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 Table of Contents  
Year : 2019  |  Volume : 31  |  Issue : 2  |  Page : 171-175

Aggressive central giant cell granuloma – A case series with literature review

Departments of Oral Medicine and Radiology, Bharati Vidyapeeth Deemed University Dental College and Hospital, Pune, Maharashtra, India

Date of Submission25-Feb-2019
Date of Acceptance19-Apr-2019
Date of Web Publication24-Jun-2019

Correspondence Address:
Dr. Manjula Hebbale
Department of Oral Medicine and Radiology, Bharati Vidyapeeth University Dental College and Hospital, Pune - 411 043, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiaomr.jiaomr_45_19

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Central giant cell granuloma (CGCG) of the maxillofacial region is generally present as an asymptomatic slowly growing localised disease to aggressive neoplasm-like rapid expansive progression typically present with localised disease. It is an uncommon benign lesion with a low incidence that occurs in the craniofacial region especially in jaw bones. It is a localised osteolytic lesion with varied biologic behavior of aggression which affects the jaw bones. There is much controversy regarding it arising as a result of trauma and its connection with the giant cell lesion seen in the long bones. As it is uncommon, it does not possess any characteristic clinical or radiologic features and resembles neoplasms; the diagnosis is initially some odontogenic or non-odontogenic neoplasm till a definitive histologic diagnosis of CGCG is made. We report five cases of an aggressive form of CGCG at different sites of involvement in the jaw bones.

Keywords: Calcitonin, giant cells, granuloma, multilocular radiolucency

How to cite this article:
Hebbale M, Giroh VR, Mhapuskar A, Hiremutt D. Aggressive central giant cell granuloma – A case series with literature review. J Indian Acad Oral Med Radiol 2019;31:171-5

How to cite this URL:
Hebbale M, Giroh VR, Mhapuskar A, Hiremutt D. Aggressive central giant cell granuloma – A case series with literature review. J Indian Acad Oral Med Radiol [serial online] 2019 [cited 2022 Nov 26];31:171-5. Available from: http://www.jiaomr.in/text.asp?2019/31/2/171/261092

   Introduction Top

Central giant cell granuloma (CGCG) is an uncommon benign but sometimes aggressive, osteolytic proliferation consisting of fibrous tissue with haemorrhage and hemosiderin deposits and the presence of osteoclast-like giant cells with reactive bone formation. Etiopathogenesis is not known but bone haemorrhage from past trauma has been suggested as a probable cause. Some considered it to be a reactive lesion to an unknown stimulus and some to a neoplastic lesion.[1] Peak incidence is in the second decade and more common in females. A most common site is anterior to mandibular first molar and often crosses the midline. Radiographically well-defined uni/multilocular radiolucency is seen with these lesions.

Patients typically present with localised disease that has an insidious natural clinical course, with solitary lesions identified incidentally.[2]

   Case Series Top

Case No 1

A 24-year-old female patient reported with pain and swelling in the right back region for two months. No history of trauma was reported. On extra oral examination, swelling was seen on the right side of the face extending from the outer canthus of eye to lower border of mandible superior-inferiorly and antero-posteriorly from the corner of mouth to angle of mandible, measuring approx. 5 × 4 cm. The overlying skin was normal in color with no signs of bleeding or ulceration. On palpation, the swelling was non-tender, firm in consistency [Figure 1]a. On intra-oral examination, a single large growth was seen involving the upper and lower right posterior vestibular mucosa, attached gingiva, extending from distal aspect of 26 to 1 cm beyond the pterygopalatine raphe and superior-inferiorly from upper buccal vestibule to lower buccal vestibule measuring approx. 3 × 4 cm in size obliterating both the upper/lower vestibular mucosa. The overlying surface was irregular, bright red, and ulcerated. Lingual tilt with 46, 47 was seen. On palpation, the growth was tender, firm in consistency. It is non-fluctuant, non-compressible, and non-pulsatile [Figure 1]b.
Figure 1: (a) Extraoral view, (b) Intraoral view, (c) CT scan (coronal section)

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Radiographically, CT showed a well-defined expansile multilocular lytic lesion measuring 5.6 cm in mediolateral dimension, 4.3 cm in anteroposterior dimension, and 5 cm in craniocaudal dimension, involving the right angle of mandible and coronoid process with enhancing soft tissue mass. Also, thinning and breach in the overlying cortex was seen [Figure 1]c.

Case No 2

A 26-year-old female patient reported with a swelling in the upper left back region of the jaw for one month. She gave a history of extraction of the upper left mobile tooth after which the swelling appeared. The swelling was painful and initially was smaller in size which increased to the present size. The pain associated with swelling was dull and intermittent. On extraoral examination, no facial asymmetry was seen [Figure 2]a. On intraoral examination, a well-defined swelling was seen involving the upper left posterior vestibular mucosa, attached gingiva, alveolar mucosa, and palatal mucosa with respect to a 24–27 region with obliteration of buccal vestibule. On palpation, the swelling was tender and firm in consistency. There was grade II mobility with 24, 25, 27, 28 [Figure 2]b. CT scan revealed well-defined mass evident in the upper left maxilla with the partial obliteration of left maxillary sinus and destruction of floor, medial, and lateral wall of maxillary sinus [Figure 2]c and [Figure 2]d.
Figure 2: (a) Extraoral view, (b) Intraoral view, (c) CT scan (coronal section), d – CT scan (axial section)

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Case No 3

A 24-year-old male patient reported with a swelling in his lower front region of jaw for 25 days. He gave history of trauma 5 years back. The swelling was small in size and enlarged to the present size and was associated with pain, following a trauma 25 days back.

On examination, facial asymmetry was present. A diffuse swelling was seen extending superoinferiorly from lower lip to about 2 cm below the anterior lower border of the mandible and mediolaterally from the right corner of the mouth to left corner of the mouth [Figure 3]a. Intraoral examination revealed a diffuse swelling in the region of mandible extending from 36 on the left side, crossing the midline up to 46 on the right side. The swelling was extending to involve the labial and lingual mucosa. On palpation, the swelling was tender and firm in consistency. There was displacement of lower anterior teeth, i.e. 31, 32, 41, and 42 were labially tilted, whereas 33, 34, 35, 36, 43, 44, 45, 46 were lingually tilted [Figure 3]b.
Figure 3: (a) Extraoral view, (b) Intraoral view, (c) CT scan (coronal section), d – CT scan (axial section)

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Radiographically, CT scan demonstrates a lytic lesion within the mandible in the antero-posterior direction with the erosion of buccal cortex of the mandible [Figure 3]c and [Figure 3]d.

Case No 4

A 58-year-old male patient reported with the swelling in the upper front region of jaw for 3 months. He gave a history of pain for 2 months. No history of trauma was reported. On extraoral examination, swelling was seen in relation to the upper lip.

On intraoral examination, a diffuse swelling was seen in the upper anterior region extending from 11–24 regions with obliteration of labial vestibule. The overlying mucosa was normal. Swelling was tender and firm in consistency. Displacement with 21, 22, and 23 was seen [Figure 4]a.
Figure 4: (a) Intraoral view, (b) CT scan (axial section)

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Radiographically on CBCT, an ill-defined expansile osteolytic defect was seen in the maxillary anterior region with partial loss of buccal cortication. Haziness in the left maxillary sinus was seen. [Figure 4]b.

Case No 5

A 27-year-old female patient reported with pain in the lower front region of jaw for 4 years. She also noticed a nodular swelling on the inner side of her lower front teeth. She underwent surgical excision of the lesion along with surrounding bone, and the histopathological diagnosis was CGCG. Three months prior to reporting, she again noticed a similar nodular swelling in the lower left anterior region of the jaw. On extraoral examination, no facial asymmetry was seen. On intraoral examination, the swelling extends from 33 to 35 lingually. Overlying mucosa is bluish red with few haemorrhagic spots. On palpation, the swelling was firm superiorly and hard inferiorly and associated with mild tenderness. Missing teeth were 31, 32, 41, 42, 43, 44, 45, and Grade II mobility with 33, 34 was seen. Lingual tilting of 33, 35 was present. [Figure 5]a.
Figure 5: (a) Intraoral view, (b) CT scan (coronal section)

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On CT examination, an expansile, multiloculated lytic lesion was present in the left side of mandible involving the symphysis menti. Associated enhancing soft tissue was seen within the lesion. Bicortical expansion was also present [Figure 5]b.

After correlating the findings, a provisional diagnosis of benign odontogenic cyst/tumor was made for all cases.

Blood investigations such as serum calcium, serum phosphorous, serum alkaline phosphatase were carried out which were within the normal limit for all the cases.

On histopathological examination, all the above cases were found to be CGCG [Figure 6]. The above cases were treated as follows: the first three cases were managed with enbloc resection, whereas the other two cases were managed with surgical curettage [Table 1].
Figure 6: Histopathology picture showing multinucleated giant cells (40×)

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Table 1: Summary of the five cases of CGCG

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   Discussion Top

CGCG was first described by Jaffe in 1953. CGCG is considered to be reparative and reactive in nature. It is not considered to be a benign neoplasm. Jaffe coined the term “Giant cell reparative granuloma.” However, the word “reparative” has been removed since the condition is not reparative in nature.

The WHO has defined it as an intra-osseous lesion consisting of cellular fibrous tissue that contains multiple foci of haemorrhage, aggregations of multinucleated giant cells, and occasionally trabeculae of woven bone.[3] CGCG is bony lesion mainly affecting adolescence and young preferably younger than 20 years and involves mandible more than maxilla, predominantly the region anterior to the first molar in the mandible and anterior to cuspids in the maxilla.

Some believed CGCG to be related to the teeth in some way, though they were not truly thought to be an odontogenic lesion. The giant cells involved in the lesion may have been derived from the odontoclasts which led to resorption of the deciduous teeth.[4]

This might explain why they were found in a certain age group and generally found in areas of the jaws that had previously held deciduous teeth.

In our series, all patients were young expect one who was a 58-year-old male patient. The oldest reported case in literature was a 94-year-old patient.[4] The F: M ratio was 3:2 as seen in literature wherein females are more commonly affected.

The presented cases here had a different site of occurrence of the lesion, i.e. in two patients maxilla was involved (1: anterior, 1: posterior), in two patients mandible was involved (1: anterior, 1: posterior), and in one patient the lesion was crossing the midline in the mandible. The epicenter is usually anterior to the first molar in young patients, but there is a tendency for the epicenter to occur in the posterior region of the jaws after the first 2 decades of life. On the other hand in our case series, one patient who was 58 years old had the lesion in the anterior region of maxilla, which is not in accordance with studies reported in the literature.

The most common presenting sign is a painless swelling, whereas all the cases presented here had the presence of pain associated with the swelling. Few may complain of pain, paresthesia, and displacement of teeth. The swelling may cause facial asymmetry and difficulty in mastication.

The radiographic appearance of the lesion can be unilocular/multilocular. Because it is a slow growing lesion, it produces a well-defined margin. In our case series, all the cases showed well-defined margins expect one that was seen in a 58-year-old male patient wherein the margins were ill defined.

The internal structure may show the granular pattern of calcification which is organised into ill-defined, wispy septa which emanate at right angles to the periphery of the region. The aggressive forms of CGCG may displace anatomical structures, such as teeth, mandibular canal, and floor of maxillary antrum.[5] All cases showed tooth displacement, and two cases involved the maxillary antrum.

CGCG must be differentiated from aneursymal bone cyst (ABC), odontogenic keratocyst (OKC) and unicystic ameloblastoma. ABC involves ramus, and the molar region of mandible more than the maxilla is symptomatic, seen in younger age group and radiographically appears unilocular with thinning; wherein OKC is asymptomatic seen in mandible 3rd molar region, and epicentre is superior to the alveolar canal, presents as multilocular radiolucency. Unicystic ameloblastoma is asymptomatic, occurs in mandibular third molar region and radiographically appears unilocular.

Usually CGCG is unifocal in appearance; multifocal lesions should alert the clinician to the possibility of hyperparathyroidism. If bilateral, then Cherubism and Noonan's syndrome should be considered.[6]

Although CGCG is considered as benign osseous lesions, some authors divide CGCG into 2 categories based on its clinical and radiographic features.

  1. Non-aggressive lesions: they are usually slow-growing, asymptomatic and do not show cortical perforation/root resorption with fewer chances of recurrence
  2. Aggressive lesions: they are usually seen in young patients, are painful, grow rapidly, larger overall, often cause cortical perforation, root resorption, and tendency to reoccur.[7]

As all the cases showed an acute onset, pain, rapid in growth, overall larger and radiologically showed tooth displacement, cortical expansion and perforation, and the involvement of the maxillary antrum. One case also showed recurrence suggestive of its aggressive nature. Hence, it can be concluded that the present cases are an aggressive form of CGCG.

CGCG presents with two major histological features: first, a highly cellular fibroblastic stroma with plump spindle-shaped cells with a high mitotic rate. Second, the prominent multinucleated giant cells throughout the fibroblastic stroma, distributed irregularly often located most numerously around the areas of haemorrhage. The number of nuclei ranges from only a few to several dozen.[8]

Both aggressive and non-aggressive type of lesions appear the same histologically, many authors have considered biomarkers as a means of differentiating these lesions.[9]

Clinical and radiographic findings dictate the management of CGCG. Well-defined localised regions are treated with curettage and show a low rate of recurrence, whereas for extensive multiple lesions, a more radical excision is necessary.[10]

Many treatment modalities such as simple curettage, curettage with peripheral ostectomy, enucleation and en bloc resection have been done, as well as alternative medical treatments. First described in 1988, the protocol suggested is the 50/50 mixture of 2% lidocaine with 1:1,00,000 epinephrine with triamcinolone hexacetonide 20 mg/ml and to inject 2 ml/1 cm of lesion and to repeat this six times at weekly intervals works more successfully in unilocular lesions than multilocular lesions.

Calcitonin injections with varied results have been reported wherein subcutaneous injections of 100 units of calcitonin daily were given. These injections are available as human and salmon calcitonin. Calcitonin is also available as a nasal spray (200 IU/day) that controls the osteoclastogenesis and interferon alpha injection (3 × 106IU/day) is used as an adjunct to surgery, acts as antiangiogenic and inhibits bone resorption.[11],[12]

   Conclusion Top

In the literature, case reports mention the non-aggressive form of CGCG; the present case series has shown massive lesions with varied location and was aggressive in nature. Despite the characteristic histologic and immunohistochemical features, CGCG remains a diagnostic challenge to both clinicians and radiologists. There are no studies larger than individual case reports to explain the radiographic features of CGCG. Thus, we would emphasise the need for advanced imaging modalities such as CT, CBCT to facilitate the diagnosis and management strategies in the cases of aggressive forms of CGCG.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Ackerman LV, Spjut HJ. Giant cell reaction. In: Firminger H, editor. Atlas of Tumor Pathology, Tumors of Bone and Cartilage, fasc 5; ser 2. Washington, DC: American Registry of Pathology; 1962. p. 293-314.  Back to cited text no. 1
Nackos JS, Wiggins RH, Harnsberger HR. CT and MR imaging of GCG of the craniofacial bones. Am J Neuroradiol 2006;27:1651-3.  Back to cited text no. 2
Adornato MC, Paticoff KA. Intralesional corticosteroid injection for treatment of CGCG. J Am Dent Assoc 2001;132:186-90.  Back to cited text no. 3
Pogrel AM. The diagnosis and management of giant cell lesions of the jaws. Ann Maxillofac Surg 2012;2:102-106.  Back to cited text no. 4
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Murphey MD, Nomi Kos GC, Flemming DJ, Gannon FH, Temple HT, Krans Doef MJ, From the archives of AFIP. Imaging of giant cell tumor and giant cell reparative granuloma of bone, radiologic-pathologic correlation. Radiographics 2001;21:1283-1309.  Back to cited text no. 5
De Lange J, van den Akker HP, van den Berg H. Central giant cell granuloma of the jaw-A review of the literature with emphasis on therapy options. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:603-15.  Back to cited text no. 6
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Van der Waal I. Diseases of the Jaws, Diagnosis and Treatment. Wiley-Blackwell, Copenhagen: Munksgaard; 1991. p. 55-60.  Back to cited text no. 8
EcKardt A, Pogrel MA, Kaban LB, Chew K, Mayall BH. Central giant cell granulomas of the jaws-Nuclear DNA analysis using image cytometry. Int J Oral Maxillofac Surg 1989;18:3-6.  Back to cited text no. 9
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deLange J, van den Akker HP, Veldhuijzen, van Zanten GO, Engelshove HA, van den Berg H, et al. Cacitonin therapy in CGCG of the jaw: A randomised double –blind placebo-controlled study. Int J Oral Maxillofac Surg 2006;35:791-5.  Back to cited text no. 11
Kaban LB, Troulis MJ, Ebb D, August M, Hornicek FJ, Dodson TB. Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. J Oral Maxillofac Surg 2002;60:1103-11.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1]

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