Sample Chapter - Please Do Not Copy!
This is a typical chapter from Clinical Musculoskeletal Pathology by William F. Enneking. It is presented here with unrestricted access to demonstrate the features of the complete program avaiable on CD-ROM and the Web.
Giant cell tumor of bone (GCT) is a benign lesion with a wide spectrum of behavior characterized by stromal cells that fuse to form giant cells.
Age: 20 - 40
Sex: F = M
Site: It has been described in virtually every bone but has a predilection for the epiphysis of the major long bones, especially the distal femur and proximal tibia. In the spine it has a predilection for the vertebral body. It may also occur in the epiphyses of the hand and foot.
Giant cell tumor is of fibrohistiocytic origin, both from a histologic and immunologic standpoint. The lesion is, perhaps, the only giant-cell bearing lesion in which the giant cells result from fusion of the stromal cells rather than as reactive or histiocytic cells. Tissue extracts from GCT cross react with antibodies raised against extracts of malignant fibrous histiocytoma indicating their fibrohistiocytic background. Histochemical staining and electron microscopy, however, cannot distinguish them from normal osteoclasts hence, the name osteoclatoma favored by some or even reactive giant cells present in so many other skeletal lesions.
Despite being a benign lesion, the clinical course is unpredictable. A few rare lesions remain latent or quiescent for years or even decades as stage 1 lesions. The majority of the lesions (circa 60 percent are active stage 2 lesions, but a substantial minority (circa 30 percent) display locally aggressive stage 3 behavior.
Multicentric lesions occur simultaneously in rare instances (less than1 percent) and also behave in an unpredictable fashion.
Finally pulmonary metastases occur, also rarely (1 to 2 percent), without regard to the behavior of the primary lesion; i.e., a stage 2 lesion is just as likely to metastasize as a more aggressive stage 3 lesion. These metastases do not imply the lesion has undergone malignant transformation. The histologic features of the metastasis are indeed, as benign as the primary, and the clinical course is also less frequently fatal than with the malignant counterparts (see below).
The main symptom of giant cell tumor is pain. It is usually felt in or near the joint involved. In smaller bones, like the proximal fibula or distal radius, it may present as a mass increasing in size. Occasionally, the regional musculature shows disuse atrophy.
Clinical presentations:
[Photo] The patient presented with a large giant cell tumor of the distal radius and this sizable enlarging mass about the wrist. [Photo] A 36-year-old female presented with an enlarging mass about the wrist due to a stage 3 GCT of the distal radius. [Photo] An 18-year-old male presented with an enlarging mass about the lateral aspect of the knee due to a stage 2 GCT of the proximal fibula.
Not infrequently a patient with a GCT of the distal femur will present with signs and symptoms of internal derangement of the knee. Often, if the radiographic features are subtle or not appreciated, arthroscopy with negative results will follow, and the diagnosis is not made until popliteal extension or pathologic fracture makes the lesion obvious.
GCT mimicking internal derangement:
[Photo] A 26-year-old professional tennis player presented with a popliteal mass. Eighteen months earlier, he had been arthroscoped twice for symptoms of internal derangement with no relief. [X-Ray] This is the AP radiograph at the time of first arthroscopy and [X-Ray] this is the lateral view. The eventual posterior soft tissue extension made curettage/cementation impractical, and the wide resection/arthrodesis ended his tennis career. Medical-legal proceedings followed.
Latent lesions appear as subtle, radiolucent well-marginated defects in the epiphyses without deformation of the overlying cortex. There is usually more than 1 cm. of bone between the lesion and the adjacent subchondral plate. Subsequent follow-up films show either no growth or exceptionally slow progression.
A latent lesion:
[X-Ray] A 36-year-old female presented with a pathologic fracture of the femoral neck secondary to a GCT of the proximal femur. Curettage, bone grafting and internal fixation were done. [X-Ray] Follow up radiograph at five years showed a healed fracture, incorporation of the bone grafts and a small radiolucent recurrence at the lesser trochanter. As the recurrence was asymptomatic, it was elected to observe its behavior. [X Ray] Follow-up at eleven years demonstrated slight progression, but it was asymptomatic [X Ray] Follow up at fourteen years showed no change. [X-Ray] Follow up at sixteen years showed no change.
Active stage 2 lesions appear as distinct radiolucent lesions that are well marginated by a thin rim of reactive bone. Frequently, there is an impression of septation. The lesions usually extend across the adjacent physeal scar into the adjacent metaphysis, and there is a narrow zone (2 to 5 mm.) of bone between the lesion and the subchondral plate.
Active lesions:
[X-Ray] A 34-year-old female presented with a stage 2 GCT of the proximal tibia. [X-Ray] This is a magnified view of the lesion. [X-Ray] An AP radiograph reveals a stage 2 GCT of the distal femur. [X Ray] The lateral view shows the margination of the radiolucent lesion. The narrow zone of bone between the lesion and the intact subchondral plate is shown to good advantage as is the thin but intact anterior shell.
With continued enlargement, the lesion may deform the overlying cortex but if it remains well encapsulated by a continuous rim of cortical reactive bone remains as an active stage 2 lesion.
A deforming active lesion:
[X-Ray] An AP radiograph reveals that an active stage 2 GCT of the distal radius has deformed the bone but remains encapsulated. Note the impression of the enlarging lesion upon the cortex of the adjacent distal ulna. [X-Ray] The lateral view shows the pseudoseptation or "soap bubble" pattern suggestive of GCT. Again, the impression upon the distal ulna bespeaks its non aggressive behavior despite the size of the lesion.
Aggressive, or stage 3 lesions, appear as radiolucent lesions that are poorly defined by reactive bone. They often show destruction of the overlying cortex with a significant, radiolucent soft-tissue component. In addition, they frequently show subchondral-plate destruction with extension into the cavity of the joint.
Aggressive lesions:
[Gross Path] This is a composite specimen radiograph and the corresponding specimen of an aggressive stage 3 GCT of the distal femur. [X-Ray] An AP radiograph of a stage 3 GCT of the distal femur shows a significant soft-tissue component. [X-Ray] The lateral view again shows the lack of reactive containment of the anterior soft-tissue extension in this aggressive lesion. [X-Ray] An AP radiograph of an aggressive stage 3 GCT of the distal tibia reveals destruction of the subchondral plate and direct extension into the ankle joint.
Pathologic fracture is common with giant cell tumor and is seen in both stage 2 and 3 lesions. The fractures heal with external immobilization. In stage 2 lesions, despite the obvious risk of tumor extension into the soft-tissues from the fracture site, the fracture callus usually encircles the lesion, thus preventing extraosseous extension.
Pathologic fractures secondary to GCT:
[X-Ray] A lateral radiograph of a large stage 2 GCT of the distal femur three months after pathologic fracture shows telescoping of the femoral shaft into the lesion. The fracture was managed with external immobilization. [X-Ray] Magnification shows healing of the fracture. A wide excision of the distal third of the femur was done. [Gross Path] The cut surfaces of the surgical specimen show the neoplastic tissue encased by the reactive bone and fracture callus. [Macro] A coronal macrosection shows the basophilic neoplastic tissue completely encased by the fracture callus at the fracture site proximally. [X Ray] A 44-year-old dentist presented with a pathologic fracture through a stage 2 GCT of the femoral condyle. The fracture was treated with external immobilization and, subsequently, healed. Because of the concern of intra-articular tumor extension and the incongruity of the articular surfaces, a wide resection of the distal femur was done. [Gross Path] A view of the surgical specimen shows the fracture site through the articular cartilage united by callus. [Gross Path] The coronal surface of the sectioned specimen shows the mismatch of the articular surfaces, the biopsy tract plugged with bone cement and the tumor completely surrounded by callus preventing extraosseous extension into the joint cavity or soft tissues.
The isotope scan parallels the behavior of the lesion. Latent lesions have modest focal increase in uptake. Active lesions have intense focal increase in uptake, and aggressive lesions have intense increase in uptake beyond the radiographic limits of the lesion.
Focal increase in isotope uptake:
[X-Ray] This is an AP radiograph of a stage 2 GCT of the distal femur. [X-Ray] This is a magnified view of the lesion. [Iso-Scan] A regional isotope scan shows intense increased uptake beyond the radiographic limits of the lesion. [X-Ray] This is a magnified lateral view of the lesion [Iso-Scan] This is a lateral projection of the isotope scan.
Occasionally, the pattern of isotope uptake will resemble a doughnut. In this instance, the uptake is concentrated in the thin rim of reactive bone marginating the lesion, and the central radiolucent portion of the lesion has significant amounts of necrosis. This "doughnut" pattern, while suggestive of GCT, is also often seen in aneurysmal bone cyst and occasionally in other lesions.
A "doughnut" pattern in GCT:
[X-Ray] An AP radiograph shows an "expansile" GCT of the proximal fibula. [Iso-Scan] The regional isotope scan shows the "doughnut" pattern.
The same pattern in an ABC:
[X-Ray] An AP radiograph reveals a subperiosteal ABC of the scapula. [Iso-Scan] The corresponding isotope scan has a "doughnut" pattern.
The hyper-vascularity of a GCT is graphically reflected in the angiographic pattern by rapid preferential shunting of the contrast into the lesion followed by a prolonged post-injection "blush".
Preferential shunting in GCT:
[X-Ray] A Lateral radiograph shows a stage 2 GCT of the distal radius. [Angio] The early arterial phase of the angiogram shows preferential shunting into the lesion. [Angio] The mid-arterial phase shows the hypervascularity of GCT.
Another example of preferential shunting in GCT:
[X-Ray] An AP pelvic radiograph shows a GCT in the ischium and inferior pubic ramus in a 17-year-old female. [X Ray] The magnified view gives a subtle hint of a soft-tissue extension adjacent to the femoral neck. [Angio] The early-arterial phase of the angiogram shows marked shunting into the large, hypervascular soft tissue extension. [Gross Path] The coronal surface of the surgical specimen shows the vascular neoplastic tissue below the acetabulum.
A venous blush:
[X-Ray] An AP radiograph reveals a stage 3 GCT of the proximal fibula. [X-Ray] The lateral view shows areas of cortical breakthrough proximally. [Iso Scan] A regional isotope scan shows extensive intense increased uptake. [Angio] The reversed early-arterial phase of the angiogram shows marked shunting. [Angio] The late-venous phase shows the blush in the huge soft-tissue component.
Another example of a venous blush in GCT:
[X-Ray] An AP radiograph shows a stage 3 GCT of the proximal tibia. [X-Ray] Magnification shows the lateral cortical breakthrough in this aggressive lesion. [Angio] The late-venous phase of the angiogram shows the intense venous blush of this hypervascular process.
CT imaging is the best technique for evaluating cortical breakthrough of potentially aggressive GCT.
CT of cortical breakthrough in GCT:
[X-Ray] An AP radiograph of a GCT of the femoral condyle shows questionable lateral cortical breakthrough. [CT Scan] An axial CT image (bone window) shows one discrete area of cortical breakthrough. [CT Scan] A more posterior cut shows the cortex in this region to be intact.
CT is also valuable in accurately assessing the intraosseous characteristics of GCT, particularly in radiographically-obscure regions.
Visualizing intraosseous extent in GCT:
[X-Ray] An AP radiograph of the knee shows a GCT of the distal femur partially obscured by the overlying patella. [X Ray] Magnification shows the lesion to be somewhat larger than the diameter of the patella. [CT Scan] An axial CT image cut through the patella and midportion of the lesion clearly divulges the intraosseous extent and the relationship to the posterior neurovascular bundle.
When contrast is added to the CT image, it enhances the radiodensity of the lesion reflecting the vascularity of GCT and gives a substantial clue to the diagnosis. The use of contrast also improves definition of the relationship with the adjacent neurovascular structures for surgical planning.
Vascular enhancement by CT in GCT:
[CT Scan] An axial CT (bone window) is cut through the midportion of a GCT of the distal femur. [CT Scan] The same cut with contrast added shows marked enhancement of areas of the neoplastic tissue and shows the posterior neurovascular bundle filled with contrast well clear of the lesion.
CT imaging is also useful in identifying pathologic fracture in radiographically-obscure situations.
Subtle fracture identification by CT:
[X-Ray] This is an AP radiograph of an unusual suddenly-painful GCT of the femoral condyle. [X Ray] Tomography failed to reveal a suspected pathologic fracture. [CT Scan] An axial CT image showed an undisplaced pathologic fracture through the lateral femoral fracture. [Gross Path] The accuracy of the image was confirmed by inspection of the resected surgical specimen.
The T-1 weighted images have a low-intensity signal while the T-2 weighted images have a bright signal. Both images clearly delineate the intraosseous extent of the lesion and distinguish between the neoplastic tissue and surrounding reactive tissue.
MRI features of GCT:
[MRI] In this axial T-1 weighted image of a stage 2 GCT of the proximal tibia, the neoplastic tissue has a grey low-intensity signal in contrast to the bright signal of normal fatty marrow. There is a narrow black zone of reactive bone between the neoplastic tissue and normal marrow. [MRI] This is the same axial cut with a T-2 weighted image using fat-suppression technique. The neoplastic tissue has a brighter signal than the suppressed marrow fat. The intervening reactive bone between marrow and neoplasm is easily distinguished.
Frequently the images of GCT have a mottled or non-homogeneous pattern resulting from areas of hemorrhage and/or necrosis with varying concentrations of water. The combination of radiograph, CT and MRI frequently gives more accurate information than any of the techniques by themselves.
A non-homogeneous MRI signal:
[X-Ray] This is an AP radiograph of a stage 3 GCT of the proximal tibia. [X-Ray] This is a lateral view of the lesion. [CT Scan] An axial CT image shows the radiolucent lesion to be well marginated. [MRI] This axial T-1 weighted MRI confirms no extraosseous extension of the lesion at this level. [MRI] The axial T-2 weighted MRI has a sharply non-homogeneous pattern. [MRI] In contrast to the axial images, the coronally-oriented longitudinal T-1 weighted MRI clearly shows distal extraosseous penetration of the lesion into the adjacent soft tissues.
MRI imaging is, in most instances, the most sensitive technique for depicting intra-articular extension of GCT mimicking other causes of internal derangement of the knee.
Intra-articular extension on MRI:
[X-Ray] A 29-year-old male presented with signs and symptoms of internal derangement of the knee. The GCT of the distal femur was obscure in the screening radiographs. [X Ray] This lateral view showed only subtle changes. [CT Scan] An axial CT clearly showed the lesion with a suggestion of cortical disruption in the intercondylar notch. [MRI] Axial T-1 MRI showed tumor extending to the notch and an abnormal signal in the anterior cruciate ligament. [MRI] Coronal T-1 MRI showed extension of the low-intensity signal from the femoral lesion along the course of the cruciate ligament.
Upon surgical exposure, the lesion is concealed beneath normal-appearing cortical bone or reactive bone from which the soft tissues can be stripped with ease. After a window is cut in the overlying bone the tissue appears as a vascular, friable, almost spongelike tissue.
Surgical appearance of GCT:
[Surgical Path] A GCT of the sacrum is exposed. [Surgical Path] The vascular tissue of a GCT of the distal radius is shown.
The tissue can easily be removed with scalpel, curette or a gynecological suction-curette. The curettings are soft, reddish brown tissue interspersed with areas of golden-yellow tissue.
Appearance of curettings from a GCT:
[Surgical Path] A GCT of the femoral condyle is exposed. [Surgical Path] Curettings from the lesion are shown. [Surgical Path] This is a closer look at the curettings.
When the entire specimen is available for inspection, the appearance of the lesion is quite variable. In some instances, the tissue is entirely soft, vascular, friable reddish-brown viable tissue. These lesions have a homogeneous bright signal on MRI due to their high water content.
Appearance of viable GCT tissue:
[Gross Path] The interior of a GCT of the distal radius is filled with highly-vascular tissue. This tissue is composed of stromal cells, giant cells and thin-walled vascular channels. [Gross Path] The cut surfaces of another stage 3 GCT of the distal radius is composed of vascular, friable brownish tissue.
In other instances, the lesion is primarily composed of firmer, yellowish cheesy or spongy necrotic tissue with little vascular tissue. These areas are composed of necrotic neoplastic tissue and large lipid-filled histiocytes. Such lesions have a less intense but homogeneous signal on MRI.
Appearance of necrotic GCT tissue:
[Gross Path] This stage 2 GCT of the distal femur is almost entirely composed of cheesy, firm yellowish tissue.
In most instances, the lesion is composed of varying amounts of viable tissue admixed with the necrotic tissue. In these instances, the MRI signal is non-homogeneous with alternating areas of bright and darker signal.
Appearance of mixed viable and necrotic GCT tissue:
[Gross Path] The cut surfaces of this giant cell tumor of the distal femur contain a central area of cheesy yellow tissue surrounded by vascular brownish tissue. [Gross Path] This GCT is about evenly divided between soft vascular tissue and firmer, more dense yellowish tissue. [Gross Path] This is a closer look at the more dense yellowish tissue. These are the areas composed of necrotic neoplastic tissue and large lipid-filled histiocytes.
Extension from a subchondral lesion into the cavity of an adjacent joint usually takes place at the origin or insertion of intra-articular ligaments, with the cruciates in the knee being the more common.
Joint extension of GCT:
[X-Ray] An AP radiograph of a stage 3 GCT of the proximal tibia suggests intra-articular extension along the cruciate insertion into the tibial spine. [X-Ray] Tomography is suggestive but not confirmatory. (MRI was not available) [Gross Path] A superior view of the surgical specimen shows neoplastic tissue involving the site of cruciate insertion between the menisci. [Gross Path] The coronal surface of the sectioned specimen shows the proximal extension of the lesion.
Intra-articular extension directly through the articular cartilage is less common but does occur. This predilection of giant cell tumor to directly invade and destroy articular cartilage, while not unique to GCT, is seen more often with GCT than any other tumor, including malignancies.
Articular cartilage destruction in GCT:
[Gross Path] In this dissected specimen of a stage 3 giant cell tumor of the distal radius, the distal radius and the proximal carpal row were resected en bloc because of intra-articular wrist joint extension. [Gross Path] A view with the proximal carpals flexed upward exposes the articular surface of the distal radius. The articular cartilage of the carpals appears normal, but that of the distal radial cup has been destroyed by the neoplastic tissue.
Another example of articular cartilage destruction in GCT:
[X-Ray] In this AP radiograph of a recurrent stage 3 GCT of the distal tibia, the lesion has destroyed a substantial portion of the subchondral plate. [MRI] A coronal T-2 weighted MRI suggests ankle-joint extension. [Gross Path] This is an anterior view of the surgical resection specimen (distal tibia and fibula). [Gross Path] An inferior view of the surgical specimen shows invasion and destruction of articular cartilage by the vascular neoplastic tissue.
Although intra-articular dissemination via pathologic fracture is uncommon, it does occur. It must, therefore be sought for in those circumstances.
Joint extension via fracture in GCT:
[Gross Path] This is an anterior view of a specimen obtained by amputation for a GCT with joint extension via a pathologic fracture. [Gross Path] This is a coronal surface of the sectioned specimen. [Gross Path] A closer view shows a nodule of intra articular tumor beneath the pathologic fracture of the femoral condyle. [Gross Path] Anterior view of the reflected suprapatellar pouch. [Gross Path] A closer view shows nodules of transplanted GCT studding the pouch.
The principal microscopic features of giant cell tumor are cytologically bland stromal cells, uniformly-small multinucleated giant cells, generous vascularity and prominent areas of necrosis.
The stromal cells have large vesiculated nuclei with a sharply defined nuclear membrane containing one or two nucleoli. The giant cells, formed by fusion of the stromal cells, are uniformly small, and their several nuclei have the same features as the stromal cells. The tissue is often composed of a syncytium or network of giant cells, and it may be difficult to tell where the stromal cells end and the giant cells begin. These, together with the vascular elements, compose the viable, soft, friable reddish-brown neoplastic tissue of the lesion.
Pattern of stromal and giant cells in GCT:
[Micro] A panoramic view shows the usual proportion and distribution of giant cells among the stromal cells. [Micro] Medium power shows the even distribution of the giant cells. [Micro] Higher power shows the similarity between the stromal cells and the aggregates of giant cells. [Micro] High power shows the similarity of the vesiculated nuclei with sharp nuclear membranes and occasional nucleoli between the stromal and giant cells. It is difficult to distinguish the central giant cell from a cluster of unfused stromal cells along the right border of the field.
Typical vesiculated nuclei in GCT:
[Micro] A medium power field with a typical pattern of stromal and giant cells. [Micro] High power shows three giant cells with eosinophilic cytoplasm embedded in mononuclear stromal cells. All the nuclei, both stromal and giant cell, have a distinct basophilic nuclear membrane and a vesiculated nucleus punctuated by one or two basophilic nucleoli.
Vascularity in GCT:
[Micro] A medium-power field shows a typical, thin-walled vascular channel filled with RBC. [Micro] Higher magnification shows fine channels meandering through the tissue. [Micro] A high-power field shows fine vascularity between two giant cells. [Micro] This is another similar field from the same specimen. [Micro] RBC intermingle with the neoplastic cells. [Micro] A panoramic field from a GCT of the distal radius shows a prominent vascular pattern. [Micro] The channels have ill-defined, thin single cell walls often appearing to be formed by the stromal cells. [Micro] This pattern has led some to speculate that GCT may be of endothelial histogenesis.
In other areas, a quite different pattern is seen. These are the areas of firmer yellowish tissue. Here, the prominent features are large areas of necrosis containing the ghosts of multinucleated giant cells, mature fibrous tissue, granules of hemosiderin and occasional pockets of large lipid-filled histiocytes.
Ghosts of giant cells in GCT:
[Micro] A panoramic view from a stage 2 GCT of the femoral head shows a broad pale-staining swatch of necrotic tissue running vertically through the midthird of the field. Within the tissue are seen the outlines of multinucleated giant cells with no nuclear basophilia such as are seen in the viable tissue along either margin of the field.
Examples of fibrosis and hemosiderin in GCT:
[Micro] This is a panoramic view of a field containing dense fibrous tissue studded with hemosiderin. [Micro] A similar field reveals less-mature fibrous tissue studded with hemosiderin. [Micro] A panoramic view at the edge of a lesion shows a heavy deposition of hemosiderin (right edge) abutting a nodule of viable neoplastic cells.
It is not unusual to observe thrombi of tumor cells in capillaries and small venules scattered about in the tissue.
In areas where the lesion extends to and through the articular cartilage, the tumor cells appear to be directly resorbing the viable articular cartilage.
Destruction of articular cartilage by GCT:
[Micro] A composite shows a stage 3 GCT of the femoral head invading the articular cartilage of the dome of the femoral head and the corresponding histologic picture of neoplastic tissue destroying the subchondral plate, and passing through the tideline and into the cartilage. [Micro] This is a composite from the opposite surface of the joint showing the gross destruction of cartilage in the acetabulum and the corresponding tongue of GCT that replaced the destroyed cartilage. This pattern is almost unique to GCT and certainly more often seen in GCT than any other neoplastic lesion.
Another example of articular cartilage destruction by GCT:
[Gross Path] In the anterior and posterior views of a resected GCT of the distal femur, tumor is extruding through the articular cartilage of the femoral condyle (right on posterior view). [Gross Path] The coronal surfaces of the sectioned specimen show several areas of cartilage destruction and penetration. [Macro] A coronal macrosection shows basophilic neoplastic tissue engulfing articular cartilage (lower margin, central). [Micro] A panoramic view shows neoplastic tissue resorbing the deep side of the articular cartilage.
A third example of cartilage destruction by GCT:
[X-Ray] An AP radiograph reveals a recurrent GCT of the proximal tibia following curettage/cementation. Arthroscopy showed marked cartilage destruction. [CT Scan] A CT image shows the recurrence abutting the cement. [Micro] A panoramic field shows neoplastic tissue invading and destroying the articular cartilage from below. [Micro] A tongue of neoplastic tissue is invading the articular cartilage in this field. [Micro] A closer look is taken at the interface between tumor and cartilage.
Simultaneous multicentric lesions, metachronous skip lesions and lesions associated with pulmonary metastases demonstrate significant variation from the conventional course and/or behavior of giant cell tumor.
Patients with two or more separate skeletal lesions randomly scattered about the skeleton are described as suffering with multicentric giant cell tumor. There is nothing extraordinary about any one lesion; that is, each lesion has the characteristics of a conventional giant cell tumor including response to treatment.
There is no predilection for the anatomic distribution although the lesions are located in the usual epiphyseal areas. Multicentric lesions appear to be latent, active or aggressive in the same proportion as conventional lesions. The risk of recurrence and/or pulmonary metastasis is no greater than that for conventional lesions.
Multicentric GCT:
[X-Ray] A 35-year-old military aviator presented with simultaneous radiographic evidence of lesions in the ipsilateral distal femur and proximal tibia. A skeletal survey revealed other lesions in the proximal humerus, distal radius, proximal femur, distal femur, proximal tibia and proximal fibula. Exhaustive evaluation showed no evidence of an underlying metabolic disease, and serum parathormone levels remained consistently normal throughout his subsequent course. Both presenting lesions were treated with curettage and bone grafting, but both promptly recurred. An above-knee amputation was done, and he was discharged from the military. [Photo] He, subsequently, presented with a mass about the opposite knee. [X Ray] Screening radiographs showed that the lesions in the proximal tibia and fibula had progressed. [Follow up] These were managed by excision of the proximal fibular lesion and preoperative radiotherapy to the proximal tibial lesion. This was followed by curettage and cementation after which they have remained healed. [X-Ray] Next, the lesion in the femoral head became symptomatic and enlarged. [Gross Path] The femoral head and neck were excised. [Follow-up] The defect was reconstructed with a hemiarthroplasty and has remained free of recurrence. The active lesion in the proximal humerus has been successfully curetted and cemented while the lesion in the distal radius has remained latent.
Patients who present with a single lesion and develop subsequent lesions that proximally ascend an extremity are said to have metachronous skip lesions. These patients have a greater risk of subsequently developing additional lesions than their conventional counterparts, but each single lesion responds to treatment in the conventional fashion. It is thought that this represents true skip metastases rather than multicentric lesions with a hemimelic distribution.
Metachronous skip lesions:
[X-Ray] A 16-year-old female presented with a stage 2 GCT of the talus. A skeletal survey and isotope scanning revealed no other lesions. [Micro] Biopsy confirmed the diagnosis and a curettage and autogenous bone grafting was done. [X Ray] Four years later, she presented with a destructive lesion involving the distal tibial epiphysis. Skeletal survey and isotope scanning again showed no other lesions. Biopsy confirmed giant cell tumor and a below-knee amputation was done. [Gross Path] Inspection of the surgical specimen showed the distal tibial lesion and revealed that the prior lesion in the talus remained healed without recurrence. [Macro] This was confirmed by macroscopic histologic study. [X Ray] She remained well for three years after which time she developed severe pain in her below-knee stump prohibiting prosthetic use. Screening radiographs revealed a suggestive radiolucency in her osteopenic stump. [Iso-Scan] Isotope scanning showed a focal increase in uptake at this area with no other lesions elsewhere. CT imaging defined a poorly-marginated lesion. Biopsy confirmed GCT, and she was converted to an above-knee amputee. [Gross Path] The surgical specimen showed the subcortical extent of the lesion. [Macro] Macroscopic sectioning showed no other lesions. She has remained free of disease for the ensuing six years.
It is estimated that between 2 to 5 percent of patients with conventional giant cell tumor will develop a pulmonary metastases. These are patients with histologically-benign stage 2 and 3 lesions, (not patients with frank giant cell sarcoma). Although the primary skeletal lesion in these patients may contain an occasional mitotic figure and/or an intravascular thrombus of GCT, these findings are also seen in conventional giant cell tumors that are never associated with pulmonary metastases. There appears to be no method of accurately predicting which patients with conventional giant cell tumor are at risk for subsequent pulmonary metastases.
Pulmonary metastases in conventional GCT:
[X-Ray] A 20-year-old female presented with a lesion of the femoral condyle. [CT Scan] An axial CT image showed the lesion to be well marginated at this level. [CT Scan] More proximally, there was cortical breakthrough with a large soft-tissue component. [Micro] Biopsy confirmed stage 3 GCT, and a curettage with bone graft was done. [Micro] In the reactive tissue about the lesion thrombi of GCT were found in small venules. [X-Ray] Six months later a follow-up radiograph showed destruction of the grafts and enlargement of the lesion. [X-Ray] A chest radiograph showed a single large pulmonary nodule. [Micro] The nodule was excised. This panoramic field at the edge of the nodule shows normal lung interfacing with the periphery of the lesion. [Micro] Higher power shows the features of a conventional giant cell tumor.
The prognosis of patients with pulmonary metastases from conventional GCT is much better than for pulmonary metastases from sarcomas. Approximately 80 percent of such patients are cured by excision of the pulmonary nodule(s) with or without chemotherapy.
Pulmonary metastasis in GCT:
[X-Ray] A 37-year-old female presented with a stage 3 giant cell tumor of the proximal tibia. [Gross Path] A wide resection of the proximal tibia was done. [Micro] The microscopic features were typical for GCT. There was no cytologic atypia. [Follow up] Routine follow-up chest radiograph at one year showed three pulmonary nodules which were excised. The histology revealed that of conventional GCT. [Follow-up] Radiograph of the chest at last follow up fifteen years later showed no evidence of disease.
Giant cell sarcoma is a frankly malignant sarcoma of bone featured by a stroma of malignant spindle cells throughout which are scattered small multinucleated giant cells identical to those seen in conventional giant cell tumor.
Radiographically, they appear as permeative, destructive lesions often located in the metaphysis or diaphysis of the long bones, and they have little in common with conventional GCT. Their imaging studies are consistent with their frankly high-grade malignant nature. The prognosis and response to treatment is identical to that of any Stage II sarcoma, and aggressive wide surgical margins are required to obtain local control.
Example of a giant cell sarcoma:
[X-Ray] A 27-year-old male presented with a tender mass in the distal thigh. Screening radiographs demonstrated a subtle permeative lesion in the distal diaphysis/metaphysis of the femur. [X-Ray] This is a magnified lateral radiograph. [Gross Path] The sagittal surfaces of the sectioned surgical specimen show a dense, whitish tissue replacing the normal marrow with erosive defects in the overlying endosteal cortex and a posterior soft-tissue mass. [Micro] A panoramic field from the biopsy specimen shows a background of spindle shaped mesenchymal cells with scattered giant cells. [Micro] The ratio of giant cells to stromal cells is considerably lower than in conventional GCT. [Micro] The nuclei of the stromal cell are slender, fusiform and hyperchromatic in contrast to the round vesiculated stromal nuclei of GCT. [Micro] The nuclei of the giant cells (upper, central) closely resemble those in conventional GCT which can lead to misinterpretation. The difference in the stromal cells, however, is so striking that, to avoid ambiguity, some prefer to refer to this lesion as a fibrosarcoma with benign giant cells rather than a giant cell sarcoma.
It is important to emphasize that this lesion does not represent malignant transformation from a conventional GCT (which rarely, if ever, happens) but is a malignant sarcoma from the outset. It is equally important to appreciate that one or two mitoses in a conventional GCT do not make it a sarcoma requiring similar aggressive surgical treatment as a true giant cell sarcoma.
Treatment of giant cell tumor depends principally on the stage of the lesion. Other considerations such as age, site, size and patient expectations are also important and, in individual cases, may be the dominant factor. In formulating a surgical treatment plan, however, the biologic aggressiveness or behavior of the lesion as expressed by the stage is often the keystone.
Stage 1 lesions have a negligible recurrence rate following intralesional curettage. Cryosurgery or cementation with polymethylmethacrylate (PMMA) is not indicated. Occasional spontaneous healing of a stage 1 lesion has been observed.
Curettage/bone graft of a stage 1 GCT:
[X-Ray] A stage 1 lesion of the femoral head was treated by curettage and autogenous bone grafting. [Follow up] A follow-up radiograph at 22 years showed no recurrence.
Spontaneous involution of a stage 1 GCT:
[X-Ray] A 37-year-old male with a long history of multicentric giant cell tumors had this asymptomatic lesion of the distal radius discovered during routine skeletal survey. [Follow up] The patient refused surgical treatment. This follow-up radiograph was made three years later. [Follow up] This radiograph was made six years after diagnosis. There has been no subsequent progression for another seven years.
Local recurrence following curettage of active lesions is now about 20 percent if an aggressive extended curettage is possible. Extended is interpreted as being a wide exposure of the lesion, meticulous curettage, extensive water-picking of the cavity walls, removing the reactive shell about the cavity walls with a high-speed bur until normal marrow is encountered and then filling the cavity with bone graft or bone cement.
Technique of curettage:
[X-Ray] This is a presenting AP radiograph of a stage 2 GCT of the distal femur. [CT Scan] CT imaging showed no characteristics of aggressive behavior. [Surgical Path] The suction/curet apparatus used for gynecologic D and C was used to minimize the risk of tissue contamination during the curettage. [Surgical Path] The cavity is continuously lavaged during the curettage. [Surgical Path] The tissue obtained in the trap with this technique makes excellent histologic specimens. [Surgical Path] The cavity developed by the curettage through the generous window is accessible for lavage and wall removal.
If the cavity is stable with little or no risk of pathologic fracture, bone graft is preferred. Bone cement is preferred if the extent of the curettage is compromised by the location of the lesion or by its proximity to the subchondral plate or if the risk of pathologic fracture is substantial.
The majority of recurrences after curettage of stage 2 GCT occurs when the proximity of the lesion to the joint makes aggressive curettage risky in terms of inadvertent penetration of the joint or loss of joint congruity by collapse of the surgically thinned subchondral plate. In these situations, the use of bone cement reduces the risk of recurrence, both by permitting more aggressive curettage and by producing necrosis of the surrounding tissue by its exothermic heat of polymerization.
Curettage/cementation of a stage 2 GCT:
[X-Ray] This is an AP radiograph of a stage 2 GCT within a few millimeters of the subchondral plate of the distal femur. [X-Ray] The lateral view shows the proximity to the subchondral plate is anterior. [CT Scan] CT imaging shows a well-defined reactive shell indicating a stage 2 lesion. Because the proximity to the subchondral plate limited the extent of curettage anteriorly, the cavity was cemented rather than filled with bone graft. [Follow-up] At three years there was no evidence of recurrence.
Follow-up of cemented GCT:
[X-Ray] This is an AP radiograph of a GCT of the distal femur in an 18-year-old active male. [Follow up] In the follow-up radiograph at two years, the radiolucent zone represents the extent of necrosis and remodeling about the curetted cavity. [Follow-up] At six years after resumption of an active lifestyle, there is no recurrence or evidence of osteoarthritis.
There is controversy about the risk of degenerative arthritis after cementation of cavities in proximity to the subchondral plate. Long-term studies indicate that, if there is a centimeter or more of cancellous bone between the cement and the subchondral plate, the risk of degenerative arthritis is minimal. If there is less than 5 mm of intervening bone, the risk of arthritis is significant (circa 35%). For this reason, autogenous iliac bone graft of at least 1 cm is used to line the subchondral aspect of the cavity prior to cementation.
[Surgical Path] Diagrammatic representation of a GCT with less than 1 cm of cancellous bone beneath the weightbearing subchondral plate. Autogenous bone graft held in place with gelfoam prior to cementation (left) is preferred over simple cementation. Intermediate term results indicate this technique significantly reduces the incidence of late arthritis.
Degenerative changes following subchondral cementation:
[X-Ray] A 32-year-old female presented with a stage 2 GCT of the proximal tibia. [MRI] MRI imaging showed extension to the subchondral plate in a weightbearing region. [Follow-up] The lesion was packed with bone cement following an extended curettage. Within one year the patient developed signs of internal derangement of the knee. During meniscal removal, marked degenerative changes were noted in the articular cartilage. [Follow-up] The cement was removed and the cavity filled with autogenous bone graft supplemented with internal fixation. Follow-up radiographs showed significant narrowing of the articular cartilage.
[X-Ray] A 55-year-old female presented with a stage 2 GCT extending to the subchondral plate beneath the weightbearing portion of the medial tibial plateau. [Surgical Path] Thorough curettage [Surgical Path] was followed by lavage and high speed burring. [Surgical Path] The cavity was packed with cement supplemented with two screws. [Follow up] Within six months the patient developed degenerative changes that led to a total knee arthroplasty two years later.
Subchondral bone grafting/cementation for GCT:
[MRI] A 23-year-old male presented with a stage 3 GCT of the proximal tibia. MRI imaging revealed extension to the subchondral plate beneath the lateral plateau. [Follow up] The post-operative radiograph after extended curettage, subchondral bone grafting, and cementation, showed the 1 cm layer of iliac bone graft between the cement and subchondral plate. [Follow-up] The lateral projection shows the extent of the bone grafting. There had been no degenerative changes, despite an extremely active lifestyle, three years later.
There is also controversy as to whether the cement should be subsequently removed and replaced by bone graft. Long-term studies indicate no significant problems associated with cement retention; and, so, unless the patient's unusual lifestyle imposes extraordinary loads, the cement is not routinely removed. If cement is to be removed, it should not be done until the interval of high risk of recurrence (two years) has passed.
Curettage/cementation with subsequent cement removal and bone grafting: [X-Ray] A 22-year-old female presented with a stage 2 GCT of the proximal tibia. [MRI] Axial MRI showed no posterior cortical broaching or soft-tissue extension. [MRI] Coronal MRI showed extension to the subchondral plate. [Follow-up] An extended curettage/cementation without subchondral bone grafting was done. An AP radiograph at one year showed early degenerative changes. The patient did not have disabling symptoms. [Follow-up] The cement was removed and replaced by autogenous bone graft supplemented by a buttress plate. An AP radiograph at four years shows narrowed articular cartilage although the patient is asymptomatic.
Local recurrence following extended curettage for aggressive lesions with cortical broaching, soft-tissue extension or intra-articular extension is 70 percent. With the addition of cryosurgery or cementation, it is about 25 percent.
Curettage/cementation for stage 3 GCT:
[X-Ray] A 16-year-old male presented with a GCT of the distal femur. [CT Scan] CT imaging showed posterior cortical broaching with soft-tissue extension. [Follow-up] An AP radiograph done ten years post curettage and cementation showed no recurrence. [Follow up] This lateral radiograph was done at ten years.
Aggressive lesions with extensive soft-tissue involvement are clearly high-risk candidates for curettage or marginal excision. In order to attain acceptable recurrence rates, these require wide surgical margins, usually involving resection with hemi-joint loss because of the juxta-articular location of GCT. Reconstructive alternatives include arthrodesis, osteoarticular allograft, custom prostheses and, occasionally, patellar osteoarticular autograft for lesions of the proximal tibia.
Wide resection/arthrodesis for stage 3 GCT:
[X-Ray] This is a lateral radiograph of a GCT in a 26-year-old professional tennis player presenting after two failed arthroscopies for presumed "chondromalacia". [MRI] MRI suggested posterior soft-tissue extension. [Angio] Angiography confirmed abutment of the popliteal neurovascular bundle. [Surgical Path] Wide intra-articular excision of the distal femur was reconstructed by spanning hemi-tibial and fibular autogenous bone grafts. [Follow-up] A follow-up radiograph at six years shows no recurrence.
Wide resection/modular prosthesis for stage 3 GCT:
[X-Ray] This is a lateral radiograph of a stage 3 GCT in an 84-year-old female who presented with a pathologic fracture. The fracture was treated with traction and plaster. Eight weeks later, the lesion was staged. [MRI] MRI imaging demonstrated a large, posterior soft-tissue component, and a wide resection was done. [Gross Path] The coronal surface of the sectioned specimen shows a portion of the soft-tissue extension. Primarily due to her age, a modular prosthetic total knee arthroplasty was used for reconstruction. [Follow-up] Post-operative AP radiograph at one year. [Follow-up] The lateral projection.
Wide resection/osteoarticular allograft for stage 3 GCT:
[X-Ray] This is an AP radiograph of a stage 3 GCT in a 33-year-old female who presented with a pathologic fracture. [CT Scan] An axial CT revealed a comminuted intra articular fracture. The fracture was immobilized in a cast; and, ten weeks later, a frozen section with wide excision was done. [Gross Path] In the coronal surface of the sectioned surgical section, no intra-articular implants of the lesion were found. [Follow-up] The defect was reconstructed with an osteoarticular allograft. This postoperative radiograph was made at one year. [Follow-up] A follow-up radiograph at nine years showed solid union with no evidence of graft resorption. [Follow-up] A close look showed no narrowing of the articular cartilages or degenerative changes. [Follow up] This details the appearance of the lower extremities after ten years. The knee had ligamentous stability. [Follow-up] Extension was complete. [Follow up] There was 100 degrees of flexion.
Recurrent lesions are restaged and treated by the same criteria as primary lesions. Their risk of a second recurrence is no greater than a previously untreated lesion.
Curettage/cementation of a stage 2 recurrent GCT:
[X-Ray] A stage 3 GCT of the distal femur [CT Scan] with several areas of cortical breakthrough was managed by wide hemicondylar resection. [Surgical Path] The defect was filled with a hemicondylar allograft. [X-Ray] At one year there was satisfactory function. [X-Ray] At three years a local recurrence at the tip of a screw was observed. [Follow up] The stage 2 intracortical recurrence was managed by curettage/cementation. There has been no subsequent recurrence at five years.
Patellar autogenous osteoarticular graft for stage 3 recurrent GCT:
[X-Ray] A 29-year-old female presented with collapse of the medial tibial plateau three years after curettage and cementation of a stage 3 GCT. [CT Scan] Axial CT image showed a radiolucent recurrence with cortical broaching. [Follow-up] The medial epiphysis was widely resected and repaired with an autogenous patellar osteoarticular graft buttressed with iliac corticocancellous grafts. [Follow up] This is a follow-up radiograph at six years. [Follow-up] Knee flexion is shown at six years. [Follow-up] Knee extension against resistance is shown at six years.
Lesions with pathologic fracture present special treatment problems. Many of the fractures extend intra-articularly because of the predilection for epiphyseal location of the lesion. An estimate should be made of the prefracture stage of the lesion and the method of treatment based upon that estimate. Although there is potential contamination of surrounding soft tissues or joint cavities by the fracture, the ensuing callus usually encompasses latent and active lesions so that conversion of a stage 1 or 2 lesion to a stage 3 lesion by virtue of the fracture rarely occurs. It is rarely necessary to do aggressive resections for stage 1 or 2 lesions that present with pathologic fractures. Lesions that were stage 3 prefracture should be treated as such.
Wide resection for stage 3 GCT with pathologic fracture:
[Photo] A 26-year-old female presented six weeks after the sudden onset of pain and swelling about the knee. [X Ray] Screening radiographs showed a healing pathologic fracture and suggested the lesion had considerable soft-tissue extension prior to the fracture. [MRI] MRI imaging confirmed intra-articular extension into the suprapatellar pouch anteriorly and a wide resection was elected for the presumed stage 3 lesion. [Gross Path] The surgical findings confirmed the aggressive stage. [Gross Path] The cut surfaces of the specimen showed envelopment of the lesion by fracture callus proximally but intra-articular extension along the cruciate origin distally. [Macro] The macrosection confirmed these observations.
Since both curettage and resection can be accomplished much more accurately after continuity has been restored by callus rather than when the wall of the lesion is made up of multiple loose fragments, definitive treatment is best postponed until the fracture is stabilized by enveloping callus. Treatment of the fracture is better done by external means rather than with internal fixation because of the risk of implantation by fixation devices unless it is imperative to restore joint congruity in a lesion that is otherwise amenable to curettage.
Giant cell tumor of bone often responds satisfactorily to moderate doses (circa 40 to 45 centigray) of radiation therapy. The response is accompanied by ossification of the radiolucencies although the resulting disorganized mass seldom remodels. Persistence of viable lesion with subsequent clinical recurrence occurs in 15 to 25 percent of the patients.
There is a significant risk of late sarcomatous transformation and/or radiation-induced sarcoma. The precise risk, given today's radiotherapy technique, is unknown since there is a long (5 to 10 years) latent period, but this is, probably, less than 5 percent. For this reason, definitive surgery is the preferred management when practical, and radiotherapy is employed only when adequate surgical margins are unattainable, principally for recurrent lesion about the spine.
Radiotherapy for recurrent stage 3 GCT of the lumbar spine:
[X-Ray] A 19-year-old female presented with a stage 3 GCT of the body of L-2. [CT Scan] CT imaging showed anterior cortical breakthrough with soft-tissue extension. Curettage and fibular bone grafting from L-1 to L-3 was done anteriorly. [Follow-up] This is an AP radiograph done six months postoperatively. A subsequent recurrence developed which was recuretted and 40 centigray of radiotherapy given. There has been no recurrence for five years.
Radiotherapy for stage 3 GCT of the sacrum:
[X-Ray] A 33-year-old male presented with incontinence. A screening radiograph showed a lesion involving the entire sacrum below S-1. [X-Ray] A magnified view shows extension into the sciatic notch. [CT Scan] CT imaging showed extension across the sacroiliac joint into the ilium (on your right). [Surgical Path] Posterior biopsy established a diagnosis of GCT. Definitive treatment was 50 centigray of radiation therapy. There was complete resolution of the neurologic dysfunction. [Follow-up] A follow-up radiograph at six years. demonstrated no progression with incomplete re ossification. [Follow-up] Magnification of that radiograph. There has been no subsequent recurrence at 13 years. Re ossification remains incomplete.
Radiation-induced sarcoma after radiotherapy for GCT of the sacrum:
[Photo] A 37-year-old male presented four years after receiving 50 centigray of radiation therapy for a stage 3 GCT of the sacrum with a recurrent sacral mass. [X-Ray] AP radiograph showed a large mass replacing the sacrum. [Gross Path] A marginal en bloc excision of the sacrum was done. [Micro] Histologic study showed viable benign GCT encapsulated by the radiation induced dense fibrous capsule. [Angio] At fifteen years the patient, who had remained well in the interval, developed a painful buttock mass. This angiogram shows displacement of the common iliac by a large soft-tissue mass protruding intrapelvically from the radiolucent defect in the ilium. [CT Scan] An axial CT image shows the destructive process in the posterior aspect of the ilium with a large extrapelvic extension into the buttock as well as the intrapelvic extension seen angiographically. [Micro] Biopsy revealed a highly malignant undifferentiated spindle cell sarcoma. [Micro] Another field shows grade four cellular atypia. A diagnosis of stage II-B radiation-induced sarcoma was made.
Only cases 1801.x are available in this sample chapter.
Case 1801.1Case 4175.1
Giant cell tumor of the distal femur in a 57-year-old female treated by curettage/cementation.
Case 4501.1
Giant cell tumor of the distal femur in a 26-year-old female treated by resection/arthrodesis. 17 year follow-up.
Case 4176.1
Giant cell tumor of the femoral head in a 34-year-old female.
Case 4174.1
Giant cell tumor of the proximal humerus, in a 19-year-old female treated by wide excision/reconstructed with dual autogenous fibular bone grafts.
Case 1195.1
Giant cell tumor of the ilium in a 26-year-old male misdiagnosed as primary ABC and treated by radiation therapy. Case 1195.2 - Subsequent recurrence correctly diagnosed as GCT with secondary ABC treated by hemipelvectomy.
Case 635.1
Giant cell tumor of the proximal tibia in a 55-year-old female. Treated by curettage/cementation with subsequent degenerative changes in the articular cartilage/total knee arthroplasty.
Case 4274.1
Stage 3 Giant cell tumor of the proximal tibia in a 29-year-old male treated by wide excision/arthrodesis.
Exercise 91 Quiz Mode
Exercise 91 Review Mode
Dahlin, D.C.; Cupps, R.; Johnson, E. W.: "Giant Cell Tumor: A Study of 195 Cases", Cancer, Vol. 25, 1061-1070, 1970.
Goldenberg, R; Campbell, C.J.; and Bonfiglio, M.: "Giant Cell Tumor of Bone. An Analysis of Two-Hundred and Eighteen Cases", Jour. Bone and Joint Surg., Vol. 52-A, 619-664, 1970.
Campanacci, M.; Baldini, N.; Boriani, S.; Sudanese, A.: "Giant-Cell Tumor of Bone", Jour. Bone and Joint Surg., Vol. 69-A, 105-114, 1987.