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Background: Denosumab is a human monoclonal antibody that has been used successfully in the treatment of giant cell tumors of bone. These tumors are rare and, in principle, benign, but they are highly aggressive, locally advanced, osteolytic bone tumors that can metastasize to the lungs. Denosumab is an effective treatment when these tumors cannot be surgically removed or when surgical resection is likely to lead to severe morbidity (eg, loss of limbs or joints). The aim of this systematic review and meta-analysis was to investigate patients with giant cell tumors of bone who experienced tumor progression during treatment with denosumab and to compare them with patients who experienced reduction of their giant cell tumors of bone during treatment with denosumab., Methods: Embase, Cochrane Library, and MEDLINE/PubMed databases were searched for trials submitted by January 7, 2020, that reported the efficacy and safety of denosumab in patients with giant cell tumors of bone., Results: Sixty studies were reviewed, involving a total of 1074 patients who had giant cell tumors of bone and were treated with denosumab. Of the 60 studies, 58% of the patients were from case series studies, 39% from open-label phase II studies, and 3% from case reports. The response rate for denosumab as a treatment for giant cell tumors of bone was 97.5%, with statistical significance ( P < .0001). Pain in the limbs was statistically the most common adverse event for denosumab treatment in case series studies ( P < .0001). No treatment-related deaths occurred in the reviewed studies., Conclusion: Cumulative evidence supports the addition of surgery to optimal medical therapy with denosumab to reduce tumor size, clinical symptoms, and mortality among patients with giant cell tumors of bone.

Giant cell tumors of the bone are benign but locally aggressive, and they rarely metastasize to the lungs. The purpose of this study was to retrospectively review the clinical presentation, long-term outcomes, and treatment of pulmonary metastasis of these tumors. Between 1991 and 2004, a total of 168 patients with giant cell tumors of the bone were treated at the authors' institution, 7 of whom developed lung metastasis. Four of the 7 patients were men, and mean age of these patients at initial surgery was 40 years (range, 19-56 years). All patients underwent wide excision and reconstruction or curettage and bone grafting for the bony lesions. Lung metastases were detected at a mean of 44 months after the treatment of bone lesions. Five patients had multiple metastases, and 2 had solitary pulmonary metastases. Six of these patients underwent delayed treatment, locally aggressive, or multiple recurrent and surgical procedures. All of the aforementioned procedures had similar risk factors to those previously reported in the literature. One patient had multiple giant cell tumors of the bone. At last follow-up, 2 patients had died due to complications from the pulmonary metastases or chemotherapy. One patient underwent a metastasectomy 4 years after treatment due to the progression of pulmonary metastasis. The remaining 4 patients were alive and healthy after chemotherapy or conservative treatment. Therefore, early detection, adequate treatment of the primary bone lesion, conservative treatment of lung metastases, and regular long-term follow-up are recommended., (Copyright 2016, SLACK Incorporated.)

Resently, we treated a 69-year-old patient with squamous cell carcinoma of lung with osteoclast-like giant cells which were similar with the giant cell tumor of bone. The clinical and pathological characteristics of this case were presented, and the literatures were reviewed. The tumor differed histologically from the pleomorphic carcinoma, which occurs most commonly in the lung and showed diverse pleomorphic manifestation with benign looking osteoclast-like multinucleated cells and bizarre giant cells. In addition, undifferentiated carcinoma with a sarcoma-like appearance containing small areas of papillary adenocarcinoma was evident in the tumor. Histological features and immunohistochemical staining could be helpful in differential diagnosis.

The authors reviewed 6 cases of giant cell tumor of bone with pulmonary metastases, analyzed the growth rate of the metastases, and performed flow cytometry on paraffin blocks from primary and metastatic lesions. Surgery on the pulmonary metastases was done in 3 cases. Chemotherapy was administered in all 6 cases. If the doubling time of the pulmonary metastases was more than 80 days, the case was considered to be slow growing or in regression. However, if the doubling time was approximately 30 days, the prognosis was poor. The cases were divided into 3 types according to the prognosis. After chemotherapy (cyclophosphamide), the pulmonary metastases decreased in size in 2 cases. In 2 other cases, the metastases were slow growing, and the remaining 2 patients died early. Flow cytometric analysis was performed on primary and metastatic lesions, which showed a diploid pattern in most cases, but a tetraploid pattern in 1 recurrent case. Pulmonary metastatic lesions displayed a diploid pattern in 4 cases from which materials were taken either at surgery or autopsy.

A 32-year-old man developed multiple pulmonary metastases from a giant cell tumor of bone. His metastases failed to respond to several chemotherapy regimens (high-dose methotrexate with folinic acid plus doxorubicin 90 mg/m2; cyclophosphamide + bleomycin + actinomycin D; mitoxantrone + dacarbazine; and cisplatin 110 mg/m2). He underwent surgical resection (incomplete) of > 1 kg of tumor from his right lung in March 1985, followed by chemotherapy with menogaril (to which he did not respond). In August 1985, he underwent surgical resection (again, incomplete) of > 1 kg of tumor from his left lung. At the time of surgery, the left and right lung tumors differed histopathologically, with giant cell tumor present in the right lung and sarcoma in his left lung. He received carmustine in October 1985 and mitomycin C in December 1985 without response. His multiple bilateral lung metastases had again become quite large by September 1986. At that time, he received doxorubicin 90 mg/m2 plus cisplatin 120 mg/m2, and for the first time experienced tumor reduction (minor response). He underwent a subtotal resection of right lung and chest wall metastases in December 1986, and underwent subtotal resection of left lung metastases in January 1987. Grossly visible residual tumor was left behind on both sides at the time of surgery, although none was apparent on chest radiograph. He received a final chemotherapy treatment with doxorubicin 90 mg/m2 plus cisplatin 120 mg/m2 on February 2, 1987. He remained free of evidence of residual or recurrent tumor at the time of last followup in February, 1994.

Klinefelter's syndrome with karyotype 47,XXY in patients with primary extragonadal germ cell tumors rarely occurs. The endocrinology of Klinefelter's syndrome is changed; elevated beta-human choriomic gonadotropin levels are present. Chemotherapy and thoracic surgery brought complete remission in a patient with lung metastases.

The cases of 36 patients with inoperable non-small cell lung cancers and similar anatomoclinical features were retrospectively analysed on the basis of treatment received (21 combined chemical and radiation therapy, 15 chemotherapy). The results showed 7 PR (partial response) 5 S (stable) 9 P (progression) in the group given combined chemical and radiation treatment; 2 PR, 7 S and 6 P in the group given chemotherapy alone. The patients with the best Performance Status produced the best PR figures (6/9) and the longest mean survival (10 months). Analysis of 9 patients in each group indicated that the length of survival is not affected by the timing or doses of drug treatment. Altogether the data support the view that no treatment has any influence on the prognosis for inoperable lung cancers.

Giant-cell tumor of bone rarely metastasizes to the lung. In three of six cases, lesions in lung tissue were histologically benign. In 39 such cases reported in the literature, the treatments were surgical extirpation, chemotherapy, and radiation therapy. Resection was indicated to definitely diagnose the pulmonary lesions as benign giant-cell tumors. Radiation therapy and/or chemotherapy may be beneficial as adjuvant treatment, especially where the lesions are anatomically inaccessible. Some pulmonary lesions spontaneously regress even in the absence of definitive treatment.

We reviewed the cases of seven patients with histologically benign primary giant-cell tumor of bone and histologically proved metastases to the lung. All seven had a Stage-3, aggressive, benign lesion with interruption of the cortex and soft-tissue extension. The main histological features of the primary lesion were identical to those of the pulmonary metastases. In only one of the seven patients were the metastases detected simultaneously with the primary lesion. All seven patients were treated by surgical resection of the lung nodules and chemotherapy. Of the seven patients, four were alive and free of disease after an average follow-up of nine years; two were receiving chemotherapy; and one, who had had immunosuppression for an allograft transplant, died less than one year after the discovery of the pulmonary lesions. Based on this small series, we concluded that patients with a Stage-3 giant-cell tumor of bone may be at risk for pulmonary spread of the disease. This lesion, with its benign histological picture even in lung lesions, has a favorable prognosis when treated with pulmonary resection of the nodules. However, the role for chemotherapy after pulmonary surgery is still unclear.