CLINICOTHERAPEUTIC CONFERENCE

J Oral Maxillofac Surg

68:2537-2544, 2010
Aggressive Central Giant Cell
Granuloma of the Mandible
Petr Schtz, MD,*
Khalid H. El-Bassuoni, BDS, HDD, FDSRCS Ed,
Joneja Munish, MSc, FRCPath,
Hussein H. Hamed, BDS, HDD, MSc, PhD, and
Bonnie L. Padwa, DMD, MD
Case Presentation
An 11-year-old Egyptian boy presented with mild pain in his
left lower jaw accompanied by swelling. Clinical examination
showed a hard, tender mandibular enlargement extending
from the chin to the left molar area. The orthopantomogram
(OPG) showed poorly dened multilocular radiolucency in-
volving the mandibular body from the right lateral incisor to
the left rst molar (Fig 1A). There were discrete signs of
resorption of root apices of the adjacent teeth. Computed
tomography examination disclosed a large expansive osteo-
lytic lesion with a soap bubble appearance and erosion of both
vestibular and lingual mandibular cortices (Fig 1B).
Incisional biopsy was performed under local anesthesia.
Sections contained spindle cells within brous stroma and
irregularly distributed multinucleated giant cells clustering
around areas of hemorrhage. Periphery of the lesion
showed reactive osteoid tissue formation (Fig 1C).
The overall clinical, radiologic, and histopathologic picture
was consistent with central giant cell granuloma. Laboratory
investigations including complete blood count, alkaline phos-
phatase, calcium, and parathormone levels were within nor-
mal limits, while phosphorus level was slightly elevated.
Treatment Recommendations
Bonnie L. Padwa, DMD, MD
Giant cell lesions (GCLs) of the jaws are found in
the mandible more commonly than the maxilla, and
in females more often than in males. These benign
lesions occur before the age of 30 years.
1
GCLs are
usually unifocal. Multifocal lesions should alert the
clinician to the possibility of hyperparathyroidism
or, if bilateral, cherubism or Noonan syndrome.
1,2
GCLs are osteoclast-rich tumors that are histopatho-
logically indistinguishable from those seen in
cherubism and Noonan syndrome. Nevertheless, pa-
tients with isolated GCLs do not have the cherubism-
related germline SH3BP2 mutation, and the lesions do
not contain somatic SH3BP2 mutations.
3
This nding
suggests that even though all GCLs might appear the
same histologically, they likely have a different etio-
pathogenesis.
The rst description of GCLs was by Jaffe
4
in 1953.
However, confusion remains about the nature of the
lesion (reactive/inammatory, neoplastic), the cell of
origin, and the variability in clinical behavior. Thus,
an assortment of treatment modalities, with different
mechanisms of action, have been tried in patients
with a variety of lesions with inconsistent outcomes;
all of which has made deciphering the best treatment
option difcult for the practitioner.
The histopathologic features of GCLs are a large
number of multinucleated giant cells and mononu-
clear cells within a brous stroma. The giant cells in
GCL may be reactive or secondary, not the cell of
origin. Macrophages, mesenchymal cells, and bro-
blasts have all been proposed as being responsible for
the lesion.
5
There is variability in the clinical behavior of GCLs.
Rapidly growing expansile lesions with an aggressive
appearance (eg, pain, paresthesia, root resorption)
are at one end of the spectrum and small asymptom-
atic slow-growing lesions are at the other end.
Chuong et al
6
categorized the clinical and radio-
*Consultant, Head of Oral, Maxillofacial Surgery Unit, Al-Adan
Dental Center, Ministry of Health, Kuwait City, Kuwait.
Senior Registrar, Oral and Maxillofacial Surgery Unit, Al-Adan
Dental Center, Ministry of Health, Kuwait City, Kuwait.
Head of Histopathology Unit, Radiology, Nuclear Medicine and
Laboratory Center (YIACO Medical Co), Al-Adan Hospital, Kuwait
City, Kuwait.
Senior Registrar, Oral and Maxillofacial Surgery Unit, Al-Adan
Dental Center, Ministry of Health, Kuwait City, Kuwait.
Associate Professor of Oral and Maxillofacial Surgery, Harvard
School of Dental Medicine, and Oral Surgeon-in-Chief, Department
of Plastic and Oral Surgery, Childrens Hospital, Boston, MA.
Address correspondence and reprint requests to Dr Schtz: Box
3021, 22031 Salmiya, State of Kuwait; e-mail: petrschutz@yahoo.
com
2010 American Association of Oral and Maxillofacial Surgeons
0278-2391/10/6810-0024$36.00/0
doi:10.1016/j.joms.2009.06.042
2537
graphic features of aggressive GCLs: 1) size greater
than 5 cm, 2) rapid growth, 3) recurrence after cu-
rettage, 4) cortical bone thinning and/or perforation,
and 5) tooth displacement and/or resorption.
Because the cell of origin is unknown and histolog-
ically aggressive and nonaggressive GCLs appear the
same through the microscope, many groups have
considered biomarkers as a means of identifying ag-
gressive versus nonaggressive lesions and correlating
these with the clinical behavior and treatment out-
come. A wide variety of parameters, including the
number and size of the giant cells, the mean number
of nuclei per giant cell, the fractional surface area
occupied by giant cells, the DNA content, mitotic
activity, and the immunohisotologic features have
been studied in an attempt to distinguish aggressive
and nonaggressive subtypes and to predict prognosis
and response to treatment.
6-10
Aggressive/recurring
lesions have been found to have a higher number and
relative size index of giant cells and a greater frac-
tional surface area occupied by giant cells.
6,8
Addi-
tionally, aggressive subtypes have been shown to ex-
press a greater count of nucleolar organization
regions.
9
The angiogenic activity of GCLs was proposed as a
determinant of the aggressive nature of GCLs. Vered
et al
11
were unable to nd elevated vascular endothe-
lial growth factor and broblast growth factor in these
tumors and concluded that GCLs have low angiogenic
activity. Dewsnup et al
12
studied the expression of
CD34, a cellcell adhesion factor and cell-surface gly-
coprotein found in hematopoietic precursor and cap-
illary endothelial cells. They determined that clinically
aggressive giant cell tumors have an increased vascu-
lar density compared with nonaggressive lesions
based on CD34 staining. Furthermore, they suggested
that CD34 evaluation can identify aggressive lesions
amenable to antiangiogenic therapy, even at the time
of biopsy.
12
This same group subsequently showed
that CD34 staining density levels of more than 2.5%
were associated with aggressive GCLs.
13
These nd-
ings strongly suggest that the CD34 staining density
level has a high positive predictive value for biologic
behavior and might help in planning treatment and
predicting outcome.
One treatment of GCLs is enucleation and curet-
tage, with or without adjunctive therapy, such as
peripheral ostectomy
1
and liquid nitrogen cryothera-
py.
14
Although nonaggressive lesions of the jaw are
successfully managed with curettage and have a low
recurrence rate, aggressive lesions have a recurrence
rate of 70%.
15
The gold standard for the treatment of aggressive
GCL is en bloc resection.
16
Given that these lesions
frequently occur in children and resection of vital
structures for treatment of a benign lesion can result
FIGURE 1. A, OPG at the time of presentation. B, Axial computed
tomography scan shows multilocular appearance of the lesion with
erosion of both lingual and vestibular cortices. C, Photomicrograph
showing mass of granulationlike tissue containing numerous oste-
oclastlike giant cells with scattered inammatory and hemosiderin
laden macrophages. Areas of hemorrhage are present. Inset: Oc-
casional bone formation is evident with above features (H&E stain-
ing; 100).
Schtz et al. Aggressive Central Giant Cell Granuloma of The
Mandible. J Oral Maxillofac Surg 2010.
2538 AGGRESSIVE CENTRAL GIANT CELL GRANULOMA OF THE MANDIBLE
in functional, esthetic, and psychological problems,
alternatives to resection have been attempted.
17
These have included intralesional steroids, systemic
calcitonin, and systemic interferon alpha-2a com-
bined with curettage.
18-20
Vered et al
17
immunohistochemically stained
mononuclear and giant cells for glucocorticoid and
calcitonin receptors in an attempt to provide a reli-
able and practical tool for selecting an appropriate
therapeutic agent to treat GCLs. They found that the
mononuclear and giant cells of GCLs stained for both
glucocorticoid and calcitonin receptors. Flanagan et
al
21
proposed intralesional corticosteroid for GCLs.
Their reasoning was that multinucleated giant cells
are osteoclasts and dexamethasone has been shown
to inhibit osteoclast-like cells in marrow cultures.
22
Jacoway et al
23
noted the microscopic similarities
between sarcoidosis and GCLs and also suggested
treatment with corticosteroids. A few successful case
reports have been published of GCLs treated by
weekly intralesional injection with corticoste-
roids.
18,24-26
However, it is unclear from these reports
whether the lesions treated with corticosteroids were
nonaggressive or aggressive subtypes. The smattering
of case reports does not allow surgeons to evaluate
the clinical effectiveness of this therapy. A large series
or a randomized trial with reported success rates in all
types of lesions is necessary to adequately evaluate
this treatment.
Giant cells in GCLs have also been shown to have
calcitonin receptors.
27
Calcitonin inhibits osteoclast/
giant cell function and has been suggested as a treat-
ment modality. Harris
28
also noted the similarities
between GCLs and the brown tumor of hyperparathy-
roidism and hypothesized that GCLs might respond to
calcitonin. The results with calcitonin therapy have
varied; it has had no effect in some patients, and
others have developed resistance, which occurs be-
cause of a loss of receptors.
17,29
Some patients seem
to respond, although these case reports did not ap-
pear to include patients with aggressive lesions.
19,30
A randomized double-blind placebo-controlled
study in 14 patients treated with calcitonin nasal
spray showed a reduction in tumor volume of 10% or
more in 7 of 14 patients; however, complete remis-
sion was not observed. This group studied the re-
sponse in both aggressive and nonaggressive subtypes
and found a reduction/stabilization of tumor size in
nonaggressive lesions. However, decrease in tumor
size was variable in patients with aggressive lesions.
They hypothesized that the lack of predictable results
was related to an insufcient calcitonin dosage and
the short (6-month) follow-up period.
31
Kaban et al
15
proposed that GCLs are proliferative
vascular lesions that are, in part, angiogenesis-depen-
dent. They theorized that aggressive GCLs would re-
spond to antiangiogenic therapy.
15
They reported an
index case treated with interferon alpha-2a.
32
Inter-
feron alpha-2a inhibits angiogenesis and has been
used to treat infantile hemangiomas and other vascu-
lar tumors.
33-35
Interferon has also been shown to
inhibit osteoclastic bone resorption and to stimulate
osteoblasts and preosteoblasts in cell culture.
15,36,37
Adverse effects include fever, inuenza-like symp-
toms, lethargy, postnasal drip, skin rash and hair loss,
neutropenia, thrombocytopenia, elevated liver
transaminase, and spastic diplegia.
34,38
In the series of
Kaban et al,
15
15% of subjects developed signicant
side effects that limited interferon administration and
necessitated alternative therapies.
de Lange et al
19
described 2 patients in whom
calcitonin therapy failed, who were then treated with
interferon alpha-2a without surgical debulking. They
noted limited regression (40%) of the lesion.
19
Kaban
et al
20
proposed combined treatment of aggressive
GCLs with curettage, maintaining vital structures
(teeth and nerve), and adjuvant therapy with inter-
feron alpha-2a beginning 48 to 72 hours postopera-
tively. They reported successful tumor control with
decreased operative morbidity compared with en
bloc resection.
20
Of 26 patients, 16 were cured of
disease, 6 were in remission, and 4 were in active
treatment.
Based on the clinical and radiographic examination,
this patient has an aggressive GCL of the mandible.
CD34 staining of the biopsy specimen is recom-
mended to conrm the aggressive subtype.
12
The
lesion should be debulked/enucleated with preserva-
tion of vital structures (nerve and teeth). Per the
protocol developed by Kaban et al,
20
between 48 to
72 hours postoperatively, interferon-alpha-2a (Ro-
feron-A, Roche Laboratories, Nutley, NJ) or interferon-
alpha-2b (Intron A, Schering, Kenilworth, NJ) should
be started at a dose of 3,000,000 U/m
2
, administered
once daily by subcutaneous injection. The patient
should be monitored for adverse effects, including
FIGURE 2. OPG after 3 months of calcitonin therapy (4 months
after presentation): progression of the lesion is obvious in compar-
ison with initial lm.
Schtz et al. Aggressive Central Giant Cell Granuloma of The
Mandible. J Oral Maxillofac Surg 2010.
SCHTZ ET AL 2539
u-like symptoms, fever, lethargy, postnasal drip, skin
rash, and hair loss. Hematocrit, hemoglobin, white
blood cell and platelet counts, and liver function tests
should be obtained every 6 weeks.
Signicant side effects, neutropenia (absolute neu-
trophil count 1,000 K/m
3
), thrombocytopenia, el-
evated liver transaminase values (greater than 5-fold
increase above normal), or the development of anti-
thyroid antibodies are indications to stop therapy or
reduce the interferon dosage. A panoramic radio-
graph should be obtained immediately postopera-
tively, at 6 and 12 weeks postoperatively, and at
3-month intervals thereafter until the defect is lled
with bone. At that time, computed tomography can
be used to conrm bone regeneration and interferon
therapy can be discontinued. A patient can be con-
sidered cured if no evidence has been found of a GCL
2 years after completion of therapy.
20
This case serves to illuminate the challenges clini-
cians face when treating patients with GCL of the jaw.
Understanding the etiopathogenesis of this lesion and
identifying markers for behavior subtypes that can
guide the best treatment of patients are exciting op-
portunities for additional study.
Subsequent Course
After evaluation of therapeutic options and consultation
with the patients family, the decision was made to start
treatment with an intranasal spray of calcitonin. The patient
received a daily dose of 200 UI Miacalcin (Calcitonin-
salmon) Nasal Spray (Novartis, Basel, Switzerland) and with
this medication he left Kuwait for summer holidays in his
home country.
On return from holidays 3 months later he presented
with obvious progression: his face was distinctly asymmetric
and the OPG showed expansion of osteolytic process that
now extended from the right canine to the left second molar
(Fig 2). Calcitonin therapy was discontinued, and the pa-
tient received an intralesional injection of 30 mg triamcin-
olone acetonide (Kenacort-A 10; Bristol-Myers Squibb, New
York, NY) mixed with local anesthetic. This injection was
repeated 3 times in 3-week intervals. The fourth application
was already difcult due to increased hardness of the lesion.
Two months after the last triamcinolone injection, the OPG
showed distinctive ossication of the lesion but no decrease
in size (Figs 3A,B). It was decided to perform reshaping of
the mandible with curettage of accessible portions of the
lesion, followed by antiangiogenic therapy with interferon-
alpha.
The surgery was performed 8 months after the rst pre-
sentation. Under general anesthesia, the lesion was exposed
from marginal paradental incision; the left mental nerve was
identied and protected, and the excess of mandibular bone
was resected using burs and chisels. Accessible soft por-
tions of the lesion were curetted taking care to avoid root
apices and inferior alveolar nerve (Fig 4). The postoperative
healing was uneventful and the patient regained normal
facial appearance after resolution of postoperative edema
(Fig 5). The function of the mental nerve was preserved.
The patient was started on daily doses of 3 MIU interferon-
FIGURE 3. A, OPG after the fourth injection of triamcinolone, 7
months after presentation. There are signs of increased ossication,
but no decrease in size. B, Facial appearance of the patient at the
same time.
Schtz et al. Aggressive Central Giant Cell Granuloma of The
Mandible. J Oral Maxillofac Surg 2010.
FIGURE 4. OPG taken immediately after surgical reshaping and
curettage: note persistence of a substantial part of the lesion.
Schtz et al. Aggressive Central Giant Cell Granuloma of The
Mandible. J Oral Maxillofac Surg 2010.
2540 AGGRESSIVE CENTRAL GIANT CELL GRANULOMA OF THE MANDIBLE
alpha-2a (Roferon-A) subcutaneously 3 months after the
operation. This delay was caused by the difculty the family
faced in obtaining funding for this treatment, which is not
covered by health insurance for non-Kuwaitis.
The treatment was supervised by a pediatric oncologist
experienced in the administration of interferon. Baseline
complete blood cell count and liver function tests were
obtained and repeated every 6 weeks. Minimal side effects
were recorded and the patient completed a 1-year treat-
ment course without interruption. Clinical examination and
OPGs were repeated at 6 weeks and then at 3-month inter-
vals. There were signs of gradual remodeling and return to
normal trabecular pattern (Fig 6). One year after discontin-
uation of interferon therapy (3 years after initial presenta-
tion), the patient is without clinical symptoms and the only
remaining radiologic abnormality is a small hyperostosis of
the mandibular margin in the right canine area (Fig 7).
Discussion
Central giant cell granuloma (CGCG) of the jaws is
a benign lesion histologically characterized by the
presence of giant cells in cellular richly vascularized
stroma of spindle cells. Although originally termed
giant cell reparative granuloma,
4
it is not a granu-
loma in the strict histologic sense, and it is not repar-
ative clinically, often demonstrating neoplastic fea-
tures.
39
CGCG belongs together with giant cell tumor,
brown tumor of hyperparathyroidism, and cherubism
to so-called GCLs, which can be difcult to distinguish
solely by microscopic examination.
9
Giant cell tumor
of the long bones is practically identical with CGCG
of the jaws on histopathologic examination, and is
considered by some authors as a manifestation of the
same disease, where age and local factors are respon-
sible for different clinical characteristics.
9,40,41
Clinical behavior of CGCG is variable. Some lesions
are asymptomatic and slow growing and react favor-
ably to simple treatment with curettage; others are
fast growing, painful, and lead to teeth displacement
and root resorption, destruction of cortical bone, and
facial deformity. This latter variant is termed aggres-
sive subtype of CGCG and has a high recurrence rate
after simple curettage.
9,42
So far only clinical signs
and symptoms and radiologic features have been the
main criteria to differentiate between nonaggressive
and aggressive lesions.
43
Recently, it was reported
that higher levels of glycoprotein CD34 are associated
with aggressive lesions and that CD34 staining density
level is a test with a high sensitivity and specicity,
and high positive predictive value for the biological
behavior of GCLs.
12,13
FIGURE 5. Facial appearance of the patient 8 months after oper-
ation, during interferon-alpha therapy.
Schtz et al. Aggressive Central Giant Cell Granuloma of The
Mandible. J Oral Maxillofac Surg 2010.
FIGURE 6. OPG at the time of discontinuation of interferon alpha
therapy: nearly complete remodeling of the mandible is obvious.
Schtz et al. Aggressive Central Giant Cell Granuloma of The
Mandible. J Oral Maxillofac Surg 2010.
FIGURE 7. Follow-up OPG 1 year after discontinuation of
therapy.
Schtz et al. Aggressive Central Giant Cell Granuloma of The
Mandible. J Oral Maxillofac Surg 2010.
SCHTZ ET AL 2541
The etiology of CGCG remains unknown, but the
occurrence of CGCG in patients with anomalies with
a known genetic origin such as neurobromatosis
type 1 and Noonan syndrome suggests that a genetic-
related etiology might be possible.
43
Because only 1
instance of familial giant cell granuloma occurrence
has been reported, DNA aberration probably occurs
spontaneously in a specic group of cells, causing the
focal lesions, and is not hereditary.
44
Conventional therapycurettage or resection
can result in loss of teeth, facial disgurement, or
even discontinuity defects of the jaws in advanced
cases.
1,14,45,46
Moreover, overall recurrence rates
range from 11% to 49% for curettage alone
43
and can
be as high as 72% for aggressive subtype.
42
In an effort to avoid deleterious consequences of
radical surgical treatment, different pharmacologic
therapies based on presumptions regarding origin of
lesional cells were arbitrarily used with different suc-
cess. These included intralesional application of cor-
ticosteroids and systemic treatment with calcitonin,
interferon-alpha, imatinib, or bisphosphonates.
The earliest of these nonsurgical therapeutic strat-
egies was the intralesional application of corticoste-
roid proposed in 1988 by Jacoway et al.
24,47
The
original rationale stated for this treatment was his-
topathologic resemblance of CGCG to sarcoid.
24
However this resemblance is only supercial and
CGCG lesions lack macrophage granulomas character-
istic for sarcoid, as was shown immunohistochemi-
cally.
48
A contemporary explanation for the effect of
corticosteroid therapy on CGCG is the inhibition of
extracellular production of lysosomal proteases and
apoptotic action on osteoclast-like cells.
49
On the
other hand, corticosteroids are also known to en-
hance bone resorption; some cases are unresponsive
to corticosteroid therapy or may even display accel-
erated growth.
48
Calcitonin therapy of CGCG was introduced as an
alternative treatment of aggressive CGCG by Har-
ris
28
in 1993. It is based on the discovery of expres-
sion of several osteoclast-specic characteristics by
the giant cells in CGCG.
21
According to contempo-
rary knowledge, osteoclasts are not the proliferat-
ing tumor cells in CGCG, but they differentiate
from peripheral blood mononuclear cells that ex-
press its receptor activator of nuclear factor B
(RANK). Expression of RANK is a necessary step in
the origin of osteoclasts. Differentiation takes place
under the inuence of proliferating spindle-shaped
stroma cells expressing cytokine RANKL.
50
Calcito-
nin, peptide hormone produced by the C-cells of the
thyroid gland, inhibits the bone-resorbing activity of
osteoclasts. The mechanism of action of calcitonin
remains unclear.
51
de Lange et al
19
successfully treated 4 patients with
calcitonin and Pogrel
48
achieved complete remission
in 8 of 10 patients; however, de Lange et al
52
did not
get the same favorable results in any of their later 14
patients. Review
21
of previously reported series from
the English-language literature with the addition of 5
new cases showed that of a total 34 reported cases
treated exclusively with calcitonin, 22 (64.7%) achieved
complete resolution. In the other 12 cases, additional
surgical curettage or excision was necessary. The calci-
tonin administration course in this group ranged be-
tween 6 and 64 months, with a mean of 23.9 months.
Recently, it was reported that the relative percent-
age of immunohistochemically stained mononuclear
and giant cells for calcitonin and/or glucocorticoid
receptors in CGCG can serve as a tool for selecting
either calcitonin or glucocorticoid therapy.
17
Employment of interferon-alpha in the management
of aggressive variant of CGCG, which is usually highly
vascularized, was inspired by its earlier success in the
treatment of infantile hemangiomas.
53
Interferon-
alpha is a cytokine with immunomodulatory and
antiangiogenic properties. Interferon-alpha therapy
limits proliferation of various neoplastic lesions by
depriving them of neovascular supply. The mecha-
nism of action of interferon is the inhibition of pro-
duction of angiogenesis stimulators: vascular endothe-
lial growth factor and basic broblast growth factor.
Recent research suggests that CGCG is not a true
proliferative vascular lesion, but the immunoreactiv-
ity of the lesional cells for angiogenic factors is as-
sumed to play an important role in the osteoclasto-
genesis process contributing to the growth of the
lesion.
11
Interferon-alpha was introduced into clinical appli-
cation in 1989 to treat a child with pulmonary heman-
giomatosis, and later the use of interferon alpha-2a
was reported for treating life-threatening hemangio-
mas and other vascular tumors.
20
The rst known
case report of treatment of a CGCG with alpha-2a-
interferon was published in 1999 by Kaban et al.
32
This was followed by subsequent reports on success-
ful application of a treatment protocol combining
conservative surgery with postoperative adjuvant
treatment by interferon-alpha in 26 patients.
15,20
Bisphosphonates are used in the treatment of os-
teoporosis, hypercalcemia of malignancy, Pagets dis-
ease, multiple myeloma, and various skeletal metasta-
ses. Landesberg et al
54
suggested employment of
bisphosphonates as a primary or adjunctive treatment
for GCLs of the jaws, giant cell tumors of the appen-
dicular skeleton, pediatric osteogenesis imperfecta, -
brous dysplasia, Gauchers disease, and osteomyelitis.
They reported on the treatment of 3 patients with GCLs
of the jaws, the term they prefer over CGCG. Only 1
2542 AGGRESSIVE CENTRAL GIANT CELL GRANULOMA OF THE MANDIBLE
case managed by a single infusion of zoledronic acid was
completely successful.
Another addition to the arsenal of anti-osteolytic
agents is imatinib. Imatinib is a protein tyrosine kinase
inhibitor that is used to treat chronic myeloid leukemia
and gastrointestinal stromal tumors. The effect of ima-
tinib on osteoclasts is a dose-dependent decrease in
RANK.
55
de Lange et al
56
reported on treatment of a
patient with Stickler syndrome and an aggressive CGCG
of the mandible by a combination of interferon-alpha
and imatinib after the failure of initial treatment with
intralesional corticosteroid and systemic calcitonin.
Our patient fullled criteria
42
for diagnosing aggres-
sive variant of CGCG: lesion larger than 5 cm, teeth
displacement with root resorption, cortical bone ero-
sion documented by computed tomography examina-
tion. The extent of the lesion made conventional
conservative surgical treatment (curettage) unfeasible
and the only viable surgical option was segmental
resection with continuity defect reconstruction by
transfer of microvascular free bone ap, followed by
placement of implants and prosthetic rehabilitation.
Such a procedure would have burdened the patient
with considerable surgical morbidity, cosmetic con-
sequences, and nancial expenses.
From available alternative pharmacological thera-
pies, we decided on intranasal application of salmon
calcitonin as the rst line of treatment. Intranasal
spray can be easily self-administered and is accompa-
nied by minimal side effects.
19,51,52
No regular labo-
ratory monitoring is necessary. On the other hand
intralesional application of corticosteroid is painful
and necessitates regular ofce visits. Interferon-alpha
as monotherapy can stabilize the lesion or lead to
partial regression,
31
but its administration can be ac-
companied by serious side effects and therefore re-
quires regular laboratory monitoring.
15,57
No improvement can be expected in x-ray examina-
tion for the rst 4 to 6 months of calcitonin therapy
48
;
however, our patient displayed obvious progression,
clinically and radiologically, 3 months after the initia-
tion of treatment, and his parents were alarmed and
not willing to continue obviously ineffective treat-
ment. This lack of response prompted us to switch
therapy to intralesional corticosteroids. Triamcino-
lone acetonide administration achieved considerable
ossication of the lesion, making it amenable to re-
shaping, but no reduction in size, and intolerable
cosmetic deformity persisted. Subsequent conserva-
tive surgical intervention was successful in full cos-
metic rehabilitation of the patient without any dele-
terious consequences like loss of teeth, external scars,
or neurosensory decit. The following adjuvant ther-
apy with interferon-alpha was based on the latest
therapeutic recommendations available at that time
58
and achieved its goal despite the initial delay caused
by social circumstances of the patients family.
The presented case illustrates that perseverance
and employment of all available therapeutic options
can optimize the results of management of aggressive
CGCG and spare the patients mutilating surgery that
does not seem any more justiable as the rst line of
treatment.
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