Central Giant Cell Tumour-A Case Series

Introduction

The World Health Organization defines Central Giant Cell Granuloma (CGCG) as “a benign but occasionally aggressive osteolytic proliferation, characterized by fibrous tissue containing hemorrhage, hemosiderin deposits, osteoclast-like giant cells, and reactive bone formation”.¹

There is uncertainty over the etiology of CGCG. According to Jaffe, this tumour is a locally reparative bone response to inflammation, trauma, or bleeding.² There have been suggestions that it could be an endocrine lesion. They are not odontogenic, nor restricted to the jaws. The tumour is neither reparative nor a granuloma. Presently, the overwhelming body of data indicates that the lesion previously identified as a reparative granuloma of the central giant cells (CGCs) is actually a benign tumour of osteoclast precursors, and is thus more appropriately referred to as a CGC tumour. The lesion previously known as an aneurysmal bone cyst can also be thought of as a fast-growing variation of a CGC tumour due to the presence of macroscopic rather than microscopic blood-filled spaces.

The clinical manifestation of a CGC tumour might vary, exhibiting symptoms such as asymptomatic swelling or an aggressive progression. Due to intrinsic vascularity and thinning of the mucosa and cortex, the enlarged lesion may appear blue. Incidence of the lesion is low with female preponderance occurring in younger age group below 30 years. Chuong et al., classified these lesions as aggressive or non-aggressive based on factors such as the presence of pain, rapid growth, root resorption, cortical perforation, and recurrence tendency.³ The CGC tumour typically appears radiographic as a multilocular, radiolucent lesion with smooth or jagged margins that significantly thins the cortices. Additionally, it has been reported to resorb interradicular bone and displace teeth. Additionally, it could partially resorb tooth roots.

The treatment protocol includes surgical and conservative non-surgical methods. The surgical protocol includes aggressive curettage of the lesion and its bony cavity with or without chemical cauterization. Non-surgical methods include the use of intra-lesional steroids, systemic Calcitonin therapy, Interferon therapy, Bisphosphonates.

Case 1

An 8-year-old Male patient reported a chief complaint of an enlarged swelling in the left middle third of the face for 3 months which was initially smaller but gradually increased to the present size associated with pain, watery left eye (epiphora)left nostril obstruction, and snoring with a history of trauma 3 months back. The past medical, dental, and family history were not contributory. Clinical examination revealed facial asymmetry. On inspection, a roughly spherical swelling measuring 3 x 2 cm was noted in the left anterior maxilla with obliteration of the nasolabial fold. The skin overlying the swelling appeared normal, with no visible pulsations. On palpation, the swelling was firm in consistency, nontender, noncompressible, and non-reducible with no association with lymphadenopathy. Intra-oral examination reveals a solitary swelling obliterating the upper anterior vestibule, measuring 3 x 4 cm in greatest diameter, extending mediolaterally from left central incisor to left first deciduous molar and involving one-third of left hard palate with missing lateral incisor. Displacement of right central incisor was noted. No abnormality was detected in relation to oral mucosa.

Non-contrast computed tomographic scan revealed a multiloculated expansile cystic lesion measuring 38 x 56 mm in the left anterior maxilla. Cortical expansion was seen with loss of continuity at places. No calcifications were noted.

The differential diagnosis of CGC Tumour, Adenomatoid Odontogenic Tumour, Odontogenic Myxoma were considered. Aspiration biopsy revealed blood-tinged fluid. Incisional biopsy was carried out under LA. Microscopic examination revealed highly cellular fibrous connective tissue with numerous multinucleated giant cells that resemble osteoclast-like cells with areas of haemorrhage, scattered lymphocytes, and endothelial lined capillaries engorged with RBCs suggestive of CGC tumour.

Laboratory values for serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone were assessed to rule out the brown tumour of hyperparathyroidism.

A conservative approach with use of intra lesional steroid -Triamcinolone 10 mg/mL injected into the lesion using 1 mL for each 1 cm of the tumour was considered. Triamcinolone mixed with Local Anaesthesia in a ratio of 1:1 was given weekly for a period of six weeks followed by 200 IU of calcitonin via an intranasal route once daily. Following intralesional steroid injections and calcitonin therapy, curettage was done under general anaesthesia. Patient is under regular follow-up.

Case 2

A 30-year-old Male patient reported with a chief complaint of an enlarged asymptomatic swelling in the right lower third of the face for 6 months which was initially smaller but gradually increased to present size. The past medical, dental, and family history were not significant. Clinical examination revealed facial asymmetry. On inspection, a roughly spherical swelling measuring 4x1 cm was noted in the right posterior mandible. The skin overlying the swelling appeared normal. On palpation, the swelling was firm, nontender, noncompressible, non-reducible. Intra-oral examination reveals a solitary swelling obliterating the lower right buccal vestibule extending from right central incisor to right second molar. No abnormality was detected in relation to oral mucosa.

The panoramic radiograph showed a large unilocular radiolucency in the mandibular body, extending from the right lateral incisor to the right first molar, accompanied by radicular resorption of the associated teeth. The lower border of the mandible appeared thinned but remained intact without discontinuity.

Aspiration biopsy revealed blood-tinged fluid. Incisional biopsy was carried out under LA. Microscopic examination revealed capsule with radially arranged collagen bundles with numerous endothelial lined capillaries. Spaces of varying sizes filled with RBCs were noted suggestive of Aneurysmal Bone Cyst.

Laboratory values for serum calcium, phosphorus, alkaline phosphatase and parathyroid hormone were assessed to rule out the brown tumour of hyperparathyroidism.

A conservative approach with use of intra lesional steroid - Triamcinolone 10 mg/mL injected into the lesion using 1 mL for each 1 cm of the tumour was considered. Triamcinolone mixed with Local Anaesthesia in a ratio of 1:1 was given weekly for a period of 6 weeks followed by 200 IU of calcitonin via an intranasal route once daily. The patient is under regular follow-up.

Case 3

A 42-year-old Female patient reported with a chief complaint of an enlarged asymptomatic swelling in the left lower third of the face for 1 year which was initially smaller gradually increased to present size. The patient was a known case of hypothyroidism for 10 years and under medication (thyronorm 100 mg), diagnosed with Mitral Regurgitation and Rheumatic Heart Disease under medication (T. Prlomet XL 25 and T. Dytorplus LS 10) past dental, and family history were not contributory. Clinical examination revealed facial asymmetry. On inspection, a roughly spherical diffuse swelling measuring 4x2 cm was noted in the left posterior mandible. The skin overlying the swelling appeared normal. On palpation, the swelling was firm, nontender, noncompressible, non-reducible. Intra oral examination reveals a solitary swelling obliterating the lower left buccal vestibule extending from left second premolar to left third molar. No abnormality was detected in relation to oral mucosa.

Panoramic radiograph revealed a large unilocular radiolucency in the body of mandible extending from left second premolar to left third molar with no radicular resorption of the associated teeth. There was thinning but no discontinuity of the lower border of mandible.

Aspiration biopsy revealed blood-tinged fluid. Incisional biopsy was conducted under LA. Microscopic examination revealed highly cellular fibrous connective tissue with numerous multinucleated giant cells that resemble osteoclast-like cells with areas of haemorrhage suggestive of CGCG.

Laboratory values for serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone were assessed to rule out the brown tumour of hyperparathyroidism.

A conservative approach with use of intra lesional steroid -Triamcinolone 10 mg/mL injected into the lesion using 1 mL for each 1 cm of the tumour was considered. Triamcinolone mixed with Local Anaesthesia in a ratio of 1:1 was given weekly for a period of 6 weeks. Following intra lesional steroid injections, curettage was done under general anaesthesia. The patient is under regular follow-up.

Discussion

Central giant cell tumours have been the subject of much debate and discussion. It is still unknown that the makeup is what the lesion's actual biological. According to Jaffe, this tumour is thought to be the bone's locally reparative response to inflammation, damage, or bleeding.⁴ Eventually, the word "reparative" was abandoned. The tumour is neither reparative nor a true granuloma. Furthermore, a central giant cell "lesion" and what has been described in the literature as an aneurysmal bone cyst are identical in terms of histopathologic characteristics and biologic behaviour. Aneurysmal bone cyst can be conceptualized as a rapidly proliferating variant of a CGC tumour because it has macroscopic rather than microscopic blood-filled spaces. It is now more appropriate to refer to the lesion that was originally diagnosed as a CGC reparative granuloma as a CGC tumour because it is a benign tumour of osteoclast precursors.

From asymptomatic, indolent slow-growing tumours with thinning and perforation to aggressive tumours that rapidly hollow out bone, displacing neighbouring structures like teeth and nerves and causing pain, CGC tumours can behave in a variety of ways clinically. Although the lesion is unencapsulated, instead of infiltrating into nearby structures, it expands, pushing away and displacing them.⁵ Perineural invasion and infiltration into surrounding soft tissues are typically not observed. CGC granuloma appears as multi-locular radiolucency on radiograph, usually without cortication and with scalloped edges.⁶

Surgery is the standard course of treatment for central giant cell tumours. The necessity for such severe thera-pies in a benign reactive lesion-like CGC granuloma is called into doubt by the associated morbidities, which include functional and cosmetic damage, loss of teeth, tooth buds, and neurosensory abnormalities.⁷ According to Hutter et al., aggressive forms of central giant cell granulomas (CGCGs) have always been difficult to treat because of their high recurrence rate of 55-62% after curettage, which necessitates extensive and repeated surgical management at great functional and aesthetic impairment.⁸

The giant cells have osteoclast receptors and either represent osteoclast precursors or are themselves osteoclasts, medical treatments aimed at antagonising the activity and proliferation of osteoclasts have been used including corticosteroid injections, calcitonin, IFN, Bisphosphonates. The use of corticosteroids in the treatment of CGCG was initially documented by Jacoway et al., in 1988. It is hypothesised that steroids cause osteoclast-like cells to undergo apoptosis and prevent giant cells from producing extracellular bone resorption mediating lysosomal proteases.⁹ Giant cells in CGCGs were shown to be osteoclasts using osteoclast-specific monoclonal antibodies, which resulted in using calcitonin as a treatment for CGCC.¹⁰

Calcitonin inhibits bone resorption and increases osteoblastic activity. Interferon alpha, which has anti-angiogenic properties, has been employed as an adjuvant considering the vascularity of CGCG.

In case 1 post six weeks of intralesional steroids (Triamcinolone 10 mg/mL -1 mL for each 1 cm of the tumour) patient reported with decrease in nasal obstruction and epiphora. Post 7 months of calcitonin therapy patient reported with decrease in size of swelling. Radiographic signs of ossification of the lesion were noted. Following reduction in size surgical curettage under GA was employed. Laboratory values for serum calcium, phosphorus, alkaline phosphatase was within normal limits following calcitonin therapy.

A conservative approach with use of intra lesional steroid - Triamcinolone 10 mg/mL injected into the lesion using 1 mL for each 1 cm of the tumour was considered for case 2 for 6 weeks. The patient was under regular follow-up. Follow up radiograph showed increase in size of the lesion. Considering no response to treatment, patient was started on intranasal calcitonin spray (200 IU/day). Calcitonin therapy was given for 7 months. Post calcitonin therapy the growth of the lesion had plateaued. The patient is under regular follow up.

Surgical curettage under GA was done in Case 3 post intra lesional steroid injection (Triamcinolone 10 mg/ mL -1 mL for each 1 cm of the tumour) given weekly for a period of 6 weeks as the lesion did not respond to the treatment.

Central Giant Cell Tumour is a benign but aggressive lesion. Its aggressive form can cause extensive bony destruction. Early diagnosis and management can greatly improve morbidity and long-term outcomes. With morbidities associated with surgical interventions which include functional, cosmetic impairment, loss of teeth, neurosensory disturbances, non-surgical interventions can be considered a reasonable choice as these treatment options are associated with minimal morbidity and do not prevent further surgical therapy should they be unsuccessful.

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Conflict of Interest

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