European Spine Journal

, Volume 26, Supplement 1, pp 236–242 | Cite as

Giant cell tumor of the thoracic spine completely removed by total spondylectomy after neoadjuvant denosumab therapy

  • Noritaka Yonezawa
  • Hideki MurakamiEmail author
  • Satoshi Kato
  • Akihiko Takeuchi
  • Hiroyuki Tsuchiya
Case Report



Denosumab, a novel monoclonal antibody that targets the receptor activator of nuclear factor-κB (RANK) ligand (RANKL), has recently been used to treat patients with giant cell tumor of bone (GCTB). However, few reports have described the clinical results of denosumab therapy for spinal GCTB and evaluated treatment efficacy with respect to the entirety of the resected vertebra after denosumab therapy.


We present the case of a 51-year-old man with T12 GCTB that was completely removed by a total spondylectomy following 10 courses of neoadjuvant denosumab therapy. Post-therapy radiological findings indicated epidural tumor reduction in the spinal canal and sclerotic rim formation. However, the affected vertebra collapsed despite denosumab therapy and a massive bridging callus formation was present between the spinal GCTB and adjacent vertebra.


These morphological changes made the tumor margins unclear and increased the difficulty of dissection of the segmental arteries from the vertebral body and en bloc corpectomy by a posterior-approach. Pathological findings indicated increased woven bone at the peripheral lesion of the resected vertebra and RANKL-positive stromal cells remained around the woven bone.


These findings support that GCTB stromal cells survived around the newly formed woven bone after long-term denosumab treatment and total surgical resection of such primary spinal lesions as the gold-standard treatment, even following administration of denosumab. Surgeons should note that prolonged adjuvant denosumab therapy may increase the difficulty of performing a posterior-approach total en bloc spondylectomy.


Giant cell tumor Denosumab Total spondylectomy Spine RANKL 



The authors thank Yoshikazu Tanzawa for the patient referral and provision biopsy specimen.

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest concerning the materials or methods used in the study or the findings specified in this paper.

Supplementary material

Supplementary material 1 (MP4 456086 kb)


  1. 1.
    Balke M, Henrichs MP, Gosheger G, Ahrens H, Streitbuerger A, Koehler M, Bullmann V, Hardes J (2012) Giant cell tumors of the axial skeleton. Sarcoma 2012:410973. doi: 10.1155/2012/410973 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Roux S, Amazit L, Meduri G, Guiochon-Mantel A, Milgrom E, Mariette X (2002) RANK (receptor activator of nuclear factor kappa B) and RANK ligand are expressed in giant cell tumors of bone. Am J Clin Pathol 117(2):210–216. doi: 10.1309/BPET-F2PE-P2BD-J3P3 CrossRefPubMedGoogle Scholar
  3. 3.
    Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S (2010) Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol 11(3):275–280. doi: 10.1016/S1470-2045(10)70010-3 CrossRefPubMedGoogle Scholar
  4. 4.
    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 (2013) 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 14(9):901–908. doi: 10.1016/S1470-2045(13)70277-8 CrossRefPubMedGoogle Scholar
  5. 5.
    Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, Jun S, Jacobs I (2012) Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res 18(16):4415–4424. doi: 10.1158/1078-0432.CCR-12-0578 CrossRefPubMedGoogle Scholar
  6. 6.
    Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SP, Pienkowski A, Vaz G, Wunder JS, Seeger LL, Feng A, Roberts ZJ, Bach BA (2015) Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol 22(9):2860–2868. doi: 10.1245/s10434-015-4634-9 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Mattei TA, Ramos E, Rehman AA, Shaw A, Patel SR, Mendel E (2014) Sustained long-term complete regression of a giant cell tumor of the spine after treatment with denosumab. Spine J 14(7):e15–e21. doi: 10.1016/j.spinee.2014.02.019 CrossRefPubMedGoogle Scholar
  8. 8.
    Randhawa SS, Kwan AK, Chiu CK, Chan CY, Kwan MK (2016) Neurological recovery in two patients with cauda equina syndrome secondary to L5 lumbar spine giant cell tumour after treatment with denosumab without surgery. Asian Spine J 10(5):945–949. doi: 10.4184/asj.2016.10.5.945 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kajiwara D, Kamoda H, Yonemoto T, Iwata S, Ishii T, Tsukanishi T, Ohtori S, Yamazaki M, Okawa A (2016) Denosumab for treatment of a recurrent cervical giant-cell tumor. Asian Spine J 10(3):553–557. doi: 10.4184/asj.2016.10.3.553 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Agarwal A, Larsen BT, Buadu LD, Dunn J, Crawford R, Daniel J, Bishop MC (2013) Denosumab chemotherapy for recurrent giant-cell tumor of bone: a case report of neoadjuvant use enabling complete surgical resection. Case Rep Oncol Med 2013:496351. doi: 10.1155/2013/496351 PubMedPubMedCentralGoogle Scholar
  11. 11.
    Kumar R, Meis JM, Amini B, McEnery KW, Madewell JE, Rhines LD, Benjamin RS (2016) Giant cell tumor of cervical spine presenting as acute asphyxia: successful surgical resection after down-staging with denosumab. Spine (Phila Pa 1976). doi: 10.1097/BRS.0000000000001951 Google Scholar
  12. 12.
    de Carvalho Cavalcante RA, Silva Marques RA, dos Santos VG, Sabino E, Fraga AC Jr, Zaccariotti VA, Arruda JB, Fernandes YB (2016) Spondylectomy for giant cell tumor after denosumab therapy. Spine (Phila Pa 1976) 41(3):E178–E182. doi: 10.1097/BRS.0000000000001191 CrossRefGoogle Scholar
  13. 13.
    Goldschlager T, Dea N, Boyd M, Reynolds J, Patel S, Rhines LD, Mendel E, Pacheco M, Ramos E, Mattei TA, Fisher CG (2015) Giant cell tumors of the spine: has denosumab changed the treatment paradigm? J Neurosurg Spine 22(5):526–533. doi: 10.3171/2014.10.SPINE13937 CrossRefPubMedGoogle Scholar
  14. 14.
    Lau CP, Huang L, Wong KC, Kumta SM (2013) Comparison of the anti-tumor effects of denosumab and zoledronic acid on the neoplastic stromal cells of giant cell tumor of bone. Connect Tissue Res 54(6):439–449. doi: 10.3109/03008207.2013.848202 CrossRefPubMedGoogle Scholar
  15. 15.
    van der Heijden L, Dijkstra PD, van de Sande MA, Kroep JR, Nout RA, van Rijswijk CS, Bovee JV, Hogendoorn PC, Gelderblom H (2014) The clinical approach toward giant cell tumor of bone. Oncologist 19(5):550–561. doi: 10.1634/theoncologist.2013-0432 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Gaston CL, Bhumbra R, Watanuki M, Abudu AT, Carter SR, Jeys LM, Tillman RM, Grimer RJ (2011) Does the addition of cement improve the rate of local recurrence after curettage of giant cell tumours in bone? J Bone Jt Surg Br 93(12):1665–1669. doi: 10.1302/0301-620X.93B12.27663 CrossRefGoogle Scholar
  17. 17.
    Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC, Wunder JS (2010) The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study. J Bone Jt Surg Br 92(10):1475–1479CrossRefGoogle Scholar
  18. 18.
    Boriani S, Bandiera S, Casadei R, Boriani L, Donthineni R, Gasbarrini A, Pignotti E, Biagini R, Schwab JH (2012) Giant cell tumor of the mobile spine: a review of 49 cases. Spine (Phila Pa 1976) 37(1):E37–E45. doi: 10.1097/BRS.0b013e3182233ccd CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Noritaka Yonezawa
    • 1
  • Hideki Murakami
    • 1
    Email author
  • Satoshi Kato
    • 1
  • Akihiko Takeuchi
    • 1
  • Hiroyuki Tsuchiya
    • 1
  1. 1.Department of Orthopedic SurgeryKanazawa University School of MedicineKanazawaJapan

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