Giant cell granuloma and neurofibroma in the mandible of a patient with neurofibromatosis type 1: a long-term follow-up case report with radiological and surgical aspects and a review of the literature.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain is frequently performed on patients with neurofibromatosis type 1 (NF1), to detect and follow-up intracranial findings. In addition, NF1-related pathologies can appear in the jaws. This case study investigates if it is advantageous to assess the depicted parts of the jaws in the imaging of NF1 patients with intracranial findings, thereby detecting jaw pathologies in their initial stages. CASE PRESENTATION: We report on the 3-year management with clinical and radiological follow-ups of a central giant cell granuloma and a neurofibroma in the mandible of a patient with NF1 who underwent examinations with brain MRIs. A review of the mandible in the patient's MRIs disclosed lesions with clear differences in progression rates. CONCLUSION: NF1-related jaw pathologies may be detected in the early stages if the depicted parts of the jaws are included in the assessment of the imaging of NF1 patients with intracranial findings. This could impact the treatment of eventual pathologies before lesion progression and further damage to the vicinity.

Peripheral giant cell lesion of the oral cavity in a 12-year-old child: A rare case report.

ABSTRACT: Giant cell lesion of the oral cavity in a pediatric population is a very rare entity. Peripheral giant cell granuloma (PGCG) is one such non-neoplastic lesion-causing gingival tumor. Here, a case of successful management of PGCG in a 12-year-old child is presented with a two-year follow-up. Clinical, radiographic, and histological features of PGCG are discussed with the importance of a long-term follow-up of the lesion.

Prevalence of Histopathologic Types of Gingival Lesions in the Iranian Population: A 22-Year Retrospective Study.

OBJECTIVES: Gingiva is one of the supporting tissues around the teeth that can be affected by various neoplastic or nonneoplastic lesions. Previous studies have examined several types of gingival lesions, but the lack of a standardized classification system has hindered meaningful comparisons. Additionally, many studies focused primarily on reactive lesions. Our study aims to contribute to the understanding of gingival lesions by investigating their prevalence across age groups, genders, sites, and by their clinical presentation. This research could lead to improved diagnostic accuracy and treatment strategies. MATERIALS AND METHODS: This retrospective study explores the prevalence of gingival lesions based on biopsies during a 22-year span. The patient's demographic details, including age, gender, and lesion's clinical presentation were systematically collected. These lesions were categorized into six groups. Descriptive statistics, χ2 test of independence, and one-way ANOVA were used for data analysis. RESULTS: Among the 7668 biopsied lesions, 684 (8.9%) lesions were located in the gingiva, with a greater occurrence in women (63.5%). Soft tissue tumors represented the most prevalent group in the gingival lesions (72.1%), and peripheral giant cell granuloma (PGCG) was the most frequent lesion (21.2%), followed by, pyogenic granuloma (19.3%), peripheral ossifying fibroma (17.8%) and focal fibrous hyperplasia (7.6%); all of which predominantly affected women, with mean ages falling in the fourth decade of life. Squamous cell carcinoma was recognized as the most common malignancy. CONCLUSION: In this study, PGCG was found to be the most common lesion in the gingiva in Iranian population. Further analysis using a unanimous categorization is required to confirm these results.

Orbital Giant Cell Reparative Granuloma: A Case Report.

Giant cell reparative granuloma has a very low incidence and is thought to be a response to trauma. While there have been only a few reported cases of orbital giant cell reparative granuloma, we recently observed such a case and analyzed 16 previously reported cases of this type. It is important to note that further investigation is necessary to fully understand the relationship between giant cell reparative granuloma and trauma.

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.

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.

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.

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.

DNA methylation profile discriminates sporadic giant cell granulomas of the jaws and cherubism from their giant cell-rich histological mimics.

Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).

Aggressive giant cell lesion of mandible-confusing to common: true neoplasm versus reactive lesion.

Destructive lesions in the craniofacial region especially in the jawbones, if associated with giant cells, include a spectrum of lesions that pose difficulty in diagnosis. The nature of such a lesion in the jawbones is questionable about whether it is a reactive/benign lesion or aggressive/non-aggressive. Clinical, radiological and histopathological correlation may be a reliable indicator to differentiate between the qualities of the lesion, which directly accounts for effective and individual planning of the treatment. Here we present a case of a woman in her late 20s with an unusual destructive lesion of the mandible.

A large-cohort study of 2971 cases of epulis: focusing on risk factors associated with recurrence.

BACKGROUND: To analyze the clinicopathological features of different histological subtypes of epulis, and evaluate the risk factors associated with recurrence. MATERIALS AND METHODS: A retrospective study including 2971 patients was performed. The patients' sex, age, location, size, histological subtypes, recurrence information, oral hygiene habits, periodontitis symptoms and smoking history were retrieved from the patient medical records and follow-up information. RESULTS: Among the 2971 cases, focal fibrous hyperplasia (FFH) was the most common lesion (60.92%), followed by peripheral ossifying fibroma (POF) (29.32%), pyogenic granuloma (PG) (8.08%) and peripheral giant cell granuloma (PGCG) (1.68%). The peak incidence of epulis was in the third and fourth decade of life, with a mean age of 45.55 years. Female predominance was found in all types of lesions with a female to male ratio of 1.71:1. PG had the highest recurrence rate (17.18%), followed by POF (12.98%), FFH (9.55%) and PGCG (8.82%). Histological subtypes were significantly correlated with the recurrence of epulis (P = 0.013). Regular supportive periodontal therapy (P = 0.050) had a negative correlation with recurrence, whereas symptoms of periodontitis (P < 0.001) had a positive correlation with the recurrence of epulis. CONCLUSIONS: Controlling the periodontal inflammation and regular supportive periodontal therapy might help reduce the recurrence of epulis.

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.

Giant cell epulis.

Giant cell epulis (peripheral giant cell granuloma) typically appears as a reactive benign lesion in the oral cavity in areas following local irritation or chronic trauma. Here we describe the case of a 45-year-old male patient who presented with the chief complaint of a large gingival mass in the anterolateral maxilla. There had been progressive growth within the past few months, with increased painless discomfort during mastication. The patient also reported bleeding during interdental cleaning. A full physical work-up led to the suspicion of giant cell epulis alongside other differentials including mucosal hemangioma and squamous cell carcinoma, with unremarkable laboratory values. Imaging including computed tomography showed signs of previous insertion of metal implants on either side of the lesion alongside mucosal hyperplasia. A confirmatory biopsy was taken and showed multiple giant cells on a reactive bed of stroma, in line with the diagnosis of giant cell epulis. Oral inflammatory conditions such as giant cell epulis have greater chances of local recurrence and, therefore, careful investigation with timely and accurate diagnosis is imperative for appropriate early treatment. Complete surgical excision should then be employed to prevent relapses, as incomplete removal can lead to further recurrence. Identification and eradication of potential sources of irritation should also be considered when treating the patient, to avoid further recurrence.

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.

Annular elastolytic giant cell granuloma in a woman with metabolic syndrome.

Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin condition. It belongs to a group of skin and elastic fiber disorders. When it affects sun-exposed skin, it is also called actinic granuloma. The etiology and pathogenesis are still debated. However, sun-induced actinic damage to elastic fibers is acknowledged as the primary triggering factor, though the pathogenesis of instances in sun-covered areas is unknown. The most commonly linked systemic illness is diabetes mellitus. Different case reports show an association of this disease with hematological conditions, infections, sarcoidosis, and protoporphyria. Multisystemic involvement was also reported in a case. The disease is clinically recognized by erythematous non-scaly annular patches and plaques with raised borders and hypopigmented or skin-colored centers, sometimes atrophic. It is usually asymptomatic or mildly itchy. The presence of an inflammatory infiltration with non-palisading granulomas, multinucleate large cells, elastin degradation, and elastophagocytosis, as well as the absence of necrobiosis and mucin, are histopathological characteristics. We report a 5-year history of annular elastolytic giant cell granuloma in a 66-year-old woman with a history of type two diabetes mellitus, hypertension, and fatty liver disease (steatosis). She presented with asymptomatic polymorphic erythematous skin lesions mainly in sun-exposed areas.

A Unique Case of Aggressive Central Giant Cell Granuloma in a 10-Year-Old Boy With 16p13.11 Microdeletion Syndrome.

Central giant cell granuloma (CGCG) is a rare disease characterized by sporadic, benign, intraosseous mandibular lesions of unknown etiology. Histologically, these lesions are indistinguishable from brown tumors of hyperparathyroidism and cherubism, and occasionally have been associated with different syndromes raising a question for genetic etiology. The CGCG has varied presentation ranging from nonaggressive and indolent to aggressive, destructive, and recurrent, often posing diagnostic and therapeutic challenges. Herein, we present the first case of a 10-year-old boy with CGCG and 16p13.11 microdeletion syndrome, highlight the diagnostic challenges inherent to this heterogeneous disorder, and discuss the genetics and treatment approaches of these complex lesions.

Dermoscopy of annular elastolytic giant cell granuloma.

Annular elastolytic giant cell granuloma is an uncommon granulomatous cutaneous disease that usually affects sun-exposed skin. Non-scarring alopecia is a possible presentation. Although histopathology is mandatory for the diagnosis, dermoscopy may help to narrow down the clinical differential diagnosis. The authors report a case of annular elastolytic giant cell granuloma in the scalp of a female adult patient, showing multiple yellowish/orange follicular dots in a diffuse erythemato-whitish background in the dermoscopy.

Brown Tumors Belong to the Spectrum of KRAS -driven Neoplasms.

Brown tumors are rare and generally self-limiting mass lesions of bone occurring in the context of hyperparathyroidism. Although commonly regarded as endocrine-driven tumor-like lesions, we detected pathogenic hotspot KRAS mutations in 10/16 brown tumors (62%) with similar frequencies found in cases affecting the peripheral and axial skeleton. Pathogenic mutations in other driver genes of the RAS-MAPK pathway were not identified. Our findings suggest brown tumors to represent true neoplasms driven by the activation of the RAS-MAPK signaling pathway. The frequent regression of brown tumors after normalization of hyperparathyroidism points to a second hit mediated by endocrine stimulation to be required for tumor development. Our findings underline the pathogenic relation of brown tumors to nonossifying fibroma and giant cell granuloma of the jaws which both appear histologically similar to brown tumors and are also driven by RAS-MAPK signaling pathway activation.