91吃瓜

Central giant cell granuloma (CGCG); Giant cell lesion; mandible; Jaw tumors; Oral pathology; Histopathology; Differential diagnosis; Surgical curettage; Calcitonin therapy; Hyperparathyroidism.

Introduction

First described by Jaffe in 1953, Central Giant Cell Granuloma (CGCG) of the jawbones is considered a benign, non-neoplastic proliferative lesion, although some forms may exhibit aggressive behavior [1]. The term “giant cell” relates to the multinucleated osteoclast-like cells observed in histological samples. CGCG occurs almost exclusively in the jaws, primarily affecting the anterior mandible. Despite its benign nature, it can be locally aggressive and challenging to manage in certain cases. Central Giant Cell Granuloma (CGCG) is a benign yet often enigmatic intraosseous lesion primarily affecting the jawbones, particularly the mandible [2]. First described by Jaffe in 1953, CGCG has since been a subject of continued investigation due to its unpredictable clinical behavior and diagnostic complexity. While considered non-neoplastic, CGCG can exhibit locally aggressive tendencies, including rapid growth, root resorption, tooth displacement, and cortical bone perforation traits more commonly associated with malignant lesions [3].

Central Giant Cell Granuloma (CGCG) is a non-neoplastic, intraosseous lesion of the jaws, first described by Jaffe in 1953. Although considered benign, CGCG exhibits a wide spectrum of biological behavior, from slow-growing indolent lesions to aggressive, rapidly expanding masses capable of causing extensive bone destruction [4]. The lesion primarily affects children and young adults under the age of 30, with a higher predilection for females and a frequent occurrence in the anterior mandible [5]. Clinically, CGCG may be asymptomatic or present with symptoms like pain, swelling, cortical expansion, and displacement or resorption of adjacent teeth. Radiographically, it appears as a unilocular or multilocular radiolucency, often with well-defined margins [6]. However, due to similarities in presentation with other giant cell-containing lesions, a thorough differential diagnosis is essential. Histopathological examination remains the gold standard for diagnosis, revealing a proliferation of multinucleated giant cells dispersed within a fibrocellular stroma with variable hemorrhagic and osteoid components.

Epidemiologically, CGCG accounts for approximately 7% of all benign jaw lesions and shows a distinct age and gender predilection, occurring most frequently in patients under 30 years of age with a notable female predominance [7]. The lesion typically presents in the anterior mandible, often crossing the midline, which can help distinguish it from other jaw pathologies. Clinically, CGCG may be asymptomatic and discovered incidentally on routine radiographs, or it may present with facial swelling, pain, and functional disturbances such as tooth mobility or paresthesia in more aggressive cases [8]. Radiographically, CGCG usually appears as a radiolucent lesion that may be unilocular or multilocular with well-defined or poorly defined margins. These features can mimic a variety of other jaw lesions, including ameloblastoma, odontogenic cysts, aneurysmal bone cysts, and even malignancies. Histologically, CGCG is characterized by multinucleated giant cells scattered within a vascular fibrous stroma. However, this histological pattern is not pathognomonic and overlaps with other entities such as brown tumors of hyperparathyroidism and giant cell tumors of long bones, necessitating careful differential diagnosis supported by biochemical analysis. The pathogenesis of CGCG remains incompletely understood. Several theories have been proposed, including reactive, inflammatory, or even neoplastic origins. Genetic studies have identified molecular alterations in aggressive variants, but no definitive causative mutations have been universally accepted.

Treatment of CGCG poses a clinical challenge, especially when the lesion exhibits aggressive behavior. Traditional surgical approaches such as curettage or resection can lead to significant morbidity, particularly in young patients. As a result, there has been growing interest in conservative medical management, including the use of corticosteroids, calcitonin, and interferon-α, and more recently, RANKL inhibitors like denosumab. These therapies aim to minimize the need for extensive surgery while controlling lesion progression. Despite these advances, the recurrence rate remains a concern, particularly in aggressive forms, highlighting the need for careful long-term monitoring.

Etiology and pathogenesis

The exact etiology of CGCG remains uncertain. Several theories propose that it results from a reactive, reparative process following intraosseous hemorrhage or trauma. Others suggest a possible relation to metabolic conditions such as hyperparathyroidism, especially in cases resembling brown tumors. Recent studies point toward a possible genetic or molecular component, such as abnormalities in the SH3BP2 gene, which is associated with Cherubism—a condition with histological features similar to CGCG.

CGCG is commonly classified into two types based on clinical and radiographic features:

Painless

Slow-growing

Less than 5 cm in diameter

Minimal cortical perforation

Pain and rapid expansion

Root resorption and cortical bone thinning/perforation

Higher recurrence rates post-treatment

Epidemiology

• Predominantly occurs in individuals under 30 years of age.
• Female-to-male ratio is approximately 2:1.
• The mandible is more commonly affected than the maxilla.
• Anterior regions of the jaws are more frequently involved, often crossing the midline.
• Swelling of the jaw
• Facial asymmetry
• Tooth displacement or mobility
• Occasionally associated with pain or paresthesia
• Expansion of the cortical bone
• Root resorption in some cases
• Unilocular or multilocular radiolucency
• Well-defined or poorly defined margins
• Radiographic appearance may mimic other odontogenic lesions like ameloblastoma or odontogenic myxoma
• Cortical expansion and thinning
• Tooth displacement or root resorption in aggressive forms
• Highly cellular connective tissue stroma
• Numerous multinucleated giant cells scattered throughout
• Areas of hemorrhage and hemosiderin deposits
• Occasional presence of osteoid or bone trabeculae
• Immunohistochemical studies may reveal markers such as CD68 (indicative of macrophage lineage)

Differential diagnosis

The differential diagnosis for CGCG includes:

• Brown tumor of hyperparathyroidism
• Aneurysmal bone cyst
• Cherubism
• Ameloblastoma
• Odontogenic keratocyst
• Giant cell tumor of bone (rare in jaws)
• Curettage, Preferred for small, non-aggressive lesions; recurrence rate may be up to 20%.
• En bloc resection, Indicated for large, aggressive, or recurrent lesions.
• Peripheral ostectomy, May be added to reduce recurrence.

Non-surgical/adjunctive therapies

• Intralesional corticosteroids, Aim to reduce lesion size pre-surgically.
• Calcitonin therapy, Inhibits osteoclastic activity.
• Interferon-alpha, Used in aggressive cases; has anti-angiogenic properties.
• Bisphosphonates, Inhibit bone resorption; limited data in CGCG.
• Denosumab, Monoclonal antibody targeting RANKL; promising but requires further research due to potential rebound effects and osteonecrosis risk.
• Recurrence rates vary depending on the surgical approach.
• Long-term follow-up (minimum 3–5 years) is essential, especially for aggressive forms.

The prognosis of CGCG is generally favorable, especially in non-aggressive cases treated with conservative surgery. Aggressive lesions, however, pose a higher risk of recurrence and may require a multidisciplinary treatment approach.

Conclusion

Central Giant Cell Granuloma is a unique jaw lesion with a wide spectrum of clinical behaviors. Early diagnosis, comprehensive radiographic and histopathological evaluation, and appropriate treatment planning are essential for optimal outcomes. Advances in pharmacologic therapies may offer less invasive options for management, particularly in pediatric or high-risk surgical candidates. Multidisciplinary collaboration between oral surgeons, radiologists, and pathologists is key in the successful management of CGCG. Central Giant Cell Granuloma, though benign, represents a challenging entity in oral and maxillofacial pathology due to its variable clinical behavior and diagnostic overlap with other lesions. Accurate diagnosis involves a multidisciplinary approach including clinical assessment, radiographic imaging, biochemical evaluation, and histological analysis. Treatment should be individualized based on lesion characteristics, patient age, and potential functional and cosmetic implications. While conservative therapies offer hope in reducing surgical morbidity, surgical management remains the mainstay for aggressive cases. Early intervention and continued research into molecular mechanisms are vital for optimizing outcomes and developing targeted therapies in the future.