World Journal of

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Submit a Manuscript: https://www.f6publishing.com World J Clin Cases 2021 May 16; 9(14): 3394-3402

DOI: 10.12998/wjcc.v9.i14.3394 ISSN 2307-8960 (online)

CASE REPORT

Tenosynovial giant cell tumor involving the cervical spine: A case

report

Jing-Hui Zhu, Miao Li, Yan Liang, Jian-Huang Wu

ORCID number: Jing-Hui Zhu 0000- Jing-Hui Zhu, Miao Li, Yan Liang, Jian-Huang Wu, Department of Spine Surgery, Xiangya
0002-7257-8165; Miao Li 0000-0001- Hospital, Central South University, Changsha 410008, Hunan Province, China
9202-818X; Yan Liang 0000-0003-
3835-2370; Jian-Huang Wu 0000- Corresponding author: Jian-Huang Wu, PhD, Chief Physician, Department of Spine Surgery,
0001-6604-8128. Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan
Province, China. [email protected]
Author contributions: Zhu JH
reviewed the literature and drafted
the manuscript; Li M analyzed and Abstract
interpreted the imaging findings;
Liang Y contributed to manuscript
BACKGROUND
drafting; Wu JH was responsible
Tenosynovial giant cell tumors (TGCTs) are a frequent benign proliferative
for the revision of the manuscript
disease originating from the synovial membrane. However, TGCTs rarely occur in
the spine. The purpose of this paper is to report a case of TGCT occurring in the
for important intellectual content;
cervical spine. Although the disease is rare, it is essential to consider the
all authors have read and
possibility of TGCT in axial skeletal lesions. Awareness of spinal TGCTs is
approved the final manuscript.
important because their characteristics are similar to common spinal tumor
Supported by The National Natural lesions.
Science Foundation of China
CASE SUMMARY
(General Program), No. 81472073;
A 49-year-old man with a 2-year history of neck pain and weakness in both lower
and the Natural Science
extremities was referred to our ward. Imaging revealed a mass extending from the
Foundation of Hunan Province of
left epidural space to the C4-5 paravertebral muscles with uneven enhancement.
China, No. 2019JJ40518.
The tumor originated in the synovium of the C4-5 lesser joint and eroded mainly
Informed consent statement: the C4-5 vertebral arch and spine. Puncture biopsy was suggestive of a giant cell-
Informed written consent was rich lesion. The patient had pulmonary tuberculosis, and we first administered
obtained from the patient for
anti-tuberculosis treatment. After the preoperative requirements of the anti-
publication of this report and any
tuberculosis treatment were met, we used a posterior cervical approach to
accompanying images.
completely remove the mass after fixation with eight pedicle screws. The mass
was identified as a TGCT by postoperative immunohistochemical analysis.
Conflict-of-interest statement: The Recurrence was not detected after 1 year of follow-up.
authors declare that they have no
CONCLUSION
conflict of interest to report.
Spinal TGCTs are often misdiagnosed. The radiological changes are not specific.
CARE Checklist (2016) statement: The ideal treatment comprises complete excision with proper internal fixation,
The authors have read the CARE which can significantly reduce postoperative recurrence.
Checklist (2016), and the
manuscript was prepared and Key Words: Tenosynovial giant cell tumors; Cervical vertebrae; Spinal diseases; Tumor;
revised according to the CARE Spine; Case report
Checklist (2016).

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 Zhu JH et al. TGCT involving the cervical spine

Open-Access: This article is an ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
open-access article that was
selected by an in-house editor and
fully peer-reviewed by external Core Tip: This paper reviews a rare case of a tenosynovial giant cell tumor (TGCT)
reviewers. It is distributed in growing in the spine, eroding the C4-5 vertebral arches and the spinous processes, the
accordance with the Creative radiological features of which mimic those of other neoplastic lesions. The definitive
Commons Attribution diagnosis of TGCT is made by immunohistochemistry. The ideal treatment comprised
NonCommercial (CC BY-NC 4.0) complete resection of the mass and appropriate internal fixation. By reviewing the
license, which permits others to diagnostic and therapeutic history and analyzing the clinical and radiological
distribute, remix, adapt, build manifestations, a better understanding of the characteristics of TGCTs of the spine can
upon this work non-commercially, be achieved, helping to improve their diagnosis and treatment.
and license their derivative works
on different terms, provided the
original work is properly cited and Citation: Zhu JH, Li M, Liang Y, Wu JH. Tenosynovial giant cell tumor involving the cervical
the use is non-commercial. See: htt spine: A case report. World J Clin Cases 2021; 9(14): 3394-3402
p://creativecommons.org/License URL: https://www.wjgnet.com/2307-8960/full/v9/i14/3394.htm
s/by-nc/4.0/ DOI: https://dx.doi.org/10.12998/wjcc.v9.i14.3394

Manuscript source: Unsolicited

manuscript

Specialty type: Orthopedics INTRODUCTION

Country/Territory of origin: China Tenosynovial giant cell tumors (TGCTs) are fibrous histiocytic tumors originating
from the tendon sheath, synovium, or sac. The pathological features are mononuclear
Peer-review report’s scientific synovial cell proliferation, osteoclast-like multinucleated giant cells, and hemosiderin
quality classification macrophages, and TGCTs rarely cause bone destruction[1]. In most cases, TGCTs
Grade A (Excellent): 0 involve the small joints of the fingers and hands (approximately 90%), and they can
Grade B (Very good): B also occur in the elbows and knees (approximately 10%). In rare cases, TGCTs appear
Grade C (Good): 0 on the synovial membrane of the spinal accessory joints[2].
Grade D (Fair): 0
Here, we report the case of a patient with paralysis of both lower limbs caused by
compression of the spinal cord due to bone destruction caused by a TGCT behind C4-
Grade E (Poor): 0
5, which we surgically treated.
Received: December 30, 2020 By reviewing the diagnostic and therapeutic history of this case and analyzing the
clinical and radiological manifestations, a better understanding of the characteristics of
Peer-review started: December 30,
TGCTs of the spine can be achieved, helping to improve their diagnosis and treatment.
2020
Although TGCTs are rare in the spine, they are similar to common spinal tumors in
First decision: February 12, 2021 many features and TGCTs should be considered in the differential diagnosis when we
Revised: February 21, 2021 diagnose axial skeletal lesions.
Accepted: March 3, 2021
Article in press: March 3, 2021
Published online: May 16, 2021
CASE PRESENTATION
P-Reviewer: Sabouri AS
S-Editor: Zhang H Chief complaints
A 49-year-old man with a 2-year history of neck pain and weakness in both lower
L-Editor: Wang TQ
extremities was referred to our ward.
P-Editor: Yuan YY
History of present illness
The patient was treated conservatively at the outpatient clinic of Xiangya Hospital,
Central South University, over the previous four months. After 4 mo of strict
conservative treatment, including nutritional support, pain relief, and herbal medicine
interventions, the patient's symptoms were not relieved, and the weakness in both
lower limbs progressed even more.

History of past illness

The patient had a history of pulmonary tuberculosis in both upper lungs for 4 years
and was not on regular anti-tuberculosis medication.

Personal and family history

The patient had no specific personal or family history.

Physical examination
The patient had decreased muscle strength (grade 3) in both lower extremities,

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Zhu JH et al. TGCT involving the cervical spine

significant sensory loss in the left thumb and index finger, active bilateral tendon
reflexes, no Hoffmann's sign, and no significant abnormalities in the remaining
extremities on physical examination.

Laboratory examinations
The tuberculosis infection T-cell spotting test was positive, but sputum smears on
three consecutive days were negative for acid-fast bacilli. The erythrocyte sedi-
mentation rate was increased, at 48 mm/h (normal range < 15 mm/h), and the results
of other routine laboratory tests were normal.

Imaging examinations
Plain X-ray radiography of the cervical spine showed destructive lesions in the
appendage area of the C4-5 vertebrae (Figure 1A). A computed tomography (CT) scan
of the cervical spine showed bone destruction and a soft tissue mass in the appendage
area of the C4-5 vertebrae (Figure 1B). Spiral CT three-dimensional reconstruction
showed the outline of bone destruction in the appendage area of C4-5 (Figure 1C). The
nature of the mass was to be determined, considering the possibility of a benign bone
tumor. A contrast-enhanced magnetic resonance imaging (MRI) scan revealed a
neoplastic lesion extending from the left epidural space to the paravertebral muscles at
C4-5. The lesion was isointense on T1-weighted imaging (T1WI) and heterogeneously
hypointense on T2-weighted imaging (T2WI) and showed heterogeneous enhan-
cement (Figure 1D). There were no obvious abnormalities in the signals of the
remaining cervical vertebrae, and no obvious abnormally enhanced foci were observed
after enhancement, suggesting that osteoblastoma was likely. A total bone single-
photon emission computed tomography (SPECT) scan showed a slight increase in
bone metabolism in the upper cervical vertebrae and the 9th thoracic vertebra,
suggesting that positive changes were likely.

FINAL DIAGNOSIS
The patient was diagnosed with a TGCT.

TREATMENT
After the preoperative requirements of the antituberculosis treatment were met, we
were ready to perform surgery. After anesthesia was successfully induced, cranial ring
arch traction was established. The operation was performed via the posterior approach
of the cervical spine. The posterior structure of C2-C7 was exposed by incision and
dissection to the paravertebral muscles on both sides. Bilateral pedicle screws were
implanted at C2 and C7, and a pair of lateral mass screws were implanted bilaterally at
C3, on the left side at C4, on the right side at C5, and bilaterally at C6. After that,
titanium rods were connected to the screws. After fixation, the corresponding lamina
was removed, and the egg-sized mass was visible, with an obvious boundary at the
lower edge of C3, at C4/5, and at the upper edge of the C6 spinous process
(Figure 2A). The cervical spinal canal as well as the nerve roots was decompressed
until the spinal cord was relaxed and free of pressure; spinal cord pulsations were
observed to return, and exploration of the spinal canal showed patency (Figure 2B).
The surgical field was then soaked in distilled water, rinsed with saline, and
thoroughly hemostatic. Next, an autologous cancellous bone graft was placed, and a
silicone drain was left in place. Finally, the wound was sutured layer by layer and
covered with a sterile dressing, the circumference of the neck was protected, the
cranial ring arch was removed, and the patient was sent to the postanesthesia care unit
and returned to the ward. The entire procedure took 4.5 h.

OUTCOME AND FOLLOW-UP

The tumor and adjacent normal tissue were completely removed and sent for
cryosection and routine pathological examinations (Figure 2C). Lymphatic, plasma-
like, and multinucleated cellular infiltrates were seen in the spine at the C4-5 level, and
routine pathology and immunohistochemistry were needed to exclude hematopoietic
tumors (Langerhans’ histiocytic hyperplasia, etc.), as shown by the cryosection

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 Zhu JH et al. TGCT involving the cervical spine

Figure 1 Preoperative X-ray, computed tomography, and magnetic resonance imaging images. A: Plain X-ray of the cervical spine showing
destructive lesions (orange arrow) in the appendage area of the C4-5 vertebras; B: Plain computed tomography (CT) of the cervical spine showing bone destruction
(orange arrow) and a soft tissue mass in the appendage area of the C4-5 vertebras; C: CT three-dimensional imaging of the cervical spine showing the outline of
bone destruction (orange arrow) in the appendage area of C4-5; D: Magnetic resonance imaging showing bone destruction and soft tissue formation (orange arrow)
in the C4-C5 accessory region, suggesting the possibility of an invasive, benign bone tumor (e.g., osteoblastoma), and significant compression of the spinal cord and
stenosis at the corresponding plane.

Figure 2 Intraoperative images. A: Operative view of the lesion between the C3 and C6 spinous process lamina; B: View of the surgeon after lesion removal
and spinal canal and nerve root canal decompression; C: Nodular fragment of tissue, measuring 7.2 cm × 6.5 cm × 5.4 cm after resection.

examination results. Tumor tissues were taken for routine pathology combined with
immunohistochemistry, with the following results: CD138 (-), CD68 (+), H3.3G34W (-),
EMA (-), SATB2 (-), vimentin (+), S-100 (+), CD1a (-), Langerin (-), CD163 (-), and Ki67
(+, 10%), suggesting tendon sheath giant cells (Figure 3). Comprehensive consideration
of the histopathological and immunohistochemical findings indicated that the tumor
was a TGCT.
X-ray radiography performed 4 d after the surgery showed that the screws and
titanium rods were in a good position, with no obvious loosening. The neck pain
disappeared, the muscle strength of both lower extremities returned to grade 4, and
limb sensation returned to normal after 2 wk of postoperative rehabilitation. There
were no signs of internal fixation loosening on X-ray examination and no signs of local
recurrence on MRI at the follow-up 1 year postoperatively (Figure 4).

DISCUSSION
TGCTs generally occur in the fingers, as well as in the ankles, wrists, and small joints
of the lower limbs, but rarely in the spine[3]. Kleinman et al[3] first reported the case of
a 65-year-old woman with a TGCT located in the cervical spine in 1980[3]. According
to Wang et al[4], the cervical spine is the most common site of spinal TGCTs, followed
by the lumbar spine and thoracic spine[4]. TGCTs of the spine usually originate from
the synovium of the facet joints, grow diffusely outside the joints, and invade nearby

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Zhu JH et al. TGCT involving the cervical spine

Figure 3 Pathological images of the mass. The histopathological analysis mainly showed proliferating monocytes and osteoclastic multinucleated giant cells.
A: Image at 40 × magnification; B: Image at 200 × magnification.

Figure 4 X-ray and magnetic resonance imaging review images at 1 year postoperatively. A: X-ray showing good fixation with no loosening of the
internal fixation; B: Magnetic resonance imaging showing no signs of recurrence (orange arrow).

vertebrae[5].
The most common origin of TGCTs has been reported to be the synovial membranes
of the facet joints and bursa, depending on the location and growth characteristics,
which can be classified as localized or diffused[6]. The diffuse type of TGCT affects the
synovial membranes of large joints, such as the knees, hips, ankles, and elbows, while
the localized type usually involves the tendons of the hands and feet[6]. TGCTs are
also divided into intraarticular and extraarticular according to the site of growth.
Intraarticular, diffuse TGCTs are also known as hyperpigmented villous nodular
synovitis (PVNS); extraarticular tumors are slowly growing lesions with an excellent
prognosis and can usually be removed completely. The etiology of PVNS is still
controversial. Some scholars believe that it is an abnormality in lipid metabolism
secondary to inflammatory trauma, others insist that it is a response to chronic trauma
and recurrent bleeding, and others insist that it is a tumor[7-9]. The different types of
TGCTs share the same morphological features on microscopy, mainly consisting of
large synovial-like monocytes, small mononuclear histiocytes, and osteoclast-like giant
cells.
Although there is no conclusive evidence regarding the cell of origin of TGCTs,
most authors agree that TGCTs originate from fibroblasts and histiocytes of the
synovium[10]. West et al[11] determined that the colony-stimulating factor 1 (CSF1)
gene encoding the CSF1 receptor ligand is translocated in only 2% to 16% of tumor
cells, suggesting that only a minority of TGCT cells are tumor cells[11]. By reviewing
81 cases of TGCT, Rao et al[12] demonstrated that the process of diffuse TGCT (also
known as PVNS) formation is neoplastic[12]. TGCTs have been classified as fibrous
histiocytic tumors in the World Health Organization (2012) classification of soft tissue
and bone tumors.

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 Zhu JH et al. TGCT involving the cervical spine

TGCTs of the cervical spine originate in the synovium of the trabecular joint and
grow out of the joint, but in one case, it was reported that the tumor bulged into the
trabecular joint[6]. In our case, the tumor most likely originated in the cervical facet
joints in the corresponding segments and grew slowly extra-articularly, eroding the
spinous processes and vertebral plates, with clear borders of the lesion observed
intraoperatively. Typically, giant cell tumors of the tendon sheaths present as slow-
growing, extraarticular masses with clear borders that cause little discomfort[13]. If the
tumor does not compress the spinal cord, the patient may be asymptomatic, but if it
compresses the spinal cord and nerve roots, it may manifest as a series of neurological
symptoms, so the size and location of the tumor determine whether the tumor can be
detected at an early stage[14]. In our case, the patient initially developed a series of
symptoms related to compression of the spinal cord and the C6 nerve root, which led
to the discovery of a giant cell tumor of the cervical spine.
The classical appearance of tenosynovial cell tumors on X-rays is only a soft tissue
mass, but sometimes they can also show calcification and, in rare cases, a periosteal
reaction, which is not classical and makes the differential diagnosis difficult[15]. CT
images of TGCTs show low soft tissue density; lesions may occasionally show high
density with iron-containing heme, and images of eroded bone may be seen inci-
dentally. In terms of MRI, TGCTs presented hypointense or isointense signals on T1WI
and moderate hypointense signals on T2WI. The hypointense signals on T2WI are
particularly affected by the amount of iron-containing heme, but other influences
include lipids, fibrous tissue, cyst formation, and cellular components[2,16].
In our reported case, CT revealed bone destruction and a soft tissue mass of an
undetermined nature in the C4-5 adnexal region, and a benign bone tumor was
considered likely. MRI indicated bone destruction and soft tissue formation in the C4-5
adnexal region, and a benign bone tumor with aggressive manifestations was
considered likely (most likely an osteoblastoma). SPECT demonstrated slightly
increased bone metabolism in the high cervical and 9th thoracic vertebrae, with a high
likelihood of the lesion being benign. None of the radiographs could confirm the
diagnosis of a TGCT, and we considered the differential diagnosis to include a giant
cell tumor of bone, nerve sheath tumor, neurofibroma, tendinous fibroma, synovial
sarcoma, and osteoblastoma, so we chose to perform a biopsy to help confirm the
diagnosis. The pathological results of preoperative CT-guided biopsy showed only a
small amount of giant cell-rich tissue, and the final mass dissected intraoperatively
was sent for routine pathological testing and further immunohistochemistry to
confirm the diagnosis of a TGCT. This suggests that single-modality imaging and
preoperative and intraoperative pathological examinations may not always confirm
the diagnosis and that further immunohistochemical analysis will ultimately lead to
accurate conclusions and provide better guidance for further postoperative treatment.
Currently, the primary treatment for TGCTs of the spine is surgery, and internal
fixation is not necessary due to the absence of bone destruction and intervertebral
instability. In our case, there was significant bone destruction, and to remove the
tumor completely, a portion of the posterior cervical column had to be removed, so we
performed internal fixation after tumor removal. The primary consideration for
surgical intervention is its propensity for local recurrence, which is closely related to
the extent of surgical resection. Furlong et al[17] showed that in the follow-up of
patients with TGCTs of the spine, no recurrence was found from 4 mo to 9 years after
major or extensive tumor resection in five of the patients, while four of them
experienced recurrence after incomplete resection for various reasons and thus also
underwent secondary resection[17]. Furlong et al[17] also concluded that the diffuse
growth pattern, the number of osteoclast-like giant cells, and the degree of epidural
involvement were all associated with local recurrence, whereas the size and location of
the tumor at the time of resection, patient sex, collagen content, and presence or
absence of trabecular joint involvement were not associated with patient prog-
nosis[17]. The complete removal of TGCTs is usually considered to be of paramount
importance for the prognosis, and every effort should be made to achieve major total
resection during the first surgery. However, in the spine, especially spinal
attachments, it is not possible to perform complete total resection, so in cases where
total resection is not possible, performing subtotal resection has the potential for early
recurrence. This suggests the importance of postoperative follow-up. The local
recurrence rate of TGCTs in the spinal region is estimated to be approximately 20%,
which is comparable to the recurrence rate of TGCTs in the adnexal skeleton[6].
Patients are usually advised to be followed at regular intervals of 3 mo, 6 mo, 1 year, 2
years, 3 years, and 5 years, during which a timely reoperation to remove the TGCT is
necessary once recurrence is detected.

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There is no clear data in the literature to support whether radiation therapy after
primary tumor resection helps prevent postoperative recurrence. The current
consensus is that radiotherapy is given only to patients who, for various reasons, are
unable to have their lesions removed[17]. TGCTs express high levels of CSF1R, which
suggests that some chemotherapy regimens may also be effective for treatment. 1p11-
13 is the most common region of structural rearrangement in TGCTs, and the most
common chromosomal translocation is t(1:2)(p13:q37), where genetic fusions of CSF1
to COL6A3 were identified in molecular pathology studies[11,18]. CSF1, also known as
macrophage colony-stimulating factor, is an important inflammatory mediator of
inflammatory arthritis, and CSF1 expression is upregulated in both chronic inflam-
mation and tumors[19]. CSF1 regulates the growth, proliferation, and differentiation of
mononuclear macrophages and the generation of osteoclasts while facilitating the
migration of endothelial progenitor cells from the bone marrow into the peripheral
blood. The CSF1 chromosomal translocation in tumor cells allows the accumulation of
a large number of reactive CD68-positive macrophages[19]. CSF1R is a tyrosine kinase
class III receptor encoded by the tumor suppressor gene c-fms and is primarily
expressed in mononuclear macrophages, which require CSF1 to function via CSF1R.
West et al[11] concluded that the COL6A3-CSF1 gene fusion resulted in the over-
expression of CSF1 and that CSF1 was only expressed in cells in which a COL6A3-
CSF1 chromosomal translocation had occurred[11]. Conversely, Cupp et al[20] found
that CSF1 expression was also upregulated in cases of TGCTs without a COL6A3-CSF1
chromosomal translocation, indicating that the upregulation of CSF1 expression was
not related to the occurrence of a chromosomal translocation at the CSF1 locus, and
suggested that targeting CSF1/CSF1R may be the most promising treatment for
TGCTs[20,21]. Several publications have reported favorable results when imatinib is
used in patients with incomplete tumor resection and recurrence[22-24]. Imatinib
inhibits tumor growth by inducing CSF1R activation[24]. Cassier et al[24] conducted an
international multicenter retrospective study to evaluate the efficacy of imatinib in
locally advanced/metastatic PVNS/TGCTs, with 1 case of complete remission, 2 cases
of partial remission, and 8 cases of stable disease among 16 patients, and these results
fully confirm the efficacy of imatinib in PVNS/TGCTs[24]. In addition, many scholars
have applied nilotinib and emactuzumab in recurrent cases and achieved good
therapeutic results, indicating that molecularly targeted therapies are promi-
sing[21,25-28]. On August 2, 2020, the Food and Drug Administration announced the
approval of the novel oral drug pexidartinib (Turalio, Daiichi Sankyo) for the
treatment of adult patients with symptomatic TGCTs who are severely limited in
physical function and whose condition cannot be improved by surgery. This new oral
drug is also effective in inhibiting CSF1R to produce therapeutic effects[29].

CONCLUSION
We report a rare case of TGCT originating from the synovium of the C4-5 facet joint.
The radiological changes were not specific and puncture biopsy was only informative;
immunohistochemistry was needed for final confirmation of the diagnosis. The ideal
treatment comprised complete resection of the mass and appropriate internal fixation,
with complete resection or incomplete resection determining the likelihood of
postoperative revision. Adjuvant radiotherapy and chemotherapy are currently used
in cases of unresectable, residual, or recurrent disease. A review of this case will
provide a better understanding of the characteristics of TGCTs of the spine and
improve their diagnosis and treatment.

ACKNOWLEDGEMENTS
We would like to thank our patient for generously allowing us to share his case and
Dr. Zhou JY for providing the pathological images.

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