Giant cell tumor of bone is a challenging clinicopathologic entity. Giant cell tumor of bone is a benign but potentially aggressive lesion with local recurrence and metastasis
11,15,16.
Risk factors suggested for the development of lung metastases are local recurrence 4,5,8,11,16, location of the primary giant cell tumors (distal radius, proximal femur and sacrum) 5,8,11,15, Musculoskeletal Tumor Society Stage 2 or 3 lesion 4,6,8,11,12,15,16 and immunocompromised state 11. Aggressive, destructive primary lesions require wide excision, because such tumors tend to metastasize readily.
The cause of the metastasis is unclear. There have been many hypotheses regarding why bening giant cell tumors metastasize. Mechanisms that have been implicated include vascular invasion and iatrogenic seeding at the time of surgery 9,11,13,14. It has been shown that giant cell tumors exhibit thrombi in vascular and lymphatic channels beyond the confines of the original tumor 9,11,14-17. However, vascular invasion does not correlate convincingly with pulmonary metastases 6,9. Vascular metastasis is not the only pathway for giant cell; lymph node metastases have also been reported 4,9. Vascular invasion is a common feature of stage-3 giantcell lesions 11. Iatrogenic seeding at the time of surgery has been postulated as another mechanism for metastasis, pulmonary lesions often occured before or simultaneously with surgical intervention 11,14. It does not seem likely that operations play a major role in metastasis. Some authors have suggested that metastasis can be predicted by aggressive histologic grades 17 or radiographic appearance 12. Several large series have found histologic grading and radiographic appearance (roentgenographically aggressive, especially those with soft-tissue extension) to be an unreliable predictor for giant cell tumor metastasis 2,9,13-14. Deoxyribonucleic acid flow cytometric analysis has also been found to have limited value in predicting the behaviour of this tumor 14. Almost all cases with lung metastasis studied by DNA flow cytometry have been reported to be diploid1. Chromosomal analysis has shown abnormalities in most giant cell tumors 14. Bertoni et al 11 and Enneking 15 developed a modified staging system for giant cell tumors that is based on a combination of pathologic, radiographic and clinical findings. Aggressive lesions as defined by Enneking’s staging and recurrence were found to be risk factors for pulmonary metastasis 14. Enneking stage III tumors, despite their reported rarity, account for the majority of pulmonary metastasis 4,11,16. For this reason, wide excision is the initial treatment of choice for local control of stage-3 giant cell lesions 11.
Computed tomography scanning is helpful in diagnosing metastases. Plain radiograph and computed tomography of the chest should be obtained in patients with giant cell tumor at follow-up with six months intervals. Computed tomography scans of the chest can help to delineate the number of lesions, mediastinal involvement and are valuable in preoperative planning for surgical removal of the metastases 5. With appropriate window cuts, additional lesions not seen in plain radiographs can often be detected. Serial chest radiographs are recommended in patients with recurrence of giant cell tumors.
The outcome and degree of pulmonary disease progression in patients with metastatic giant cell tumors in the lungs are variable. The pulmonary metastatic lesions were divided into 3 types: [1] spontaneous regression or growing cessation, [2] continuously slow growing and [3] rapid growing 7,16.
The results after surgery, chemotherapy and radiotherapy have varied in different series. Metastases have been asymptomatic for long periods without any treatment 9,17 and in some cases metastases have regressed without treatment 9,10. The authors’ findings concur with other case reports that extensive surgical excision of metastases result in excellent long term survival (very good survival rates 80%) 4-6,8,9,12,14,17. If complete resection of all lung metastases can not be done, the survival rates are still high, because the incompletely resected tumors may stabilize and/or regress spontaneously or because the patients receive adjuvant chemotherapy or/and radiotherapy 4,6,8,9,11,16,17. Some literature strongly favours surgical extirpation of all pulmonary nodules 4,13.
There is little information regarding chemotherapy alone for metastatic giant cell tumor of bone 1,5,8. The role for chemotherapy after pulmonary surgery is still unclear 11. Most patients die from the side effects of chemotherapy treatment, rather than the metastases 4,5,8,13,14,16.
Radiotherapy has been used selectively as primary treatment with acceptable control rates for unresectable, recurrent and difficult primary spinal tumors 1,14. The current authors found results of only eleven patients treated with radiotherapy for lung metastasis before current series 1,6,8,10,12,13,14,16. Only three patients were treated with whole-lung radiotherapy 1. Of the eleven patients, two had progressive disease 1,14, one died of chemotherapy-related complications 6, one had radiotherapy-induced malignancy 14, and other seven had a good response to treatment. Radiotherapy has been reported in the literature for treatment of unresectable pulmonary metastases with variable results 1,6,8,10,12,13,14,16. It is recommended that radiation therapy alone should be reserved only for symptomatic, inoperable lesions in the lung 13.
Several patients were treated by chemotherapy and radiotherapy for unresectable giant cell tumor metastases in the literature 6,8,16. Feigenberg et al. 1 reported three patients treated with whole-lung radiotherapy, surgical excision and chemotherapy. From the authors’ literature search, no patients were treated with whole-lung radiotherapy and chemotherapy. We used whole-lung radiotherapy and chemotherapy for the inoperable patient.
We recommend whole-lung radiotherapy and chemotherapy for patients who have lung metastasis arising from giant cell tumors of bone in case they refuse surgery or if they are not candidates for surgery with unresectable or progressive pulmonary lesions.