Brown Tumor in Jaw Associated with Hyperparathyroidism: A Case Report

Objective: The purpose of this study was to retrospectively analyze the demographic characteristics of patients with central giant cell granulomas (CGCGs) and peripheral giant cell granulomas (PGCGs) in Iranian population.Methods: The data were obtained from records of 1019 patients with CGCG and PGCG of the jaws referred to our department between 1972 and 2010. This 38-year retrospective study was based on existing data. Information regarding age distribution, gender, location of the lesion and clinical signs and symptoms was documented. Results: A total of 1019 patients were affected GCGLs including 435 CGCGs and 584 PGCGs during the study. The mean age was 28.91 ± 18.16. PGCGs and CGCGs had a peak of occurrence in the first and second decade of life respectively. A female predominance was shown in CGCG cases (57.70%), whereas PGCGs were more frequent in males (50.85%). Five hundred and ninety-eight cases of all giant cell lesions (58.7 %) occurred in the mandible. Posterior mandible was the most frequent site for both CGCG and PGCG cases. The second most common site for PGCG was posterior maxilla (21%), whereas anterior mandible was involved in CGCG (19.45%). The majority of patients were asymptomatic. Conclusions: In contrast to most of previous studies PGCGs occur more common in the first decade and also more frequently in male patients. Although the CGCGs share some histopathologic similarities with PGCGs, differences in demographic features may be observed in different populations which may help in the diagnosis and management of these lesions.Bangladesh Journal of Medical Science Vol.15(2) 2016 p.220-223

Background Central giant cell granuloma (CGCG) presents as a locally invasive, intraosseous lesion characterized by the accumulation of multinucleated giant cells amidst a matrix of hemorrhage and reactive fibrous tissue that infiltrates bone trabeculae. This idiopathic non-neoplastic proliferative lesion primarily affects the mandible, typically presenting as either unilocular or multilocular radiolucencies on X-rays. Although trauma or intraosseous hemorrhages are potential triggers, the precise histogenesis and etiology remain unclear. CGCG predominantly occurs in children and young adults, with a slight female predilection. Methods and materials A retrospective analysis of 21 cases of CGCG diagnosed at the Oral Pathology/Pathology department of Temple University Hospital between 2015 and 2022 was conducted. Each case was evaluated based on various parameters, including age, gender, presenting symptoms, radiographic findings, clinical differential diagnosis, and histological confirmation. The primary radiographic technique employed for diagnosis was X-ray imaging of the mandible and maxilla. The histological examination involved cutting paraffin-embedded tissue into 5-micrometer-thick sections, which were then stained using routine hematoxylin and eosin (H&E) stain. Notably, no specialized histochemical or immunohistochemical stains were utilized in the evaluation process. Results In our study, we reviewed 21 cases; 9 were male, 11 were female, and one had no available gender data.The age range was 15-76 years, with a mean of 50 years. The mandible was the most commonly affected location (17 cases; 81%)while the maxilla was less commonly involved (4 cases; 19%). Many CGCG lesions were asymptomatic (13 cases; 62%); eight cases (38%) were symptomatic, with painand fullness of the affected dental region being the main manifestations. In a few cases, conditions such as brown tumor (severe hyperparathyroidism) and odontogenic neoplasms, such as ameloblastoma, were suspected clinically and radiographically. The diagnosis of CGCG with associated acute and chronic inflammation was confirmed in all the cases. Histological evaluation of routinely stained slides was the main diagnostic tool utilized. No special stains or molecular studies were required to establish the final diagnosis. Conclusions Our investigation has determined that CGCG exhibits a non-neoplastic nature, displaying a spectrum of behaviors ranging from non-aggressive to aggressive tendencies. While CGCG is predominantly observed in the mandible, rare instances of involvement in the maxilla have also been documented. Importantly, no confirmed association with neoplastic lesions was identified during our analysis. The clinical course of CGCG tends to be indolent, with some cases presenting in association with impacted teeth. It's noteworthy that CGCG can present features mimicking neoplastic conditions, such as ameloblastoma, or localized lesions linked to systemic disorderssuch as hyperparathyroidism (brown tumor).

Statement of the Problem: There are some differences between clinical features of central giant cell granulomas (CGCGs) and peripheral giant cell granulomas (CGCGs) despite their same microscopic features. The possible role of angiogenesis in this issue is still a matter of debate. Purpose: The aim of the present study was to compare microvessel density (MVD) between CGCGs and PGCGs of the oral cavity using CD31 and CD34.Materials and Method: Immunohistochemical staining was performed on 18 PGCGs and 19 CGCGs using a monoclonal antibody against CD34 and CD31. MVD was assessed and compared between the lesions using t-test for statistical analysis. p< 0.05 was considered significant.Results:The expression levels of both CD34 and CD31 were significantly higher in CGCGs compared to PGCGs (p< 0.002 and p< 0.001, respectively). Significant differences in MVD assessed by both markers were observed between males and females in PGCGs (p< 0.05), but not CGCGs (p< 0.2). Conclusion:The combined evaluation of old- and newly-formed vessels by pan-endothelial cell markers showed differences between CGCGs and PGCGs, supporting the possible vascular-proliferative nature of the former. Whether this difference has a part in their diverse biologic behaviors and the role which pre-existent vessels play in comparison to neo-formed vasculature, requires further investigation.

Introduction: Giant cell granuloma is a relatively common lesion in oral cavity. Central giant cell granuloma usually treated with surgical excision with good prognosis. However in few cases, the lesion exhibits more aggressive behaviour, high recurrence rate and poor prognosis. It is difficult to identify these cases based on histological features so the need for diagnostic markers is of paramount importance to spare patients unwanted effects. Aim: To investigate expression of Ki67, CD31, CD68 and P53 proteins in peripheral and central (aggressive and non-aggressive) giant cell granuloma and whether their expression level can be used to differentiate between aggressive and non-aggressive types. Material and methods: A total of 33 cases; 15 cases of peripheral giant cell granuloma, 10 cases of nonaggressive central giant cell granuloma and 8 cases of aggressive central giant cell granuloma were tested for Ki64, CD31, CD68 and P53 expression using immunohistochemical staining. Results: Ki67 was expressed in all study cases with significantly higher levels in aggressive variant. CD31 expressed in all cases with significantly higher levels in peripheral giant cell granuloma. CD68 was expressed in all cases with no significant differences. P53 was only identified in central giant cell granuloma with significantly higher levels in aggressive type. Conclusion: Ki67 and P53 expression might be useful markers to identify aggressive central giant cell granuloma.

Cancer cannibalism is used to differentiate benign tumors from malignant, but recently the phenomenon has been demonstrated in giant cell tumor of tendon sheath (localized type). Microscopically and pathogenetically, this tumor is similar to central giant cell granuloma (CGCG) and peripheral giant cell granuloma (PGCG) of oral cavity. Hence, attempt has been made to study the cannibalistic giant cells (GCs) in CGCG and PGCG with their correlation with the biological behavior. Surgically treated 16 CGCG and 23 PGCG cases with adequate clinical and radiographic documentation were selected. Quantification of cannibalistic GCs was performed using routine HE stain. Hundred GCs were examined in each section, and number of cannibalistic cells was expressed in percentage. Ten cases were randomly selected for further immunohistochemical analysis with CD68 and bcl-2. Cannibalism was found in all the cases (100%). The frequency of occurrence of cannibalistic GCs ranged from 20% to 56% with a mean of 33.62 ± 8.9. CGCG showed significantly higher mean cannibalistic GC frequency (38.06 ± 10.15) than PGCG (30.04 ± 5.63). In aggressive CGCG, mean cannibalistic GC frequency was significantly higher (42.20 ± 10.4) than non-aggressive type (31.17 ± 6.014). Similarly, recurrent cases showed significantly higher mean cannibalistic cell frequency (43 ± 6.26) than non-recurrent cases (30.81 ± 6.66). Immunohistochemistry results showed histiocytic nature of GCs as well as mononuclear cells. The internalized cells did not expressed bcl-2, suggesting that the internalization induces apoptotic cell death. Assessment of frequency of cannibalistic cells in CGCG and PCGC could help in predicting the biological behavior of the tumor.

Objective. The aim of this case report was to document a case of implant associated central giant cell granuloma (CGCG) and review the literature on implant associated and intrabony lesions. CGCG is most common in females and usually seen in the mandible from anterior to posterior. Based on its clinical, radiological, and histological findings, it can be classified as aggressive and non-aggressive forms. Trauma is considered a major etiological factor for the lesion. Even peripheral giant cell granuloma has been shown as a peri-implant lesion, CGCG has not been reported as an implant-associated pathology. In this case report, we reported that CGCG developed after implant placement in 8 months. 39-year-old female patient with partial edentulism in the posterior mandible presented to our clinic. She had reported that she lost her posterior mandible teeth for more than six years. Initial clinical and radiological examination revealed that she showed localized slight to moderate chronic periodontitis, horizontal ridge deficiency (in the posterior mandible), and cavities. A total of six implants were placed at the same time. At 8-month of the surgery, she showed a radiolucency area #34 area. The lesion was enucleated, and the defect area was filled up with a xenogeneic bone substitute. The healing was uneventful. The histological examination determined the lesion was CGCG. The lesion showed no recurrency for 4.8 years.

Central giant cell granuloma and peripheral giant cell granuloma of the jaw and oral cavity are identical in histopathologic features, although they are different in pathogenesis and clinical behavior. The aim of present study was to compare CD 68 and factor VIII related antigen (VIII-RA ) immunoreactivity in central giant cell granuloma and peripheral giant cell granuloma to determine the biologic nature and clinical behavior of these lesions which may lead to a better or new treatment modality. CD68 and factor VIII-RA expression were examined immunohistochemically in 22 cases of central giant cell granuloma (10 aggressive and 12 non- aggressive ) and 19 cases of peripheral giant cell granuloma. The Kruskal-Wallis test followed by the Dunn test was used for data analysis. CD68 expression was observed in approximately 100% of multinucleated giant cells and 50% of mononuclear cells. Overexpression of factor VIII-RA in the endothelial cells of capillary like vessels in the periphery of the lesions was prominent. A statistical significant difference for CD68 intensity score in mononuclear cells among three groups (P=0.016) was observed. Indeed, factor VIII-RA intensity score in the endothelial cells of central giant cell granuloma and peripheral giant cell granuloma showed significant difference (P=0.004). These findings support the histiocyte/macrophage nature of multinucleated giant cells and mononuclear cells. Overexpression and high intensity score of CD68 in mononuclear cells and the high intensity score of factor VIII-RA in endothelial cells represent less aggressive behavior in central giant cell granuloma.

Central giant cell granulomas (CGCGs) are uncommon but the most aggressive benign intraosseous tumors of jaws, with an unpredictable outcome. They account for less than 7% of all benign jaw lesions, with a female to male ratio of about 2:1. The classical “brown tumor” is commonly seen in the long bones, pelvis, and ribs. Facial bone involvement is rare and usually appears as solitary or multilocular soap bubble like radiolucencies. CGCGs are traditionally treated by both surgical and intralesional injection, with a variable recurrence rate. Here, we report a 12-year-old female patient with mandibular brown tumor as a first sign of secondary hyperthyroidism induced due to vitamin D deficiency and hypocalcemia.

Background:Central and Peripheral giant cell granulomas of jaws are uncommon, benign, reactive disorders that are characterized by the presence of numerous multinucleated giant cells and mononuclear cells within a stroma. The origin of the multinucleated giant cells is controversial; probably originating from fusion of histiocytes, endothelial cells and fibroblasts.Objective:To assess the expression of CD34 and CD68 in central and peripheral giant cell granulomas to understand the origin of these multinucleated giant cells.Materials and Methods:Twenty cases of Central and Peripheral giant cell granulomas were evaluated immunohistochemically for CD34 and CD68 proteins expression.Results:Immunopositivity for CD34 was seen only in cytoplasm of endothelial cells of blood vessels; whereas, consistent cytoplasmic immunopositivity for CD68 was seen in few stromal cells. Statistical significance was seen in mean number of multinucleated giant cells, mean number of nuclei in multinucleated giant cells, CD68 expression and ratio of macrophages to multinucleated giant cells among two lesions.Conclusion:Although the central giant cell granulomas share some clinical and histopathological similarities with peripheral giant cell granulomas, differences in mean number of nuclei in multinucleated giant cells and CD68 immunoreactivity may underlie the distinct clinical behavior.

ObjectiveGiant cell lesions of the jaws (GCLJ) may rarely occur in the setting of RASopathy syndromes such as Noonan syndrome or neurofibromatosis I. Recently, central giant cell granulomas (CGCG), the most common of the GCLJ, have been recognized as benign neoplasms characterized by Ras/MAPK signaling pathway mutations. This provides a rational basis for understanding GCLJ in RASopathy syndromes as syndromically occurring CGCG. This review aims to summarize the clinicopathologic features of syndromic CGCG and to review the salient clinical and craniofacial features of the syndromes in which they may rarely occur.Material and MethodsAn electronic search in 3 databases was performed, looking for GCLJ/CGCG in RASopathy syndromes.Results124 CGCG in 56 patients were identified across 6 RASopathy syndromes. Median age at syndromic CGCG diagnosis is 11 years; 69.6% (39/56) patients developed two or more CGCG; 58.9% (33/56) presented with bilateral posterior mandibular CGCGs, mimicking cherubism. Of 88 CGCG with follow-up, 22.4% (13/58) of excised/resected CGCG recurred while 46.7% (14/30) of monitored CGCG showed continued growth.ConclusionSyndromic CGCG involves multiple RASopathy syndromes and may mimic cherubism or, when solitary, sporadically occurring CGCG. Familiarity with other clinical findings of RASopathy syndromes is critical for appropriate diagnosis and patient management.

Introduction Central giant cell granuloma (CGCG) is a benign tumor-like lesion of a bone, mainly localized in mandible. It usually occurs in children and young adults under 30 y.o., predominantly in females. The etiology of the disease remains unknown. Clinically, two different types of CGCG have been distinguished – an unaggressive one, in which the granuloma grows slowly, often asymptomatically, and aggressive type which is characteristic for increased bone destruction, severe pain, large size, rapid growth, high recurrence rate and complications such as root resorption, tooth displacement or cortical bone perforation. The treatment of CGCG depends on its type. In cases of granulomas of aggressive behaviour the following therapeutic procedures have been proposed: intralesial corticosteroid injections, interferon and calcitonin therapy as well as immunotherapy with anti-bone resorptive human monoclonal antibody like denosumab. However, in most cases nonsurgical management remains insufficient. Also, local curettage of the lesion results in high risk of recurrence. Therefore, radical surgical resection, commonly combined with bone reconstruction, is the most recommended way of treatment for aggressive of CGCG. Case report The authors present a case of a 31-year-old female patient treated at the Department of Oncological and Reconstructive Surgery, Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology in Gliwice due to central giant cell granuloma of a mandible. The resection of CGCG localized in mandible on the right side together with fibular free flap reconstruction has been performed, with satisfactory aesthetic effect. Positive staining for CD68 and CD31 was found in immunohistochemic examination and expression of Ki67 marker was 13%. No complications were reported in the postoperative period. The six-month follow up revealed no recurrences. Conclusions The authors claim that radical surgical management should be performed in all patients with CGCG of aggressive behaviour. Fibular free flap is recommended for reconstruction in large bone defects. It results in tumor-free margins at the resection and satisfactory cosmetic outcome. Quality of life and facial appearance can be improved with dental implantation after certain disease-free period. A regular follow-up is essential as an element of holistic oncological process.

Central Giant Cell Granulomas

Giant cell granulomas of the jaws are lesions that arise either peripherally in periodontal ligament and mucoperiosteum or centrally in the bone. The aim of this study was to evaluate expression of CD68 and tartrate-resistant acid phosphatase (TRAP) proteins in multinucleated giant cells and mononuclear cells. Formalin-fixed and paraffin-embedded tissue section of 20 specimens of central giant cell granuloma and 20 cases of peripheral giant cell granuloma were immunohistochemically analyzed for CD68 and TRAP proteins expression rate using Biotin-Streptavidin method. In central giant cell granuloma, more than 99% of multinucleated giant cells were positive for TRAP antibody and about 90% were positive for CD68. In mononuclear cells of this lesion, 14% of cases were positive with TRAP antibody and 8% with CD68. In peripheral giant cell granuloma, TRAP antibody was positive in 99% of giant cells and in 13% of mononuclear cells. A proportion of 97% of giant cells and 6% of mononuclear cells reacted positively with CD68. Immunohistochemical evidence of this study shows that giant cells and a group of mononuclear cells of stroma in both peripheral and central giant cell granuloma express TRAP antibody severely that is specific for osteoclast. Also, these cells are positive reactive to CD68, which is the macrophage marker and therefore it can be mentioned that giant cells are osteoclast, although their origins are macrophagic/monocytic or their precursors, and maybe mononuclear cells in stroma have a role in formation of giant cells.

Angiogenesis is a fundamental process that affects physiologic reactions and pathological processes such as tumour development and metastasis. It is the process of formation of new microvessel from the preexisting vessels. The purpose of this study was to evaluate angiogenesis, macrophage index and correlate the impact of macrophages on angiogenesis in the central and peripheral giant cell granulomas by evaluating immunohistochemically microvessel density, microvessel perimeter and macrophage index. Immunohistochemical analysis was carried on 20 cases of central and peripheral giant cell granulomas each for CD34 and CD68 proteins expression. Inferential statistical analysis was performed using Independent student t-test to assess the microvessel density, microvessel perimeter and macrophage index on continuous scale between Group I and Group II. Level of significance was determined at 5%. Further bivariate analysis using Pearson correlation test was carried out to see the relationship between microvessel density and macrophage index in each group. Microvessel density, micro vessel perimeter and macrophage index was higher in central giant cell granuloma compared to that of peripheral giant cell granuloma. Correlation between microvessel density and macrophage index among these two lesions was statistically insignificant. Angiogenesis as well as the number of macrophages appeared to increase in Central Giant Cell Granuloma in present study. These findings suggest that macrophages may up regulate the angiogenesis in these giant cell granulomas and angiogenesis do have a role in clinical behaviour. However, we could not establish a positive correlation between microvessel density and macrophage index as the values were statistically insignificant. This insignificance may be presumed due to fewer samples taken for study.

Purpose: The aim of the current study was to compare vascularity and angiogenic activity in peripheral and central giant cell granulomas (GCGs) of the jaws as reflected by vascular endothelial growth factor (VEGF). Patients and Method: 3 males and 7 females complaining of peripheral giant cell granuloma (PGCGs) and fifteen (5 males & ten females) with central giant cell granuloma (CGCGs) were selected to assess and compare the VEGF immunoexpression in multinucleated giantcells, and mononuclear surrounding stroma. Results: The expression levels of VEGF were greater in CGCGs compared to PGCGs and in aggressive CGCG more than non-aggressive. Conclusion: The vascularity and level of angiogenesis within aggressive CGCGs are higher than those in non-aggressive lesions. The stronger VEGF expression, the higher clinical behavior aggressiveness of the different giant cells granuloma lesions.