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The Turkish Journal of Pediatrics 2005; 47: 75-81 Case

Intralesional corticosteroid injection for central giant cellgranuloma: A case report and review of the literature

Bahar Sezer, Banu Koyuncu, Murat Gomel, Tayfun GünbayDepartment of Oral and Maxillofacial Surgery, Ege University Faculty of Dentistry, Ýzmir, Turkey

SUMMARY: Sezer B, Koyuncu B, Gomel M, Günbay T. Intralesionalcorticosteroid injection for central giant cell granuloma: A case report and reviewof the literature. Turk J Pediatr 2005; 47: 75-81.

Central giant cell granuloma (CGCG) is a benign intraosseous lesion of thejaws that is found predominantly in children and young adults. Although benign,it may be locally aggressive, causing extensive bone destruction, toothdisplacement and root resorption. The common therapy is aggressive curettage,peripheral ostectomy or resection, which may be associated with loss of teethand, in younger patients, loss of dental germs. A number of alternative non-surgical approaches have been advocated in recent years for the managementof CGCGs. These include intralesional corticosteroid injections, calcitonininjections and subcutaneous ααααα-interferon injections.

In this article, an 11-year-old boy with a CGCG is successfully treated withcorticosteroid injections and this treatment is discussed within a review ofthe literature.

Key words: central giant cell granuloma, mandible, treatment, intralesionalcorticosteroid injection.

Central giant cell granuloma (CGCG) is definedby the World Health Organization as anintraosseous lesion consisting of cellular fibroustissue that contains multiple foci ofhemorrhage, aggregations of multinucleatedgiant cells and occasionally trabeculae of wovenbone1. Its etiology is unknown and its biologicalbehavior poorly understood2,3. CGCG is anonneoplastic lesion that is found exclusivelyin the maxilla and the mandible1.

It is an uncommon lesion that accounts for lessthan 7% of all benign lesions of the jaws in tooth-bearing areas2,7. The mandibular/maxillary ratiohas been reported as being from 2:18 to 3:15.

Central giant cell granuloma commonly occursin children and young adults, with a slightpredilection for females. The anterior portion ofthe mandible has been identified as a morecommon location for CGCG development, withthe lesion frequently crossing the midline3,9.There are reports of CGCG behaving like a slowgrowing neoplasm: expansile and destructive,displacing teeth, enveloping and often erodingdental root ends, perforating the cortex andleading to pathologic fractures1-12. When in the

maxilla, CGCG can invade the floor of themaxillary sinus or the orbit, as well as the nasalfossae. Mandibular CGCG may expand and evenpenetrate the cortical bone. The majority ofCGCGs (87.5% present as an expansileradiolucency, either unilocular or multilocular,with well-defined or ill-defined margins3,4,8.Based on its clinical behavior and radiographicfeatures, CGCG has been classified as one ofthe following;1. Non-aggressive, which is characterized by a

slow, almost asymptomatic growth that doesnot perforate the cortical bone or induce rootresorption. This variety has a low tendencyto recur.

2. Aggressive, which is characterized by pain,rapid growth, expansion and/or perforationof the cortical bone, radicular resorption, anda high tendency to recur. The aggressivelesions are found in younger patients5,12.

The traditional treatment of CGCG of the jawshas been surgical excision either bycurretage2,3,5,14-16 or en bloc resection17,depending on the following factors: aggressiveversus non-aggressive behavior, location, size and

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radiographic appearance13,18,19. There are nohistologic differences between the aggressive andnon-aggressive varieties12,18-22. Other treatmentshave included radiation10 and systemic injectionsof calcitonin18,23-25 and α-interferon19,21,26.

Many authors have reported cases of CGCGtreated with corticosteroids13,27-32. Thisnonsurgical approach is very important in youngpatients with developing dentition. Investigatorsreported successful treatment of CGCG withintralesional steroid injections in children13,29.

The purpose of this case report was to use aless-invasive therapeutic approach for thetreatment of CGCG affecting the mandible inan 11-year-old boy.

Case Report

An 11-year-old previously healthy boy wasreferred with a painless, bony hard swelling ofthe left side of the jaw. It was first noticed byhis parents three months before the consultationand had then slowly increased in size. There wasno history of fever, discomfort, pain, sensorydisturbance, difficulty in mastication, bad taste,or traumatic injury. Extraoral examinationrevealed non-tender expansile mass of the leftmandibular body; the lesion produced nosignificant facial asymmetry or marked deformity.There was no skin erythema or apparent cervicalor submandibular lymphadenopathy.

Intraoral examination revealed buccal expansionfrom the mesial side of the left permanent canineto the distal side of the left permanent primarysecond molar (Fig. 1). The swelling was hardon palpation, consistent with bone, and wascovered with normal mucosa. Pressure did not

Fig. 1. Osteolytic lesion in the left body in the mandible.

Fig. 2. Panoramic radiograph shows a 3.5x2 cmpartially corticated radiolucent lesion extending frommesial area of the left permanent first premolar to

mesial area of the left permanent first premolar.

elicit any exudates or any tenderness, and therewas no presence of paresthesia. There wasminimal swelling of the lingual aspect of themandible, and dentition was normal; the leftmandibular teeth were non-tender and immobile.

Radiographs of the patient included apanoramic view, occlusal view, cross-sectionaltomographies, axial computed tomographiesand three-dimensional computerizedtomography (CT) scan. These revealed well-circumscribed, unilocular radiolucency (Fig. 2).

The three-dimensional CT sections showed theoutline of the tumor (33x18x23 mm) expandingthe bony alveolar cortical plate of the mandible(Figs. 3, 4). The lesion extended from themesial root surface of the left permanent firstpremolar to the mesial root surface of the leftpermanent first molar. The vertical extensionwas from the gingival third of the mandibularpremolar teeth to the basal bone of themandible, with enveloping but no resorption ofthe roots of the teeth noted. Moderate buccalexpansion was present, with thinning of thecortical plate, and the labial bony cortex wasmissing in the narrow area between premolars.

Within the radiolucency appeared a radiopaquestructure consistent with the calcification. Onthe basis of the clinical and radiographicfindings, the differential diagnoses includedodontogenic keratocyst, central giant cellgranuloma, aneurysmal bone cyst andameloblastic fibroma.

Local anesthetic was administered and a needleaspiration of the lesion was performed; no cysticor hemorrhagic fluid was aspirated. An

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Fig. 3, 4: CAT scans show expansive radiolucency (arrows) that had partially eroded thebuccal cortical plate of the left mandibular body.

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incisonal biopsy of the lesion was performed.The cortex was perforated in a small area thatfits an area between permanent premolars.On entering the area, we found the lesion to bea friable, readily bleeding solid mass. Results ofthe biopsy were consistent with a diagnosis ofCGCG. Laboratory values for serum calcium,phosphorus, alkaline phosphates, andparathyroid hormone were within normal limits,as were the blood cell count and differential.Because of the possible mutilation (defect anddeformities) that could arise as a result ofsurgery, the corticosteroid intralesional injectiontreatment was proposed to the parents of thepatient, with the understanding that surgerywas left as an option if the steroid treatmentwas not fully successful.Treatment was started with a 5 ml injection ofKenocort-A (10 mg/ml) and lidocaine solution 2%with epinephrine 1:200,000 50% mixture byvolume). The solution (4 ml Kenacorte-A andlidocaine) was administered with a 5 cm disposablesyringe with a 1 in # 22 G needle and injected byclinically estimating the site where the cortical bonewas more expanded and, therefore, the thinnestpoint. Once inside the lesion, the needle wasredirected to inject small amounts into differentareas. Identical injections were administered everyseven days for a total of six injections.At monthly intervals, oral and radiographicexaminations were performed. Six months later,the patient reported that the lesion appeared tohave decreased in size and panoramic radiographshowed increased opacification (Fig. 5).

One year later, radiographs revealed reossificationof the area (Fig. 6). Apices of the associated teethin this region had developed properly. Eighteenmonths later, CT scan showed completeresolution of the lesion (Figs. 7,8).

Fig. 5: Panoramic radiograph taken six monthsafter the completion of treatment shows bone

healing with increased opacification.

Fig. 6: Panoramic radiograph taken 12 months afterthe completion of treatment shows almost complete

healing of the lesion due to new bone formation.

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Fig. 7, 8: CAT scans taken 18 months after the initial infection show a resolution of the lesion withalmost complete healing by reossification.

The patient was last seen three years afterbeginning treatment without evidence ofrecurrence or side effects associated with thesteroid treatment.

Discussion

The conventional therapy of CGCG has beenlocal curettage, and this has been associated witha high success rate and a low recurrence rate16.However, some studies have suggestedrecurrence rates as high as 70% after enucleationor curettage12,18-21,24,28. There are no availablebiologic markers to predict clinical behavior, andstandard histologic techniques do not help theclinician determine prognosis12,13,18,22.Consequently, a number of different treatmentoptions have been recommended, includingaggressive curettage possibly coupled withadjunctive treatment such as liquid nitrogencryotherapy, Carnoy�s solution3,5,14-15 and (goldstandard for therapy en bloc resection withnegative histologic margins17, which result in amajor facial deformity. This is of great concern,especially in children and young adults withdeveloping dentition and jaws.

A number of alternative nonsurgical therapieshave been described for the management ofCGCG. Radiotherapy has not proven to be astatisfactory alternative, because irradiation ofgiant cells lesions may provoke malignantdegradation33. Other alternative treatmentsinclude pharmacologic therapy with α-interferon

or calcitonin, which are administrated viasubcutaneous injection over severalmonths18,19,21,23-26. Interferon-alpha has beenused to treat patients with metastatic or locallyadvanced, non-resectable, life threatening giantcell lesions of long bones and jaws that haverequired frequent palliative treatments19,21,28. Ithas been used for these tumors based on theassumption that the lesions are vascular innature26. Calcitonin treatment has also beenadvocated since it was first suggested in 199325.The original rationale for the use of calcitoninwas that the lesion is identical histologically tothe brown tumor of hyperparathyroidism, andtherefore an as-yet-unidentified parathormone-like hormone may induce this lesion24,25. Resultsof these treatments have been variable18.Calcitonin and interferon therapy arecomplicated owing to the great amount ofdiscomfort, possible side effects and the relativelylong duration of treatment, which is not welltolerated by some patients, especially children3.Intralesional corticosteroid injection is anotheralternative nonsurgical method. In 1988, Jacowayet al.31 treated a case of CGCG with intralesionalcorticosteroid injections, which producedexcellent results.

Jacoway et al.31, indicating the microscopicsimilarities between sarcoidosis and CGCGssuggested that similar therapeutic regimens wouldbe of value in treating both conditions34-36. Thisperception has been supported by reports showingthat intralesional steroid injections into bone

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cysts resulted in growth of fibrous connectivetissue and reossification within three years37.

Studies by Flanagan et al.38 indicated thatmultinucleated giant cell granulomas of the jawsare osteoclasts, and that dexamethasone�sinhibition of osteoclast-like cells in marrowcultures31 suports the use of intralesionalcorticosteroid for CGCGs27-30.

In addition, it has been shown that the avianosteoclasts and the osteoclast-like multinucleatedgiant cells of the giant cell tumor of bonerespond in vitro to treatment with 17 βglucuronidase (17β-E2) by decreased boneresorption activity32,39. Osteoclasts accomplishbone resorption by secreting lysosomalproteases13. Kremer et al.40 demonstratedsteroid-dose-dependent decrease in the secretedlevel of these enzymes and an increase in theintracellular level. The initial decrease wasobserved between 4 and 18 hours after beginningtreatment and a marked decrease was observedafter 24 hours. In addition, it has beenexperimentally shown that steroids induceapoptosis in rat osteoclasts41-42.

According to Carlos and Sedano13, intralesionalcorticosteroid injections may cause cessation ofbone resorption via the following twomechanisms:

1. Inhibition of the extracellular production oflysosomal proteases43.

2. Steroidal apoptotic action on osteoclast-likecells44-46.

Terry and Jacoway32 published a protocolderived by Francis Howell for treatment ofCGCGs of the jaws. This protocol consists ofthe intralesional injection of a mixtureconsisting of equal parts of triamcinoloneactinide (Kenalog 10; 10 mg/ml) and localanesthetic (Marcaine 0.5% with epinephrine1:200,000). The suggested dose is 2 ml/2 cmof radiolucency. The injections are given inmultiple locations throughout the lesion in aweekly regimen for at least six weeks31,32. Inthe reported patient, the CGCG responded wellto the same intralesional corticosteroid therapyprotocol as in this study. Complete calcificationoccurred two years after beginning treatment.These responses were similar to previousreports of intralesional corticosteroid therapyin children.

Because of no side effect, short duration oftreatment and no discomfort, this therapy is a veryattractive option, particulary for children and youngadults, versus other medical treatments3,13,29.Suppression of adrenal hormone production occurswhen a sufficient amount of corticosteroid isadministered daily; however, these patients receivea weekly low dose of steroid that does not afteradrenal gland function13.

Our case exhibited no side effects related tosteroid treatment, which was well tolerated, asin the similar previous reports. In addition, a21/2-year-old girl with CGCG was also reportedto have been similarly treated with excellentresults and without side effects or recurrence13.

Generally, the advantages of intralesionalcorticosteroid therapy in the treatment ofselected cases of CGCGs include the following:

1. The less invasive nature of the procedure29.Because of the usually expansive growth of theCGCG, the thin bony cortex overlying the lesionmay be easily perforated by a thin needle27,29.

2. The probable lower cost to the patient andlower risk than other alternative treatments3,27,29.

3. The option to treat the lesion surgically orby other alternative medical treatments in thefuture if necessary24,32.

Before the dental professional can startadministration of intralesional corticosteroidinjections, confirmation of the lesion via biopsyis mandatory. Because the histologic features ofCGCG of the jaw are indistinguishable from thebrown tumors of hyperparathyroidism, the lattercondition should be ruled out by performing theappropriate blood work-up before institutingtreatment. In addition, the clinician mustperform a careful pretreatment evaluation in allpatients to prevent any untoward side effects totherapy. Patients with diabetes mellitus, pepticulcer, infection and compromised immunesystems would probably not benefit from thistreatment for obvious reasons.

The treatment of CGCG with intralesionalinjections of steroids can be used as an alternativeto surgery. The technique is simple andinexpensive and, most important, saves the vitalstructures, thus avoiding a large facial deformity.

We believe that sufficient evidence exists towarrant nonsurgical therapy as the first choicein managing giant-cell lesions in bone,especially in children.

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