Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 29 (2017) 122128

Contents lists available at ScienceDirect

Journal of Oral and Maxillofacial Surgery,

Medicine, and Pathology
journal homepage: www.elsevier.com/locate/jomsmp

Case Report

The challenge in the treatment of central giant cell granuloma What

is the best approach?
Natlia B. Daroit a, , Ricardo G. de Marco a,1 , Manoel SantAnna Filho b,2 ,
Guilherme G. Fritscher a,3
a
Oral and Maxillofacial Surgery of So Lucas University Hospital, Pontical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681, Prdio 06,
Porto Alegre/RS, CEP: 90619-900, Brazil
b
Oral and Maxillofacial Surgery of School of Dentistry in Pontical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681, Prdio 06, Porto
Alegre/RS, CEP: 90619-900, Brazil

a r t i c l e i n f o a b s t r a c t

Article history: The central giant cell granuloma consists of a non-neoplastic benign proliferative process, which repre-
Received 25 February 2016 sents about 7% of lesions of the jaws. There are many choices to be performed regarding treatment; an
Accepted 10 May 2016 aggressive curettage or total resection is traditionally recommended, which ends up being mutilating.
Available online 19 November 2016
Conservative therapies, alternatively or in combination with surgery, are used to minimize the anatom-
ical, functional and esthetic post-surgical damage. Furthermore, there are reported cases of complete
Keywords:
regression of the lesions spontaneously. If the treatment results in loss of teeth, the prosthetic rehabil-
Giant cell granuloma
itation phase begins after epithelialization of the surgical wound and focuses on restoring the patients
Treatment
Mouth rehabilitation
esthetics, speech and swallowing, as well as their self-esteem. The goal of this study is to discuss therapies
and procedures for this pathology, and it also describes two clinical cases: from diagnosis and treatment,
to rehabilitation and follow up of these patients. Finally, follow up is crucial for successful treatment.
2016 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.

1. Introduction
The World Health Organization denes the central giant cell
granuloma (CGCG) as an intraosseous lesion consisting of brous
tissue containing multiple foci of hemorrhage, aggregations of
multinucleated giant cells and occasionally trabeculae of bone tis-
sue [1].
In 1986 Chuong classied it into: aggressive, which is charac-
terized by one or more aspects: pain, paresthesia, root resorption,
rapid growth, cortical perforation and a high rate of recurrence;
and nonaggressive, which presents itself asymptomatic, evolves
slowly, does not produce root resorption and exhibits a low rate
of recurrence [2]. CGCG affects mainly children and young adults,
Asian AOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian
Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathol-
ogy; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese
Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants.
Corresponding author. Tel.: +55 51 8191 5410/51 3779 5030.
E-mail addresses: nataliadaroit@yahoo.com.br (N.B. Daroit),
ricardogdemarco@hotmail.com (R.G. de Marco), manoel@ufrgs.br
(M. SantAnna Filho), guilherme.fritscher@pucrs.br (G.G. Fritscher).
1 ment of CGCG can be performed employing many techniques, from
Tel.: +55 51 9648 6596.
2
Tel.: +55 513308 5011.
3
Tel.: +55 51 9916 6945.
approximately 75% of cases until the age of 30 [3]. The mandibular
bone is affected in 70% of cases [4].
Differential diagnosis should include ameloblastoma, cheru-
bism, and aneurysmal bone cyst. In addition, CGCG is histologically
similar to brown tumor of hyperparathyroidism, which should be
excluded by biochemical exams [4]. When the lesion presents a
unilocular defect, the hypothesis of maxillofacial cysts should be
discarded [5].
The etiology of CGCG is unknown, however, it may be associated
with a local trauma, repair processes, or developmental distur-
bance, or even be dened as an inammatory lesion, a true tumor
or an endocrine lesion [6]. Due to the fact that the origin of the
lesion is not clear, the professional facing this pathology may use
different approaches.
The treatment of this lesion is very challenging because there
are several therapies and procedures, from the most conservative,
such as corticosteroids, calcitonin, interferon and bisphospho-
nates [711], to more radical therapies such as surgical enucleation
with curettage to resection [1214]. A comparative table of the pos-
itive and negative aspects of each procedure against CGCG, which
will be discussed posteriorly, is shown below (Table 1).
The rehabilitation of the defect resulting from surgical treat-
a removable tooth or implant supported prosthesis to bone grafts
[12]. Follow up must be a stage of great importance in CGCG since

http://dx.doi.org/10.1016/j.ajoms.2016.05.009
2212-5558/ 2016 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.
 N.B. Daroit et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 29 (2017) 122128 123

Table 1
Comparison of treatment alternatives for CGCG.

Administration Cost Success rate Recurrence Morbidity

Curettage 0 + + +
Resection 0 + + ++
Calcitonin ++ + + +
The patient can perform
(subcutaneous injections
or nasal spray)
Intralesional steroids + + +
The professional should (more successfully
apply numerous painful in unilocular
injections and the nal lesions)
stage occur a difculty of
application.
Interferon + + + +
(subcutaneous injections) (adjunctive a
surgery)
Bisphosphonates + + + ? +
(oral or intravenous) (new approach,
requires follow-up)
Spontaneous regression 0 0 + ? ++
(new approach,
requires follow-up)

+, positive aspect; , negative aspect; +, controversy aspect; 0, not applicable.

the recurrence rate varies considerably from 11% to 49% for nonag-
gressive lesions, while reaching 72% for aggressive [11].
This study aims to discuss the treatment options for this pathol-
ogy, highlighting positive and negative aspects of each of them, and
presenting the clinical management of 2 cases of CGCG. This study
followed the Declaration of Helsinki on medical protocol and ethics,
and the regional Ethical Review Board of the Scientic Committee
of the School of Dentistry of PUCRS approved the work.
2. Case reports
maxillary sinus to the bone crest inferiorly, with displacement of
teeth 12 and 13 (Fig. 1).
The diagnostic hypotheses were CGCG, keratocystic odonto-
genic tumor, aneurysmal bone cyst and ameloblastic broma.
Incisional biopsy of the lesion was performed and sent for
histopathological examination.
Histologically, the appearance was young connective tissue
with proliferation of cylindrical and polyhedral cells and foreign
body type giant cells (Fig. 2), with CGCG as the nal diagnosis.
Thus, serum levels of calcium, phosphate, alkaline phosphatase
and parathyroid hormone (PTH) were requested to rule out hyper-
parathyroidism, with results within normal limits.
Initially, conservative treatment with intranasal salmon cal-
citonin 20 mg, 1/day, was determined. This therapy was not
successful due to the fact that the patient did not make contin-
uous use of it, and the lesion remained the same size. Computed
tomography was performed, showing invasion in the right maxil-
lary sinus, compromising its walls, and also in the right nasal cavity
causing deviation of the nasal septum to the left (Fig. 3). Thus, total
surgical resection of the lesion under general anesthesia was done
(Fig. 4).
After epithelialization of the wound, a partial removable dental
prosthesis was made for the patient (Fig. 5). Follow up of the lesion

Fig. 1. Panoramic radiograph showing a radiolucent area in the region between

teeth 11 through 15, from the boundaries of the maxillary sinus to the bone crest,
with displacement of teeth 12 and 13.

2.1. Case 1

A male patient, age 14, Caucasian, with no systemic impairment,

sought care at the Oral and Maxillofacial Surgery Service at the
School of Dentistry of PUCRS, whose main complaint was an asymp-
tomatic swelling. Upon extraoral clinical examination, an elevation
of the upper lip and nasal wing on the right side was observed, while
intraorally a swelling covered by normal mucosa, involving teeth
11, 12, 13, 14 and 15 was observed.
Upon radiographic examination, the lesion presented a radiolu- Fig. 2. Photomicrograph of young connective tissue with proliferation of cylindrical
cent appearance from tooth 11 to 15, being the upper limit the and polyhedral cells and foreign body type giant cells (hematoxylin/eosin).
124 N.B. Daroit et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 29 (2017) 122128

Fig. 3. (A) Coronal tomographic section showing inltration of the lesion in the right maxillary sinus, compromising its walls and also the right nasal cavity, causing deviation
of the nasal septum to the left. (B) Axial tomographic section showing osteolysis of the buccal cortical of the right maxilla and bone expansion with thinning of the palatal
cortical.

with the Oral and Maxillofacial Surgery division of PUCRS showed
no signs of clinical or radiographic recurrence of the lesion in an
18-month period.
2.2. Case 2
Female patient, 31 years old, Caucasian, with no systemic
impairment, sought care at the same service, whose main
complaint was an asymptomatic swelling in the left maxillary
region, with an evolution of approximately 3 months.
Upon extraoral clinical examination, an elevation of the
upper lip on the left side was noticed. Intraorally, an exo-
phytic lesion in the left maxillary region, rm to palpation,
between teeth 23 and 24 (Fig. 6) was observed. A sen-
sitivity test was conducted on such teeth with positive
results.

Fig. 4. (A) Aspect of intraosseous lesion. (B) Transoperative aspect of the surgical site, showing the boundaries of the resection of the lesion. (C) The immediate post-operative
aspect. (D) View of the surgical specimen in the anteroposterior direction. (E) View of the surgical specimen in the posterior-anterior direction.
 N.B. Daroit et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 29 (2017) 122128
Fig. 5. (A) Postoperative anteroposterior aspect. (B) Postoperative lateral aspect. (C) Postoperative occlusal aspect. (D) Anteroposterior aspect of removable prosthesis. (E)
Lateral aspect of the removable prosthesis. (F) Occlusal aspect of the removable prosthesis.
Radiographically, an ill-dened unilocular radiolucent area was
evidenced involving teeth 23 and 24, with tooth displacement
(Fig. 7).
The diagnostic hypotheses, considering the clinical and radio-
graphic ndings, were CGCG, traumatic bone cyst, ameloblastoma,
keratocystic odontogenic tumor, odontogenic myxoma, and
aneurysmal bone cyst.
Histopathological diagnosis after incisional biopsy conrmed
CGCG. Serum levels of calcium, phosphate, alkaline phosphatase
and parathyroid hormone (PTH) were requested, with results
within normal limits.
An attempt was made to obtain salmon calcitonin via Unied
Health System (SUS), unsuccessfully. Computed tomography of
the region was performed, showing a lesion of inltrative aspect
that compromised soft tissues of the left maxillary region, involv-
ing the maxillary bone which presented osteolysis. There were
hyperdense areas within the lesion that could be translated as
bone fragments. The inltration extended to the base of the left
nasal wing, also causing thinning of the bone portion of the oor
Fig. 6. Clinical aspect of the lesion in the left maxilla.
125
of the left maxillary sinus without signs of it being invaded (Fig. 8),
thus surgical resection was chosen (Fig. 9).
In the postoperative period the surgical wound had com-
plete epithelialization, with no oroantral communication, thus the
patient was referred to confection of a dental prosthesis (Fig. 10).
Fig. 7. Panoramic radiograph showing a radiolucent area involving teeth 23 and 24.
3. Discussion
The treatment of CGCG is a challenge; literature shows several
studies with many alternatives and various success rates [1418]. In
this paper we discuss different types of therapy in order to help the
professional who is handling the case to make the decision together
with the patient, considering the pros and cons of each of them.
The surgical treatment, as shown in the present case reports,
was recommended for being the most traditional, with higher suc-
cess rates, and therefore a lower chance of recurrence of the lesion
[1214]. Curettage is associated with a higher rate of lesion recur-
rence which can reach 1149% for nonaggressive lesions [11]; when
compared to surgical resection, which is more aggressive, it is asso-
ciated with a low rate of recurrence of the pathology [12].
We emphasize that other more conservative therapies can be
great alternatives before performing a more mutilating treatment,
particularly when attending children, or when the lesion involves
important anatomic structures, such as teeth. Salmon calcitonin
acts by inhibiting giant cells and their osteoclastic function [19],
and studies using calcitonin nasal spray daily, noted a decrease in
the size of the lesion, with increase in bone repair with no signs
126 N.B. Daroit et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 29 (2017) 122128

Fig. 8. Axial tomographic sections showing swelling in soft tissue and osteolysis of the maxillary cortical bone.

of recurrence. Thus, even if complementary surgery is required
in certain cases, with the use of calcitonin, there is a decrease
and denition of lesion limits, reducing the extent of damage and
post-surgical morbidity [16,20]. It is known that this drug acts
on the calcitonin receptors present on CGCG, however, not all of
the lesions have receptors; in this way the treatment becomes
ineffective, which explains the variability in success rate [21].
This was the rst choice of treatment for both patients, due to
the fact that besides being painless, the patient could administer
the drug himself. However, due to the high cost patients were not
able to acquire the medication, nor was it provided by the Unied
Health System, hence it was discontinued, becoming an ineffective
treatment, as shown in our cases.
Intralesional steroid injection has been reported with good
results; the most utilized drug is triamcinolone [22]. The mecha-
nism that best explains the use of this medication is that lysosomal
proteases produced by giant cells are inhibited, and steroids also
induce apoptosis of osteoclast-like cells [15]. Special attention
should be given to the side effects of administration of this drug,
such as cushingoid appearance [23]; additionally, after a period
of administration, peripheral bone formation is observed causing
technical difculty for intralesional injection, and so the lesion
tends to recur [20].
Kaban et al. propose the use of an antiangiogenic drug, being
interferon administered daily by subcutaneous injection the most
utilized. This therapy alone is not able to inhibit proliferating tumor
cells and osteoclast activity, so it must serve as an adjunct to
surgery, thus, the use is normally post-surgical [9]. The positive
aspect is that this drug has properties that differentiate mesenchy-
mal cells into osteoblasts, aiding in bone formation [17]. Despite
some promising results, and besides this treatment being expen-
sive, there are reports in literature of systemic complications, from

Fig. 9. (A) Transoperative aspect of the surgical site showing the boundaries of the resection of the lesion. (B) The immediate post-operative aspect. (C) View of the surgical
specimen in the anteroposterior direction. (D) View of the surgical specimen in the inferosuperior direction.
 N.B. Daroit et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 29 (2017) 122128
Fig. 10. (A) Post-operative intraoral photograph after 30 days. (B) Intraoral photograph at 6 months postoperatively. (C) Lateral view of the dental prosthesis.
the simplest such as headache, fever, and chills, to more serious
immune-mediated ones such as drug-induced lupus [24].
Recently, bisphosphonates such as alendronate sodium and
zoledronic acid have been administered for CGCG adjunct to other
therapies with some good results [10,18]. The mechanism through
which this medication works is avoiding osteoclast progenitor for-
mation and then, the bone reabsorption is impaired [25]. The risk
of osteonecrosis of the jaw is associated with the use of this drug,
especially the intravenous form, but this side effect depends on the
length of treatment, the route of administration and predisposing
factors such as history of trauma, dental surgery or dental infection
[26].
Total spontaneous regression after incisional biopsy has been
described in some case reports [27,28]. Berti et al. suggest that sur-
gical intervention for establishing the diagnosis causes a blood clot
to form inside the lesion, thus decreasing osteoclast activity and
activating the osteoblasts, resulting in bone repair. This type of pro-
cedure is also found in the treatment of aneurysmal bone cysts or
traumatic bone cysts in which some authors infer that they are very
similar pathogenetically [29,30].
Based on these cases and on the current literature, we suggest
that the rst choice should be a non-invasive treatment, mainly
calcitonin or corticoids, due to a longer usage period, cost and
good results. If the use of adjuvant therapies is not a possibil-
ity, surgery should be performed, and particular attention should
be given to post-surgical prosthetic rehabilitation aiming at the
quality of life of patients. The postoperative follow-up should be
performed with strict attention in order for the treatment to be
successful.
Ethical approval
The regional Ethical Review Board of Scientic Committee of
the School of Dentistry and Ethics Committee of PUCRS approved
the work, the patients were informed and gave consent to this
publication.
Conict of interest
The authors declare that there is no conict of interests regard-
ing the publication of this paper.
Acknowledgments
So Lucas University Hospital of PUCRS and School of Dentistry
of PUCRS.
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