Background: Giant cell tumour (GCT) of bone is generally a benign tumour composed of mononuclear stromal cells and characteristic multinucleated giant cells that exhibit osteoclastic activity. It usually develops in long bones but can occur in unusual locations. The typical appearance is a lytic lesion with a well-defined but non-sclerotic margin that is eccentric in location, extends near the articular surface, and occurs in patients with closed physes.
Objective: The current study was planned to summarise our experiences with GCTB, and to evaluate individual effect of bone cement, high-speed burring and hydrogen per oxide (H2O2) on local recurrence. GCT can mimic or be mimicked by other benign or malignant lesions at both radiological evaluation and histological analysis. In the past, the mainstay of treatment was surgical, primarily consisting of curettage with cement placement, with recurrence rates of 15%-25%. Recurrence is suggested by development of progressive lucency at the cement-bone interface.
Results: Of the 21 patients who started the study, 4(19%) were lost to follow-up, and 17(81%) represented the final study sample. Of them, 16(94.11%) patients underwent the curettage procedure with adjuvant therapy and reconstruction with bone grafts taken from iliac crest. In 3(26.3%) patients, no adjuvant was used. Total of 6 (42.1%) patients had local recurrence and 3(50%) of them were those who were treated without any adjuvant; 2(33.3%) with phenol and 1(16.6%) with PMMA.
Conclusion: The results of the present study suggest that an "aggressive curettage" with the use of adjuvant reduces the recurrence rate in a disease whose aggressiveness is not easy to predict.
Keywords: Bone tumour, Giant cell tumour, Extremity, Surgery, Curettage, Resection, Wide excision. (JPMA 65: S-105 (Suppl. 3); 2015).
Giant cell tumour of bone (GCTB) is an intermediate, locally aggressive but rarely metastasising tumour, representing 5% of primary bone tumours and 20% of benign bone tumours.1 It occurs mostly between the ages of 30-50 years and rarely arises in the immature skeleton. There is a slight predominance for female patients.1,2 At presentation, 15%-20% of patients have a pathologic fracture due to substantial cortical destruction followed by relatively minor trauma. GCTB is typically seen solitary, mostly located in the meta-epiphyseal region of long bones (85%), but may also occur in the axial skeleton (10%) or occasionally in the small bones of hands and feet (5%).2,3 At the latter location, so-called giant cell lesion of the small bones — a different entity — should be considered.4 Approximately 1%-4% of otherwise conventional patients develop pulmonary metastases.3,5-9 These metastases often have relatively indolent behaviour. Multifocal GCTB is rare, appearing either simultaneously or metachronously. In these presentations, so-called brown tumours associated with hyperparathyroidism should be ruled out by blood biochemistry because they are histologically barely distinguishable from GCTBs. Malignant transformation has been described in less than 1% of all GCTBs and may be either primary (i.e., sarcomatous progression) or, more commonly, secondary (mostly radiation induced).1
The main problem in the management of GCTB is local recurrence after surgical treatment: 27%-65% after isolated curettage;2,3 12%-27% after curettage with adjuvants such as high-speed burr, phenol, liquid nitrogen, or polymethylmethacrylate (PMMA);2,10-12 and 0%-12% after en bloc resection.2,13 In clinical practice, the choice of surgical treatment depends mostly on the feasibility of curettage and local adjuvants versus resection, but also in part on the expected risk for local recurrence in each individual patient. Soft tissue extension, for example, is commonly present and increases the risk for local recurrence.14,15 Pathological fractures are also common, and although this does not in itself increase recurrence risk, it may render curettage technically more difficult. In general, the aim for joint preservation is justified, considering the benign but locally aggressive nature, young patient population, and significant complications including need for revision surgery after resection and reconstruction with tumour prostheses.16-19
The current study was planned to summarise our experiences with GCTB, and to evaluate individual effect of bone cement, high-speed burring and hydrogen per oxide (H2O2) on local recurrence.
Materials and Methods
The descriptive case series was conducted at the Department of Orthopaedics, Punjab Medical College, Faisalabad, Pakistan, and affiliated hospitals from July 2011 to June 2014. Patients meeting the inclusion criteria were admitted through the outpatient department (OPD) and those lost to follow-up were excluded. Non-probability but purposive sampling technique was used. Risks and benefits were discussed. We analysed the differences in local recurrence rates, functional results, and complications between wide excision and curettage with adjuvant therapy in management of the patients diagnosed with primary lesions after follow-up.
The data collected consisted of clinical notes, operative notes, radiographic images, pathological reports, as well as gross and microscopic imaging. They were asked to sign an informed consent form for surgery and allow the use of data for research purposes. The lesions were graded according to Campanacci et al.6 as Grade I, Grade II, or Grade III. Any pathological fractures were noted. Intra-compartmental or extra-compartmental tumour growth was identified on the basis of preoperative imaging studies, including computed tomography (CT) and magnetic resonance imaging (MRI) and on the basis of intraoperative findings. The compartmental extension was graded T1 or T2 according to the system of Enneking et al.12,13 and Wolf and Enneking.14 All surgical specimens were reviewed by a consultant pathologist specialising in bone and soft tissue pathology and histologically classified as benign GCT.
For intralesional procedures, a wide cortical window was created to observe the tumour cavity. The tumour tissue was removed with a curette. The borders of the tumour cavity then were cleared away with a high speed burr. The tumour cavity was inspected with a dental mirror or an endoscope to verify the removal of all tumour tissue. Further, 89 per cent phenol was applied in the borders of the cavity with cotton-tipped applicators and then neutralised with alcohol in 16 patients. Finally, the tumour cavity was packed carefully with autologous and/or allogenic bone grafts and PMMA. Procedures in which polymethylmethacrylate packing was combined with bone grafting were subsumed into PMMA treatment groups.
For follow-up, patients were contacted via phone and serial radiographs of primary site and chest were taken every 3-4 months for the first 2 years and every 6 months for the next year and annually thereafter.
Data was analysed via SPSS 19 to find percentages and frequencies of study variables. Descriptive statistics were used to calculate mean and standard deviations.
Of the 21 patients who started the study, 4(19%) were lost to follow-up, and 17(81%) represented the final study sample. Of them, 16(94.11%) patients underwent the curettage procedure with adjuvant therapy and reconstruction with bone grafts taken from iliac crest.
In 3(26.3%) patients, no adjuvant was used. Total of 6 (42.1%) patients had local recurrence and 3(50%) of them were those who were treated without any adjuvant; 2(33.3%) with phenol and 1(16.6%) with PMMA (Table-2).
Using the Musculoskeletal Tumour Society system to evaluate average function,17 the results were 25.56 points for the wide excision group and 25.64 points for the curettage group, respectively.
Intralesional procedures were the most common surgical treatment and of the 16(94%) patients treated with intralesional surgery and PMMA void filling, 7(43.7%) received additional local phenol and alcohol treatment; 3(43%) with PMMA and 4(57%) with phenol alone. Six (37.5%) patients were treated solely with PMMA and no additional adjuvants. Wide resections were performed in 1(5.88%) patient (Figure-3, 4),
Reconstructions after wide resections included arthroplasties 1(5.88%), (Figure-4) The mean interval between surgery and recurrence was 16.3±12.4 months (range: 4-36 months) (Figure-5).
Giant cell tumour of bone (GCTB) is a benign but locally aggressive tumour that usually involves the end of long bone. Its histogenesis remains unclear. It is characterised by a proliferation of mononuclear stromal cells and the presence of many multinucleated giant cells with homogenous distribution. The name giant cell tumour was suggested by Cooper and Travers19 in 1818. Virchow19,20 suggested a malignant potential in 1846. Ne´laton,20 a French doctor, was the first to recognise the similarities of the multinucleated giant cell with osteoclasts in 1860. In 1912, Bloodgood21 reported on the benign nature of GCT. Most of current knowledge of this specific bone tumour has come from Jaffe et al.22
GCT has a significant incidence, accounting for 20% of all benign bone tumours and 5% of all bone tumours.23 Higher incidence has been reported for Chinese population, in which it can be up to 20% of all bone tumours.24 Although some series show a slight female predominance,25 but most support that there is no gender predilection in GCT. GCTB most frequently occurs in young adults between 20 and 40 years of age.26 Occurrence before epiphyseal plate closure is exceptional.27 GCT can be seen in patients over 50 years old. Though less frequent, this disease needs to be included in the differential diagnosis process of a lytic bone lesion.28
Intralesional curettage has been established as the preferred treatment for most GCTs. Wide resection is reserved for tumours with extensive destruction, impossible joint salvage, and when expendable bones like fibular head or distal ulna are affected.14,16,23,27,28 We analysed the recurrence-free survival after treatment of GCT with an emphasis on the impact of surgical approach, adjuvant therapy, tumour presentation and demographic factors on the risk of recurrence.
Similar to previous reports,1,3,6,15,22,28 we found that wide resection was associated with a lower risk of recurrence than intralesional surgery. When intralesional procedures are performed, local adjuvants (PMMA, phenol, H2O2, and cryotherapy) have been reported to improve tumour control.1,3,5,11,28,29 Campanacci et al. showed a rate of recurrence of 27% out of all intralesional procedures, 8% in mariginal excisions and 0% in wide excisions, and 90% of recurrences occurred in the first three years after surgery.29 We found that PMMA's use decreased the risk of local recurrence. Similar risk reductions have been observed by others,1,3,22 and have been attributed to thermal and toxic effects on tumour cells.33 Additionally, PMMA may decrease the risk of collapse and allow for more aggressive tumour removal as a result of its mechanical properties. Considering the importance of thorough tumour removal, this capacity may overshadow the effects of heat-mediated tumour effects; a suggestion that was also made by Gher et al.33 Similar results were reported by Klenke et al.34 in their retrospective study of 46 patients. The use of PMMA with intralesional curettage lowers the recurrence rate from the average of 32% to 14%. The recurrence rates seen for wide resection are near 5-6%, but they entail considerable loss of function. In another series, Klenke et al. reported on the recurrence rates of GCT in 118 patients treated with wide resection and intralesional curettage and the rates are 5% and 25%, respectively. However, they suggested the use of curettage with PMMA, since this procedure lowers the recurrence rate and it provides equivalent tumour control compared to resection.36,40 Phenol is a commonly used adjuvant for GCT treatment. Phenol induces tumour necrosis24,26,37,41 with few adverse effects.. However, tissue penetration is poor and limits tumour necrosis to superficial cell layers.34 Balke et al. found a negligible necrotising effect of phenol and discounted it as an adjuvant after curettage of bone tumours.2,19,21,33 Others have also reported little effect of phenol on recurrence.1,35-38 However, Durr et al. did report decreased local recurrence with the use of phenol.39 We did not find any effect of adjuvant phenol treatment on GCT recurrence. Age at diagnosis independently predicted recurrence regardless of the status of the disease and the aggressiveness of the chosen treatment: recurrence rate decreased as the patient's age increased. The greater risk of young patients having recurrence has been reported  and may be associated with increased bone turnover in young people.21,34,40,41 This hypothesis is supported by studies showing inhibition of bone turnover with bisphosphonates reducing the risk of recurrence.7,9,17,43 Other demographic and disease-related variables (gender, location, tumour grade, soft tissue extension, and pathologic fracture) had no influence on local recurrence in our patients. Previous studies have also shown that gender, location, and tumour grade did not influence recurrence.1,3,43 The prognostic relevance of soft tissue expansion and pathological fractures is controversial.1,3,15,22,31,38,40,43 Becker et al. found that the prevalence of soft tissue extension influenced the risk of local recurrence41 and O'Donnell et al. reported that pathological fractures were associated with an increased recurrence rate.43
The aggressiveness of the treatment should be considered when interpreting the correlation of soft tissue expansion or pathological fractures and local recurrence. In tumours with and without pathological fractures, wide resections were performed in 47% and 14%, respectively. Thus, patients with pathological fractures more commonly received resections. In this retrospective study, this may underestimate the risk of recurrence in patients with pathological fractures. The rate of pulmonary metastases in our study patients was 0%, similar to previous studies reporting ranges from 0% to 4%.3,4,8,10,15,20,30,39,42,44 Although GCT is classified as a benign lesion but few patients develop progressive lung metastases with poor outcomes.2,6,44 It is difficult to quantify the real morbidity (physical and emotional) of patients who experience recurrence and require repeat surgery. Based on the results of this study, we recommend intralesional surgery for treating most GCTs; the selection of bone graft versus PMMA remains individualised. Because young age is a risk factor for local recurrence, we favour the use of PMMA in young patients as the best way to minimise recurrence and preserve the native joint. Similarly, when little bone stock remains or for patients with questionable compliance for a limited weight-bearing rehabilitation, methylmethacrylate is favoured for its immediate stability.
The combination of adjuncts (PMMA, burring, H2O2) reduces the likelihood of recurrence compared to curettage alone and therefore should be recommended as the standard treatment. If the tumour reaches close to the articulating surface, a strut/cancellous bone graft can be performed without risking a higher recurrence rate. Use of PMMA as an adjuvant significantly reduces the recurrence rate following intralesional treatment of benign GCT, and it appears to be the therapy of choice for primary as well as recurrent Giant Cell Tumour of Bone.
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