Oncology

Giant-cell tumour of bone

THE LONG-TERM RESULTS OF TREATMENT BY CURETTAGE AND BONE GRAFT

W. Zhen, H. Yaotian, L. Songjian, L. Ge, W. Qingliang

From the Fourth Military University, Xian City, China

Giant-cell tumour of bone (GCT) is a locally benign aggressive tumour. The use of adjuvant agents, such as phenol or liquid nitrogen has been recommended to destroy the remaining tumour cells after curettage, and lling of the defect with methylmethacrylate cement has been advocated. Between 1957 and 1992 we treated 92 patients with a GCT with 50% aqueous zinc chloride solution and bone grafting. Their mean age at the time of surgery was 31 years (15 to 59) and the mean follow-up was 11 years (5 to 31). Twelve (13%) had a local recurrence and one had a wound infection. Two developed degenerative changes around the knee. Eighty-six (93%) achieved good or excellent function. Three had moderate function, and three needed amputation. Our ndings indicate that treatment with an aqueous solution of zinc chloride and reconstructive bone grafting after curettage gives good results.

W. Zhen, MD, Professor H. Yaotian, MD, PhD, Professor L. Songjian, MD, Associate Professor L. Ge, MD, Professor W. Qingliang, MD, Professor Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xian City, Shannxi 710032, China. Correspondence should be sent to Professor W. Zhen. 2004 British Editorial Society of Bone and Joint Surgery doi:10.1302/0301-620X.86B2. 14362 $2.00 J Bone Joint Surg [Br] 2004;86-B:212-6. Received Received 26 March 2003; Accepted after revision 13 June 2003 212

Giant-cell tumour of bone (GCT) is one of the most common primary bone tumours in China. It is locally aggressive and its clinical behaviour is difcult to predict based on its microscopic appearance alone. The ideal form of treatment for lesions which arise near major joints remains controversial. Most surgeons recommend the use of adjuvant agents, such as phenol or liquid nitrogen, to kill remaining tumour cells after curettage, and advocate lling the defect with methylmethacrylate,1-6 but the long-term results with regard to the function of the joint and recurrence have been poor. We have used a technique devised by Professor Yupu7 which involves extensive curettage, adjuvant 50% zinc chloride and reconstructive bone grafting. We now report our long-term results and describe the recurrence and complications.

Patients and Methods

Between 1957 and 1992, we treated 92 patients (95 tumours) with an histologically proven GCT involving a long bone, by curettage, adjuvant aqueous 50% zinc chloride and autogenous bone grafting with or without added allograft. They have been followed up for a minimum of ve years. There were 43 men (46.7%) and 49 women (53.3%) with a mean age at the time of diagnosis of 31 years (15 to 59). Of the 95 GCTs, 36 (38%) were in the distal femur, 27 (28%) in

the proximal tibia, eight (8%) in the proximal femur, ve (5%) in the proximal humerus, three (3%) in the distal radius, three (3%) in the distal humerus, four (4%) in the sacrum, three (3%) in the ilium, two (2%) in the talus, one (1%) in a metacarpal joint and one (1%) in the distal tibia. All patients had plain radiographs of the lesion and a chest lm. According to the grading system of Campanacci et al,4 19 lesions (20%) were grade I, 48 (51%) were grade II, and 28 (29%) were grade III. Ten patients (11%) presented with a rst local recurrence and two (3%) with a second local recurrence. The primary lesions had been treated elsewhere by simple curettage and bone grafting or cement. If the clinical and radiological presentation was characteristic of a benign GCT, biopsy (frozen section) and surgery were performed at the same session. If the presentation was atypical, open incisional biopsy was performed and further surgery was delayed until the histological evaluation had been completed. Sixty-eight lesions were treated by a combination of autogenous graft and allograft and 27 by autogenous graft alone. Six patients with grade-II lesions presented with a closed pathological fracture of the distal femur or proximal tibia. They were treated by open reduction, curettage, 50% zinc chloride, bone grafting and internal xation.
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Table I. Details of patients who had a local recurrence Time of Status of recurrence Treatment of tumour (yrs) recurrence Primary Primary Primary Primary Second First Primary First softtissue mass Primary First Primary First 25.0 16.0 1.0 13.0 2.0 1.0 5.0 1.5 Duration of follow-up after treatment of recurrence (yrs)

Case 1 2 3 4 5 6 7 8

Gender F F F F F F F F

Age 28 23 21 29 46 20 29 36

Site Proximal tibia Distal femur Proximal humerus Distal femur Distal femur Distal femur Distal femur Distal femur Distal femur Distal femur Proximal tibia Proximal femur

Grade II II III II II II II III

Pathological fracture Yes No Yes No Yes No No No

Status at latest follow-up Disease-free Disease-free Disease-free Disease-free Death Pulmonary metastasis Alive Disease-free Disease-free

En-bloc resection and 2.0 osteoarticular allograft 3.0 Curettage 50% ZnCl2 Bone graft Amputation 15.0 Curettage 50% ZnCl2 Bone graft Amputation Curettage 50% ZnCl2 Bone graft Curettage 50% ZnCl2 Bone graft Wide soft-tissue excision Curettage 50% ZnCl2 Bone graft Curettage 50% ZnCl2 Bone graft Curettage 50% ZnCl2 Bone graft Amputation 17.0 0.5 13.0 10.0 10.0

9 10 11 12

F M F M

52 25 32 26

III II II III

Yes No No No

3.0 4.0 6.0 2.0

5.0 7.0 2.0 2.0

Disease-free Disease-free Disease-free Pulmonary metastasis Alive

The histological grade was not identied since it has been reported to have little relation to local recurrence.8 Operative technique. After exposure of the involved bone and soft tissues, extensive curettage was undertaken after a cortical window had been elevated to allow visualisation of the entire tumour. If there was extension of the tumour into the soft tissues, the pseudocapsule was dissected circumferentially and excised completely. The entire intraosseous lesion was removed by a large curette and macroscopically normal bone exposed. The cavity was irrigated with sterile water and four to six swabs soaked in 50% zinc chloride solution were used to cauterise the walls for ve minutes. This process was repeated three times after which the cavity was irrigated with sterile water again to ensure that all the zinc chloride solution had been removed. The surrounding normal soft tissue was carefully protected from the zinc chloride. Finally, reconstruction was performed by packing the cavity with autogenous iliac bone graft. Corticocancellous allograft bone chips from the bone bank were added when necessary to ll the defect completely. Post-operative management. Prophylactic antibiotics were given for three to ve days after the operation. The wound was examined on the third post-operative day. Patients with lesions of the lower limbs remained non-weight-bearing for six weeks. Radiographs were then taken to eliminate a fracture and to conrm incorporation of the graft. If healing had progressed satisfactorily, weight-bearing was allowed. The patients were reviewed clinically and radiographically every three months for two years, bi-annually for a further three years and annually thereafter.
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Analysis of data. All medical records and radiographs were reviewed by an orthopaedic oncologist and a musculoskeletal radiologist. The site and stage of each lesion were recorded and the rate of local recurrence, fracture, neurapraxia, wound complications, and degenerative changes noted. Functional evaluation was undertaken according to the system described by Enneking et al.5

Results
The mean follow-up was for 11 years (5 to 31); 46 (50%) were followed for more than ve years; 31 (33%) were for between ten and 15 years and 15 (16%) for more than 20 years. Local recurrence. Twelve patients (13%) had a local recurrence (Table I) in the distal femur in eight (67%), in the proximal tibia in two (17%), in the proximal femur in one (8%) and in the proximal humerus in one (8%). Recurrence took place after a mean of six years and eight months (1 to 25 years). In ve patients (42%) it occurred within two years of operation; in two (17%) within four years and in ve (42%) more than ve years after operation. Thus 80 patients were cured and all were free from disease at their most recent follow-up. Three patients (3%) (cases 5, 6 and 12), who initially presented with a rst or second local recurrence, subsequently developed pulmonary metastases. One died and the other two were treated by radiotherapy and remain alive but with disease. Three patients with extensive recurrent lesions were treated by amputation. Another patient (case 1) who had a pathological fracture through a local recurrence in the proximal tibia 25 years

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Table II. Literature review of rate of local recurrence after intralesional treatment of giant-cell tumour of bone Author/s Dahlin, Crupps and Johnson15 Goldenberg, Campbell and Bonglio16 Larsson, Lorentzon and Boquist17 Marcove et al18 Sung et al11 McDonald et al9 Jacobs and Clemency19 Campanacci et al4 Waldram and Sneath20 ODonnell et al21 Blackley et al2 Present study Number of patients 37 136 30 52 34 85 12 151 19 60 59 92 Recurrence (%) 41 54 47 23 41 34 17 27 37 25 12 13 Adjuvant therapy Cytotoxic Cryosurgery Phenol/alcohol Phenol/alcohol Cryosurgery Cytotoxic Bone cement Burr drilling 50% ZnCl2 Follow-up (yrs) >2 >2 >2 >2 >2 >2 >3 >2 >2 4 7 10

after operation was treated by en-bloc resection and an osteoarticular allograft. One patient who developed a softtissue mass at the site of operation with peripheral calcication seen on the radiographs was managed by en-bloc resection of the mass, which proved histologically to be recurrent GCT. Wound complication. Late deep bone infection occurred in one patient with a GCT of the distal tibia two months after operation. This settled after treatment with intravenous antibiotics for 12 days. There was no neurological decit in the four patients who had been treated for a GCT of the sacrum. Degenerative changes. Clinical and radiological evidence of degenerative changes of the knee developed ten years after operation in two patients. These were assumed to be primary rather than secondary to the tumour since there were similar symptoms in the contralateral knee. Function. The function was good or excellent in 86 patients (93%), and moderate in three. It was considered to be poor in the three patients who had undergone amputation.

Discussion
Our aim was to determine the efcacy of curettage combined with the use of zinc chloride and reconstruction by bone grafting in the treatment of GCT. Since GCT is a benign, aggressive lesion, absence of local recurrence, rather than survival of the patient, is the major criterion used to assess the outcome of surgical treatment. We have shown that this is a satisfactory form of treatment. Many authors have reported good function of joints after the combined use of curettage and chemical cauterisation in the treatment of GCT of bone adjacent to major joints.1,2,6-9 However, some local recurrences have been reported. Twelve patients (13%) in our series had a local recurrence which is low compared with other reports in the literature (Table II). Thorough curettage of the tumour and elimination of the remaining cells with an adjuvant are essential for the surgical treatment of GCT of bone. The tumour often extends into the surrounding normal bone (Fig. 1) and meticulous treatment of the wall of the cavity using 50% aqueous zinc

Anteroposterior (a) and lateral (b) radiographs showing a GCT with extensive invasion of the proximal tibia.

Fig. 1a

Fig. 1b
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Fig. 2 Photomicrograph showing tumorous cells in dilated vessels around a GCT (haematoxylin and eosin x100).

Fig. 3 Photomicrograph showing giant cells within the lumen of venules (haematoxylin and SMA x400).

chloride is required to destroy the remaining cells and thus to reduce the rate of local recurrence.10 Several authors have claimed that most recurrences take place within two years of curettage,4,9,11 while Campanacci et al4 suggested three years. There was local recurrence in 12 patients in our series at a mean of six years and eight months (1 to 25 years) after operation. Late recurrences after more than ten years occurred in 3.3% of patients. Recently, an increasing number of late recurrences have been reported. Scull et al12 reported four among 369 cases of GCT of bone taking place 19, 30, 20 and 27 years after surgery. It is assumed that the mechanism of recurrence is the activation of remaining dormant tumour cells. It has been shown that when GCT cells in culture are exposed to a low concentration of zinc chloride they are usually in the G0/G1 phase of cell cycle rather than in the S phase. It is suggested that the concentration of zinc chloride in different layers of the cavity wall may vary and that concentrations which destroy tumour cells may not be present in the deeper layers.13 All recurrences occurred near major joints, the commonest site being the distal femur, where the recurrence rate was 22%. This is the commonest site for GCT, and it may be that curettage near major joints is not undertaken as thoroughly as that near minor ones. The 50% zinc chloride solution can destroy normal soft tissues. Experimental studies have shown that a 1 cm3 of tumour tissue is inactivated after immersion in a 50% aqueous solution of zinc chloride for three minutes, without affecting the healing of bone graft.10 No side-effects of the treatment were seen. The solution can be obtained in ampules from pharmaceutical companies. Although most GCTs appear to be benign, some studies have identied proliferative biological behaviour.7,9,13 There were three patients in our study who had local recurrences with extensive invasion of tumour. Two had repeated occurrences associated with malignant change and required amputation. Another three patients developed
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pulmonary metastases after local recurrence. One died and two have survived but have disease after radiotherapy. This suggests that the prognosis of GCT of bone may be determined by histological factors. The remaining tumour cells, which are implicated as the cause of local recurrence, reside in the periphery of the lesion where the tumour and host tissues interact. GCT cells not only invade surrounding normal bone, but tumour cells may be seen in dilated vessels around the lesion (Fig. 2). Smooth muscular actin (SMA) staining of the venules conrmed their invasion by multinuclear giant cells with thinning and disintegration of the vessel wall (Fig. 3). As shown in several clinical studies simple curettage with bone grafting may have a recurrence rate of between 40% and 60%,1,2,6,7,11,14 while curettage in combination with an adjuvant greatly reduced the recurrence rate, as was conrmed in our study. The lesion should be adequately exposed and the cortical window in bone large enough to allow inspection of the entire lesion. The part of the wall of the cavity which is composed of soft tissue or a thin bony shell should be excised. The remaining cristae and septa in the cavity should also be excised in order to eliminate the space which is inaccessible using a curette. When the wall of the cavity contains many small holes caused by local invasion of the tumour, each hole should be meticulously cleared. They usually do not penetrate the periosteum, but a dead space may easily form between them and the periosteum. The cavity should be packed snugly with cancellous bone graft to reduce the space for surviving tumour cells to grow in as much as possible. Wide excision of the soft tissue should be performed if the lesion perforates the cortex. Despite the seemingly benign histological appearance, local recurrence and malignant change may occur requiring amputation. Pulmonary metastases may also recur and may respond to radiotherapy.
No benets in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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