Journal of Research in Medical and Dental Science 2020, Volume 9, Issue S1, Page No: 50-56 Copyright CC BY-NC 4.0 Available Online at: www.jrmds.in eISSN No. 2347-2367: pISSN No. 2347-2545

Unusual presentation of Aggressive Giant cell with non-vital tooth Case report: The importance of using CBCT in diagnosis of the non-odonto- genic .

Sandra H El-khatib1*, Dontra B Scott2, Asgeir Sigurdsson3 Pediatric and Orthodontics Department, King Saud University, Riyadh, Saudi Arabia Department of Endodontics, College of Dentistry, New York University, New York, USA

ABSTRACT Introduction: This case reports a Central Giant Cell Granuloma (CGCG); a that is uncommon, idiopathic, and be- nign. However, it can be quite invasive and has reported high rate of recurrence. Its radiographic similarity to routine

Method: a 55-year-old Caucasian man presented with tenderness on palpation of the apical area of upper canine, patient inflammatory peri-radicular lesions can lead to not only delay in diagnosis, but also further delay in successful treatment.- cal radiograph. Based on radiographic signs and symptoms the patient underwent regular endodontic treatment. During thehad endodontic no other symptoms. visits, there A large was aperiapical suspicion lesion of a more associated complex with diagnosis. the canine A CBCT and firsttaken premolar that further was increased realized on the a concernperiapi about the lesion such that a biopsy was thought to be needed. Result: Evaluation of every single detail of a radiographic image, signs and symptoms must be taken in consideration. If there is a large radiolucent lesion on the radiographic image, CBCT image should be considered, which is a very versatile tool for early diagnosis of Odontogenic and Non–Odontogenic lesions especially with cases of unusual presentation. The - ulomas. Conclusion:Diagnosis is confirmed The importance by histological of computed biopsy tomography-guided and blood tests, which biopsy are in important the diagnosis tools of to such diagnose inaccessible the Giant lesions, Cell Gran cone beam images help in detecting cases misdiagnosed non-odontogenic lesions from the normal digital periapical radiograph

Keywords:films. CBCT, Biopsy, Radicular cyst, Central Giant Cell Granuloma (CGCG)

HOW TO CITE THIS ARTICLE: Sandra H. El-khatib, Dontra B. Scott, Asgeir Sigurdsson, Unusual presentation of Aggressive Giant cell Granuloma with non-vital tooth Case report: The importance of using CBCT in diagnosis of the non-odontogenic lesions, J Res Med Dent Sci, 2021, 9(S1): 50-56.

Corresponding author: Sandra H. El-khatib population is estimated to be 0.0001%. The sur- e-mail: [email protected] vival rate after the surgical therapy and removing Received: 09/03/2021 the lesion is 76.1% after 5 years [5]. It occurs most Accepted: 23/03/2021 in young adults with a female predilection and is the most common in mandibular posterior. Giant INTRODUCTION cell reparative granuloma accounts for 17% of all benign lesions of the jaw [6]. described by Jaffe in 1953 as a giant-cell reparative The Central Giant Cell Granuloma (CGCG) was first benign interosseous lesion that might be aggres- that it was not a true neoplasm, but it might be the sive World osteolytic Health Organizationproliferation definesconsisting the ofCGCG cellular as a resultgranuloma of a localof the reparative jaw bones. reaction It was hypothesized[1]. The cen- - rhage, aggregations of multinucleated giant cells, non-odontogenic Multilocular radiolucency of the [7].fibrous CGCG tissue belongs and to contains the family many so-called foci of GCLs, hemor to- jaws,tral giant it may cell also granuloma appear asis classifieda Monocular as a radiolu benign- gether with brown tumor of the hyperparathyroid- cent. Clearly, this idiopathic lesion is not derived - from pulpal pathosis. But its presentation around guish solely by microscopic examination [8]. The the roots of teeth can lead to incorrect diagnosis radiographicism, giant cell appearance tumor. In which of the is CGCG difficult may to be distin con- [2-4]. The incidence of CGCG in the Netherland’s fused with other jaw lesions. Typically, it has a well

Journal of Research in Medical and Dental Science | Vol. 8 | Issue 7 | November 2020 50 Sandra H El-khatib, et al. J Res Med Dent Sci, 2021, 9 (S1):50-56 demarcated margin; can produce adjacent root di- with symptomatic periapical periodontitis for both vergence; create smooth, concave root resorption; teeth #5 and #6. The Treatment plan was Endodon- - tic therapy for both teeth #5 and #6 was recom- ing to location, as central giant cell granuloma in mended. boneand cross or peripheral the midline. giant CGCGs cell granulomaare classified, in gingiva.accord METHODS AND MATERIALS The most troublesome characteristic of the CGCG is its locally aggressive destructive nature and high The endodontic therapy was initiated for each tooth recurrence rate [9]. The present report illustrates a on separate dates. Local anesthesia used was 1.8 mL rare case of CGCG, with an atypical clinical presen- of 2% lidocaine with 1:100,000 epinephrine (Xylo- tation; attention has been focused on Cone Beam Computed Tomography (CBCT), guided biopsy and and palatally. Rubber dam application was applied. a surgical treatment. caine; Dentsply, York, PA) via infiltration buccally chamber was sclerosed and no vital pulp tis- CASE PRESENTATION sueThe was canine observed was treated (Figure first, 1). The access working was opened, length A 55 years old Caucasian man was referred to the was measured using apex locator and a periapical post graduate endodontics clinic. The patient’s chief x-ray (Figure 2). The tooth was instrumented by complaint was tenderness above the maxillary right canine on palpation. His medical history reveals - type I diabetes that was well controlled, and an al- pointmentrotary ProTaper the premolar files with was a working treated. length Upon accessof 25.5- lergy to cats and dust. The patient’s dental history ingmm theto a tooth, F2 size it (Figure was noted 3). During that the the pulp following chamber ap revealed no reports of previous buccal swelling, or was sclerosed but a vital pulp tissue was detected. facial pain, and he denied any history of traumatic dental injury [10-14]. On the Clinical Examination, the Extra Oral Exam- ination revealed normal appearance with no swell- ing but tenderness on palpation above the upper

Intra Oral Examination revealed normal appear- ancemaxillary to the right oral canine mucosa, and with first no premolar. swelling Whileand there the was no pain to percussion on either tooth #5 or #6, but tenderness on palpation above the upper maxil-

Figure 1 (A and B): Microscopic pictures shows pulp chamber sclero- no tenderness on palpation of the adjacent palatal sis in tooth #5 and #6 andlary buccalright canine regions. and Class first premolarV composite [15]. restorations There was were in place on both teeth. The Tooth Sensibility Tests consist of two different tests: the cold test using endo ice and the analytic technology electric pulp test (EPT). All upper teeth, and canine #6 responded with in normal limits to theseexcept tests, the maxillarythere was upperno response left first in premolareither of the #5 two teeth # 5 and #6 to neither of the tests. Both teeth gave no response on cold test and EPT with reading 80. The Radiographic Findings from the Figure 2: Periapical radiograph exhibited large well defined unilocu- lar round shaped radiolucency of approximately 30 mm that involved radiolucency of approximately 30 mm that involved both the canine and first premolar. The periodontal ligament space periapical radiographs revealed large well-defined (PDL) of the canine was noted to be wide and irregular, for the first premolar it was considered to be more regular. There was no appar- The Diagnosis Based on the clinical test results and ent displacement of the involved teeth on the periapical film and no both the canine and first premolar. root resorption was detected. presence of radiopacity in the crowns of both teeth. periapical radiograph findings, was necrotic pulp

Journal of Research in Medical and Dental Science | Vol. 8 | Issue 7 | November 2020 51 Sandra H El-khatib, et al. J Res Med Dent Sci, 2021, 9 (S1):50-56

After the second endodontic visit, it was decided to investigate the periapical lesion further with a lim- - tive treatment was recommended because of the factited thatfield the of view premolar cone hadbeam vital exposure. tissue present. This adjunc Also, because it was noted at the second visit for the ca- nine that the anesthetic needle passed easily into a lumen, indicating a very minimal cortical bone cov- erage facial to the radiographic radiolucency. In ad- dition to the extent of the radiolucent lesion on the periapical radiograph was of concern and therefore Figure 3: X-Ray shows working length of teeth #5 and #6. Initial film with angulation shows large unilocular radiolucent lesion associated with tooth #5,#6 expanded to tooth no.#4 the lesion [16]. a CBCT image would help elucidate the exact size of This indicated a possible misdiagnosis for the pre- Cone beam computed tomography radiograph molar. The premolar was instrumented by rotary Imaging findings: non-corticated, unilocular radiolucency of the an- terior right maxilla. The There radiolucency was a extended well-defined, an- (FigureProTaper 4). files Irrigation to a working used for length both ofteeth 20.5 was mm sodi for- teriorly to the maxillary right lateral incisor, poste- umpalatal hypochlorite, root and 20 EDTA, mm chlorohexidinefor buccal root andto a calcium F1 size riorly to the maxillary right second premolar, and hydroxide intracanal medicament was placed for 1 week. Obturation was completed using thermal and the antero-medial wall of the right maxillary vertical condensation technique and AH plus sealer sinus.superiorly The throughpalatal cortexthe floor was of thenoted right to nasalbe thinned cavity (Figure 5). (Figure 6). The buccal cortex overlying the canine

in–first the premolarsuperior area region (Figure was 7).thinned and expanded, and notably the expansion flowed over normal bone

Figure 4: Master cone x-ray of teeth #5 and #6 before obturation

Figure 6: Reconstruction view of cone beam Panoramic reconstruction of the 40 x 40 mm cone beam CT study of the anterior right maxilla shows the well-defined, non-corticated, unilocular radiolucency ex- tending from the maxillary right second premolar anteriorly to the maxillary right canine region. The radiolucency has perforated the anteromedial wall of the right maxillary sinus and extended into the sinus cavity.

Figure 5: x-ray shows obturation of teeth #5 and #6. post-operative film with parallel technique shows the extension of the lesion.

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1:100,000 epinephrine (X) to involve the entire sur- - tion, and suturing, all surgical procedures were per- formedgical site. with With an the Operating exception Microscope of incisions, (OPMI flap elevaPICO; Carl Zeiss, Göttingen, Germany). A vertical incision was performed with a #15 scalpel

following an intrasulcular incision. The tissue was blade and a triangular full thickness flap was raised-

gently reflected toward the apical area with a Mol Figure 7: Bucco-palatal image of the cone beam CT study shows the wereten 2– kept 4 curettes moistened (G Hartzell with sterile and salineSon Inc, throughout Concord, well-defined, non-corticated, unilocular radiolucency has expanded CA). The tissues exposed by the reflection of the flap and perforated the labial cortex, overflowing onto adjacent, intact, normal bone. The overflow feature (arrow) is the second key finding that is not consistent with the pathophysiology of radicular cysts. lesionthe surgery was tonoted avoid [18,19]. the bone Complete or the soft-tissue perforation flap Imaging impression: offrom the drying buccal out. cortex Upon was reflection observed, the Figureextent (5).of the A right maxilla were considered to be consistent with benign developmental Thecystic findings process, of favoring the anterior uni- × 4cm non-pulsating lesion extending from the apex cystic ameloblastoma over keratocystic odontogen- ofwell-defined tooth #4 to irregular the apical shaped region dark of tooth tan #6brown was 3cmnot- ic tumor () and biopsy was ed. The lesion had embedded itself in the mucoperi- advised (Figure 8). osteum and required careful separation. A small incisional biopsy was performed using a #15 scalpel blade to remove a 1cm × 1cm section of the lesion to submit for histological examination. Tissues were approximated and adapted using 6-0 Vicryl interrupted and sling sutures. Firm pres-

dampened with sterile saline for 5 to 10 minutes tosure ensure was appliedclose adaptation to the tissues of the with soft a tissue gauze to swab the remaining bone. Post-operative written and verbal instructions were given. Patient was advised to take analgesics (ibuprofen 400 mg every six hours or Figure 8: Axial image of the cone beam CT study shows the well-de- paracetamol 500 mg every six hours) as required fined, non-corticated, unilocular radiolucency of the anterior right (Figure 9). maxilla lacking the balloon-like, hydraulic expansion associated with radicular cysts. Surgical treatment Patient presented to the post graduate endodontic clinic for incisional biopsy of the lesion that was procedureidentified viawere the reviewed cone beam with imaging. the patient The and surgical con- sentprocedure, was obtained. risk and All benefits procedures associated were performed with the by an endodontic post graduate resident (DS) un- the apices of the teeth to be treated and the adja- Figure 9: Picture after reflecting the soft tissue for biopsy, shows com- der local anesthesia [17]. Infiltration buccally over plete perforation of the buccal cortex with a well-defined irregular cent teeth was undertaken using 1.8 mL of 2% li- shaped dark tan brown 3cm x 4cm non-pulsating lesion extending docaine with 1:50,000 epinephrine (Xylocaine; from the apex of tooth #4 to the apical region of tooth #6 was noted. The lesion had embedded itself in the mucoperiosteum and required careful separation. and palatally with 3 mL of 2% lidocaine containing Dentsply, York, PA) followed by infiltration buccally

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- tureof CGCG (2,10). have The not CGCG been usually clearly demonstrates defined, and radiothere- graphicare many and of clinical conflicting features descriptions of a benign in lesion the litera with some aggressive characteristics. The Cone Beam Computed Tomography (CBCT) is an extra-oral imaging system which was developed in the late 1990s. It produces 3-D scans of the max- illo-facial skeleton at a lower radiation dose than more traditional CT. A CBCT scan should be con- sidered after a comprehensive clinical examination Figure 10: The Microscopic description showed a portion of soft tissue and after periapical 2-D radiographic evaluation composed of cellular fibrous connective tissue with abundant diffuse- ly scattered multi-nucleated giant cells extravagated red blood cells [12-13]. In our presented case, there was a debate are seen in background. Residual and Reactive bone are also seen. whether to do a cone beam or not and whether to Differential Diagnosis was given wither its Brown Tumor Disease or Central Giant Cell Granuloma as they have the same Microscopic His- harvest a biopsy or not. Initially it was believed tology Appearance. that the lesion was of odontogenic origin and as- The Gross pathology of the biopsy described an sociated with non-vital tooth (endodontic lesion) and therefore no need to expose the patient for the dark tan and brown tissue. The microscopic de- radiation, and more cost. scriptionirregular showed shaped a rough-surfaced portion of soft tissue portion composed of firm, As a CBCT scan should only be considered if an ad- ditional information from the 3-D images will aid diffusely scattered multi-nucleated giant cells. in the diagnosis [14]. It has shown that CBCT has Extravagatedof cellular fibrous red connectiveblood cells tissue were withseen abundant in back- - ground [20,21]. Residual and reactive bone was ing periapical periodontitis compared to periapi- also seen (Figure 10). A Differential diagnosed was calsignificantly 2D radiograph, higher using diagnostic human accuracy histopathological in detect given either Central giant cell granuloma or brown tumor of hyperthyroidism. Patient was referred to up 38% more periapical lesions were detected with the oral surgery department for further evaluation CBCTfindings compared as a reference with periapical standard [15].radiographs Additionally, [16] and possible sectional surgery, where the total le- and CBCT has twice the odds of detecting a periapi- sion would be removed. Laboratory Blood tests cal lesion than with conventional radiographs [17]. were requested for differentiation between CGCG It has been suggested that CBCT aids in diagnosis and brown tumor lesions (Figure 11). of nonodontogenic lesions such as CGCG (14) and it can also aid in management of CGCG. As CBCT Component Standard Range Patient Value is needed for the Pre-surgical assessment prior PTH, INTACT 15 - 75 pg/mL 48 to complex peri-radicular surgery, and to identify CALCIUM 8.3 - 10.3 mg/dL 9.3 which treatment is preferred for management of GLUCOSE 70 - 100 mg/dL 227 the CGCG depending on the aggressiveness of the Figure 11: The above table of Blood Test Result shows normal Calcium CGCG lesion [14,16]. level in patient’s blood and does not shows Hyperthyroidism which exclude Brown Tumor Disease and proves its Central Giant Cell Gran- After assessment of the CBCT image and identi- uloma. fying the aggressiveness, its deep extent, and its DISCUSSION close relationship to the surroundings anatom- ical structures, it has been decided that only an In the present report, we describe a rare case of excisional biopsy will be done in the endodontic CGCG developing close to non-vital tooth maxilla department, and then depending on the histolog- canine without any history of pain or facial swell- ing. In contrast to radicular cyst, CGCG is non-odon- oral maxilla-facial department for complete surgi- togenic bone lesion, that looks similar to radicular calical excisionfindings and the managementpatient would if beneeded. referred CGCG to hasthe cyst in radiographic examination, but on a cone various histopathological differential diagnosis beam image it shows the difference in expansion, includes: Brown Tumour of hyperparathyroidism, destruction, and invasion. The radiologic features PGCG, , GCT, Aneurysmal bone cyst and

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Fibrous dysplasia [2]. In our microscopic histolog- much better prognosis. This is due to its aggres- ical investigation taken from the biopsy, we could siveness and has chance to turn into malignant le- not identify the diagnosis if it is a CGCG or a brown sion if left for long time. There is a high incidence tumor of hyperparathyroidism. They have the sim- of the CGCGs clinicopathologic features associated ilar microscopic histological picture, and our case with necrotic teeth or teeth that had received pre- was presenting similar clinical features. The only vious . This incidence is 20% way to differentiate between the two, is by the lab- of CGCG were associated with necrotic teeth and oratory blood tests. The brown tumor associated 88% were associated with previous endodontic with hyperthyroidism has increase of calcium in treatment [22]. Though it is not clear if the CGCG the blood. So, the laboratory tests were request- is responsible for the need for endodontic treat- ment or if the presence of the lesion was misdiag- lesion. That diagnosis was made due to absence of nosed as a periapical lesion of endodontic origin. increaseed, and the of diagnosisthe calcium was in confirmedthe patient to blood be a CGCGlabo- In this case report, the endodontic misdiagnosis ratory test. was at the beginning of the treatment until fur- ther investigation and CBCT were requested due Several alternative treatments have been suggest- ed in the literature, including interferon alpha-2a, the fact a vital pulp tissue was encountered in the calcitonin and intra-lesional corticosteroid injec- premolar.to the large Nowadays,size of the periapicalthe advance radiolucency technology and of tion. Surgical methods that have been described CBCT allowed more image accuracy, 3-D anatomic for removal of aggressive CGCRGs, include curet- details and low dose exposure [12-17]. It is rec- tage and cryosurgery, curettage and peripheral - osteotomy, excision and followed by reconstruc- ation in case of large periapical radiolucency, to tion by using an autologous iliac crest bone graft includeommended the CGCGs and emphasized in the differential for CBCT diagnosis consider to [7,18]. The traditional therapy of CGCRG has been the endodontic treatment. CGCGs malignant trans- surgical local curettage, and this has been report- formation is rare but might occur if left untreated. ed with a high success rate or about 76.1% - 80% An early diagnosis of CGCGs is therefore crucial to [5,]). Non-surgical treatment of CGCRG has though avoid serious complications [22-24]. been suggested as a good treatment option for small, slowly, enlarging lesions [7,19,20]. Success- The patient in this case report had an aggressive ful treatment of painful, large, and rapidly growing variant of CGCG: The lesion was larger than 5 cm, lesions is more likely achieved by surgical remov- the cortical bone erosion was demonstrated by al. Many authors do agree that a correct diagnosis CBCT examination. It was fast growing and the and complete surgical excision with curettage is extent and aggressiveness of the lesion anteri- effective in complete resolution of the CGCG le- or-posterior and mesiodistal, which made conven- sions [5,7,20,21]. tional conservative surgical treatment (curettage) unfeasible. Therefore, the patient was referred to This case report had a misleading diagnosis at the the oral-maxilla facial department for complete beginning between the odontogenic endodontic sectional excision. This case shows also that even diagnosis and non- odontogenic CGCG diagnosis, due to presence of endodontic signs and symp- all the criteria for diagnosis of aggressive one, be- toms associated with a necrotic tooth, periapical causeaggressive in this variants case it was of CGCG asymptomatic, do not always there fulfill was radiolucent and tenderness on palpation. It is not no swelling, no tooth displacement or root resorp- possible to state if the non-odontogenic CGCG le- tion [2,6,8,9]. It is worth noting that there is no sion origin in our case was associated by the end- histological differences between the aggressive odontic or it just occurred by chance at and non-aggressive varieties. Literatures have the same time [22], or if the CGCG lesion caused agreed upon using their clinical behavior to mark the pulpal necrosis in the canine due to the extent their aggressiveness progression. and aggressiveness of the CGCG lesion, that caused excessive pressure on the neurovascular bundle to CONCLUSION the tooth. CGCG is a bony lesion that can be misdiagnosed as The CGCG is a rare lesion, that has high incidence an apical lesion of endodontic origin. The current of misdiagnoses with other lesions, which compli- case report presents a case of unusual presenta- cates the fact that the early detection of CGCG gives tion of a CGCG. The CGCG lesion was associated

Journal of Research in Medical and Dental Science | Vol. 9 | Issue S1 | April 2021 55 Sandra H El-khatib, et al. J Res Med Dent Sci, 2021, 9 (S1):50-56 with nonvital tooth, and the correct extent of the le- lesions of the jaws: a clinicopathologic study. J Oral Maxil- sion was not appreciated until a CBCT examination lofac Surg 1986; 44:708-13. was done. The suggested way for differentiation is 10. Kaffe I, Ardekian L, Taicher S, et al. Radiologic features by using CBCT and surgical biopsy after full evalu- of central giant cell granuloma of the jaws. Oral Surgery. ation of clinical examination and endodontic tests. 1996; 81:720-6. Early accurate diagnosis of CGCG is crucial, to avoid 11. - serious complications and malignant transforma- tematic review of the radiographic characteristics with the additionStavropoulos of 20 F, newKatz J.cases. Central Dentomaxillofac giant cell : Radiol. 2002;a sys tion. 31:213-7. ACKNOWLEDGMENTS 12. Patel S, Dawood A, Whaites E. 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