GIANT CELL TUMOR OF BONES: MANAGEMENT BY DIFFERENT SURGICAL TECHNIQUES

ABSTRACT

Objective: To evaluate the clinical outcome of  different  surgical techniques used in the treatment of giant cell tumor of long bones and their effect on the rate of local recurrence.

Methods: Thirty-seven patients with giant cell tumor of the long bones have been treated between July 1994 and July 2003.  All patients were evaluated by clinical examination, plain X-ray, computerized axial tomography and magnetic resonance imaging. Biopsy was taken in all cases to confirm the diagnosis and to define the histological grade of the tumor. Thirty- one patients were treated primarily by curettage and six were treated primarily by wide excision.  Selection of the surgical technique was based on site and size of the lesion, soft tissue involvement (intra- or extra-compartmental), tumor grade (histological and radiological) and if recurrent or not. Patients were followed-up for a minimum of two years.

Results: The mean age of our patients at presentation was 29.3 years (ranged from 19 to 52 years) and at last follow up visit 32.1 years (range 24 to 55 years). Seventeen patients were males and twenty were females, (male to female ratio was (1:1.2). According to the classification of Campanacci et al (3 patients were grade I, 24 patients were grade II and 10 were grade III). There were no mortalities among our cases. Local recurrence occurred in 9 out of 31 patients treated by curettage.

Conclusion: The main primary treatment of giant cell tumor is surgery. The use of local adjuvant therapy as part of treatment of giant cell tumor helps in decreasing the rate of recurrence. Curettage must be extensive to be effective and requires a large cortical window. Wide excision is used in extremely large lesions with cortical bone breakthrough and extension into soft tissue, when the joint could not be preserved and in cases where resection results in no significant morbidity.

Key words: Adjuvant therapy, Bone cement, Curettage, Giant cell bone tumor, Reconstruction, Resection.

JRMS April 2008; 15(1): 23-30

Introduction

The histogenesis of giant cell tumor (GCT) of the bone is still uncertain. Its histolopathology does not predict the clinical outcome. Many controversies are still present regarding the best method of treatment.  Giant cell tumor (GCT) of the bone has been classified by the World Health Organisation (WHO) as "an aggressive, potentially malignant lesion".  Almost 75%-80% of GCTs have a benign course. The rate of local recurrence can range from 20% to 50% according to the method of treatment. Malignant transformation at recurrence is not uncommon and reported to happen in about 10% of cases. Approximately 1-4% of giant cell tumors give pulmonary metastases even in cases of benign histopathology.^(1-4)

The most accepted hypothesis regarding the pathogenesis of GCT and its neoplastic character is the mononuclear spindle-shaped (fibro-osteoblast like) stromal cells. These cells are genetically unstable, and by secreting a lot of cytokines and other factors they stimulate the immigration of blood monocytes into the tumor tissue and promote the formation of the osteoclast - like giant cells. The characteristic cell types, the monocyes and the giant cells, are therefore simply reactive components of GCT, while the spindle shaped stromal cells represent the neoplastic component of the tumor.⁽⁵⁾

GCTs represent 5% of all primary bone tumors and 21% of all benign bone tumors. It has a slight female predominance (1.2 -1.5: 1), and occurs most commonly in the third and fourth decades of life.^(6-8) Less than 5% occur in skeletally immature patients.⁽⁹⁾ Approximately 50% of GCTs  are located about the knee  at the distal femur and proximal tibia. Most GCTs are solitary lesions (less than 1% are multicentric).^(1,6-8) Pain is the most common presenting symptom, while swelling and deformity are associated with large lesions. The incidence of pathological fracture at presentation is 10-30%.^{(6-8, 10)}

The diagnosis of GCT of bones depends mainly on clinical and radiological examination (plain x-ray, computerized tomography and magnetic resonance imaging) of the site of the lesion. Preoperative biopsy should be taken to confirm the diagnosis and to define the grade of the malignancy.^(1,11,12)

The grading system adopted by Campanacci et al⁽⁷⁾  classifies patients with GCTs, according to their radiological findings, into  grade I: means no cortical thinning; Grade II: means some cortical thinning and erosion but no breakthrough; and grade III: means breakingthrough and extension into the soft tissue.

The staging system adopted by Enneking in 1986⁽¹²⁾ is also used to stage patients with GCT. It depends on the tumor grade (G), location of the tumor: intra-compartmental or extra- compartmental (T) and presence or absence of metastasis (T).

Surgery is the main treatment of GCTs of long bones with different modalities have been investigated and used.^{(6-8, 11, 13-18)}

GCT is not radio-resistant as it was previously believed. It is reported by many authors that there is local control of 75%-85%.^{(19- 21)} 

In this study we describe our nine- year experience with the treatment of GCTs of long bones with different surgical modalities.  Attention was directed towards determination of the rate of initial local recurrence, factors that might predispose to recurrence and the results of secondary procedures for the treatment of recurrences.

Methods

Between July 1994 and July 2003, a total of forty-three patients with giant cell tumor (GCT) of the long bones have been treated at the hospitals of the Royal Medical Services (RMS). Of these, Thirty-seven were included in the present study on the basis the documentations available.

All patients were evaluated by clinical examination, routine laboratory tests, local plain X-ray, chest x-ray, computerized tomography and magnetic resonance imaging. Biopsy was taken in all cases to confirm the diagnosis and to define the histological grade of the tumor. The lesions were classified according to the radiographic parameters considered by Campanacci et al⁽⁷⁾ into grade I, II or III. Different surgical modalities were used including:  curettage with bone grafting; curettage with bone cement filling; Curettage and Adjuvant with  bone cement and / or Bone graft; wide surgical resection;  wide surgical resection with custom- made total joint arthroplasty;  wide surgical resection with arthrodesis. Curettage was done through a large cortical window by the manual curette and by the dental burr in some cases. The adjuvant local therapy used in our cases were hydrogen peroxide (H₂O₂) and electrical cautery.  Selection of the surgical technique was based on the site and size of the lesion, soft tissue involvement (intra- or extra-compartmental), tumor grade (histological and radiological) and if recurrent or not. Patients were followed-up, clinically and  radiologically a minimum of two years (2-9 years) to detect local recurrence, pulmonary metastasis, local complications of surgery and to assess the functional outcomes  the patients.

Results

The mean age of our patients at presentation was 29.3 years (ranged from 19 to 52Years) and at last follow up visit 32.1 years (range 24 to 55 years). Seventeen patients were males and twenty were females, (male to female ratio was (1:1.2). According to the classification of Campanacci et al,⁽⁷⁾ four patients were grade I, 29 patients were stage II and 4 were grade III) Fig. 1.  The distribution of the tumor according to the anatomical site showed that approximately 62% of the lesions are located about the  knee,  at  the  distal  femur  and  proximal  tibia Table I. Three patients had   pathological fractures at the time of presentation.

Fig. 1. Distribution of the patients with GCT according to the radiological grade of Campanacci et al

Table I. Distribution of GCTs depending on the site

Table II. Distribution of GCT cases according to primary treatment modality

Fig. 2(a,b). GCT affecting the proximal humerus, large in size, causing severe bone destruction (a), treated by shoulder hemi- arthroplasty (b)

Fig. 3(a,b,c). Patient with GCT of the distal femur treated primarily by curettage and bone grafting (a); by curettage and adjuvant therapy with bone cement filling of the cavity for first recurrence (b); and a third surgery of wide resection and reconstruction by an endoprosthesis  (custom- made total knee arthroplasty) for the second recurrence (c)

Modalities of primary treatment we used in our patients are shown in Table II.  Six lesions were treated by primary wide resection; five of them were present at sites where their removal do not produce significant structural or functional deficit; and one was large in size, causing sever bone destruction and affecting the proximal humerus. This female patient was treated by pre-operative embolization, to decrease the bleeding intra-operatively, and shoulder hemi-arthroplasty Fig. 2. Thirty- one of our patients were treated by curettage using the manual curette and sometime the dental burr. Adjuvant therapy (H₂O₂) was used in thirteen cases. The cavity was filled with autogenous bone graft, bone cement or both.

Nine (24%) of the thirty- seven patients had a local recurrence Table III. All but one recurrence occurred within three years after the primary operation. The majority of recurrences occurred in patients with grade III tumors. The three patients who presented with pathological fracture have developed local recurrence. Patients who got local recurrence have been treated primarily by curettage and bone grafting (6 cases) and curettage and bone cement (3 cases). Lesions managed by curettage and local adjuvant therapy with bone cement and/or bone graft have no recurrences after a minimum follow-up of two years.

All patients with local recurrence, except one, have been treated, secondarily, by curettage (using the burr), adjuvant therapy, bone cement and subchondral bone graft. One patient, with recurrence in the distal radius, was treated by wide excision and a wrist arthrodesis (Case No. 7). This patient developed lung metastasis during follow-up, six months after his second surgery. One patient developed a second recurrence (Case No. 3), with perforation of the articular surface of the distal femur, for which a third surgery of wide resection and reconstruction by an endoprosthesis (custom- made total knee arthroplasty) was done (Fig. 3). This patient got a fracture of his tibia, at the site of the endoprosthesis, which was treated conservatively and Primary recurrence in case no. 6 has been treated by wide excision and wrist arthrodesis.

Table III. Data of the patients who had a local recurrence

Primary recurrences in all other cases have been treated by Curettage +Adjuvant   +Bone graft + Bone Cement Case no. 3 developed a second recurrence which was treated by wide excision and a custom- made endoprosthesis (Total Knee Arthroplasty).

 healed after 4 months.  One patient, with GCT of upper tibia, had rupture of the patellar tendon 4 weeks post-operatively and reconstruction was done. None of our patients died during the follow-up period, and amputation was not done for any.

Discussion   

Typically, GCTs occur in the third and fourth decades of life, and the age distribution in our series is consistent with that published in previous reports.^(7,8)  There were slightly more female patients (54%) than male patients. This finding is also in agreement with some earlier studies, but not with others.⁽⁶⁾ The tumor is uncommon in patients with open physis.^(7,9) The youngest patient in our series is 19 year old.

Some authors^(7,14,17,22) have attempted to correlate the clinical behavior and incidence of recurrence with the initial radiographic grade. Others ^(15,18,23) found no correlation between the radiographic appearance of the lesions and their clinical behavior. Although statistically insignificant, because of the small number, we observed a strong correlation in our series, especially for lesions of grade III.

Pathological fracture might be the primary presentation in 4%-32% of patients with GCTs.  Eckardt⁽²²⁾  treated these cases, in his series,  by immediate  open  biopsy  and  wide excision. Sung etal⁽⁶⁾  and  Goldenberg et al,⁽⁸⁾ in  two separate studies,have recommended immediate curettage and bone grafting with additional external fixation. Dreinhofer et al ⁽¹⁰⁾ have treated ten GCTs with fracture at the time of diagnosis by curettage and bone cementing and reported recurrence in two (20%). In our study three patients presented with fracture (8%), one has been treated with curettage and bone grafting and the other two with curettage and bone cementing and all developed local recurrence. 

Because GCT is a locally aggressive yet benign disease, intralesional treatment is a limb- sparing option with good outcomes.⁽¹⁾

Many different methods of  treatment of GCTs are reported in the current literature including: curettage; curettage and bone grafting; curettage and insertion of bone cement (polymethylmethacrylate);  cryotherapy (liquid nitrogen)  after curettage of the cavity; curettage and a chemical or electrical adjuvant (phenol, zinc oxide, alcohol, H₂O₂, argon beam coagulation  and electrical cauterization of the inner surface of the cavity) prior to the insertion of bone cement or a bone graft; primary resection;radiotherapy; and  embolization of the feeding vessels.^{(6-8, 13-21)}

Although intra-lesional procedures remain the treatment of choice for most GCTs, wide resection offers the lowest recurrence rate (0-20%) and is recommended for lesions in certain locations (proximal fibula, proximal radius, distal ulna, and clavicle) where it leaves no functional deficits.

Table V. The rate of recurrence after different intralesional treatments of primary GCT of bone (minimum follow-up > 2 years)

Table IV. Recurrence rate in relation to the primary treatment