Aggressive Central Giant Cell

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CLINICOTHERAPEUTIC CONFERENCE

J Oral Maxillofac Surg68:2537-2544, 2010

Aggressive Central Giant Cell

Granuloma of the MandiblePetr 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 hisleft lower jaw accompanied by swelling. Clinical examination

showed a hard, tender mandibular enlargement extendingfrom the chin to the left molar area. The orthopantomogram(OPG) showed poorly defined multilocular radiolucency in-

volving the mandibular body from the right lateral incisor tothe left first molar (Fig 1A). There were discrete signs ofresorption of root apices of the adjacent teeth. Computedtomography 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 fibrous stroma andirregularly distributed multinucleated giant cells clusteringaround areas of hemorrhage. Periphery of the lesionshowed reactive osteoid tissue formation (Fig 1C).

The overall clinical, radiologic, and histopathologic picturewas consistent with central giant cell granuloma. Laboratoryinvestigations 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, andin females more often than in males. These benignlesions occur before the age of 30 years.1 GCLs areusually unifocal. Multifocal lesions should alert theclinician to the possibility of hyperparathyroidismor, if bilateral, cherubism or Noonan syndrome.1,2

GCLs are osteoclast-rich tumors that are histopatho-logically indistinguishable from those seen incherubism and Noonan syndrome. Nevertheless, pa-tients with isolated GCLs do not have the cherubism-related germline SH3BP2 mutation, andthe lesions donot contain somatic SH3BP2 mutations.3 This findingsuggests that even though all GCLs might appear thesame histologically, they likely have a different etio-pathogenesis.

The first description of GCLs was by Jaffe4 in 1953.However, confusion remains about the nature of thelesion (reactive/inflammatory, neoplastic), the cell oforigin, and the variability in clinical behavior. Thus,an assortment of treatment modalities, with differentmechanisms of action, have been tried in patients

with a variety of lesions with inconsistent outcomes;all of which has made deciphering the best treatmentoption difficult for the practitioner.

The histopathologic features of GCLs are a large

number of multinucleated giant cells and mononu-clear cells within a fibrous stroma. The giant cells inGCL may be reactive or secondary, not the cell oforigin. Macrophages, mesenchymal cells, and fibro-blasts have all been proposed as being responsible forthe lesion.5

There is variability in the clinical behavior of GCLs.Rapidly growing expansile lesions with an aggressiveappearance (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 al6 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


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


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
mailto:[email protected]:[email protected]:[email protected]:[email protected]


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graphic features of aggressive GCLs: 1) size greaterthan 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 thesame through the microscope, many groups have

considered biomarkers as a means of identifying ag-gressive versus nonaggressive lesions and correlatingthese with the clinical behavior and treatment out-come. A wide variety of parameters, including thenumber and size of the giant cells, the mean numberof nuclei per giant cell, the fractional surface areaoccupied by giant cells, the DNA content, mitoticactivity, and the immunohisotologic features havebeen studied in an attempt to distinguish aggressiveand nonaggressive subtypesandto predict prognosisand response to treatment.6-10 Aggressive/recurringlesions 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 organizationregions.9

The angiogenic activity of GCLs was proposed as adeterminant of the aggressive nature of GCLs. Veredet al11were unable to find elevated vascular endothe-lial growth factor and fibroblast growth factor in thesetumors and concluded that GCLs have low angiogenicactivity. Dewsnup et al12 studied the expression ofCD34, a cellcell adhesion factor and cell-surface gly-

coprotein found in hematopoietic precursor and cap-illary endothelial cells. They determined that clinicallyaggressive giant cell tumors have an increased vascu-lar density compared with nonaggressive lesionsbased on CD34 staining. Furthermore, they suggestedthat CD34 evaluation can identify aggressive lesionsamenabletoantiangiogenic therapy, even at the timeof biopsy.12 This same group subsequently showedthat CD34 staining density levels of more than 2.5%

were associated with aggressive GCLs.13 These find-ings strongly suggest that the CD34 staining densitylevel has a high positive predictive value for biologicbehavior and might help in planning treatment and

predicting outcome.One treatment of GCLs is enucleation and curet-

tage, with or without adjunctive therapy, such asperipheral ostectomy1 and liquid nitrogen cryothera-py.14 Although nonaggressive lesions of the jaw aresuccessfully managed with curettage and have a lowrecurrencerate, aggressive lesions have a recurrencerate of 70%.15

The gold standard forthetreatment of aggressiveGCL is en bloc resection.16 Given that these lesionsfrequently occur in children and resection of vitalstructures for treatment of a benign lesion can result

FIGURE 1. A, OPG at the time of presentation. B, Axial computedtomography scan shows multilocular appearance of the lesion witherosion of both lingual and vestibular cortices. C, Photomicrographshowing mass of granulationlike tissue containing numerous oste-oclastlike giant cells with scattered inflammatory and hemosiderinladen 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 TheMandible. J Oral Maxillofac Surg 2010.

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in functional, esthetic, and psychological problems,alternatives to resection have been attempted.17

These have included intralesional steroids, systemiccalcitonin, and systemic interferon alpha-2a com-bined with curettage.18-20

Vered et al17 immunohistochemically stainedmononuclear and giant cells for glucocorticoid and

calcitonin receptors in an attempt to provide a reli-able and practical tool for selecting an appropriatetherapeutic agent to treat GCLs. They found that themononuclear and giant cells of GCLs stained for bothglucocorticoid and calcitonin receptors. Flanagan etal21 proposed intralesional corticosteroid for GCLs.Their reasoning was that multinucleated giant cellsare osteoclasts and dexamethasone has been shownto inhibit osteoclast-like cells in marrow cultures.22

Jacoway et al23 noted the microscopic similaritiesbetween sarcoidosis and GCLs and also suggestedtreatment with corticosteroids. A few successful case

reports have been published of GCLs treated byweekly intralesional injection with corticoste-roids.18,24-26 However, it is unclear from these reports

whether the lesions treated with corticosteroids werenonaggressive or aggressive subtypes. The smatteringof case reports does not allow surgeons to evaluatethe clinical effectiveness of this therapy. A large seriesor a randomized trial with reported success rates in alltypes of lesions is necessary to adequately evaluatethis treatment.

Giant cells in GCLshave also been shown to havecalcitonin receptors.27 Calcitonin inhibits osteoclast/

giant cell function andhas been suggested as a treat-ment modality. Harris28 also noted the similaritiesbetween GCLs and the brown tumor of hyperparathy-roidism and hypothesized that GCLs might respond tocalcitonin. The results with calcitonin therapy have

varied; it has had no effect in some patients, andothers have developed resistance, which occurs be-cause of a loss of receptors.17,29 Some patients seemto respond, although these case reports did not ap-pear to include patients with aggressive lesions.19,30

A randomized double-blind placebo-controlledstudy in 14 patients treated with calcitonin nasalspray 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 subtypesand found a reduction/stabilization of tumor size innonaggressive lesions. However, decrease in tumorsize was variable in patients with aggressive lesions.They hypothesized that the lack of predictable results

was related to an insufficient calcitonindosage andthe short (6-month) follow-up period.31

Kaban et al15 proposed that GCLs are proliferativevascular lesions that are, in part, angiogenesis-depen-dent. They theorized that aggressive GCLs would re-

spond to antiangiogenic therapy.15 They reported anindex case treated with interferon alpha-2a.32 Inter-feron alpha-2a inhibits angiogenesis and has beenused to treat infantile hemangiomas and other vascu-lar tumors.33-35 Interferon has also been shown toinhibit osteoclastic bone resorption and to stimulateosteoblasts and preosteoblasts in cell culture.15,36,37

Adverse effects include fever, influenza-like symp-toms, lethargy, postnasal drip, skin rash and hair loss,neutropenia, thrombocytopenia, elevated livertransaminase,and spastic diplegia.34,38 In the series ofKaban et al,15 15% of subjects developed significantside effects that limited interferon administration andnecessitated alternative therapies.

de Lange et al19 described 2 patients in whomcalcitonin therapy failed, who were then treated withinterferon alpha-2a without surgical debulking. Theynoted limited regression (40%) of the lesion.19 Kabanet al20 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 withdecreased operative morbidity compared with enbloc resection.20 Of 26 patients, 16 were cured ofdisease, 6 were in remission, and 4 were in activetreatment.

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 confirm the aggressive subtype.12 The

lesion should be debulked/enucleated with preserva-tion of vital structures (nerve and teeth). Per theprotocol developed by Kaban et al,20 between 48 to72 hours postoperatively, interferon-alpha-2a (Ro-feron-A, Roche Laboratories, Nutley, NJ) or interferon-alpha-2b (Intron A, Schering, Kenilworth, NJ) shouldbe started at a dose of 3,000,000 U/m2, administeredonce daily by subcutaneous injection. The patientshould be monitored for adverse effects, including

FIGURE 2. OPG after 3 months of calcitonin therapy (4 monthsafter presentation): progression of the lesion is obvious in compar-ison with initial film.


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flu-like symptoms, fever, lethargy, postnasal drip, skinrash, and hair loss. Hematocrit, hemoglobin, whiteblood cell and platelet counts, and liver function testsshould be obtained every 6 weeks.

Significant side effects, neutropenia (absolute neu-trophil count 1,000 K/m3), thrombocytopenia, el-evated liver transaminase values (greater than 5-foldincrease above normal), or the development of anti-thyroid antibodies are indications to stop therapy orreduce the interferon dosage. A panoramic radio-graph should be obtained immediately postopera-tively, at 6 and 12 weeks postoperatively, and at3-month intervals thereafter until the defect is filled

with bone. At that time, computed tomography canbe used to confirm bone regeneration and interferontherapy can be discontinued. A patient can be con-

sidered cured if no evidence has been found of a GCL2 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 andidentifying markers for behavior subtypes that canguide the best treatment of patients are exciting op-

portunities for additional study.

Subsequent Course

After evaluation of therapeutic options and consultationwith the patients family, the decision was made to starttreatment with an intranasal spray of calcitonin. The patientreceived a daily dose of 200 UI Miacalcin (Calcitonin-salmon) Nasal Spray (Novartis, Basel, Switzerland) and withthis medication he left Kuwait for summer holidays in hishome country.

On return from holidays 3 months later he presentedwith obvious progression: his face was distinctly asymmetricand the OPG showed expansion of osteolytic process thatnow 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 wasrepeated 3 times in 3-week intervals. The fourth application

was already difficult due to increased hardness of the lesion.Two months after the last triamcinolone injection, the OPGshoweddistinctive ossification of the lesion but no decreasein size (Figs 3A,B). It was decided to perform reshaping ofthe mandible with curettage of accessible portions of thelesion, followed by antiangiogenic therapy with interferon-alpha.

The surgery was performed 8 months after the first pre-

sentation. Under general anesthesia, the lesion was exposedfrom marginal paradental incision; the left mental nerve wasidentified and protected, and the excess of mandibular bone

was resected using burs and chisels. Accessible soft por-tions of the lesion were curettedtaking care to avoid rootapices and inferior alveolar nerve (Fig 4). The postoperativehealing was uneventful and the patient regained normalfacial 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, 7months after presentation. There are signs of increased ossification,but no decrease in size. B, Facial appearance of the patient at thesame time.


FIGURE 4.OPG taken immediately after surgical reshaping andcurettage: note persistence of a substantial part of the lesion.




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alpha-2a (Roferon-A) subcutaneously 3 months after theoperation. This delay was caused by the difficulty the familyfaced in obtaining funding for this treatment, which is notcovered by health insurance for non-Kuwaitis.

The treatment was supervised by a pediatric oncologistexperienced in the administration of interferon. Baselinecomplete blood cell count and liver function tests wereobtained and repeated every 6 weeks. Minimal side effects

were recorded and the patient completed a 1-year treat-ment course without interruption. Clinical examination andOPGs were repeated at 6 weeks and then at 3-month inter-

vals. There were signs of gradualremodeling and return tonormal 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 ofthe mandibular margin in the right canine area (Fig 7).

Discussion

Central giant cell granuloma (CGCG) of the jaws isa benign lesion histologically characterized by thepresence of giant cells in cellular richly vascularizedstroma 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 cherubismto so-called GCLs, which can be difficult to distinguishsolely by microscopic examination.9 Giant cell tumorof the long bones is practically identical with CGCGof the jaws on histopathologic examination, and isconsidered by some authors as a manifestation of thesame disease, where age and local factors are respon-sible for different clinical characteristics.9,40,41

Clinical behavior of CGCG is variable. Some lesionsare asymptomatic and slow growing and react favor-ably to simple treatment with curettage; others arefast growing, painful, and lead to teeth displacement

and root resorption, destruction of cortical bone, andfacial deformity. This latter variant is termed aggres-sive subtype of CGCGandhas a high recurrence rateafter simple curettage.9,42 So far only clinical signsand symptoms and radiologic features have been themain criteria to differentiate between nonaggressiveand aggressive lesions.43 Recently, it was reportedthat higher levels of glycoprotein CD34 are associated

with aggressive lesions and that CD34 staining densitylevel is a test with a high sensitivity and specificity,and high positivepredictive value for the biologicalbehavior of GCLs.12,13

FIGURE 5.Facial appearance of the patient 8 months after oper-ation, during interferon-alpha therapy.


FIGURE 6.OPG at the time of discontinuation of interferon alphatherapy: nearly complete remodeling of the mandible is obvious.


FIGURE 7. Follow-up OPG 1 year after discontinuation oftherapy.


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The etiology of CGCG remains unknown, but theoccurrence of CGCG in patients with anomalies witha known genetic origin such as neurofibromatosistype 1 and Noonan syndrome suggests that a genetic-related etiology might be possible.43 Because only 1instance of familial giant cell granuloma occurrencehas been reported, DNA aberration probably occursspontaneously in a specific group of cells, causing thefocal lesions, and is not hereditary.44

Conventional therapycurettage or resectioncan result in loss of teeth, facial disfigurement, oreven discontinuity defects of the jaws in advancedcases.1,14,45,46 Moreover, overall recurrence ratesrange from 11% to 49% for curettage alone43 and canbe as high as 72% for aggressive subtype.42

In an effort to avoid deleterious consequences ofradical surgical treatment, different pharmacologictherapies based on presumptions regarding origin oflesional 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 Theoriginal rationale stated for this treatment was his-topathologic resemblance of CGCG to sarcoid.24

However this resemblance is only superficial andCGCG 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 ofextracellular production of lysosomal proteases andapoptotic action on osteoclast-like cells.49 On theother hand, corticosteroids are also known to en-hance bone resorption; some cases are unresponsiveto corticosteroid therapy or may even display accel-erated growth.48

Calcitonin therapy of CGCG was introduced as analternative treatment of aggressive CGCG by Har-ris28 in 1993. It is based on the discovery of expres-sion of several osteoclast-specific characteristics bythe giant cells in CGCG.21 According to contempo-

rary knowledge, osteoclasts are not the proliferat-ing tumor cells in CGCG, but they differentiatefrom peripheral blood mononuclear cells that ex-press its receptor activator of nuclear factor B(RANK). Expression of RANK is a necessary step inthe origin of osteoclasts. Differentiation takes placeunder the influence of proliferating spindle-shapedstroma cells expressing cytokine RANKL.50 Calcito-nin, peptide hormone produced by the C-cells of thethyroid gland, inhibits the bone-resorbing activity ofosteoclasts. The mechanism of action of calcitoninremains unclear.51

de Lange et al19 successfully treated 4 patients withcalcitonin and Pogrel48 achieved complete remissionin 8 of 10 patients; however, de Lange et al52 did notget the same favorable results in any of their later 14patients. Review21 of previously reported series fromthe English-language literature with the addition of 5new cases showed that of a total 34 reported casestreated exclusively with calcitonin, 22 (64.7%) achievedcomplete resolution. In the other 12 cases, additionalsurgical 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 mononuclearand giant cells for calcitonin and/or glucocorticoidreceptors in CGCG can serve as a tool for selectingeither calcitonin or glucocorticoid therapy.17

Employment of interferon-alpha in the managementof aggressive variant of CGCG, which is usually highly

vascularized, was inspired by its earlier success in thetreatment of infantile hemangiomas.53 Interferon-alpha is a cytokine with immunomodulatory andantiangiogenic properties. Interferon-alpha therapylimits proliferation of various neoplastic lesions bydepriving 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 fibroblast growth factor.Recent research suggests that CGCG is not a trueproliferative 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 thelesion.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 first knowncase 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 adjuvanttreatment 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 al54 suggested employment ofbisphosphonates as a primary or adjunctive treatmentfor GCLs of the jaws, giant cell tumors of the appen-dicular skeleton, pediatric osteogenesis imperfecta, fi-brous dysplasia, Gauchers disease, and osteomyelitis.They reported on the treatment of 3 patients with GCLsof the jaws, the term they prefer over CGCG. Only 1



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case managed by a single infusion of zoledronic acid wascompletely successful.

Another addition to the arsenal of anti-osteolyticagents is imatinib. Imatinib is a protein tyrosine kinaseinhibitor that is used to treat chronic myeloid leukemiaand gastrointestinal stromal tumors. The effect of ima-tinib on osteoclasts is a dose-dependent decrease inRANK.55 de Lange et al56 reported on treatment of apatient with Stickler syndrome and an aggressive CGCGof the mandible by a combination of interferon-alphaand imatinib after the failure of initial treatment withintralesional corticosteroid and systemic calcitonin.

Our patient fulfilled criteria42 for diagnosing aggres-sive variant of CGCG: lesion larger than 5 cm, teethdisplacement with root resorption, cortical bone ero-sion documented by computed tomography examina-tion. The extent of the lesion made conventionalconservative surgical treatment (curettage) unfeasibleand the only viable surgical option was segmental

resection with continuity defect reconstruction bytransfer of microvascular free bone flap, followed byplacement of implants and prosthetic rehabilitation.Such a procedure would have burdened the patient

with considerable surgical morbidity, cosmetic con-sequences, and financial expenses.

From available alternative pharmacological thera-pies, we decided on intranasal application of salmoncalcitonin as the first line of treatment. Intranasalspray 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 painfuland necessitates regular office visits. Interferon-alphaas monotherapy can stabilize the lesion or lead topartial 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 first 4 to 6 months of calcitonin therapy48;however, our patient displayed obvious progression,clinically and radiologically, 3 months after the initia-tion of treatment, and his parents were alarmed andnot willing to continue obviously ineffective treat-

ment. This lack of response prompted us to switchtherapy to intralesional corticosteroids. Triamcino-lone acetonide administration achieved considerableossification of the lesion, making it amenable to re-shaping, but no reduction in size, and intolerablecosmetic 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 deficit. The following adjuvant ther-apy with interferon-alpha was based on the latesttherapeutic recommendations available at that time58

and achieved its goal despite the initial delay causedby social circumstances of the patients family.

The presented case illustrates that perseveranceand employment of all available therapeutic optionscan optimize the results of management of aggressiveCGCG and spare the patients mutilating surgery thatdoes not seem any more justifiable as the first line oftreatment.

References

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