Treatment of Giant Cell Tumor of Long Bones: Clinical Outcome and Reconstructive Strategy for Lower and Upper Limbs

By Keiichi Muramatsu, MD; Koichiro Ihara, MD; Toshihiko Taguchi, MD
ORTHOPEDICS 2009; 32:491

Abstract

Giant cell tumor of bone is a rare and unpredictable lesion. Standard treatment ranges from surgical curettage to wide resection, with reports of varying oncological and functional results. Twenty-three consecutive cases of giant cell tumor of long bones were treated in 10 years. Fifteen men and 8 women had a mean age of 38 years (range, 17-82 years). Average follow-up was 45 months (range, 12-180 months). The most common tumor sites were the proximal tibia (10 cases), distal femur (8), and distal radius (3). All patients remained free of recurrence at the time of final follow-up. Functional outcomes as evaluated by the Musculoskeletal Tumor Society measure were successful, with an average score of 26.6 points (range, 22-30 points).

To avoid local recurrence around the knee joint, we recommend radical intralesional curettage with a high-speed drill burr, adjunctive therapy with cryosurgery, and filling with polymethylmethacrylate. Primary total knee arthroplasty is acceptable for older patients. For giant cell tumor of the upper limb or for young patients, biological reconstruction should be applied.

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Giant cell tumor of bone is an aggressive bone tumor that arises adjacent to the subchondral bone of major joints. It is thought to originate at the metaphyseoepiphyseal junction and may extend into the metaphysis.¹ The areas of bone most often involved are the distal femur, proximal tibia, proximal humerus, and distal radius. Although histologically benign, giant cell tumor shows locally destructive behavior and frequent local recurrence postoperatively. In large series, the postoperative recurrence rate has been reported to vary from 4% to 50%.^2-12 This has led surgeons to enhance the surgical procedure with adjuvants such as liquid nitrogen,^13,14 acrylic cement,¹⁵ phenol,^5,10 hydrogen peroxide,¹⁶ or radiation therapy.¹⁷ Wide resection is associated with better local control, but often impairs limb function due to the sacrifice of a significant segment of bone.^4,10

Treatments ranging from surgical curettage to wide resection and varying oncological and functional results have so far been reported in the literature. This article describes the clinical outcome of patients with giant cell tumor of bone and discusses the presently accepted surgical gold standard for this lesion.

Materials and Methods

Patients

From 1988 to 2007, 31 patients who met the histological criteria of giant cell tumor of bone were treated at our institution. Twenty-three cases were giant cell tumor of long bones and 8 were of spine, hand, and foot. Fifteen men and 8 women had a mean age of 38 years (range, 17-82 years). Average follow-up was 45 months (range, 12-180 months). The tumors were present in the proximal tibia (n = 10), distal femur (n = 8), distal radius (n = 3), proximal humerus (n = 1), and femur (n = 1). At the time of diagnosis, all patients had reported pain for at least 1 month, and 2 patients had a pathologic fracture. At presentation, 20 lesions were primary tumors and 3 were recurrent lesions following treatment at other institutions.

Progression of giant cell tumor was evaluated with the most commonly used system: Campanacci grading.⁴ From radiographic, magnetic resonance imaging (MRI), and operative findings, grades were determined as follows: grade I tumors were intraosseous lesions; grade II tumors were extraosseous lesions without loss of cortical continuity and with a thin cortex; and grade III tumors were extraosseous lesions that broke through the cortex and extended into soft tissue. Pathological fractures were classified as grade III. Using these criteria, 14 patients were evaluated as grade II and 9 as grade III. Medical records and pre- and postoperative radiographs, computed tomography (CT) scans, and MRIs were reviewed.

Operative and Reconstructive Procedures

The type of treatment and reconstruction chosen following resection depended on the location of the tumor, Campanacci grading, and patient age (Table 1). Four patients underwent wide resection of the tumor. In 19 patients, the giant cell tumor was treated with modified intralesional curettage. The procedure included extended bone curettage consisting of wide exteriorization of the lesion and vigorous curettage of grossly abnormal cancellous and cortical bone. A high-speed burr was used to facilitate tumor removal. The folds separating the bone cavity were completely curetted, and this procedure was repeated until all areas of the cavity had been covered. In lesions at the proximal tibia and distal femur, bone peg holes were created with a high-speed burr to increase stabilization of the polymethylmethacrylate (PMMA) filler (Figure 1). In the next step, adjuvant cryosurgery using liquid nitrogen was applied in 19 patients to destroy residual tumor cells, and the cavity was cleaned with normal saline. This procedure was repeated 3 times. Cryosurgery was not applied to patients treated with wide resection of the giant cell tumor and with a high risk of frostbite due to liquid nitrogen leak.

Figure 1: Operative procedure of giant cell tumor included extended bone curettage consisting of wide exteriorization of the lesion and vigorous curettage of grossly abnormal cancellous and cortical bone. The folds separating the bone cavity were completely curetted with a high-speed burr (A). Bone pegs were created with a high-speed burr to increase stabilization of the PMMA filler (B). The large cavity resulting from extended curettage was filled with PMMA (C).

In 12 patients with giant cell tumor of the proximal tibia and distal femur, the large cavity resulting from extended curettage was filled with PMMA (Figure 2). Primary reconstruction with total knee arthroplasty (TKA) was performed in 2 patients, aged 82 and 64 years. In 2 patients with pathological fracture, after the undisplaced fracture was stabilized with a plate and screws, the cavity was filled with PMMA. In 17- and 18-year-old patients with giant cell tumor of the distal femur and proximal tibia, nonvascularized fibula grafts were used to support the subchondral bone of the knee joint. In 2 patients, massive bone defect of the femur condyle following wide resection of recurrent giant cell tumor was reconstructed with double-folded free vascularized fibula graft. In 4 patients with lesions in the upper limb, the bony defect resulting from extended curettage or wide resection was reconstructed using biological materials. In 3 patients with giant cell tumor of the distal radius, bony defects were filled with calcium phosphate in 2 patients (Figure 3) and a free vascularized fibula head graft was applied for the third patient. In a patient with giant cell tumor of the proximal humerus, allogenous cancellous bone grafts were used for reconstruction.

Figure 2: Preoperative radiograph (A) and MRI (B) of a 47-year-old man showing 2 giant cell tumors in the distal femur close to the joint surface. The patient was treated with extended curettage and adjuvant cryosurgery, and a large defect was filled with PMMA (C). The Musculoskeletal Tumor Society score was 28 points at 2-year follow-up.

Functional Evaluation

Functional evaluation was performed according to the Musculoskeletal Tumor Society score system.¹⁸ This system for upper and lower limbs involves 6 factors including pain, function, and emotional acceptance. A maximum 5 points for each factor results in a maximum possible score of 30 points. Functional assessment was performed at most recent follow-up. The functional results were compared using an unpaired t test.

Results

Oncological Results

Of the 18 patients with GCT around the knee joint (10 proximal tibia and 8 distal femur), 16 underwent intralesional curettage, cryosurgery with liquid nitrogen, and high-speed burring, and the bony cavity was filled with PMMA in 12 patients. Total knee arthroplasty was primarily applied in 2 patients, whose Musculoskeletal Tumor Society scores were 22 and 26 points, respectively. Free vascularized fibula graft was used in 2 patients and bony union was achieved. A nonvascularized fibula graft in an 18-year-old patient resulted in collapse of the subchondral bone of the tibia, but the final Musculoskeletal Tumor Society score was 26 points with no additional reconstruction. Following intralesional curettage in 3 patients with distal radius giant cell tumor, the bony cavity was filled with calcium phosphate materials in 2 and vascularized fibula head transfer was performed in the third after wide resection of the distal radius.

All patients remained free of local recurrence at final follow-up. Postoperative complications were reported in 4 cases, comprising 3 with skin frostbite around the lesion and 1 with hematoma. The frostbite healed conservatively within 2 months postoperatively. None of the cases had postoperative infection. Three cases had distant metastatic lesions in the lung and 1 underwent thoracotomy (Figure 4).

Figure 3: Preoperative radiograph of a 19-year-old woman showing a giant cell tumor of the distal radius (A). After extended curettage, the radius was stabilized with a plate and screws and bony defects were filled with calcium phosphate (B). The Musculoskeletal Tumor Society score was 28 points at 1-year follow-up. Figure 4: A 55-year-old man had distant metastatic lesions in the lung and underwent thoracotomy.

Functional Results

The overall functional results evaluated by Musculoskeletal Tumor Society score were successful. The average score was 26.6 points (range, 20-30 points). Although surgical resections and reconstructive procedures varied for each patient, no statistical difference existed in scores according to tumor presentation, Campanacci grading, or tumor site.

Discussion

Recurrence Rate After Giant Cell Tumor Surgery

To date, the postoperative recurrence rate reported for giant cell tumor has been surprisingly high (Table 2). Campanacci et al⁴ reported a recurrence rate of 34% after intralesional excision, 7% after marginal excision, and none after wide excision. O’Donnell et al¹⁹ reviewed 60 patients with giant cell tumor of the long bone treated with curettage and filled with cement. They reported an initial rate of local recurrence of 25%, with an average time of 4 years. Similarly, Blackley et al² reviewed 59 patients with giant cell tumor treated with curettage and bone grafting. Their overall recurrence rate was 12% with a mean time of 80 months. Malawer et al¹³ treated 102 patients with giant cell tumor by curettage, burr drilling of the tumor’s inner walls, and cryosurgery using liquid nitrogen for an overall recurrence rate of 7.9% after a mean follow-up of 6.5 years. McGough et al²⁰ studied the impact of local recurrence of giant cell tumor and concluded that incomplete initial surgery, a delay >6 months in diagnosing the recurrence, and subchondral recurrence of the tumor were contributing factors in failure to salvage the joint.

Most patients diagnosed with giant cell tumor of bone are young and active with a normal life expectancy. The aims of treatment are to remove the tumor completely and to preserve the affected joint. These aims have not changed, but the approach and the results of treatment have changed with time.

Adjuvant Procedures to Reduce Recurrence Rate

To reduce recurrence, most surgeons recommend the use of adjuvant agents such as phenol^4,10 and liquid nitrogen^13,14 to kill remaining giant cell tumor cells after curettage and advocate filling the defect with PMMA. However, no clear evidence exists as to whether these adjuvants are effective; hence, they remain controversial.^12,21 From retrospective studies, adjuvant liquid nitrogen, or cryosurgery, has been reported to provide the highest cure rate,¹ but its use has not gained popularity. One reason is the difficulty in handling this product. We experienced 2 patients who suffered hypothermal injury following repeated cryosurgery. Some reports have shown that fracture rates increased significantly with the use of cryosurgery.^13,14

High-speed mechanical burring was performed until the folds separating the bone cavity were completely curetted. This appears to reduce giant cell tumor recurrence because it allows for deeper and more thorough curettage. To our knowledge, however, there has been no reported evidence in support of this. Turcotte et al¹² found in a large study of sarcomas that the nature of the filling material, the type of adjuvant method, or any combination of both failed to have a statistically significant impact on the recurrence rate. For Campanacci grade I and II giant cell tumor lesions, Prosser et al¹¹ recommended primary curettage without adjuvant treatment or filling agents because these had no significant effect on the recurrence rate. In our series, we experienced no recurrence of 19 giant cell tumors after extended curettage in combination with cryosurgery, high-speed burring, and thermal injury by PMMA. We have no obvious explanation for the successful outcomes, but clearly these combinations appear to be effective for the local control of giant cell tumor.

Some authors have reported that giant cell tumors of the distal radius are particularly aggressive and have a high rate of local recurrence.^19,22,23 A more aggressive surgical approach has been recommended. However, other authors disagree with this approach and suggest the radius should be treated like any other long bone.²⁴ Sheth et al²² consider giant cell tumor of the distal radius a site-specific occurrence and have described its important features. As the lesion grows, the dorsal and palmer cortices expand and the shell is easily permeated by the tumor because the periosteal and cortical barrier is weak compared to the femur or tibia. Giant cell tumor rarely extends through the articular cartilage to involve the radiocarpal and radioulnar joints. We experienced no recurrences, even with Campanacci grade III lesions in the distal radius.

Filler Material After Curettage and Functional Outcomes

The ideal filler material for use after curettage of the lesion may differ for weight-bearing and nonweight-bearing bones. In many institutions, the residual defect is filled with PMMA, especially for lesions around the knee joint.²⁵ Although the usefulness of PMMA as an adjuvant has recently been questioned,¹² it has several advantages as a cavity filler: it provides immediate mechanical stability, allowing for early weight bearing; it can avoid the need for internal fixation; it allows for early detection of recurrence at the bone–cement interface; it may have a cytotoxic effect on tumor cells, meaning heat necrosis can be induced a few millimeters deep in adjacent bone; and it is easy and inexpensive to use.

However, some surgeons prefer to use bone graft rather than PMMA to avoid the possibility of osteoarthritis developing.²⁶ The biological basis for PMMA use has not been clarified, and its thermal effect on the adjacent joint cartilage eventually leads to degenerative changes. So far there are only a few reports on the long-term effects of cement with respect to cartilage degeneration. Lackman et al²⁷ described 63 patients treated for giant cell tumor by curettage and cementing, of whom 46 had lesions in either the distal femur or the proximal tibia. Only 1 patient developed osteoarthritis after a mean follow-up of 108 months. Function was good after curettage of giant cell tumor and filling, as shown by a Musculoskeletal Tumor Society score of 31 of a maximum 35 points. Vult von Steyern et al²⁵ reviewed 9 patients with a mean follow-up of 11 years after curettage and cementing of giant cell tumor and found no evidence that long-term presence of cement close to the knee joint was associated with the development of osteoarthritis.

In our study, 10 similar cases were reviewed and none had developed osteoarthritis. The 18-year-old patient reconstructed with nonvascularized fibula graft suffered from collapsed subchondral bone of the tibia. Two cases that previously had severe osteoarthritis were reconstructed with TKA. At present, PMMA seems the most suitable material to fill large bone defects around weight-bearing joints.

Reconstruction using biological materials is recommended for giant cell tumors of the distal radius or upper limb (Figure 5).^28-30 Cheng et al²⁴ reviewed 12 patients with giant cell tumor of the distal radius. Of these, 6 underwent curettage and were reconstructed with autogenous iliac bone graft. Sufficient autogenous cancellous bone graft was used to fill the moderate cavity following curettage of giant cell tumor of the distal radius. The other 6 patients underwent en block resection and reconstruction by autogenous fibular or osteochondral allografts. Functional results were good even in the en block resection group, achieving a Musculoskeletal Tumor Society score of 69%.

Figure 5: Treatment strategy of giant cell tumor of long bone. Abbreviations: FVFG, free vascularized fibula graft; NVFG, nonvascularized fibula graft; PMMA, polymethylmethacrylate; TKA, total knee arthroplasty.

We experienced 3 patients with distal radius giant cell tumor. In 2, the bone cavity was filled with calcium phosphate. Biological bone substitutes have the advantage of immediate stabilization without the disadvantage of donor site morbidity.³¹ In the other patient, the distal radius invaded by giant cell tumor was resected en block and reconstructed by vascularized fibula head graft. No recurrence occurred at 5-year follow-up, and the functional score was successful with good stability of the radiocarpal joint. In another case with upper-limb giant cell tumor, reconstruction using cancellous bone allografts resulted in successful functional outcomes.

Current Standard of Treatment

The wide variability in behavior of giant cell tumor among patients can create difficulty in determining appropriate treatment strategies. The essential factor in the treatment of giant cell tumor is meticulous curettage of the affected bone. Standard treatment has ranged from surgical curettage to wide resection, with varying results reported for all modalities.

It is generally accepted that intralesional curettage with high-speed drill burr, adjunctive therapy with cryosurgery, and filling with bone graft or cement is currently the most effective treatment for grade I and II giant cell tumor (Figure 5). Controversy remains over the best treatment for grade III lesions with soft tissue extension or with fractures. Wang et al³² treated 24 patients with grade III giant cell tumor using the above modality and suggested this should be considered as the first choice. Our study also suggests this modality can be applied to grade III lesions, but that wide resection should be applied for some cases.

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Authors

Drs Muramatsu and Taguchi are from the Department of Orthopedic Surgery, Yamaguchi University School of Medicine, and Dr Ihara is from the Department of Orthopedic Surgery, Kanmon Medical Center, Yamaguchi, Japan.

Drs Muramatsu, Ihara, and Taguchi have no relevant financial relationships to disclose.

Correspondence should be addressed to: Keiichi Muramatsu, MD, Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

DOI: 10.3928/01477447-20090527-08