Skip to main content
Erschienen in: Clinical Orthopaedics and Related Research® 9/2015

01.09.2015 | Case Report

A High-grade Sarcoma Arising in a Patient With Recurrent Benign Giant Cell Tumor of the Proximal Tibia While Receiving Treatment With Denosumab

verfasst von: Luis A. Aponte-Tinao, MD, Nicolas S. Piuzzi, MD, Pablo Roitman, MD, German L. Farfalli, MD

Erschienen in: Clinical Orthopaedics and Related Research® | Ausgabe 9/2015

Einloggen, um Zugang zu erhalten

Abstract

Background

A giant cell tumor of bone is a primary benign but locally aggressive neoplasm. Malignant transformation in a histologically typical giant cell tumor of bone, without radiotherapy exposure, is an uncommon event, occurring in less than 1% of giant cell tumors of bone. Although surgery is the standard initial treatment, denosumab, a monoclonal antibody drug that inhibits receptor activator of nuclear factor-κB ligand (RANKL), has shown considerable activity regarding disease and control of symptoms in patients with recurrence, unresectable, and metastatic giant cell tumors of bone.

Case Description

We report the case of a 20-year-old woman with a recurrent benign, giant cell tumor of bone, who had a bone sarcoma develop while receiving denosumab treatment.

Literature Review

To our knowledge, there have been no reports of infection or malignancy with low-dose denosumab administration for osteoporosis. However, while there are relatively few reported side effects, the safety of denosumab and adverse events seen with higher doses, as used in treatment of giant cell tumors of bone are not well defined.

Clinical Relevance

Denosumab has become a valuable adjunct for treatment of recurrent or unresectable giant cell tumor of bone. It is not clear if our patient’s malignant transformation of a giant cell tumor of bone while receiving denosumab treatment was caused by denosumab, but it is important to be aware of the possibility if more cases occur. Future studies should focus on the safety of high-dose denosumab administration in patients with a benign unresectable giant cell tumor of bone.
Literatur
1.
Zurück zum Zitat Bertoni F, Bacchini P, Staals EL. Malignancy in giant cell tumor of bone. Cancer. 2003;97:2520–2529.PubMedCrossRef Bertoni F, Bacchini P, Staals EL. Malignancy in giant cell tumor of bone. Cancer. 2003;97:2520–2529.PubMedCrossRef
2.
Zurück zum Zitat Bone HG, Chapurlat R, Brandi ML, Brown JP, Czerwinski E, Krieg MA, Mellström D, Radominski SC, Reginster JY, Resch H, Ivorra JA, Roux C, Vittinghoff E, Daizadeh NS, Wang A, Bradley MN, Franchimont N, Geller ML, Wagman RB, Cummings SR, Papapoulos S. The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab. 2013;98:4483–4492.PubMedCentralPubMedCrossRef Bone HG, Chapurlat R, Brandi ML, Brown JP, Czerwinski E, Krieg MA, Mellström D, Radominski SC, Reginster JY, Resch H, Ivorra JA, Roux C, Vittinghoff E, Daizadeh NS, Wang A, Bradley MN, Franchimont N, Geller ML, Wagman RB, Cummings SR, Papapoulos S. The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab. 2013;98:4483–4492.PubMedCentralPubMedCrossRef
3.
Zurück zum Zitat Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69:106–114.PubMed Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69:106–114.PubMed
4.
Zurück zum Zitat Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, Kroep J, Grimer R, Reichardt P, Rutkowski P, Schuetze S, Skubitz K, Staddon A, Thomas D, Qian Y, Jacobs I. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14:901–908.PubMedCrossRef Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, Kroep J, Grimer R, Reichardt P, Rutkowski P, Schuetze S, Skubitz K, Staddon A, Thomas D, Qian Y, Jacobs I. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14:901–908.PubMedCrossRef
5.
Zurück zum Zitat Ferrari-Lacraz S, Ferrari S. Do RANKL inhibitors (denosumab) affect inflammation and immunity? Osteoporos. Int. 2011;22:435–446.PubMedCrossRef Ferrari-Lacraz S, Ferrari S. Do RANKL inhibitors (denosumab) affect inflammation and immunity? Osteoporos. Int. 2011;22:435–446.PubMedCrossRef
6.
Zurück zum Zitat Grote HJ, Braun M, Kalinski T, Pomjanski N, Back W, Bleyl U, Böcking A, Roessner A. Spontaneous malignant transformation of conventional giant cell tumor. Skeletal Radiol. 2004;33:169–175.PubMedCrossRef Grote HJ, Braun M, Kalinski T, Pomjanski N, Back W, Bleyl U, Böcking A, Roessner A. Spontaneous malignant transformation of conventional giant cell tumor. Skeletal Radiol. 2004;33:169–175.PubMedCrossRef
7.
Zurück zum Zitat Hefti FL, Gächter A, Remagen W, Nidecker A. Recurrent giant-cell tumor with metaplasia and malignant change, not associated with radiotherapy: a case report. J Bone Joint Surg Am. 1992;74:930–934.PubMed Hefti FL, Gächter A, Remagen W, Nidecker A. Recurrent giant-cell tumor with metaplasia and malignant change, not associated with radiotherapy: a case report. J Bone Joint Surg Am. 1992;74:930–934.PubMed
8.
Zurück zum Zitat Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH. Giant cell tumor of bone: risk factors for recurrence. Clin Orthop Relat Res. 2011;469:591–599.PubMedCentralPubMedCrossRef Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH. Giant cell tumor of bone: risk factors for recurrence. Clin Orthop Relat Res. 2011;469:591–599.PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Li J, Zhu Y, Wei Y. Fibrosarcoma development 15 years after curettage and bone grafting of giant cell tumor of bone. Orthopedics. 2014;37:e512–516.PubMedCrossRef Li J, Zhu Y, Wei Y. Fibrosarcoma development 15 years after curettage and bone grafting of giant cell tumor of bone. Orthopedics. 2014;37:e512–516.PubMedCrossRef
10.
Zurück zum Zitat Mak IW, Evaniew N, Popovic S, Tozer R, Ghert M. A translational study of the neoplastic cells of giant cell tumor of bone following neoadjuvant denosumab. J Bone Joint Surg Am. 2014;96:e127.PubMedCrossRef Mak IW, Evaniew N, Popovic S, Tozer R, Ghert M. A translational study of the neoplastic cells of giant cell tumor of bone following neoadjuvant denosumab. J Bone Joint Surg Am. 2014;96:e127.PubMedCrossRef
11.
Zurück zum Zitat Marui T, Yamamoto T, Yoshihara H, Kurosaka M, Mizuno K, Akamatsu T. De novo malignant transformation of giant cell tumor of bone. Skeletal Radiol. 2001;30:104–108.PubMedCrossRef Marui T, Yamamoto T, Yoshihara H, Kurosaka M, Mizuno K, Akamatsu T. De novo malignant transformation of giant cell tumor of bone. Skeletal Radiol. 2001;30:104–108.PubMedCrossRef
12.
Zurück zum Zitat McDonald DJ, Sim FH, McLeod RA, Dahlin DC. Giant-cell tumor of bone. J Bone Joint Surg Am. 1986;68:235–242.PubMed McDonald DJ, Sim FH, McLeod RA, Dahlin DC. Giant-cell tumor of bone. J Bone Joint Surg Am. 1986;68:235–242.PubMed
13.
Zurück zum Zitat Mori Y, Tuchiya H, Karita M, Nonomura A, Nojima T, Tomita K. Malignant transformation of a giant cell tumor 25 years after initial treatment. Clin Orthop Relat Res 2000;381:185–191.PubMedCrossRef Mori Y, Tuchiya H, Karita M, Nonomura A, Nojima T, Tomita K. Malignant transformation of a giant cell tumor 25 years after initial treatment. Clin Orthop Relat Res 2000;381:185–191.PubMedCrossRef
14.
Zurück zum Zitat Muscolo DL, Ayerza MA, Aponte-Tinao LA. Giant cell tumours of bone. Curr Orthop. 2001;15:41–50.CrossRef Muscolo DL, Ayerza MA, Aponte-Tinao LA. Giant cell tumours of bone. Curr Orthop. 2001;15:41–50.CrossRef
15.
Zurück zum Zitat Nascimento AG, Huvos AG, Marcove RC. Primary malignant giant cell tumor of bone: a study of eight cases and review of the literature. Cancer. 1979;44:1393–1402.PubMedCrossRef Nascimento AG, Huvos AG, Marcove RC. Primary malignant giant cell tumor of bone: a study of eight cases and review of the literature. Cancer. 1979;44:1393–1402.PubMedCrossRef
16.
Zurück zum Zitat Ortiz-Cruz EJ, Quinn RH, Fanburg JC, Rosenberg AE, Mankin HJ. Late development of a malignant fibrous histiocytoma at the site of a giant cell tumor. Clin Orthop Relat Res. 1995;318:199–204.PubMed Ortiz-Cruz EJ, Quinn RH, Fanburg JC, Rosenberg AE, Mankin HJ. Late development of a malignant fibrous histiocytoma at the site of a giant cell tumor. Clin Orthop Relat Res. 1995;318:199–204.PubMed
17.
Zurück zum Zitat Raskin KA, Schwab JH, Mankin HJ, Springfield DS, Hornicek FJ. Giant cell tumor of bone. J Am Acad Orthop Surg. 2013;21:118–126.PubMedCrossRef Raskin KA, Schwab JH, Mankin HJ, Springfield DS, Hornicek FJ. Giant cell tumor of bone. J Am Acad Orthop Surg. 2013;21:118–126.PubMedCrossRef
18.
Zurück zum Zitat Rock MG, Sim FH, Unni KK, Witrak GA, Frassica FJ, Schray MF, Beabout JW, Dahlin DC. Secondary malignant giant-cell tumor of bone: clinicopathological assessment of nineteen patients. J Bone Joint Surg Am. 1986;68:1073–1079.PubMed Rock MG, Sim FH, Unni KK, Witrak GA, Frassica FJ, Schray MF, Beabout JW, Dahlin DC. Secondary malignant giant-cell tumor of bone: clinicopathological assessment of nineteen patients. J Bone Joint Surg Am. 1986;68:1073–1079.PubMed
19.
Zurück zum Zitat Sakkers RJ, van der Heul RO, Kroon HM, Taminiau AH, Hogendoorn PC. Late malignant transformation of a benign giant-cell tumor of bone: a case report. J Bone Joint Surg Am. 1997;79:259–262.PubMed Sakkers RJ, van der Heul RO, Kroon HM, Taminiau AH, Hogendoorn PC. Late malignant transformation of a benign giant-cell tumor of bone: a case report. J Bone Joint Surg Am. 1997;79:259–262.PubMed
20.
Zurück zum Zitat Sinningen K, Tsourdi E, Rauner M, Rachner TD, Hamann C, Hofbauer LC. Skeletal and extraskeletal actions of denosumab. Endocrine. 2012;42:52–62.PubMedCrossRef Sinningen K, Tsourdi E, Rauner M, Rachner TD, Hamann C, Hofbauer LC. Skeletal and extraskeletal actions of denosumab. Endocrine. 2012;42:52–62.PubMedCrossRef
21.
Zurück zum Zitat Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, Miller K, Sieber P, Karsh L, Damião R, Tammela TL, Egerdie B, Van Poppel H, Chin J, Morote J, Gómez-Veiga F, Borkowski T, Ye Z, Kupic A, Dansey R, Goessl C. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012;379:39–46.PubMedCentralPubMedCrossRef Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, Miller K, Sieber P, Karsh L, Damião R, Tammela TL, Egerdie B, Van Poppel H, Chin J, Morote J, Gómez-Veiga F, Borkowski T, Ye Z, Kupic A, Dansey R, Goessl C. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012;379:39–46.PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11:275–280.PubMedCrossRef Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11:275–280.PubMedCrossRef
23.
Zurück zum Zitat Thomas DM. RANKL, denosumab, and giant cell tumor of bone. Curr Opin Oncol. 2012;24:397–403.PubMedCrossRef Thomas DM. RANKL, denosumab, and giant cell tumor of bone. Curr Opin Oncol. 2012;24:397–403.PubMedCrossRef
24.
Zurück zum Zitat Unni K. Giant Cell Tumor / Malignancy in Giant Cell Tumor of Bone. Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases. 5th ed. Philadelphia, PA: Lippincott-Raven; 1996:263–289. Unni K. Giant Cell Tumor / Malignancy in Giant Cell Tumor of Bone. Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases. 5th ed. Philadelphia, PA: Lippincott-Raven; 1996:263–289.
25.
Zurück zum Zitat Xu SF, Adams B, Yu XC, Xu M. Denosumab and giant cell tumour of bone: a review and future management considerations. Curr Oncol. 2013;20:e442–447.PubMedCentralPubMedCrossRef Xu SF, Adams B, Yu XC, Xu M. Denosumab and giant cell tumour of bone: a review and future management considerations. Curr Oncol. 2013;20:e442–447.PubMedCentralPubMedCrossRef
Metadaten
Titel
A High-grade Sarcoma Arising in a Patient With Recurrent Benign Giant Cell Tumor of the Proximal Tibia While Receiving Treatment With Denosumab
verfasst von
Luis A. Aponte-Tinao, MD
Nicolas S. Piuzzi, MD
Pablo Roitman, MD
German L. Farfalli, MD
Publikationsdatum
01.09.2015
Verlag
Springer US
Erschienen in
Clinical Orthopaedics and Related Research® / Ausgabe 9/2015
Print ISSN: 0009-921X
Elektronische ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-015-4249-2

Weitere Artikel der Ausgabe 9/2015

Clinical Orthopaedics and Related Research® 9/2015 Zur Ausgabe

Symposium: Research Advances After a Decade of War

Extremity Injury and War: A Historical Reflection

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.