Pain is usually of several months duration and is reduced by rest. It is likely related to associated pathologic fracture, which may cause the acute onset of pain and lead to clinical presentation in 10% of patients (9). Neurologic symptoms may be associated with spine lesions.
Lesion Location
The location of GCT is one of the most important features suggesting the diagnosis because approximately 84%–99% of lesions extend to within 1 cm of subarticular bone (7,11,26,27). The exact site of origin of GCT has been controversial, although in our opinion and experience these lesions arise on the metaphyseal side of the epiphyseal plate (19,20,24,28,29). This accounts for the fact that in the rare instances of lesions affecting skeletally immature patients, location is in metadiaphyseal rather than metaepiphyseal bone because the open epiphyseal plate acts as a barrier to tumor growth (Fig 2). Similarly, we are unaware of any occurrences of GCT isolated to the epiphysis of a long bone in a skeletally immature patient (28).
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Figure 2a. GCT of the distal radius in a skeletally immature 16-year-old patient. (a) Anteroposterior radiograph of the wrist reveals a multiloculated lytic lesion in the distal radius with mild expansile remodeling. The lesion is centered in the metadiaphysis owing to lesion origin on the metaphyseal side of the epiphyseal plate (arrowheads) and a barrier to growth caused by the open physis (arrow). (b) Photograph of the coronally sectioned whole mounted specimen (H-E stain) clearly demonstrates that the majority of the lesion is in the metadiaphysis, except where the growth plate has partially closed and the GCT has extended to subchondral bone (arrows). The open component of the physis laterally (black arrowheads) is a barrier to tumor growth in this region. Areas of fibrosis (white arrowheads) and hemorrhage (*) are also seen.
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Figure 2b. GCT of the distal radius in a skeletally immature 16-year-old patient. (a) Anteroposterior radiograph of the wrist reveals a multiloculated lytic lesion in the distal radius with mild expansile remodeling. The lesion is centered in the metadiaphysis owing to lesion origin on the metaphyseal side of the epiphyseal plate (arrowheads) and a barrier to growth caused by the open physis (arrow). (b) Photograph of the coronally sectioned whole mounted specimen (H-E stain) clearly demonstrates that the majority of the lesion is in the metadiaphysis, except where the growth plate has partially closed and the GCT has extended to subchondral bone (arrows). The open component of the physis laterally (black arrowheads) is a barrier to tumor growth in this region. Areas of fibrosis (white arrowheads) and hemorrhage (*) are also seen.
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The most common specific location of GCT is about the knee (50%–65% of cases) (2,6–11,30–33). The single most common site is the distal femur (23%–30% of cases) (Fig 3), followed by the proximal tibia (20%–25%) (Fig 4), distal radius (10%–12%) (Fig 5), sacrum (4%–9%) (Figs 6, 7), and proximal humerus (4%–8%) (6–11,23, 30–37). Other, less frequent sites of involvement include the proximal femur (4% of cases), innominate bone (3%), vertebral bodies (3%–6%), distal tibia (2%–5%), proximal fibula (3%–4%), hand and wrist (1%–5%), and foot (1%–2%) (38–52). GCTs occurring in other anatomic sites are rare (53,54). GCTs can also occur in sesamoid bones, particularly the patella (the largest sesamoid bone) (Fig 8) and apophyses (eg, the greater trochanter), which are considered epiphyseal equivalents in terms of bone neoplasm origin (20,55).
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Figure 3a. GCT of the distal femur in a 35-year-old man. (a, b) Lateral knee (a) and specimen (b) radiographs show a geographic lytic lesion with a narrow zone of transition and no rim of sclerosis (arrowheads) centered on the metaphyseal side of the closed growth plate (arrows in b). (c) Angiogram reveals marked tumor stain (*) reflecting lesion hypervascularity and eccentric lesion location in the medial condyle. (d) Lateral bone scintigram shows marked radionuclide uptake in the femoral GCT. There is also increased uptake in the adjacent patella and tibia, findings that reflect hyperemia and disuse osteopenia rather than tumor extension. (e) CT scan shows lack of mineralization in the lesion and anterior expansile remodeling of bone. (f) Axial T1-weighted MR image (repetition time msec/echo time msec = 500/20) shows marrow replacement with intermediate-signal-intensity tissue (straight arrow) and associated anterior soft-tissue extension (curved arrow). The signal intensity of the lesion was identical at T2-weighted MR imaging. (g, h) Photographs of the sagittally sectioned gross specimen (g) and the whole mounted specimen (H-E stain) (h) show the GCT (*) extending to subchondral bone with a hemorrhagic region inferiorly (arrowhead). Soft-tissue extension (arrow) is seen where the hyaline cartilage (n) ends anteriorly.
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Figure 3b. GCT of the distal femur in a 35-year-old man. (a, b) Lateral knee (a) and specimen (b) radiographs show a geographic lytic lesion with a narrow zone of transition and no rim of sclerosis (arrowheads) centered on the metaphyseal side of the closed growth plate (arrows in b). (c) Angiogram reveals marked tumor stain (*) reflecting lesion hypervascularity and eccentric lesion location in the medial condyle. (d) Lateral bone scintigram shows marked radionuclide uptake in the femoral GCT. There is also increased uptake in the adjacent patella and tibia, findings that reflect hyperemia and disuse osteopenia rather than tumor extension. (e) CT scan shows lack of mineralization in the lesion and anterior expansile remodeling of bone. (f) Axial T1-weighted MR image (repetition time msec/echo time msec = 500/20) shows marrow replacement with intermediate-signal-intensity tissue (straight arrow) and associated anterior soft-tissue extension (curved arrow). The signal intensity of the lesion was identical at T2-weighted MR imaging. (g, h) Photographs of the sagittally sectioned gross specimen (g) and the whole mounted specimen (H-E stain) (h) show the GCT (*) extending to subchondral bone with a hemorrhagic region inferiorly (arrowhead). Soft-tissue extension (arrow) is seen where the hyaline cartilage (n) ends anteriorly.
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Figure 3c. GCT of the distal femur in a 35-year-old man. (a, b) Lateral knee (a) and specimen (b) radiographs show a geographic lytic lesion with a narrow zone of transition and no rim of sclerosis (arrowheads) centered on the metaphyseal side of the closed growth plate (arrows in b). (c) Angiogram reveals marked tumor stain (*) reflecting lesion hypervascularity and eccentric lesion location in the medial condyle. (d) Lateral bone scintigram shows marked radionuclide uptake in the femoral GCT. There is also increased uptake in the adjacent patella and tibia, findings that reflect hyperemia and disuse osteopenia rather than tumor extension. (e) CT scan shows lack of mineralization in the lesion and anterior expansile remodeling of bone. (f) Axial T1-weighted MR image (repetition time msec/echo time msec = 500/20) shows marrow replacement with intermediate-signal-intensity tissue (straight arrow) and associated anterior soft-tissue extension (curved arrow). The signal intensity of the lesion was identical at T2-weighted MR imaging. (g, h) Photographs of the sagittally sectioned gross specimen (g) and the whole mounted specimen (H-E stain) (h) show the GCT (*) extending to subchondral bone with a hemorrhagic region inferiorly (arrowhead). Soft-tissue extension (arrow) is seen where the hyaline cartilage (n) ends anteriorly.
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Figure 3d. GCT of the distal femur in a 35-year-old man. (a, b) Lateral knee (a) and specimen (b) radiographs show a geographic lytic lesion with a narrow zone of transition and no rim of sclerosis (arrowheads) centered on the metaphyseal side of the closed growth plate (arrows in b). (c) Angiogram reveals marked tumor stain (*) reflecting lesion hypervascularity and eccentric lesion location in the medial condyle. (d) Lateral bone scintigram shows marked radionuclide uptake in the femoral GCT. There is also increased uptake in the adjacent patella and tibia, findings that reflect hyperemia and disuse osteopenia rather than tumor extension. (e) CT scan shows lack of mineralization in the lesion and anterior expansile remodeling of bone. (f) Axial T1-weighted MR image (repetition time msec/echo time msec = 500/20) shows marrow replacement with intermediate-signal-intensity tissue (straight arrow) and associated anterior soft-tissue extension (curved arrow). The signal intensity of the lesion was identical at T2-weighted MR imaging. (g, h) Photographs of the sagittally sectioned gross specimen (g) and the whole mounted specimen (H-E stain) (h) show the GCT (*) extending to subchondral bone with a hemorrhagic region inferiorly (arrowhead). Soft-tissue extension (arrow) is seen where the hyaline cartilage (n) ends anteriorly.
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Figure 3e. GCT of the distal femur in a 35-year-old man. (a, b) Lateral knee (a) and specimen (b) radiographs show a geographic lytic lesion with a narrow zone of transition and no rim of sclerosis (arrowheads) centered on the metaphyseal side of the closed growth plate (arrows in b). (c) Angiogram reveals marked tumor stain (*) reflecting lesion hypervascularity and eccentric lesion location in the medial condyle. (d) Lateral bone scintigram shows marked radionuclide uptake in the femoral GCT. There is also increased uptake in the adjacent patella and tibia, findings that reflect hyperemia and disuse osteopenia rather than tumor extension. (e) CT scan shows lack of mineralization in the lesion and anterior expansile remodeling of bone. (f) Axial T1-weighted MR image (repetition time msec/echo time msec = 500/20) shows marrow replacement with intermediate-signal-intensity tissue (straight arrow) and associated anterior soft-tissue extension (curved arrow). The signal intensity of the lesion was identical at T2-weighted MR imaging. (g, h) Photographs of the sagittally sectioned gross specimen (g) and the whole mounted specimen (H-E stain) (h) show the GCT (*) extending to subchondral bone with a hemorrhagic region inferiorly (arrowhead). Soft-tissue extension (arrow) is seen where the hyaline cartilage (n) ends anteriorly.
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Figure 3f. GCT of the distal femur in a 35-year-old man. (a, b) Lateral knee (a) and specimen (b) radiographs show a geographic lytic lesion with a narrow zone of transition and no rim of sclerosis (arrowheads) centered on the metaphyseal side of the closed growth plate (arrows in b). (c) Angiogram reveals marked tumor stain (*) reflecting lesion hypervascularity and eccentric lesion location in the medial condyle. (d) Lateral bone scintigram shows marked radionuclide uptake in the femoral GCT. There is also increased uptake in the adjacent patella and tibia, findings that reflect hyperemia and disuse osteopenia rather than tumor extension. (e) CT scan shows lack of mineralization in the lesion and anterior expansile remodeling of bone. (f) Axial T1-weighted MR image (repetition time msec/echo time msec = 500/20) shows marrow replacement with intermediate-signal-intensity tissue (straight arrow) and associated anterior soft-tissue extension (curved arrow). The signal intensity of the lesion was identical at T2-weighted MR imaging. (g, h) Photographs of the sagittally sectioned gross specimen (g) and the whole mounted specimen (H-E stain) (h) show the GCT (*) extending to subchondral bone with a hemorrhagic region inferiorly (arrowhead). Soft-tissue extension (arrow) is seen where the hyaline cartilage (n) ends anteriorly.
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Figure 3g. GCT of the distal femur in a 35-year-old man. (a, b) Lateral knee (a) and specimen (b) radiographs show a geographic lytic lesion with a narrow zone of transition and no rim of sclerosis (arrowheads) centered on the metaphyseal side of the closed growth plate (arrows in b). (c) Angiogram reveals marked tumor stain (*) reflecting lesion hypervascularity and eccentric lesion location in the medial condyle. (d) Lateral bone scintigram shows marked radionuclide uptake in the femoral GCT. There is also increased uptake in the adjacent patella and tibia, findings that reflect hyperemia and disuse osteopenia rather than tumor extension. (e) CT scan shows lack of mineralization in the lesion and anterior expansile remodeling of bone. (f) Axial T1-weighted MR image (repetition time msec/echo time msec = 500/20) shows marrow replacement with intermediate-signal-intensity tissue (straight arrow) and associated anterior soft-tissue extension (curved arrow). The signal intensity of the lesion was identical at T2-weighted MR imaging. (g, h) Photographs of the sagittally sectioned gross specimen (g) and the whole mounted specimen (H-E stain) (h) show the GCT (*) extending to subchondral bone with a hemorrhagic region inferiorly (arrowhead). Soft-tissue extension (arrow) is seen where the hyaline cartilage (n) ends anteriorly.
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Figure 3h. GCT of the distal femur in a 35-year-old man. (a, b) Lateral knee (a) and specimen (b) radiographs show a geographic lytic lesion with a narrow zone of transition and no rim of sclerosis (arrowheads) centered on the metaphyseal side of the closed growth plate (arrows in b). (c) Angiogram reveals marked tumor stain (*) reflecting lesion hypervascularity and eccentric lesion location in the medial condyle. (d) Lateral bone scintigram shows marked radionuclide uptake in the femoral GCT. There is also increased uptake in the adjacent patella and tibia, findings that reflect hyperemia and disuse osteopenia rather than tumor extension. (e) CT scan shows lack of mineralization in the lesion and anterior expansile remodeling of bone. (f) Axial T1-weighted MR image (repetition time msec/echo time msec = 500/20) shows marrow replacement with intermediate-signal-intensity tissue (straight arrow) and associated anterior soft-tissue extension (curved arrow). The signal intensity of the lesion was identical at T2-weighted MR imaging. (g, h) Photographs of the sagittally sectioned gross specimen (g) and the whole mounted specimen (H-E stain) (h) show the GCT (*) extending to subchondral bone with a hemorrhagic region inferiorly (arrowhead). Soft-tissue extension (arrow) is seen where the hyaline cartilage (n) ends anteriorly.
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Figure 4a. Benign metastasizing GCT of the proximal tibia in a 30-year-old woman. (a) Anteroposterior radiograph shows an eccentric lytic metaepiphyseal lesion extending to subchondral bone with a narrow zone of transition (arrow). (b) Bone scintigram reveals increased radionuclide uptake peripherally and photopenia centrally ("donut sign"). (c) CT scan demonstrates mild expansion and sclerosis about the GCT (arrows) but no soft-tissue mass. (d) On a coronal T2-weighted MR image (2,000/80), the GCT demonstrates predominantly intermediate signal intensity with several high-signal-intensity foci (arrowheads) corresponding to secondary ABC regions. (e) Chest CT scan shows multiple pulmonary nodules in both lungs (arrowheads). (f) Photograph of the coronally sectioned whole mounted specimen (H-E stain) reveals a GCT extending to subchondral bone with ABC regions (white *) and solid areas (black *).
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Figure 4b. Benign metastasizing GCT of the proximal tibia in a 30-year-old woman. (a) Anteroposterior radiograph shows an eccentric lytic metaepiphyseal lesion extending to subchondral bone with a narrow zone of transition (arrow). (b) Bone scintigram reveals increased radionuclide uptake peripherally and photopenia centrally ("donut sign"). (c) CT scan demonstrates mild expansion and sclerosis about the GCT (arrows) but no soft-tissue mass. (d) On a coronal T2-weighted MR image (2,000/80), the GCT demonstrates predominantly intermediate signal intensity with several high-signal-intensity foci (arrowheads) corresponding to secondary ABC regions. (e) Chest CT scan shows multiple pulmonary nodules in both lungs (arrowheads). (f) Photograph of the coronally sectioned whole mounted specimen (H-E stain) reveals a GCT extending to subchondral bone with ABC regions (white *) and solid areas (black *).
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Figure 4c. Benign metastasizing GCT of the proximal tibia in a 30-year-old woman. (a) Anteroposterior radiograph shows an eccentric lytic metaepiphyseal lesion extending to subchondral bone with a narrow zone of transition (arrow). (b) Bone scintigram reveals increased radionuclide uptake peripherally and photopenia centrally ("donut sign"). (c) CT scan demonstrates mild expansion and sclerosis about the GCT (arrows) but no soft-tissue mass. (d) On a coronal T2-weighted MR image (2,000/80), the GCT demonstrates predominantly intermediate signal intensity with several high-signal-intensity foci (arrowheads) corresponding to secondary ABC regions. (e) Chest CT scan shows multiple pulmonary nodules in both lungs (arrowheads). (f) Photograph of the coronally sectioned whole mounted specimen (H-E stain) reveals a GCT extending to subchondral bone with ABC regions (white *) and solid areas (black *).
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Figure 4d. Benign metastasizing GCT of the proximal tibia in a 30-year-old woman. (a) Anteroposterior radiograph shows an eccentric lytic metaepiphyseal lesion extending to subchondral bone with a narrow zone of transition (arrow). (b) Bone scintigram reveals increased radionuclide uptake peripherally and photopenia centrally ("donut sign"). (c) CT scan demonstrates mild expansion and sclerosis about the GCT (arrows) but no soft-tissue mass. (d) On a coronal T2-weighted MR image (2,000/80), the GCT demonstrates predominantly intermediate signal intensity with several high-signal-intensity foci (arrowheads) corresponding to secondary ABC regions. (e) Chest CT scan shows multiple pulmonary nodules in both lungs (arrowheads). (f) Photograph of the coronally sectioned whole mounted specimen (H-E stain) reveals a GCT extending to subchondral bone with ABC regions (white *) and solid areas (black *).
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Figure 4e. Benign metastasizing GCT of the proximal tibia in a 30-year-old woman. (a) Anteroposterior radiograph shows an eccentric lytic metaepiphyseal lesion extending to subchondral bone with a narrow zone of transition (arrow). (b) Bone scintigram reveals increased radionuclide uptake peripherally and photopenia centrally ("donut sign"). (c) CT scan demonstrates mild expansion and sclerosis about the GCT (arrows) but no soft-tissue mass. (d) On a coronal T2-weighted MR image (2,000/80), the GCT demonstrates predominantly intermediate signal intensity with several high-signal-intensity foci (arrowheads) corresponding to secondary ABC regions. (e) Chest CT scan shows multiple pulmonary nodules in both lungs (arrowheads). (f) Photograph of the coronally sectioned whole mounted specimen (H-E stain) reveals a GCT extending to subchondral bone with ABC regions (white *) and solid areas (black *).
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Figure 4f. Benign metastasizing GCT of the proximal tibia in a 30-year-old woman. (a) Anteroposterior radiograph shows an eccentric lytic metaepiphyseal lesion extending to subchondral bone with a narrow zone of transition (arrow). (b) Bone scintigram reveals increased radionuclide uptake peripherally and photopenia centrally ("donut sign"). (c) CT scan demonstrates mild expansion and sclerosis about the GCT (arrows) but no soft-tissue mass. (d) On a coronal T2-weighted MR image (2,000/80), the GCT demonstrates predominantly intermediate signal intensity with several high-signal-intensity foci (arrowheads) corresponding to secondary ABC regions. (e) Chest CT scan shows multiple pulmonary nodules in both lungs (arrowheads). (f) Photograph of the coronally sectioned whole mounted specimen (H-E stain) reveals a GCT extending to subchondral bone with ABC regions (white *) and solid areas (black *).
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Figure 5a. (a, b) GCT of the distal radius with pseudotrabeculation in a 25-year-old man. (a) Anteroposterior radiograph of the wrist shows a lytic metaepiphyseal lesion extending to subchondral bone with a pathologic fracture (arrowheads) and apparent internal trabeculation. (b) CT scan reveals that the apparent multiloculation is caused by endosteal scalloping creating ridges (arrows). (c) GCT of the radius in a different patient. Photograph of a dried bone specimen clearly shows endosteal ridges (arrowheads).
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Figure 5b. (a, b) GCT of the distal radius with pseudotrabeculation in a 25-year-old man. (a) Anteroposterior radiograph of the wrist shows a lytic metaepiphyseal lesion extending to subchondral bone with a pathologic fracture (arrowheads) and apparent internal trabeculation. (b) CT scan reveals that the apparent multiloculation is caused by endosteal scalloping creating ridges (arrows). (c) GCT of the radius in a different patient. Photograph of a dried bone specimen clearly shows endosteal ridges (arrowheads).
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Figure 5c. (a, b) GCT of the distal radius with pseudotrabeculation in a 25-year-old man. (a) Anteroposterior radiograph of the wrist shows a lytic metaepiphyseal lesion extending to subchondral bone with a pathologic fracture (arrowheads) and apparent internal trabeculation. (b) CT scan reveals that the apparent multiloculation is caused by endosteal scalloping creating ridges (arrows). (c) GCT of the radius in a different patient. Photograph of a dried bone specimen clearly shows endosteal ridges (arrowheads).
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Figure 6a. GCT of the sacrum crossing the sacroiliac joint in a 20-year-old woman. Anteroposterior radiograph (a) and CT scan (b) show a large, destructive lesion of the sacrum (arrowheads in a, large arrowheads in b) with an associated soft-tissue mass (*) and extension across both sacroiliac joints to involve the iliac bones (small arrowheads in b).
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Figure 6b. GCT of the sacrum crossing the sacroiliac joint in a 20-year-old woman. Anteroposterior radiograph (a) and CT scan (b) show a large, destructive lesion of the sacrum (arrowheads in a, large arrowheads in b) with an associated soft-tissue mass (*) and extension across both sacroiliac joints to involve the iliac bones (small arrowheads in b).
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Figure 7a. GCT of the sacrum in a 39-year-old woman. (a) Anteroposterior radiograph of the pelvis shows a multiloculated lytic lesion in the mid- and distal sacrum (arrowheads). (b) CT scan reveals osseous expansion with a large soft-tissue mass anteriorly (arrow). (c, d) Sagittal T1-weighted (600/20) (c) and axial T2-weighted (2,500/80) (d) MR images also show the lesion arising from the sacrum with a large extraosseous component anteriorly (arrow). A focus of hemorrhage is also seen (arrowhead). The majority of the tumor has low to intermediate signal intensity on the T2-weighted image. (e) Photograph of the sagittally sectioned gross specimen reveals an intraosseous component (arrowhead) and soft-tissue extension (white *) with a pseudocapsule anteriorly (arrows) and normal sacrum superiorly (black *).
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Figure 7b. GCT of the sacrum in a 39-year-old woman. (a) Anteroposterior radiograph of the pelvis shows a multiloculated lytic lesion in the mid- and distal sacrum (arrowheads). (b) CT scan reveals osseous expansion with a large soft-tissue mass anteriorly (arrow). (c, d) Sagittal T1-weighted (600/20) (c) and axial T2-weighted (2,500/80) (d) MR images also show the lesion arising from the sacrum with a large extraosseous component anteriorly (arrow). A focus of hemorrhage is also seen (arrowhead). The majority of the tumor has low to intermediate signal intensity on the T2-weighted image. (e) Photograph of the sagittally sectioned gross specimen reveals an intraosseous component (arrowhead) and soft-tissue extension (white *) with a pseudocapsule anteriorly (arrows) and normal sacrum superiorly (black *).
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Figure 7c. GCT of the sacrum in a 39-year-old woman. (a) Anteroposterior radiograph of the pelvis shows a multiloculated lytic lesion in the mid- and distal sacrum (arrowheads). (b) CT scan reveals osseous expansion with a large soft-tissue mass anteriorly (arrow). (c, d) Sagittal T1-weighted (600/20) (c) and axial T2-weighted (2,500/80) (d) MR images also show the lesion arising from the sacrum with a large extraosseous component anteriorly (arrow). A focus of hemorrhage is also seen (arrowhead). The majority of the tumor has low to intermediate signal intensity on the T2-weighted image. (e) Photograph of the sagittally sectioned gross specimen reveals an intraosseous component (arrowhead) and soft-tissue extension (white *) with a pseudocapsule anteriorly (arrows) and normal sacrum superiorly (black *).
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Figure 7d. GCT of the sacrum in a 39-year-old woman. (a) Anteroposterior radiograph of the pelvis shows a multiloculated lytic lesion in the mid- and distal sacrum (arrowheads). (b) CT scan reveals osseous expansion with a large soft-tissue mass anteriorly (arrow). (c, d) Sagittal T1-weighted (600/20) (c) and axial T2-weighted (2,500/80) (d) MR images also show the lesion arising from the sacrum with a large extraosseous component anteriorly (arrow). A focus of hemorrhage is also seen (arrowhead). The majority of the tumor has low to intermediate signal intensity on the T2-weighted image. (e) Photograph of the sagittally sectioned gross specimen reveals an intraosseous component (arrowhead) and soft-tissue extension (white *) with a pseudocapsule anteriorly (arrows) and normal sacrum superiorly (black *).
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Figure 7e. GCT of the sacrum in a 39-year-old woman. (a) Anteroposterior radiograph of the pelvis shows a multiloculated lytic lesion in the mid- and distal sacrum (arrowheads). (b) CT scan reveals osseous expansion with a large soft-tissue mass anteriorly (arrow). (c, d) Sagittal T1-weighted (600/20) (c) and axial T2-weighted (2,500/80) (d) MR images also show the lesion arising from the sacrum with a large extraosseous component anteriorly (arrow). A focus of hemorrhage is also seen (arrowhead). The majority of the tumor has low to intermediate signal intensity on the T2-weighted image. (e) Photograph of the sagittally sectioned gross specimen reveals an intraosseous component (arrowhead) and soft-tissue extension (white *) with a pseudocapsule anteriorly (arrows) and normal sacrum superiorly (black *).
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Figure 8a. GCT of the patella with a pathologic fracture in a 26-year-old woman. (a) Lateral radiograph of the knee shows an aggressive, destructive lytic lesion of the patella, particularly inferiorly, with a pathologic fracture (arrowheads). (b) CT scan shows marrow replacement by the patellar GCT (white arrow) and patchy low attenuation in the femur representing disuse osteoporosis (black arrows). Both femoral and patellar areas demonstrated increased radionuclide uptake at bone scintigraphy. (c) Sagittal proton-density-weighted MR image (2,000/16) reveals heterogeneous, predominantly low signal intensity in the patellar GCT (*). (d) Photograph of the axially sectioned gross specimen reveals an intact osseous shell (arrowheads) with a GCT in the patellar marrow (*).
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Figure 8b. GCT of the patella with a pathologic fracture in a 26-year-old woman. (a) Lateral radiograph of the knee shows an aggressive, destructive lytic lesion of the patella, particularly inferiorly, with a pathologic fracture (arrowheads). (b) CT scan shows marrow replacement by the patellar GCT (white arrow) and patchy low attenuation in the femur representing disuse osteoporosis (black arrows). Both femoral and patellar areas demonstrated increased radionuclide uptake at bone scintigraphy. (c) Sagittal proton-density-weighted MR image (2,000/16) reveals heterogeneous, predominantly low signal intensity in the patellar GCT (*). (d) Photograph of the axially sectioned gross specimen reveals an intact osseous shell (arrowheads) with a GCT in the patellar marrow (*).
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Figure 8c. GCT of the patella with a pathologic fracture in a 26-year-old woman. (a) Lateral radiograph of the knee shows an aggressive, destructive lytic lesion of the patella, particularly inferiorly, with a pathologic fracture (arrowheads). (b) CT scan shows marrow replacement by the patellar GCT (white arrow) and patchy low attenuation in the femur representing disuse osteoporosis (black arrows). Both femoral and patellar areas demonstrated increased radionuclide uptake at bone scintigraphy. (c) Sagittal proton-density-weighted MR image (2,000/16) reveals heterogeneous, predominantly low signal intensity in the patellar GCT (*). (d) Photograph of the axially sectioned gross specimen reveals an intact osseous shell (arrowheads) with a GCT in the patellar marrow (*).
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Figure 8d. GCT of the patella with a pathologic fracture in a 26-year-old woman. (a) Lateral radiograph of the knee shows an aggressive, destructive lytic lesion of the patella, particularly inferiorly, with a pathologic fracture (arrowheads). (b) CT scan shows marrow replacement by the patellar GCT (white arrow) and patchy low attenuation in the femur representing disuse osteoporosis (black arrows). Both femoral and patellar areas demonstrated increased radionuclide uptake at bone scintigraphy. (c) Sagittal proton-density-weighted MR image (2,000/16) reveals heterogeneous, predominantly low signal intensity in the patellar GCT (*). (d) Photograph of the axially sectioned gross specimen reveals an intact osseous shell (arrowheads) with a GCT in the patellar marrow (*).
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Imaging Features
As with other bone tumors, the differential diagnosis of GCT is usually based on its radiographic appearance and location. Lesions invariably demonstrate geographic bone lysis, most commonly associated with a narrow zone of transition and lacking surrounding sclerosis (80%–85% of cases) (Figs 3–5). Although the majority (42%–93%) of lesions are eccentrically located (Figs 3, 4), lesions that are large at presentation more frequently appear central in location (Figs 2, 5) (26,27,56). In some studies, a sclerotic rim has been reported to be rare (1%–2% of lesions) (24,26,27). In our experience, however, although a thick rim of sclerosis is rare, areas of peripheral sclerosis are not infrequent, particularly at CT, at which it has been reported in up to 20% of cases (Fig 4c) (56,57). Geographic lysis with more aggressive growth and a wide zone of transition is seen in approximately 10%–20% of cases (Figs 6–8) (6–11).
Cortical thinning of bone is invariably apparent at radiography performed at clinical presentation. Expansile remodeling of bone is also frequently seen (47%–60% of cases) (Figs 2, 5) (6,26). Cortical penetration is seen in 33%–50% of cases, often with an associated soft-tissue mass (Fig 3) (26,56–60). Periosteal reaction is relatively unusual and is reported at radiography in 10%–30% of cases (24,56). Pathologic fracture, which may be complete or incomplete, is seen in 11%–37% of patients (Figs 5a, 8) (20,30,56). At radiography, GCTs often demonstrate prominent trabeculation (33%–57% of cases) with a resultant multiloculated appearance (Figs 2, 5) (20, 24,26,28,56). We agree with Manaster and Doyle (6) that this finding has been overemphasized and that this appearance frequently represents pseudotrabeculation from osseous ridges created by endosteal scalloping. This pseudotrabeculation is often well demonstrated by comparing radiographic findings with CT findings (Fig 5).
Bone scintigraphy (static imaging) demonstrates increased radionuclide uptake in the vast majority of GCTs (Fig 3d) (56,61–63). Increased radionuclide uptake peripherally with photopenia centrally (donut sign) was seen in 57% of cases reported by Levine et al (61) (Fig 4b). Blood pool imaging, dynamic bone scintigraphy, and imaging with gallium–67 also typically reveal increased radionuclide uptake, although usually to a lesser degree than delayed (static) bone scintigraphy (56,61). Increased radiotracer uptake in bone across an articulation and in adjacent joints is common (62% of cases) and should not be mistaken for tumor extension (56,61). As with other hyperemic bone neoplasms, this phenomenon, referred to as "contiguous bone activity" or "extended pattern of uptake," is related to increased blood flow and disuse osteoporosis (Figs 3, 8) (61–68).
Angiography of GCT is only infrequently performed since the advent of CT and MR imaging (or MR angiography) but usually reveals a hypervascular lesion (60%–65% of cases) (Fig 3c) (58,69–71). Lesions are hypovascular in 26%–30% of cases and avascular in 10% (56,69–71). Preoperative transcatheter arterial embolization can be used to reduce blood loss during surgical resection (56).
As with other musculoskeletal neoplasms, CT and MR imaging allow superior delineation and staging of GCTs (60,72). CT improves detection of cortical thinning, pathologic fracture, periosteal reaction, and degree of osseous expansile remodeling compared with radiography (26,56). CT also helps confirm the absence of mineralization in GCT, although callus formation related to healing pathologic fracture may be seen (Figs 3–5, 7). The solid portions of GCT demonstrate attenuation similar to that of muscle. Soft-tissue extension is common at CT and MR imaging and was seen at CT in 33%–44% of cases in studies by Levine et al (56) and Hudson et al (26) (Figs 3, 6, 7). As with other musculoskeletal neoplasms, MR imaging is superior to CT in delineating soft-tissue tumor extent because of its improved contrast resolution. Conversely, CT is superior to MR imaging in evaluating periosteal reaction, pathologic fracture, and the absence of matrix mineralization. In our experience, soft-tissue extension typically occurs at the metaphyseal end of the lesion because the cartilage at the epiphyseal margin is a barrier to tumor extension (Fig 3). This also explains why joint involvement is unusual despite the subarticular spread of GCT. However, there are exceptions to this general rule—for example, the relatively common involvement of the sacroiliac joint and extension into the iliac bone by sacral GCTs as described in 38% of cases by Smith et al (Fig 6) (73).
MR imaging of GCT frequently reveals a relatively well-defined lesion with a low-signal-intensity margin representing either osseous sclerosis or a pseudocapsule (Fig 7). However, more invasive and aggressive growth may also be seen (Figs 3, 6). Interestingly, in our experience but unlike in previous studies, the solid components of GCT demonstrate low to intermediate signal intensity at T1- and T2-weighted MR imaging in the vast majority of cases (Figs 3, 4, 7) (74). This feature can be useful in excluding other subarticular lesions such as large solitary subchondral cyst, intraosseous ganglion, Brodie abscess, and clear cell chondrosarcoma that demonstrate high signal intensity at T2-weighted MR imaging. The cause of this appearance has been reported as hemosiderin deposition, although we believe it is more likely related to increased cellularity or high collagen content (74–76).
ABC components in GCT are relatively common (14% of lesions) (6–11,72,74,77–83). In addition, GCT is the most common lesion associated with secondary ABC, accounting for 39% of these lesions (79). Cases of GCT with prominent ABC elements may have a more aggressive radiographic appearance, reflecting the expansile cystic component (Figs 9, 10). These cystic areas are typically well seen at CT and MR imaging, although the latter modality is superior in this regard because of improved contrast resolution (Fig 10). The ABC regions frequently exhibit fluid levels at both modalities, although imaging plane (seen only in axial and sagittal planes), patient positioning, and timing of imaging (10 minutes may be required for sedimentation to occur) are also factors that contribute to increased detection of this component (Fig 10) (84). These ABC areas demonstrate low attenuation at CT, low or high signal intensity at T1-weighted MR imaging, and markedly increased signal intensity at T2-weighted MR imaging (Fig 10) (77–83). At advanced imaging, the solid components of GCT are easily distinguishable from the ABC areas. In our experience with lesions containing prominent ABC components, the solid regions of GCT are often lobular areas found predominantly in the periphery of a neoplasm. Recognition of and distinction between the cystic (ABC) and solid areas of a GCT can be vital for patient treatment for two important reasons: first, to prevent misdiagnosis of the lesion as a primary ABC, which should contain only cystic components; and second, to allow biopsy to be directed at the solid portions of the lesions, which harbor diagnostic tissue, as opposed to ABC regions, which yield nonspecific blood. Contrast-enhanced CT or MR imaging can also help distinguish cystic from solid regions (Fig 10). Cystic areas enhance with a thin and delicate peripheral and septal pattern. In contrast, the solid regions of a GCT enhance diffusely, reflecting the hypervascular tissue seen at pathologic analysis (Fig 10) (85).
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Figure 9a. GCT of the proximal humerus with a large secondary ABC component in a 17-year-old girl. Specimen radiograph (a) and photographs of the coronally sectioned gross specimen (b) and the whole mounted specimen (H-E stain) (c) show aggressive geographic lysis with cortical destruction (large arrowheads in a) and a wide zone of transition extending to subchondral bone. A large, hemorrhagic cystic (ABC) component is also seen (*). However, solid regions of GCT are seen peripherally (small arrowheads in a, arrowheads in b and c), some of which demonstrate prominent fibrosis (F).
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Figure 9b. GCT of the proximal humerus with a large secondary ABC component in a 17-year-old girl. Specimen radiograph (a) and photographs of the coronally sectioned gross specimen (b) and the whole mounted specimen (H-E stain) (c) show aggressive geographic lysis with cortical destruction (large arrowheads in a) and a wide zone of transition extending to subchondral bone. A large, hemorrhagic cystic (ABC) component is also seen (*). However, solid regions of GCT are seen peripherally (small arrowheads in a, arrowheads in b and c), some of which demonstrate prominent fibrosis (F).
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Figure 9c. GCT of the proximal humerus with a large secondary ABC component in a 17-year-old girl. Specimen radiograph (a) and photographs of the coronally sectioned gross specimen (b) and the whole mounted specimen (H-E stain) (c) show aggressive geographic lysis with cortical destruction (large arrowheads in a) and a wide zone of transition extending to subchondral bone. A large, hemorrhagic cystic (ABC) component is also seen (*). However, solid regions of GCT are seen peripherally (small arrowheads in a, arrowheads in b and c), some of which demonstrate prominent fibrosis (F).
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Figure 10a. GCT of the distal radius with a large secondary ABC component in a 17-year-old girl. (a) Anteroposterior radiograph shows marked expansile remodeling caused by a multiloculated lytic lesion of the distal radius extending to subchondral bone. (b) Coronal contrast material-enhanced T1-weighted MR image (500/12) reveals diffuse enhancement of solid portions of a GCT (arrowheads) and peripheral enhancement about the ABC regions (*). (c, d) Coronal (c) and axial (d) T2-weighted MR images (5,000/108) reveal markedly increased signal intensity in the ABC areas (black *), with fluid levels (arrows in d) and low signal intensity in the small solid regions (white *). (e, f) Photograph of the sectioned gross specimen (e) and photomicrograph (original magnification, x200; H-E stain) (f) also reveal ABC regions (*) with thin lining along the cyst wall (arrowheads) and solid GCT components (arrow).
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Abstract
LEARNING OBJECTIVES FOR TEST...
