Non-aggressive Central Giant Cell Granuloma Research Articles

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.

Immunohistochemical Assessment of Angiogenesis and Cell Proliferation in Aggressive versus Non-aggressive Central Giant Cell Granuloma.

Immunohistochemical Assessment of Angiogenesis and Cell Proliferation in Aggressive versus Non-aggressive Central Giant Cell Granuloma.

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.

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.

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.

Assessment of Vascular Density, Myofibroblastic Activity and Cellular Cannibalism in Aggressive versus Non-Aggressive Central Giant Cell Granuloma of the Jaws

Assessment of Vascular Density, Myofibroblastic Activity and Cellular Cannibalism in Aggressive versus Non-Aggressive Central Giant Cell Granuloma of the Jaws

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.

Central giant cell granulomas of the jaws: retrospective radiographic analysis of 13 patients.

This study was performed to retrospectively analyse the imaging features of 13 patients with central giant cell granulomas (CGCGs) examined at a single institution. The orthopantomography and cone beam computed tomography images of 13 patients histopathologically diagnosed with CGCGs were retrospectively analysed. Patients aged > 30years underwent measurement of their calcium and parathyroid hormone levels. No cases of hyperparathyroidism were identified in the study group. Thirteen lesions of 13 patients (7 female, 6 male) were included in this study. The patients' ages ranged from 8 to 79years at the time of presentation. Among the 13 lesions, 2 (15.4%) were in the maxilla and 11 (84.6%) were in the mandible. Eight lesions (61.5%) were unilocular and 5 lesions (38.5%) were multilocular with a soap bubble appearance. Three of the lesions were > 5cm, and the remaining ten lesions were < 5cm; five of these smaller lesions met at least three of the aggressiveness criteria. Therefore, according to these criteria, eight aggressive and five non-aggressive CGCGs were examined in this series. The distinction between aggressive and non-aggressive CGCGs is extremely important because it leads to changes in the individual treatment protocol that is applied. It may be possible to minimise recurrence after treatment by detecting findings such as cortical perforation or thinning, cortical bone expansion, and the presence of root resorption.

An insight into the cannibalistic behavior of giant cell granulomas of the jaws.

Background:Cellular cannibalism is defined as a large cell engulfing a smaller one within its cytoplasm. It is predominantly a feature of aggressive malignancies but has recently been demonstrated in giant cell (GC) lesions such as GC tumor of tendon sheath, central GC granuloma (CGCG) and peripheral GC granuloma (PGCG).Aim:The aim of the study is to assess the cannibalistic GCs in CGCG and PGCG and correlate with aggressiveness of the lesion.Settings and Design:Archival data of histopathologically confirmed cases of CGCG (n = 40) and PGCG (n = 25) were studied in the Department of Oral Pathology, Maulana Azad Institute of Dental Sciences.Materials and Methods:Quantification of cannibalistic cells was performed using H&E stain on microscopic sections. One hundred GCs were examined in each slide, and the number of cannibalistic cells was expressed in percentage.Results:GC cannibalism was observed in all cases. The mean number of cannibalistic GCs in CGCG was 44.67 which was significantly higher (P = 0.028) than PGCG (mean 28.04). In aggressive (n = 18) CGCG, the mean number of cannibalistic GCs was 51.27 which was significantly higher (P = 0.019) than cannibalistic GCs in nonaggressive (n = 22) CGCG (mean 39.27). No significant difference was observed between the number of cannibalistic cells in recurrent (mean = 52.9) and nonrecurrent (mean = 49.2) cases of CGCG (P > 0.05). Two of the nine cases treated initially by steroid showed fewer and smaller cannibalistic GCs with vesicular nuclei.Conclusion:There was a clear distinction in the mean cannibalistic count between aggressive and nonaggressive CGCG. Hence, the aggressiveness of the lesion could be assessed following which appropriate treatment modality can be constituted.

Central Giant Cell Granuloma of the Jaws: Correlation between Vascularity and Biologic Behavior

Introduction: Giant cell lesions of the bone comprise a group of jaw bone pathologies. Different pathogeneses such as reactive, vascular or neoplastic have been proposed for these lesions. In addition, differentiating between aggressive and nonaggressive central giant cell granuloma (CGCG) of the jaws based on histopathologic features is still impossible and due to different treatment protocols for the two groups, correct diagnosis is necessary. The purpose of this study was to compare the expression of CD34 between aggressive and nonaggressive CGCGs of the jaws. Methods & Materials: This retrospective study was carried out on 16 paraffin blocks in each aggressive and nonaggressive CGCGs group. The expression of CD34 was evaluated with immunohistochemical technique. Afterwards, t-test was used for quantitative evaluation and comparison of CD34 expression among the two groups. Eventually, statistical analysis was performed using Spss20 software. Significance was assigned at p < 0.05. Results: In the present study, the average age of patients in aggressive and nonaggressive groups was 20.93±8.08 and 26.18±16.97, respectively. In both groups, female predilection was observed. Mandible was the most common site of involvement in the aggressive group and the distribution of nonaggressive lesions was equal between both jaws. Although the expression of CD34 in the aggressive group was higher than the nonaggressive group, no statistically significant difference was seen (p=0.15). Conclusion: According to the results of the current study, it appears that CD34 protein cannot be used for identifying the clinical behavior of CGCGs.

Pharmacological and surgical therapy for the central giant cell granuloma: A long-term retrospective cohort study.

This is a retrospective cohort study of patients with a central giant cell granuloma (CGCG) treated at a single center to assess and compare the different surgical and non-surgical approaches. A cohort with a single histologically proven non-syndrome-related CGCG was selected and reviewed. Patients were allocated to group I (surgery), group II (pharmacotherapy), and group III (pharmacotherapy and surgery). The primary outcome was long-term radiologic response using computed tomography. Secondary outcomes were intermediate radiologic responses and occurrence and severity of side effects. Thirty-three subjects were included in the study. The surgical group (n=4) included 1 patient with progression during follow-up and a relatively high post-surgical morbidity. Twenty-nine patients started on various pharmacological treatment regimens (groups II and III). Fourteen patients could be managed without additional surgery. One of these lesions showed progression during follow-up. The other 15 lesions underwent additional surgery, and none showed progression during follow-up. Interferon treatment was associated with the most side effects. Pharmacological agents have a role in the treatment of aggressive and non-aggressive CGCGs by limiting the renewed progression during long-term follow up and the extent and morbidity of surgical treatment.

Cellular cannibalism in giant cells of central giant cell granuloma of jaw bones and giant cell tumors of long bones.

The aim of the present study was to investigate the relationship of central giant cell granuloma (CGCG) and giant cell tumor of long bones (GCT) with respect to cannibalistic giant cells (GCs). Sixteen cases each of CGCG and GCT were histopathologically analyzed for cannibalistic GCs. One hundred GCs were examined in each section, and the number of cannibalistic GCs was expressed in percentage. Cannibalistic GCs were seen in all cases of CGCG and GCT (100%). GCT showed significantly higher mean cannibalistic GC frequency (44.81 ± 1.013) than CGCG (32.06 ± 1.398), aggressive CGCG (38.17 ± 1.579), non-aggressive CGCG (28.40 ± 0.6360), non-recurrent CGCG (30.42 ± 1.417), and recurrent CGCG (37.00 ± 2.483). In aggressive CGCG, the mean cannibalistic GC frequency was significantly higher (38.17 ± 1.579) than the non-aggressive variant (28.40 ± 0.6360). Recurrent CGCG cases showed significantly higher mean cannibalistic GC frequency (37.00 ± 2.483) than non-recurrent cases (30.42 ± 1.417). Similarly, recurrent GCT showed significantly higher mean cannibalistic GC frequency (47.4 ± 4.97) than non-recurrent GCT (43.63 ± 3.1). The distinctness of CGCG and GCT was observed in terms of mean cannibalistic GC count. The assessment of cannibalistic GC in CGCG and GCT could help in predicting the biological behavior and grading of the tumor.

Expression of Ki67, CD31, CD68 and P53 in Peripheral and Central Giant Cell Granuloma of the Jaws

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.

Computer assisted histomorphologic comparision and the expression of AgNORs in the central and peripheral giant cell lesions of the oral cavity and giant cell tumor of the long bone

Objective:Computer-assisted image analysis was attempted to ascertain, if any of the previously described histologic features along with argyrophilic nucleolar organizer regions (AgNORs) could be used to determine the aggressiveness of the central giant cell granuloma of the jaws (CGCG), peripheral giant cell granuloma of the oral cavity (PGCG) and giant cell tumor of the long bones (GCT).Study Design:The study consisted of 20 cases of CGCG, 20 cases of PGCG and 5 cases of GCT. The histological features included were number of giant cells, number of nuclei in each giant cell, number of blood vessels, fractional surface area (FSA) and relative size index (RSI) of giant cells. The histologic parameters were measured using Motic image plus analyzer and AgNORs were evaluated using silver stain.Results:The statistical analysis showed significant differences among various histological parameters between CGCG, PGCG and GCT. A statistically significant difference was noted for the mean number of nuclei, FSA and RSI when GCT was compared with CGCG and PGCG. FSA of histologically aggressive central giant cell granuloma (HA-CGCG) was more compared to histologically non-aggressive central giant cell granuloma (HNA-CGCG). No statistical correlation was observed for AgNORs of multinucleated giant cells and mononuclear cells among CGCG, PGCG and GCT.Conclusion:Based on the present study findings, CGCG and GCT are distinct and separate entities and not a continuum of a single disease process. Histological parameters alone have a little implication on predicting clinical behavior of CGCG. AgNORs alone as a proliferative marker has a limited value in assessing the proliferation potential of giant cell lesions.

Incidence of central giant cell granuloma of the jaws with clinical and histological confirmation: an archival study in Northern India

To record the demographics, and correlate histological findings in central giant cell granulomas (CGCGs) of the jaws with their clinical behaviour, 30 paraffin-embedded samples of CGCG were retrieved from the archives of the Department of Oral Pathology and Microbiology, Subharti Dental College, Meerut, India. The diagnosis in each case was made on the basis of clinical, radiographic, and histological findings. Data about age, sex, anatomical site, presentation, radiological features, and laboratory investigations were analysed. Histomorphometric analyses were made in each case with respect to the number of giant cells, mean number of nuclei and giant cells, fractional surface area occupied by giant cells, index of relative size, and mitotic activity. The peak incidence of CGCG was during the second decade of life with a slight female predilection, and the mandible was the most common site. Of the 30 samples considered, 20 tumours were classified clinically as non-aggressive, and 10 as aggressive, based on their clinical behaviour. Histomorphometric analysis showed significant changes between the two groups with respect to the number of giant cells, the fractional surface area, and the mitotic activity. The data obtained showed clinical and histomorphometric features that may be reliable indicators for the differentiation between aggressive and non-aggressive CGCG. These data should be taken into consideration to improve planning of individual treatment and follow-up.

Central giant cell granuloma of the jaws: clinical and radiological evaluation of 22 cases

The objective was to investigate the clinical and radiological characteristics of central giant cell granulomas (CGCGs) of the jaws. A retrospective analysis of a 20-year database was performed regarding both clinical and radiological features of 22 patients affected with CGCGs of the jaws. Fourteen women and 8 men were included with the age range of 7-81 years (mean 31.7 years). Among the 22 lesions, 16 were located in the mandible and 6 in the maxilla. Painless swelling was the most common clinical feature in 18 of all cases. Limited mouth opening was noted in 2 patients where the lesions involved the condyle. Radiographically, 13 lesions were homogeneously osteolytic and 9 lesions were trabeculated. Fifteen lesions were unilocular and 14 lesions presented with well-defined but not sclerotic margins. CT images in 5 patients clearly showed the trabeculation within the lesions. The follow-up ranged from 1.5 to 11 years with a mean period of 5 years. Three out of 9 aggressive and 1 out of 13 nonaggressive lesions developed recurrence. Diagnosis of CGCGs of the jaws depends on both correct interpretation of clinical, radiographic and pathological data. Differentiation between aggressive and nonaggressive CGCGs should be considered to improve individual treatment planning.

Central giant cell granuloma of the jaws: A clinical, radiologic, and histopathologic study of 26 cases

The clinical behavior of central giant cell granuloma (CGCG) of the jaws is variable and difficult to predict. Clinical data and follow-up information of 26 patients with CGCG were analyzed. Histologic features were correlated with the clinical course of the disease. In 16 patients the CGCGs were asymptomatic; 10 lesions presented with aggressive growth, pain, massive swelling, root resorption, cortical perforation, and/or recurrence. These patients were younger and the lesions were larger than in the nonaggressive group. The histomorphometric analysis proved a significant increase in large giant cells, fractional surface area, and mitotic activity in aggressive CGCG lesions. Immunohistologic investigation (Ki-67 and p53 stain) revealed no significant differences. After surgical treatment, 3 patients with aggressive lesions developed a recurrence. The data show that clinical and histomorphometric features may be reliable indicators for the differentiation between aggressive and nonaggressive CGCG. This should be accounted for to improve the individual planning of the treatment and follow-up.

Central giant cell granulomas of the jaws: phenotype and proliferation-associated markers.

Central giant cell granulomas (CGCGs) are jaw tumors of unknown origin that often exhibit an aggressive, though unpredictable, clinical course. The purpose of this study was to determine the immunoprofile of the mononuclear cells that seem to be responsible for the biologic behavior of these tumors. Numbers of cells in cell cycle were also determined and compared in clinically aggressive and non-aggressive CGCGs. Sixteen aggressive and 12 non-aggressive CGCGs were immunohistochemically stained with antibodies to CD34, CD68, factor XIIIa, alpha-smooth muscle actin, prolyl 4-hydroxylase, Ki-67, and p53 protein. Cell populations and numbers of cells in cell cycle were determined through microscopic quantitative assessment. CD34-positive cells were limited to support vessels. CD68-positive mononuclear cells constituted a small population of cells in all tumors. With two exceptions, factor XIIIa-positive cells were rarely seen. Alpha-smooth muscle actin staining was present in approximately half the tumors, and occasionally large numbers of positive cells were seen. Most mononuclear cells were positive for fibroblast-associated antigen. No phenotypic differences were detected between aggressive and non-aggressive tumors. P53 protein did not appear to be overexpressed in CGCGs. Ki-67 staining showed that only mononuclear cells were in cell cycle, and that there were no differences between aggressive and non-aggressive tumors. We conclude that CGCGs are primarily fibroblastic (and myofibroblastic) tumors in which macrophages appear to play a secondary role. Tumor cells show no differentiation toward endothelial cells or macrophage-related dendrocytes (factor XIIIa). Cellular phenotypes and numbers of cells in cell cycle are similar in both aggressive and non-aggressive tumors.