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.

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.

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).

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.

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.

Excision of a Benign Peripheral Giant Cell Granuloma in the Oral Mucosa of the Anterior Mandibular Teeth with a 975-nm Diode Laser: A Case Report of a 39-Year-Old Woman.

BACKGROUND Peripheral giant cell granuloma, or epulis, is a common and benign oral lesion that can grow rapidly. Diode lasers are increasingly used to excise soft-tissue lesions because the technique preserves tissue for histopathology while controlling bleeding. Here, we report the excision of a 2-cm benign peripheral giant cell granuloma of the oral mucosa by 975-nm infrared diode laser, with rapid wound healing and good tissue preservation for histological analysis. CASE REPORT A 39-year-old woman presented with a large red-purple lesion in the oral mucosa of the lower jaw, near teeth 41 and 32. According to the patient, despite the absence of pain, the lesion caused difficulty while eating, speaking, and maintaining oral hygiene. The periodontal assessment included the following parameters: clinical attachment level, gingival recession, pocket probing depth, Loe-Silness gingival index, and tooth mobility index. The lesion was excised under local anesthesia using a 975-nm diode laser, and histopathology reports confirmed the diagnosis of peripheral giant cell granuloma. Six weeks after removal of the peripheral giant cell granuloma, all periodontal parameters were improved except for clinical attachment level and gingival recession. CONCLUSIONS Excision by 975-nm infrared diode laser can maintain tissue integrity for histopathology while allowing complete excision and control of bleeding. Soft lasers can provide advantages such as reduced bleeding, less operative and postoperative pain, decreased mechanical trauma, increased patient acceptability, and rapid wound healing without sutures, and they can be used to successfully remove peripheral giant cell granulomas.

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.

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.

Giant Cell Tumor and Giant Cell Reparative Granuloma of Bone of the Head: CT and MR Imaging Findings.

BACKGROUND: This study aimed to determine the features and differentiation of Giant Cell Reparative Granuloma (GCRG) and Giant Cell Tumor (GCT) of the head on CT and MRI. METHODS: This retrospective study included six patients with histopathology-confirmed head GCRG and 5 patients with histopathology-confirmed head GCT. All images were independently reviewed by two radiologists. The growth pattern, bone changes, MRI signal intensity, enhancement patterns and other image features were recorded. All patients received CT scans and MR images. RESULTS: All the lesions were located centrally in the bone. Osteolytic bone destruction and expansive growth patterns were observed on CT images. Four of six cases broke the cortical bone with residual cortical bone, and the last two showed a thin cortex in GCRG. Five cases broke the cortical bone with residual cortical bone in GCT. There were enhancing septations in GCT lesions on contrast- enhanced T1-Weighted Images (T1WI) while enhancing septations were not present in GCRG cases. The size of GCT lesions was larger than that of GRCG. GCRG and GCT showed iso-low signals on T1WI and iso-high signals on T2-Weighted Images (T2WI). There was a case with cystic or necrotic lesions in each of the two types of lesions. Osteolytic bone destruction and expansive growth patterns were observed in GCTs and GCRGs. CONCLUSION: The size of the GRCG lesion was smaller than that of the GCT. The presence of enhancing septations and the size of the lesion may distinguish GCTs from GCRG.

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.

A new TRPV4 mutation in a case of multiple central giant cell granulomas of the jaws.

Sporadic central giant cell granulomas of the jaws (GCGJ) are often solitary lesions, characterized by KRAS, FGFR1, and TRPV4 somatic mutations. Multifocal lesions may occur and are associated with hyperparathyroidism or underlying syndromes such as cherubism, which is marked by SH3BP2 mutations, and RASopathies, which are caused by mutations in the FGFR-RAS-RAF-MEK-ERK signaling cascade. The diagnosis of multiple GCGJ can be challenging. The present case reports a 14-year-old boy with multiple central GCGJ and no obvious syndromic trait. Sanger sequencing-based analysis revealed wild-type sequences for SH3BP2 (exon 9), KRAS (exons 2-4), and FGFR1 (exons 9 and 10) genes. A rare TRPV4 somatic mutation (p.Val708Met) was detected in the lesion on the right side of the mandible, whereas the other tumor and the normal oral mucosa revealed wild-type TRPV4 sequences. This report expands the spectrum of TRPV4 somatic mutations in central GCGJ.

Rare hybrid tumor of odontogenic fibromyxoma and central giant cell granuloma in maxilla: First reported case.

Fibromyxoma is a locally aggressive rare benign tumor of mesenchymal origin with or without odontogenic epithelium. The etiology of this tumor remains unknown and it is responsible for approximately 3-8% of all cysts and tumors. Another locally destructive benign lesion is central giant cell granuloma (CGCG) which contains osteoclast-like multinucleated giant cells. CGCG accounts for about 7% of all benign jaw tumors, which usually affects younger females. A hybrid lesion with histologic features of both central fibromyxoma and CGCG has not been reported in the literature so far. In the present article, we report the first case of a hybrid tumor comprising odontogenic fibromyxoma with CGCG in a female along with a brief review of its clinical presentation, radiographic features, histological features, and management.

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.