Year : 2008 | Volume
: 19 | Issue : 1 | Page : 78--82
Central giant cell granuloma of the anterior maxilla
Amar A Sholapurkar, Keerthilatha M Pai, Auswaf Ahsan
Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Manipal, Karnataka - 576 104, India
Amar A Sholapurkar
Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Manipal, Karnataka - 576 104
Central giant cell granuloma (CGCG) formerly called giant cell reparative granuloma is a non-neoplastic proliferative lesion of unknown etiology. It occurs most commonly in the mandible. The case reported here resembled a wide variety of conditions that led to a misdiagnosis both on clinical and radiographic examination but was histopathologically diagnosed as CGCG. We describe a case of central giant cell granuloma arising from the anterior maxilla to highlight to the general dental practitioner the importance of histopathology in the diagnosis of this enigmatic lesion.
|How to cite this article:|
Sholapurkar AA, Pai KM, Ahsan A. Central giant cell granuloma of the anterior maxilla.Indian J Dent Res 2008;19:78-82
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Sholapurkar AA, Pai KM, Ahsan A. Central giant cell granuloma of the anterior maxilla. Indian J Dent Res [serial online] 2008 [cited 2022 Dec 8 ];19:78-82
Available from: https://www.ijdr.in/text.asp?2008/19/1/78/38938
Central giant cell granuloma (CGCG) is an intraosseous lesion consisting of cellular fibrous tissue that contains multiple foci of hemorrhage, aggregations of multinucleated giant cells and occasionally trabeculae of woven bone.  CGCG, as described by Jaffe in 1953 is an idiopathic non-neoplastic proliferative lesion.  The term reparative giant cell granuloma was at one time widely accepted as CGCG was considered primarily to be a local reparative reaction of bone, possibly to intramedullary hemorrhage or trauma. The use of the term reparative has subsequently been discontinued since the lesion represents essentially a destructive process. 
Giant cell tumor is often confused with giant cell granuloma. However, a giant cell tumor can be distinguished based on the fact that it occurs commonly between the ages of 25-40 years, usually involving the long bones and is more aggressive in nature, with frequent recurrence after curettage. Microscopically, the giant cells are osteoclastic and almost uniformly distributed, whereas in giant cell granuloma, foreign body type giant cells with irregular distribution and vacuolation are seen. The stroma in giant cell granuloma is collagenised or edematous, whereas in giant cell tumor the stroma is made up of plump tumor cells.
A diagnosis of CGCG is made based on histopathology. This statement is substantiated by the case reported here which presented with clinical features that lead to a clinical differential diagnosis which included a wide range of conditions such as radicular cyst, adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic cyst (CEOC), desmoplastic ameloblastoma, fibrous dysplasia and a radiographic differential diagnosis of AOT.
A 27-year-old male patient presented to the department of Oral Medicine with a swelling on the right side of the face since three months. The swelling was reported to be insidious in onset and had progressed slowly from a small lesion to the present size. It was also reported that two of his anterior teeth had become mobile three weeks back. The patient gave a history of trauma of anterior teeth five to six years back. The swelling was not associated with any systemic symptoms. There was no paraesthesia or nasal discharge. Medical history and family history were noncontributory. The patient did not report of any deleterious oral habits.
Extraoral examination revealed a diffuse swelling on the right side of the face [Figure 1] causing obliteration of nasolabial fold [Figure 2] resulting in facial asymmetry. The overlying skin was normal. The swelling had no localized elevation of temperature. There was no associated lymphadenopathy.
Intraoral examination revealed a fair oral hygiene and a full complement of teeth. There was a swelling in the labial aspect extending from the midline in relation to the upper right central incisor to the second premolar posteriorly obliterating the labial sulcus [Figure 3]. It had a smooth surface with no evidence of fluctuation on palpation. Swelling also extended palatally [Figure 4] and was non-tender and hard on palpation. The upper right central incisor and canine showed Grade I mobility. The swelling also caused slight displacement of the upper right incisors. Ellis Class 1 fracture was noted in relation to the upper right and left central incisors. There was no discoloration of the teeth. The teeth were non-tender on percussion.
Clinically, there was a swelling of the maxilla involving the labial as well as palatal aspect. Based on the history and clinical examination the following differential diagnoses were continued.
Radicular cyst, the most common type of cyst in the jaws arises from teeth (may be associated with trauma) and produces no symptoms unless secondarily infected. The incidence of radicular cyst is greater in the third to sixth decades and has a male predominance. Most of them are found in the maxilla, especially around the incisors and canines. It may cause displacement of adjacent teeth and expansion of jaw. All the above clinical findings in our case were in favor of radicular cyst.
Adenomatoid odontogenic tumor is another diagnosis to be considered. It is an uncommon tumor of odontogenic origin. It most commonly occurs in the second decade and has predilection for females. It is a slow-growing and painless tumor, associated with missing tooth. It most frequently (70%) occurs in the maxilla in the incisor-canine-premolar region. It may cause displacement of adjacent teeth and expansion of jaw. Adenomatoid odontogenic tumor can present as both central and peripheral variants. In our case the swelling was not associated with embedded tooth. Hence extra-follicular variant of AOT was considered in the differential diagnosis.
Fibrous dysplasia was also considered in the differential diagnosis. The monostotic form of fibrous dysplasia most often involves the jaws where the maxilla is commonly affected. It has a predilection for females and is discovered in younger age group. It causes expansion of the affected jaw and displacement of teeth.
Calcifying epithelial odontogenic cyst (CEOC) was also considered in our differential diagnosis. It has a wide age distribution at 10-19 years with a mean age of 36 years and second incidence occurs during the seventh decade. Clinically the lesion usually appears as a slow-growing, painless swelling. It has nearly equal distribution between jaws. Most occur anterior to the first molar, especially associated with cuspids and incisors. In most cases it causes expansion of bone and may destroy the cortical plate along with displacement of teeth.
An uncommon odontogenic neoplasm (desmoplastic variant of ameloblastoma) was also considered in our case. This lesion has a propensity to occur in the anterior maxilla. The age and gender of patients with this variant does not differ significantly from patients with other types of ameloblastoma. The typical location was consistent with the desmoplastic variant of ameloblastoma. At this stage aneurysmal bone cyst and CGCG were not considered because they are common in the mandible.
Vitality test revealed that maxillary right central incisor, lateral incisor and first premolar were non vital. Intraoral periapical (IOPA) view radiograph of upper right anterior region [Figure 5] revealed an ill-defined radiolucency in relation to the apices and interradicular area of the upper right incisors, canine and first premolar with no evidence of foci of calcification. Displacement of roots of lateral incisor and canine was observed. Significant resorption of roots of 12 and 14 was noted. Maxillary occlusal radiograph [Figure 6] showed ill-defined radiolucency in the palatal aspect in relation to the apices of the upper right incisors, canine and premolars. Orthopantomogram [Figure 7] revealed an ill-defined radiolucency in relation to the apices and interradicular area of 11, 12, 13 and 14 with no evidence of foci of calcification. Displacement of roots of 12 and 13 and marked resorption of roots of 12 and 14 were noted. The radiolucency was found to be crossing the midline. The floor of maxillary sinus was found to be intact. Computed tomography (CT) scan of the lesion at the level of maxillary sinus in the coronal section [Figure 8] showed a radiolucent lesion arising from inferior aspect of the right maxilla with no areas of calcification. The lesion caused superior displacement of the floor of the maxillary sinus without causing gross destruction. The floor of the nasal fossa was intact. Axial CT scan [Figure 9] showed radiolucency with a corticated margin.
Intraoral aspiration of the lesion was attempted with a 20-gauge needle under local anesthesia but it did not yield any aspirate.
After the investigations were carried out, we ruled out radicular cyst, CEOC and fibrous dysplasia. An unproductive aspirate ruled out cystic lesions like radicular cyst and CEOC. The absence of characteristic ground glass appearance in the radiograph and presence of a radiolucent lesion in both coronal and axial CT scans eliminated fibrous dysplasia from the diagnosis. Desmoplastic variant of ameloblastoma was also ruled out because it typically presents with a mixed radiolucent and radiopaque appearance within the dense fibrous septa. Negative aspiration did not rule out AOT because this lesion may or may not be associated with aspirate. This lesion was still considered in the differential diagnosis based on the fact that the lesion may appear completely radiolucent or a mixed radiolucent radiopaque radiographically. Hence based on history, clinical features and investigations we considered AOT in our diagnosis.
Incisional biopsy was done from the intraoral site, from the labial aspect, under local anesthesia. Histopathologic examination [Figure 10],[Figure 11] revealed numerous multinucleated giant cells which were distributed in a stroma that was highly cellular comprising both spindle-shaped and round cells and were found mostly in the areas of hemorrhages. The giant cells were numerous and distributed randomly, the nuclei mainly confined to the center of the cells leaving a clear zone of cytoplasm at the periphery. Ingested RBCs and scanty collagen were also seen. These findings were consistent with diagnosis of CGCG. It is difficult to distinguish this lesion histologically from brown tumor of hyperparathyroidism. Hence serum levels of calcium, phosphorus and alkaline phosphatase were advised which were found to be in normal limits (calcium → 9.3 mg/dl, phosphorus → 4.1 mg/dl and alkaline phosphatase → 92 U L). Brown tumor of hyperparathyroidism was excluded by demonstrating normal levels of serum calcium, phosphorus and alkaline phosphatase levels, thus establishing the diagnosis of central giant cell granuloma of the anterior maxilla.
The lesion was surgically excised under general anesthesia. The specimen [Figure 12] was brown in color and firm in consistency. During surgical procedure, the lesion was found to be communicating with maxillary sinus and involving the right nasal floor. Cystic fluid was not encountered during the surgery. Patient was prescribed analgesics and antibiotics and recalled after 10 days for suture removal.
Central giant cell granuloma is a non-neoplastic proliferative lesion of unknown etiology. It occurs most commonly in the mandible than in the maxilla. But our case involved the maxilla. Most mandibular lesions occur anterior to first molars and often cross the midline. It strikingly occurs more commonly on the right than left side.  Central giant cell granuloma also occurs in other bones of the facial skeleton and cranial vault. It rarely occurs outside the craniofacial bones, but it has been described in the short tubular bones of hands and feet.  Giant cell granulomas of the jaw bones may be peripheral or central. Peripheral lesions present as pedunculated or sessile lesions on the gingiva while central lesions are endosteal. In most of the cases, females have more predilection than males in the ratio of 2:1. , It occurs most commonly in children or young adults.  Trauma has been considered as an important etiologic factor in the initiation of this lesion. The lesions increase by accumulation of tissue which is produced by slow, minute, continuous hemorrhages of multicentric nature due to trauma and some defect in the capillaries. 
Association of t (X; 4) (q22; q31.3) in the etiology of giant cell granuloma has been reported. 
The clinical behavior of CGCG is variable. It ranges from slow-growing, asymptomatic swelling to an aggressive lesion which manifests with pain. The most common presenting sign of CGCG is a painless swelling with noticeable facial asymmetry. Alternatively, the abnormality may be disclosed as a purely incidental finding during radiographic examination of the jaws made for an unrelated purpose. In only about 25% of the cases, the lesion is accompanied by pain. Palpation of the suspect bone area may elicit tenderness. The lesions develop without paresthesia. Teeth in association with the lesion may become mobile but maintain their vitality.
The radiological appearance of CGCG is variable. Usually the lesion appears as a unilocular or multilocular radiolucency. It may be well-defined or ill-defined and shows variable expansion and destruction of the cortical plate. The radiological appearance of the lesion is not pathognomonic and may be confused with that of many other lesions of jaws. The final diagnosis eventually rests on histopathology because the clinical and radiological features are not specific. Central giant cell granuloma of the jaw usually presents as a painless solitary radiolucent expansion in most of the cases. Some lesions are more destructive with a marked tendency to recur. A more aggressive type of such lesion will require more radical treatment. The recurrence rate is reported to be 13-22%,  with most treatment failures manifesting within the first two years of the therapy. The management of CGCG will depend on the clinical and radiographic findings. Generally, curettage of well-defined localized lesions is associated with a low rate of recurrence. In extensive lesions with radiographic evidence of perforation of cortex, a more radical excision is mandatory. In such cases even partial maxillectomy has to be done. The medical management of CGCG as an adjunct to surgery includes treatment with steroids or calcitonin  which inhibits osteoelastic activity. Interferon-alpha appears useful in the management of aggressive CGCG, presumably due to its anti-angiogenic effects.  Bisphosphonates have been administered intravenously in CGCG with promising results. 
The clinical behavior of this lesion is quite variable and difficult to predict. Hence we suggest that CGCG should also be considered in the differential diagnosis of the swellings in maxillary anterior area even though it has a marked propensity to occur in the mandibular anterior area.
We would like to thank Drs. Rashmi Lahiri and Vivek Garg, Dept of General Pathology, Kasturba Medical College, Manipal for their help in preparing and interpreting the slide and providing the photomicrographs.
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