|Year : 2018 | Volume
| Issue : 4 | Page : 197-201
Salmon calcitonin - a boon in the management of central giant cell granuloma
D Nivethitha Gangai, G V. Murali Gopika Manoharan
Department of Oral Medicine and Radiology, Tamil Nadu Government Dental College and Hospital, The Tamil Nadu Dr. M. G. R Medical University, Chennai, Tamil Nadu, India
|Date of Web Publication||18-Dec-2018|
D Nivethitha Gangai
Department of Oral Medicine and Radiology, Tamil Nadu Government Dental College and Hospital, The Tamil Nadu Dr. M. G. R Medical University, Chennai, Tamil Nadu
Central giant cell granuloma is an uncommon, benign, proliferative lesion of unknown etiology, most commonly affecting anterior mandible of younger age group. Early diagnosis may be of benefit to the patient as conservative treatment modalities may be used as compared to radical surgical treatment. Calcitonin as a therapy for central giant cell granuloma of the jaws is a promising alternative to surgical curettage, particularly for larger lesions. We report a case of central giant cell granuloma of mandible in a 14-year-old female patient, who is being treated solely with intranasal spray of salmon calcitonin for 14 months showing greater results.
Keywords: Calcitonin, central giant cell granuloma, intranasal spray
|How to cite this article:|
Gangai D N, Manoharan G V. Salmon calcitonin - a boon in the management of central giant cell granuloma. SRM J Res Dent Sci 2018;9:197-201
|How to cite this URL:|
Gangai D N, Manoharan G V. Salmon calcitonin - a boon in the management of central giant cell granuloma. SRM J Res Dent Sci [serial online] 2018 [cited 2020 Apr 7];9:197-201. Available from: http://www.srmjrds.in/text.asp?2018/9/4/197/247844
| Introduction|| |
Central giant cell granuloma of the jaws is an uncommon, benign, destructive, proliferative lesion of unknown etiology. Although surgical management is the main modality of treatment, conservative management with intra-lesional corticosteroids, calcitonin, interferon alpha or denosumab also plays an effective role. We report a case of 14-year-old female patient with histopathologically proven central giant cell granuloma of mandible treated with intranasal spray of calcitonin showing successful results.
| Case Report|| |
A 14-year-old female patient reported to the Department of Oral Medicine and Radiology, with the chief complaints of swelling over the left side of the lower jaw of 1-week duration associated with localized, continuous, dull aching pain with a history of trauma 1 month back. The past medical history, past dental history, and family history were not contributory.
Clinical examination revealed facial asymmetry [Figure 1]. On inspection, a solitary swelling of size 2” ×2” was observed over the left side of the mandible irregular in shape, extending anteriorly to symphysis region, posteriorly to the left parasymphysis of the mandible, superiorly to the level of angle of the mouth and inferiorly up to 1 cm below the lower border of the mandible, with ill-defined margins, smooth surface, with no secondary changes. On palpation, it was firm, tender, not compressible, not reducible, fixed, and the skin over the swelling was pinchable.
On intraoral examination, on inspection, a single swelling was noted in the labial and buccal vestibular region of 36–42 of size 5” ×2”, oblong shape, extending anteriorly from 42, posteriorly up to 36 region, superiorly up to 0.5 cm below the free gingival margin of 36–42, inferiorly obliterating the buccal vestibule, with well-defined margins and smooth surface [Figure 2]. On palpation, it was tender, firm, compressible, fixed and without any palpable pulsations. Grade I mobility of 42, 41, 31, 32 was elicited; the teeth were nontender on percussion.
Investigations revealed blood-tinged fluid on aspiration; Pulp vitality test showed no response in teeth 37–44.
Based on the history and clinical findings, the case was provisionally diagnosed as odontogenic keratocyst left mandibular region, with differential diagnosis of dental cyst, ameloblastoma and central giant cell granuloma.
The results of all hematological studies were within normal limits.
Radiographs [Figure 3]a, [Figure 3]b, [Figure 3]c revealed a well-defined multi-locular radiolucency in the symphysis and left parasymphysis region of the mandible extending from mesial aspect of 43 to distal aspect of 35, widening of PDL space with loss of lamina dura. There was no evidence of root resorption. The lower border of mandible was thin and intact. Computed tomography (CT) scan [Figure 4]a and [Figure 4]b revealed well-defined, expansile lytic, multilocular lesion involving symphysis and left parasymphysis of mandible, showing soft-tissue density in its internal structure with labial and lingual perforation in 33–35 region.
|Figure 3: (a-c) Pre treatment radiographs showing well-defined multilocular radiolucency from 43 to 35 region and widening of periodontal ligament space with loss of lamina dura|
Click here to view
|Figure 4: (a) Computed tomography scan showing well-defined expansile, lytic multilocular lesion with bicortical perforation in 33 to 35 region. (b) Pre treatment three-dimensional reconstruction image|
Click here to view
Under general anesthesia, incisional biopsy was done. Histopathological examination [Figure 5] showed proliferation of multinucleated giant cells in a background of collagenized stroma with extravasation of red blood cells and residual bone formation, and the report was suggestive of central giant cell granuloma.
|Figure 5: Proliferation of multinucleated giant cells in a background of collagenised stroma|
Click here to view
Laboratory values for serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone were within normal limits, ruling out the brown tumor of hyperparathyroidism.
The patient was prescribed with Salmon calcitonin nasal spray 2200 IU (delivers 200 IU per actuation).
| Discussion|| |
Central giant cell granuloma is an uncommon, benign, destructive, proliferative lesion of unknown etiology. Most commonly females of younger age group, <30 years of age, are affected. The mandible is most commonly affected than maxilla, with the epicenter of the lesion in the anterior region crossing midline. Nonaggressive lesions are characterized by slow growth, absence of root resorption/cortical perforation and associated new bone formation. Aggressive lesions are characterized by rapid growth and are associated with pain, cortical perforation and root resorption.
Radiographic features include well-defined radiolucency with relatively smooth/ragged borders, sometimes with faint trabeculae. In larger lesions, there are definite loculations. Cortical plates are thin, expanded and may become perforated. Displacement of teeth by the lesion is usually present.
Histological features are characterized by loose fibrillar connective tissue stroma interspersed with proliferative fibroblasts and small capillaries with prominence of multinucleated giant cells of different sizes. Foci of new trabeculae of osteoid/bone are seen usually around the lesion.
Treatment would include surgical/conservative management. Surgically either excision or curettage may be done and the lesion fills in with new bone and heal with occasional recurrence.
Medical management would include intralesional injection of corticosteroids, exogenous calcitonin administration (lesions may stabilize or regress after several months of therapy); Interferon-alpha (antiangiogenic); denosumab (useful in targeting osteoclast-like action), while X-ray radiation is contraindicated.
Hutter et al. reported that the management of aggressive forms of central giant cell granulomas (CGCGs) has always posed a challenging problem owing to their high recurrence rate of 55%–62% following curettage, which results in a need for repetitive and extensive surgical management with a significant functional and esthetic impairment. Therefore, conventional management should be considered, especially in younger patients.
In 1988, Jacoway et al. first reported on the treatment of CGCG with corticosteroids, and later in 1994, Terry and Jacoway presented four patients treated with steroids; however, there are no controlled studies published on this therapy and the mode of action is not fully understood. In vitro it was shown that dexamethasone, on the one hand, stimulates the proliferation and differentiation of osteoclast precursors, but on the other hand inhibits lacunar resorption by mature osteoclasts isolated from giant cells tumors of the bone. It is hypothesized that steroids inhibit the extracellular production of bone resorption mediating lysosomal proteases by the giant cells and induce apoptosis of osteoclast-like cells. As a result, the administration of corticosteroids inhibits bone resorption. However, the fact that corticosteroids are also known to enhance bone resorption and cause osteoporosis is contradictory.
Based on an immunohistochemical study, using osteoclast-specific monoclonal antibodies, the therapeutic concept for the administration of calcitonin in the treatment of CGCCs, was introduced, which demonstrated that giant cells in CGCGs are osteoclasts (Chambers et al., 1985). The multinucleated giant cells further exhibit all the cytochemical and functional features of osteoclasts.
Giant cells also express calcitonin receptors. Giant cells are directly inhibited in their function by calcitonin that causes an increasing influx of calcium into the bones and thus functions antagonistically to parathormone. In 1993, Harris first reported the use of human calcitonin as a therapy for central giant cell granuloma of the mandible. Aggressive central giant cell granulomas may be eliminated by administering human calcitonin 0.5 mg (100 IU) subcutaneously for 1 year. Salmon calcitonin nasal spray can be substituted. The bioavailability of the nasal spray is 3%–25% and the time to peak concentration varies between 0.26 and 0.75 h. The maximum plasma concentrations occurring within the first hour following nasal administration are lower than those with subcutaneous injection; however, the absorption by nasal route is more prolonged.
The daily dose of calcitonin administrated as a nasal spray was 200 IU. It has the advantage of avoiding daily injections, which could lower patient compliance, and the side effects are considerably low. However, the low absorbance that ranges between 20% and 100% limits its usage. During calcitonin injections, calcification within the lesions usually occurred after 12 months or more months of treatment. In our case, the radiological bone filling of the lesion was seen as early as 6 months. After completion of 14 months of treatment, the reparative bone formation is well appreciated in the radiographs [Figure 6]a and [Figure 6]b. Posttreatment CBCT reveals evidence of reparative bone formation in the regions of mandibular symphysis and left parasymphysis region [Figure 7]a and [Figure 7]b. The size of the swelling has appreciably regressed clinically [Figure 8].
|Figure 6: (a) After 14 months of treatment, radiographs showing evidence of reparative bone formation filling the lesion. (b) After 14 months of treatment, radiographs showing evidence of reparative bone formation filling the lesion|
Click here to view
|Figure 7: (a) Post treatment computed tomography scan showing reparative bone formation. (b) Post treatment three-dimensional reconstruction image|
Click here to view
| Conclusion|| |
Occasionally, central giant cell granulomas of the jaws may be the first clinical sign of hyperparathyroidism. Hence, hyperparathyroidism has to be ruled out after confirming histopathologically. Conservative treatment modalities should be considered as radical surgical treatment could result in loss of teeth, serious mutilation of the jaws and hence disfigurement of the face. Calcitonin as a therapy for central giant cell granuloma of the jaws is a promising alternative to surgical curettage particularly for larger lesions. However, further investigations into dosages and treatment duration on therapy are necessary before an optimal treatment protocol can be suggested.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the parent has given her consent for images and other clinical information to be reported in the journal. The parent understands that name and initial will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Shafer WG, Hine MK, Levy BM. Textbook of Oral Pathology. 7th
ed. Philadelphia: Saunders 2012; p. 137.
Burket LW, Greenberg MS, Glick M, Ship JA. Burket's Oral Medicine: Diagnosis and Treatment. 11th
ed. Hamilton, ON: B C Decker Inc.; 2008. p. 145.
Pogrel MA. Calcitonin therapy for central giant cell granuloma. J Oral Maxillofac Surg 2003;61:649-53.
Hutter RV, Worcester JN, Francis KC, Foote FW, Stewart FW. Benign and malignant giant cell tumors of bone. A clinicopathological analysis of the natural history of the disease. Cancer 1962;15:653-90.
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.
Rachmiel A, Emodi O, Sabo E, Aizenbud D, Peled M. Combined treatment of aggressive central giant cell granuloma in the lower jaw. J Craniomaxillofac Surg 2012;40:292-7.
Nouri H, Hedi Meherzi M, Ouertatani M, Mestiri M, Zehi K, Douik M, et al.
Calcitonin use in giant cell bone tumors. Orthop Traumatol Surg Res 2011;97:520-6.
Harris M. Central giant cell granulomas of the jaws regress with calcitonin therapy. Br J Oral Maxillofac Surg 1993;31:89-94.
de Lange J, van den Akker HP, Veldhuijzen van Zanten GO, Engelshove HA, van den Berg H, Klip H, et al.
Calcitonin therapy in central giant cell granuloma of the jaw: A randomized double-blind placebo-controlled study. Int J Oral Maxillofac Surg 2006;35:791-5.
Vered M, Shohat I, Buchner A, Dayan D, Taicher S. Calcitonin nasal spray for treatment of central giant cell granuloma: Clinical, radiological, and histological findings and immunohistochemical expression of calcitonin and glucocorticoid receptors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:226-39.
de Lange J, Rosenberg AJ, van den Akker HP, Koole R, Wirds JJ, van den Berg H, et al.
Treatment of central giant cell granuloma of the jaw with calcitonin. Int J Oral Maxillofac Surg 1999; 28:372-6.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]