Central Giant Cell Granuloma

Central giant cell granuloma is a benign intraosseous lesion of the jaws made of multinucleated giant cells in a fibrous, vascular stroma. It is non-neoplastic or low grade neoplastic in nature and can behave aggressively.

It is found mainly in patients under 30, in women more than men, and in the mandible in about two thirds, mostly anterior to the first molars and often crossing the midline. Behaviour is classified as non-aggressive or aggressive.

Pathophysiology. The cause is unknown. Reactive and neoplastic theories exist, with activating mutations in the KRAS, FGFR1 and TRPV4 genes in many cases, and links to trauma and haemorrhage.

Giant cells are osteoclast like and they resorb bone, and RANK ligand signalling is the target of denosumab.

Aggressive features are pain, rapid growth over weeks to months, size over 5 cm, cortical perforation, root resorption, tooth displacement and recurrence after surgery.

A painless swelling of the jaw, found on a radiograph or because of expansion and facial asymmetry, and loose or displaced teeth. Aggressive forms cause pain, paraesthesia, cortical perforation and rapid growth, and the overlying mucosa can be blue or red.

Multiple lesions suggest hyperparathyroidism, cherubism, neurofibromatosis type 1, Noonan syndrome or other syndromes.

• Panoramic radiograph: unilocular or multilocular radiolucency with fine septa and scalloped borders, with root resorption or displacement and cortical expansion.
• CT or MRI: extent, cortical perforation and soft tissue involvement.
• Biopsy and histology: multinucleated giant cells in a fibrovascular stroma, with haemorrhage and haemosiderin, and reactive bone formation.
• Serum calcium, phosphate, alkaline phosphatase and parathyroid hormone to exclude brown tumour of hyperparathyroidism, which looks the same on histology.
• Genetic and clinical assessment when lesions are multiple or syndromic features exist.

Differential diagnosis.

• Brown tumour of hyperparathyroidism
• Cherubism
• Aneurysmal bone cyst
• Odontogenic myxoma and ameloblastoma
• Odontogenic keratocyst
• Giant cell tumour of bone
• Fibrous dysplasia and ossifying fibroma

• Surgical treatment: curettage with peripheral ostectomy for non-aggressive lesions. Recurrence is about 10 to 20% for non-aggressive and 30 to 70% for aggressive lesions, with figures of lower certainty. Resection with margins is used for large, recurrent or aggressive lesions.
• Non-surgical options to spare the patient from major surgery, particularly in children and in lesions near tooth buds and nerves:
  • Intralesional triamcinolone acetonide 10 mg/mL, mixed 1 to 1 with local anaesthetic, injected at a volume of 2 mL for every 1 cm of lesion, weekly for 6 weeks. Evidence is from case series.
  • Calcitonin 100 IU subcutaneously daily (or 200 IU intranasally daily) for 12 months, with adequate calcium and vitamin D. Check calcium, and avoid in allergy to salmon proteins. Evidence is limited.
  • Denosumab 120 mg subcutaneously on days 1, 8 and 15, then every 4 weeks, for aggressive or recurrent disease, with calcium 500 mg and vitamin D 400 IU daily. Check serum calcium before and during treatment and give a dental review before starting, because of the risk of hypocalcaemia and osteonecrosis of the jaw. It is contraindicated in pregnancy and is used with caution in children because of rebound hypercalcaemia on stopping. Evidence is from case series.
• Treat primary hyperparathyroidism when found, and the lesion often regresses.
• Antibiotics only for infection with spread: amoxicillin 500 mg orally three times daily for 5 days (reduce to 500 mg every 12 hours at eGFR 10 to 30), or clindamycin 300 mg four times daily in penicillin allergy.

Special groups. Pregnancy rules out denosumab and calcitonin is used with caution. Children need coordination with paediatrics and endocrinology.

Monitoring. Radiographs every 3 to 6 months during drug treatment and every 6 months for 2 years after surgery, then annually for at least 5 years. Calcium, phosphate and alkaline phosphatase during denosumab, including after stopping.

Referral and escalation. Refer to oral and maxillofacial surgery. Refer to endocrinology for abnormal calcium or parathyroid hormone. Urgent referral for rapid growth, pain or neurological signs.