CASE REPORT

Central giant cell granuloma: treatment with calcitonin,triamcinolone acetonide, and a cystic finding 3 yearsand 6 months after the primary treatment

Marcelo Bonifácio da Silva Sampieri & Renato Yassutaka Faria Yaedú &

Paulo Sérgio Silva Santos & Eduardo Sanches Gonçales &

Eduardo Santa’Ana & Alberto Consolaro & Lyzete Berriel Cardoso

Received: 20 May 2012 /Accepted: 18 October 2012 /Published online: 31 October 2012# Springer-Verlag Berlin Heidelberg 2012

AbstractBackground Central giant cell granuloma is a benign condi-tion of the jaws which may present an aggressive behavior.Case report A 9-year-old boy was complaining of swellingin the floor of the mouth. A solid swelling was observed inthe area of the lower incisors. From the radiographic exam,we observed a radiolucent image in the mandibular bonewith well-defined limits extending from the apical region oftooth 33 to the apical region of tooth 42.Discussion Due to the diagnosis and the age of the patient, wechose a conservative treatment, administering subcutaneousinjections of calcitonin. During this treatment, no reduction tothe lesion was observed. Therefore, we chose to treat thelesion with triamcinolone acetonide. Monthly follow-upsdemonstrated good lesion reduction and the absence of anyclinical symptoms during the first 2 years. After a 3-yearfollow-up, the patient returned, presenting mobility of thelower incisors. A significant increase in the size of the lesionwas observed. After a biopsy, with the removal of tissue whichhad the appearance of a cyst capsule, microscopic analyseswere found to be compatible with a secondarily infected cyst.Two months following this procedure, the patient did notpresent tooth mobility anymore and the oral mucosa presented

a normal aspect. Following a radiographic exam, full lesionrepair was observed. These conservative treatments should bethe first option in cases of central giant cell granuloma and thepatient must be observed for a long period of time, until nofurther clinical or radiographic signs of lesions are observed.

Keywords Giant cell epulis . Central giant cell granuloma .

Calcitonin . Triamcinolone acetonide

Background

Central giant cell granuloma is a benign osteolytic conditionof the jaw. It can exhibit aggressive biological behavior,characterized by swelling, pain, rapid growth, cortical perfo-ration, tooth displacement, and root resorption [1, 2]. Typicalclinical examination findings present a smooth surface. Ra-diographic images of central giant cell granuloma appear asradiolucent unilocular or multilocular images [3–5]. The cen-tral giant cell granuloma is a benign condition, defined byWHO as a localized benign but sometimes aggressive osteo-lytic proliferation consisting of fibrous tissue with hemorrhageand haemosiderin deposits, presence of osteoclast-like giantcells, and reactive bone formation [6]. The extra osseouscounterpart is called peripheral giant cell granuloma(PGCG). This is a relatively frequent benign reactive lesionof the gingiva, originating from the periosteum or periodontalmembrane following local irritation or chronic trauma. PGCGmanifests as a red-purple nodule located in the region of thegingiva or edentulous alveolar margins.

Central giant cell granuloma is more prevalent in childrenand young adults (<30 years) than in adults and is twice asfrequent in the mandible than the maxilla [7–9]. In themaxilla, the lesion is usually located in the anterior area.

M. B. da Silva Sampieri :R. Y. F. Yaedú : P. S. S. Santos :E. S. Gonçales : E. Santa’Ana :A. Consolaro : L. B. CardosoDepartment of Stomatology, Bauru School of Dentistry,University of São Paulo (FOB-USP),Al. Dr. Octávio Pinheiro Brisola, 9-75,Bauru, SP, Brazil 17012-901

M. B. da Silva Sampieri (*)Department of Stomatology, Discipline of Oral Surgery,Al. Dr. Octávio Pinheiro Brisola, 9-75,Bauru, SP, Brazil 17012-901e-mail: mar_sampieri@hotmail.com

Oral Maxillofac Surg (2013) 17:229–234DOI 10.1007/s10006-012-0370-5

Many kinds of treatments have been suggested for centralgiant cell granuloma. The most common ones are simplecurettage, curettage with peripheral ostectomy, and marginalbone resection. However, these treatments present high re-currence rates in different studies [9–14]. Eisenbud et al. [9]performed a survey with cases of central giant cell granulo-ma of the jaws. They treated 18 patients with curettage andperipheral ostectomy. After a 2-year follow-up, only twopatients presented recurrence. In the same survey, they trea-ted five patients only with curettage, and there was norecurrence. Chuong et al. [14] performed a study with cen-tral giant cell granuloma. Five patients were treated withonly curettage. After a 5-year follow-up, none of the patientspresented with recurrence. The lesions in 17 patients wereclinically classified as nonaggressive (group I) or aggressive(group II). In general, group II lesions were found to affectchildren at an earlier age, were larger at the time of diagno-sis, and recurred more frequently than group I lesions.Aggressive lesions are characterized by one or more of thefollowing features: pain, paraesthesia, root resorption, rapidgrowth, cortical perforation, and a high recurrence rate aftersurgical curettage. The following histologic parameters wereassessed: fractional surface area occupied by giant cells(FSA), relative size index of giant cells (RSI), stromalcharacteristics, mitotic index, inflammatory cells, and he-mosiderin content. Histologic differences between the twogroups were not as clear as the differences in biologicbehavior. However, the aggressive lesions had a higherRSI, and recurrent giant cells lesions had a higher RSI andFSA; these parameters warrant further study. In addition,electron microscopic differences in a small number of ag-gressive and nonaggressive lesions were documented.

Some non-surgical options such as subcutaneous injectionof calcitonin or calcitonin nasal spray and the intralesionalinjection of corticosteroids (triancil) have shown effectivenessin the treatment of central giant cell granuloma.

Calcitonin is a hormone peptide produced by thyroid Ccells which can inhibit the activity of multinucleated giantcells in central giant cell granuloma. These multinucleatedgiant cells have particular features of osteoclasts in bonelacunar resorption [15]. Harris [16] was the first to proposethe injection of daily subcutaneous calcitonin as an alterna-tive to surgery for aggressive central giant cell granuloma;in a survey of four patients, full remission of the lesions wasachieved. In a work performed by Pogrel [17] with ninepatients treated with subcutaneous injections of calcitonin,no lesion reduction in the first 4 to 6 months of therapy wasobserved, but later, complete remission of lesions occurredin eight of these patients during an 18-month treatmentperiod.

Borges et al. [18] treated four patients with calcitonin, ofwhom one (male, 29 years old) was treated with subcutane-ous injections of calcitonin (100 IU) for 6 months and

calcitonin nasal spray (200 IU) for another 6 months. In thiscase, the lesion presented well-defined radiographic bound-aries, avoiding risks of mutilation. This patient later under-went surgery. A second patient (male, 19 years old) and athird patient (female, 15 years old) were treated with calci-tonin nasal spray (200 IU) with 12- and 28-month follow-ups, respectively. Both patients presented satisfactory bonerepair and did not have any recurrences. A fourth patient(female, 6 years old) presented an extensive lesion whichinvolved the mandible from the mandibular base up to thealveolar ridge, causing excessive facial asymmetry on theleft side. A hemimandibulectomy was proposed by an oto-rhinolaryngologist; however, a more conservative treatmentwas also proposed, which was readily accepted by thepatient. After 6 months of treatment with calcitonin nasalspray (200 IU), the lesion size was greatly reduced.

Several studies have revealed the efficacy of the intrale-sional injection of steroids in the treatment of central giantcell granuloma [19–21]; however, in some cases, this actu-ally provoked an increase in the size of the lesion [8]. Carlosand Sedano [20] evaluated the effect of intralesional injec-tions of corticosteroids in four patients. In three of them,residual lesions stayed the same without recurrences orcollateral effects during a follow-up of 5 years and 4 months.Nogueira et al. [22] adopted a protocol that consisted ofinjections of triancil with equal parts of anesthetic (lidocaine2 % with epinephrine 1:200,000). The dosage used was1.0 ml/cm3 of radiolucency in a total of six applications,twice a week. In 15 of these patients, a good response to themedicine was observed. In seven of the above-mentionedpatients, there was no need for further procedures. Otherprocedures consisted of curettage and osteoplasty. Thefollow-up periods varied from 4 to 8 years. This goodresponse was determined by the absence of further symp-toms, by the increase of radiopacity in the radiographies,and by the increasing degree of difficulty in injecting thesolution during the sequence of applications. Based onnumerous instances in the literature, Marx and Stern [10]reported a complete resolution rate of 65 % with intrale-sional injections of corticosteroids. Berti et al. [23] reported acase of central giant cell granuloma that experienced sponta-neous resolution after an incisonal biopsy; however, this re-port is not well corroborated in other articles in the literature.Rajeevan [24] treated one case of central giant cell gran-uloma with intra lesional injections of corticosteroids (tri-amcinolone acetonide). By the end of the sixth month, amarked reduction in facial swelling and almost completefilling of the osteolytic areas with new bone was noted. Inthe present case, the patient had a lesion which wasconsistent with central giant cell granuloma. The possibil-ity of performing a conservative treatment and the effi-ciency of this treatment motivated us to produce this paper(Table 1).

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Case report

A 9-year-old male leukoderma patient complaining of swell-ing in the floor of the mouth was referred to our clinic.During the clinical exam, a swelling was observed on themandibular ridge in the region of the lower incisors (Fig. 1).The mucosa had normal coloring; a little pain was presentand the lower incisors showed positive response to the pulpvitality test. In the radiographic, an intraosseous radiolucentlesion with well-defined boundaries, extending from theapical region of tooth 33 up to the apical region of tooth42 was observed (Fig. 2). The parathormone rate was nor-mal. Thus, we excluded the possibility of a brown tumor ofhyperparathyroidism. An incisonal biopsy was performed,and the microscopic exam revealed the presence of multi-nucleated giant cells in diffuse form in the highly cellular-ized connective tissue made up of spindle cells and ovoidcells. These findings were compatible with the diagnosis forcentral giant cell granuloma (Fig. 3).

In reference to this diagnosis and due to the patient's age,we decided on a conservative method of treatment. Theinitial treatment began with six applications of subcutaneouscalcitonin (60 mg, three times a week), totaling 48 doses.

During this treatment, the patient presented with nausea andvomiting, so we were unable to achieve the 60 desireddoses. During the application of calcitonin, we did not seeany signs of radiographic or clinical improvement of thelesion. Therefore, we opted for intralesional injections of2 ml of corticosteroid triancil in equal parts with the anes-thetic articaine (2 % with norepinephrine 1:200,000) for atotal of six doses of weekly applications (Fig. 4). Monthlyfollow-ups showed good reduction in the lesion size and theabsence of clinical symptoms during the next 2 years(Fig. 5). After 3 years and 6 months, the patient returnedto our clinic, presenting tooth mobility in the lower incisors.During the clinical exams, the patient presented swelling inthe gums at the lingual area of lower incisors. In the panoramicradiograph, we could see an increase in lesion size (Fig. 6). Allthe lower incisors presented pulp vitality. After 7 days follow-ing the last radiographic exam, we performed lesion aspira-tion, which revealed a bloody, yellow content. Then, we madea marsupialization, and part of a possible cystic lining wasremoved and sent for microscopic analysis. The diagnosisindicated a secondarily infected cyst. The patient wasinstructed to clean the cavity with chlorhexidine 0.12 % for7 days. Three months after this procedure, the patient did not

Table 1 Types of treatment for giant cell central granuloma

Authors Number Treatment Follow-up Results

Eisenbud et al. [9] 18 Curettage+peripheral ostectomy 2 years Recurrence in 2 cases

Eisenbud et al. [9] 5 Curettage 5 years Lesion repair

Pogrel et al. [17] 9 Injection of calcitonin 18 months Lesion repair

Borges et al. [18] 1° Injection of calcitonin 6 months

Borges et al. [18] 1° Calcitonin nasal spray 6 months Lesion reduction+surgery

Borges et al. [18] 2° Calcitonin nasal spray 12 months Lesion repair

Borges et al. [18] 3° Calcitonin nasal spray 28 months Lesion repair

Borges et al. [18] 4° Calcitonin nasal spray 6 months Great reduction in lesion size

Carlos [20] 4 Injection of corticosteroids 5 years No recurrences in three patients (lesions remain the same)

Nogueira et al. [22] 15 Injection of corticosteroids 4 to 8 years Lesion repair in seven patients

Rajeevan [24] 1 Injection of corticosteroids 6 months Great reduction in lesion size

Fig. 1 Swelling observed on the mandibular ridge in the region of thelower incisors

Fig. 2 An intraosseous radiolucent lesion with well-defined bound-aries, extending from the apical region of tooth 33 up to the apicalregion of tooth 42

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have any more tooth mobility and the oral mucosa had anormal aspect. After 5 years and 8 months from the firstclinical exam, we noted total lesion repair through a panoram-ic radiograph and a periapical radiograph (Fig. 7). The patientwas then referred for orthodontic treatment to correct hisocclusion. The patient returns to our clinic twice a year.

Discussion

Central giant cell granuloma may exhibit an aggressivebiological behavior, characterized by swelling, pain, rapidgrowth, bone expansion, cortical perforation, and root re-sorption [1, 2]. In the present case, the patient presentedswelling in the lingual gums of the lower incisors. There

was no clinical sign of peripheral giant cell granulomabecause the lesion was restricted to the bone, and therewas no presence of any local irritation or chronic trauma.This fact is consistent with relevant literature. A radiograph-ic exam demonstrated a radiolucent unilocular area involv-ing the mandibular midline, which is consistent with theliterature [3–5]. Central giant cell granuloma is more fre-quent in children or young adults (<30 years) than amongadults, and the condition is twice as frequent in the mandiblethan the maxilla [7, 8]. In the case in question, the patientwas 9 years old at the time of the first exam, when themandible was affected. Surgical procedures vary accordingto the lesion. With aggressive or recurrent lesions, boneresection, including healthy bone, is an option, but it resultsin large surgical defects which are undesirable in children oryoung adults (due to the aesthetic damage caused). Mainly,non-surgical methods such as daily doses of calcitonin andintralesional injections of corticosteroids are used [19, 21].In this case, when the patient came to our clinic he was9 years old. Despite his age (9 years old), the lesion did notpresent features of aggressive type giant cell granulomasuch as pain, paraesthesia, root resorption, rapid growth, orcortical perforation. Because of the absence of these symp-toms and due to the possibility of a large defect which couldhave resulted from surgical treatment followed by the loss ofteeth (lower incisors), we chose non-surgical treatment with

Fig. 3 The diagnosis for central giant cell granuloma

Fig. 4 Intralesional injections of 2 ml of corticosteroid triancil in equalparts with the anesthetic articaine (2 % with norepinephrine 1:200,000)for a total of six doses of weekly applications

Fig. 5 Monthly follow-ups showing good reduction in the lesion sizeand the absence of clinical symptoms during the next 2 years

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calcitonin nasal spray because we considered it less invasivethan the injection of corticosteroids. At the time of thistreatment, since calcitonin nasal spray was not availablewe used subcutaneous injections of calcitonin, which weconsider to be less invasive than injections of corticosteroidsdirectly in the lesion.

Due to collateral effects (nausea and vomiting) and non-reduction of the lesion, we chose to use intralesional injec-tions of triancil. Terry and Jacoway [11] published a proto-col for the treatment of central giant cell granuloma whichconsisted of intralesional injections of a solution with equalparts triamcinolone acetonide (Kenalog—10,10 ml/mg) anda local anesthetic (0.5 % marcaine with epinephrine1:200,000). The suggested dose is 1.0 ml/cm3 of radiolu-cency. The injection is administered to distinct sites all overthe lesion once a week for at least 6 weeks. In our case,triancil (the Brazilian equivalent of Kenalog®) was admin-istered weekly in doses of 2 ml along with articaine duringthe course of 6 weeks. This treatment is consistent with that

of Terry and Jacoway [11], Kermer [19], Kurtz [21], andNogueira [22]. This seemed to be a very reasonable practicedue to the simple technique, low cost, rapid reaction, and theprevention of both functional and esthetic defects [19].

In our literature review, we did not find any cases whereodontogenic or non-odontogenic cysts originated from giantcell central granuloma. In our case, the exacerbation of someclinical signs taken through an aspirated puncture revealedcontent similar to cystic content. Yoon [25] related a simul-taneous occurrence of a odontogenic keratocyst and a giantcell granuloma-like lesion in the mandible. However, in thiscase, there was a small component of giant cell granuloma,which suggests that the giant cell granuloma may have had areactive origin. Lombardi [26] reported that localizationaround the roots of teeth, especially if these have been rootfilled or if the vitality is negative or doubtful, can creatediagnostic difficulty and delay the appropriate diagnosis andtreatment. It is important to follow up the healing process ofpre-existing periapical radiolucencies of root-filled teeth orthose that appear following root canal treatment and, incases of failure or persistent radiolucency and clinical symp-toms, to perform surgery and to submit the specimen forhistological examination. In such a context, it is important toconsider that macroscopic examination does not allow oneto distinguish between central giant cell granulomas andeither periapical granulomas or cysts [27]. There have beenreports of ten lesions in eight patients with a rare andhistologically distinctive lesion composed of giant cell gran-uloma and fibrous tissue containing dispersed epithelialislands [28]. It is not possible assert whether this lesion isa variant of giant cell granuloma or of odontogenic fibroma,although some of the clinical, radiological, and histologicalfeatures are more in keeping with giant cell granuloma. It ispossible that this lesion is a new specific entity. In our case,the primary treatment was based on the histological featuresthat revealed the presence of multinucleated giant cells indiffuse form in the highly cellularized connective tissuemade up of spindle cells and ovoid cells. The patient had agood reduction in the lesion size and the absence of clinicalsymptoms over the course of 3 years and 6 months, whichshowed that the treatment was satisfactory. However, afterthis period of time, the patient presented tooth mobility inthe lower incisors. Another biopsy was performed, revealinga cystic cavity coated with a stratified pavement epitheliumwith a great infiltration of polymorpho and mononuclearleukocytes. Unlike Yoon [25], in the present case, the centralgiant cell granuloma did not have a reactive origin, being theprimary lesion. Unlike what was suggested by Lombardi[26], the teeth involved in the lesion had positive pulpvitality, which could not be confused with periapical gran-ulomas or cysts. Probably the cystic finding appeared afterthe central giant cell granuloma. In other words, the twolesions did not occur simultaneously and the central giant

Fig. 6 Panoramic radiograph showing an increase in lesion size

Fig. 7 Total lesion repair through a panoramic radiograph and aperiapical radiograph

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cell granuloma was not a reactive lesion. During injectionsof triamcinolone acetonide, we moved the needle in differ-ent directions. During some of these movements, we mayhave injured the pericoronary follicle of the canine tooth,which may have caused the development of a cyst.

According to Nogueira et al. [22], a satisfactory responseto the treatment would be determined by the absence ofsymptoms and by an increase in radiopacity during thepostoperative period. In this present case, after a 4-yearfollow-up, the patient did not present any more signs orsymptoms. Furthermore, a total lesion repair was observedin the radiographs.

The intralesional injection of corticosteroids (triamciloneacetonide) and treatment with calcitonin represents an effec-tive and conservative mode of treatment (resulting in partialor total lesion repair). Often, these procedures avoid theneed for large bone resection and large facial defects. Thisconservative method of treatment should be the first optionin cases of central giant cell granuloma. However, thepatient's condition must be monitored for a long period (atleast 4 years) until no further clinical or radiographic signsof a lesion can be observed.

Conflict of interest The authors declare that they have no conflictsof interest.

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