Jaffe considered the lesion to be a local reparative reaction of bone, possibly to intramedullary hemorrhage or trauma. The word "reparative" no longer is used since the lesion involves a destructive process. Controversy exists about whether the CGCG and giant tumor of long bones are separate entities or represent the same disease process and manifest themselves differently in regard to the sites of occurrence and age of the patient. CGCG usually occurs in the first three decades of life and has a predilection for females.^2,3 It is an uncommon lesion, accounting for less than 7 percent of all benign jaw lesions.⁴ Although most CGCGs of the jaws are slow-growing, circumscribed lesions that respond well to simple curettage, a smaller number demonstrate aggressive clinical behavior.

	CASE REPORT

TOP ABSTRACT CASE REPORT RADIOLOGY PATHOLOGY DISCUSSION TREATMENT CONCLUSION REFERENCES

 
A 9-year-old boy came to the Mayo Clinic, Section of Orthodontics, Rochester, Minn., for an initial orthodontic consultation in May 1999. The patient’s chief complaint was that his two front permanent teeth were overlapping. His medical history revealed that he had been struck by a truck at 4 years of age, which caused facial trauma and required stitches to the head. Extraoral examination revealed a healthy boy with a symmetrical, somewhat full face (Figure 1). We noted a convex profile with slight mandibular retrognathia. The results of the temporomandibular joint examination were within normal limits.

View larger version (104K): [in this window] [in a new window]   Figure 1. Frontal extraoral photograph of a 9-year-old boy with a symmetrical, somewhat full face.

View larger version (114K): [in this window] [in a new window]   Figure 2. Intraoral midline photograph. Note that the maxillary right central incisor was displaced distally, so that it completely overlapped the maxillary right lateral incisor to the facial aspect.

Cephalometric analysis revealed a skeletal Class II discrepancy. The maxillary incisors were labially proclined. The panoramic and periapical films and the posteroanterior cephalogram showed a large, well-defined unilocular maxillary radiolucency between the maxillary central incisors (Figure 3). A degree of divergence between the roots of the teeth adjacent to the lesion could be seen radiographically. We assumed that this lesion had most likely caused the displacement of the maxillary central incisor.

View larger version (70K): [in this window] [in a new window]   Figure 3. Maxillary anterior periapical radiographs. Note the large, well-defined unilocular maxillary radiolucency between the maxillary central incisors (arrows).

Surgery. After general anesthetic was administered, the oral and maxillofacial surgeon placed a gingival incision from the right to left canines and exposed the anterior premaxilla. A bulging lesion in the anterior right maxillary area was immediately encountered. The surgeon reflected a large palatal flap and noted some bulging in the right anterior palate. However, the cortex was relatively intact and thick. In the anterior region, the surgeon completely isolated the lesion via subperiosteal dissection and removed it in total. The lesion was approximately 2 centimeters in all directions.

Superiorly, the floor of the nose had been destroyed and the anterior nasal spine had resorbed, but the nasal mucosa was intact. A small piece of tissue submitted for frozen-section histopathologic evaluation revealed that the lesion was a CGCG. All flaps were repositioned and sutured. The surgeon made a soft-tissue window in the anterior midline flap and lightly packed the osseous defect with iodoform gauze, which remained in place for 10 days. The patient tolerated the procedure well and there were no postoperative complications.

	RADIOLOGY

TOP ABSTRACT CASE REPORT RADIOLOGY PATHOLOGY DISCUSSION TREATMENT CONCLUSION REFERENCES

 
The radiographic findings of CGCG are not specifically diagnostic and may be confused with those of many other jaw lesions. The lesions may manifest themselves as unilocular or multilocular radiolucent defects.⁵ Cohen and Hertzanu⁶ radiographically evaluated 16 cases of CGCG and found that 50 percent were unilocular and 50 percent were multilocular. The borders may be well-defined or ill-defined and exhibit variable expansion and destruction of the cortical plates. According to a study by Horner,⁷ the most significant radiologic sign is the presence of a "wispy" opacification overlying the lesion. The most common location of a CGCG, as seen on a radiograph, is in the mandible, anterior to the permanent first molars.⁷ One of the most consistent radiographic features is root divergence of teeth adjacent to the lesion.^6,7

	PATHOLOGY

TOP ABSTRACT CASE REPORT RADIOLOGY PATHOLOGY DISCUSSION TREATMENT CONCLUSION REFERENCES

 
A variety of histologic features and patterns can be seen in a CGCG of the jaws. Common to all is the presence of few to many multinucleated giant cells in a stroma composed of ovoid-shaped to spindle-shaped mesenchymal cells⁵ (Figure 4). The giant cells typically possess four to eight randomly arranged nuclei that may be hyperchromatic, oval, stippled or any combination of the three, with prominent nucleoli. Vessels in the stroma often are engorged with red blood cells, and hemosiderin pigment is readily seen, particularly in areas of extravasated blood.³ Histologic differentiation between CGCG and giant cell tumor of long bones is not easy. Auclair and colleagues² suggested that these lesions represent a spectrum of a single disease process modified by the age of the patient and the site of occurrence.

View larger version (193K): [in this window] [in a new window]   Figure 4. Low-power magnification of histologic specimen (x 25, hematoxylin and eosin stain). Arrows indicate many multinucleated giant cells in a stroma of mesenchymal cells.

	DISCUSSION

TOP ABSTRACT CASE REPORT RADIOLOGY PATHOLOGY DISCUSSION TREATMENT CONCLUSION REFERENCES

 
Significant controversy has surrounded the classification of giant cell lesions of the maxillofacial skeleton. The main controversy has revolved around the relationship between the giant cell granuloma and the true giant cell tumor of bone. Some investigators have proposed that the CGCG and giant cell tumor of bone are varying expressions of the same neoplastic process. Waldron and Shafer¹¹ concluded that these lesions are similar and probably identical. On the other hand, many investigators, citing radiologic and histologic differences, have concluded that the CGCG and giant cell tumor of bone are separate and distinct entities.^12–14

Before 1953, giant cell lesions of the jaws usually were diagnosed as giant cell tumors and generally were considered to be similar to the giant cell tumor of long bones. The term "giant cell reparative granuloma" was used by Jaffe¹ in 1953 to describe "the giant cell lesion of jaw bones." It was his belief that these jaw lesions only mimicked the true giant cell tumor of bone and had numerous clinical and histologic differences. Jaffe stated that the jaw lesions were not true neoplasms, but rather represented a local reparative reaction. Little evidence exists to demonstrate that the lesion is a reparative response. Owing to the fact that the lesion is inconsistent with a reparative response, the term "reparative" has been dropped. These lesions now are designated as CGCGs.

Uncertain etiology. Despite many references in the literature to the nature of CGCG, the etiology of this common disease entity remains obscure and the role of the giant cell itself has escaped definition. Certainly, a legitimate skepticism has emerged about the alleged relationship to trauma and repair. Although the etiology of CGCG remains uncertain, Ash¹⁵ indicated that the lesion probably arises as the result of trauma involving intraosseous hemorrhage. Batsakis¹⁴ suggested that injury imposed on the periodontal membrane, the odontogenic mesenchyma, the dental sac or the ancestral cells of the dental sac probably is the initiating insult. A history of trauma often is elicited, but the theory of traumatic etiology is continually challenged.

The majority of giant cell lesions of the jaws are slow-growing, circumscribed processes that respond well to simple curettage.

Waldron and Shafer¹¹ analyzed 38 cases of CGCG and found that a history of injury to the jaws was mentioned in so few cases that little credence can be given to the etiologic significance of this factor. It is possible that this lack of injury history only reflects poor history-taking by the clinicians involved. It may be significant that no acute injury in the period immediately preceding the development of the lesion was mentioned in any case history. We might assume that trauma is not a significant etiologic factor, or that the development of the lesion is not a fulminating one resulting from trauma, but may extend over a relatively long period, during which the traumatic episode may have been forgotten.¹¹ It is interesting that in our case described above, the patient had a history of trauma at 4 years of age, but the CGCG lesion was not noticed until he was 9 years old. Whether trauma played a role in this case remains unknown.

CGCGs typically appear as unilocular or multilocular radiolucent lesions that develop in the tooth-bearing areas of the jaws previously occupied by the primary dentition. The lesion usually is located in close proximity to the teeth; however, there have been cases reported of CGCGs in edentulous patients.⁶ These lesions have a predilection for females and typically occur in the first three decades of life. The occurrence rate is higher in the mandible than in the maxilla, with a predilection for the anterior segment. Mandibular CGCGs often cross the midline.

Clinical behavior. The clinical behavior of CGCG of the jaws can vary considerably. The majority of giant cell lesions of the jaws are slow-growing, circumscribed processes that respond well to simple curettage; however, a significant number of lesions exhibit an aggressive clinical behavior. These aggressive cases are characterized by pain, resorption of roots of adjacent teeth, destruction and perforation of the cortical bone, and a tendency for the lesion to recur after curettage. Reported recurrence rates vary widely, ranging from 10 to 69 percent.^16,17 Because of the possibility of recurrence, orthodontic treatment should be deferred to ensure complete ossification of the wound site.

A number of different jaw lesions, both malignant and benign, contain multinucleated giant cells. The malignant lesions include osteogenic sarcoma, fibrosarcoma, malignant fibrous histiocytoma and malignant giant cell tumor. The benign lesions include fibrous dysplasia, ossifying fibroma, cementifying fibroma, aneurysmal bone cyst, cherubism, brown tumor of hyperparathyroidism and giant cell granuloma.⁸ In the case presented here, the radiographs showed a maxillary midline lesion; therefore, differential diagnoses also should include nasopalatine duct cyst, median palatine cyst and odontogenic keratocyst.

	TREATMENT

TOP ABSTRACT CASE REPORT RADIOLOGY PATHOLOGY DISCUSSION TREATMENT CONCLUSION REFERENCES

 
CGCGs of the jaws usually are treated via surgical curettage.^5,18 If multiple lesions appear, surgical treatment becomes further complicated. In such cases, surgery may lead to extensive resection. Invariably, there is considerable bleeding, which makes it difficult to determine if removal has been complete. This may explain the wide variation in reported recurrence rates. Recurrent lesions often respond to further curettage, although with very aggressive lesions, curettage is not always curative. In these lesions, en bloc resection with immediate reconstruction is appropriate.^5,8 The margins of a CGCG may be thermally sterilized with either laser or cryoprobes; however, the superiority of these procedures over the more conventional peripheral ostectomy remains to be demonstrated.¹⁹

Conventional therapy involving surgical resection in the case of large lesions can result in serious mutilations of the jaw and, hence, the face. Loss of teeth and dental germs in young patients also is unavoidable. In these instances, a nonsurgical approach is an attractive alternative. In 1988, Jacoway and colleagues²⁰ first described an alternative treatment involving local injection of corticosteroids. However, before administering the intralesional corticosteroid injections, the clinician must confirm the presence of the lesion via biopsy. Jacoway and colleagues advocated a technique that involves intralesional injections of equal parts of triamcinolone and 0.5 percent bupivacaine with 1:200,000 epinephrine. Twenty milliliters of solution per 2 cm of radiolucency is injected on a weekly basis until bone regeneration is noted radiographically.²⁰ The literature contains a few reports of successful treatment by corticosteroid injection.^21,22

Calcitonin also has been reported as a treatment for CGCG.^23,24 Researchers and clinicians believe that giant cells are directly inhibited in their function by calcitonin. In 1993, Harris²⁵ described four patients, all of whom responded to calcitonin treatment. He described a technique to eliminate aggressive CGCGs by administering human calcitonin (0.5 milligrams) deep subcutaneously for one year. This avoids the need for mutilating surgery in growing children.²⁵

Eisenbud and colleagues²⁶ reported on 37 cases of CGCG. Twelve (32 percent) of their patients were treated with a combined endodonticsurgical approach. In these 12 patients, a total of 71 teeth were devitalized, and the root canals were filled with gutta-percha before surgery. Sixty-two teeth (87 percent) survived the surgical procedure and were in place and functioning two years or more after the surgery. Nine teeth (13 percent) were lost despite preoperative endodontic therapy, because of inadequate residual alveolar bone support.

The authors believe it is advantageous to complete endodontic therapy before surgery on all teeth whose radiographs indicate that the roots are adjacent to or enveloped by the lesion. It is characteristic of the giant cell granuloma that the disease extends into the interradicular areas, often up to and involving the alveolar bone crest. If endodontic therapy is performed in advance of curettage and periapical ostectomy, the surgeon can explore in all directions and remove all suspected tissue aggressively, without being concerned about the roots of the teeth.²⁶

	CONCLUSION

TOP ABSTRACT CASE REPORT RADIOLOGY PATHOLOGY DISCUSSION TREATMENT CONCLUSION REFERENCES

 
We have presented a case of a young boy who initially sought orthodontic treatment for maxillary incisor malalignment. On further examination, he was diagnosed as having a CGCG in the anterior maxilla. Dentists need to be aware of possible oral pathology when malaligned teeth exist. They should include CGCG in the differential diagnosis for patients with greatly displaced teeth and facial deformity.

View larger version (130K): [in this window] [in a new window]   Dr. Allen is a graduate student in orthodontics, Mayo Graduate School of Medicine, Department of Dental Specialties, Section of Orthodontics, Mayo Clinic, W-4A, 200 First Street S.W., Rochester, Minn. 55905, e-mail "allen.david@mayo.edu". Address reprint requests to Dr. Allen.