Aggressive Central Giant Cell Granuloma Research Articles

Giant Cells, Giant Impact: A Case of Aggressive Central Giant Cell Granuloma in the Mandible

Giant Cells, Giant Impact: A Case of Aggressive Central Giant Cell Granuloma in the Mandible

Case report on aggressive central giant cell granuloma of mandible

Central giant cell granuloma (CGCG) is an uncommon, benign but aggressive osteolytic neoplasm of the craniomaxillofacial region, histologically characterized by an abundance of evenly distributed multinucleated giant cells within a sea of spindle-shaped mesenchymal stromal cells, scattered throughout the fibrovascular connective tissue stroma containing areas of hemorrhage. A rapid diagnostic assessment, together with an adequate histopathologic verification, is essential to improve the management and the prognosis of this locally destructive lesion. A rare case of a large destructive CGCG involving the entire right side of mandible, causing extensive bony resorption, and buccal, medial as well as inferior border cortical expansion, in a young female is presented. It was treated successfully by surgical excision under general anesthesia.

Maxillary central giant cell granuloma: An unusual presentation with a difficult management

Central giant cell granuloma (CGCG) is a rare benign intraosseous aggressive lesion commonly occurring in the mandible with its 2 subtypes, non-aggressive and a relatively rare aggressive type. The present case is a rare aggressive CGCG at an unusual maxillary region associated with swelling, rapid growth, pain and cortical growth perforation. The clinical, radiographic, and histopathological features along with difficult management have been described in detail.

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.

An unusual radiological manifestation of a mandibular central giant cell granuloma

Central giant cell granuloma (CGCG) is an uncommon benign osseous lesion of the jaw. We present the case of an aggressive CGCG in a 16-year-old boy with a 5-month history of facial swelling and nasal obstruction. He was referred for a radiology consult for multiple expanding swellings on the right hemi-face. The swellings were reported to have an insidious onset, slow progression and no association with paresthesia, nasal discharge, or systemic symptoms. Extra oral examination revealed a diffuse swelling on the right side of the face which obliterated the nasolabial fold causing facial asymmetry. A face and neck computed tomography (CT) showed expansile multi loculated lytic lesions of the right mandibular ramus which involved the condyle and hard palate. Similar lesions were also found in the skull base. Scans showed fine internal septations and internal ground glass haze. It also revealed involvement of several teeth roots and surrounding soft tissues. A pre-operative intra-oral biopsy of the lesion revealed multinucleated giant cells, comprising of both spindle-shaped and round cells. Differential diagnosis helped determine the lesions as CGCG. This case helps to demonstrate the wide variation in the clinical, radiological, and histopathological features of CGCG and the importance of thorough investigation for timely diagnosis.

Intra-lesional Steroid Treatment of Mandibular Central Giant Cell Granuloma

Central giant cell granuloma (CGCG) is a non-neoplastic benign lesion. CGCG can be treated by various modalities of which surgery is the most common treatment but have possible variable recurrence rates. Other treatment modalities like calcitonin and intralesional steroid have showed good long-term result in many clinical cases. As CGCG occurs commonly in young adults and children of less than 30 years, noon-surgical treatment is a better and least invasive option. The case of an 18-year-old Saudi female is represented with an aggressive mandible CGCG which has been treated with steroid intralesional injections on a weekly basis for six weeks that has been observed as a good treatment option for CGCG clinically.

Aggressive Central Giant Cell Granuloma of the Jaw and Adjuvant Denosumab Therapy: Decreased Morbidity and Preserved Function in a 3 Patient Case Series

We show the benefits of denosumab as adjuvant treatment of gnathic central giant cell granulomas (CGCGs) in 3 female patients, ages 18 to 65. This case series contributes to the growing experience in the medical therapy of these aggressive lesions, and demonstrates denosumab’s potential to decrease surgical morbidity. Central giant cell lesions of the jaw can be locally aggressive and thereby result in severe tissue destruction. Several medications have been evaluated as adjuvant therapy for CGCGs, with investigation of denosumab being the most recent. Our goal was to definitively treat patients with large CGCGs while minimizing unnecessary tissue and function loss. All 3 patients were offered adjuvant therapy with denosumab, since surgical resection alone would have resulted in large segmental defects requiring jaw reconstruction with free tissue transfer. Treatment instead consisted of lesion curettage and adjuvant denosumab therapy. The denosumab treatment protocol we used was based on what is currently recommended for unresectable giant cell tumors of bone (GCTB). Patients have been monitored for 40 months with clinical and radiographic exams, and 2 of them have also had histological evaluation following initiation of denosumab treatment. The 3 patients improved subjectively after the first few denosumab injections and had objective clinical and radiographic improvement after less than 6 months of therapy. Medication treatment length ranged from 10 to 15 months. Radiographic exams showed cortical thickening, resolution of cortical perforations, and calcification within a previously radiolucent region. Our findings are consistent with previous reports, and further support for the use of denosumab in locally aggressive central giant cell lesions. Our patients have thus far avoided large segmental resections, temporomandibular joint disarticulation, and sensory loss which would have resulted from surgical treatment alone. These 3 cases show that denosumab can be effective as adjuvant therapy in the treatment of aggressive gnathic CGCGs.

Aggressive central giant cell granuloma of the mandible: A case report and review of literature

Mandibular aggressive central giant cell granuloma is a rare non-neoplastic giant cell tumour characterised by pain, bone destruction, tooth root resorption, jawbone cortical perforation, and high recurrence rate. This is a case of a 10-year-old boy who presented to the Dental Surgical outpatient clinic of University of Uyo Teaching Hospital with a three-year history of left jaw swelling. The clinical diagnosis was fibrous dysplasia of the left hemi-mandible. Consequently, left hemi-mandibulectomy was performed, and subsequent histopathological diagnosis was aggressive central giant cell granuloma of the mandible. This article presents this rare diagnosis and explores its classification, aetiopathogenesis, clinico-pathological features and management.

Correlation of density of microvessels and myofibroblasts with the aggressiveness of central giant cell granulomas of jaws: A preliminary study.

Central giant cell granuloma (CGCG) is a fairly common lesion involving the jaw bones. CGCG can show relatively innocuous biological behaviour or it may show clinicoradiological features suggestive of aggressive biological behaviour. To date, there are no histological parameters which can be used to predict the behaviour of these lesions. This study was conducted to assess the utility of parameters of angiogenesis, i.e., total vascular area (TVA), mean vascular area (MVA) and microvessel density (MVD), and density of myofibroblasts in aggressive and non-aggressive CGCGs. The study was undertaken as a retrospective study. A total of 20 previously diagnosed cases (10 non-aggressive and 10 aggressive) of CGCGs were included in the study. The sections were subjected to immunohistochemistry using the markers CD34 and α-SMA. For the assessment of vascular parameters, image J software was used. The density of myofibroblasts was determined in each case ranging from score-1 to 4, using the criteria given by Sridhara et al. The correlation between mean values of vascular parameters and density of myofibroblasts with aggressiveness of CGCG was assessed using Mann-Whitney U test. The result of Mann-Whitney U test suggested that the differences between the values of TVA (P < 0.001), MVA (P < 0.003) and density of myofibroblasts, i.e., SMA mean (P < 0.001) and SMA score (P < 0.001), in two groups are statistically significant. The formula for the assessment of aggressiveness was obtained using discriminant analysis. Angiogenesis and density of myofibroblasts significantly differ in aggressive and non-aggressive cases of CGCGs. The aggressiveness of CGCG case can be predicted using the obtained formula by entering the values of vascular parameters and myofibroblasts.

Locally invasive CGCG of mandible: A case report

Background: Central giant cell granuloma (CGCG) is a benign, aggressive, destructive osteolytic lesion of osteoclastic origin. The three competing theories are that it could be a reactive lesion, a developmental anomaly or a benign neoplasm.CGCG of the jawbones can be classified as non-aggressive or aggressive. It has been observed that in a majority of the cases, the non-aggressive lesions are usually slow growing, symptom free and the treatment includes conservative surgical procedures. The treatment of aggressive CGCG is en-bloc resection which has a low recurrence rate, but requires major reconstruction. Case Report: The following report illustrates the differential diagnosis, surgery, final diagnosis and pathology of a non-aggressive CGCG in an 11-year-old boy, which was managed by curettage with peripheral ostectomy not requiring major reconstruction of the mandible. Conclusion: Surgery has always been considered to be the traditional treatment and it is still the most accepted. By preserving bone continuity prosthetic rehabilitation via implants can be safely performed. Keywords: Central giant cell granuloma, Non-aggressive lesion, En-bloc resection, Peripheral ostectomy.

Case reports: An aggressive central giant cell granuloma of the jaws in two pediatric patients

Central giant cell granuloma (CGCG) is a relatively uncommon and benign, non-neoplastic jaw lesion which occurs in children and young patients. It has been classified into two types based on its clinico-radiologic features into a slow growing asymptomatic, nonaggressive lesion, and an aggressive type encountered in younger patients growing rapidly into a large size, perforating the cortex, causing root resorption, and has a tendency to recur. Approximately 70% have the biological behavior of a non-aggressive, asymptomatic, slow-growing lesion, whereas the remaining 30% show an aggressive, progressively destructive behavior. However, care should be used to differentiate aggressive and non-aggressive granulomas. Histologically, aggressive lesions show a large area occupied by giant cells, great size, greater nucleolar organization and high expression of CD34 adhesion factors. Many surgeons choose the surgical treatment, which can be curettage, wide excision or resection with safety margins depending on the extent and behavior of the lesion as their preferred treatment option. We report two cases of aggressive central giant cell granuloma in pediatric patients, the clinical presentation and its treatment.

Reconstruction of bilateral ramus-condyle unit defect using custom titanium prosthesis with preservation of both condyles

BackgroundNovel technologies for management and reconstruction of complex bony defects regarding both function and facial appearance are interestingly used in maxillofacial surgery. In the current study, we demonstrated reconstruction of a bilateral ramus-condyle unit (RCU) defect while preserving both condyles by a novel designed titanium prosthesis using virtual surgical planning (VSP), computer-aided design and manufacturing (CAD/CAM), and Selective Laser Melting (SLM) technologies. Materials and methodsA 3D customized titanium prosthesis was designed for a 49 -year-old patient with bilateral mandibular aggressive central giant cell granuloma (CGCG) according to mandibular normal anatomy and structure while preserving bilateral intact condyles. Finite element study was performed to investigate the effects of new design strength and the stress shielding phenomenon. The design of macro-pores inside the body of prosthesis allowed it to act as a scaffold for bone tissue engineering under load bearing conditions. ResultsAnalysis of the strength and stress shielding phenomenon demonstrated favorable outcomes regarding the novel design. For instance, there was no stress shielding in any of the preserved condyles with regard to the size and distribution of stresses. Also, the stress distribution around the pores showed that these pores had no effect on the strength of the prosthesis. Thirty month follow-ups after reconstruction of bilateral RCU defect showed normal jaw function with a favorable facial appearance and mandibular contour. ConclusionWe design a novel patient-specific prosthesis with desirable biomechanical features for reconstruction of bilateral RCU defect after resection of the benign tumor with preservation of bilateral intact condyles.

Central giant cell granuloma in a 10-year-old pediatric patient - A rare entity in posterior mandible with CBCT findings: A case report

Central giant cell granuloma (CGCG) of bone constitutes about 7% of all benign lesions of the jawbones. CGCG, as described by Jaffe in 1953, is an idiopathic non-neoplastic proliferative lesion. The mandible anterior to the first molar is the frequently affected site, and has a tendency to cross the midline. Though CGCG is a benign reactive osseous lesion, it has been classified into two types based on its clinic-radiologic features into a slow growing asymptomatic, nonaggressive lesion, and an aggressive type encountered in younger patients which is painful and grows rapidly into a large size, perforating the cortex causing root resorption, and has a tendency to recur. We report a rare case of aggressive CGCG with massive destruction in molar region and angle of mandible.

Diagnostic difficulty of an aggressive and recurrent giant cell granuloma: a short case report

Introduction: The central giant cell granuloma (CGCG) is a rare benign lesion of the jaws, rarely aggressive,mostly affecting the mandible in children and young adults. The diagnosis may be difficult, complementaryhistological analyses being necessary to differentiate it from other giant cell tumours. Observation: A 28-year-old woman consulted for a painful gingival swelling surrounding the inferior right second molar. Cone Beam (CBCT) showed anunilocular radiolucent mandibular lesion. Histological examination performed after the curettage of the lesion could not differentiate between a peripheral GCG with bone extension, a giant cell tumour (GCT) or a CGCG. The patient was lost of view for 4 months until an aggressive recurrence. Asegmental mandibulectomy in disease-free margin was performed. Immunohistochemical and genetic testscomplementary to histology finally permitted to concludeto a CGCG. The patient presented no recurrence in 4 years of follow-up. Discussion: Surgical removal in disease-free margin is the gold standard treatment in aggressive CGCG. Nonetheless, literature reports alternative pharmacological treatments alone or in addition to surgery. In this case, the aggressiveness of the tumour and the absence of patient compliance for follow-up have led to the decision of a radical treatment of the recurrence. Conclusion: Aggressive CGCG requires a rapid diagnosis and a primary disease-free margin surgical resection to avoid mutilating treatment of the recurrence.

An aggressive central giant cell granuloma of maxilla: Diagnostic dilemma, Precise differential diagnosis and successful traditional surgical approach: A case report

Abstract Central Giant Cell Granuloma (CGCG) is a benign, proliferative, intraosseous and non-odontogenic lesion of unknown etiology accounting for approximately 10% of all benign lesions of the jawbones. Lesion usually occurs in patients younger than 30 years, is more common in females than males, and is more common in mandible than maxilla. The clinical feature of CGCG ranges from a slow growing asymptomatic swelling to a rapidly enlarging aggressive lesion. CGCG of the jaws are histologically benign lesions characterized by the presence of giant cells in the richly vascularized stroma of the spindle cells. Differential diagnosis should be performed with other lesions that have multinucleated giant cells (MGCs). Definitive diagnosis relies on correct interpretation of clinical, radiographical and histopathological data. The treatment of CGCG ranges from curettage to resection. Alternative treatments are worthy of consideration, although surgical excision remains the treatment of choice. The aim of this presented case highlights a diagnostic challenge of an aggressive CGCG arising from the maxilla and to discuss a precise differential diagnosis, as well as the surgical approach and follow up which is decisive for successful conventional surgical treatment with no lesion recurrence.

ACTIVATION OF SHH SIGNALING PATHWAY AND RELATIONSHIP WITH MYOFIBROBLASTS

Objective: This study investigated components of the HH pathway (SHH, GLI1, and cyclin D1) in central giant cell granulomas (CGCG). The relationship between these proteins and myofibroblasts was also studied. Material and Methods: Twelve cases of non-aggressive CGCG and 11 cases of aggressive CGCG were studied using immunohistochemistry for SHH, GLI1, Cyclin D1, and SMA. Results: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (P > .05). All cases of CGCG showed significantly higher expression of SMA compared to the other proteins (P < .01). A positive correlation (P = .04) was only observed between SHH and GLI1 for all cases of CGCG. Furthermore, a positive correlation between SHH and GLI1 in non-aggressive CGCG (P = .04) and between GLI1 and cyclin D1 in aggressive CGCG (P = .03) were observed. There was also a negative correlation between the expression of SHH and SMA in non-aggressive CGCG (P = .031). Conclusions: This study provided insights into the activation of the SHH pathway in CGCG. In addition, the activation of this pathway may play some role in the differentiation of stromal myofibroblasts, but this differentiation process would occur at the expense of maturation of these lesions. Objective: This study investigated components of the HH pathway (SHH, GLI1, and cyclin D1) in central giant cell granulomas (CGCG). The relationship between these proteins and myofibroblasts was also studied. Material and Methods: Twelve cases of non-aggressive CGCG and 11 cases of aggressive CGCG were studied using immunohistochemistry for SHH, GLI1, Cyclin D1, and SMA. Results: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (P > .05). All cases of CGCG showed significantly higher expression of SMA compared to the other proteins (P < .01). A positive correlation (P = .04) was only observed between SHH and GLI1 for all cases of CGCG. Furthermore, a positive correlation between SHH and GLI1 in non-aggressive CGCG (P = .04) and between GLI1 and cyclin D1 in aggressive CGCG (P = .03) were observed. There was also a negative correlation between the expression of SHH and SMA in non-aggressive CGCG (P = .031). Conclusions: This study provided insights into the activation of the SHH pathway in CGCG. In addition, the activation of this pathway may play some role in the differentiation of stromal myofibroblasts, but this differentiation process would occur at the expense of maturation of these lesions.

USE OF INTRALESIONAL CORTICOID AND CALCITONIN NASAL SPRAY IN THE TREATMENT OF CENTRAL GIANT CELL GRANULOMA: CASE REPORT

Central giant cell granuloma (CGCG) is a benign intraosseous lesion of the jaw bones that has the surgical therapy as conventional treatment. This study aimed to report the case of a patient with conservatively treated aggressive CGCG in mandible. A 29-year-old female patient presented a volumetric increase of the buccal and lingual mandible cortices, with hard consistency areas and crepitus compatible with cortical bone destruction. An incisional biopsy was performed and the histopathological examination confirmed the diagnosis. Treatment was initiated with intralesional injection of triamcinolone hexacetonide 25 mg/mL. An increase and partial calcification of the lesion was observed. The use of calcitonin salmon nasal spray (200 IU/d) was introduced for 3 months, after full calcification. The patient remains in radiographic clinical follow-up without evidence of recurrence or growth. The combination of corticosteroids and calcitonin was shown to be effective in treating aggressive CGCG as a conservative alternative to surgical resection.

Central giant cell granuloma: A clinicopathological and immunohistochemical study of macrophages, blood vessels, lymphatic vessels and regulatory proteins

ObjectiveThis study seeks to investigate immunohistochemical parameters that could distinguish non-aggressive Central giant cell granuloma (CGCG) from aggressive CGCG, two groups of lesions which differ in their clinical and radiographic features and prognosis. Material and methods12 cases of non-aggressive CGCG and 11 cases of aggressive CGCG were investigated and associated the immunohistochemical expression of macrophages (CD68 and CD163), blood vessels (CD34 and CD105), lymphatic vessels (D2-40) and regulator proteins (p63 and Ki-67). Clinical and radiographic features were also studied. ResultsAssociations between all proteins in non-aggressive and aggressive CGCG were not significant (p > 0.05). With respect to non-aggressive CGCG, there were no significant correlations, while in aggressive CGCG there was a significant positive correlation between CD68 and CD163 (p = 0.031), between CD34 and D2-40 proteins (p = 0.04), whereas a significant negative correlation was observed between CD105 and CD68 (p = 0.040). However, regardless of aggressiveness of CGCG, there was a significant positive correlation between CD68 and CD163 (p = 0,04). Among the clinical and immunohistochemical aspects, only the symptomatology was a significant risk factor for the occurrence of aggressive CGCG (OR = 12.00/p = 0.016). ConclusionMacrophages and angiogenesis contribute to their maintenance and development of CGCG. In addition, immunohistochemistry used here was not able to differentiate their aggressiveness. However, symptomatology was proved to be a risk factor for the occurrence of aggressive CGCG. It is possible that clinical features, particularly symptomatology, represent the most appropriate parameter to attempt to distinguish GCCG.

Potential role of Hedgehog signaling pathway and myofibroblastic differentiation in central giant cell granuloma-A preliminary study.

This study investigated components of the Hedgehog (HH) signaling pathway (SHH, GLI1), cyclin D1, and smooth muscle actin (SMA) in central giant cell granulomas (CGCG). The relationship between these proteins and myofibroblasts was also studied. Twelve cases of non-aggressive CGCG and 11 cases of aggressive CGCG were studied using immunohistochemistry for SHH, GLI1, Cyclin D1, and SMA. Associations between all proteins in non-aggressive and aggressive CGCG were not significant (P>.05). All cases of CGCG showed significantly higher expression of SMA compared with the other proteins (P<.01). A positive correlation (P=.04) was only observed between SHH and GLI1 for all cases of CGCG. Furthermore, a positive correlation between SHH and GLI1 in non-aggressive CGCG (P=.04) and between GLI1 and cyclin D1 in aggressive CGCG (P=.03) were observed. There was also a negative correlation between the expression of SHH and SMA in non-aggressive CGCG (P=.031). This study provided insights into the activation of the HH signaling pathway in CGCG. In addition, the activation of this pathway (SHH and GLI1) might play some role in the differentiation of stromal myofibroblasts, although these markers including Cyclin D1 and SMA do not indicate aggressiveness of the CGCG. Furthermore, this myofibroblastic differentiation process would occur at the expense of maturation of these lesions.

An aggressive central giant cell granuloma in a pediatric patient: case report and review of literature

BackgroundCentral giant cell granulomas are benign tumours of the mandible, presenting in children and young adults. Divided into non- and aggressive subtypes, the aggressive subtype is relatively rare and can occasionally progress rapidly, resulting in significant morbidity.Case presentationWe present a case of an aggressive central giant cell granuloma (CGCG) in a six year-old female. The lesion originated in the right mandibular ramus and progressed rapidly to involve the condyle. Diagnosis was made using a combination of imaging and pathology. A timely en bloc resection of the hemi-mandible was performed with placement of a reconstructive titanium plate and condylar prosthesis.ConclusionOur case demonstrates the importance of considering CGCG in the differential diagnosis of rapidly progressive mandibular lesions in the pediatric population. Prompt diagnosis and management can greatly improve long-term outcomes.