Please cite this article in press as: Aoki T, et al. Successful treatment by intralesional steroid injection in management of central giantcell granuloma of the jaw—Report of two cases. Asian J Oral Maxillof Surg (2012), doi:10.1016/j.ajoms.2011.11.007

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Case report

Successful treatment by intralesional steroid injection in management of centralgiant cell granuloma of the jaw—Report of two cases

Takayuki Aokia,!, Kazunari Karakidab, Haruo Sakamotob, Hiroshi Yamazakia, Mitsunobu Otsurua,Masashi Sasakia, Yuki Sakamotoa, Ken-ichi Aoyamaa, Yoshihide Otaa, Akihiro Kanekoa

a Department of Oral and Maxillofacial Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japanb Department of Oral and Maxillofacial Surgery, Tokai University Hachioji Hospital, 1838, Ishikawamachi, Hachioji, Tokyo 192-0032, Japan

a r t i c l e i n f o

Article history:Received 26 April 2011Received in revised form 9 November 2011Accepted 21 November 2011Available online xxx

Keywords:Central giant cell granulomaJawSteroidNonsurgical treatmentSurgery

a b s t r a c t

Intralesional steroid injections were administered in two patients with central giant cell granuloma ofthe jaw (CGCG). In these patients, intralesional corticosteroid injections resulted in disappearance of thelesions and callus formation at the sites of bone resorption on radiographs during follow-up. Surgicalcurettage or excision and radiation therapy have been reported as treatments for CGCG, in additionto intralesional steroid injection. However, CGCG occurs predominantly in young adults. Consideringthe tissue defects caused by surgical treatments and side effects of drugs, intralesional steroid injectionappears to be the most minimally invasive procedure and to yield favorable results. In treatment of CGCG,intralesional corticosteroid injection, a minimally invasive procedure, could be considered the first choicefor treatment of CGCG, while surgery should be performed for recurrence.

© 2011 Asian Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rightsreserved.

1. Introduction

Central giant cell granuloma (CGCG) is widely considered to benon-neoplastic lesions. According to the World Health Organiza-tion, CGCG is an intraosseous lesion consisting of cellular fibroustissue that contains multiple foci of hemorrhage, multinucleatedgiant cells, and trabecules of woven bone [1,2]. CGCG was originallyseparated from other giant cell lesions of bone by Jaffe in 1953 anddescribed as central giant cell reparative granulomas, since at thattime they were believed to be reparative lesions that might healspontaneously [3].

However, some CGCG exhibit aggressive behavior similar tothat of neoplasms [2,4,5]. Non-aggressive lesions account for mostcases, exhibit few or no symptoms, demonstrate slow growth, andare associated with neither cortical perforation nor root resorp-tion of the teeth involved in the lesions. Aggressive lesions arecharacterized by pain, rapid growth, cortical perforation, and rootresorption. They exhibit a marked tendency to recur after treat-ment, compared with non-aggressive types. More than 60% of allcases occur before age 30, and approximately 65% of cases arereported in women [2]. CGCG is found exclusively in the jaw, andapproximately 70% arise in the mandible [2]. Lesions are more

! Corresponding author. Tel.: +81 463 93 1121; fax: +81 463 91 5902.E-mail address: taoki123jp@ybb.ne.jp (T. Aoki).

common in the anterior portions of the jaw, and mandibular lesionsfrequently cross the midline. CGCG is very rarely located in theregion of the mandibular ramus to the condylar head, and thereare few case reports of it in this region in the literature [5]. Themost common treatment of CGCG of the jaw is surgery includingcurettage or complete en-bloc resection [6–8]. However, aggressivesurgery of the jaw can cause dysfunction of mastication and havepoor cosmetic effects. Recently, therefore, non-surgical treatmentssuch as intralesional corticosteroid have been performed in a fewcases of CGCG, and have been reported to yield favorable results[6–12]. We describe here two patients with CGCG of the mandiblewith successful treatment with intralesional corticosteroid.

2. Case reports

2.1. Case 1

A 3-year-old boy was referred to our department with a pain-less swelling in the right preauricular region of approximately 2months’ duration, according to his mother. His medical and fam-ily histories were unremarkable. Clinical examination revealeda swelling in the right mandible without trismus, occlusal dis-turbance, or paresthesia of the mandibular nerve. The overlyingmucosa was normal in color and texture. Panoramic radiographyrevealed a well-defined unilocular radiolucent lesion, extendingfrom the right mandibular ramus to the condylar head (Fig. 1). CT

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Please cite this article in press as: Aoki T, et al. Successful treatment by intralesional steroid injection in management of central giantcell granuloma of the jaw—Report of two cases. Asian J Oral Maxillof Surg (2012), doi:10.1016/j.ajoms.2011.11.007

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Fig. 1. Panoramic radiography revealed a well-defined unilocular radiolucent lesion, extending from the left mandibular ramus to the condylar head.

revealed an expansive, well-defined lesion, which had producedthinning of the right mandibular ramus (Fig. 2a and b).

An incisional biopsy was performed under general anesthesia.Histological examination revealed some fragments composed offibrous tissue with extensive proliferation of histiocytoid cells withnumerous multinucleated giant cells accompanied by marked hem-orrhage (Fig. 3a–c). Hemosiderin deposition was pronounced, withnumerous hemosiderin-laden cells (Fig. 3d). No osteoid formationwas observed. A diagnosis of CGCG was made. Case 1 was consid-ered to be a non-aggressive lesion since there was no pain, corticalperforation, or rapid growth despite its occupation of the entiremandibular ramus.

Results of laboratory investigations performed to rule out browntumors of hyperparathyroidism for parathyroid hormone (PTH),PTH-related peptide (PTHrP), calcium, and phosphorus were withinnormal limits. Since surgical treatment of this patient mighthave resulted in physical and psychological disorders, such asdevelopmental disorder of the mandible, dysfunction of mastica-tion, and facial deformities, non-surgical treatment was discussed,and intralesional corticosteroid injection was accepted by thepatient’s parents. Injection of triamcinilone acetonide (Kenacort-A 20 mg) was performed in the lesion throughout the regionof the right cheek weekly for 5 weeks. After three injections,

the lesion appeared to be decreased in size and harder, andsubsequent injections required more force. CT examination per-formed 2 weeks after the last injection revealed rapid resolutionof the lesion. CT examination 6 months after the last injectionrevealed bone remodeling and formation on the right mandibu-lar ramus (Fig. 2c and d). The patient was last seen 6 yearsafter the beginning of treatment, without evidence of recur-rence.

2.2. Case 2

A 12-year-old girl was referred to our department with a pain-less swelling in the right mandibular region of approximately 2months’ duration. Her medical and family histories were unre-markable. Intraoral examination revealed marked expansion of thebuccal cortical plate of the right mandibular body and ascend-ing ramus, though the overlying mucosa was of normal color andtexture. CT examination revealed an expansive, well-defined mul-tilocular radiolucent lesion, which had produced thinning of theright ascending ramus (Fig. 4a). Incisional biopsy was performedunder local anesthesia and confirmed the diagnosis of CGCG (Fig. 5).This case was considered a non-aggressive lesion based on clinicalbehavior.

Fig. 2. CT before the injection revealed an expansive, well-defined lesion, which had produced thinning of the right mandibular ramus (a and b). CT examination 6 monthsafter the last injection revealed bone remodeling and formation on the right mandibular ramus (c and d).

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Fig. 3. Histological appearance on biopsy. The biopsy specimen shows some fragments composed of fibrous tissue with extensive proliferation of histiocytoid cells withnumerous multinucleated giant cells accompanied by marked hemorrhage (a–c). Hemosiderin deposition is pronounced, and hemosiderin-laden cells are numerous (d). Noosteoid formation is observed.

Laboratory values for serum calcium, phosphate, alkaline phos-phatase, PTH, and PTHrP were within normal limits. Injection oftriamcinilone acetonide (Kenacort-A 40 mg) was performed in thelesion throughout the region of the right cheek and gingiva weekly

for 10 weeks. Four months after the last injection, the lesionappeared to be almost calcified on CT examination (Fig. 4b). Onthe last examination, performed almost 5 years and 6 months afterthe beginning of treatment, there was no evidence of recurrence.

Fig. 4. CT examination revealed an expansive, well-defined multilocular radiolucent lesion, which had produced thinning of the right ascending ramus (a). Four months afterthe last injection, the lesion appeared to be almost calcified on CT examination (b).

Please cite this article in press as: Aoki T, et al. Successful treatment by intralesional steroid injection in management of central giantcell granuloma of the jaw—Report of two cases. Asian J Oral Maxillof Surg (2012), doi:10.1016/j.ajoms.2011.11.007

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Fig. 5. The section of the incisional biopsy showed a large number of multinucleatedgiant cells in a highly vascular connective tissue.

3. Discussion

CGCG is divided into aggressive and non-aggressive types onthe basis of clinical and radiographic features [2,5]. The aggressivetype appears to be commonly found in young adults and to exhibitaggressive growth accompanied by bone expansion, and has a highrate of recurrence. On the other hand, the non-aggressive type isgenerally an asymptomatic painless swelling, grows slowly, andexhibits no cortical perforation or root resorption of teeth [2,5,9].But, there are no histologic differences between the aggressive andthe non-aggressive varieties [2,5,9].

Radiographically, CGCG presents as a well defined radiolucentdefect, which may be unilocular or multilocular [2,6,10,11]. Thelesion rarely extends outside the periostium of the jaw bones.The differential diagnosis, based on radiographic findings, includesodontogenic cysts, odontogenic tumors such as ameloblastoma,simple bone cyst, and aneurysmal bone cyst, in addition to CGCG[10–12]. Definitive diagnosis requires histopathological exami-nation, since it is difficult to establish the diagnosis based onimaging findings alone. Histopathologically, CGCG exhibits mult-inucleated giant cells in a background of ovoid to spindle-shapedmesenchymal cells [1,2,6,10]. The giant cells are typically seen ina hemorrhagic field containing numerous poorly defined vascularchannels, which may be quite prominent. A patchy distributionof cellular elements is one feature that helps differentiate CGCGfrom true giant-cell tumors. In addition, hemorrhage, hemosiderindeposition, and hemosiderin-laden cells are also observed in CGCG,allowing it to be distinguished from true giant-cell tumors [2,5,10].Because the histological features of CGCG of the jaw are indistin-guishable from those of brown tumors due to hyperparathyroidism,laboratory investigations are required to rule out brown tumorsbefore treatment. In the two patients presented here, the labora-tory values for parathyroid hormone (PTH), PTH-related peptide(PTHrP), calcium, and phosphorus were all normal, suggesting lackof hyperparathyroidism [10,13].

Treatments for CGCG may be broadly divided into surgical andnonsurgical treatments [2,5–15]. Nonsurgical treatments include(1) corticosteroids, (2) interferon alfa (IFN-!), and are now beinginvestigated [2,5–14]. In the two patients presented here, intrale-sional corticosteroid injections resulted in disappearance of thelesions and callus formation at the sites of bone resorption, demon-strating the usefulness of this nonsurgical approach. In vitro it wasshown that dexamethasone on the one hand stimulates the pro-liferation and differentiation of osteoclast precursors, but on the

other hand inhibits lacunar resorption by mature osteoclasts iso-lated from giant cells tumors of the bone [6,15]. Regarding themechanism of action of intralesional steroid injection in treat-ments of CGCG of the jaw, on the basis of the experimentalevidence, it is hypothesized that the extracellular production ofbone resorption mediating lysosomal proteases by the giant cellsis inhibited and steroids induce apoptosis of osteoclast-like cells[6,9]. Although these patients were cases of non-aggressive type,it is unknown whether intralesional corticosteroid injection is alsouseful for the aggressive type of CGCG. Moreover, no reports inwhich the effectiveness of intralesional corticosteroid injection forCGCG is described separately for the aggressive type and non-aggressive type are available. However, no histological differencesare observed between the aggressive and non-aggressive types, andit appears that intralesional corticosteroid injection may also beeffective for the aggressive type. Kurtz et al. have noted that the pro-tocol for this type of treatment consists of the intralesional injectionof a mixture consisting of equal parts of triamcinolone acetonideand a local anesthetic [8]. The suggested dosage is 2 mL/2 cmof radiolucency. However, because large-volume injections mayproduce pain due to increase in tissue pressure after injections,triamcinolone acetonide alone was administered without a localanesthetic to our patients. The injections are given in multiple loca-tions throughout the lesion in a weekly regimen for at least 6 weeks[8].

It has been sporadically reported that administration of IFN-!-2a to patients with CGCG has not yielded improvement [2,6,14].However, numerous reports suggest that IFN-! administered asmonotherapy for aggressive CGCG is capable of terminating therapid growth of lesions and consolidating or even diminishing theirsize, though additional surgery is probably still required to elimi-nate lesions [2,6,14]. Total remission of lesions cannot be achieved,despite high doses of IFN, probably because IFN has no directinhibiting effect on proliferating tumor cells. The effectiveness ofmonotherapy with interferon alfa-2a has thus been questioned.

Furthermore, radiation therapy has reportedly been successfulin treating CGCG [16]. However, since CGCG is not life-threateningand is likely to resolve with other types of treatments, radiationtherapy, which is the maximally-invasive procedure, should not beperformed in patients with CGCG.

Regarding surgical management of CGCG, since curettage hasreportedly resulted in both resolution and recurrence of CGCG,complete en-bloc resection is desirable [5]. However, CGCG, isfound predominantly in young adults. Since surgical excision ismore likely to cause tissue defects or effects on growth in thebones of the jaw, intralesional steroid injection, which is a mini-mally invasive procedure and less costly, should be considered thefirst choice for treatment of CGCG, while surgical treatment shouldbe performed for recurrent CGCG.

4. Conclusion

Two patients with CGCG of the jaw were treated with intrale-sional steroid injections, demonstrating the usefulness of thistreatment. Intralesional corticosteroid injection, a minimally inva-sive procedure, could be considered the first choice for treatmentof CGCG, while surgery should be performed for recurrence.

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