Central giant cell granuloma of the jaws-long-term clinical and radiological outcomes of surgical and pharmacological management.

OBJECTIVES: To compare long-term results of different treatment modalities in central giant cell granuloma of the maxillofacial-skeleton. Primary resection may result in major defects. Alternative treatments include pharmacological agents. As yet there has been no consensus on the use of the variety of treatment options, and few studies have reported clarifying long-term results. MATERIALS AND METHODS: This retrospective study on 22 patients with 25 lesions evaluated clinical, radiological and histological features, treatment preformed and lesion recurrence. Success was defined as regression/calcification and failure as recurrence, progression or un-responsiveness. RESULTS: Of the presenting patients, 77% were under age 40. Lesion prevalence was higher in the anterior mandible and left posterior maxilla. Most cases exhibited pain, tooth-mobility or mucosal-expansion. The appearance was predominantly unilocular in the maxilla and multilocular in the mandible, which also exhibited higher prevalence of cortical perforation. Up to 80% of lesions were classified as aggressive. Intralesional steroids/calcitonin were used in 7 cases. Mean follow-up was 39.8 months. Two cases showed recurrence. In 71% of the cases treated pharmacologically, calcification/regression were observed. CONCLUSIONS: Our analysis indicates better outcomes using a combined approach, including both pharmacological and surgical treatments in large aggressive lesions. Pharmacological treatment resulted in decreased size or well-defined lesions, thus reducing the need for extensive bone resection. Dual treatment with corticosteroids and calcitonin showed no superior outcomes, but a larger cohort should be assessed. CLINICAL RELEVANCE: There are several protocols for treatment of central-giant-cell-granuloma lesions, but most are not fully established. It is important to report results that contribute to the establishment of proven protocols. This report attempts to establish the relevance of the combined approach: pharmacological treatment followed by surgical resection.

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.

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.

Response of Central Giant Cell Granuloma of the Jaw to Imatinib.

Central giant cell granuloma of the jaw (CGCJ) can be locally aggressive and result in facial and dental deformity. A child with CGCJ was treated surgically and with denosumab with a response but life-threatening toxicity. Imatinib, a tyrosine kinase inhibitor, was prescribed based on clinical similarities between CGCJ and cherubism, for which Imatinib has been effective. Within 2 months, a computed tomographic scan showed significant ossification, which increased over the following 8 months. This case suggests that tyrosine kinase inhibitors may be an effective option, and one with limited toxicity, for CGCJ.

[Experience with Denosumab in central giant-cell granuloma]. / Experiencia con Denosumab en granuloma central de células gigantes.

INTRODUCTION: Central Giant Cell Granuloma is an infrequent bone lesion located mainly in the maxillary bone. The main treatment is surgery with wide margins, so it sometimes causes great morbidity and esthetic al terations. Denosumab, a RANK-ligand inhibitor monoclonal antibody, has been presented as a valid therapeutic alternative in the treatment of these lesions. OBJECTIVE: to describe the clinical and radio logical response after treatment with Denosumab in a patient with unresected giant cell granuloma. CLINICAL CASE: 12-year-old boy who consulted due to a 24-hour maxillary swelling, without other associated symptoms. Examination revealed a tumor in the upper left maxilla with bulging of the ip- silateral gingiva. A CT scan was performed which showed a large expansive intraosseous lesion in the maxillary alveolar ridge. The biopsy of the lesion was compatible with Central Giant Cell Granuloma. Due to the size and location of the lesion, initial treatment with Denosumab, a human monoclonal antibody with action on RANK-ligand, was indicated. After 10 months of treatment, the patient showed a favorable clinical and radiological response, with a size decrease of the lesion and metabolic activity. As an adverse effect, the boy presented mild hypocalcemia, resolved after supplementation with calcium. CONCLUSION: the use of Denosumab as the first line of treatment in Giant Cell Granu loma may be an adequate therapeutic option in adolescents with lesions that are difficult to resect.

Granuloma de células gigantes mandibular. Tratamiento de una recidiva y rehabilitación dental: presentación de un caso / Giant cell granuloma of the jaw. Treatment of a recurrence and dental rehabilitation: a case report

El granuloma de células gigantes (GCG) es una patología de etiología no esclarecida que aparece tras traumatismos o procesos inflamatorios. Puede ser asintomático, debutar como una masa de comportamiento inflamatorio o comportarse de forma localmente agresiva. El diagnóstico resulta de la combinación de datos clínicos, radiológicos e histológicos. El tratamiento puede ser quirúrgico, mediante cirugías más o menos extensas, así como médico con diferentes fármacos.Se presenta el caso de un paciente intervenido de un GCG mandibular que acudió a nuestra consulta con una recidiva de la lesión, manejada quirúrgicamente mediante resección segmentaria y reconstrucción con colgajo libre de peroné, añadiendo al tratamiento la rehabilitación dental para realizar un manejo global del caso. (AU)

Giant cell granuloma (GCG) is a pathology of unclear aetiology that appears after trauma or inflammatory processes. It may be asymptomatic, have an early presentation as a mass with inflammatory reaction, or behave in a locally aggressive manner. Diagnosis results from a combination of clinical, radiological and histological data. Treatment can be surgical, with more or less extensive surgery, as well as medical with different drugs.We present the case of a patient who underwent surgery for a mandibular GCG who came to our hospital with a recurrence of the lesion, which was managed surgically by segmental resection and reconstruction with a fibula free flap, adding dental rehabilitation to the treatment for a global management of the case. (AU)

Denosumab for central giant cell granuloma in an Australian tertiary paediatric centre.

BACKGROUND: Central giant cell granulomas (CGCG) are rare osteolytic, benign but often locally aggressive tumours of bone. Surgical curettage may not be possible in extensive lesions and resection carries high morbidity, especially in growing children, and previous medical therapies have had variable efficacy and high recurrence rates. Interruption of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling holds promise as an effective therapeutic strategy for these tumours. AIMS: To evaluate the efficacy and safety of our protocol for denosumab treatment of CGCG in children. METHODS: Retrospective review of 4 patients treated with denosumab using a standardised protocol for CGCG in a tertiary paediatric centre. Denosumab 70 mg/m2 was given 4-weekly, followed by 2 doses of zoledronate 0.025 mg/kg, aimed at preventing rebound hypercalcaemia. RESULTS: Treatment of CGCG resulted in metabolic remission in all patients, but recurrence, detected by positron emission tomography (PET), occurred at 6 months in three patients and 12 months in one patient. Three patients developed symptomatic hypercalcaemia 4-5 months and one patient asymptomatic hypercalcaemia 7 months after cessation of denosumab, with 3 requiring additional bisphosphonate treatment. CONCLUSIONS: Denosumab produced a radiological and metabolic response in our patients, but metabolic recurrence occurred in all patients. PET imaging was effective for monitoring treatment response and early detection of recurrence. Incidence of rebound hypercalcaemia in this paediatric cohort was high. We present proposed changes to our protocol with the aim of producing sustained remission and preventing rebound hypercalcaemia.

A Retrospective Study of 105 Patients with Elastolytic Giant Cell Granuloma and a Proposal for a New Clinical Classification.

Elastolytic giant cell granuloma, an idiopathic granulomatous dermatosis, is characterized by annular plaques on sun-exposed areas, and has been termed actinic granuloma or annular elastolytic giant cell granuloma. Many atypical clinical manifestations and lesions involving sun-protected areas have been reported. The aims of this retrospective study of 105 patients were to summarize the clinical and histological features of patients with this condition; to provide evidence for the viewpoint that elastolytic giant cell granuloma is a better term to include all clinical morphological types presenting with elastolysis, elastophagocytosis, and an infiltrate of multinucleated giant cells histologically; and to establish a new clinical classification. The varying clinical manifestations were further categorized into annular, papular, giant, mixed and generalized forms. The pathological manifestations were classified into giant cell, necrobiotic, histiocytic, sarcoidal and mixed patterns. Diabetes mellitus or impaired glucose tolerance were the most commonly identified comorbidities. Oral low-dose corticosteroid may be an effective treatment.

Clinical and Radiologic Response of Central Giant Cell Granuloma to Denosumab: A 6-Year Prospective Observational Study.

Central giant cell granuloma (CGCG) is a rare lesion of the jaw occurring in young adults and adolescents. Surgery, the traditional mainstay of therapy, is associated with significant morbidity. Denosumab, a humanised monoclonal antibody to RANKL, is effective in a related entity, giant cell tumour of bone (GCTB), but experience in the more indolent CGCG is limited. This prospective observational study of all denosumab-treated CGCG at a tertiary referral centre (2015-2021) aimed to evaluate the safety, efficacy and recurrence risk using denosumab in CGCG at lower-frequency dosing than used for GCTB. All received standardised, time-limited courses of denosumab 120 mg with stepwise increase in dosing interval based on response. They were followed for up to 75 months using a radiation-minimising protocol: 3-monthly clinical, biochemical and radiological assessment (orthopantomograms, cone beam CT). Eight patients, median age 20.5 years [IQR 6], received 13 initial doses [IQR 10] of denosumab 120 mg. Radiologic response was seen after 5.5 doses [IQR 4.5]: ossification in all and size reduction in three. Recurrence occurred in four of seven completing therapy, observed 12 months post-cessation [IQR 6.5]. Larger baseline size, aggressive subtype and fewer than 12 initial doses were more common in the recurrence group. There was no osteonecrosis of the jaw. Hypocalcaemia occurred in one receiving modified dosing. This study represents the largest, most diverse cohort of denosumab-treated CGCG with the longest follow-up in literature. It demonstrates the efficacy of lower-frequency, time-restricted course of denosumab but highlights the risk of recurrence. Long-term follow-up is critical.

Sclerostin Immunohistochemical Staining in Aggressive Maxillofacial Giant Cell Lesions: Initial Results and Potential Therapeutic Target.

INTRODUCTION: Maxillofacial (MF) giant cell lesions (GCLs) are benign, often locally aggressive lesions with potential for recurrence. Systemic treatments have included interferon alpha, calcitonin, bisphosphonates, and denosumab. Sclerostin (SOST) is typically thought to be a negative regulator of bone metabolism and anti-SOST agents have been used to treat osteoporosis; however, its role in central giant cell granuloma is unknown. The purpose of this study was to evaluate the expression of SOST in MF GCLs. MATERIALS AND METHODS: This was a retrospective study of patients with MF GCLs treated at a single institution between 1993 and 2008 with a minimum follow-up of 6 months. Representative tissue was used to create a tissue microarray and SOST immunohistochemical (IHC) staining and grading was performed. The primary outcomes were IHC staining of the stromal cells and giant cells. The secondary outcomes included correlation of IHC staining and patient predictor variables including clinically benign and aggressive lesions. All analyses were completed using univariate statistical tests. RESULTS: A total of 37 subjects were included (29 clinically aggressive and 8 clinically benign). Sclerostin staining was present in 30 of 37 subjects (81%). Of these, 22 (60%) had stromal cell staining and 28 (76%) had giant cell staining. The presence or absence of staining, of either cell type, was not associated with aggressiveness, presence of clinical symptoms, tumor size, previous interferon therapy, previous surgery, or the race or age of the patient. DISCUSSION: Maxillofacial GCLs have an overall high level of SOST staining; however, the role of SOST in treatment and prognosis is unknown and warrants further study.

Non-surgical treatment as an alternative for the management of central giant cell granuloma: a systematic review.

OBJECTIVE: To evaluate the effectiveness of non-surgical treatment as an alternative in the management of central giant cell granuloma (CGCG). MATERIAL AND METHODS: A literature search was carried out in accordance with the PRISMA statement in order to answer the question "Are non-surgical treatments effective as an alternative in the treatment of CGCG?". Two examiners independently assessed eligibility, risk of bias, and extracted data, which included therapeutic protocol, side effects, and need for surgical supplementation. RESULTS: Among 1712 studies, 15 were included, totaling 145 patients. Calcitonin, intralesional corticosteroids, and denosumab were the medications used. For calcitonin (n = 61), complete remission was found in 30 cases. For intralesional triamcinolone (n = 68), reduction in size was observed in most cases (n = 39). Four cases received subcutaneous denosumab and showed absence of active bone metabolism in the region, of which three presented ossification. Combination of drug therapies (n = 29) was reported in one study and included subcutaneous interferon and oral imatinib. More and less side effects were found for interferon and corticosteroids, respectively. Forty percent of patients required additional surgical treatment. CONCLUSION: Despite the side effects presented and the need for additional surgery in some patients, in general, all non-surgical treatments could provide positive results as an alternative for the management of CGCG, especially with regard to reducing the size of the lesion. CLINICAL RELEVANCE: CGCG is a benign bone lesion that mainly affects young individuals. Although the most common therapy is surgery, its contraindication in some patients, the large extension, and high recurrence rate of the aggressive variant have led the search for non-surgical therapies.

HAS Carnoy's solution a role in the management of recurrent peripheral giant cell granuloma?

OBJECTIVE: this study aimed to evaluate the efficacy of local application of Carnoy's solution following the surgical excision of recurrent PGCG. PATIENTS AND METHODS: 40 patients who sought treatment for recurrent PGCG were included in this study. According to the type of treatment the patients were classified randomly into two equal groups. The lesions in all patients were excised down to the alveolar bone followed by aggressive curettage. Then only in group II, Carnoy's solution was applied for 5 min. Clinical follow-up was done for 1 year to evaluate the tissue healing. RESULTS: patients were 23 females and 17 males, with an average of 35.9years. Recurrent PGCGs occurred most commonly in fifth decade of life (25 %). Maxilla (57.5 %) was involved more than the mandible. The lesions were found posteriorly in 27cases and anteriorly in 13cases. The average size of the lesions was 2.9 cm. Histologically, foci of calcifications occurred in 12cases. Recurrence occurred in 5 cases: 4 in group I and 1 in group II. Bone healing was appropriate in all patients without sequestration. CONCLUSION: the use of Carnoy's solution following surgical removal of recurrent PGCG decreases their recurrence rates. The technique is safe, and conservative with low tissue morbidity.

Mechanisms of acute hypercalcemia in pediatric patients following the interruption of Denosumab.

PURPOSE: Denosumab is a fully human monoclonal anti-RANK-L antibody that is clinically used to counteract the bone loss induced by exacerbated osteoclast activity. Indeed, its binding to RANK-L prevents the interaction RANK-L/receptor RANK that is essential for osteoclastogenesis and bone resorbing activity. Although there are many medications available to treat bone loss diseases, including bisphosphonates, Denosumab is highly effective since it reduces the bone erosion. The use in pediatric patients is safe. However, some concerns are related to the interruption of the treatment. Indeed, in this study, we reported hypercalcemia in two pediatric patients and alterations of circulating osteoclast precursors. METHODS: Peripheral Blood Mononuclear Cells (PBMC) were isolated from two pediatric patients with hypercalcemia after Denosumab interruption and from 10 controls. Cytofluorimetric analysis and in vitro osteoclastogenesis experiments were performed. RESULTS: Increase of CD16-CD14+CD11b+ cells was revealed in PBMC from patients reflecting the enhanced in vitro osteoclastogenesis. CONCLUSION: Our data suggest that precautions must be taken when Denosumab therapy is interrupted and gradual decrease of dose and/or timing of treatment should be performed. To prevent the onset of hypercalcemia that could be in the discontinuation phase, cytofluorimetric analysis of PBMC should be performed to evaluate osteoclast precursors.

Dilemma in the Treatment of a Central Giant Cell Granuloma.

Management of central giant cell granuloma (CGCG) presents a clinical challenge. While eradicating a lesion known for its high recurrence rate calls for radical surgical approaches, these cause significant esthetic and functional impairment. We present an eight-year-old boy suffering from an extraordinarily large CGCG expanding into the mandible and base of the mouth in the whole anterior region. Combined treatment with surgical intervention and corticosteroid application was successfully applied, and all six attached dental germs could be preserved. Different approaches for clinical management in pediatric cases are discussed.

Denosumab for the management of central giant cell granuloma of the jaws-a case series.

Denosumab has been suggested as a medical treatment for central giant cell granuloma of the jaws. This study included eight patients, seven female and one male, aged between 19 and 32 years, with biopsy-proven central giant cell granuloma of the mandible. The patients were treated with subcutaneous injections of 120 mg of denosumab in a regime consisting of three injections at weekly intervals followed by five injections at monthly intervals over a 6-month period. They were followed up for between 60 and 71 months clinically and radiographically with panoramic radiographs and cone beam computed tomography scans. All of the lesions became calcified radiographically and asymptomatic clinically. They did not reduce in size, but to date only one patient has requested surgical remodeling. There has been no recurrence or regrowth in over 5 years.