European Journal of Orthopaedic Surgery & Traumatology

https://doi.org/10.1007/s00590-019-02554-9

UP-TO DATE REVIEW AND CASE REPORT • SPINE - TUMORS

Can Denosumab cure giant cell tumors of the spine? A case report

and literature review
Francisco Xará‑Leite1,2   · Luís Coutinho1,2 · Carolina Fleming3 · Manuel Magalhães4 · Vânia Oliveira1,5 ·
Ricardo Rodrigues‑Pinto6,7 · Pedro Cardoso1,5

Received: 9 August 2019 / Accepted: 12 September 2019

© Springer-Verlag France SAS, part of Springer Nature 2019

Abstract
Background  Bone giant cell tumors, although benign, may be locally aggressive and cause severe morbidity; in some cases,
they can also disseminate at distance and cause death. Denosumab has been approved to treat unresectable bone giant cell
tumors or when surgery is likely to result in severe morbidity. Furthermore, its curative potential has been recently suggested.
Case  An 18-year-old girl presented with a spinal giant cell tumor at T9. Neo-adjuvant denosumab was administered for
9 months with great clinical and analytical tolerance. A posterior left T9 costo-transversectomy and vertebral body curet-
tage was performed and the spine stabilized. Interestingly, histopathology examination of the surgical specimens found no
evidence of tumoral cells. Denosumab was reinstated until completion of 12 months of treatment.
Conclusion  Denosumab has an important but still limited role in the treatment of spinal giant cell tumors. Here, it resulted
in complete histological resolution of the tumor, potentially widening its applicability from a strictly neo-adjuvant to a
curative role.

Keywords  Giant cell tumor · GCT​ · Spine · Denosumab

Introduction
Bone giant cell tumors (BGCTs) are typically benign
although often aggressive tumors, comprising about 5% of
all bone neoplasms [1]. They are more prevalent in females
and occur mainly in the third and fourth decades of life.
Spine giant cell tumors (SGCTs) are distinctly rare above
the sacrum, where they are diagnosed in 1.4–9% of the cases
[2, 3].
Surgery can be curative if adequate resection is accom-
plished. In the absence of such complete resection, recur-
rence rates of 55% have been reported for primary tumors
[4]. However, depending on the location, this may require
extremely mutilating procedures, such as en bloc verte-
brectomies, which are associated with low recurrence rates

1
* Francisco Xará‑Leite Instituto de Ciências Biomédicas Abel Salazar, Porto,
franciscoxdl@gmail.com Portugal
2
Luís Coutinho Department of Orthopaedics, Centro Hospitalar Universitário
luisplcoutinho@gmail.com do Porto, Largo do Prof. Abel Salazar, 4099‑001 Porto,
Portugal
Carolina Fleming
3
u12643@chporto.min‑saude.pt Department of Pathology, Centro Hospitalar Universitário
do Porto, Porto, Portugal
Manuel Magalhães
4
manuel.magalhaes@gmail.com Department of Oncology, Centro Hospitalar Universitário
do Porto, Porto, Portugal
Vânia Oliveira
5
vaniacoliveira@gmail.com Musculoskeletal Tumors Unit, Department of Orthopaedics,
Centro Hospitalar Universitário do Porto, Porto, Portugal
Ricardo Rodrigues‑Pinto
6
ric_pinto@hotmail.com FEBOT Instituto de Ciências Biomédicas Abel Salazar,
Porto, Portugal
Pedro Cardoso
7
pffcardoso@gmail.com Spinal Unit, Department of Orthopaedics, Centro Hospitalar
Universitário do Porto, Porto, Portugal

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but significantly higher morbidity when compared to intra-
lesional resections such as curettage [5]. Accordingly, poten-
tial adjuvant treatments which reduce recurrence while still
allowing the advantages of intra-lesional resections have
always been sought. These included radiation therapy, which
can control local growth but is associated with secondary
malignant transformation [6, 7], embolization, with unreli-
able long-term responses in spite of successful symptomatic
control [8], and bisphosphonates or other drugs, with no
robust evidence of sustained response. All adjuvants men-
tioned have limited evidence supporting their use (level III
or IV) [5].
On a cellular level, BGCTs are characterized by oste-
oclast-like multinucleated giant cells expressing receptor
activator of nuclear factor-kappa B (RANK), among a sea
of mononuclear stromal cells that express RANK ligand
(RANKL), which plays a key role in osteoclast activation
[1]. The monoclonal antibody denosumab, a RANKL spe-
cific inhibitor, prevents their pairing, therefore reducing
BGCT-induced bone destruction [9]. Denosumab has been
approved to treat unresectable BGCTs or when surgery is
likely to result in severe morbidity, with excellent results
[10–12]. Furthermore, it is currently the only adjuvant
Fig. 1  MRI images (T1 Fat-Sat
sequences) in sagittal (a), coro-
nal (b) and axial (c) views and
CT-scan images in bone win-
dow (d) and soft tissue window
(e) of the original osteolytic
mass at T9 level, before deno-
sumab treatment
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European Journal of Orthopaedic Surgery & Traumatology
treatment modality with level II evidence supporting its
application on SGCTs [5, 13]. Even though it has also been
described to cause sustained complete regression of the
tumor [14], denosumab still mostly serves a neo-adjuvant
role, as well as in post-surgery control of the disease.
Here, we present a case of SGCT in which complete his-
tological remission was achieved after denosumab treatment.
Patient consent was sought and obtained for this publication.
Case presentation
An 18-year-old girl presented to the orthopedic clinic with
a 4-month left paravertebral dorsal pain, persistent in spite
of oral analgesia. Pain did not radiate, and her neurologic
examination was normal. Initial X-ray was normal, but fur-
ther investigation through MRI identified an osteolytic mass
at the level of T9, involving the left posterior part of the ver-
tebral body, pedicle and transverse and inferior articular pro-
cesses, extending marginally to the superior articular process
of T10 (Fig. 1). A CT-guided biopsy was performed. Histo-
pathological analysis showed typical giant multinucleated
cells surrounded by mononucleated cells with eosinophilic
European Journal of Orthopaedic Surgery & Traumatology

cytoplasm, diagnosing a SGCT (Fig. 2). Bone scan and CT
excluded lung disease.
After discussion in multi-disciplinary meeting, deno-
sumab was initiated (120  mg, once every 28  days) for
9 months with great clinical and analytical tolerance apart
from a minor episode of toothache yielding no relevant
oral pathology, but it delayed the administration of the 7th
dose. Dorsal pain resolved within 1 month of institution
of treatment. A control CT-scan at 9 months revealed a
better definition of the mass, with a perilesional sclerotic
halo (Fig. 3).
Posterior left T9 costo-transversectomy, pedicle resec-
tion and vertebral body curettage of the lesion were per-
formed, and the spine was stabilized with T8–T10 pedicle
screws (CD HORIZON SOLERA Spinal System 4.75 mm;
Medtronic, Memphis TN, USA) (Fig. 4). Interestingly, his-
topathology examination found no evidence of remaining

Fig. 2  Bone biopsy of giant cell

tumor: typical giant multinu-
cleated cells surrounded by
mononucleated cells with
eosinophilic cytoplasm are vis-
ible with H&E staining at 100×
(a) and at 200× (b)

Fig. 3  CT-scan images (bone

window) in sagittal (a), coronal
(b) and axial (c) views at
9 months of treatment with
denosumab

Fig. 4  Intra-operative fluor-
oscopy images in AP (a) and
lateral (b) views

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GCT cells in the specimens sent, a finding confirmed in
slide review (Fig. 5).
Immediate postoperative rehabilitation showed no com-
plications. After surgery, denosumab was reinstated for 3
additional cycles, until completion of a total of 12 months
of treatment.
Two years after surgery and 3 years after initiation of
denosumab treatment, the patient displays no recurrence
of localized dorsal pain besides occasional minor postural
discomfort which subsides with oral paracetamol (Fig. 6).
Discussion
SGCTs, particularly the ones localized in the mobile spine,
have a very high rate of unresectability and are associated
with a high risk of pathological fracture. Axial pain is the
most common symptom, and although usually benign, they
present a small but not negligible metastatic potential—most
commonly to the lungs—which associates with an overall
mortality rate of 15% [1]. Balancing higher morbidity with
Fig. 5  Surgical specimen
product of curettage after
denosumab treatment showing
areas of loose connective tissue
(a) and foam cells (b) with no
evidence of giant cell tumor
(H&E staining, 100×)
Fig. 6  CT-scan images (bone
window) in sagittal (a), coronal
(b, c) and axial (d) views at
24 months of follow-up and
22 months after completion of
the treatment with denosumab
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European Journal of Orthopaedic Surgery & Traumatology
the minimization of recurrence becomes the surgeon’s main
challenge and renders adjuvant therapies paramount to their
approach. However, given their rarity, little evidence is avail-
able. A systematic review by Charest-Morin and colleagues
supports the use of denosumab in SGCT’s progression con-
trol, with response rates surpassing 90%, but considers the
available evidence of low quality [15]. This highlights the
importance of case descriptions such as this, providing clini-
cians with higher insight into potential treatment options.
In the presented case, denosumab was extremely effective
as a neo-adjuvant treatment, not only reducing the patient’s
symptoms but effectively stabilizing the mass with the pro-
motion of a perilesional sclerotic halo and allowing for a
less invasive surgical approach. Still, the most interesting
fact about this case description rests in the absence of BGCT
cells at pathological analysis of the surgical specimen, open-
ing the possibility for a potential curative role of denosumab
and raising the question whether the concomitant surgical
procedure could have theoretically been unnecessary. As
stated previously, although such results have been described
in the literature [14], patient characteristics that might
European Journal of Orthopaedic Surgery & Traumatology
potentiate this outcome are yet to be determined. Naturally,
further studies with large patient samples are needed before
any step is taken toward a single-agent treatment modality
with denosumab.
Finally, recurrence after denosumab plus surgery has
been reported to be 15% in BGCTs, highlighting the impor-
tance of a diligent follow-up protocol, especially in the first
3 years after surgery [1]. Nevertheless, reinstatement of the
treatment appears to still yield a favorable response [16].
In conclusion, denosumab has been gaining an increas-
ingly important role in recent years in the treatment of
BGCTs–SGCTs in particular—allowing significantly less
morbid surgical procedures as well as successful long-term
management of unresectable masses. A potential role as
curative treatment has been suggested, such as in the pre-
sent case, which is co-substantiated by histological analysis.
However, studies with larger cohorts are needed to confirm
this potential additional benefit.
Compliance with ethical standards  12. Kumar R, Meis JM, Amini B et al (2017) Giant cell tumor of
Conflict of interest  The authors declare that they have no conflicts of
interest in relation to this article.
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