SCIENTIFIC ARTICLE
Denosumab, a Potential Alternative to the Surgical Treatment of Distal Radius Giant Cell Tumor of Bone: Case Report Min Jung Park, MD, MMSc, Kristen N. Ganjoo, MD, Amy L. Ladd, MD
Juxta-articular giant cell tumors can pose major surgical challenges. Aggressive distal radius giant cell tumors often require complex reconstructive procedures that are associated with numerous complications. We present a case of a 25-year old man with a Campanacci grade 3 giant cell tumor of the distal radius that was successfully treated with denosumab without complex reconstructive procedures. At 3.5-year follow-up and 1-year drug free period, the patient remained asymptomatic without histologic evidence of recurrent tumor. With denosumab therapy, patients can potentially avoid surgery and achieve a successful outcome. (J Hand Surg Am. 2015;-(-):-e-. Copyright Ó 2015 by the American Society for Surgery of the Hand. All rights reserved.) Key words Denosumab, giant cell tumor, distal radius.
G
IANT CELL TUMOR OF BONE occurs mostly in people 20 to 40 years old.1 The presenting symptoms include rest pain, especially at night, pain with activity, and swelling. The patients typically seek treatment about 3 to 6 months after the onset of symptoms and can present with pathologic fractures.1 The lesion is most commonly found in the distal femur, proximal tibia, and distal radius. Although giant cell tumor of bone is a benign condition with the rare occurrence of distant metastases, the locally aggressive nature of the lesion makes the management challenging. Most of the primary lesions can be classified as Enneking stage 2 or Campanacci grade 2.2 Typical incidence of recurrence after surgical resection of giant cell tumor in
From Southern California Permanente Medical Group, Antelope Valley Medical Offices, Lancaster; Division of Medical Oncology, Stanford Hospitals and Clinics, Stanford; and the Robert A Chase Hand and Upper Limb Center, Stanford Hospitals and Clinics, Red Wood City, CA. Received for publication December 30, 2014; accepted in revised form March 12, 2015. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article. Corresponding Author: Min Jung Park, MD, MMSc, Southern California Permanente Medical Group, Antelope Valley Medical Offices, 615 W Avenue L, Lancaster, CA 93534; e-mail: [email protected]. 0363-5023/15/---0001$36.00/0 http://dx.doi.org/10.1016/j.jhsa.2015.03.018
general is 59% without adjuvant therapy, and 22% with adjuvant therapy.3 Wide or radical resection can improve the disease-free survival. Reconstructive procedures, however, such as osteoarticular allograft transplantation and vascularized or nonvascularized fibula graft, are associated with complications including graft failure, nonunion, infection, and donor site morbidities.4 Intralesional curettage and bone grafting can be used for smaller Campanacci grade 2 lesions, but recurrence rate can approach 45% without local adjuvants.5 Recurrence rate has been reported to decrease to 20% with local adjuvant therapy.1 The local adjuvants include phenol, alcohol, cyclophosphamide, and cauterization. These are largely cytotoxic6 and in some instances may increase the surgical complication rate.7 Campanacci grade 3 giant cell tumors of the distal radius can be challenging to manage as they present with ill-defined borders with cortical destruction and soft-tissue extension. These lesions frequently need en bloc resection and complex reconstruction.4,8 A monoclonal antibody denosumab, a receptor activator of nuclear factor kappa-B ligand, showed promising results in recent clinical trials of inoperable giant cell tumors.9,10 However, to our knowledge, there is no available literature on juxta-articular giant cell tumor successfully treated with denosumab with a drug free follow-up period.
Ó 2015 ASSH
r
Published by Elsevier, Inc. All rights reserved.
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1
2
DENOSUMAB FOR TREATMENT OF GIANT CELL TUMOR OF DISTAL RADIUS
FIGURE 1: A Presenting posteroanterior and B lateral radiographs of left wrist.
FIGURE 2: A Presenting T1 coronal, B T2 coronal, and C T2 sagittal MRIs of left wrist.
We report a 3.5-year follow-up on a patient treated with denosumab for a Campanacci grade 3 giant cell tumor of the distal radius and thereby avoided complex reconstructive procedures.
time of initial injury when he complained of pain while lifting a heavy object. He was referred to our clinic with complaints of persistent wrist swelling. The radiographs during initial consultation suggested a giant cell tumor (Fig. 1). No antecedent history of pulmonary problems existed. We performed a comprehensive staging work-up including left wrist magnetic resonance imaging (MRI), chest radiograph, chest computed tomography, and incisional biopsy, which demonstrated absence of
PRESENTATION OF THE CASE A 25-year-old, right-handed man presented to clinic for subspecialty consultation for persistent left wrist pain and swelling following a work-related injury sustained 6 months earlier. No radiographs were obtained at the J Hand Surg Am.
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Vol. -, - 2015
DENOSUMAB FOR TREATMENT OF GIANT CELL TUMOR OF DISTAL RADIUS
determined based on a previously described drug response period of 6 months and the fact that most recurrences are reported within 2 years of surgical resection.3,9e11 The patient had monthly serum tests that monitored calcium, magnesium, creatinine, and phosphate. Common adverse effects associated with denosumab include arthralgia, headache, nausea, fatigue, back pain, and extremity pain. Hypocalcemia and hypophosphatemia are known to occur.10 During the treatment, the patient developed transient, asymptomatic hypophosphatemia which required oral supplementation of 1,000 mg per day for 7 days. The laboratory abnormality resolved after the supplementation. The patient completed 2 years of the denosumab therapy at regular 4-week intervals, without any noteworthy treatment-related adverse effects. At the 2-year follow-up, the wrist radiographs (Fig. 4) and MRI studies (Fig. 5) showed evidence of resolution of the giant cell tumor with new sclerotic bone formation. Incisional biopsy confirmed cortical bone formation and no multinucleated giant cells (Fig. 6). Chest radiographs did not show any evidence of metastasis. The patient remained pain-free 3.5 years after initiation of the treatment. Wrist extension was 90 on the right versus 85 on the affected left side. Wrist flexion was 90 on the right versus 80 on the left. Supination was 70 on the right versus 50 on the left. Pronation was 75 bilaterally. Jamar grip strength in
FIGURE 3: Presenting biopsy specimen at 10 magnification.
other lesions. The MRI studies (Fig. 2) and incisional biopsy (Fig. 3) confirmed the diagnosis of giant cell tumor of bone. At the time of the presentation, dorsal swelling at the wrist was clearly visible because of mass effect. Surgical discussion included reconstructive procedures such as en bloc resection and reconstruction with allograft. During the treatment strategy discussions, we obtained medical oncologic consultation and on their recommendation, enrolled the patient for a trial of denosumab treatment. The patient received 120 mg by subcutaneous injection weekly for 4 weeks, then monthly thereafter for a total of 2 years. The 2-year treatment period was
FIGURE 4: A Last follow-up posteroanterior and B lateral radiographs demonstrating contrasting sclerotic lines within the lesion.
J Hand Surg Am.
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DENOSUMAB FOR TREATMENT OF GIANT CELL TUMOR OF DISTAL RADIUS
FIGURE 5: A T1 coronal, B T2 postcontrast coronal, and C postcontrast sagittal MRIs demonstrating bone formation within the lesion, 2 years after the initiation of the denosumab therapy.
destruction.12 Denosumab, initially developed to treat osteoporosis, has been shown to be an effective treatment option for patients with large tumor burden or metastatic giant cell tumor,13 even in the setting of recurrence.9 Although simply reducing the tumor burden for the purpose of en bloc resection can be a treatment strategy,14 the current case suggests that Campanacci grade 3 lesions could be successfully treated with denosumab. We preferred an incisional biopsy rather than a core needle biopsy, as it was easier to access multiple biopsy sites for better accuracy. Staging work-up is also important because of the possibility of metastasis, especially in high-grade lesions.1,15 The U.S. Food and Drug Administration previously has approved the use of denosumab for treatment of inoperable giant cell tumors. All patients undergoing denosumab therapy should be monitored for potential adverse effects during the treatment period. Hypocalcemia, osteonecrosis of the jaw, and hypophosphatemia are reported potential complications of denosumab therapy. For patients with high-grade giant cell tumor of distal radius, oncology consultation to explore possible treatment with denosumab should be considered.
FIGURE 6: Two-year follow-up biopsy at 10 magnification.
the 3rd position was 46 kg on the right and 41 kg on the left. The patient remained on denosumab 6 months following the 2-year biopsy results for maintenance and monitoring; therefore, total time of medication was 2.5 years. At the last follow-up (3.5 y), the patient had been off denosumab for 12 months without evidence of recurrence. The patient is scheduled for yearly follow-up hereafter and instructed to follow up sooner if he experiences any symptoms.
REFERENCES
DISCUSSION Campanacci grade 1 lesions represent latent disease with well-defined margin and intact cortex. Grade 2 lesions are active diseases with relatively welldefined margin but no radiolucent rim, and the cortex is thinned with expansion. Grade 3 giant cell tumors can be challenging to manage, as they are aggressive, with indistinct borders and with cortical J Hand Surg Am.
1. Raskin KA, Schwab JH, Mankin HJ, Springfield DS, Hornicek FJ. Giant cell tumor of bone. J Am Acad Orthop Surg. 2013;21(2):118e126. 2. Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69(1):106e114. 3. Balke M, Ahrens H, Streitbuerger A, et al. Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol. 2009;135(1):149e158. 4. Flouzat-Lachaniette CH, Babinet A, Kahwaji A, Anract P, Biau DJ. Limited arthrodesis of the wrist for treatment of giant cell tumor of the distal radius. J Hand Surg Am. 2013;38(8):1505e1512.
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DENOSUMAB FOR TREATMENT OF GIANT CELL TUMOR OF DISTAL RADIUS
5. Miller G, Bettelli G, Fabbri N, Capanna R. Curettage of giant cell tumor of bone. Introduction: material and methods. Chir Organi Mov. 1990;75(1 Suppl):203. 6. Savadkoohi DG, Sadeghipour P, Attarian H, Sardari S, Eslamifar A, Shokrgozar MA. Cytotoxic effect of drugs eluted from polymethylmethacrylate on stromal giant-cell tumour cells: an in vitro study. J Bone Joint Surg Br. 2008;90(7):973e979. 7. Ruggieri P, Mavrogenis AF, Ussia G, Angelini A, Papagelopoulos PJ, Mercuri M. Recurrence after and complications associated with adjuvant treatments for sacral giant cell tumor. Clin Orthop Relat Res. 2010;468(11):2954e2961. 8. Clarkson PW, Sandford K, Phillips AE, et al. Functional results following vascularized versus nonvascularized bone grafts for wrist arthrodesis following excision of giant cell tumors. J Hand Surg Am. 2013;38(5):935e940. 9. Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012;18(16):4415e4424. 10. Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant
J Hand Surg Am.
11.
12.
13.
14.
15.
r
5
cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14(9):901e908. Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11(3):275e280. Campanacci M, Giunti A, Olmi R. [Metaphyseal and diaphyseal localization of giant cell tumors]. Chir Organi Mov. 1975;62(1): 29e34. Karras NA, Polgreen LE, Ogilvie C, Manivel JC, Skubitz KM, Lipsitz E. Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol. 2013;31(12): e200ee202. Agarwal A, Larsen BT, Buadu LD, et al. Denosumab chemotherapy for recurrent giant-cell tumor of bone: a case report of neoadjuvant use enabling complete surgical resection. Case Rep Oncol Med. 2013;2013:496351. Bertoni F, Present D, Sudanese A, Baldini N, Bacchini P, Campanacci M. Giant-cell tumor of bone with pulmonary metastases. Six case reports and a review of the literature. Clin Orthop Relat Res. 1988;(237):275e285.
Vol. -, - 2015
Denosumab, a Potential Alternative to the Surgical Treatment of Distal Radius Giant Cell Tumor of Bone: Case Report Min Jung Park, MD, MMSc, Kristen N. Ganjoo, MD, Amy L. Ladd, MD
Juxta-articular giant cell tumors can pose major surgical challenges. Aggressive distal radius giant cell tumors often require complex reconstructive procedures that are associated with numerous complications. We present a case of a 25-year old man with a Campanacci grade 3 giant cell tumor of the distal radius that was successfully treated with denosumab without complex reconstructive procedures. At 3.5-year follow-up and 1-year drug free period, the patient remained asymptomatic without histologic evidence of recurrent tumor. With denosumab therapy, patients can potentially avoid surgery and achieve a successful outcome. (J Hand Surg Am. 2015;-(-):-e-. Copyright Ó 2015 by the American Society for Surgery of the Hand. All rights reserved.) Key words Denosumab, giant cell tumor, distal radius.
G
IANT CELL TUMOR OF BONE occurs mostly in people 20 to 40 years old.1 The presenting symptoms include rest pain, especially at night, pain with activity, and swelling. The patients typically seek treatment about 3 to 6 months after the onset of symptoms and can present with pathologic fractures.1 The lesion is most commonly found in the distal femur, proximal tibia, and distal radius. Although giant cell tumor of bone is a benign condition with the rare occurrence of distant metastases, the locally aggressive nature of the lesion makes the management challenging. Most of the primary lesions can be classified as Enneking stage 2 or Campanacci grade 2.2 Typical incidence of recurrence after surgical resection of giant cell tumor in
From Southern California Permanente Medical Group, Antelope Valley Medical Offices, Lancaster; Division of Medical Oncology, Stanford Hospitals and Clinics, Stanford; and the Robert A Chase Hand and Upper Limb Center, Stanford Hospitals and Clinics, Red Wood City, CA. Received for publication December 30, 2014; accepted in revised form March 12, 2015. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article. Corresponding Author: Min Jung Park, MD, MMSc, Southern California Permanente Medical Group, Antelope Valley Medical Offices, 615 W Avenue L, Lancaster, CA 93534; e-mail: [email protected]. 0363-5023/15/---0001$36.00/0 http://dx.doi.org/10.1016/j.jhsa.2015.03.018
general is 59% without adjuvant therapy, and 22% with adjuvant therapy.3 Wide or radical resection can improve the disease-free survival. Reconstructive procedures, however, such as osteoarticular allograft transplantation and vascularized or nonvascularized fibula graft, are associated with complications including graft failure, nonunion, infection, and donor site morbidities.4 Intralesional curettage and bone grafting can be used for smaller Campanacci grade 2 lesions, but recurrence rate can approach 45% without local adjuvants.5 Recurrence rate has been reported to decrease to 20% with local adjuvant therapy.1 The local adjuvants include phenol, alcohol, cyclophosphamide, and cauterization. These are largely cytotoxic6 and in some instances may increase the surgical complication rate.7 Campanacci grade 3 giant cell tumors of the distal radius can be challenging to manage as they present with ill-defined borders with cortical destruction and soft-tissue extension. These lesions frequently need en bloc resection and complex reconstruction.4,8 A monoclonal antibody denosumab, a receptor activator of nuclear factor kappa-B ligand, showed promising results in recent clinical trials of inoperable giant cell tumors.9,10 However, to our knowledge, there is no available literature on juxta-articular giant cell tumor successfully treated with denosumab with a drug free follow-up period.
Ó 2015 ASSH
r
Published by Elsevier, Inc. All rights reserved.
r
1
2
DENOSUMAB FOR TREATMENT OF GIANT CELL TUMOR OF DISTAL RADIUS
FIGURE 1: A Presenting posteroanterior and B lateral radiographs of left wrist.
FIGURE 2: A Presenting T1 coronal, B T2 coronal, and C T2 sagittal MRIs of left wrist.
We report a 3.5-year follow-up on a patient treated with denosumab for a Campanacci grade 3 giant cell tumor of the distal radius and thereby avoided complex reconstructive procedures.
time of initial injury when he complained of pain while lifting a heavy object. He was referred to our clinic with complaints of persistent wrist swelling. The radiographs during initial consultation suggested a giant cell tumor (Fig. 1). No antecedent history of pulmonary problems existed. We performed a comprehensive staging work-up including left wrist magnetic resonance imaging (MRI), chest radiograph, chest computed tomography, and incisional biopsy, which demonstrated absence of
PRESENTATION OF THE CASE A 25-year-old, right-handed man presented to clinic for subspecialty consultation for persistent left wrist pain and swelling following a work-related injury sustained 6 months earlier. No radiographs were obtained at the J Hand Surg Am.
r
Vol. -, - 2015
DENOSUMAB FOR TREATMENT OF GIANT CELL TUMOR OF DISTAL RADIUS
determined based on a previously described drug response period of 6 months and the fact that most recurrences are reported within 2 years of surgical resection.3,9e11 The patient had monthly serum tests that monitored calcium, magnesium, creatinine, and phosphate. Common adverse effects associated with denosumab include arthralgia, headache, nausea, fatigue, back pain, and extremity pain. Hypocalcemia and hypophosphatemia are known to occur.10 During the treatment, the patient developed transient, asymptomatic hypophosphatemia which required oral supplementation of 1,000 mg per day for 7 days. The laboratory abnormality resolved after the supplementation. The patient completed 2 years of the denosumab therapy at regular 4-week intervals, without any noteworthy treatment-related adverse effects. At the 2-year follow-up, the wrist radiographs (Fig. 4) and MRI studies (Fig. 5) showed evidence of resolution of the giant cell tumor with new sclerotic bone formation. Incisional biopsy confirmed cortical bone formation and no multinucleated giant cells (Fig. 6). Chest radiographs did not show any evidence of metastasis. The patient remained pain-free 3.5 years after initiation of the treatment. Wrist extension was 90 on the right versus 85 on the affected left side. Wrist flexion was 90 on the right versus 80 on the left. Supination was 70 on the right versus 50 on the left. Pronation was 75 bilaterally. Jamar grip strength in
FIGURE 3: Presenting biopsy specimen at 10 magnification.
other lesions. The MRI studies (Fig. 2) and incisional biopsy (Fig. 3) confirmed the diagnosis of giant cell tumor of bone. At the time of the presentation, dorsal swelling at the wrist was clearly visible because of mass effect. Surgical discussion included reconstructive procedures such as en bloc resection and reconstruction with allograft. During the treatment strategy discussions, we obtained medical oncologic consultation and on their recommendation, enrolled the patient for a trial of denosumab treatment. The patient received 120 mg by subcutaneous injection weekly for 4 weeks, then monthly thereafter for a total of 2 years. The 2-year treatment period was
FIGURE 4: A Last follow-up posteroanterior and B lateral radiographs demonstrating contrasting sclerotic lines within the lesion.
J Hand Surg Am.
3
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Vol. -, - 2015
4
DENOSUMAB FOR TREATMENT OF GIANT CELL TUMOR OF DISTAL RADIUS
FIGURE 5: A T1 coronal, B T2 postcontrast coronal, and C postcontrast sagittal MRIs demonstrating bone formation within the lesion, 2 years after the initiation of the denosumab therapy.
destruction.12 Denosumab, initially developed to treat osteoporosis, has been shown to be an effective treatment option for patients with large tumor burden or metastatic giant cell tumor,13 even in the setting of recurrence.9 Although simply reducing the tumor burden for the purpose of en bloc resection can be a treatment strategy,14 the current case suggests that Campanacci grade 3 lesions could be successfully treated with denosumab. We preferred an incisional biopsy rather than a core needle biopsy, as it was easier to access multiple biopsy sites for better accuracy. Staging work-up is also important because of the possibility of metastasis, especially in high-grade lesions.1,15 The U.S. Food and Drug Administration previously has approved the use of denosumab for treatment of inoperable giant cell tumors. All patients undergoing denosumab therapy should be monitored for potential adverse effects during the treatment period. Hypocalcemia, osteonecrosis of the jaw, and hypophosphatemia are reported potential complications of denosumab therapy. For patients with high-grade giant cell tumor of distal radius, oncology consultation to explore possible treatment with denosumab should be considered.
FIGURE 6: Two-year follow-up biopsy at 10 magnification.
the 3rd position was 46 kg on the right and 41 kg on the left. The patient remained on denosumab 6 months following the 2-year biopsy results for maintenance and monitoring; therefore, total time of medication was 2.5 years. At the last follow-up (3.5 y), the patient had been off denosumab for 12 months without evidence of recurrence. The patient is scheduled for yearly follow-up hereafter and instructed to follow up sooner if he experiences any symptoms.
REFERENCES
DISCUSSION Campanacci grade 1 lesions represent latent disease with well-defined margin and intact cortex. Grade 2 lesions are active diseases with relatively welldefined margin but no radiolucent rim, and the cortex is thinned with expansion. Grade 3 giant cell tumors can be challenging to manage, as they are aggressive, with indistinct borders and with cortical J Hand Surg Am.
1. Raskin KA, Schwab JH, Mankin HJ, Springfield DS, Hornicek FJ. Giant cell tumor of bone. J Am Acad Orthop Surg. 2013;21(2):118e126. 2. Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69(1):106e114. 3. Balke M, Ahrens H, Streitbuerger A, et al. Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol. 2009;135(1):149e158. 4. Flouzat-Lachaniette CH, Babinet A, Kahwaji A, Anract P, Biau DJ. Limited arthrodesis of the wrist for treatment of giant cell tumor of the distal radius. J Hand Surg Am. 2013;38(8):1505e1512.
r
Vol. -, - 2015
DENOSUMAB FOR TREATMENT OF GIANT CELL TUMOR OF DISTAL RADIUS
5. Miller G, Bettelli G, Fabbri N, Capanna R. Curettage of giant cell tumor of bone. Introduction: material and methods. Chir Organi Mov. 1990;75(1 Suppl):203. 6. Savadkoohi DG, Sadeghipour P, Attarian H, Sardari S, Eslamifar A, Shokrgozar MA. Cytotoxic effect of drugs eluted from polymethylmethacrylate on stromal giant-cell tumour cells: an in vitro study. J Bone Joint Surg Br. 2008;90(7):973e979. 7. Ruggieri P, Mavrogenis AF, Ussia G, Angelini A, Papagelopoulos PJ, Mercuri M. Recurrence after and complications associated with adjuvant treatments for sacral giant cell tumor. Clin Orthop Relat Res. 2010;468(11):2954e2961. 8. Clarkson PW, Sandford K, Phillips AE, et al. Functional results following vascularized versus nonvascularized bone grafts for wrist arthrodesis following excision of giant cell tumors. J Hand Surg Am. 2013;38(5):935e940. 9. Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012;18(16):4415e4424. 10. Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant
J Hand Surg Am.
11.
12.
13.
14.
15.
r
5
cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14(9):901e908. Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11(3):275e280. Campanacci M, Giunti A, Olmi R. [Metaphyseal and diaphyseal localization of giant cell tumors]. Chir Organi Mov. 1975;62(1): 29e34. Karras NA, Polgreen LE, Ogilvie C, Manivel JC, Skubitz KM, Lipsitz E. Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol. 2013;31(12): e200ee202. Agarwal A, Larsen BT, Buadu LD, et al. Denosumab chemotherapy for recurrent giant-cell tumor of bone: a case report of neoadjuvant use enabling complete surgical resection. Case Rep Oncol Med. 2013;2013:496351. Bertoni F, Present D, Sudanese A, Baldini N, Bacchini P, Campanacci M. Giant-cell tumor of bone with pulmonary metastases. Six case reports and a review of the literature. Clin Orthop Relat Res. 1988;(237):275e285.
Vol. -, - 2015
