CASE SERIES

Novel adjuvant calcitonin therapy

following surgical resection for central
giant cell granuloma – Case series with
literature review
Department of Oral and Maxillofacial Surgery, Mahatma Gandhi Dental College and Hospital,
Jaipur

ABSTRACT
Central Giant Cell Granuloma is a non-neoplastic lesion characterized by fibrous tissue with
hemorrhagic foci, multinucleated giant cells, and sometimes bone trabeculae, commonly
affecting the central mandible region. Treatment ranges from surgical approach to medical
approach which includes complete resection to enucleation or use of steroids, interferons and
calcitonin therapy. Calcitonin salmon nasal spray 200 IU/day for the next 12-18 months after
surgery, is used to prevent lesion recurrence. Nasal spray shows better patient compliance with
fewer side effects. This paper attempts to explain the safety and effectiveness of calcitonin nasal
spray as an adjunct to surgery for CGCG in 4 patients with different sites of involvement in the
jaw.

KEYWORDS: Central giant cell granuloma, calcitonin, jaw, case series

INTRODUCTION
Central Giant Cell Granuloma (CGCG) was first described by Jaffe in 1953, which was named as
‘giant cell reparative granuloma’. According to the World Health Organization (WHO), CGCG
is defined as 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.1 CGCG is more commonly seen in mandible than maxilla affecting adolescent females
commonly under the age of thirty. Aggressive lesions are often seen with tooth pain and
mobility, root resorption and cortical perforation with a recurrence rate of 13-49%. 2 Diagnosis is
made by excisional biopsy or FNAC at lesion site.

The histologic features of fibrosis and multiple foci of hemorrhage are similar to cherubism,
brown tumor of hyperparathyroidism, fibrous dysplasia and aneurismal bone cyst.3

Management of CGCG ranges from simple curettage in non-aggressive cases to enucleation in

aggressive forms with adjunct therapy, which includes interferon therapy, administration of
calcitonin or steroids.4

Calcitonin is suggested as a therapeutic agent based on its action on multinucleated giant cells in
CGCG as they possess osteoclast-specific characteristics including lacunar bone resorption.5 The
role of calcitonin in the treatment of CGCGs is to antagonize osteoclastic bone resorption and
reduce bone resorption, potentially promoting lesion regression and healing.

CGCG is relatively rare condition of the jaw which presents with a variety of clinical symptoms
and radiographic appearances while posing diagnostic challenges at the same time. So this report
would be a significant contribution to the literature.

CASE 1
A 15-year-old female reported to OPD of the department of Oral and Maxillofacial Surgery with
chief complaints of pain and swelling in the upper right tooth region since a month. Swelling had
gradually increased to present size. She had no other relevant medical history and was not on any
medications. She had no history of traumatic injury to the anterior maxilla. Extraoral
examination revealed mild swelling in right maxillary region. Intraoral examination revealed
swelling with respect to 13 to 16 teeth region, measuring approximately 3x2 cm in diameter and
reaching upto midline on the palatal side with no active pus discharge or open wound. The
swelling was hard in consistency with well-defined margins and non-tender on palpation.
 Figure 1A Figure 1B

Figure 1- Pre operative clinical pictures of patient

1A- Facial asymmetry resulting from a lesion of the right side of the maxilla

1B- Intraoral view shows the palatal extension of the lesion

CT angiography of the neck showed heterogeneously enhancing expansile soft tissue density
lesion along the floor of right maxilla in region of lateral incisor, canine and 1 premolar tooth
adjacent to soft palate extending into right maxillary sinus, nasal and oral cavity with marked
breach of their cortical margins.

Fig.2: Arrow indicates central giant cell granuloma of the maxilla. Radiograph of the patient
shows the extent of lesion indicated
Fine needle aspiration cytology (FNAC) from the swelling was done, which revealed
cytosmears, mainly hemorrhagic and showing blood and its components only. No malignant cells
were seen.

After taking into consideration the clinical examination, CT angiography and FNAC, a surgical
treatment was planned under GA followed by calcitonin therapy.

Fig.3: Intraoperative pictures showing the lesion and biopsy sample respectively.

Figure 4: Post operative clinical picture and radiograph respectively.

CASE 2
A 24-year-old female reported to OPD of dept of OMFS with chief complaint of progressively
increasing swelling in lower right back tooth region associated with pain for 6 months. She had
neither any relevant medical history nor any history of traumatic injury to the mandible. Extra-
oral examination revealed hard non tender swelling in the right body of mandible. Intra-oral
examination revealed swelling present in 45 to 47 region along with tenderness on percussion.
CBCT Mandible revealed an ill-defined osteolytic lesion in right mandible.

Figure 5: Pre operative clinical pictures of patient, Radiographic imaging showing extent of
lesion, Intra operative clinical pictures of patient

After taking into consideration the clinical examination, CT and HPE into account, a surgical
treatment was planned under GA followed by calcitonin therapy.

CASE 3
A 30 year male came to opd of OMFS with a complaint of pus discharge in upper left back tooth
region since 1 month.The pain was mild, localised in upper left back teeth region. He had a
history of hypertension since 4 months. CT scan revealed solitary ill-defined expansile lesion
extending from tooth 24 to edentulous 28 region medio-laterally and superio-inferiorly from the
nasal floor cortex to the orbital floor.
 Fig.6: Radiographic imaging showing extent of lesion, Intra operative clinical pictures of
patient along with specimen
After taking into consideration the clinical examination, CT and HPE into account, a surgical
treatment was planned under GA

CASE 4
A 6-year male reported to the OPD of OMFS with complain swelling in upper front teeth region
and difficulty in mastication since 1.5 years. He had history of trauma fall and injury to upper
teeth region 2 years back. Patient was asymptomatic for 6 months. This was followed by gradual
onset of swelling and bloody discharge from swelling on biting hard food. Patient underwent
incisional biopsy in anterior maxilla 2 weeks back under department of OMFS in Mahatma
Gandhi Hospital.
Extraoral examination revealed incompetent upper lip. Intra oral examination showed a bony
hard non ulcerated swelling present in anterior maxilla extending from alveolus to palatal region.
The CT angiography of the neck showed a large, multi-loculated lesion in the midline maxilla
with thin peripheral and septal calcifications. It intensely enhanced in the arterial phase, supplied
by the bilateral facial arteries from the external carotid arteries, which were prominent. No
vascular nidus or early draining veins were seen.
The CBCT revealed a radiolucent lesion with multilocular radiolucency in the anterior maxilla,
extending antero-posteriorly from the buccal to the palatal cervical plate, measuring
approximately 27.7 mm with bucco palatal expansion.
Figure 7: Pre operative clinical pictures of patient, Post operative clinical photo and radiograpgh

In all these patients, HPE revealed mononuclear cells in sheets along with multinucleated giant
cells which were evenly distributed along with bone fragments and fibrosis in between,
suggestive of CGCG.

Lab investigations showed normal calcium, phosphorus, alkaline phosphatase, PTH and
parathyroid hormone related protein. Calcitonin nasal spray (SALMON) was started 7 days post
operatively to prevent recurrence. Dosage prescribed 200 IU twice a day in alternate nostril for 3
months after surgery for all cases.

On 1 month follow up, clinical examination revealed a mild decrease in swelling and a
significant decrease in pain. The patients were planned for recall every month after blood
investigations including serum calcium, serum phosphorus, serum alkaline phosphatase, PTH
and parathyroid hormone related protein to check for changes in the lesion

DISCUSSION
CGCG is a benign though occasionally malignant osteolytic tumour localized primarily in the
mandible and maxilla. Surgical excision of the lesions has become an alternative possibility
because of the use of such pharmaceuticals like calcitonin, especially for patients who are at high
risk in undergoing surgical operation or those patients with multiple and recurrent lesions.

R. Tabrizi et al performed a double blinded randomized control trial on 24 patients divided into
two groups, one that received calcitonin nasal spray 200IU once a day with curettage and the
other one received placebo with curettage, both for 3 months after surgery. All patients were
followed up for 5 years. The results showed that calcitonin nasal spray may reduce the frequency
of recurrence in aggressive central giant cell granuloma of the jaws.6
Another randomised control trial by J. de Lange et al revealed that nasal calcitonin may help
decrease tumor volume in central giant cell granuloma patients, but complete remission was not
observed in this study.7

A. Abdel-Fattah et al. in a RCT showed that nasal calcitonin, being more efficacious than
subcutaneous injections, may reduce the risk of recurrence of central giant cell granuloma of the
jaws.8

Another study revealed remission in 50% patients with calcitonin therapy.9

The nasal spray formulation can lead to nausea, epistaxis, rhinitis, and ulceration of the nasal
mucosa.10

Standardized treatment standards are necessary, as seen by the variation in calcitonin delivery
techniques in research. To optimize therapeutic advantages, future research should concentrate
on determining the best dosage, mode of administration and length of treatment. Long-term
surveillance research is also required to validate the efficacy of calcitonin treatment in
minimizing CGCG recurrence.

Calcitonin treatment provides a feasible alternative to surgery for managing central giant cell
granuloma, providing substantial reduction of lesion size and low recurrence rates with minimal
adverse effects. Although current data is encouraging, more high-quality and standardized
clinical trials are necessary to confirm definitive treatment guidelines and long-term
effectiveness. Enhanced recognition and acceptance of calcitonin as a therapeutic option may
improve patient results and decrease the necessity for invasive surgical procedures.
References:

1. Patel VI, Amrutha GM. Central Giant Cell Granuloma of Maxilla: A Case Report. Indian J Otolaryngol
Head Neck Surg. 2022;74(Suppl 2):1661-1664. doi:10.1007/s12070-021-02794-4

2. Yadav S, Singh A, Kumar P, Tyagi S. Recurrent case of central giant cell granuloma with multiple soft
tissue involvement. Natl J Maxillofac Surg. 2014;5(1):60-66. doi:10.4103/0975-5950.140181

3. Verma P, Verma KG, Verma D, Patwardhan N. Craniofacial brown tumor as a result of secondary
hyperparathyroidism in chronic renal disease patient: A rare entity. J Oral Maxillofac Pathol JOMFP.
2014;18(2):267-270. doi:10.4103/0973-029X.140779

4. Doshi A, Bhola N, Agarwal A. Giant Cells, Giant Impact: A Case of Aggressive Central Giant Cell
Granuloma in the Mandible. Cureus. 16(4):e58881. doi:10.7759/cureus.58881

5. Allon DM, Anavi Y, Calderon S. Central giant cell lesion of the jaw: Nonsurgical treatment with
calcitonin nasal spray. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(6):811-818.
doi:10.1016/j.tripleo.2009.02.013

6. Tabrizi R, Fardisi S, Zamiri B, Amanpour S, Karagah T. Can calcitonin nasal spray reduce the risk of
recurrence of central giant cell granuloma of the jaws? A double-blind clinical trial. Int J Oral
Maxillofac Surg. 2016;45(6):756-759. doi:10.1016/j.ijom.2016.02.016

7. de Lange J, van den Akker HP, Veldhuijzen van Zanten GO, Engelshove HA, van den Berg H, Klip H.
Calcitonin therapy in central giant cell granuloma of the jaw: a randomized double-blind placebo-
controlled study. Int J Oral Maxillofac Surg. 2006;35(9):791-795. doi:10.1016/j.ijom.2006.03.030

8. Tabrizi R. Re: Can calcitonin nasal spray reduce the risk of recurrence of central giant cell granuloma of
the jaws?-a response. Int J Oral Maxillofac Surg. 2017;46(3):404. doi:10.1016/j.ijom.2016.07.008

9. Camarini C, de Souza Tolentino E. Non-surgical treatment as an alternative for the management of

central giant cell granuloma: a systematic review. Clin Oral Investig. 2022;26(2):2111-2132.
doi:10.1007/s00784-021-04193-z

10. McLaughlin MB, Awosika AO, Jialal I. Calcitonin. In: StatPearls. StatPearls Publishing; 2024.
Accessed May 31, 2024. http://www.ncbi.nlm.nih.gov/books/NBK537269/