Central giant cell granuloma in the posterior region of mandible mimicking a fibro-osseous lesion and hemangioma: a case report.

BACKGROUND: A central giant cell granuloma (CGCG) is a benign, proliferative, intraosseous, and non-odontogenic lesion occurring primarily in children and young adults. On the histological level, it is characterized by numerous multinucleated giant cells scattered randomly throughout a sea of spindle-shaped mesenchymal stromal cells which are dispersed throughout the fibrovascular connective tissue stroma containing areas of haemorrhage. When it comes to radiographic features, CGCG can have an array of variations, ranging from well-defined expansile lesions to ill-defined and destructive lesions, with or without expansion. CASE PRESENTATION: This case report reviews an 11-year-old Caucasian patient with a chief complaint of slow-growing swelling involving the right posterior mandibular region. The cone beam computed tomography (CBCT) revealed an ill-defined mixed lesion mimicking both fibro-osseous lesion and hemangioma. However, microscopic examination revealed multinucleated giant cells in a fibrous stroma suggestive of central giant cell granuloma. CONCLUSION: Our intent in reporting this case is to highlight the importance of thorough clinical, radiographical and histopathological examination for accurate diagnosis and therapeutic interventions as well as to emphasize the importance of taking different possibilities into consideration when examining bony swellings in the head and neck region.

Central Giant Cell Granuloma of the Mandible: A Case Report.

This article presents a clinical case of a central giant cell granuloma (CGCG) resembling a periapical lesion of endodontic origin. A 39-year-old, otherwise healthy male patient was referred to the department of oral and maxillofacial surgery for its diagnosis and subsequent management. The patient presented with an asymptomatic, progressively increasing intraoral swelling associated with the mandibular left para-symphysis region. On radiographic evaluation, a unilocular radiolucent lesion involving 33-34 teeth was noted. An incisional biopsy presented a giant cell lesion, following which surgical curettage was done. Histopathological examination was in accordance with the diagnosis of CGCG. Therefore, it is imperative for clinicians to accurately diagnose and rule out similarly presenting lesions.

Central Giant Cell Granuloma: Negotiating the Diagnostic and Management Dilemmas.

Introduction: Giant cell lesions of orofacial region although rare in presentation, have diagnostic and treatment challenges due to overlapping clinical, radiological, and histopathological signs. Background: We happened to come across a case, which presented to us with an aggressive jaw lesion of nonodontogenic origin, mimicking a malignancy and putting us in a conundrum with regard to work up and treatment. The sequential work up not only helped us reach a definitive diagnosis but also led us the draw algorithms for diagnosis of Giant cell lesions and management of Central giant cell granuloma. Conclusion: Meticulous planning along with molecular studies helps in better delineating one giant cell lesion from other.

Incidence, treatment method and recurrence rate in giant cell granulomas: Retrospective study.

Central and peripheral giant cell granulomas are benign entities mostly seen in mandibular anterior region at female individuals, usually with observed recurrence. Their etiology is still unclear, as is the optimal method for treating them. The aim of this study was to evaluate the incidence, treatment methods, recurrence rates, and initial and definitive correlation of central and peripheral giant cell granulomas. Patients who were referred to our clinic between 2013 and 2023 and who had the lesions' definitive diagnosis as "central giant cell granuloma" (CGCG) or "peripheral giant cell granuloma" (PGCG) were included in the study. Demographic data, recurrence rates, treatment methods, lesion location, clinical behaviors, and sizes were noted on the reports. A total of 30 lesions in 23 patients (14 PGCG and 9 CGCG) were evaluated in this study. The mean follow-up time was 62.6 months; 8 of 23 patients had systemic disease. While only 1 patient was observed to have cortical bone destruction in PCGC, all patients were found to have cortical bone destruction in CGCG (p < 0.05). In both lesions, the correlation of preliminary and definitive diagnosis was evaluated, and it was found to be 50% in PGCG while it was 77.7% in CGCG. The recurrence rates were 21.4% in PGCG and 33.3% in CGCG. Curettage was applied in all patients. Additional treatments (intralesional steroid injections, denasumab applications, resection, and graft application) were performed in 5 patients who were found to have CGCG (p = 0.004). However, there was no significant relation between treatment method and recurrence in CGCG (p > 0.05). Various peripheral lesions could mimic PGCG; thus, curettage therapy could be appropriate in the treatment of PGCG. Nevertheless, in some cases of CGCG, additional treatment methods could be more effective for preventing recurrence and any other complications.

Evaluation of the relationship between the expression of AgNOR and Ki67 with the recurrence rate in central granulomatous giant cell lesions: A case-control.

OBJECTIVES: Giant cell granuloma is a local nonneoplastic lesion that is divided into two categories, based on its site of occurrence: Central and peripheral giant cell granuloma. Central giant cell granuloma is an intraosseous lesion that has a tendency to recure even in surgically treated cases. Several studies have proven that there is an association between different lesions clinical behavior and their histological features. The aim of this study was to evaluate the expression of AgNOR and Ki67 in lesions with and without recurrency. MATERIAL AND METHODS: Files and records of 35 patients who had been histologically diagnosed with central giant cell granuloma were investigated. Histological features were studied after performing AgNOR staining and Ki67 marker. The data were analyzed by chi-square, Fisher, and T-test. RESULTS: Acquired data indicated that the count of AgNOR staining and Ki67 marker was significantly higher in lesions with recurrency than the lesions with no recurrency. The same results were attained from Ki67 intensity. CONCLUSION: The current study indicated that AgNOR staining and Ki67 marker have prognostic value in predicting recurrency of central giant cell granuloma lesions.

Denosumab as treatment of central giant cell granuloma of the jaws. a scoping review.

Denosumab has been considered a treatment option for Central Giant Cell Granuloma (CGCG) a benign locally aggressive osteolytic lesion of the jaws. This study aimed to perform a scoping review of CGCG treated with Denosumab. The research question was: What is Denosumab's effectiveness in treating CGCG of the jaws? Studies that used Denosumab as a treatment for CGCGs in the jaws were selected following PRISMA-ScR guidelines, using Pubmed/Medline, Scopus, and Springer Link databases, among others. Demographics, clinical information, dosing, efficacy, adverse drug reactions (ADRs), and imaging tests used to assess the evolution of the lesions were extracted. Twenty-one studies were selected. Sixty patients with a mean age of 23.2 years were treated with Denosumab, 42% with 120 mg subcutaneously monthly, additional doses on days 1, 8, and 15 for month 1 in adults. In children, dosing was adjusted by weight to 60 or 70 mg. To avoid ADRs 500 mg of calcium and 400 IU of vitamin D orally were used. Initial effective response was reported after 1-3 months, with recurrence of 19.6% and ADRs in 74% of cases. Denosumab is effective for CGCG with monthly subcutaneous doses of 120 mg, 60 or 70 mg in patients < 45 or 50 kg for ≥ 12 months with calcium and vitamin D supplementation until remission changes are observed. Extensive or refractory lesions were the main indications. Common ADRs were hypo and hypercalcemia. Further studies are needed to define dose and supplementation protocols to avoid ADRs during and after therapy.

Central giant-cell granuloma in a patient with neurofibromatosis type 1: 7 years of follow-up.

Neurofibromatosis type 1 (NF1) is an autosomally dominant tumor suppressor syndrome and multisystem disease. Central giant-cell granulomas (CGCGs) can be seen in patients with NF1. A 21-year-old female was diagnosed with two CGCGs, one in the mandible and then one in the maxilla, in a 7-year period. Increased incidence of CGCGs in NF1 patients was thought to be caused by an underlying susceptibility to developing CGCG-like lesions in qualitatively abnormal bone, such as fibrous dysplasia. However, germline and somatic truncating second-hit mutations in the NF1 gene have been detected in NF1 patients with CGCGs, validating that they are NF1-associated lesions. Oral manifestations in patients with NF1 are very common. Knowledge of these manifestations and the genetic link between NF1 and CGCGs will enhance early detection and enable optimal patient care.

Imaging of Fibro-osseous Lesions and Other Bone Conditions of the Jaws.

This review directs the focus on the imaging features of various fibro-osseous lesions and other bone lesions that can be of similar presentation. Broad diagnosis of "fibrous osseous lesion" may culminate in improper treatment and management. Radiographic discriminating factors between these entities are highlighted and summarized to improve the diagnostic process when encountering these lesions.

Multiple central giant cell granuloma of the jaws: diagnostic signposts of Noonan syndrome and RASopathy.

Noonan syndrome (NS) is a phenotypically variable inherited multi-system disorder. Maxillofacial findings can be diagnostic, especially in the evaluation of discrete facial dysmorphia. Diagnostic landmark findings of therapeutic relevance for the jaws such as central giant cell granuloma (CGCG) are rare in NS. However, recent molecular genetic studies indicate that these rare, benign lesions are neoplasms and more common in specific syndromes grouped under the umbrella term RASopathies. A specialist surgical diagnosis can be helpful in identifying the underlying disease. This report outlines diagnosis and treatment of a case of CGCG for which jaw diagnosis became the key to identifying a syndromic disease.

Maxillofacial challenge: Rare presentation of central giant cell tumor involving both maxilla and mandible.

INTRODUCTION AND IMPORTANCE: Central giant cell tumor (CGCT) of bone is an uncommon yet locally aggressive neoplasm originating from undifferentiated mesenchymal cells in bone marrow. This case report explores a rare presentation in the maxilla extending to the mandible, emphasizing the complexity of CGCT management and the need for a multidisciplinary approach. CASE PRESENTATION: A 35-year-old female presented with a progressively enlarging non-tender, firm swelling on the left maxilla and a similar mandibular swelling. Paraesthesia of the left lower lip and chin accompanied the mandibular swelling. CT scans and 3D reconstructions revealed expansive osteolytic defects affecting the maxilla and mandible. Biochemical tests supported a central giant cell tumor diagnosis. Histopathology confirmed spindle cell proliferation and multinucleated giant cells in both lesions. Surgical intervention involved excision and reconstruction. A five-month follow-up showed no recurrence, affirming the treatment's success. CLINICAL DISCUSSION: Central giant cell tumors (CGCTs) of bone are primarily benign, arising from undifferentiated mesenchymal cells. While mostly benign, they carry a rare potential for malignancy. Diagnosis involves imaging (CT, MRI, bone scintigraphy) and confirmation through biopsy. Surgical resection is the standard treatment, with radiotherapy considered in challenging cases. Recurrence rates vary with the extent of surgical intervention. Alternative treatments like cryotherapy and chemotherapy show varying success. CONCLUSION: This case emphasizes the necessity of precise histopathological diagnosis for CGCT management. The intricate nature of maxillary involvement, coupled with mandibular association, mandates a multidisciplinary approach. Surgery, while the primary treatment, should be judiciously determined based on tumor characteristics and recurrence.

Central giant cell granuloma: Off-label treatment with Denosumab in a patient with Noonan syndrome.

This study aims to describe the utilization of Denosumabࣨ, a human monoclonal antibody against the RANK-L receptor, in a mandibular giant cell granuloma (GCG) with a significant local aggressiveness component that was unresponsive to surgical treatment. We present a case of a 19-year-old male patient diagnosed with Noonan syndrome, who presented a multifocal giant cell granuloma with aggressive behaviour resistant to surgical treatment. Due to the functional and aesthetic implications associated with a surgical procedure, a decision was made to initiate medical treatment using Denosumabࣨ. Throughout the treatment, the patient presented excellent clinical and analytical tolerance, with no reported adverse effects. Surgical intervention remains the preferred approach for GCG. Denosumabࣨ emerges as an alternative, either as neoadjuvant treatment or as definitive therapy for unresectable or resectable tumors associated with significant morbidity. It leads to size stabilization and regression of the tumour stage.

Central giant cell granuloma formation in an edentulous area in the posterior portion of mandible: A case report.

INTRODUCTION: Central Giant Cell Granuloma (CGCG) is a non-neoplastic benign lesion. It is primarily observed in the maxilla and mandible, with the mandible being the more reported site of the lesion. The lesion often manifests in the anterior regions of the mandible, extending occasionally across the midline. This case reports a rare presentation in the posterior portion of the mandible, in an edentulous area. PRESENTATION OF CASE: A 33-year-old female with a history of extraction of teeth 36 and 37 six months ago presented with a main complaint of a mass in the oral cavity. The oral examination revealed an expansive multilocular mass (4 × 3 cm) located on the alveolar ridge in the left posterior portion of the mandible, extending around tooth 33 with an intact masseter muscle. The histopathological findings were consistent with CGCG. Consequently, the lesion was surgically removed with no clinical or radiological recurrence observed during the 4-month post-operative follow-up. DISCUSSION: While previous reports of CGCG in the posterior portion of the jaw showed destructive lesions that caused mandibular ramus destruction along with swollen masseter muscle, this case reports no involvement of the masseter muscle. Also, while some studies linked CGCG to tooth-bearing regions, our case suggests a possible traumatic link even after extraction. CONCLUSIONS: This case presents a rare CGCG occurrence in the posterior jaw, notably without masseter muscle involvement. It also indicates that CGCG can manifest in edentulous regions.

Morphological analysis of cell cannibalism: An auxiliary tool in the prediction of central giant cell granuloma clinical behavior.

Central giant cell granuloma (CGCG) is a benign jaw lesion with variable clinical behavior. Cell cannibalism is a cellular process associated with aggressiveness and invasion in malignant neoplasms. Here, we morphologically investigated cell cannibalism as an auxiliary method to predict CGCG clinical behavior. Cell cannibalism was quantitatively evaluated in 19 cases of peripheral giant cell granuloma (PGCG), 38 cases of CGCG (non-aggressive and aggressive), and 19 cases of giant cell tumor of bone (GCT) stained with hematoxylin and eosin. T-test was performed to assess the differences between the variables analyzed (p ≤ 0.05). Cell cannibalism was identified in 21% of non-aggressive CGCGs and 68.4% of aggressive CGCGs. A significantly higher amount of cannibal multinucleated giant cells (CMGC) was observed in aggressive CGCG compared to PGCG and non-aggressive CGCG (p = 0.042; p = 0.044, respectively). There were no significant differences in the CMGC index between non-aggressive CGCG and PGCG (p = 0.858) and between aggressive CGCG and GCT (p = 0.069). CGGC cases that exhibited rapid growth and tooth displacement and/or root resorption had a higher amount of CMGC (p = 0.035; p = 0.041, respectively). Cell cannibalism can be identified in CGCG through routine anatomopathological examination. The quantification of CMGC can help to predict the clinical behavior of central giant cell granuloma.

Peripheral giant cell granuloma as a sign of hyperparathyroidism in a patient under hemodialysis: A case report and review of literature.

Peripheral giant cell granuloma (PGCG) is a benign reactive exophytic oral lesion that originates from the periosteum or the periodontal ligament. It exclusively develops on the gingiva or alveolar mucosa. Hyperparathyroidism (HPT) is a possible etiology for its development. HPT is an endocrine disorder characterized by increased secretion of the parathyroid hormone (PTH). This case report describes a case of recurring PGCG in a patient diagnosed with secondary HPT after paraclinical assessment.

Surgical excision of peripheral giant cell granuloma of the maxilla: a case report.

Peripheral giant cell granuloma (PGCG) is described as an elevated lesion that is located mostly on the gingival mucosa and alveolar crest, consecutive to irritative factors and trauma. It predominantly occurs more in the mandible than the maxilla, and it is usually seen in the 4th to the 6th decades. The clinical appearance of this lesion is red-bluish in color, presenting a similar tissue to the one observed in the liver, usually measuring less than 2 cm. The treatment of the PGCG is the surgical excision. The recurrence of this lesion is rarely described in the literature. The present case highlights the importance of considering the traumatic extractions as one of the main uncommon etiologic factors, leading to the development of peripheral giant cell granuloma. It precisely describes the diagnosis, the treatment of a peripheral giant cell granuloma located in maxillary canine-premolar region, occurred consecutively after ancient traumatic extractions of the 13 and 14 since 1 year. This paper also reports a maxillary location of giant cell granuloma, while the literature reports more commonly the mandibular location. This lesion was excised surgically, and healed uneventually, and in which the follow-up didn´t show any sign of recurrence.

Denosumab in Giant Cell Rich Tumors of Bone: An Open-Label Multicenter Phase II Study.

BACKGROUND: Since giant cell tumors of bone (GCTB) and other giant cell rich tumors of bone (GCRTB) share the histological presence of osteoclastic giant cells and expression of RANK/RANKL, we hypothesized that GCRTB will respond similarly to denosumab as GCTB. The primary objective of this study was to determine the efficacy of denosumab in patients with GCRTB that have recurred or require morbid surgery. METHODS: In this open-label, multicenter, phase II trial, patients with GCRTB were included (June 2018-March 2020). Recruitment was stopped because of low accrual. Patients received denosumab (120 mg) subcutaneously (SC) on day 1 of every 4-week cycle with a loading dose of 120 mg SC on days 8 and 15. RESULTS: Three patients were enrolled. One withdrew consent before start of study. The remaining patients had central giant cell granuloma of the jawbone (CGCG). Median treatment duration was 15 cycles (range 12-18). In both subjects, improvement in ossification of lesions was seen. Median follow-up was 28.5 months (range 20-37). One patient developed a recurrence for which surgery was performed. CONCLUSION: Due to critical emerging real-world data of denosumab in GCRTBs, the study was prematurely stopped and not supportive of use of denosumab for this indication. (ClinicalTrials.gov Identifier: NCT03605199).

Expansive Oral Giant Cell Granuloma in a Pediatric Patient.

Aim: This article describes a peripheral oral giant cell granuloma (POGCG) in a pediatric patient and its surgical management and histological characteristics. Background: Peripheral oral giant cell granuloma (POGCG) is a hyperplastic reactive lesion formed by a proliferation of mononuclear cells and osteoclast-type giant cells in vascular tissue, occasionally with bone formation. Generally found in women and adults, POGCG has rarely been described in children. Case description: An 8-year-old girl was consulted for an exophytic lesion in the anterior area of the upper jaw, which had increased in volume in the preceding weeks. An excisional biopsy of the tumor was performed with an electrosurgical pencil. The pathological diagnosis was POGCG. Conclusion: Excision followed by additional therapy, such as scaling and curettage, should be the first option in the treatment of POGCG. Clinical significance: Early detection of these lesions involving the periodontium is important in order to reduce bone loss and avoid pathological dental migration. How to cite this article: Cahuana-Bartra P, Brunet-Llobet L, Suñol-Capella M, et al. Expansive Oral Giant cell Granuloma in a Pediatric Patient. Int J Clin Pediatr Dent 2023;16(2):405-408.

Oral giant cell tumor or giant cell granuloma: How to know?

Introduction: The distinction between giant cell tumors and giant cell granulomas is challenging, as both entities have overlapping diagnostic criteria, especially in oral locations. The two entities have similar clinical and radiological presentations, but they differ in their prognoses. Objective: The main objective of this study was to list the clinical, radiological, histological, and prognostic features of maxillomandibular giant cell tumors and giant cell granulomas cases n order to assess their value as a diagnostic referral factor that may allow the distinction between maxillo-mandibular giant cell granuloma and giant cell tumor. Study design: Data of maxillomandibular giant cell granulomas and giant cell tumors were assessed through a scoping review and a pre-existing systematic review of literature. We have also realized a bicentric retrospective study. Results: Various criteria facilitate the differential diagnosis like age, size, locularity and presence of necrosis zone but not the gender. The most discriminating factors was symptomatology (reported in 72% of GCTs while only 15% of GCGs) and the distribution pattern of giant cells in the stroma (homogeneously dispersed in 80% of GCTs versus grouped in clusters in 86.7% of GCGs). Recurrences were most described for giant cell tumors than giant cell granulomas. Malignant transformation and pulmonary metastasis were exclusively reported for giant cell tumors. Conclusion: As clinical and radiological elements are not sufficient to distinguish between these two entities, immunohistochemistry and molecular genetics can be represent diagnostic biomarkers to distinguish giant cell granulomas and giant cell tumors in oral cavity. We have attempted to define the main criteria for the differentiation of giant cell tumor and giant cell granuloma and propose a decision tree for the management of single maxillomandibular giant cell lesions.

Bony Canal Method of Dexamethasone Injections in Aggressive Form of Central Giant Cell Granuloma-Case Series.

Central Giant Cell Granuloma constitutes approximately 7% of benign tumors of the jaws. The aggressive form of CGCG clinically behaves like a classic semi-malignant neoplasm. In the literature, the suggested method of treatment of aggressive forms of CGCG is curettage or resection with the margin of 0.5 cm. Surgical treatment, especially in the developmental age, entails disturbances in the growth and differentiation of tissues and deforms and disturbs the functioning of the stomatognathic system. Alternative treatment methods of the CGCG presented in this article lead to the patient avoiding a mutilating procedure and improve their quality of life. The aim was to present alternative method of treatment of aggressive forms of Central Giant Cell Lesion of the jaws-injections of dexamethasone into the tumor mass through drilled bony canals. Here, we present the three cases of aggressive forms of CGCG of jaws treated with dexamethasone injections into the tumor mass. Two cases resulted in regression of the tumor, which was confirmed in histologic evaluation after remodeling surgery. Those two patients were uneventful and showed no signs of tumor recurrence at 8 and 9 years of thorough follow-up, respectively. The third patient was qualified for the mandible resection due to the enlargement of the lesion and destruction of the cortical bone. According to our observations, if the proper patient discipline, and thorough, careful clinical and radiological examinations are provided, the dexamethasone injections could be a recommended method of treatment of intraosseous giant cell granuloma. The indication is restricted to the cases with preserved bony borders despite deformation. Additionally, leaving vital teeth in the lesion is also possible.

Significant association between FGFR1 mutation frequency and age in central giant cell granuloma.

Central giant cell granulomas (CGCG) are rare intraosseous osteolytic lesions of uncertain aetiology. Despite the benign nature of this neoplasia, the lesions can rapidly grow and become large, painful, invasive, and destructive. The identification of molecular drivers could help in the selection of targeted therapies for specific cases. TRPV4, KRAS and FGFR1 mutations have been associated with these lesions but no correlation between the mutations and patient features was observed so far. In this study, we analysed 17 CGCG cases of an Italian cohort and identified an interesting and significant (p=0.0021) correlation between FGFR1 mutations and age. In detail, FGFR1 mutations were observed frequently and exclusively in CGCG from young (<18 years old) patients (4/5 lesions, 80%). Furthermore, the combination between ours and previously published data confirmed a significant difference in the frequency of FGFR1 mutations in CGCG from patients younger than 18 years at the time of diagnosis (9/23 lesions, 39%) when compared to older patients (1/31 lesions, 0.03%; p=0.0011), thus corroborating our observation in a cohort of 54 patients. FGFR1 variants in young CGCG patients could favour fast lesion growth, implying that they seek medical attention earlier. Our observation might help prioritise candidates for FGFR1 testing, thus opening treatment options with FGFR inhibitors.